CIBINQO is indicated for the treatment of adults and pediatric patients 12 years of age and older with refractory, moderate-to-severe atopic dermatitis whose disease is not adequately controlled with other systemic drug products, including biologics, or when use of those therapies is inadvisable.
Limitations of Use: CIBINQO is not recommended for use in combination with other JAK inhibitors, biologic immunomodulators, or with other immunosuppressants.
IMPORTANT SAFETY INFORMATION
WARNING: SERIOUS INFECTIONS, MORTALITY, MALIGNANCY, MAJOR ADVERSE CARDIOVASCULAR EVENTS, AND THROMBOSIS
SERIOUS INFECTIONS
Patients treated with CIBINQO may be at increased risk for developing serious infections that may lead to hospitalization or death. The most frequent serious infections reported with CIBINQO were herpes simplex, herpes zoster, and pneumonia.
If a serious or opportunistic infection develops, discontinue CIBINQO and control the infection.
Reported infections from Janus kinase (JAK) inhibitors used to treat inflammatory conditions:
• Active tuberculosis, which may present with pulmonary or extrapulmonary disease. Test for latent TB before and during therapy; treat latent TB prior to use. Monitor all patients for active TB during treatment, even patients with initial negative, latent TB test.
• Invasive fungal infections, including cryptococcosis and pneumocystosis. Patients with invasive fungal infections may present with disseminated, rather than localized, disease.
• Bacterial, viral (including herpes zoster), and other infections due to opportunistic pathogens.
Avoid use of CIBINQO in patients with an active, serious infection, including localized infections. The risks and benefits of treatment with CIBINQO should be carefully considered prior to initiating therapy in patients with chronic or recurrent infections or those who have resided or traveled in areas of endemic tuberculosis or endemic mycoses.
Patients should be closely monitored for the development of signs and symptoms of infection during and after treatment with CIBINQO, including the possible development of tuberculosis in patients who tested negative for latent tuberculosis infection prior to initiating therapy.
Consider yearly screening for patients in highly endemic areas for TB. CIBINQO is not recommended for use in patients with active TB. For patients with a new diagnosis of latent TB or prior untreated latent TB, or for patients with a negative test for latent TB but who are at high risk for TB infection, start preventive therapy for latent TB prior to initiation of CIBINQO.
Viral reactivation, including herpes virus reactivation (eg, herpes zoster, herpes simplex), was reported in clinical studies with CIBINQO. If a patient develops herpes zoster, consider interrupting CIBINQO until the episode resolves.
Hepatitis B virus reactivation has been reported in patients receiving JAK inhibitors. Perform viral hepatitis screening and monitoring for reactivation in accordance with clinical guidelines before starting therapy and during therapy with CIBINQO. CIBINQO is not recommended for use in patients with active hepatitis B or hepatitis C.
JAK=Janus kinase; AD=atopic dermatitis.
Committed to Patient Support
Helping patients unlock access and reimbursement support for CIBINQO™ (abrocitinib)
*Eligibility required. No membership fees. This is not health insurance. The maximum benefit per patient is $15,000 per calendar year. Only for use with commercial insurance. If you are enrolled in a state or federally funded prescription insurance program, you may not use the copay card. See full terms and conditions below. pay as little as $ 0
per month*
Copay Savings Card: TERMS AND CONDITIONS
By using the Pfizer Dermatology Patient AccessTM Copay Savings Card, you acknowledge that you currently meet the eligibility criteria and will comply with the terms and conditions described below:
• You are not eligible to use this card if you are enrolled in a state or federally funded prescription insurance program, including but not limited to Medicare, Medicaid, TRICARE, Veterans Affairs health care, a state prescription drug assistance program, or the Government Health Insurance Plan available in Puerto Rico (formerly known as “La Reforma de Salud”).
• You must have commercial insurance. Offer is not valid for cash-paying patients.
• By using this copay card at participating pharmacies, eligible patients with commercial prescription drug insurance coverage for CIBINQO™ (abrocitinib) may pay as little as $0 per month. Eligible patients with commercial prescription drug coverage may receive a maximum benefit of $15,000 per calendar year, which is defined by the date of enrollment through December 31st of the enrollment year. After a maximum of $15,000, you will be responsible for paying the remaining monthly out-of-pocket costs.
• By using this copay card at participating pharmacies, eligible patients with commercial prescription drug insurance coverage for EUCRISA® (crisaborole) may pay as little as $10 per tube. Eligible patients with commercial prescription drug insurance coverage that does not cover EUCRISA may pay as little as $100 per tube. Individual savings are limited to $970 per tube. Individual patient savings are limited to $3,880 in maximum total savings per calendar year.
• This copay card is not valid when the entire cost of your prescription drug is eligible to be reimbursed by your commercial insurance plan or any other health or pharmacy benefit program.
• You must deduct the value of this copay card from any reimbursement request submitted to your commercial insurance plan, either directly by you or on your behalf.
• You are responsible for reporting use of the copay card to any commercial insurer, health plan, or other third party that pays for or reimburses any part of the prescription filled using the copay card, as may be required. You should not use the copay card if your insurer or health plan prohibits use of manufacturer copay cards.
• This copay card is not valid where prohibited by law.
• Copay card cannot be combined with any other savings, free trial, or similar offer for the specified prescription.
• Copay card will be accepted only at participating pharmacies.
• If your pharmacy does not participate, you may be able to submit a request for a rebate in connection with this offer.
• This copay card is not health insurance.
• Offer good only in the United States and Puerto Rico.
• Copay card is limited to 1 per person during this offering period and is not transferable.
• A copay card may not be redeemed more than once per 30 days per patient.
• No other purchase is necessary.
• Data related to your redemption of the copay card may be collected, analyzed, and shared with Pfizer, for market research and other purposes related to assessing Pfizer’s programs. Data shared with Pfizer will be aggregated and de-identified; it will be combined with data related to other copay card redemptions and will not identify you.
• Pfizer reserves the right to rescind, revoke, or amend this offer at any time without notice.
• Offer expires 12/31/2025.
For questions or additional support, call 1-833-956-3376, write to Pfizer Inc. at PO Box 29387, Mission, KS 66201, or visit the CIBINQO website at www.CIBINQO.com or the EUCRISA website at www.EUCRISA.com.
INDICATION
MORTALITY
In a large, randomized postmarketing safety study in rheumatoid arthritis (RA) patients 50 years of age and older with at least one cardiovascular risk factor comparing another JAK inhibitor to TNF blocker treatment, a higher rate of all-cause mortality (including sudden cardiovascular death) was observed with the JAK inhibitor. CIBINQO is not approved for use in RA patients.
MALIGNANCIES
Malignancies, including non-melanoma skin cancer (NMSC), were reported in patients treated with CIBINQO. Lymphoma and other malignancies have been observed in patients receiving JAK inhibitors used to treat inflammatory conditions. Perform periodic skin examination for patients who are at increased risk for skin cancer. Exposure to sunlight and UV light should be limited by wearing protective clothing and using broad-spectrum sunscreen.
In a large, randomized postmarketing safety study of another JAK inhibitor in RA patients, a higher rate of malignancies (excluding non-melanoma skin cancer [NMSC]) was observed in patients treated with the JAK inhibitor compared to those treated with TNF blockers. CIBINQO is not approved for use in RA patients. A higher rate of lymphomas was observed in patients treated with the JAK inhibitor compared to those treated with TNF blockers. A higher rate of lung cancers was observed in current or past smokers treated with the JAK inhibitor compared to those treated with TNF blockers. Patients who are current or past smokers are at additional increased risk.
Consider the benefits and risks for the individual patient prior to initiating or continuing therapy with CIBINQO, particularly in patients with a known malignancy (other than a successfully treated NMSC), patients who develop a malignancy when on treatment, and patients who are current or past smokers.
MAJOR ADVERSE CARDIOVASCULAR EVENTS (MACE)
Major adverse cardiovascular events were reported in patients treated with CIBINQO. In RA patients 50 years of age and older with at least one cardiovascular risk factor treated with another JAK inhibitor, a higher rate of major adverse cardiovascular events (MACE) (defined as cardiovascular death, myocardial infarction, and stroke), was observed when compared with TNF blockers. CIBINQO is not approved for use in RA patients. Patients who are current or past smokers are at additional increased risk. Discontinue CIBINQO in patients that have experienced a myocardial infarction or stroke.
Consider the benefits and risks for the individual patient prior to initiating or continuing therapy with CIBINQO, particularly in patients who are current or past smokers and patients with other cardiovascular risk factors. Patients should be informed about the symptoms of serious cardiovascular events and the steps to take if they occur.
THROMBOSIS
Deep vein thrombosis (DVT) and pulmonary embolism (PE) have been reported in patients treated with CIBINQO. Thrombosis, including PE, DVT, and arterial thrombosis have been reported in patients receiving JAK inhibitors used to treat inflammatory conditions. Many of these adverse reactions were serious and some resulted in death. In RA patients 50 years of age and older with at least one cardiovascular risk factor treated with another JAK inhibitor, a higher rate of overall thrombosis, DVT, and PE were observed when compared with TNF blockers. CIBINQO is not approved for use in RA patients.
Avoid CIBINQO in patients that may be at increased risk of thrombosis. If symptoms of thrombosis occur, discontinue CIBINQO and treat patients appropriately.
CONTRAINDICATION
CIBINQO is contraindicated in patients taking antiplatelet therapies, except for low-dose aspirin (≤ 81 mg daily), during the first 3 months of treatment.
LABORATORY ABNORMALITIES
Hematologic Abnormalities: Treatment with CIBINQO was associated with an increased incidence of thrombocytopenia and lymphopenia.
Prior to CIBINQO initiation, perform a complete blood count (CBC). CBC evaluations are recommended at 4 weeks after initiation and 4 weeks after dose increase of CIBINQO. Discontinuation of CIBINQO therapy is required for certain laboratory abnormalities.
Lipid Elevations: Dose-dependent increase in blood lipid parameters were reported in patients treated with CIBINQO. Lipid parameters should be assessed approximately 4 weeks following initiation of CIBINQO therapy, and thereafter patients should be managed according to clinical guidelines for hyperlipidemia. The effect of these lipid parameter elevations on cardiovascular morbidity and mortality has not been determined.
IMMUNIZATIONS
Prior to initiating CIBINQO, complete all age-appropriate vaccinations as recommended by current immunization guidelines, including prophylactic herpes zoster vaccinations. Avoid vaccination with live vaccines immediately prior to, during, and immediately after CIBINQO therapy.
RENAL IMPAIRMENT
Avoid use in patients with severe renal impairment or end stage renal disease, including those on renal replacement therapy.
HEPATIC IMPAIRMENT
Avoid use in patients with severe hepatic impairment.
ADVERSE REACTIONS
Most common adverse reactions (≥ 1%) in subjects receiving 100 mg and 200 mg include: nasopharyngitis, nausea, headache, herpes simplex, increased blood creatine phosphokinase, dizziness, urinary tract infection, fatigue, acne, vomiting, oropharyngeal pain, influenza, gastroenteritis. Most common adverse reactions (≥ 1%) in subjects receiving either 100 mg or 200 mg also include: impetigo, hypertension, contact dermatitis, upper abdominal pain, abdominal discomfort, herpes zoster, and thrombocytopenia.
Inform patients that retinal detachment has been reported in CIBINQO clinical trials. Advise patients to immediately inform their healthcare provider if they develop any sudden changes in vision.
DRUG INTERACTIONS
Monitor appropriately or dose titrate P-gp substrate where small concentration changes may lead to serious or life-threatening toxicities when coadministered with CIBINQO. See Prescribing Information for clinically relevant drug interactions.
USE IN PREGNANCY
Available data from pregnancies reported in clinical trials with CIBINQO are not sufficient to establish a drug-associated risk for major birth defects, miscarriage, or other adverse maternal or fetal outcomes. Advise females of reproductive potential that CIBINQO may impair fertility.
There is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to CIBINQO during pregnancy. Pregnant women exposed to CIBINQO and health care providers are encouraged to call 1-877-311-3770 or visit CIBINQOPregnancyRegistry.com.
LACTATION
Advise women not to breastfeed during treatment with CIBINQO and for one day after the last dose.
INDICATION
CIBINQO is indicated for the treatment of adults and pediatric patients 12 years of age and older with refractory, moderate-to-severe atopic dermatitis whose disease is not adequately controlled with other systemic drug products, including biologics, or when use of those therapies is inadvisable. Limitations of Use: CIBINQO is not recommended for use in combination with other JAK inhibitors, biologic immunomodulators, or with other immunosuppressants.
Please see full Important Safety Information throughout and full Prescribing Information, including BOXED WARNING, and Medication Guide.
WARNING: SERIOUS INFECTIONS, MORTALITY, MALIGNANCY, MAJOR ADVERSE CARDIOVASCULAR EVENTS, and THROMBOSIS
Serious Infections
Patients treated with CIBINQO may be at increased risk for developing serious infections that may lead to hospitalization or death; The most frequent serious infections reported with CIBINQO were herpes simplex, herpes zoster, and pneumonia. If a serious or opportunistic infection develops, discontinue CIBINQO and control the infection. Reported infections from Janus kinase (JAK) inhibitors used to treat inflammatory conditions:
• Active tuberculosis, which may present with pulmonary or extrapulmonary disease. Test for latent TB before and during therapy; treat latent TB prior to use. Monitor all patients for active TB during treatment, even patients with initial negative, latent TB test.
• Invasive fungal infections, including cryptococcosis and pneumocystosis. Patients with invasive fungal infections may present with disseminated, rather than localized, disease.
• Bacterial, viral, including herpes zoster, and other infections due to opportunistic pathogens. Avoid use of CIBINQO in patients with an active, serious infection including localized infections. The risks and benefits of treatment with CIBINQO should be carefully considered prior to initiating therapy in patients with chronic or recurrent infections.
Patients should be closely monitored for the development of signs and symptoms of infection during and after treatment with CIBINQO, including the possible development of tuberculosis in patients who tested negative for latent tuberculosis infection prior to initiating therapy.
Mortality
In a large, randomized, postmarketing safety study in rheumatoid arthritis (RA) patients 50 years of age and older with at least one cardiovascular risk factor comparing another JAK inhibitor to TNF blocker treatment, a higher rate of all-cause mortality, including sudden cardiovascular death, was observed with the JAK inhibitor. CIBINQO is not approved for use in RA patients.
Malignancies
Malignancies were reported in patients treated with CIBINQO. Lymphoma and other malignancies have been observed in patients receiving JAK inhibitors used to treat inflammatory conditions. In RA patients treated with another JAK inhibitor, a higher rate of malignancies (excluding non-melanoma skin cancer (NMSC)) was observed when compared with TNF blockers. Patients who are current or past smokers are at additional increased risk.
Major Adverse Cardiovascular Events
Major adverse cardiovascular events were reported in patients treated with CIBINQO. In RA patients 50 years of age and older with at least one cardiovascular risk factor treated with another JAK inhibitor, a higher rate of major adverse cardiovascular events (MACE) (defined as cardiovascular death, myocardial infarction, and stroke), was observed when compared with TNF blockers. Patients who are current or past smokers are at additional increased risk. Discontinue CIBINQO in patients that have experienced a myocardial infarction or stroke.
Thrombosis
Deep venous thrombosis (DVT) and pulmonary embolism (PE) have been reported in patients treated with CIBINQO. Thrombosis, including PE, DVT, and arterial thrombosis have been reported in patients receiving JAK inhibitors used to treat inflammatory conditions. Many of these adverse reactions were serious and some resulted in death. In RA patients 50 years of age and older with at least one cardiovascular risk factor treated with another JAK inhibitor, a higher rate of thrombosis was observed when compared with TNF blockers. Avoid CIBINQO in patients at risk. If symptoms of thrombosis occur, discontinue CIBINQO and treat appropriately.
INDICATIONS AND USAGE
CIBINQO is indicated for the treatment of adults and pediatric patients 12 years of age and older with refractory, moderate-to-severe atopic dermatitis whose disease is not adequately controlled with other systemic drug products, including biologics, or when use of those therapies is inadvisable.
Limitations of Use CIBINQO is not recommended for use in combination with other JAK inhibitors, biologic immunomodulators, or with other immunosuppressants.
DOSAGE AND ADMINISTRATION
Recommended Testing, Evaluations, and Procedures Prior to Treatment Initiation
Perform the following tests and evaluations prior to CIBINQO initiation:
• Tuberculosis (TB) infection evaluation – CIBINQO initiation is not recommended in patients with active TB. For patients with latent TB or those with a negative latent TB test who are at high risk for TB, start preventive therapy for latent TB prior to initiation of CIBINQO
• Viral hepatitis screening in accordance with clinical guidelines – CIBINQO initiation is not recommended in patients with active hepatitis B or hepatitis C
• A complete blood count (CBC) – CIBINQO initiation is not recommended in patients with a platelet count <150,000/mm3, an absolute lymphocyte count <500/mm3, an absolute neutrophil count <1,000/mm3, or a hemoglobin value <8 g/dL
Complete any necessary immunizations, including herpes zoster vaccinations, in agreement with current immunization guidelines prior to CIBINQO initiation.
Recommended Dosage
The recommended dosage of CIBINQO is 100 mg orally once daily. If an adequate response is not achieved with CIBINQO 100 mg orally daily after 12 weeks, consider increasing dosage to 200 mg orally once daily. Discontinue therapy if inadequate response is seen after dosage increase to 200 mg once daily.
CIBINQO can be used with or without topical corticosteroids. If a dose is missed, administer the dose as soon as possible unless it is less than 12 hours before the next dose, in which case skip the missed dose. Thereafter, resume dosing at the regular scheduled time.
Recommended Dosage in Patients with Renal Impairment
Renal Impairment
CIBINQO dosage recommendation in patients with mild renal impairment (60-89 mL/minute) is 100 mg once daily. For patients with moderate renal impairment (30-59 mL/ minute), the recommended dosage is 50 mg once daily.
CIBINQO is not recommended for patients with severe or End-Stage Renal Disease (ESRD). Severe renal impairment and End-Stage Renal Disease include patients on renal replacement therapy.
In subjects with mild and moderate renal impairment, if an adequate response is not achieved after 12 weeks, dose of CIBINQO can be doubled.
CIBINQO is not recommended for patients with severe renal impairment or ESRD.
Recommended Dosage in CYP2C19 Poor Metabolizers
In patients who are known or suspected to be CYP2C19 poor metabolizers, the recommended dosage of CIBINQO is 50 mg once daily. If an adequate response is not achieved with CIBINQO 50 mg orally daily after 12 weeks, consider increasing dosage to 100 mg orally once daily. Discontinue therapy if inadequate response is seen after dosage increase to 100 mg once daily.
Dosage Modifications due to Strong Inhibitors
In patients taking strong inhibitors of cytochrome P450 (CYP) 2C19 reduce the dosage to 50 mg once daily. If an adequate response is not achieved with CIBINQO 50 mg orally daily after 12 weeks, consider increasing dosage to 100 mg orally once daily. Discontinue therapy if inadequate response is seen after dosage increase to 100 mg once daily.
Treatment Discontinuation due to Serious Infections or Hematologic Adverse Reactions
Serious or Opportunistic Infections
If a patient develops a serious or opportunistic infection, discontinue CIBINQO and control the infection. The risks and benefits of treatment with CIBINQO should be carefully considered prior to reinitiating therapy with CIBINQO.
Hematologic Abnormalities
• Discontinue CIBINQO if platelet count <50,000/mm3 and
follow with CBC until >100,000/mm3
• Treatment should be temporarily discontinued if ALC is less than 500 cells/mm3 and may be restarted once ALC return above this value
• Treatment should be temporarily discontinued if ANC is less than 1,000 cells/mm3 and may be restarted once ANC return above this value
• Treatment should be temporarily discontinued if Hb is less than 8 g/dL and may be restarted once Hb return above this value
CBC evaluations are recommended at baseline, 4 weeks after treatment initiation and 4 weeks after dosing increase of CIBINQO. Laboratory evaluations may be extended for patients on chronic CIBINQO therapy who develop hematologic abnormalities.
DOSAGE FORMS AND STRENGTHS
• 50 mg: Pink, oval, film-coated tablet debossed with “PFE” on one side and “ABR 50” on the other.
• 100 mg: Pink, round, film-coated tablet debossed with “PFE” on one side and “ABR 100” on the other.
• 200 mg: Pink, oval, film-coated tablet debossed with “PFE” on one side and “ABR 200” on the other.
CONTRAINDICATIONS
CIBINQO is contraindicated in patients taking antiplatelet therapies, except for low-dose aspirin (≤81 mg daily), during the first 3 months of treatment.
WARNINGS AND PRECAUTIONS
Serious Infections The most frequent serious infections reported in clinical studies with CIBINQO for atopic dermatitis were herpes simplex, herpes zoster, and pneumonia. Serious infections leading to hospitalization or death, including tuberculosis and bacterial, invasive fungal, viral, and other opportunistic infections, have occurred in patients receiving JAK inhibitors used to treat inflammatory conditions.
Avoid use of CIBINQO in patients with active, serious infection including localized infections.
Consider the risks and benefits of treatment prior to initiating CIBINQO in patients:
• with chronic or recurrent infection
• who have been exposed to tuberculosis
• with a history of a serious or an opportunistic infection
• who have resided or traveled in areas of endemic tuberculosis or endemic mycoses
• with underlying conditions that may predispose them to infection
Closely monitor patients for the development of signs and symptoms of infection during and after treatment with CIBINQO. If a patient develops a serious or opportunistic infection, discontinue CIBINQO. Initiate complete diagnostic testing and appropriate antimicrobial therapy. The risks and benefits of treatment with CIBINQO should be carefully considered prior to reinitiating therapy with CIBINQO.
Tuberculosis Evaluate and test patients for TB before starting CIBINQO therapy and consider yearly screening for patients in highly endemic areas for TB. CIBINQO is not recommended for use in patients with active TB. For patients with a new diagnosis of latent TB or prior untreated latent TB, or for patients with a negative test for latent TB but who are at high risk for TB infection, start preventive therapy for latent TB prior to initiation of CIBINQO. Monitor patients for the development of signs and symptoms of TB, including patients who were tested negative for latent TB infection prior to initiating therapy. Viral Reactivation Viral reactivation, including herpes virus reactivation (e.g., herpes zoster, herpes simplex), was reported in clinical studies with CIBINQO. If a patient develops herpes zoster, consider interrupting CIBINQO until the episode resolves.
Hepatitis B virus (HBV) reactivation has been reported in patients receiving JAK inhibitors. Perform viral hepatitis screening and monitoring for reactivation in accordance with clinical guidelines before starting therapy and during therapy with CIBINQO. CIBINQO is not recommended for use in patients with active hepatitis B or hepatitis C. Monitor patients with inactive HBV for expression of HBV DNA during therapy with CIBINQO. If HBV DNA is detected during therapy with CIBINQO, consult a liver specialist.
Mortality
In a large, randomized, postmarketing safety study of another JAK inhibitor in rheumatoid arthritis (RA) patients 50 years of age and older with at least one cardiovascular risk factor, a higher rate of all-cause mortality, including sudden cardiovascular death, was observed in patients
Mortality (continued)
treated with the JAK inhibitor compared with TNF blockers. CIBINQO is not approved for use in RA.
Consider the benefits and risks for the individual patient prior to initiating or continuing therapy with CIBINQO.
Malignancy and Lymphoproliferative Disorders
Malignancies, including non-melanoma skin cancer (NMSC), were observed in clinical studies with CIBINQO for atopic dermatitis.
Perform periodic skin examination for patients who are at increased risk for skin cancer. Exposure to sunlight and UV light should be limited by wearing protective clothing and using broad-spectrum sunscreen.
Malignancies, including lymphomas, have occurred in patients receiving JAK inhibitors used to treat inflammatory conditions. In a large, randomized, postmarketing safety study of another JAK inhibitor in RA patients, a higher rate of malignancies (excluding non-melanoma skin cancer (NMSC)) was observed in patients treated with the JAK inhibitor compared to those treated with TNF blockers. CIBINQO is not approved for use in RA. A higher rate of lymphomas was observed in patients treated with the JAK inhibitor compared to those treated with TNF blockers. A higher rate of lung cancers was observed in current or past smokers treated with the JAK inhibitor compared to those treated with TNF blockers. In this study, current or past smokers had an additional increased risk of overall malignancies.
Consider the benefits and risks for the individual patient prior to initiating or continuing therapy with CIBINQO, particularly in patients with a known malignancy (other than a successfully treated NMSC), patients who develop a malignancy when on treatment, and patients who are current or past smokers.
Major Adverse Cardiovascular Events
Major adverse cardiovascular events were reported in clinical studies of CIBINQO for atopic dermatitis.
In a large, randomized, postmarketing safety study of another JAK inhibitor in RA patients 50 years of age and older with at least one cardiovascular risk factor, a higher rate of major adverse cardiovascular events (MACE) defined as cardiovascular death, non-fatal myocardial infarction (MI), and non-fatal stroke was observed with the JAK inhibitor compared to those treated with TNF blockers. CIBINQO is not approved for use in RA. Patients who are current or past smokers are at additional increased risk.
Consider the benefits and risks for the individual patient prior to initiating or continuing therapy with CIBINQO, particularly in patients who are current or past smokers and patients with other cardiovascular risk factors. Patients should be informed about the symptoms of serious cardiovascular events and the steps to take if they occur. Discontinue CIBINQO in patients that have experienced a myocardial infarction or stroke.
Thrombosis
Deep venous thrombosis (DVT) and pulmonary embolism (PE) were observed in patients receiving CIBINQO in the clinical studies for atopic dermatitis.
Thrombosis, including DVT, PE, and arterial thrombosis have been reported in patients receiving JAK inhibitors used to treat inflammatory conditions. Many of these adverse reactions were serious and some resulted in death.
In a large, randomized, postmarketing safety study of another JAK inhibitor in RA patients 50 years of age and older with at least one cardiovascular risk factor, higher rates of overall thrombosis, DVT, and PE were observed compared to those treated with TNF blockers. CIBINQO is not approved for use in RA.
Avoid CIBINQO in patients that may be at increased risk of thrombosis. If symptoms of thrombosis occur, discontinue CIBINQO and evaluate and treat patients appropriately.
Laboratory Abnormalities
Hematologic Abnormalities Treatment with CIBINQO was associated with an increased incidence of thrombocytopenia and lymphopenia. Prior to CIBINQO initiation, perform a CBC. CBC evaluations are recommended at 4 weeks after initiation and 4 weeks after dose increase of CIBINQO.
Discontinuation of CIBINQO therapy is required for certain laboratory abnormalities.
Lipid Elevations Dose-dependent increase in blood lipid parameters were reported in patients treated with CIBINQO. Lipid parameters should be assessed approximately 4 weeks following initiation of CIBINQO therapy and thereafter patients should be managed according to clinical guidelines for hyperlipidemia. The effect of these lipid parameter
elevations on cardiovascular morbidity and mortality has not been determined.
Immunizations
Prior to initiating CIBINQO, complete all age-appropriate vaccinations as recommended by current immunization guidelines including prophylactic herpes zoster vaccinations. Avoid vaccination with live vaccines immediately prior to, during, and immediately after CIBINQO therapy.
ADVERSE REACTIONS
The following clinically significant adverse reactions are described elsewhere in the labeling:
• Serious Infections
• Mortality
• Malignancy and Lymphoproliferative Disorders
Clinical Trials Experience
• Major Adverse Cardiovascular Events
• Thrombosis
• Laboratory Abnormalities
Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.
The safety of CIBINQO was evaluated in four randomized, placebo-controlled clinical trials (2 monotherapy, 1 combination therapy with topical corticosteroid, and 1 dose-ranging) and one long-term extension trial in subjects with moderate to severe atopic dermatitis (AD). A total of 1623 subjects with moderate to severe atopic dermatitis were treated with CIBINQO in these clinical trials representing 1428 patient-years of exposure. There were 634 subjects with at least 1 year of exposure to CIBINQO.
In the placebo-controlled clinical trials, a total of 1198 subjects were exposed to CIBINQO with 608 subjects receiving CIBINQO 100 mg once daily and 590 subjects receiving CIBINQO 200 mg once daily for up to 16 weeks. The median age of subjects was 33.0 years, 124 subjects (8.1%) were 12 to less than 18 years old and 94 subjects (6.1%) were 65 years of age or older. The majority of subjects were White (68.7%) and male (53.9%).
Adverse reactions occurring at ≥1% in any of the treated groups and at a higher rate than in the placebo group are presented in the table below. A total of 61 (5.1%) subjects treated with CIBINQO were discontinued from the trials due to adverse reactions. The safety profile of CIBINQO in the monotherapy and the combination trial(s) were similar.
Adverse Reactions from Placebo-Controlled Trials
Reported in ≥1% of CIBINQO Treated Subjects with Moderate to Severe Atopic Dermatitis and at Higher Rate than Placebo for up to 16 Weeks
b Herpes simplex also includes oral herpes, ophthalmic herpes, herpes dermatitis, genital herpes.
Specific Adverse Reactions
Exposure adjusted incidence rates were adjusted by trial size for all the adverse reactions reported in this section.
Overall Infections In the placebo-controlled trials, for up to 16 weeks, overall infections were reported in 90 subjects (126.8 per 100 patient-years) treated with placebo, 211 subjects (168.8 per 100 patient-years) treated with CIBINQO 100 mg and 204 subjects (159.5 per 100 patient-years) treated with CIBINQO 200 mg. In all 5 clinical trials, including the long-term extension trial, overall infections were reported in 427 subjects (91.8 per 100 patient-years) treated with CIBINQO 100 mg and 394 subjects (103.2 per 100 patient-years) treated with CIBINQO 200 mg.
Serious Infections In the placebo-controlled trials, for up to 16 weeks, serious infections were reported in 2 subjects (2.6 per 100 patient-years) treated with placebo, 6 subjects (3.9 per 100 patient-years) treated with CIBINQO 100 mg, and 2 subjects (1.3 per 100 patient-years) treated with CIBINQO 200 mg. In all 5 clinical trials, including the long-term extension trial, serious infections were reported in 18 subjects (2.3 per 100 patient-years) treated with CIBINQO 100 mg and 16 subjects (2.3 per 100 patient-years) treated with CIBINQO 200 mg. The most commonly reported serious infections were herpes simplex, herpes zoster, and pneumonia.
Herpes Zoster In the placebo-controlled trials, for up to 16 weeks, opportunistic infections were generally cases of multidermatomal cutaneous herpes zoster. Herpes zoster was reported in 0 subjects treated with placebo, 3 subjects (1.9 per 100 patient-years) treated with CIBINQO 100 mg and 8 subjects (5.1 per 100 patient-years) treated with CIBINQO 200 mg. In all 5 clinical trials, including the long-term extension trial, herpes zoster was reported in 16 subjects (2.0 per 100 patient-years) treated with CIBINQO 100 mg and 35 subjects (5.2 per 100 patient-years) treated with CIBINQO 200 mg.
Malignancy In the placebo-controlled trials, for up to 16 weeks, no malignancy was reported in subjects treated with placebo or CIBINQO 100 mg and in 1 patient (0.65 per 100 patient-years) treated with CIBINQO 200 mg. In all 5 clinical trials, including the long-term extension trial, malignancy was reported in 4 subjects (0.5 per 100 patient-years) treated with CIBINQO 100 mg and 2 subjects (0.3 per 100 patient-years) treated with CIBINQO 200 mg.
Thrombosis In all clinical trials, including the long-term extension trial, pulmonary embolism was reported in 3 subjects (0.4 per 100 patient-years), who were treated with CIBINQO 200 mg. Deep vein thrombosis was reported in 2 subjects (0.3 per 100 patient-years) who were treated with CIBINQO 200 mg. No thrombosis occurred in subjects treated with CIBINQO 100 mg.
Major Adverse Cardiovascular Events In the placebocontrolled trials, for up to 16 weeks, major adverse cardiovascular event (MACE) was reported in 1 subject (0.6 per 100 patient-years) treated with CIBINQO 100 mg. In all 5 clinical trials, including the long-term extension trial, MACE was reported in 1 patient (0.1 per 100 patient-years) treated with CIBINQO 100 mg and 2 subjects (0.3 per 100 patient-years) treated with CIBINQO 200 mg.
Thrombocytopenia In the placebo-controlled trials, for up to 16 weeks, treatment with CIBINQO was associated with a dose-related decrease in platelet count. Maximum effects on platelets were observed within 4 weeks, after which the platelet count returned towards baseline despite continued therapy. In all 5 clinical trials, including the long-term extension trial 6 subjects (0.9 per 100 patient-years) treated with CIBINQO 200 mg had adverse reactions of thrombocytopenia, no subjects treated with CIBINQO 100 mg had an adverse reaction of thrombocytopenia.
Lymphopenia In the placebo-controlled trials, for up to 16 weeks, confirmed ALC <500/mm3 occurred in 2 subjects (1.2 per 100 patient-years) treated with CIBINQO 200 mg and 0 subjects treated with CIBINQO 100 mg or placebo. Both cases occurred in the first 4 weeks of exposure.
Lipid Elevations In the placebo-controlled trials, for up to 16 weeks, there was a dose-related percent increase in low-density lipoprotein cholesterol (LDL-c), total cholesterol, and high-density lipoprotein cholesterol (HDL-c) relative to placebo at Week 4 which remained elevated through the final visit in the treatment period. Adverse reactions related to hyperlipidemia occurred in 1 subject (0.6 per 100 patient-years) exposed to CIBINQO 100 mg, 3 subjects (2.0 per 100 patient-years) exposed to CIBINQO 200 mg.
Retinal Detachment In the placebo-controlled trials, for up to 16 weeks, retinal detachment occurred in 1 subject (0.6 per 100 patient-years) treated with CIBINQO 100 mg. In all 5 clinical trials, including the long-term extension trial, retinal detachment occurred in 2 subjects (0.3 per 100 patient-years) treated with CIBINQO 100 mg.
Specific Adverse Reactions (continued)
Creatine Phosphokinase Elevations (CPK) In the placebocontrolled trials, for up to 16 weeks, events of blood CPK increased were reported in 6 subjects (7.5 per 100 patient-years) treated with placebo, 11 subjects (6.9 per 100 patient-years) treated with 100 mg of CIBINQO and 19 subjects (12.3 per 100 patient-years) treated with 200 mg of CIBINQO. Most elevations were transient, there were no reported adverse reactions of rhabdomyolysis.
Adolescent Subjects (12 to less than 18 years of age) The safety of CIBINQO was assessed in a trial of 284 subjects 12 to less than 18 years of age with moderate-to-severe atopic dermatitis (Trial-AD-4). The safety profile of CIBINQO in these subjects, assessed through the initial treatment period of 12 weeks and the long-term period (213 with at least 52 weeks of abrocitinib exposure), was similar to the safety profile from trials in adults with atopic dermatitis.
DRUG INTERACTIONS
Effects of Other Drugs on CIBINQO
The table below includes drugs with clinically significant drug interactions affecting CIBINQO.
Clinically Significant Drug Interactions Affecting CIBINQO
Strong CYP2C19 Inhibitors
Clinical Impact Coadministration of CIBINQO with strong CYP2C19 inhibitors increases the combined exposure of abrocitinib and its two active metabolites, M1 and M2 which may increase the adverse reactions of CIBINQO.
Intervention Dosage reduction of CIBINQO is recommended when coadministered with strong CYP2C19 inhibitors.
Moderate to Strong Inhibitors of both CYP2C19 and CYP2C9
Clinical Impact Coadministration of CIBINQO with drugs that are moderate to strong inhibitors of both CYP2C19 and CYP2C9 increases the exposure of abrocitinib and its two active metabolites, M1 and M2 which may increase the adverse reactions of CIBINQO.
Intervention Avoid concomitant use of CIBINQO with drugs that are moderate to strong inhibitors of both CYP2C19 and CYP2C9.
Strong CYP2C19 or CYP2C9 Inducers
Clinical Impact
Coadministration of CIBINQO with strong CYP2C19 or CYP2C9 inducers decreases the combined exposure of abrocitinib and its two active metabolites, M1 and M2, which may result in loss of or reduced clinical response.
Intervention Avoid concomitant use of CIBINQO with strong CYP2C19 or CYP2C9 inducers.
Effects of CIBINQO on Other Drugs
The table below includes clinically significant drug interactions affecting other drugs.
Clinically Significant Interactions Affecting Other Drugs
P-gp Substrate Where Small Concentration Changes May Lead to Serious or Life-threatening Toxicities
Clinical Impact Coadministration of CIBINQO with P-gp substrate increases plasma concentrations of P-gp substrates and may result in potential adverse reactions of the P-gp substrate where small concentration changes may lead to serious or life-threatening toxicities (e.g., digoxin).
Intervention Monitor appropriately or dose titrate P-gp substrate where small concentration changes may lead to serious or life-threatening toxicities when coadministered with CIBINQO.
Antiplatelet Therapy Drugs
Clinical Impact
USE IN SPECIFIC POPULATIONS
Pregnancy
Pregnancy Exposure Registry There is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to CIBINQO during pregnancy. Pregnant women exposed to CIBINQO and health care providers are encouraged to call 1-877-311-3770 or visit CIBINQOPregnancyRegistry.com.
Risk Summary Available data from pregnancies reported in clinical trials with CIBINQO are not sufficient to establish a drug-associated risk for major birth defects, miscarriage, or other adverse maternal or fetal outcomes. In animal reproduction studies, oral administration of abrocitinib to pregnant rats and rabbits during organogenesis at exposure 11 or 4 times the maximum recommended human dose (MRHD) based on AUC comparison, respectively, resulted in maternal dystocia and skeletal variations in rats and no adverse effects in rabbits (see Animal Data).
The background risks of major birth defects and miscarriage for the indicated population are unknown. All pregnancies carry some risk of birth defects, loss, or other adverse outcomes. The background risks in the U.S. general population of major birth defects and miscarriages are 2-4% and 15-20% of clinically recognized pregnancies, respectively.
Animal Data In an embryofetal development study, abrocitinib was administered orally to pregnant rats at doses of 10, 30, or 60 mg/kg/day during the period of organogenesis. No fetal malformations were observed. Abrocitinib increased the incidence of skeletal variations of short 13th ribs at 30 mg/kg/ day (11 times the MRHD based on AUC comparison). Increased embryofetal lethality and additional skeletal variations (cervical arches with reduced ventral processes, thickened ribs, and unossified metatarsals) were noted at 60 mg/kg/day (17 times the MRHD based on AUC comparison).
In an embryofetal development study, abrocitinib was administered orally to pregnant rabbits at doses of 10, 30, or 75 mg/kg/day during the period of organogenesis. No abrocitinib-related maternal or developmental toxicity was noted at doses up to 75 mg/kg/day (4 times the MRHD based on AUC comparison).
In a prenatal and postnatal development study, abrocitinib was administered orally to pregnant rats at doses of 10, 30, and 60 mg/kg/day beginning on gestation day 6 and continuing through lactation day 20. Dystocia with prolonged parturition and reduced offspring body weights were noted at 30 mg/kg/ day (11 times the MRHD based on AUC comparison). Postnatal survival was markedly decreased at 60 mg/kg/day (17 times the MRHD based on AUC comparison). No maternal toxicity was observed at 10 mg/kg/day (2.4 times the MRHD based on AUC comparison). No abrocitinib-related effects on postnatal developmental, neurobehavioral, or reproductive performance of offspring was noted at doses up to 30 mg/kg/ day (11 times the MRHD based on AUC comparison).
Lactation
Risk Summary There are no data on the presence of abrocitinib in human milk, the effects on the breast-fed infant, or the effects on milk production. Abrocitinib was secreted in milk of lactating rats (see Animal Data). When a drug is present in animal milk, it is likely that the drug will be present in human milk. Because of the serious adverse findings in adults, including risks of serious infections, malignancy, and thrombosis, advise women not to breastfeed during treatment with CIBINQO and for one day after the last dose (approximately 5-6 elimination half-lives).
Animal Data Lactating female rats were orally administered a single dose of 10 mg/kg abrocitinib on lactation day 12. Abrocitinib AUC was approximately 5 times greater in milk than in plasma.
Females and Males of Reproductive Potential Infertility Females Based on the findings in rats, oral administration of CIBINQO may impair female fertility. Impaired fertility in female rats was reversible 1 month after cessation of abrocitinib oral administration.
Pediatric Use
The safety and effectiveness of CIBINQO have not been established in pediatric patients below 12 years of age.
Juvenile Animal Toxicity Data In a juvenile animal toxicity study, abrocitinib was administered orally to juvenile rats at doses of 5, 25, and 75 mg/kg/day beginning on postnatal day 10 (approximately equivalent to a human infant) and continuing through postnatal day 63 (approximately equivalent to an adolescent). Abrocitinib caused a reversible, dose-related decrease in the primary spongiosa in the metaphysis of the proximal tibia and distal femur. Abrocitinib produced adverse effects on bone development at all dose levels. Abrocitinib caused irreversible dose-related small or misshapen femoral heads at doses ≥5 mg/kg/day (0.8 times the MRHD based on AUC comparison).
Abrocitinib also irreversibly decreased femur size and caused paw malrotation and limb impairment at doses ≥25 mg/kg/day (7.2 times the MRHD based on AUC comparison). At 75 mg/kg/ day (27 times the MRHD based on AUC comparison), paw fractures generally corresponded to limb impairment, a fractured tibia was noted in a single female. Irreversible bone findings have not been observed in older animals.
Geriatric Use
A total of 145 (4.6%) patients 65 years of age and older, while 25 (0.8%) were 75 years of age and older, were enrolled in CIBINQO clinical trials. Clinical trials of CIBINQO did not include sufficient numbers of patients 65 years of age and older to determine whether they respond differently from younger adult patients.
A higher proportion of patients 65 years of age and older discontinued from clinical trials compared to younger patients. Among all patients exposed to CIBINQO, including the long-term extension trial, confirmed ALC <500/mm3 occurred only in patients 65 years of age and older. A higher proportion of patients 65 years of age and older had platelet counts <75,000/ mm3. The incidence rate of herpes zoster in patients 65 years of age and older treated with CIBINQO (7.40 per 100 patient-years) was higher than that of patients 18 to less than 65 years of age (3.44 per 100 patient-years).
Renal Impairment
In patients with severe (eGFR <30 mL/min) and moderate (eGFR 30-59 mL/min) renal impairment, the combined exposure (AUCinf,u) of abrocitinib and its two active metabolites, M1 and M2, is increased compared to patients with normal renal function (eGFR ≥90 mL/min). This may increase the risk of adverse reactions such as infections.
CIBINQO is not recommended for use in patients with severe renal impairment and ESRD including those on renal replacement therapy. A dosage reduction in patient with moderate renal impairment is recommended. No dosage adjustment is required in patients with mild renal impairment (eGFR 60-89 mL/min).
CIBINQO has not been studied in patients on renal replacement therapy. In Phase 3 clinical trials, CIBINQO was not evaluated in patients with atopic dermatitis with baseline creatinine clearance values less than 40 mL/min.
Hepatic Impairment
Avoid use of CIBINQO in patients with severe (Child Pugh C) hepatic impairment.
Dosage adjustment is not required in patients with mild (Child Pugh A) or moderate (Child Pugh B) hepatic impairment based on similar combined exposure (AUCinf,u) of abrocitinib and its two active metabolites, M1 and M2 compared to patients with normal hepatic function. In clinical trials, CIBINQO was not evaluated in patients with severe (Child Pugh C) hepatic impairment.
CYP2C19 Poor Metabolizers
In patients who are CYP2C19 poor metabolizers, the AUC of abrocitinib is increased compared to CYP2C19 normal metabolizers due to reduced metabolic clearance. Dosage reduction of CIBINQO is recommended in patients who are known or suspected to be CYP2C19 poor metabolizers based on genotype or previous history/experience with other CYP2C19 substrates.
OVERDOSAGE
Coadministration of CIBINQO with antiplatelet therapy drugs may increase the risk of bleeding with thrombocytopenia.
Intervention Antiplatelet drugs, except for low-dose aspirin (≤81 mg daily), during the first 3 months of treatment are contraindicated with CIBINQO.
The safety and effectiveness of CIBINQO in pediatric patients 12 years of age and older weighing 25 kg or more with atopic dermatitis has been established. In trials Trial-AD-1 and Trial-AD-2, 124 adolescent subjects 12 to less than 18 years old with moderate-to-severe atopic dermatitis were enrolled and randomized to receive either CIBINQO 100 mg (N=51), 200 mg (N=48), or matching placebo (N=25) in monotherapy. Additional 284 adolescent subjects 12 to less than 18 years of age with moderate-to-severe atopic dermatitis, were enrolled and randomized to receive either CIBINQO 100 mg (N=95) or 200 mg (N=94) or matching placebo (N=95) in combination with topical corticosteroids in Trial-AD-4. Efficacy and adverse reaction profile were consistent between the pediatric patients and adults.
There is no experience regarding human overdosage with CIBINQO. There is no specific antidote for overdose with CIBINQO. In case of an overdose, call Poison Control Center at 1-800-222-1222 for latest recommendations.
Rx only
This brief summary is based on CIBINQO™ (abrocitinib) Prescribing Information LAB-1424-2.0.
Issued: February 2023.
The product’s label may have been updated. For full Prescribing Information, visit CIBINQOPI.com.
See CIBINQO full Prescribing Information at CIBINQOPI.com.
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ISSUE 11 | WINTER 2024
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72 Game On Crack! Dot! Bam! If you're curious about Mahjong, here's where to start.
With the Commercial Bridge Program offered exclusively through our Enhanced Services Specialty Pharmacy (SP) Network*, you can be confident that your eligible patients will get access to OPZELURA.†
To qualify, a patient must: Getting started:
• Have commercial prescription drug insurance
• Have been prescribed OPZELURA according to the prescribing information
• Have tried and failed a topical medication
• Have been denied coverage for OPZELURA by their payer through a prior authorization (PA)
1. Send your prescription to a participating pharmacy (see QR code)
2. Provide the SP information required for a PA
3. Submit the PA to the payer per SP’s direction
4. Eligible patients can receive OPZELURA for $35 per tube after payer responds with a PA denial
*OPZELURA is widely available at pharmacies. Other offers and services may apply.
†Terms and conditions apply. Terms of this program may change at any time.
Get patients to the other side.
Scan the QR code or visit opzeluraontrachcp.com to find a participating Specialty Pharmacy.
ENHANCED SERVICES
SPECIALTY PHARMACY NETWORK
- Northeast 1750626453
Tarbell Rd Syracuse, NY 13206 888-843-2040888-842-3977
Noble Health Services - Southeast 1417469388 2506 Lakeland Dr, #201 Jackson, MS 39232
866-420-4041601-420-4040
Nationwide, Puerto Rico
Nationwide, Puerto Rico Polaris Specialty Rx1053486795 410 Cloverleaf Dr Baldwin Park, CA 91706
626-626-9400800-540-3400Nationwide Professional Arts Specialty Pharmacy 1194890731 128 Curran Ln Lafayette, LA 70506 888-237-4737855-724-6797Nationwide Quality Drug Clinical Care
18 Technology Dr, #104 Irvine, CA 92618 833-210-5964833-210-5968
OPZELURA is indicated for the topical short-term and non-continuous chronic treatment of mild to moderate atopic dermatitis in non-immunocompromised adult and pediatric patients 12 years of age and older whose disease is not adequately controlled with topical prescription therapies or when those therapies are not advisable.
OPZELURA is indicated for the topical treatment of nonsegmental vitiligo in adult and pediatric patients 12 years of age and older.
Limitations of Use: Use of OPZELURA in combination with therapeutic biologics, other JAK inhibitors, or potent immunosuppressants such as azathioprine or cyclosporine is not recommended.
IMPORTANT SAFETY INFORMATION
SERIOUS INFECTIONS
Patients treated with oral Janus kinase inhibitors for inflammatory conditions are at risk for developing serious infections that may lead to hospitalization or death. Reported infections include:
• Ac tive tuberculosis, which may present with pulmonary or extrapulmonary disease.
• Invasive fungal infections, including cryptococcosis and pneumocystosis.
• Bacterial, viral, including herpes zoster, and other infections due to opportunistic pathogens.
Avoid use of OPZELURA in patients with an active, serious infection, including localized infections. If a serious infection develops, interrupt OPZELURA until the infection is controlled. Carefully consider the benefits and risks of treatment prior to initiating OPZELURA in patients with chronic or recurrent infection. Closely monitor patients for the development of signs and symptoms of infection during and after treatment with OPZELURA.
Serious lower respiratory tract infections were reported in the clinical development program with topical ruxolitinib.
No cases of active tuberculosis (TB) were reported in clinical trials with OPZELURA. Cases of active TB were reported in clinical trials of oral Janus kinase inhibitors used to treat inflammatory conditions. Consider evaluating patients for latent and active TB infection prior to administration of OPZELURA. During OPZELURA use, monitor patients for the development of signs and symptoms of TB.
Viral reactivation, including cases of herpes virus reactivation (e.g., herpes zoster), were reported in clinical trials with Janus kinase inhibitors used to treat inflammatory conditions including OPZELURA. If a patient develops herpes zoster, consider interrupting OPZELURA treatment until the episode resolves.
Hepatitis B viral load (HBV-DNA titer) increases, with or without associated elevations in alanine aminotransferase and aspartate aminotransferase, have been reported in patients with chronic HBV infections taking oral ruxolitinib. OPZELURA initiation is not recommended in patients with active hepatitis B or hepatitis C. MORTALITY
In a large, randomized, postmarketing safety study in rheumatoid arthritis (RA) patients 50 years of age and older with at least one cardiovascular risk factor comparing an oral JAK inhibitor to tumor necrosis factor (TNF) blocker treatment, a higher rate of all-cause mortality, including sudden cardiovascular death, was observed with the JAK inhibitor. Consider the benefits and risks for the individual patient prior to initiating or continuing therapy with OPZELURA.
MALIGNANCIES
Malignancies were reported in patients treated with OPZELURA. Lymphoma and other malignancies have been observed in patients receiving JAK inhibitors used to treat inflammatory conditions. In RA patients treated with an oral JAK inhibitor, a higher rate of malignancies (excluding non-melanoma skin cancer (NMSC)) was observed when compared with TNF blockers. Patients who are current or past smokers are at additional increased risk.
Consider the benefits and risks for the individual patient prior to initiating or continuing therapy with OPZELURA, particularly in patients with a known malignancy (other than successfully treated non-melanoma skin cancers), patients who develop a malignancy when on treatment, and patients who are current or past smokers.
Non-melanoma skin cancers, including basal cell and squamous cell carcinoma, have occurred in patients treated with OPZELURA. Perform periodic skin examinations during OPZELURA treatment and following treatment as appropriate. Exposure to sunlight and UV light should be limited by wearing protective clothing and using broad-spectrum sunscreen.
MAJOR ADVERSE CARDIOVASCULAR EVENTS (MACE)
In RA patients 50 years of age and older with at least one cardiovascular risk factor treated with an oral JAK inhibitor, a higher rate of major adverse cardiovascular events (MACE) (defined as cardiovascular death, myocardial infarction, and stroke), was observed when compared with TNF blockers. Patients who are current or past smokers are at additional increased risk. Discontinue OPZELURA in patients who have experienced a myocardial infarction or stroke.
Consider the benefits and risks for the individual patient prior to initiating or continuing therapy with OPZELURA, particularly in patients who are current or past smokers and patients with other cardiovascular risk factors. Patients should be informed about the symptoms of serious cardiovascular events and the steps to take if they occur. Discontinue OPZELURA in patients that have experienced a myocardial infarction or stroke.
THROMBOSIS
Thromboembolic events were observed in trials with OPZELURA. Thrombosis, including pulmonary embolism (PE), deep venous thrombosis (DVT), and arterial thrombosis have been reported in patients receiving JAK inhibitors used to treat inflammatory conditions. Many of these adverse reactions were serious and some resulted in death. In RA patients 50 years of age and older with at least one cardiovascular risk factor treated with an oral JAK inhibitor, a higher rate of thrombosis was observed when compared with TNF blockers. Avoid OPZELURA in patients at risk. If symptoms of thrombosis occur, discontinue OPZELURA and treat appropriately.
Thrombocytopenia, Anemia, and Neutropenia
Thrombocytopenia, anemia, and neutropenia were reported in the clinical trials with OPZELURA. Consider the benefits and risks for individual patients who have a known history of these events prior to initiating therapy with OPZELURA. Perform CBC monitoring as clinically indicated. If signs and/or symptoms of clinically significant thrombocytopenia, anemia, and neutropenia occur, patients should discontinue OPZELURA.
Lipid Elevations
Treatment with oral ruxolitinib has been associated with increases in lipid parameters including total cholesterol, low-density lipoprotein (LDL) cholesterol, and triglycerides. Adverse Reactions
In atopic dermatitis, the most common adverse reactions (≥1%) are nasopharyngitis (3%), diarrhea (1%), bronchitis (1%), ear infection (1%), eosinophil count increased (1%), urticaria (1%), folliculitis (1%), tonsillitis (1%), and rhinorrhea (1%).
In nonsegmental vitiligo, the most common adverse reactions (incidence ≥1%) are application site acne (6%), application site pruritus (5%), nasopharyngitis (4%), headache (4%), urinary tract infection (2%), application site erythema (2%), and pyrexia (1%).
Pregnancy
There is a pregnancy registry that monitors pregnancy outcomes in pregnant persons exposed to OPZELURA during pregnancy. Pregnant persons exposed to OPZELURA and healthcare providers should report OPZELURA exposure by calling 1-855-463-3463.
Lactation
Advise women not to breastfeed during treatment with OPZELURA and for approximately four weeks after the last dose (approximately 5-6 elimination half-lives). Please see Brief Summary of Full Prescribing Information, including Boxed Warning, on the following pages.
OPZELURA® (ruxolitinib) cream, for topical use
Brief Summary of FULL PRESCRIBING INFORMATION
INDICATIONS AND USAGE: OPZELURA is indicated for the topical short-term and non-continuous chronic treatment of mild to moderate atopic dermatitis in non-immunocompromised adult and pediatric patients 12 years of age and older whose disease is not adequately controlled with topical prescription therapies or when those therapies are not advisable and for the topical treatment of nonsegmental vitiligo in adult and pediatric patients 12 years of age and older.
Limitations of Use: Use of OPZELURA in combination with therapeutic biologics, other JAK inhibitors, or potent immunosuppressants such as azathioprine or cyclosporine is not recommended.
WARNING: SERIOUS INFECTIONS, MORTALITY, MALIGNANCY, MAJOR ADVERSE CARDIOVASCULAR EVENTS, AND THROMBOSIS
SERIOUS INFECTIONS
Patients treated with oral Janus kinase inhibitors for inflammatory conditions are at risk for developing serious infections that may lead to hospitalization or death [see Warnings and Precautions and Adverse Reactions]
Reported infections include:
• Active tuberculosis, which may present with pulmonary or extrapulmonary disease.
• Invasive fungal infections, including cryptococcosis, and pneumocystosis.
• Bacterial, viral, including herpes zoster, and other infections due to opportunistic pathogens.
Avoid use of OPZELURA in patients with an active, serious infection, including localized infections. If a serious infection develops, interrupt OPZELURA until the infection is controlled.
The risks and benefits of treatment with OPZELURA should be carefully considered prior to initiating therapy in patients with chronic or recurrent infection.
Patients should be closely monitored for the development of signs and symptoms of infection during and after treatment with OPZELURA [see Warnings and Precautions]
MORTALITY
In a large, randomized, postmarketing safety study in rheumatoid arthritis (RA) patients 50 years of age and older with at least one cardiovascular risk factor comparing an oral JAK inhibitor to tumor necrosis factor (TNF) blocker treatment, a higher rate of all-cause mortality, including sudden cardiovascular death, was observed with the JAK inhibitor [see Warnings and Precautions]
MALIGNANCIES
Malignancies were reported in patients treated with OPZELURA. Lymphoma and other malignancies have been observed in patients receiving JAK inhibitors used to treat inflammatory conditions. In RA patients treated with an oral JAK inhibitor, a higher rate of malignancies (excluding non-melanoma skin cancer (NMSC)) was observed when compared with TNF blockers. Patients who are current or past smokers are at additional increased risk [see Warnings and Precautions]
MAJOR ADVERSE CARDIOVASCULAR EVENTS (MACE)
In RA patients 50 years of age and older with at least one cardiovascular risk factor treated with an oral JAK inhibitor, a higher rate of major adverse cardiovascular events (MACE) (defined as cardiovascular death, myocardial infarction, and stroke), was observed when compared with TNF blockers. Patients who are current or past smokers are at additional increased risk. Discontinue OPZELURA in patients who have experienced a myocardial infarction or stroke [see Warnings and Precautions]
THROMBOSIS
Thromboembolic events were observed in trials with OPZELURA. Thrombosis, including pulmonary embolism (PE), deep venous thrombosis (DVT), and arterial thrombosis have been reported in patients receiving JAK inhibitors used to treat inflammatory conditions. Many of these adverse reactions were serious and some resulted in death. In RA patients 50 years of age and older with at least one cardiovascular risk factor treated with an oral JAK inhibitor, a higher rate of thrombosis was observed when compared with TNF blockers. Avoid OPZELURA in patients at risk. If symptoms of thrombosis occur, discontinue OPZELURA and treat appropriately [see Warnings and Precautions].
WARNINGS AND PRECAUTIONS
Serious Infections: Serious and sometimes fatal infections due to bacterial, mycobacterial, invasive fungal, viral, or other opportunistic pathogens have been reported in patients receiving oral Janus kinase inhibitors. Serious lower respiratory tract infections were reported in the clinical development program with topical ruxolitinib. Avoid use of OPZELURA in patients with an active, serious infection, including localized infections. Consider the risks and benefits of treatment prior to initiating OPZELURA in patients: with chronic or recurrent infection; with a history of a serious or an opportunistic infection; who have been exposed to tuberculosis; who
have resided or traveled in areas of endemic tuberculosis or endemic mycoses; or with underlying conditions that may predispose them to infection. Closely monitor patients for the development of signs and symptoms of infection during and after treatment with OPZELURA. Interrupt OPZELURA if a patient develops a serious infection, an opportunistic infection, or sepsis. Do not resume OPZELURA until the infection is controlled.
Tuberculosis: No cases of active tuberculosis (TB) were reported in clinical trials with OPZELURA. Cases of active TB were reported in clinical trials of oral Janus kinase inhibitors used to treat inflammatory conditions. Consider evaluating patients for latent and active TB infection prior to administration of OPZELURA. During OPZELURA use, monitor patients for the development of signs and symptoms of TB.
Viral Reactivation: Viral reactivation, including cases of herpes virus reactivation (e.g., herpes zoster), were reported in clinical trials with Janus kinase inhibitors used to treat inflammatory conditions including OPZELURA. If a patient develops herpes zoster, consider interrupting OPZELURA treatment until the episode resolves.
Hepatitis B and C: The impact of Janus kinase inhibitors used to treat inflammatory conditions including OPZELURA on chronic viral hepatitis reactivation is unknown. Patients with a history of hepatitis B or C infection were excluded from clinical trials. Hepatitis B viral load (HBV-DNA titer) increases, with or without associated elevations in alanine aminotransferase and aspartate aminotransferase, have been reported in patients with chronic HBV infections taking oral ruxolitinib. OPZELURA initiation is not recommended in patients with active hepatitis B or hepatitis C.
Mortality: In a large, randomized, postmarketing safety study of an oral JAK inhibitor in rheumatoid arthritis (RA) patients 50 years of age and older with at least one cardiovascular risk factor, a higher rate of all-cause mortality, including sudden cardiovascular death, was observed in patients treated with the JAK inhibitor compared with TNF blockers. Consider the benefits and risks for the individual patient prior to initiating or continuing therapy with OPZELURA.
Malignancy and Lymphoproliferative Disorders: Malignancies, including lymphomas, were observed in clinical trials of oral JAK inhibitors used to treat inflammatory conditions. Patients who are current or past smokers are at additional increased risk. Malignancies, including lymphomas, have occurred in patients receiving JAK inhibitors used to treat inflammatory conditions. In a large, randomized, postmarketing safety study of an oral JAK inhibitor in RA patients, a higher rate of malignancies (excluding non-melanoma skin cancer) was observed in patients treated with the JAK inhibitor compared to those treated with TNF blockers. A higher rate of lymphomas was observed in patients treated with the JAK inhibitor compared to those treated with TNF blockers. A higher rate of lung cancers was observed in current or past smokers treated with the JAK inhibitor compared to those treated with TNF blockers. In this study, current or past smokers had an additional increased risk of overall malignancies. Consider the benefits and risks for the individual patient prior to initiating or continuing therapy with OPZELURA, particularly in patients with a known malignancy (other than successfully treated non-melanoma skin cancers), patients who develop a malignancy when on treatment, and patients who are current or past smokers.
Non-melanoma Skin Cancers: Non-melanoma skin cancers including basal cell and squamous cell carcinoma have occurred in patients treated with OPZELURA. Perform periodic skin examinations during OPZELURA treatment and following treatment as appropriate. Exposure to sunlight and UV light should be limited by wearing protective clothing and using broad-spectrum sunscreen.
Major Adverse Cardiovascular Events (MACE): In a large, randomized, postmarketing safety study of an oral JAK inhibitor in RA patients 50 years of age and older with at least one cardiovascular risk factor, a higher rate of major adverse cardiovascular events (MACE) defined as cardiovascular death, non-fatal myocardial infarction (MI), and non-fatal stroke was observed with the JAK inhibitor compared to those treated with TNF blockers. Patients who are current or past smokers are at additional increased risk. Consider the benefits and risks for the individual patient prior to initiating or continuing therapy with OPZELURA, particularly in patients who are current or past smokers and patients with other cardiovascular risk factors. Patients should be informed about the symptoms of serious cardiovascular events and the steps to take if they occur. Discontinue OPZELURA in patients that have experienced a myocardial infarction or stroke.
Thrombosis: Thromboembolic events were observed in clinical trials with OPZELURA. Thrombosis, including deep vein thrombosis (DVT), pulmonary embolism (PE), and arterial thrombosis have been reported in patients receiving JAK inhibitors used to treat inflammatory conditions. Many of these adverse reactions were serious and some resulted in death. In a large, randomized, postmarketing safety study of an oral JAK inhibitor in RA patients 50 years of age and older with at least one cardiovascular risk factor, higher rates of overall thrombosis, DVT, and PE were observed compared to those treated with TNF blockers. Avoid OPZELURA in patients who may be at increased risk of thrombosis. If symptoms of thrombosis occur, discontinue OPZELURA and evaluate and treat patients appropriately.
Thrombocytopenia, Anemia, and Neutropenia: Thrombocytopenia, anemia , and neutropenia were reported in the clinical trials with OPZELURA. Consider the benefits and risks for individual patients who have a known history of these events prior to initiating therapy with OPZELURA. Perform CBC monitoring as clinically indicated. If signs and/or symptoms of clinically significant thrombocytopenia, anemia, and neutropenia occur, patients should discontinue OPZELURA.
Lipid Elevations: Treatment with oral ruxolitinib has been associated with increases in lipid parameters including total cholesterol, low-density lipoprotein (LDL) cholesterol, and triglycerides.
ADVERSE REACTIONS
Clinical Trials Experience: Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. Atopic Dermatitis: In two double-blind, vehicle-controlled clinical trials
(TRuE-AD1 atopic group, and 4% and at OPZELURA adverse 4 (1%)
Urticaria 3 (1%)
Adverse OPZELURA pyrexia, acneiform
Nonsegmental TRuE-V2), vitiligo of subjects Asian. ≥ 1% and period any treatment 26 (6%) 5 (2%), site erythema
Adverse the OPZELURA hypertension, dermatitis influenza-like DRUG Drug known may increase decrease Strong inhibitors ruxolitinib
USE IN Pregnancy
Pregnancy outcomes persons exposure
Risk Summary are not other adverse of ruxolitinib adverse
The background populations other birth defects Data Animal of organogenesis, rabbits. weight 60 mg/kg/day. systemic exposure affected lower highest approximately study lactation embryofetal function
Lactation
Risk Summary on the of lactating present serious breastfeed last dose Data: (30 mg/kg) for up the maternal several
or with patients for treatment with opportunistic trials with kinase patients for OPZELURA reactivation (e.g., used to herpes inflammatory unknown. trials. elevations reported in is not inhibitor least one sudden inhibitor patient lymphomas, conditions. Malignancies, to treat an oral non-melanoma skin treated with the cancers those additional individual patients cancers), current or cell and Perform treatment as protective postmarketing least one (MACE) stroke Patients benefits and OPZELURA, other serious patients OPZELURA. (PE), and used to serious and an oral cardiovascular compared to increased OPZELURA and anemia , and benefits prior to indicated. If anemia, and increases (LDL) varying directly rates clinical trials
(TRuE-AD1 and TRuE-AD2), 499 adult and pediatric subjects 12 years of age and older with atopic dermatitis were treated with OPZELURA twice daily for 8 weeks. In the OPZELURA group, 62% of subjects were females, and 71% of subjects were White, 23% were Black, and 4% were Asian. The adverse reactions reported by ≥ 1% of OPZELURA treated subjects and at a greater incidence than in the vehicle arm through week 8 are as follows for OPZELURA (N=499) vs Vehicle (N=250), respectively: Subjects with any treatment emergent adverse event (TEAE) 132 (27%) vs 83 (33%), Nasopharyngitis 13 (3%) vs 2 (1%), Bronchitis 4 (1%) vs 0 (0%), Ear infection 4 (1%) vs 0 (0%), Eosinophil count increased 4 (1%) vs 0 (0%), Urticaria 4 (1%) vs 0 (0%), Diarrhea 3 (1%) vs 1 (<1%), Folliculitis 3 (1%) vs 0 (0%), Tonsillitis 3 (1%) vs 0 (0%), and Rhinorrhea 3 (1%) vs 1 (<1%).
Adverse reactions that occurred in TRuE-AD1 and TRuE-AD2 in < 1% of subjects in the OPZELURA group and none in the vehicle group were: neutropenia, allergic conjunctivitis, pyrexia, seasonal allergy, herpes zoster, otitis externa, Staphylococcal infection, and acneiform dermatitis.
Nonsegmental Vitiligo: In two double-blind, vehicle-controlled clinical trials (TRuE-V1 and TRuE-V2), 449 adult and pediatric subjects 12 years of age and older with nonsegmental vitiligo were treated with OPZELURA twice daily for 24 weeks. In the OPZELURA group, 55% of subjects were females, and 81% of subjects were White, 5% were Black, and 4% were Asian. The adverse reactions reported by OPZELURA treated subjects with an incidence of ≥ 1% and at least 1% greater incidence than in the vehicle arm in the 24-week double-blind period are as follows for OPZELURA (N=449) vs Vehicle (N=224), respectively: Subjects with any treatment emergent adverse event (TEAE) 214 (48%) vs 79 (35%), Application site acne 26 (6%) vs 2 (1%), Application site pruritus 23 (5%) vs 6 (3%), Nasopharyngitis 19 (4%) vs 5 (2%), Headache 17 (4%) vs 6 (3%), Urinary tract infection 7 (2%) vs 1 (<1%), Application site erythema 7 (2%) vs 1 (<1%), and Pyrexia 6 (1%) vs 0 (0%)
Adverse reactions that occurred in TRuE-V1 and TRuE-V2 in ≥ 0.5% to < 1% of subjects in the OPZELURA group and none in the vehicle group were: application site dermatitis, hypertension, anxiety, application site discoloration, application site folliculitis, contusion, dermatitis contact, diarrhea, ear infection, gastritis, gastroenteritis, hordeolum, influenza-like illness, insomnia, nasal congestion, and vomiting.
DRUG INTERACTIONS
Drug interaction studies with OPZELURA have not been conducted. Ruxolitinib is known to be a substrate for cytochrome P450 3A4 (CYP3A4). Inhibitors of CYP3A4 may increase ruxolitinib systemic concentrations whereas inducers of CYP3A4 may decrease ruxolitinib systemic concentrations.
Strong Inhibitors of CYP3A4: Avoid concomitant use of OPZELURA with strong inhibitors of CYP3A4 as there is a potential to increase the systemic exposure of ruxolitinib and could increase the risk of OPZELURA adverse reactions.
USE IN SPECIFIC POPULATIONS
Pregnancy
Pregnancy Exposure Registry: There is a pregnancy registry that monitors pregnancy outcomes in pregnant persons exposed to OPZELURA during pregnancy. Pregnant persons exposed to OPZELURA and healthcare providers should report OPZELURA exposure by calling 1-855-463-3463.
Risk Summary: Available data from pregnancies reported in clinical trials with OPZELURA are not sufficient to evaluate a drug-associated risk for major birth defects, miscarriage, or other adverse maternal or fetal outcomes. In animal reproduction studies, oral administration of ruxolitinib to pregnant rats and rabbits during the period of organogenesis resulted in adverse developmental outcomes at doses associated with maternal toxicity. The background risks of major birth defects and miscarriage for the indicated populations are unknown. All pregnancies carry some risk of birth defects, loss, or other adverse outcomes. The background risk in the U.S. general population of major birth defects and miscarriage is 2-4% and 15-20%, respectively.
Data
Animal Data: Ruxolitinib was administered orally to pregnant rats or rabbits during the period of organogenesis, at doses of 15, 30, or 60 mg/kg/day in rats and 10, 30, or 60 mg/kg/day in rabbits. There were no treatment-related malformations at any dose. A decrease in fetal weight of approximately 9% was noted in rats at the highest and maternally toxic dose of 60 mg/kg/day. This dose resulted in systemic exposure approximately 22 times the clinical systemic exposure at the maximum recommended human dose (MRHD; the clinical systemic exposure from ruxolitinib cream, 1.5% applied twice daily to 25-40% atopic dermatitisaffected body surface area is used for calculation of multiples of human exposure). In rabbits, lower fetal weights of approximately 8% and increased late resorptions were noted at the highest and maternally toxic dose of 60 mg/kg/day. This dose resulted in systemic exposure approximately 70% the MRHD clinical systemic exposure. In a pre-and post-natal development study in rats, pregnant animals were dosed with ruxolitinib from implantation through lactation at doses up to 30 mg/kg/day. There were no drug-related adverse effects on embryofetal survival, postnatal growth, development parameters or offspring reproductive function at the highest dose evaluated (3.1 times the MRHD clinical systemic exposure).
Lactation
Risk Summary: There are no data on the presence of ruxolitinib in human milk, the effects on the breastfed child, or the effects on milk production. Ruxolitinib was present in the milk of lactating rats. When a drug is present in animal milk, it is likely that the drug will be present in human milk. Because of the serious adverse findings in adults, including risks of serious infections, thrombocytopenia, anemia, and neutropenia, advise women not to breastfeed during treatment with OPZELURA and for approximately four weeks after the last dose (approximately 5-6 elimination half-lives).
Data: Lactating rats were administered a single dose of [14C]-labeled ruxolitinib (30 mg/kg) on postnatal Day 10, after which plasma and milk samples were collected for up to 24 hours. The AUC for total radioactivity in milk was approximately 13 times the maternal plasma AUC. Additional analysis showed the presence of ruxolitinib and several of its metabolites in milk, all at levels higher than those in maternal plasma.
Pediatric Use: Atopic Dermatitis:
The safety and effectiveness of OPZELURA for the topical treatment of mild-to-moderate atopic dermatitis have been established in pediatric patients aged 12 to 17 years of age. Use of OPZELURA in this age group is supported by evidence from TRuE-AD1 and TRuE-AD2, which included 92 pediatric subjects aged 12 to 17 years with mild-to-moderate atopic dermatitis. No clinically meaningful differences in safety or effectiveness were observed between adult and pediatric subjects. The safety and effectiveness of OPZELURA in pediatric patients younger than 12 years of age with atopic dermatitis have not been established. Nonsegmental Vitiligo: The safety and effectiveness of OPZELURA for the topical treatment of nonsegmental vitiligo have been established in pediatric patients aged 12 to 17 years of age. Use of OPZELURA in this age group is supported by evidence from TRuE-V1 and TRuE-V2, which included 55 pediatric subjects aged 12 to 17 years with nonsegmental vitiligo. No clinically meaningful differences in safety or effectiveness were observed between adult and pediatric subjects. The safety and effectiveness of OPZELURA in pediatric patients younger than 12 years of age with nonsegmental vitiligo have not been established. Juvenile Animal Toxicity Data: Oral administration of ruxolitinib to juvenile rats resulted in effects on growth and bone measures. When administered starting at postnatal day 7 (the equivalent of a human newborn) at doses of 1.5 to 75 mg/kg/day, evidence of fractures occurred at doses ≥ 30 mg/kg/day, and effects on body weight and other bone measures [e.g., bone mineral content, peripheral quantitative computed tomography, and x-ray analysis] occurred at doses ≥ 5 mg/kg/day. When administered starting at postnatal day 21 (the equivalent of a human 2-3 years of age) at doses of 5 to 60 mg/kg/day, effects on body weight and bone occurred at doses ≥ 15 mg/kg/day, which were considered adverse at 60 mg/kg/day. Males were more severely affected than females in all age groups, and effects were generally more severe when administration was initiated earlier in the postnatal period. These findings were observed at systemic exposures that are at least 40% the MRHD clinical systemic exposure.
Geriatric Use: Of the 1249 total subjects with atopic dermatitis in clinical trials with OPZELURA, 115 (9%) were 65 years of age and older. No clinically meaningful differences in safety or effectiveness were observed between subjects less than 65 years and subjects 65 years and older.
Of the 831 total subjects enrolled with nonsegmental vitiligo in clinical trials with OPZELURA, 65 (8%) were 65 years of age and older. Clinical trials of OPZELURA in subjects with nonsegmental vitiligo did not include sufficient numbers of subjects 65 years of age and older to determine whether they respond differently from younger adult subjects.
PATIENT COUNSELING INFORMATION
Advise the patient or caregivers to read the FDA-approved patient labeling (Medication Guide). Infections: Inform patients that they may be at increased risk for developing infections, including serious infections, when taking Janus kinase inhibitors. Instruct patients to tell their healthcare provider if they develop any signs or symptoms of an infection. Advise patients that Janus kinase inhibitors increase the risk of herpes zoster, and some cases can be serious [see Warnings and Precautions]
Malignancies and Lymphoproliferative Disorders: Inform patients that Janus kinase inhibitors may increase the risk for developing lymphomas and other malignancies including skin cancer. Instruct patients to inform their health care provider if they have ever had any type of cancer. Inform patients that periodic skin examinations should be performed while using OPZELURA. Advise patients that exposure to sunlight, and UV light should be limited by wearing protective clothing and using a broad-spectrum sunscreen [see Warnings and Precautions]
Major Adverse Cardiovascular Events: Advise patients that events of major adverse cardiovascular events (MACE) including non-fatal myocardial infarction, non-fatal stroke, and cardiovascular death, have been reported in clinical studies with Janus kinase inhibitors used to treat inflammatory conditions. Instruct all patients, especially current or past smokers or patients with other cardiovascular risk factors, to be alert for the development of signs and symptoms of cardiovascular events [see Warnings and Precautions]
Thrombosis: Advise patients that events of DVT and PE have been reported in clinical studies with Janus kinase inhibitors used to treat inflammatory conditions. Instruct patients to tell their healthcare provider if they develop any signs or symptoms of a DVT or PE [see Warnings and Precautions].
Thrombocytopenia, Anemia , and Neutropenia: Advise patients of the risk of thrombocytopenia, anemia, and neutropenia with OPZELURA. Instruct patients to tell their healthcare provider if they develop any signs or symptoms of thrombocytopenia, anemia , or neutropenia [see Warnings and Precautions]
Administration Instructions: Advise patients or caregivers that OPZELURA is for topical use only [see Dosage and Administration]
Advise patients to limit treatment to one 60 gram tube per week or one 100 gram tube per 2 weeks [see Dosage and Administration].
Pregnancy: Inform patients to report their pregnancy to Incyte Corporation at 1-855-463-3463 [see Use in Specific Populations]
Lactation: Advise a patient not to breastfeed during treatment with OPZELURA and for about four weeks after the last dose [see Use in Specific Populations]
Manufactured for: Incyte Corporation 1801 Augustine Cut-off Wilmington, DE 19803
As we approach the holiday season, it’s not the festive lights, carolers, mistletoe, or peppermint candy canes that truly define this time of year, but the opportunity to pause and reflect on what truly matters.
Whether you are surrounded by family or spending time on your own, the demands of work should take a backseat for some muchneeded rest. This season is a reminder to prioritize self-care, since beyond a certain age, none of us are making it to the top of Santa's "nice" list. Take time to be joyful, breathe in the crisp air, and appreciate yourself.
In this issue, we continue to express our gratitude for the vibrant community that is BCoD, as reflected in the smiles, embraces, learnings, and connections of our national conference. We are deeply thankful to our partners, whose ongoing support drives our mission forward. Special thanks go to the dermatologists who have advocated for their BCs, recognizing the vital role they play in ensuring access to prescribed therapies.
This year, BCoD launched a member
donation drive to support those who may not have otherwise been able to attend. We hope that, moving forward, more dermatologists will invest in their staff’s professional development, increasing practice efficiency and patient satisfaction.
BCoD is excited to continue empowering BCs in 2025 with innovative and impactful resources, including:
• Digital biologic binders
• Complimentary office setup and advisory services for practices nationwide
By Margaret VanLoock, PhD PRESIDENT AND FOUNDER, DERMATOLOGY SPECIALTY SERVICES
Navi ting
Access
A Biologic Coordinator’s Perspective on HELPING PATIENTS
As a biologic coordinator (BC), helping patients access medication can be both challenging and rewarding. Additionally, for many patients, navigating insurance coverage, specialty pharmacies and financial assistance programs can be overwhelming, especially when also dealing with a medical condition. Through my own experience, I understand the emotional toll associated with denied access to treatment and am forever grateful for my exceptional healthcare team who fought for me. This experience profoundly shaped my role as a BC, making me more compassionate and steadfast when fighting for my patients.
Not only do patients have you, their BC, as an advocate, but they also have an ardent friend to help in this fight—the Johnson & Johnson (J&J) Tremfya withMe program. J&J is laser-focused on helping patients access treatment, a fact that was obvious when I visited the company headquarters this past June. While there, I could see that J&J and their employees recognized the struggles that many patients face when filling Tremfya. Their commitment to patient advocacy is evident in the newly revamped patient access program, Tremfya withMe. This solution offers a comprehensive suite of support services that assists patients in starting and staying on Tremfya with the help of Nurse Guides, Field Reimbursement Managers, Enhanced Specialty Pharmacy Services, Prescription and Cost Support, Case Managers and a new non-commercial specialty pharmacy, Access Therapy Center.
NURSE GUIDES
Interestingly, 95% of patients that currently have the support of a Tremfya withMe Nurse Guide would recommend the service to other Tremfya patients. This is not surprising considering that patients have the same Nurse Guide throughout their treatment journey. The friendship and trust that develops between patients and their Nurse Guides can provide encouragement and comfort during treatment. The guides, who are all registered nurses, can assist patients with injection training, financial support options, treatment expectations, and remind patients to schedule their Tremfya shipment. They do not provide medical advice, but they will direct patients to call their prescriber for help with medical questions or concerns.
FIELD REIMBURSEMENT MANAGERS (FRMS)
The FRM is Tremfya’s boots-on-the-ground representative that can access patient protected health information (PHI). This, in conjunction with the Enhanced Specialty Pharmacy Services, allows the FRM to help expedite Tremfya prescriptions that may be delayed and help resolve financial issues involving copay cards and surprise pharmacy bills. FRMs will notify offices when patients need a new prior authorization (PA) or if a patient is late filling their medication. In my experience, the FRMs are one of the most valuable resources offered by
Tremfya withMe, and I encourage all BCs to communicate with their FRM regularly.
PRESCRIPTION AND COST SUPPORT
Tremfya withME offers Insurance Benefits Investigations (BI), CoPay Card Programs and Patient Assistance Programs. Representatives from Tremfya withMe will perform a BI to help identify a patient’s prescription coverage, initiate a Prior Authorization that can be submitted by the prescriber’s office and identify patients with maximizer and accumulator plans. This is important as Tremfya withMe offers a specific
“The friendship and trust that develops between patients and their Nurse Guides can provide encouragement and comfort during treatment.”
copay card program for patients with these plans. Additionally, it provides the Delay and Denial Program for commercial patients whose PA determination takes longer than five business days or for those whose PA has been denied. Tremfya withMe offers Patient Assistance for uninsured or underinsured patients that meet the program guidelines. The Tremfya withMe non-commercial pharmacy, Access Therapy Center, ships Tremfya directly to patients on the Delay and Denial and Patient Assistance Programs.
CASE MANAGERS
The Tremfya withMe Case Managers work directly with FRMs, Nurse Guides, and the Enhanced Specialty Pharmacy liaisons to
help patients access Tremfya. Every office has a dedicated case manager, and each office can personalize their communication preferences. I contact my case manager through the J&J provider portal, where I can send secure messages that include PHI. Case Managers will also reach out to patients directly to request financial information, activate appropriate copay cards, and set up Nurse Guides. All of the Tremfya withMe programs can be accessed with a simple eRX to Access Therapy Center or a completed Patient Enrollment Form. Together, the Tremfya withMe suite of programs provides both the patients and BCs a unique set of tools to help make navigating treatment easier and less complicated. The J&J and Tremfya withMe team fight hard for your patients—just like you!
FOURTH ANNUAL BCOD NATIONAL CONFERENCE 2024
convened in Orlando, FL, October 27-29 to bring together biologic coordinators and office staff from across the country for education and networking.
AP Photography & Videography
Committed to Patient Support
This year marked the fourth annual BCoD Conference, and we were thrilled to host a record number of attendees.
More than 280 BCs registered for the event and over 35 exhibiting partners were in attendance. Members from near and far joined us to immerse themselves in knowledge, skill development, and networking.
MOVING FORWARD
As the first and only association to serve biologic coordinators exclusively, BCoD's membership continues to grow exponentially. We are excited to continue offering innovative programs to our members and strengthening our collaboration with our partners to advance patient access.
FUN FA CTS
2024 CONFERENCE
ATTENDANCE
Record number of BC attendees
RESOURCES
At last year's conference, BCoD introduced the first-ever BC certification program In 2024, they pushed innovation further with an unprecedented biologic binder asset. Special thanks to Neo Cuellar for leading the initiative, and to Heather Sawrey and Kereen Crider for their contributions.
GOING THE DISTANCE
Members traveled from as far as Washington state: 3,000 miles
2 members flew on an airplane for the first time to attend this conference
1 member endured a long 23-hour trip to get there due to a car crash
1 dedicated member drove 30 miles to and from the hotel every day, because it was sold out and they still wanted to attend
MEMBER TESTIMONY
“My conference experience was incredibly memorable, as I had the chance to meet both seasoned professionals in the field and newcomers like me. Listening to their stories and experiences was music to my ears, offering knowledge I would have never learned elsewhere. Becoming a BC is deeply rewarding, because much like when I was a pharmacy technician, I’ve always had a passion for helping others. This role allows me to do even more of that. I’m grateful to be part of an association like BCoD—it’s such a positive and supportive environment. Thank you all for your dedication and for assisting both veterans and newcomers like me!”
PATIENT IMPACT AWARDS
BCoD recognizes the dedication, passion, and impact that BCs bring to their patients. From the outset, we have honored those who tirelessly fight for their patients. Access Dermatology has consistently highlighted individuals nominated by their own practices. This year, we also launched the Patient Impact Awards (PIA), an initiative designed to recognize individuals dedicated to enhancing patient access through peer acknowledgment, with special recognition presented at the Fourth Annual BCoD Conference. While we celebrate those featured in this year's PIA list, we also acknowledge that many others, who are equally deserving, are not listed—and we want to recognize the entire community of biologic coordinators.
CONGRATULATIONS TO THE AWARD WINNERS!
AILIN SERNA
Maria Cartaya MD PA MIAMI, FL
ALISA REDMON
Southeastern Skin Cancer & Dermatology MADISON, AL
AMY BRENNAN
Dermatology Associates WINCHESTER, MA
ANA FONES
Florida Center for Pediatric Dermatology ORLANDO, FL
ANGELA WARREN
Raleigh Dermatology RALEIGH, NC
ANGELIA
DAVILA
West Michigan Dermatology GRANDVILLE, MI
ANA UHLINSKYY
Scott Sanders, MD Dermatology NEW CITY, NY
BRITTNEY MCLAUGHLIN
Carolina Mountain Dermatology ASHEVILLE, NC
BRITTNEY MORRISON
MidState Skin Institute OCALA, FL
BROOKE PENALOZA
Dermatology REDMOND, WA
CAROLYN WILLIAMS
Piedmont Plastic Surgery & Dermatology HUNTERSVILLE, NC
CASEY FINDLEY
Current Dermatology SYLVA, NC
CATHERINE DUVALL
USDP of Kingwood and Radiant Dermatology KINGWOOD, TX
CHERA-LEE PREISER
Fayette Area Dermatology FAYETTEVILLE, GA
CHRISTINE RAMIG
Optima Dermatology COLLINSVILLE, IL
CLAUDIA ORELLANA
Radiant Dermatology HOUSTON, TX
CYNTHIA SALAZAR
Wright Dermatology PLANO, TX
DENAE NORMAN
Altru Health System Specialty Pharmacy GRAND FORKS, ND
DIANA GOMEZ
Dermatology Consultants of Frisco FRISCO, TX
ERICA MAYA
CNOS Clinic
DAKOTA DUNES, SD
ERIKA WOCKEN
Monarch Dermatology & Surgery LOVELAND, CO
HEATHER SAWREY
George Washington University WASHINGTON DC
HOLLY REUTZEL
Tooele Dermatology TOOELE, UT
IOANA COMAN
Medical Dermatology Associates of Chicago CHICAGO, IL
JAMIE ANDERSON
Dermatology & Skin Surgery Center Cary CARY, NC
JANA SANTI
Premier Dermatology NEWARK, DELAWARE
JESICA AMEZQUITA
Duly Health and Care GLEN ELLYN, IL
KAYLA WITOWSKI
Lowcountry Dermatology CHARLESTON, SC
KEREEN CRIDER
Porter Premiere Dermatology and Surgery Center MELBOURNE, FL
KERRA RUDER
Missouri Dermatology Laser and Vein Center ST. LOUIS, MO
KIMBERLY LINEBERRY
Asheboro Dermatology ASHEBORO, NC
KIRSTIE BARTON
English Dermatology/Platinum Dermatology
SUN TAN VALLEY, AZ
KRISTIN GILLASPIE
Premier Dermatology CREST HILL, IL
LESLIE JONES
Advanced Dermatology ARLINGTON, TN
LINDA DI MATTEO
Forefront Dermatology FRANKLIN, WI
LINDSAY GEIGEL
Advanced Dermatology MAITLAND, FL
LUBA GRISHCHUK
Frontier Dermatology Partners KEIZER, OREGON
MARGARET VANLOOCK
Mobile Dermatology / Dermatology Specialty Services MOBILE, AL
MARY SULLIVANWHALEN
Mary Sullivan-Whalen
MELISSA BAILEY
Dermatology for the Family NORWALK, CT
MELISSA TOWNSEND
Advanced Dermatology SEWELL, NJ
NEOMIA (NEO) CUELLAR
A to Z Dermatology EL MIRAGE, AZ
SHANNON HUEY
Epiphany Dermatology CHARLESTON, SC
SHANNON MATTINGLY
MidCounty Dermatology ST. LOUIS, MO
SHANNON RAE TUMINELLO
The Dermatology Clinic BATON ROUGE, LA
SHAYLI NAGELKERK
Piedmont Plastic Surgery and Dermatology CHARLOTTE, NC
SHEILA FREEMAN
William E. Freeman,MD WARNER ROBINS, GA
SHELLY DENTON
Stutz Dermatology ROCHESTER, MI
STEVE RAHIMPOUR
Irradiance Dermatology LOS ANGELES, CA
TARA BIGGERS
Dermatology Group of The Carolinas STANLEY, NC
TERRI DEVIN
Sienna Dermatology MISSOURI CITY, TX
TRINITY HOKE
Piedmont Plastic Surgery and Dermatology HICKORY, NC
VERONICA PARTIDA
Dermatology Institute & Skin Care Center SANTA MONICA, CA
BC OD
THANK YOU!
We are deeply grateful to our 2024 sponsors. Your support drives our mission to educate BCoD members and enhance the patient journey to treatment.
The energy, passion, and advocacy you brought to our conference halls was inspiring, and we truly feel the strength of our shared community.
It has been a transformative journey since you stood in support of us four years ago. We are proud to call you partners, and we eagerly anticipate the incredible impact we will continue to make together in the years ahead. Thank you to each and every one of you.
CRAIG SCHUETTE CO-FOUNDER & EXECUTIVE DIRECTOR BCOD FOUNDER, ACCESS DERMATOLOGY
GRATITUDE FOR OUR ESTEEMED PARTNERS
DIAMOND PARTNER
PLATINUM PARTNERS
GOLD PARTNERS
PARTNERS
SILVER
BY HANNAH DEELY
ROSENTHAL Cotton and Cashmere Knit Beanie, kerrirosenthal.com
Pickleball Paddle Necklace, betteridge.com HERMÈS
Skis in D’Adresse Ashwwod, hermes.com
COZY PRESENTS TO PAMPER THE HIBERNATORS AT HEART
VERDURA 18K Yellow Gold and Diamond Zodiac Necklace, famillegreenwich.com
GRAY MALIN
3-in-1 Holiday Puzzle, back40mercantile.com
BROCHU WALKER
UNHIDE
Marshmallow Blanket (made of 90% Recycled Materials), unhide.us
Medium InsideOut Diamond Hoops, hcreidjewelers.com
HUDSON GRACE
Nuno Splatter Stoneware Mug, hudsongrace.com
TOGETHER WE ADVANCE
MEMBER BENEFITS
Join the Biologic Coordinators of Dermatology (BCoD) and discover a world of member benefits designed to elevate your professional journey and enhance patient care.
EDUCATIONAL TRAINING
Exclusive invites to educational trainings, webcasts, and meetings. RESOURCES
Office and patient resources for easier approvals and workflow management.
PROFESSIONAL DEVELOPMENT
Content designed for personal and professional growth.
IMPROVE PATIENT OUTCOMES
Tools and insights that enhance patient outcomes.
COMMUNITY
A platform that connects you with peers nationwide.
By Nicole Glor
Face Yoga
Takes a Holistic Approach to Aging
LIFT YOUR FACE WITH A WORKOUT DESIGNED TO KEEP YOU LOOKING TONED AND YOUNG
e’ve all heard of Booty Camp, Brazilian Butt Lift workouts, and Yoga
Butt...but why don’t we work out our other cheeks? Introducing Face Yoga — fitness for your face!
The Face Yoga method is a series of exercises designed to work the facial muscles to maintain suppleness and youthfulness, combined with breath control and simple meditation for health and relaxation. Through the daily practice of a series of facial exercises, Face Yoga method relaxes and tones facial muscles and lifts and firms the skin for a natural, non-surgical alternative to facelifts.
“Face Yoga lifts and firms the skin for a natural, non-surgical alternative to facelifts.”
I am certified by the FitFace Method, and I was happy to also learn self-face massage techniques, facial acupressure to drain lymphomas and relax the face, and how to use tools like the Gua Sha and face rollers. You can get face yoga personal training sessions or join a class.
Many of us have problem areas such as forehead lines, drooping eyelids, eye bags, drooping cheeks, laugh lines, lip lines and double chins. The face yoga experience tones all these areas! There are a number of exercises for the large face muscles and the small face muscles, including the eye-opener, forehead calmer, forehead lift, ultimate eye lift temple toner, bottom eyelid lift, ultimate lip lift, brow booster, cheek builder, cheek volumizer, ultimate neck lift, and the double chin vanisher.
FIT FACE EXERCISES
FOREHEAD LIFT:
Place your fingers on your forehead, lift the forehead upwith your fingers and use your forehead muscles to try and pull your fingersdown. As you do this, also use your eyebrow muscles and close the eyes; this will create resistance and cause the muscle to strengthen. Repeat three times for 30 seconds.
CHEEK BUILDER:
Suck in your cheeks and make sure you are not biting the inside of your mouth. You can keep your mouth slightly open to avoid this while keeping your cheeks sucked and smile at the same time. Hold this pose for 30 seconds and repeat three times.
DOUBLE-CHIN
VANISHER:
Place your hands under your jaw, place your tongue on the floor of your mouth push your tongue down with medium pressure. Use your hands to push upwards under your chin. Hold for 30 seconds and repeat three times.
Be sure to breathe though the entire workout! Remember, beauty is meant to heal and uplift you (and your face cheeks, too)!
NICOLE GLOR’S BIO
Nicole Glor is the author of The Slimnastics Workout and Squirrel Yoga for Sunshine (Amazon) and the star of 15 NikkiFitness videos youtube.com/ NikkiFitness.
She has been featured in over 500 nationalmedia outlets and is also a certified yoga instructor, face yoga expert,health coach and a group fitness instructor at Equinox
FACE YOGA SESSION
EXPLORING YOUR FACIAL POSTURE
MEDITATION ON WHAT YOU ARE GRATEFUL FOR AND LIKE ABOUT YOURSELF
HEAD MASSAGE
GUA SHA TOOLS WITH NATURAL OILS OR YOUR OWN SERUM
FACE YOGA EXERCISES FOR 30 SECONDS FOR EACHPOSTURE, THREE TIMES
FACIAL ACUPRESSURE FOR LYMPHATIC DRAINAGE AND RELAXATION
FACE ROLLER COOL DOWN
MEDITATION ON INTERNAL AND EXTERNAL BEAUTY WITH JOY AND FUN AT THE CENTER
TO SCHEDULE A GROUP CLASSOR PRIVATE SESSION email: nikki@nikkifitness.com
INSTAGRAM: @nikkifitness @nikkifitness_face_yoga
Once a prescribing decision has been made to prescribe TREMFYA® (guselkumab), enroll patients in
A dedicated support program for TREMFYA® patients
TREMFYA withMe provides a range of dedicated support to help make it easier for patients as they begin, and continue, their TREMFYA® treatment journey.
If a patient has been prescribed TREMFYA® for approved on-label use and is 18 or older, they are eligible for this program.
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Here’s how you can sign up patients. Scan or Visit: Visit tremfyawithme.com/ healthcare-professionals to sign up patients and for more information. Scan this QR CODE with your phone’s camera
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TheTREMFYAwithMe Guide
At the core of the program is a TREMFYA withMe Guide, a dedicated and qualified healthcare professional* who can work one-on-one with patients to:
Answer questions about prescription fulfillment and cost support
Patients will receive education on specialty medication fulfillment and options that could make their treatment more affordable.
Connect patients to injection support
You are the best person to review the injection process with your patients and help them understand what to expect. The TREMFYA withMe Guide is also available, after you have talked with your patients, if they have questions about injections.
Help with treatment expectations
Patients will get information on what to expect with their TREMFYA® treatment.
Provide regular updates and reminders at the patient’s request
Patients may receive support to help them stay on track with their treatment, plus updates on their TREMFYA® treatment journey.
Our goal is to provide a live person who can compassionately deliver the precise information that patients may want to help them with their treatment.
The TREMFYA withMe Guide can also help patients access other channels of support.
*Guides do not provide medical advice.
THE RISE OF FITNESS RETREATS
Train to
By Georgette Yacoub
Tr sform
Liz Pitassi just got out of a nine-year relationship. and her travel bug was back. She was into CrossFit and saw Lauren Fisher, a professional CrossFit athlete, post about a fitness retreat she was hosting in Bali—one with a $2,600 price tag.
She called her oldest brother, Ryan, in hopes he’d justify her spending that type of money on a fitness retreat. “I didn’t grow up in a stable financial home, so from the time I could work, I did all the things I had to to make sure I was good, and financially independent,” she said. By 32, she had paid her way through college, bought two homes and had a healthy savings account—in fact, she had only ever written one check larger than $1,000 prior to that, and it was for her home.
Ryan let her finish before his voice came through on the other line. “I have three questions,” he said. “One, do you really want to go?”
“Yes,” she said.
“Two, can you afford it?”
“Yes.”
“Three, what are you waiting for?”
So she signed up.
That week, she got in sweaty workout sessions at CrossFit Wanderlust, but she also took a surfing lesson, hung out on the beach with Balinese dogs, rented a scooter to poke around the island and woke up at 3:00 AM to hike up Mount Batur and watch the sunrise over an active volcano.
When asked what part of the retreat was most impactful, she replied, “Just going.”
VIN MICELI
has attended more than 15 fitness retreats as a speaker, sponsor and attendee with the mindset that some of the most special things that come out of these types of events are what happens in between the workouts.
“You find two types of people at these events—those who are successful looking to network or tap into something they lost, like their fitness or doing something hard,” Miceli says. “The other side of that spectrum are the people who spend their last $2,000 and are at the end of their rope—trying to connect, to grow,
to heal a thing.”
One of the most impactful summits that Miceli has ever been to was the Action Cultivates Excellence (ACE) Summit, a weekend designed to redefine masculinity. In between the wellness and fitness activities, Miceli experienced something he never quite experienced before.
“I found a level of emotional growth that happens around a group of men when they don’t feel the need to be manly,” he said. “When there were only men in the room, these guys were sharing things they’d normally never say out loud. Even for me, it was immensely impactful.”
“A well-executed retreat can fill your cup in a way other things can’t.”
— VIN MICELI
ABOVE: A yoga session overlooking the Aegean Sea at Helios’ Mykonos retreat. RIGHT: Vin Miceli (center) has attended 15 retreats, including the HPLT Experience in Antigua (below).
KATY INGULLI
is a yoga instructor, wellness expert and private trainer who can be found in places like the Maldives and Tuscany teaching yoga for Helios Retreats.
At these retreats, there is typically a fitness class at 8 a.m., yoga at 9 and then a big brunch at 10. The afternoon is spent just hanging out or doing an excursion—like camel rides in Morocco or a wine tasting and picnic on the hilltops of Tuscany. The late afternoon usually has another fitness class, another yoga class, dinner and then an opportunity to leisurely hang out, maybe watch a movie on the beach
or hang at the hotel pool.
“It’s an opportunity to escape, to put your phone down and just enjoy an entire day that is sort of planned out for you—not in a super structured way,” says Ingulli.
From her perspective, people sign up for these types of fitness retreats to mark a new beginning— the commitment to a healthier lifestyle, a divorce or even just a way to travel alone without quite being alone.
“They are so happy by the end because not only have they made new friends, but they spent a good amount of time working out, being outside, getting fresh air,” says Ingulli. “I’ve had a bunch of people come back for other retreats.”
Retreats are transformative. In fact, the fitness aspects seem to take a backseat to the other impact that people like Miceli and Ingulli experience. Miceli says, “The network of people you find yourself with for that time have always yielded me a friendship, a client, a vendor, a business partner— something that lasted far more than just the week or weekend.”
If price point is an issue, Miceli encourages you to evaluate the way you think about the retreats. He encourages those around him to try to make it work, within reason, if everything else about the retreat aligns with what they are looking for. “A well-executed retreat can fill your cup in a way other things can’t,” he says.
RIGHT: In addition to fitness sessions, the retreats also offer excursions— like a quad bike tour of Mykonos and a sunset camel ride in the Sahara. BELOW: Retreat attendees enjoying the outdoors on a hike in Greece.
ABOVE: Guests often leave these retreats not only with a sense of personal growth, but also having made deep connections with new friends.
ZORYVE® IT RELIEVE IT ANYWHERE
ZORYVE treats it, wherever patients need it, with an easy, once-daily, steroid-free topical1,2
MILD TO MODERATE ATOPIC DERMATITIS
CREAM 0.15%, DOWN TO 6 YEARS OLD
NOW AVAILABLE
Symptoms illustrated. Not actual patients.
SEBORRHEIC DERMATITIS
FOAM 0.3%, DOWN TO 9 YEARS OLD
PLAQUE PSORIASIS
ZORYVE is for topical use only and not for ophthalmic, oral, or intravaginal use.1,2
IMPORTANT SAFETY INFORMATION
CREAM 0.3%, DOWN TO 6 YEARS OLD
ZORYVE is contraindicated in patients with moderate to severe liver impairment (Child-Pugh B or C).
Flammability: The propellants in ZORYVE foam are flammable. Avoid fire, flame, and smoking during and immediately following application. The most common adverse reactions (≥1%) for ZORYVE cream 0.15% for atopic dermatitis include headache (2.9%), nausea (1.9%), application site pain (1.5%), diarrhea (1.5%), and vomiting (1.5%).
The most common adverse reactions (≥1%) for ZORYVE foam 0.3% for seborrheic dermatitis include nasopharyngitis (1.5%), nausea (1.3%), and headache (1.1%).
The most common adverse reactions (≥1%) for ZORYVE cream 0.3% for plaque psoriasis include diarrhea (3.1%), headache (2.4%), insomnia (1.4%), nausea (1.2%), application site pain (1.0%), upper respiratory tract infection (1.0%), and urinary tract infection (1.0%).
Please see accompanying brief summaries of full Prescribing Information for ZORYVE cream and brief summary of full Prescribing Information for ZORYVE foam.
INDICATIONS
ZORYVE cream, 0.15%, is indicated for topical treatment of mild to moderate atopic dermatitis in adult and pediatric patients 6 years of age and older.
ZORYVE foam, 0.3%, is indicated for the treatment of seborrheic dermatitis in adult and pediatric patients 9 years of age and older.
ZORYVE cream, 0.3%, is indicated for topical treatment of plaque psoriasis, including intertriginous areas, in adult and pediatric patients 6 years of age and older.
31% ATOPIC DERMATITIS
ofpatientsachieved vIGA-AD Success at Week 4 with ZORYVE, some as early as Week1 (vs 14% atWeek 4 with vehicle).3,7*
32% of patients achieved WI-NRS Success at Week 4 with ZORYVE, with results observed within 24 hours (vs 17% at Week 4 with vehicle).7*
77% of patients achieved IGA Success at Week 8, some as early as Week 2 (vs 53% at Week 8 with vehicle)2,3† SEBORRHEIC DERMATITIS
PLAQUE PSORIASIS
40% of patients achieved IGA Success atWeek8, some as early asWeek 4 (vs 7% atWeek 8 withvehicle)8‡
Pivotal Study Designs
*Two Phase 3 multicenter, randomized, double-blind, vehicle-controlled studies (INTEGUMENT-1 & INTEGUMENT-2) evaluated 1337 participants with mild to moderate atopic dermatitis ages 6 years and older. Participants applied ZORYVE or vehicle once daily. Primary endpoint was vIGA-AD Success at Week 4; ZORYVE cream = 884, vehicle = 453. WI-NRS Success at Week 4 was a key secondary endpoint; ZORYVE cream = 542, vehicle = 271.1
†Two multicenter, randomized, double-blind, vehicle-controlled studies (STRATUM and Trial 203) evaluated 683 participants with moderate to severe seborrheic dermatitis treated with ZORYVE or vehicle once daily for 8 weeks. STRATUM: ZORYVE foam = 304, vehicle = 153. Trial 203: ZORYVE foam = 154, vehicle = 72. Primary endpoint was IGA Success at Week 8.2
‡Two Phase 3 randomized, parallel, double-blind, vehicle-controlled, multicenter studies (DERMIS-1 and DERMIS-2) evaluated 881 participants with plaque psoriasis treated with ZORYVE or vehicle once daily for 8 weeks. ZORYVE = 576, vehicle = 305. Primary endpoint was IGA Success at Week 8.1
IGA Success/vIGA-AD Success = Achievement of Clear/Almost Clear and a ≥2-grade improvement from baseline.
IGA = Investigator Global Assessment. vIGA-AD = Validated Investigator Global Assessment—Atopic Dermatitis.
WI-NRS Success defined as a ≥4-point improvement for patients with a baseline score ≥4. WI-NRS scale: 0 (no itch) to 10 (worst imaginable itch). WI-NRS = Worst Itch Numeric Rating Scale.
References: 1. ZORYVE® cream. Prescribing information. Arcutis Biotherapeutics, Inc; 2024. 2. ZORYVE® foam. Prescribing information. Arcutis Biotherapeutics, Inc; 2023. 3. Data on File. Arcutis Biotherapeutics, Inc. 4. Pickett K, Loveman E, Kalita N, Frampton GK, Jones J. Educational interventions to improve quality of life in people with chronic inflammatory skin diseases: systematic reviews of clinical effectiveness and cost-effectiveness. Health Technol Assess. 2015;19(86). 5. Hessler-Waning M, Heinecke G. Diagnosis and management of common inflammatory skin diseases in older adults. Clin Geriatr Med. 2024;40: 11-23. 6. Harvard Health Publishing. Special Health Reports – Inflammatory skin conditions: eczema, seborrheic dermatitis, and psoriasis. Harvard Medical School Guide; 2023. Accessed June 18, 2024. https://www.health.harvard.edu/diseases-and-conditions/inflammatory-skin-conditions-eczema-seborrheic-dermatitis-and-psoriasis. 7. Simpson E, Boguniewicz M, Eichenfield L, et al. Pooled efficacy, patient-reported outcomes, and safety of roflumilast cream 0.15% from the INTEGUMENT-1 and INTEGUMENT-2
Phase 3 clinical trials of adults and children with atopic dermatitis. Poster presented at: American Academy of Dermatology Annual Meeting; March 8-12, 2024; San Diego, CA. 8. Lebwohl M, Gooderham MJ, Guenthner ST, et al. Pooled efficacy and safety results from the DERMIS-1 and DERMIS-2 Phase 3 trials of once-daily roflumilast cream 0.3% for the treatment of plaque psoriasis. Poster presented at: American Academy of Dermatology Annual Meeting; March 25-29, 2022; Boston, MA.
Brief Summary of Prescribing Information for ZORYVE® (roflumilast) cream, 0.15%, for topical use. See package insert for full Prescribing Information.
INDICATIONS AND USAGE
ZORYVE cream, 0.15%, is indicated for topical treatment of mild to moderate atopic dermatitis in adult and pediatric patients 6 years of age and older.
DOSAGE AND ADMINISTRATION
Use ZORYVE cream, 0.15%, for the treatment of mild to moderate atopic dermatitis. Apply ZORYVE cream to affected areas once daily and rub in completely. Wash hands after application, unless ZORYVE cream is for treatment of the hands.
ZORYVE cream is for topical use only and not for ophthalmic, oral, or intravaginal use.
CONTRAINDICATIONS
ZORYVE cream is contraindicated in patients with moderate to severe liver impairment (Child-Pugh B or C).
ADVERSE REACTIONS
Clinical Trials Experience
Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.
In two multicenter, randomized, double-blind, vehicle-controlled trials (INTEGUMENT-1 and INTEGUMENT-2), 1336 adult and pediatric subjects 6 years of age or older with mild to moderate atopic dermatitis were treated with ZORYVE cream, 0.15%, or vehicle cream once daily for 4 weeks.
The median age was 20 years (range 6 to 91). The majority of the subjects were female (57%) and White (60%). The median body surface area (BSA) affected was 10% (range 3% to 88%).
The proportion of subjects who discontinued treatment due to an adverse reaction was 1.6% for subjects treated with ZORYVE cream, 0.15%, and 1.1% for subjects treated with vehicle cream.
Table 1 presents adverse reactions that occurred in at least 1% of subjects treated with ZORYVE cream, 0.15%, and for which the rate exceeded the rate for vehicle cream.
Table 1. Adverse Reactions Reported in ≥1% of Subjects with Atopic Dermatitis Treated with ZORYVE Cream, 0.15%, (and More Frequently than Vehicle Cream) for 4 Weeks in Trials INTEGUMENT-1 and INTEGUMENT-2
Adverse Reaction
ZORYVE Cream, 0.15% (N=885)
The adverse reaction of insomnia was reported in fewer than 1% of subjects treated with ZORYVE cream, 0.15%.
USE IN SPECIFIC POPULATIONS
Pregnancy
Risk Summary
There are insufficient data available on the use of ZORYVE cream in pregnant women to inform a drug-associated risk of major birth defects, miscarriage, or other adverse maternal or fetal outcomes. In animal reproduction studies, roflumilast administered orally to pregnant rats and rabbits during the period of organogenesis produced no fetal structural abnormalities at doses up to 36 and 31 times the maximum recommended human dose (MRHD), respectively. Roflumilast induced post-implantation loss in rats at oral doses greater than or equal to 12 times the MRHD. Roflumilast induced stillbirth and decreased pup viability in mice at oral doses 19 and 59 times the MRHD, respectively. Roflumilast has been shown to adversely affect pup post-natal development when dams were treated with an oral dose 59 times the MRHD during pregnancy and lactation periods in mice.
The background risk of major birth defects and miscarriage for the indicated population is unknown. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively.
Clinical Considerations
Labor and delivery
Avoid using ZORYVE cream during labor and delivery. There are no human studies that have investigated effects of ZORYVE cream on preterm labor or labor at term; however, animal studies showed that oral roflumilast disrupted the labor and delivery process in mice.
Data
Animal data
In an embryo-fetal development study, pregnant rats were dosed orally during the period of organogenesis with up to 1.8 mg/kg/day roflumilast (36 times the MRHD on a mg/m2 basis). No evidence of structural abnormalities or effects on survival rates were observed. Roflumilast did not affect embryo-fetal development at a maternal oral dose of 0.2 mg/kg/day (4 times the MRHD on a mg/m2 basis).
In a fertility and embryo-fetal development study, male rats were dosed orally with up to 1.8 mg/kg/day roflumilast for 10 weeks and females for 2 weeks prior to pairing and throughout the organogenesis period. Roflumilast induced pre- and post-implantation loss at maternal oral doses greater than or equal to 0.6 mg/kg/day (12 times the MRHD on a mg/m2 basis). Roflumilast did not cause fetal structural abnormalities at maternal oral doses up to 1.8 mg/kg/day (35 times the MRHD on a mg/m2 basis).
In an embryo-fetal development study in rabbits, pregnant does were dosed orally with 0.8 mg/kg/day roflumilast during the period of organogenesis. Roflumilast did not cause fetal structural abnormalities at the maternal oral doses of 0.8 mg/kg/day (31 times the MRHD on a mg/m2 basis).
In pre- and post-natal developmental studies in mice, dams were dosed orally with up to 12 mg/kg/day roflumilast during the period of organogenesis and lactation. Roflumilast induced stillbirth and decreased pup viability at maternal oral doses greater than 2 mg/kg/day and 6 mg/kg/day, respectively (19 and 59 times the MRHD on a mg/m2 basis, respectively). Roflumilast induced delivery retardation in pregnant mice at maternal oral doses greater than 2 mg/kg/day (19 times the MRHD on a mg/m2 basis). Roflumilast decreased pup rearing frequencies at a maternal oral dose of 6 mg/kg/day during pregnancy and lactation (59 times the MRHD on a mg/m2 basis). Roflumilast also decreased survival and forelimb grip reflex and delayed pinna detachment in mouse pups at a maternal oral dose of 12 mg/kg/day (116 times the MRHD on a mg/m2 basis).
Lactation
Risk Summary
There are no data on the presence of roflumilast or its metabolite in human milk, the effects on the breastfed infant, or the effects on milk production.
Roflumilast and/or its metabolites are excreted into the milk of lactating rats. When a drug is present in animal milk, it is likely that the drug will present in human milk. The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for ZORYVE cream and any potential adverse effects on the breastfed infant from ZORYVE cream or from the underlying maternal condition.
Clinical Considerations
To minimize potential exposure to the breastfed infant via breast milk, use ZORYVE cream on the smallest area of skin and for the shortest duration possible while breastfeeding. To avoid direct infant exposure, advise breastfeeding women not to apply ZORYVE cream directly to the nipple or areola. If applied to the patient’s chest, avoid exposure via direct contact with the infant’s skin.
Data
Animal data
Roflumilast and/or its metabolite concentrations measured 8 hours after an oral dose of 1 mg/kg given to lactating rats were 0.32 and 0.02 mcg/g in the milk and pup liver, respectively.
Pediatric Use
The safety and effectiveness of ZORYVE cream, 0.15%, for the topical treatment of mild to moderate atopic dermatitis have been established in pediatric patients 6 years of age and older. Use of ZORYVE cream, 0.15%, in this age group is supported by data from two 4-week, vehicle-controlled, safety and efficacy trials which included 615 subjects 6 to 17 years of age, of whom 406 received ZORYVE cream, 0.15%. Use of ZORYVE cream, 0.15%, in pediatric patients 6 years of age and older is also supported by data from 481 pediatric subjects treated with ZORYVE cream, 0.15%, in open-label trials, of which 104 were treated for 52 weeks. The safety and effectiveness of ZORYVE cream, 0.15%, have not been established in pediatric patients younger than 6 years of age.
Geriatric Use
There were 184 patients 65 years of age and older in clinical studies for plaque psoriasis and atopic dermatitis.
Of the 885 patients treated with ZORYVE cream, 0.15%, in the 2 controlled clinical studies for atopic dermatitis, 36 (4.1%) were 65 to 74 years of age and 8 (0.9%) were 75 years of age and older. No overall differences in safety or effectiveness were observed between these subjects and younger subjects. Other reported clinical experience has not identified differences in responses between the geriatric and younger patients, but greater sensitivity of some older individuals cannot be ruled out.
Hepatic Impairment
Oral roflumilast 250 mcg once daily for 14 days was studied in subjects with hepatic impairment. The systemic exposure of roflumilast and roflumilast N-oxide were increased in subjects with moderate (Child-Pugh B) hepatic impairment. ZORYVE cream is contraindicated in patients with moderate to severe liver impairment (Child-Pugh B or C). No dosage adjustment is needed in patients with mild (Child-Pugh A) hepatic impairment.
PATIENT COUNSELING INFORMATION
Advise the patient or caregiver to read the FDA-approved patient labeling (Patient Information).
Lactation
Advise patients to use ZORYVE cream on the smallest area of skin and for the shortest duration possible while breastfeeding. Instruct patients who are breastfeeding not to apply ZORYVE cream directly to the nipple or areola to avoid direct infant exposure. Instruct patients to avoid inadvertent contact of treated areas with infant skin.
Brief Summary of Prescribing Information for ZORYVE® (roflumilast) foam, 0.3%, for topical use. See package insert for full Prescribing Information.
INDICATIONS AND USAGE
ZORYVE foam, 0.3%, is indicated for the treatment of seborrheic dermatitis in adult and pediatric patients 9 years of age and older.
DOSAGE AND ADMINISTRATION
Shake can prior to each use. Apply a thin layer of ZORYVE foam, 0.3%, once daily to affected areas on skin and/or scalp when they are not wet. Rub in completely.
Wash hands after application.
Avoid fire, flame, and smoking during and immediately following application. ZORYVE foam, 0.3%, is for topical use only and not for ophthalmic, oral, or intravaginal use.
CONTRAINDICATIONS
ZORYVE foam, 0.3%, is contraindicated in patients with moderate to severe liver impairment (Child-Pugh B or C).
WARNINGS AND PRECAUTIONS
Flammability
The propellants in ZORYVE foam, 0.3%, are flammable. Avoid fire, flame, and smoking during and immediately following application.
ADVERSE REACTIONS
Clinical Trials Experience
Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.
In two multicenter, randomized, double-blind, vehicle-controlled trials (Trial 203 and STRATUM), 683 adult and pediatric subjects 9 years of age or older with seborrheic dermatitis were treated with ZORYVE foam, 0.3%, or vehicle foam once daily for 8 weeks. The combined trial population was 79% White, 11% Black, and 5% Asian; for ethnicity, 79% identified as non-Hispanic/Latino and 21% identified as Hispanic/Latino. Fifty percent (50%) were male and 50% were female. The median age was 41 years (range 9 to 87 years). The median body surface area (BSA) affected was 2.5%.
Table 1 presents adverse reactions that occurred in at least 1% of subjects treated with ZORYVE foam, 0.3%.
Table 1: Adverse Reactions Reported in ≥1% of Subjects with Seborrheic Dermatitis Treated with ZORYVE Foam, 0.3%, for 8 Weeks in Trial 203 and Trial STRATUM
Adverse Reaction ZORYVE foam, 0.3% (N=458) n (%) Vehicle foam (N=225) n (%)
Nasopharyngitis
(1.5)
(0.4) Nausea
(1.3)
In a fertility and embryo-fetal development study, male rats were dosed orally with up to 1.8 mg/kg/day roflumilast for 10 weeks and females for 2 weeks prior to pairing and throughout the organogenesis period. Roflumilast induced pre- and post-implantation loss at maternal oral doses greater than or equal to 0.6 mg/kg/day (10 times the MRHD on a mg/m2 basis). Roflumilast did not cause fetal structural abnormalities at maternal oral doses up to 1.8 mg/kg/day (29 times the MRHD on a mg/m2 basis).
In an embryo-fetal development study in rabbits, pregnant does were dosed orally with 0.8 mg/kg/day roflumilast during the period of organogenesis. Roflumilast did not cause fetal structural abnormalities at the maternal oral doses of 0.8 mg/kg/day (26 times the MRHD on a mg/m2 basis).
In pre- and post-natal developmental studies in mice, dams were dosed orally with up to 12 mg/kg/day roflumilast during the period of organogenesis and lactation. Roflumilast induced stillbirth and decreased pup viability at maternal oral doses greater than 2 mg/kg/day and 6 mg/kg/day, respectively (16 and 49 times the MRHD on a mg/m2 basis, respectively). Roflumilast induced delivery retardation in pregnant mice at maternal oral doses greater than 2 mg/kg/day (16 times the MRHD on a mg/m2 basis). Roflumilast decreased pup rearing frequencies at a maternal oral dose of 6 mg/kg/day during pregnancy and lactation (49 times the MRHD on a mg/m2 basis). Roflumilast also decreased survival and forelimb grip reflex and delayed pinna detachment in mouse pups at a maternal oral dose of 12 mg/kg/day (97 times the MRHD on a mg/m2 basis).
Lactation
Risk Summary
There are no data on the presence of roflumilast or its metabolite in human milk, the effects on the breastfed infant, or the effects on milk production.
Roflumilast and/or its metabolites are excreted into the milk of lactating rats. When a drug is present in animal milk, it is likely that the drug will be present in human milk. The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for ZORYVE foam, 0.3%, and any potential adverse effects on the breastfed infant from ZORYVE foam, 0.3%, or from the underlying maternal condition.
Clinical Considerations
To minimize potential exposure to the breastfed infant via breast milk, use ZORYVE foam, 0.3%, on the smallest area of skin and for the shortest duration possible while breastfeeding. To avoid direct infant exposure, advise breastfeeding women not to apply ZORYVE foam, 0.3%, directly to the nipple or areola. If applied to the patient’s chest, avoid exposure via direct contact with the infant’s skin.
Data
Animal data
Roflumilast and/or its metabolite concentrations measured 8 hours after an oral dose of 1 mg/kg given to lactating rats were 0.32 and 0.02 mcg/g in the milk and pup liver, respectively.
Pediatric Use
(0)
(0) Headache 5 (1.1)
The following additional adverse reactions were reported in fewer than 1% of subjects treated with ZORYVE foam, 0.3%: diarrhea and insomnia.
In 408 subjects who continued treatment with ZORYVE foam, 0.3%, for up to 24 to 52 weeks in an open-label, long-term trial, the adverse reaction profile was consistent with that observed in vehicle-controlled trials.
USE IN SPECIFIC POPULATIONS
Pregnancy
Risk Summary
There are insufficient data available on the use of ZORYVE foam, 0.3%, in pregnant women to inform a drug-associated risk of major birth defects, miscarriage, or other adverse maternal or fetal outcomes. In animal reproduction studies, roflumilast administered orally to pregnant rats and rabbits during the period of organogenesis produced no fetal structural abnormalities at doses up to 30 and 26 times the maximum recommended human dose (MRHD), respectively. Roflumilast induced post-implantation loss in rats at oral doses greater than or equal to 10 times the MRHD. Roflumilast induced stillbirth and decreased pup viability in mice at oral doses 16 and 49 times the MRHD, respectively. Roflumilast has been shown to adversely affect pup post-natal development when dams were treated with an oral dose 49 times the MRHD during pregnancy and lactation periods in mice.
The background risk of major birth defects and miscarriage for the indicated population is unknown. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively.
Clinical Considerations
Labor and delivery
Avoid using ZORYVE foam, 0.3%, during labor and delivery. There are no human studies that have investigated effects of ZORYVE foam, 0.3%, on preterm labor or labor at term; however, animal studies showed that oral roflumilast disrupted the labor and delivery process in mice.
Data
Animal data
In an embryo-fetal development study, pregnant rats were dosed orally during the period of organogenesis with up to 1.8 mg/kg/day roflumilast (30 times the MRHD on a mg/m2 basis). No evidence of structural abnormalities or effects on survival rates were observed. Roflumilast did not affect embryo-fetal development at a maternal oral dose of 0.2 mg/kg/day (3 times the MRHD on a mg/m2 basis).
The safety and effectiveness of ZORYVE foam, 0.3%, for the treatment of seborrheic dermatitis have been established in pediatric patients 9 years of age and older. Use of ZORYVE foam, 0.3%, in this age group is supported by data from two 8-week, vehiclecontrolled trials which included 32 pediatric subjects 9 to 17 years of age, of whom 17 received ZORYVE foam, 0.3%, and from open-label trials of up to 52 weeks which included 23 pediatric subjects treated with ZORYVE foam, 0.3%. The adverse reaction profile was consistent with that observed in adults.
The safety and effectiveness of ZORYVE foam, 0.3%, in pediatric patients below the age of 9 years have not been established.
Geriatric Use
Of the 683 subjects with seborrheic dermatitis exposed to ZORYVE foam, 0.3%, or vehicle for up to 8 weeks in the controlled clinical trials, 98 (14%) were 65 years of age or older, and 33 (5%) were 75 years of age or older. No overall differences in safety or effectiveness were observed between these subjects and younger subjects, and other reported clinical experience has not identified differences in responses between the elderly and younger patients, but greater sensitivity of some older individuals cannot be ruled out.
Hepatic Impairment
Oral roflumilast 250 mcg once daily for 14 days was studied in subjects with hepatic impairment. The systemic exposure of roflumilast and roflumilast N-oxide were increased in subjects with moderate (Child-Pugh B) hepatic impairment. ZORYVE foam, 0.3%, is contraindicated in patients with moderate to severe liver impairment (ChildPugh B or C). No dosage adjustment is needed in patients with mild (Child-Pugh A) hepatic impairment.
PATIENT COUNSELING INFORMATION
Advise the patient or caregiver to read the FDA-approved patient labeling (Patient Information).
Flammability
Because the propellants in ZORYVE foam, 0.3%, are flammable, instruct the patient to avoid fire, flame, and smoking during and immediately following application.
Lactation
Advise patients to use ZORYVE foam, 0.3%, on the smallest area of skin and for the shortest duration possible while breastfeeding. Instruct patients who are breastfeeding not to apply ZORYVE foam, 0.3%, directly to the nipple or areola to avoid direct infant exposure. Instruct patients to avoid inadvertent contact of treated areas with infant skin.
Brief Summary of Prescribing Information for ZORYVE® (roflumilast) cream, 0.3%, for topical use. See package insert for full Prescribing Information.
INDICATIONS AND USAGE
ZORYVE cream, 0.3%, is indicated for topical treatment of plaque psoriasis, including intertriginous areas, in adult and pediatric patients 6 years of age and older.
DOSAGE AND ADMINISTRATION
Use ZORYVE cream, 0.3%, for the treatment of plaque psoriasis. Apply ZORYVE cream to affected areas once daily and rub in completely. Wash hands after application, unless ZORYVE cream is for treatment of the hands.
ZORYVE cream is for topical use only and not for ophthalmic, oral, or intravaginal use.
CONTRAINDICATIONS
ZORYVE cream is contraindicated in patients with moderate to severe liver impairment (Child-Pugh B or C).
ADVERSE REACTIONS
Clinical Trials Experience
Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.
In two multicenter, randomized, double-blind, vehicle-controlled trials (DERMIS-1 and DERMIS-2), 881 adult and pediatric subjects 6 years of age or older with plaque psoriasis were treated with ZORYVE cream, 0.3%, or vehicle cream once daily for 8 weeks.
The median age was 47 years (range 6 to 88). The majority of the subjects were male (64%) and White (82%). The median body surface area (BSA) affected was 5.5% (range 2% to 20%). The proportion of subjects who discontinued treatment due to an adverse reaction was 1.0% for subjects treated with ZORYVE cream, 0.3%, and 1.3% for subjects treated with vehicle cream. The most common adverse reaction that led to discontinuation of ZORYVE cream, 0.3%, was application site urticaria (0.3%).
Table 1 presents adverse reactions that occurred in at least 1% of subjects treated with ZORYVE cream, 0.3%, and for which the rate exceeded the rate for vehicle cream.
Table 1. Adverse Reactions Reported in ≥1% of Subjects with Plaque Psoriasis
Treated with ZORYVE Cream, 0.3%, (and More Frequently than Vehicle Cream) for 8 Weeks in Trials DERMIS-1 and DERMIS-2
Adverse Reaction ZORYVE Cream, 0.3% (N=576) n (%) Vehicle Cream (N=305) n
In a fertility and embryo-fetal development study, male rats were dosed orally with up to 1.8 mg/kg/day roflumilast for 10 weeks and females for 2 weeks prior to pairing and throughout the organogenesis period. Roflumilast induced pre- and post-implantation loss at maternal oral doses greater than or equal to 0.6 mg/kg/day (12 times the MRHD on a mg/m2 basis). Roflumilast did not cause fetal structural abnormalities at maternal oral doses up to 1.8 mg/kg/day (35 times the MRHD on a mg/m2 basis).
In an embryo-fetal development study in rabbits, pregnant does were dosed orally with 0.8 mg/kg/day roflumilast during the period of organogenesis. Roflumilast did not cause fetal structural abnormalities at the maternal oral doses of 0.8 mg/kg/day (31 times the MRHD on a mg/m2 basis).
In pre- and post-natal developmental studies in mice, dams were dosed orally with up to 12 mg/kg/day roflumilast during the period of organogenesis and lactation. Roflumilast induced stillbirth and decreased pup viability at maternal oral doses greater than 2 mg/kg/day and 6 mg/kg/day, respectively (19 and 59 times the MRHD on a mg/m2 basis, respectively). Roflumilast induced delivery retardation in pregnant mice at maternal oral doses greater than 2 mg/kg/day (19 times the MRHD on a mg/m2 basis). Roflumilast decreased pup rearing frequencies at a maternal oral dose of 6 mg/kg/day during pregnancy and lactation (59 times the MRHD on a mg/m2 basis). Roflumilast also decreased survival and forelimb grip reflex and delayed pinna detachment in mouse pups at a maternal oral dose of 12 mg/kg/day (116 times the MRHD on a mg/m2 basis).
Lactation
Risk Summary
There are no data on the presence of roflumilast or its metabolite in human milk, the effects on the breastfed infant, or the effects on milk production.
Roflumilast and/or its metabolites are excreted into the milk of lactating rats. When a drug is present in animal milk, it is likely that the drug will present in human milk. The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for ZORYVE cream and any potential adverse effects on the breastfed infant from ZORYVE cream or from the underlying maternal condition.
Clinical Considerations
To minimize potential exposure to the breastfed infant via breast milk, use ZORYVE cream on the smallest area of skin and for the shortest duration possible while breastfeeding. To avoid direct infant exposure, advise breastfeeding women not to apply ZORYVE cream directly to the nipple or areola. If applied to the patient’s chest, avoid exposure via direct contact with the infant’s skin.
Data
Animal data
Roflumilast and/or its metabolite concentrations measured 8 hours after an oral dose of 1 mg/kg given to lactating rats were 0.32 and 0.02 mcg/g in the milk and pup liver, respectively.
Pediatric Use
In 594 subjects with plaque psoriasis who continued treatment with ZORYVE cream, 0.3%, for up to 64 weeks in open-label extension trials, the adverse reaction profile was consistent with that observed in vehicle-controlled trials.
USE IN SPECIFIC POPULATIONS
Pregnancy
Risk Summary
There are insufficient data available on the use of ZORYVE cream in pregnant women to inform a drug-associated risk of major birth defects, miscarriage, or other adverse maternal or fetal outcomes. In animal reproduction studies, roflumilast administered orally to pregnant rats and rabbits during the period of organogenesis produced no fetal structural abnormalities at doses up to 36 and 31 times the maximum recommended human dose (MRHD), respectively. Roflumilast induced post-implantation loss in rats at oral doses greater than or equal to 12 times the MRHD. Roflumilast induced stillbirth and decreased pup viability in mice at oral doses 19 and 59 times the MRHD, respectively. Roflumilast has been shown to adversely affect pup post-natal development when dams were treated with an oral dose 59 times the MRHD during pregnancy and lactation periods in mice. The background risk of major birth defects and miscarriage for the indicated population is unknown. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively.
Clinical Considerations
Labor and delivery
Avoid using ZORYVE cream during labor and delivery. There are no human studies that have investigated effects of ZORYVE cream on preterm labor or labor at term; however, animal studies showed that oral roflumilast disrupted the labor and delivery process in mice.
Data
Animal data
In an embryo-fetal development study, pregnant rats were dosed orally during the period of organogenesis with up to 1.8 mg/kg/day roflumilast (36 times the MRHD on a mg/m2 basis). No evidence of structural abnormalities or effects on survival rates were observed. Roflumilast did not affect embryo-fetal development at a maternal oral dose of 0.2 mg/kg/day (4 times the MRHD on a mg/m2 basis).
The safety and effectiveness of ZORYVE cream, 0.3%, for the topical treatment of plaque psoriasis, including intertriginous areas, have been established in pediatric patients 6 years of age and older. Use of ZORYVE cream, 0.3%, in pediatric patients 6 years of age and older is supported by data from two 8-week, vehicle-controlled, safety and efficacy trials which included 18 subjects 6 to 17 years of age, of whom 11 received ZORYVE cream, 0.3%. Use of ZORYVE cream, 0.3%, in pediatric patients 12 years of age and older is also supported by data from open-label trials of 2 and 24 weeks duration which included 18 subjects 12 to 17 years of age treated with ZORYVE cream, 0.3%. Use of ZORYVE cream, 0.3%, in pediatric patients 6 to less than 12 years of age is also supported by data from one 4-week, open-label, safety and pharmacokinetic (PK) study which included 20 pediatric subjects 6 to less than 12 years of age.
The safety and effectiveness of ZORYVE cream, 0.3%, have not been established in pediatric patients younger than 6 years of age.
Geriatric Use
There were 184 patients 65 years of age and older in clinical studies for plaque psoriasis and atopic dermatitis.
Of the 576 patients treated with ZORYVE cream, 0.3%, in the 2 controlled clinical studies for plaque psoriasis, 56 (9.7%) were 65 to 74 years of age and 21 (3.7%) were 75 years of age and older. No overall differences in safety or effectiveness were observed between these subjects and younger subjects. Other reported clinical experience has not identified differences in responses between the geriatric and younger patients, but greater sensitivity of some older individuals cannot be ruled out.
Hepatic Impairment
Oral roflumilast 250 mcg once daily for 14 days was studied in subjects with hepatic impairment. The systemic exposure of roflumilast and roflumilast N-oxide were increased in subjects with moderate (Child-Pugh B) hepatic impairment. ZORYVE cream is contraindicated in patients with moderate to severe liver impairment (Child-Pugh B or C). No dosage adjustment is needed in patients with mild (ChildPugh A) hepatic impairment.
PATIENT COUNSELING INFORMATION
Advise the patient or caregiver to read the FDA-approved patient labeling (Patient Information).
Lactation
Advise patients to use ZORYVE cream on the smallest area of skin and for the shortest duration possible while breastfeeding. Instruct patients who are breastfeeding not to apply ZORYVE cream directly to the nipple or areola to avoid direct infant exposure. Instruct patients to avoid inadvertent contact of treated areas with infant skin.
A way to get patients started on treatment while they wait for appeals
Support through the prior authorization (PA) and appeals process
A clearer path to PA approval
Resources to help patients stay on therapy
Commercial Bridge Program*
Enhanced Services Specialty Pharmacy Network†
Advanced PA guidance
Patient education and adherence tools
*Terms and conditions apply. Terms of this program may change at any time.
†OPZELURA is widely available at pharmacies. Other offers and services may apply.
INDICATIONS
OPZELURA is indicated for the topical short-term and non-continuous chronic treatment of mild to moderate atopic dermatitis in non-immunocompromised adult and pediatric patients 12 years of age and older whose disease is not adequately controlled with topical prescription therapies or when those therapies are not advisable.
OPZELURA is indicated for the topical treatment of nonsegmental vitiligo in adult and pediatric patients 12 years of age and older.
Limitations of Use: Use of OPZELURA in combination with therapeutic biologics, other JAK inhibitors, or potent immunosuppressants such as azathioprine or cyclosporine is not recommended.
IMPORTANT SAFETY INFORMATION
SERIOUS INFECTIONS
Patients treated with oral Janus kinase inhibitors for inflammatory conditions are at risk for developing serious infections that may lead to hospitalization or death. Reported infections include:
• Ac tive tuberculosis, which may present with pulmonary or extrapulmonary disease.
• Invasive fungal infections, including cryptococcosis and pneumocystosis.
• Bacterial, viral, including herpes zoster, and other infections due to opportunistic pathogens.
Avoid use of OPZELURA in patients with an active, serious infection, including localized infections. If a serious infection develops, interrupt OPZELURA until the infection is controlled. Carefully consider the benefits and risks of treatment prior to initiating OPZELURA in patients with chronic or recurrent infection. Closely monitor patients for the development of signs and symptoms of infection during and after treatment with OPZELURA.
Serious lower respiratory tract infections were reported in the clinical development program with topical ruxolitinib.
No cases of active tuberculosis (TB) were reported in clinical trials with OPZELURA. Cases of active TB were reported in clinical trials of oral Janus kinase inhibitors used to treat inflammatory conditions. Consider evaluating patients for latent and active TB infection prior to administration of OPZELURA. During OPZELURA use, monitor patients for the development of signs and symptoms of TB.
Viral reactivation, including cases of herpes virus reactivation (e.g., herpes zoster), were reported in clinical trials with Janus kinase inhibitors used to treat inflammatory conditions including OPZELURA. If a patient develops herpes zoster, consider interrupting OPZELURA treatment until the episode resolves.
Hepatitis B viral load (HBV-DNA titer) increases, with or without associated elevations in alanine aminotransferase and aspartate aminotransferase, have been reported in patients with chronic HBV infections taking oral ruxolitinib. OPZELURA initiation is not recommended in patients with active hepatitis B or hepatitis C.
MORTALITY
In a large, randomized, postmarketing safety study in rheumatoid arthritis (RA) patients 50 years of age and older with at least one cardiovascular risk factor comparing an oral JAK inhibitor to tumor necrosis factor (TNF) blocker treatment, a higher rate of all-cause mortality, including sudden cardiovascular death, was observed with the JAK inhibitor. Consider the benefits and risks for the individual patient prior to initiating or continuing therapy with OPZELURA.
MALIGNANCIES
Malignancies were reported in patients treated with OPZELURA. Lymphoma and other malignancies have been observed in patients receiving JAK inhibitors used to treat inflammatory conditions. In RA patients treated with an oral JAK inhibitor, a higher rate of malignancies (excluding non-melanoma skin cancer (NMSC)) was observed when compared with TNF blockers. Patients who are current or past smokers are at additional increased risk.
Consider the benefits and risks for the individual patient prior to initiating or continuing therapy with OPZELURA, particularly in patients with a known malignancy (other than successfully treated non-melanoma skin cancers), patients who develop a malignancy when on treatment, and patients who are current or past smokers.
Non-melanoma skin cancers, including basal cell and squamous cell carcinoma, have occurred in patients treated with OPZELURA. Perform periodic skin examinations during OPZELURA treatment and following treatment as appropriate. Exposure to sunlight and UV light should be limited by wearing protective clothing and using broad-spectrum sunscreen.
MAJOR ADVERSE CARDIOVASCULAR EVENTS (MACE)
In RA patients 50 years of age and older with at least one cardiovascular risk factor treated with an oral JAK inhibitor, a higher rate of major adverse cardiovascular events (MACE) (defined as cardiovascular death, myocardial infarction, and stroke), was observed when compared with TNF blockers. Patients who are current or past smokers are at additional increased risk. Discontinue OPZELURA in patients who have experienced a myocardial infarction or stroke.
Consider the benefits and risks for the individual patient prior to initiating or continuing therapy with OPZELURA, particularly in patients who are current or past smokers and patients with other cardiovascular risk factors. Patients should be informed about the symptoms of serious cardiovascular events and the steps to take if they occur. Discontinue OPZELURA in patients that have experienced a myocardial infarction or stroke.
THROMBOSIS
Thromboembolic events were observed in trials with OPZELURA. Thrombosis, including pulmonary embolism (PE), deep venous thrombosis (DVT), and arterial thrombosis have been reported in patients receiving JAK inhibitors used to treat inflammatory conditions. Many of these adverse reactions were serious and some resulted in death. In RA patients 50 years of age and older with at least one cardiovascular risk factor treated with an oral JAK inhibitor, a higher rate of thrombosis was observed when compared with TNF blockers. Avoid OPZELURA in patients at risk. If symptoms of thrombosis occur, discontinue OPZELURA and treat appropriately.
Thrombocytopenia, Anemia, and Neutropenia
Thrombocytopenia, anemia, and neutropenia were reported in the clinical trials with OPZELURA. Consider the benefits and risks for individual patients who have a known history of these events prior to initiating therapy with OPZELURA. Perform CBC monitoring as clinically indicated. If signs and/or symptoms of clinically significant thrombocytopenia, anemia, and neutropenia occur, patients should discontinue OPZELURA.
Lipid Elevations
Treatment with oral ruxolitinib has been associated with increases in lipid parameters including total cholesterol, low-density lipoprotein (LDL) cholesterol, and triglycerides. Adverse Reactions
In atopic dermatitis, the most common adverse reactions (≥1%) are nasopharyngitis (3%), diarrhea (1%), bronchitis (1%), ear infection (1%), eosinophil count increased (1%), urticaria (1%), folliculitis (1%), tonsillitis (1%), and rhinorrhea (1%).
In nonsegmental vitiligo, the most common adverse reactions (incidence ≥1%) are application site acne (6%), application site pruritus (5%), nasopharyngitis (4%), headache (4%), urinary tract infection (2%), application site erythema (2%), and pyrexia (1%).
Pregnancy
There is a pregnancy registry that monitors pregnancy outcomes in pregnant persons exposed to OPZELURA during pregnancy. Pregnant persons exposed to OPZELURA and healthcare providers should report OPZELURA exposure by calling 1-855-463-3463.
Lactation
Advise women not to breastfeed during treatment with OPZELURA and for approximately four weeks after the last dose (approximately 5-6 elimination half-lives). Please see Brief Summary of Full Prescribing Information, including Boxed Warning, on the following pages.
OPZELURA® (ruxolitinib) cream, for topical use
Brief Summary of FULL PRESCRIBING INFORMATION
INDICATIONS AND USAGE: OPZELURA is indicated for the topical short-term and non-continuous chronic treatment of mild to moderate atopic dermatitis in non-immunocompromised adult and pediatric patients 12 years of age and older whose disease is not adequately controlled with topical prescription therapies or when those therapies are not advisable and for the topical treatment of nonsegmental vitiligo in adult and pediatric patients 12 years of age and older.
Limitations of Use: Use of OPZELURA in combination with therapeutic biologics, other JAK inhibitors, or potent immunosuppressants such as azathioprine or cyclosporine is not recommended.
WARNING: SERIOUS INFECTIONS, MORTALITY, MALIGNANCY, MAJOR ADVERSE CARDIOVASCULAR EVENTS, AND THROMBOSIS
SERIOUS INFECTIONS
Patients treated with oral Janus kinase inhibitors for inflammatory conditions are at risk for developing serious infections that may lead to hospitalization or death [see Warnings and Precautions and Adverse Reactions].
Reported infections include:
• Active tuberculosis, which may present with pulmonary or extrapulmonary disease.
• Invasive fungal infections, including cryptococcosis, and pneumocystosis.
• Bacterial, viral, including herpes zoster, and other infections due to opportunistic pathogens.
Avoid use of OPZELURA in patients with an active, serious infection, including localized infections. If a serious infection develops, interrupt OPZELURA until the infection is controlled.
The risks and benefits of treatment with OPZELURA should be carefully considered prior to initiating therapy in patients with chronic or recurrent infection.
Patients should be closely monitored for the development of signs and symptoms of infection during and after treatment with OPZELURA [see Warnings and Precautions].
MORTALITY
In a large, randomized, postmarketing safety study in rheumatoid arthritis (RA) patients 50 years of age and older with at least one cardiovascular risk factor comparing an oral JAK inhibitor to tumor necrosis factor (TNF) blocker treatment, a higher rate of all-cause mortality, including sudden cardiovascular death, was observed with the JAK inhibitor [see Warnings and Precautions]. MALIGNANCIES
Malignancies were reported in patients treated with OPZELURA. Lymphoma and other malignancies have been observed in patients receiving JAK inhibitors used to treat inflammatory conditions. In RA patients treated with an oral JAK inhibitor, a higher rate of malignancies (excluding non-melanoma skin cancer (NMSC)) was observed when compared with TNF blockers. Patients who are current or past smokers are at additional increased risk [see Warnings and Precautions].
MAJOR ADVERSE CARDIOVASCULAR EVENTS (MACE)
In RA patients 50 years of age and older with at least one cardiovascular risk factor treated with an oral JAK inhibitor, a higher rate of major adverse cardiovascular events (MACE) (defined as cardiovascular death, myocardial infarction, and stroke), was observed when compared with TNF blockers. Patients who are current or past smokers are at additional increased risk. Discontinue OPZELURA in patients who have experienced a myocardial infarction or stroke [see Warnings and Precautions].
THROMBOSIS
Thromboembolic events were observed in trials with OPZELURA. Thrombosis, including pulmonary embolism (PE), deep venous thrombosis (DVT), and arterial thrombosis have been reported in patients receiving JAK inhibitors used to treat inflammatory conditions. Many of these adverse reactions were serious and some resulted in death. In RA patients 50 years of age and older with at least one cardiovascular risk factor treated with an oral JAK inhibitor, a higher rate of thrombosis was observed when compared with TNF blockers. Avoid OPZELURA in patients at risk. If symptoms of thrombosis occur, discontinue OPZELURA and treat appropriately [see Warnings and Precautions].
have resided or traveled in areas of endemic tuberculosis or endemic mycoses; or with underlying conditions that may predispose them to infection. Closely monitor patients for the development of signs and symptoms of infection during and after treatment with OPZELURA. Interrupt OPZELURA if a patient develops a serious infection, an opportunistic infection, or sepsis. Do not resume OPZELURA until the infection is controlled.
Tuberculosis: No cases of active tuberculosis (TB) were reported in clinical trials with OPZELURA. Cases of active TB were reported in clinical trials of oral Janus kinase inhibitors used to treat inflammatory conditions. Consider evaluating patients for latent and active TB infection prior to administration of OPZELURA. During OPZELURA use, monitor patients for the development of signs and symptoms of TB.
WARNINGS AND PRECAUTIONS
Serious Infections: Serious and sometimes fatal infections due to bacterial, mycobacterial, invasive fungal, viral, or other opportunistic pathogens have been reported in patients receiving oral Janus kinase inhibitors. Serious lower respiratory tract infections were reported in the clinical development program with topical ruxolitinib. Avoid use of OPZELURA in patients with an active, serious infection, including localized infections. Consider the risks and benefits of treatment prior to initiating OPZELURA in patients: with chronic or recurrent infection; with a history of a serious or an opportunistic infection; who have been exposed to tuberculosis; who
of endemic tuberculosis or endemic mycoses; or underlying conditions that may predispose them to infection. Closely monitor patients the development of signs and symptoms of infection during and after treatment OPZELURA. Interrupt OPZELURA if a patient develops a serious infection, an opportunistic infection, or sepsis. Do not resume OPZELURA until the infection is controlled. : No cases of active tuberculosis (TB) were reported in clinical trials Cases of active TB were reported in clinical trials of oral Janus kinase inhibitors used to treat inflammatory conditions. Consider evaluating patients administration of OPZELURA. During OPZELURA
Viral Reactivation: Viral reactivation, including cases of herpes virus reactivation (e.g., herpes zoster), were reported in clinical trials with Janus kinase inhibitors used to treat inflammatory conditions including OPZELURA. If a patient develops herpes zoster, consider interrupting OPZELURA treatment until the episode resolves.
Hepatitis B and C: The impact of Janus kinase inhibitors used to treat inflammatory conditions including OPZELURA on chronic viral hepatitis reactivation is unknown. Patients with a history of hepatitis B or C infection were excluded from clinical trials. Hepatitis B viral load (HBV-DNA titer) increases, with or without associated elevations in alanine aminotransferase and aspartate aminotransferase, have been reported in patients with chronic HBV infections taking oral ruxolitinib. OPZELURA initiation is not recommended in patients with active hepatitis B or hepatitis C.
(TRuE-AD1 atopic group, and 4% and at OPZELURA adverse 4 (1%)
Urticaria 3 (1%)
: Viral reactivation, including cases of herpes virus reactivation herpes zoster), were reported in clinical trials with Janus kinase inhibitors used treat inflammatory conditions including OPZELURA. If a patient develops herpes zoster, consider interrupting OPZELURA treatment until the episode resolves. Hepatitis B and C: The impact of Janus kinase inhibitors used to treat inflammatory conditions including OPZELURA on chronic viral hepatitis reactivation is unknown. Patients with a history of hepatitis B or C infection were excluded from clinical trials. Hepatitis B viral load (HBV-DNA titer) increases, with or without associated elevations in alanine aminotransferase and aspartate aminotransferase, have been reported OPZELURA initiation
Mortality: In a large, randomized, postmarketing safety study of an oral JAK inhibitor in rheumatoid arthritis (RA) patients 50 years of age and older with at least one cardiovascular risk factor, a higher rate of all-cause mortality, including sudden cardiovascular death, was observed in patients treated with the JAK inhibitor compared with TNF blockers. Consider the benefits and risks for the individual patient prior to initiating or continuing therapy with OPZELURA.
Adverse OPZELURA pyrexia, acneiform
Nonsegmental TRuE-V2), vitiligo of subjects Asian. ≥ 1% and period any treatment 26 (6%) 5 (2%), site erythema
In a large, randomized, postmarketing safety study of an oral JAK inhibitor in rheumatoid arthritis (RA) patients 50 years of age and older with at least cardiovascular risk factor, a higher rate of all-cause mortality, including sudden cardiovascular death, was observed in patients treated with the JAK inhibitor
Consider the benefits and risks for the individual patient
Malignancy and Lymphoproliferative Disorders: Malignancies, including lymphomas, were observed in clinical trials of oral JAK inhibitors used to treat inflammatory conditions. Patients who are current or past smokers are at additional increased risk. Malignancies, including lymphomas, have occurred in patients receiving JAK inhibitors used to treat inflammatory conditions. In a large, randomized, postmarketing safety study of an oral JAK inhibitor in RA patients, a higher rate of malignancies (excluding non-melanoma skin cancer) was observed in patients treated with the JAK inhibitor compared to those treated with TNF blockers. A higher rate of lymphomas was observed in patients treated with the JAK inhibitor compared to those treated with TNF blockers. A higher rate of lung cancers was observed in current or past smokers treated with the JAK inhibitor compared to those treated with TNF blockers. In this study, current or past smokers had an additional increased risk of overall malignancies. Consider the benefits and risks for the individual patient prior to initiating or continuing therapy with OPZELURA, particularly in patients with a known malignancy (other than successfully treated non-melanoma skin cancers), patients who develop a malignancy when on treatment, and patients who are current or past smokers.
Malignancies, including lymphomas, inhibitors used to treat inflammatory conditions.
Adverse the OPZELURA hypertension, dermatitis influenza-like DRUG Drug known may increase decrease Strong inhibitors ruxolitinib
USE IN Pregnancy
Patients who are current or past smokers are at additional increased risk. Malignancies, including lymphomas, have occurred in patients receiving JAK inhibitors used to inflammatory conditions. In a large, randomized, postmarketing safety study of an JAK inhibitor in RA patients, a higher rate of malignancies (excluding non-melanoma cancer) was observed in patients treated with the JAK inhibitor compared to those treated with TNF blockers. A higher rate of lymphomas was observed in patients treated with A higher rate of lung cancers JAK inhibitor compared to treated with TNF blockers. In this study, current or past smokers had an additional increased risk of overall malignancies. Consider the benefits and risks for the individual patient prior to initiating or continuing therapy with OPZELURA, particularly in patients with a known malignancy (other than successfully treated non-melanoma skin cancers), and patients who are current
Non-melanoma Skin Cancers: Non-melanoma skin cancers including basal cell and squamous cell carcinoma have occurred in patients treated with OPZELURA. Perform periodic skin examinations during OPZELURA treatment and following treatment as appropriate. Exposure to sunlight and UV light should be limited by wearing protective clothing and using broad-spectrum sunscreen.
Pregnancy outcomes persons exposure
Non-melanoma Skin Cancers: Non-melanoma skin cancers including basal cell squamous cell carcinoma have occurred in patients treated with OPZELURA. Perform periodic skin examinations during OPZELURA treatment and following treatment appropriate. Exposure to sunlight and UV light should be limited by wearing protective
Major Adverse Cardiovascular Events (MACE): In a large, randomized, postmarketing safety study of an oral JAK inhibitor in RA patients 50 years of age and older with at least one cardiovascular risk factor, a higher rate of major adverse cardiovascular events (MACE) defined as cardiovascular death, non-fatal myocardial infarction (MI), and non-fatal stroke was observed with the JAK inhibitor compared to those treated with TNF blockers. Patients who are current or past smokers are at additional increased risk. Consider the benefits and risks for the individual patient prior to initiating or continuing therapy with OPZELURA, particularly in patients who are current or past smokers and patients with other cardiovascular risk factors. Patients should be informed about the symptoms of serious cardiovascular events and the steps to take if they occur. Discontinue OPZELURA in patients that have experienced a myocardial infarction or stroke.
Risk Summary are not other adverse of ruxolitinib adverse
In a large, randomized, postmarketing safety study of an oral JAK inhibitor in RA patients 50 years of age and older with at least cardiovascular risk factor, a higher rate of major adverse cardiovascular events (MACE) defined as cardiovascular death, non-fatal myocardial infarction (MI), and non-fatal was observed with the JAK inhibitor compared to those treated with TNF blockers. Patients Consider the benefits risks for the individual patient prior to initiating or continuing therapy with OPZELURA particularly in patients who are current or past smokers and patients with cardiovascular risk factors. Patients should be informed about the symptoms of serious cardiovascular events and the steps to take if they occur. Discontinue OPZELURA in patients
Thrombosis: Thromboembolic events were observed in clinical trials with OPZELURA. Thrombosis, including deep vein thrombosis (DVT), pulmonary embolism (PE), and arterial thrombosis have been reported in patients receiving JAK inhibitors used to treat inflammatory conditions. Many of these adverse reactions were serious and some resulted in death. In a large, randomized, postmarketing safety study of an oral JAK inhibitor in RA patients 50 years of age and older with at least one cardiovascular risk factor, higher rates of overall thrombosis, DVT, and PE were observed compared to those treated with TNF blockers. Avoid OPZELURA in patients who may be at increased risk of thrombosis. If symptoms of thrombosis occur, discontinue OPZELURA and evaluate and treat patients appropriately.
Thrombocytopenia, Anemia, and Neutropenia: Thrombocytopenia, anemia , and neutropenia were reported in the clinical trials with OPZELURA. Consider the benefits and risks for individual patients who have a known history of these events prior to initiating therapy with OPZELURA. Perform CBC monitoring as clinically indicated. If signs and/or symptoms of clinically significant thrombocytopenia, anemia, and neutropenia occur, patients should discontinue OPZELURA.
ADVERSE REACTIONS
Thromboembolic events were observed in clinical trials with OPZELURA. Thrombosis, including deep vein thrombosis (DVT), pulmonary embolism (PE), arterial thrombosis have been reported in patients receiving JAK inhibitors used treat inflammatory conditions. Many of these adverse reactions were serious some resulted in death. In a large, randomized, postmarketing safety study of an JAK inhibitor in RA patients 50 years of age and older with at least one cardiovascular risk factor, higher rates of overall thrombosis, DVT, and PE were observed compared those treated with TNF blockers. Avoid OPZELURA in patients who may be at increased risk of thrombosis. If symptoms of thrombosis occur, discontinue OPZELURA
The background populations other birth defects Data Animal of organogenesis, rabbits. weight 60 mg/kg/day. systemic exposure affected lower highest approximately study lactation embryofetal function
Lactation
T hrombocytopenia, anemia neutropenia were reported in the clinical trials with OPZELURA. Consider the benefits and risks for individual patients who have a known history of these events prior initiating therapy with OPZELURA. Perform CBC monitoring as clinically indicated. signs and/or symptoms of clinically significant thrombocytopenia, anemia,
Lipid Elevations: Treatment with oral ruxolitinib has been associated with increases in lipid parameters including total cholesterol, low-density lipoprotein (LDL) cholesterol, and triglycerides.
Treatment with oral ruxolitinib has been associated with increases in lipid parameters including total cholesterol, low-density lipoprotein
Clinical Trials Experience: Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. Atopic Dermatitis: In two double-blind, vehicle-controlled clinical trials
Risk Summary on the of lactating present serious breastfeed last dose Data: (30 mg/kg) for up the maternal several
Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the Atopic Dermatitis: In two double-blind, vehicle-controlled clinical
(TRuE-AD1 and TRuE-AD2), 499 adult and pediatric subjects 12 years of age and older with dermatitis were treated with OPZELURA twice daily for 8 weeks. In the OPZELURA 62% of subjects were females, and 71% of subjects were White, 23% were Black, 4% were Asian. The adverse reactions reported by ≥ 1% of OPZELURA treated subjects a greater incidence than in the vehicle arm through week 8 are as follows for OPZELURA (N=499) vs Vehicle (N=250), respectively: Subjects with any treatment emergent adverse event (TEAE) 132 (27%) vs 83 (33%), Nasopharyngitis 13 (3%) vs 2 (1%), Bronchitis vs 0 (0%), Ear infection 4 (1%) vs 0 (0%), Eosinophil count increased 4 (1%) vs 0 (0%), Urticaria 4 (1%) vs 0 (0%), Diarrhea 3 (1%) vs 1 (<1%), Folliculitis 3 (1%) vs 0 (0%), Tonsillitis vs 0 (0%), and Rhinorrhea 3 (1%) vs 1 (<1%).
(TRuE-AD1 and TRuE-AD2), 499 adult and pediatric subjects 12 years of age and older with atopic dermatitis were treated with OPZELURA twice daily for 8 weeks. In the OPZELURA group, 62% of subjects were females, and 71% of subjects were White, 23% were Black, and 4% were Asian. The adverse reactions reported by ≥ 1% of OPZELURA treated subjects and at a greater incidence than in the vehicle arm through week 8 are as follows for OPZELURA (N=499) vs Vehicle (N=250), respectively: Subjects with any treatment emergent adverse event (TEAE) 132 (27%) vs 83 (33%), Nasopharyngitis 13 (3%) vs 2 (1%), Bronchitis 4 (1%) vs 0 (0%), Ear infection 4 (1%) vs 0 (0%), Eosinophil count increased 4 (1%) vs 0 (0%), Urticaria 4 (1%) vs 0 (0%), Diarrhea 3 (1%) vs 1 (<1%), Folliculitis 3 (1%) vs 0 (0%), Tonsillitis 3 (1%) vs 0 (0%), and Rhinorrhea 3 (1%) vs 1 (<1%).
Adverse reactions that occurred in TRuE-AD1 and TRuE-AD2 in < 1% of subjects in the OPZELURA group and none in the vehicle group were: neutropenia, allergic conjunctivitis, pyrexia, seasonal allergy, herpes zoster, otitis externa, Staphylococcal infection, and acneiform dermatitis.
Adverse reactions that occurred in TRuE-AD1 and TRuE-AD2 in < 1% of subjects in the OPZELURA group and none in the vehicle group were: neutropenia, allergic conjunctivitis, pyrexia, seasonal allergy, herpes zoster, otitis externa, Staphylococcal infection, and acneiform dermatitis.
Nonsegmental Vitiligo TRuE-V2), 449 adult and pediatric subjects 12 years of age and older with nonsegmental were treated with OPZELURA twice daily for 24 weeks. In the OPZELURA group, 55% subjects were females, and 81% of subjects were White, 5% were Black, and 4% were The adverse reactions reported by OPZELURA and at least 1% greater incidence than in the vehicle arm in the 24-week double-blind are as follows for OPZELURA (N=449) vs Vehicle (N=224), respectively: Subjects with treatment emergent adverse event (TEAE) 214 (48%) vs 79 (35%), Application site acne (6%) vs 2 (1%), Application site pruritus 23 (5%) vs 6 (3%), Nasopharyngitis 19 (4%) vs (2%), Headache 17 (4%) vs 6 (3%), Urinary tract infection 7 (2%) vs 1 (<1%), Application erythema 7 (2%) vs 1 (<1%), and Pyrexia 6 (1%) vs 0 (0%)
Nonsegmental Vitiligo: In two double-blind, vehicle-controlled clinical trials (TRuE-V1 and TRuE-V2), 449 adult and pediatric subjects 12 years of age and older with nonsegmental vitiligo were treated with OPZELURA twice daily for 24 weeks. In the OPZELURA group, 55% of subjects were females, and 81% of subjects were White, 5% were Black, and 4% were Asian. The adverse reactions reported by OPZELURA treated subjects with an incidence of ≥ 1% and at least 1% greater incidence than in the vehicle arm in the 24-week double-blind period are as follows for OPZELURA (N=449) vs Vehicle (N=224), respectively: Subjects with any treatment emergent adverse event (TEAE) 214 (48%) vs 79 (35%), Application site acne 26 (6%) vs 2 (1%), Application site pruritus 23 (5%) vs 6 (3%), Nasopharyngitis 19 (4%) vs 5 (2%), Headache 17 (4%) vs 6 (3%), Urinary tract infection 7 (2%) vs 1 (<1%), Application site erythema 7 (2%) vs 1 (<1%), and Pyrexia 6 (1%) vs 0 (0%)
Adverse reactions that occurred in TRuE-V1 and TRuE-V2 in ≥ 0.5% to < 1% of subjects in OPZELURA group and none in the vehicle group were: application site dermatitis, hypertension, anxiety, application site discoloration, application site folliculitis, contusion, dermatitis contact, diarrhea, ear infection, gastritis, gastroenteritis, hordeolum, influenza-like illness, insomnia, nasal congestion, and vomiting.
INTERACTIONS
Adverse reactions that occurred in TRuE-V1 and TRuE-V2 in ≥ 0.5% to < 1% of subjects in the OPZELURA group and none in the vehicle group were: application site dermatitis, hypertension, anxiety, application site discoloration, application site folliculitis, contusion, dermatitis contact, diarrhea, ear infection, gastritis, gastroenteritis, hordeolum, influenza-like illness, insomnia, nasal congestion, and vomiting.
DRUG INTERACTIONS
interaction studies with known to be a substrate for cytochrome P450 3A4 increase ruxolitinib systemic concentrations whereas inducers of decrease ruxolitinib systemic concentrations.
Drug interaction studies with OPZELURA have not been conducted. Ruxolitinib is known to be a substrate for cytochrome P450 3A4 (CYP3A4). Inhibitors of CYP3A4 may increase ruxolitinib systemic concentrations whereas inducers of CYP3A4 may decrease ruxolitinib systemic concentrations.
Strong Inhibitors of CYP3A4: Avoid concomitant use of OPZELURA with strong inhibitors of CYP3A4 as there is a potential to increase the systemic exposure of ruxolitinib and could increase the risk of OPZELURA adverse reactions.
Strong Inhibitors of CYP3A4: Avoid concomitant use of OPZELURA with strong inhibitors of CYP3A4 as there is a potential to increase the systemic exposure of ruxolitinib and could increase the risk of OPZELURA adverse reactions.
IN SPECIFIC POPULATIONS
Pregnancy
USE IN SPECIFIC POPULATIONS
Pregnancy
Pregnancy Exposure Registry outcomes in pregnant persons exposed to OPZELURA during pregnancy. Pregnant persons exposed to OPZELURA and healthcare providers should report OPZELURA exposure by calling 1-855-463-3463.
Pregnancy Exposure Registry: There is a pregnancy registry that monitors pregnancy outcomes in pregnant persons exposed to OPZELURA during pregnancy. Pregnant persons exposed to OPZELURA and healthcare providers should report OPZELURA exposure by calling 1-855-463-3463.
Summary not sufficient to evaluate a drug-associated risk for major birth defects, miscarriage, or adverse maternal or fetal outcomes. In animal reproduction studies, oral administration ruxolitinib to pregnant rats and rabbits during the period of organogenesis resulted in adverse developmental outcomes at doses associated with maternal toxicity. background risks of major birth defects and miscarriage for the indicated populations are unknown. All pregnancies carry some risk of birth defects, loss, or adverse outcomes. The background risk in the U.S. general population of major defects and miscarriage is 2-4% and 15-20%, respectively.
or with patients for treatment with opportunistic trials with kinase patients for OPZELURA reactivation (e.g., used to herpes inflammatory unknown. trials. elevations reported in is not inhibitor least one sudden inhibitor patient lymphomas, conditions. Malignancies, to treat an oral non-melanoma skin treated with the cancers those additional individual patients cancers), current or cell and Perform treatment as protective postmarketing least one (MACE) stroke Patients benefits and OPZELURA, other serious patients
Risk Summary: Available data from pregnancies reported in clinical trials with OPZELURA are not sufficient to evaluate a drug-associated risk for major birth defects, miscarriage, or other adverse maternal or fetal outcomes. In animal reproduction studies, oral administration of ruxolitinib to pregnant rats and rabbits during the period of organogenesis resulted in adverse developmental outcomes at doses associated with maternal toxicity. The background risks of major birth defects and miscarriage for the indicated populations are unknown. All pregnancies carry some risk of birth defects, loss, or other adverse outcomes. The background risk in the U.S. general population of major birth defects and miscarriage is 2-4% and 15-20%, respectively.
Data
Data: Ruxolitinib was administered orally to pregnant rats or rabbits during the period organogenesis, at doses of 15, 30 rabbits. There were no treatment-related malformations at any dose. A decrease in fetal of approximately 9% was noted in rats at the highest and maternally toxic dose of mg/kg/day. This dose resulted in systemic exposure approximately 22 times the clinical systemic exposure at the maximum recommended human dose (MRHD; the clinical systemic exposure from ruxolitinib cream, 1.5% applied twice daily to 25-40% atopic dermatitisaffected body surface area is used fetal weights of approximately 8% and increased late resorptions were noted at the highest and maternally toxic dose of approximately 70% the MRHD clinical systemic exposure. In a pre-and post-natal development in rats, pregnant animals were dosed with ruxolitinib from implantation through lactation at doses up to 30 mg/kg/day. There were no drug-related adverse effects on embryofetal survival, postnatal growth, development parameters or offspring reproductive function at the highest dose evaluated (3.1 times the MRHD clinical systemic exposure).
Lactation
Pediatric Use: Atopic Dermatitis: The safety and effectiveness of OPZELURA for the topical treatment of mild-to-moderate atopic dermatitis have been established in pediatric patients aged 12 to 17 years of age. Use of OPZELURA in this age group is supported by evidence from TRuE-AD1 and TRuE-AD2, which included 92 pediatric subjects aged 12 to 17 years with mild-to-moderate atopic dermatitis. No clinically meaningful differences in safety or effectiveness were observed between adult and pediatric subjects. The safety and effectiveness of OPZELURA in pediatric patients younger than 12 years of age with atopic dermatitis have not been established. Nonsegmental Vitiligo: The safety and effectiveness of OPZELURA for the topical treatment of nonsegmental vitiligo have been established in pediatric patients aged 12 to 17 years of age. Use of OPZELURA in this age group is supported by evidence from TRuE-V1 and TRuE-V2, which included 55 pediatric subjects aged 12 to 17 years with nonsegmental vitiligo. No clinically meaningful differences in safety or effectiveness were observed between adult and pediatric subjects. The safety and effectiveness of OPZELURA in pediatric patients younger than 12 years of age with nonsegmental vitiligo have not been established. Juvenile Animal Toxicity Data: Oral administration of ruxolitinib to juvenile rats resulted in effects on growth and bone measures. When administered starting at postnatal day 7 (the equivalent of a human newborn) at doses of 1.5 to 75 mg/kg/day, evidence of fractures occurred at doses ≥ 30 mg/kg/day, and effects on body weight and other bone measures [e.g., bone mineral content, peripheral quantitative computed tomography, and x-ray analysis] occurred at doses ≥ 5 mg/kg/day. When administered starting at postnatal day 21 (the equivalent of a human 2-3 years of age) at doses of 5 to 60 mg/kg/day, effects on body weight and bone occurred at doses ≥ 15 mg/kg/day, which were considered adverse at 60 mg/kg/day. Males were more severely affected than females in all age groups, and effects were generally more severe when administration was initiated earlier in the postnatal period. These findings were observed at systemic exposures that are at least 40% the MRHD clinical systemic exposure.
Geriatric Use: Of the 1249 total subjects with atopic dermatitis in clinical trials with OPZELURA, 115 (9%) were 65 years of age and older. No clinically meaningful differences in safety or effectiveness were observed between subjects less than 65 years and subjects 65 years and older.
Of the 831 total subjects enrolled with nonsegmental vitiligo in clinical trials with OPZELURA, 65 (8%) were 65 years of age and older. Clinical trials of OPZELURA in subjects with nonsegmental vitiligo did not include sufficient numbers of subjects 65 years of age and older to determine whether they respond differently from younger adult subjects.
PATIENT COUNSELING INFORMATION
Advise the patient or caregivers to read the FDA-approved patient labeling (Medication Guide). Infections: Inform patients that they may be at increased risk for developing infections, including serious infections, when taking Janus kinase inhibitors. Instruct patients to tell their healthcare provider if they develop any signs or symptoms of an infection. Advise patients that Janus kinase inhibitors increase the risk of herpes zoster, and some cases can be serious [see Warnings and Precautions]
Malignancies and Lymphoproliferative Disorders: Inform patients that Janus kinase inhibitors may increase the risk for developing lymphomas and other malignancies including skin cancer. Instruct patients to inform their health care provider if they have ever had any type of cancer. Inform patients that periodic skin examinations should be performed while using OPZELURA. Advise patients that exposure to sunlight, and UV light should be limited by wearing protective clothing and using a broad-spectrum sunscreen [see Warnings and Precautions]
Major Adverse Cardiovascular Events: Advise patients that events of major adverse cardiovascular events (MACE) including non-fatal myocardial infarction, non-fatal stroke, and cardiovascular death, have been reported in clinical studies with Janus kinase inhibitors used to treat inflammatory conditions. Instruct all patients, especially current or past smokers or patients with other cardiovascular risk factors, to be alert for the development of signs and symptoms of cardiovascular events [see Warnings and Precautions]
Animal Data: Ruxolitinib was administered orally to pregnant rats or rabbits during the period of organogenesis, at doses of 15, 30, or 60 mg/kg/day in rats and 10, 30, or 60 mg/kg/day in rabbits. There were no treatment-related malformations at any dose. A decrease in fetal weight of approximately 9% was noted in rats at the highest and maternally toxic dose of 60 mg/kg/day. This dose resulted in systemic exposure approximately 22 times the clinical systemic exposure at the maximum recommended human dose (MRHD; the clinical systemic exposure from ruxolitinib cream, 1.5% applied twice daily to 25-40% atopic dermatitisaffected body surface area is used for calculation of multiples of human exposure). In rabbits, lower fetal weights of approximately 8% and increased late resorptions were noted at the highest and maternally toxic dose of 60 mg/kg/day. This dose resulted in systemic exposure approximately 70% the MRHD clinical systemic exposure. In a pre-and post-natal development study in rats, pregnant animals were dosed with ruxolitinib from implantation through lactation at doses up to 30 mg/kg/day. There were no drug-related adverse effects on embryofetal survival, postnatal growth, development parameters or offspring reproductive function at the highest dose evaluated (3.1 times the MRHD clinical systemic exposure).
Lactation
Summary breastfed child, or the effects on milk production. Ruxolitinib was present in the milk lactating rats. When a drug is present in animal milk, it is likely that the drug will be present in human milk. Because of the serious adverse findings in adults, including risks of serious infections, thrombocytopenia, anemia, and neutropenia, advise women not to breastfeed during treatment with OPZELURA dose (approximately
Risk Summary: There are no data on the presence of ruxolitinib in human milk, the effects on the breastfed child, or the effects on milk production. Ruxolitinib was present in the milk of lactating rats. When a drug is present in animal milk, it is likely that the drug will be present in human milk. Because of the serious adverse findings in adults, including risks of serious infections, thrombocytopenia, anemia, and neutropenia, advise women not to breastfeed during treatment with OPZELURA and for approximately four weeks after the last dose (approximately 5-6 elimination half-lives).
Lactating rats were administered a single dose of [14C]-labeled ruxolitinib mg/kg) on postnatal Day 10, after which plasma and milk samples were collected to 24 hours. The AUC for total radioactivity in milk was approximately 13 times maternal plasma AUC. Additional analysis showed the presence of ruxolitinib and several of its metabolites in milk, all at levels higher than those in maternal plasma.
OPZELURA. (PE), and used to serious and an oral cardiovascular compared to increased OPZELURA and anemia , and benefits prior to indicated. If anemia, and increases (LDL) varying directly rates clinical trials
Data: Lactating rats were administered a single dose of [14C]-labeled ruxolitinib (30 mg/kg) on postnatal Day 10, after which plasma and milk samples were collected for up to 24 hours. The AUC for total radioactivity in milk was approximately 13 times the maternal plasma AUC. Additional analysis showed the presence of ruxolitinib and several of its metabolites in milk, all at levels higher than those in maternal plasma.
Thrombosis: Advise patients that events of DVT and PE have been reported in clinical studies with Janus kinase inhibitors used to treat inflammatory conditions. Instruct patients to tell their healthcare provider if they develop any signs or symptoms of a DVT or PE [see Warnings and Precautions]
Thrombocytopenia, Anemia , and Neutropenia: Advise patients of the risk of thrombocytopenia, anemia, and neutropenia with OPZELURA. Instruct patients to tell their healthcare provider if they develop any signs or symptoms of thrombocytopenia, anemia , or neutropenia [see Warnings and Precautions]
Administration Instructions: Advise patients or caregivers that OPZELURA is for topical use only [see Dosage and Administration]
Advise patients to limit treatment to one 60 gram tube per week or one 100 gram tube per 2 weeks [see Dosage and Administration]
Pregnancy: Inform patients to report their pregnancy to Incyte Corporation at 1-855-463-3463 [see Use in Specific Populations]
Lactation: Advise a patient not to breastfeed during treatment with OPZELURA and for about four weeks after the last dose [see Use in Specific Populations]
Manufactured for:
Incyte Corporation 1801 Augustine Cut-off Wilmington, DE 19803
yltezo® Hadlima a Hulio o Hyrimoz Idacio® Simlandi® Yuflyma® Yusimry
above: Hitting the slopes at Whistler Blackcomb
By Kim-Marie Galloway
Ski Ya Later!
GET READY FOR THE ULTIMATE CANADIAN WINTER ESCAPE
Although it seems like everyone is headed to Europe to ski this season, we direct our attention to our neighbors to the North. Canada may not sound as sexy as Courchevel, but the skiing can be better. The travel certainly is.
Here are some mountains that should be on your ski punch list.
BIG WHITE
This resort is like that secret stash of powder you tell your best friends about, only it’s an entire mountain. The whole resort is ski-in/ski-out, and the powder is like nothing you’ve ever seen. Imagine cruising into a knee-deep pile, and instead of needing ACL surgery, you watch what they call “champagne powder” explode like the puff of a dandelion.
Big White has a lot going for it. It’s only 5,700 feet, so there’s no danger of altitude sickness. And it's on the interior side of British Columbia, making the snow a dry powder, of which there is never a lack (average depth of 53 inches). Fun fact: there’s no snowmaking equipment since it’s not needed.
The mountain is also famous for “snow ghosts,” giant trees fully encased in ice. How does that happen, you ask? We’ll tell you. It’s often foggy and overcast, and when clouds touch snow, the water crystals stick and create massive ice trees. If the lift line is more than 10 to 15 minutes, locals will complain about how busy it is. There are 12 lifts—10 chairlifts, a gondola and a T-bar. In addition, there are
four magic carpets for new skiers/ snowboarders. No matter which lift you choose, there is a green run to the bottom, making it the perfect resort for beginners. It’s also a snowboarder’s paradise. USA Today named Big White the best place to snowboard in Canada and the second-best place to snowboard in North America.
Stay anywhere you like; the lifts are only steps away. But don’t miss the world-famous gun barrel coffee at the Gun Barrel Grill. The waiter pulls up alongside your table with a shotgun heated over the fire and pours flaming Grand Marnier down the barrel into a glass prepared with brandy, cacao, coffee and whipped cream.
Lift tickets start at $119 per day if purchased online. There is also night skiing for only $30. Factor in the favorable exchange rate and a lift ticket is only $87 U.S. Compare that to $259 for a day in Park City (where you won’t find a flaming gun barrel drink).
TOP, LEFT: Mother Nature puts on a celestial show. BOTTOM, LEFT: The gondola offers a spectacular view of the mountain’s “snow ghosts.” BELOW: Dry powder for days at Big White
WHISTLER BLACKCOMB
This is the largest ski resort in North America and has a seven-mile top-to-bottom run. The resort has it all: ice skating, the longest gondola in existence spanning from peak to peak, ziplining through snow-covered trees, heli-skiing, snowmobiling, snowshoeing, tubing, ice climbing, snowcat touring, Olympic bobsled riding, and the newest activity, Vallea Lumina, a magical light walk through the forest at night. If heli-skiing is on your bucket list, this is the perfect place to try it. If you can handle any run on the mountain in all conditions, you're ready to take your skiing to the next level, literally. You will be outfitted with proper powder skis, receive avalanche training and be paired with a professional guide. The terrain available for heliskiers is 50 times the size of the Whistler Blackcomb resort. Imagine untracked powder, no lift lines and a season’s worth of vertical in just a few days. This is a skier’s heaven. Whistler is on the Epic Pass, and passholders get 20 percent off heliskiing. If you’re skiing without an Epic Pass, you can save significant money by purchasing your lift tickets before the season starts.
MONTTREMBLANT
Mont-Tremblant is the most European-feeling resort of our recommendations and the most convenient. Flights from any New York airport take under two hours, followed by a 90-minute drive from Montreal. We suggest hiring a car service since you won’t need a car once you’re at the mountain. Everything you need is within walking distance in the charming pedestrian village.
If you’ve skied Stowe, MontTremblant will feel familiar. The resort sits at the highest point in the Laurentian Mountains (Stowe is the highest mountain in Vermont). Both mountains are cold, but Tremblant can be frigid, so pack plenty of toe warmers. Ironically, cold plunges are one of the cool new things to do (pun intended), and there are plenty of Nordic Spas to choose from.
Try the “thermal journey” at Spa Mont-Tremblant. For a more authentic experience, head to the
Battle of the Giants, Epic vs. IKON
Two massive mountain companies are gobbling up resorts like Hungry Hungry Hippos—the Epic pass by Vail Resorts, which is not just Vail, and the IKON pass by Alterra Mountain Company. Rare are the mountains that do not belong to one or the other. Big White is one of the few independent mountains, and in our opinion, worth skiing without a pass. Epic passholders get unlimited ski days on most of the pass’s member mountains, including Vail and Whistler Blackcomb. Also, travelers will now be able to join My Epic Gear, a membership to rent premium equipment instead of traveling with it, slope-side pick-up and dropoff. Membership costs $50 for the 2024/2025 season, with a $55 daily use fee for adults and a $45 fee for kids aged three to 12.
While IKON passholders get seven days on most in-pass mountains, read the fine print. Some passes have blackout dates.
ABOVE: No car needed to navigate the pedestrian-friendly town BELOW: The charming village of Mont-Tremblant
Scandinave Spa, where hot-andcold-plunge pools run along the Diable River. However, the frozen river itself is the ultimate cold plunge. If you want the kids to try a Nordic Spa (they aren't welcome at Scandinave), stay at Hotel Quintessence, where they can try the hot/cold plunge pools. There are also some Nordic spas with kid hours depending on age in the area.
Tremblant is on the IKON Pass and is an excellent choice for families. There are plenty of off-piste activities and, of course, poutine. The mountain has four ski faces, so there are plenty of options. Kids (and beginner adults) can cruise for almost four miles on a green beginner run. If anyone has tired legs at the end of the day, there's a free cabriolet (a gondola but not for skiers) that connects the village at both ends.
GAME ON!
CRACK! DOT! BAM! IF YOU'RE CURIOUS ABOUT MAHJONG, HERE'S WHERE TO START
By Eileen Bartels
Walk into libraries, clubs and homes and you may hear the distinct sound of game tiles being shuffled, as Mahjong is taking many towns by storm.
Consider it pickleball for the mind. Developed in 19th-century China, there are more than 40 variations. Recent enthusiasm for the game may be credited to young entrepreneurs designing contemporary tiles and fresh merchandise bringing a bit of fashion to the game.
Mahjong is a great way to socialize while challenging the mind with memorization, focus and strategy, and its intergenerational appeal makes it the perfect game for family gatherings. For younger players, it sharpens concentration, as there can be no pausing to scroll an iPhone. For aging players, it improves cognition.
Whether you’re looking for socialization or a gym for the mind, there couldn’t be more reasons to learn how to play.
Yes, it takes time to learn, but the more you play, the quicker it all comes together. Locally, many clubs and libraries are beginning to host introduction-to-Mahjong opportunities. It's like open basketball night at the gym with a coach on-hand to help. Online classes are also an excellent way to begin to build Mahjong knowledge. YouTube features a rabbit hole of videos where you can learn the basics. And to put that knowledge to practice, apps are a good way to hone your skills. Many of the better apps must be purchased but are typically less than $20.
Here's a primer to get you on your way.
THE BASICS
Mahjong is a tile game typically played with four players. For every group of four you’ll need a square table, a set of tiles, dice, racks and pushers (unique Mahjong tools used to display a player’s hand of tiles and create a “wall” from where players draw new tiles). Additional helpful tools are a neoprene mat or tablecloth that the tiles can move smoothly on.
TILES There’s a wide range of tile price and styles. If you’re just learning, you may want a set that’s simple and clear. Basic sets can be purchased on Amazon and several online retailers for less than $100. Selecting a set of tiles can be like choosing a good chess set: the nicer the set the larger the investment. Once you decide to commit, you may want to invest in a set that reflects your personality. For most play, you’re looking for a 166-piece American Mahjong standard size tile set.
MATS A neoprene mat is ideal for moving the tiles across the table with ease. Makers such as Oh My Mahjong offer beginner mats with a few of the basic rules printed on them, a helpful tool for learning.
GAME TABLES Game play is best on a roughly 32-inch square card table. A larger table works well for groups who are learning. Although the game is typically played with four people per table, playing as partners with open hands is a good way to learn. Specialty Mahjong tables are available online with built in slots for tiles and walls that replace racks and pushers.
RACKS AND PUSHERS A Mahjong rack and pusher is a unique game piece that looks a little like a complicated Scrabble rack. These come in acrylic or wood. For players who venture from the standard tile size, regular racks can be a little short but still work. Many online retailers make specialty racks to accommodate slightly larger tiles.
THE CARD
What keeps Mahjong fresh is that each year the National Mah Jongg League issues a new list of winning hands on a card that’s used during game play. Each player should have an official Mahjong card for the current year. They are best purchased directly from the NMJL’s online site. Be cautious buying cards from other retailers, particularly Amazon, as they can be counterfeit or outdated. Official cards cost $14 for standard size and $15 for a slightly larger size that’s easier to read. nationalmahjonggleague.org
WHERE TO SHOP
OH, MY MAHJONG makes play fun. There are excellent starter kits that combine tiles, racks, a mat and a travel bag (from $417 to $835). Tiles sets start at $375. You’ll be ready to hit the road with the Charleston Travel set ($419). The Aqua Pool Mat folds up for travel and floats so you can play in the pool or at the beach ($350). The Let’s Rack and Roll Bags keep racks organized ($80). From hats to totes, they offer it all. Retailer Neiman Marcus also carries tile sets and accessories from this brand. ohmymahjong. com; neimanmarcus.com
THE SOUTHERN SPARROW’S theme is “play beautifully” and the tiles reflect that. The Chinoiserie sets in breezy blue, polished pink, luxe lilac are lovely ($309) and deserving of the matching lucite display case ($64). The trellis design table mats match each set ($49) and large clear acrylic racks are available ($59). southernsparrow.com
From front to back, WHERE THE WINDS BLOW tiles are attractive on both sides. The site offers personalized sets with custom jokers and monogrammed back sides ($300 to $425). Standard tile sets with sparkly backsides start at $125. Vision impaired tiles boast larger numbers and lettering ($125). wherethewindblows.com
MY FAIR MAHJONG is a small retailer that makes fun tiles with personality in limited themes and series. The Southwest theme tiles are colorful on a soft pink background with scorpions as “dragons.” Other sets sure to reflect a player’s personality are the Texas and NYC series. These sets retail for $299 and come in a slightly larger tile size. The brand also features simple colorful table mats with scalloped edges. The Mini Travel Anywhere series is travel-themed and smaller so it can be packed up and brought on a trip ($210). Another simpler travel set retails for $64 and makes a great gift. Mahjong scoreboards, cups and coasters are also available. myfairmahjong.com
It’s easy to fall in love with THE MAHJONG LINE tiles including the charming dog jokers to the seahorse “dragons.” Themes come in a range of colors from Lucky Jade to Ceylon Blue. (Sets start at $375.) The Floating AquaMahj mat is $225, with slots for larger tiles; there are also waterproof travel cards that can be used in lieu of tiles for pool play ($75). Accessories include a travel bag with room for racks as well as mats and tiles that can be monogrammed (starting at $265). themahjongline.com
SPLURGE
DESIGNER RETAILERS KNOW THEIR AUDIENCE
Gucci gets in the game with a GG Supreme canvas case retailing for $23,000. Even at that price, this set is popular and typically backordered for several months. gucci.com
The famed Manhattan design house sells a Mahjong set in a signature Tiffany Blue Leather Box for $15,000. tiffany.com
AUTOMATIC TABLE
We’ve seen it all …
For the player who has everything, how about letting the table do the work for you? Although part of the game is the initial mixing (“washing”) of the tiles, for those who want to get right to the action, the Automatic Mahjong Table mixes and builds the “walls” for you ($800 to $1,800). usamjtable.com
VISIT THE SITES
They’re not just one-stop shopping.
In addition to being a source of great tiles, most small businesses are passionate about Mahjong and feature websites chock-full of information on how to play the game, how to find a teacher, etc. Spend time on websites and follow them on Instagram for tips on gameplay.
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