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OCTOBER 2020

CLINICAL

ALERT YOUR MONTHLY SOURCE FOR DRUG INFORMATION HIGHLIGHTS

EDITORIAL STAFF EDITOR IN CHIEF Maryam Tabatabai PharmD

TRENDING TOPICS

BEHAVIORAL HEALTH CORNER

COVID-19 UPDATE

DRUG INFORMATION HAPPENINGS & HIGHLIGHTS

PIPELINE NEWS

RECENT FDA APPROVALS

EXECUTIVE EDITOR Anna Schreck Bird PharmD DEPUTY EDITORS Jessica Czechowski PharmD Lara Frick PharmD, BCPS, BCPP Carole Kerzic RPh Leslie Pittman PharmD


TRENDING TOPICS NEW WEEKLY GROWTH HORMONE THERAPY The United States (US) Food and Drug Administration (FDA) has approved Novo Nordisk’s once-weekly human growth hormone (HGH) analog, somapacitan-beco (Sogroya®). Somapacitan-beco is indicated for the replacement of endogenous growth hormone (GH) in adults with growth hormone deficiency (GHD), which is a rare disorder caused by insufficient GH production. Management of adults with GHD includes GH replacement therapy. Recombinant GH, somatropin, is available from multiple manufacturers and is also indicated for adults with GHD. However, these products are given as daily subcutaneous (SC) injections. Somapacitan-beco provides an additional once-weekly GH therapy for adults with GHD. Somapacitan-beco is supplied as a 10 mg/1.5 mL solution in a single-patient-use prefilled pen that allows for individualizing the patient dose in 0.05 mg increments ranging from 0.05 mg to 4 mg. The patient can selfadminister the product by SC injection into the abdomen or thigh following training by a healthcare professional (HCP). The initial dose for treatment-naïve patients and those switching from daily GH therapy with somatropin is 1.5 mg once weekly. The weekly dose is titrated every 2 to 4 weeks by 0.5 mg to 1.5 mg until the desired response is reached (based on serum insulin-like growth factor 1 [IGF-1] levels), up to the maximum recommended dose of 8 mg once weekly. The dose should be decreased, as needed, due to adverse reactions and/or serum IGF-1 levels greater than the normal range. Patients who are ≥ 65 years old, have moderate hepatic impairment, or are on oral estrogen therapy require alternative starting doses. The efficacy and safety of somapacitan-beco were assessed in a randomized, double-blind, placebo-controlled, 35week study conducted in treatment-naïve adult patients with GHD. Patients received somapacitan-beco weekly, somatropin daily, or placebo. Efficacy was based on the percentage change of truncal fat, which is regulated by GH. At week 34, somapacitan-beco resulted in a -1.06% 2 | OCTOBER 2020

reduction in the change from baseline in truncal fat compared to a 0.47% increase with placebo (treatment difference, -1.53%; 95% confidence interval [CI], -2.68 to -0.38). Patients on daily somatropin also demonstrated a decrease in truncal fat (-2.23%) from baseline. Somapacitan-beco is contraindicated in patients with active malignancy, acute critical illness, hypersensitivity to the product, and active proliferative or severe nonproliferative diabetic retinopathy. It also carries a number of warnings and precautions, including an increased risk of neoplasm, glucose intolerance and diabetes, intracranial hypertension, pancreatitis, hypoadrenalism, fluid retention, hypothyroidism, and lipohypertrophy or lipoatrophy. Patients should receive a fundoscopic exam prior to starting and periodically during therapy to exclude papilledema (swelling of the optic nerve), which can be a symptom of intracranial hypertension.

BOXED WARNING REMOVED FOR DM DRUG The FDA has removed the boxed warning on the risk of amputations from the product labeling of the diabetes medications canagliflozin (Invokana®) and canagliflozin/ metformin hydrochloride (Invokamet®, Invokamet® XR). The prior boxed warning was added in 2017, following a determination that the risk for amputation was significant compared to the potential benefit of therapy for use as an adjunct to diet and exercise for decreasing blood glucose levels in adults with type 2 diabetes mellitus (DM). Other clinical benefits leading to additional indication approvals have resulted in increased benefits of the drug, and the risk of amputation is suggested to be lower than previously reported, especially with appropriate monitoring. As a result, the FDA has determined that the boxed warning should be removed. As there remains an increased risk with canagliflozin, the potential for amputation is still included in the Warnings and Precautions section of the product labeling.


TRENDING TOPICS continued

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HCTZ AND THE RISK OF SKIN CANCER

COVID-19: NOTABLE DEVELOPMENTS

The FDA has approved label changes for drugs containing hydrochlorothiazide (HCTZ) to notify HCPs and patients about the small but increased risk of non-melanoma skin cancer (basal cell skin cancer or squamous cell skin cancer) associated with HCTZ. The FDA Sentinel Initiative study determined that the increased risk of skin cancer was primarily linked to squamous cell carcinoma (SCC). In patients on HCTZ, the increased risk was about 1 additional case per 16,000 patients per year.

The FDA has approved an Emergency Use Authorization (EUA) for investigational convalescent plasma for the treatment of novel coronavirus infection (COVID-19) in hospitalized patients. Based on current evidence, the potential benefit of convalescent plasma has been determined to be greater than the potential risks. There are currently no approved alternative therapies, and COVID-19 convalescent plasma may improve disease severity or shorten the course of illness in hospitalized patients.

BEHAVIORAL HEALTH CORNER: APA SCHIZOPHRENIA GUIDELINES

The EUA allows for distribution of COVID-19 convalescent plasma and administration by HCPs for treating suspected or laboratory-confirmed COVID-19 in hospitalized patients. The FDA notes that potential adverse effects include allergic reactions, transfusionassociated circulatory overload or lung injury, and transfusion-transmitted infections. The agency also states that the EUA does not replace randomized clinical trials, which are crucial for definitively determining the safety and efficacy of COVID-19 convalescent plasma for COVID-19 illness.

The American Psychiatric Association (APA) updated their guidelines on the treatment of schizophrenia. Regarding drug therapy, patients with schizophrenia are recommended to receive treatment with an antipsychotic medication with monitoring for efficacy and adverse effects. An antipsychotic should be continued in patients with symptom improvement. The use of clozapine is recommended specifically in patients who are treatment-resistant or when the risk for suicide attempt or suicidality remains significant despite other treatment. In patients with aggressive behavior that continues to be significant despite other treatments, clozapine is suggested. Long-acting injectable (LAI) antipsychotics are suggested to be used when the patient prefers these agents or in those with a history of poor or uncertain adherence. Notable drug therapy statements on treatment of antipsychotic-related adverse effects are also provided and include the use of an anticholinergic for patients with acute dystonia. For patients with parkinsonism associated with antipsychotic therapy, APA suggests lowering the dose, switching therapy to another antipsychotic, or use of an anticholinergic. For patients with akathisia, lowering the dose, switching therapy to another antipsychotic, or use of a benzodiazepine or a beta-blocker are suggested. For moderate, severe, or disabling tardive dyskinesia, use of a reversible vesicular monoamine transporter 2 (VMAT2) inhibitor is recommended. In addition to drug therapy recommendations, the guidelines also provide recommendations regarding patient assessment, treatment planning, and psychosocial interventions.

The National Institutes of Health (NIH)’s COVID-19 Treatment Guideline Panel has released a statement on the EUA advising that the data are currently inadequate to recommend for or against use of convalescent plasma for COVID-19. Although data suggest that serious adverse reactions are rare, the long-term effects have not been evaluated. Furthermore, it should not be considered standard of care for COVID-19 patients, and prospective, sufficiently powered, controlled, randomized studies are required to assess its efficacy and safety. The FDA has announced a public meeting of the Vaccines and Related Biological Products Advisory Committee will be held on October 22, 2020. The meeting will focus on the development and approval of vaccines for the prevention of COVID-19. For more resources on COVID-19, visit the Magellan Rx Coronavirus Update webpage. For the most current information, visit the FDA, the Centers for Disease Control and Prevention (CDC), the NIH, and the World Health Organization (WHO) websites. State and local health departments also provide valuable information regarding management in local communities.


DRUG INFORMATION

HAPPENINGS & HIGHLIGHTS • Following reports of nitrosamine impurities, the FDA issued a communication regarding their work to mitigate shortages of rifampin (Rifadin®) and rifapentine (Priftin®). The agency will temporarily allow distribution of rifampin containing 1-methyl-4-nitrosopiperazine (MNP) or rifapentine containing 1-cyclopentyl-4-nitrosopiperazine (CPNP) greater than the acceptable intake limits in an effort to maintain access until impurities can be reduced or eliminated. For additional details, view the FDA’s Communication. Furthermore, the FDA has issued guidance to industry on the detection and prevention of these impurities. • Emergent, the manufacturer of the naloxone nasal spray (Narcan®), has announced the FDA approval of an extension to the shelf life of the product. Previously 24 months, the shelf life has been extended to 36 months. Naloxone nasal spray is an opioid antagonist FDA-approved for the emergency treatment of opioid overdose, as characterized by respiratory and/or central nervous system (CNS) depression.

• Bayshore has announced a voluntary recall of 1 lot of metformin hydrochloride (HCl) extended-release (ER) tablets USP, 500 mg, supplied in 1,000-count bottles and 1 lot of metformin HCl ER tablets USP, 750 mg, supplied in 100-count bottles that are within expiry. The recall is to the consumer level and is due to the detection of N-Nitrosodimethylamine (NDMA) levels above the acceptable daily intake limit. For details, view the recall announcement. For more information and for updates on NDMA in metformin-containing products, visit the FDA’s website. • Mylan has received FDA approval for the first generic version of Biogen’s dimethyl fumarate (Tecfidera®). Dimethyl fumarate is indicated for the treatment of relapsing forms of multiple sclerosis (MS) in adults, to include clinically isolated syndrome, relapsing-remitting disease, and active secondary progressive disease. It is available as an oral delayed-release capsule in the strengths of 120 mg and 240 mg. For additional details on the new generic, view the manufacturer’s press release.

DRUG INFORMATION HAPPENINGS • The American Board of Internal Medicine (ABIM) Foundation initiative, Choosing Wisely, released an American Academy of Pediatrics (AAP) section providing evidence-based recommendations on therapies and practices used for the management of asthma, respiratory disorders, and sleep conditions in pediatric patients. • The American College of Physicians (ACP) and the American Academy of Family Physicians (AAFP) have published a new clinical practice guideline on the management of acute pain associated with non-low back musculoskeletal injuries in outpatient adults. • The American Society of Hematology (ASH) published 2020 guidelines for treating newly-diagnosed acute myeloid leukemia (AML) in older adults. • The US Preventive Services Task Force (USPSTF) has issued a final recommendation on behavioral counseling for sexually transmitted infections (STIs). Behavioral counseling is recommended for all sexually active adolescents and for adults who are at increased risk for STIs (Grade B).

4 | OCTOBER 2020


PIPELINE

NEWS

UPCOMING PRESCRIPTION DRUG/BIOSIMILAR USER FEE ACT (PDUFA/BsUFA) DATES DRUG NAME MANUFACTURER

FORMULATION THERAPEUTIC CLASS

PROPOSED CLINICAL USE

ANTICIPATED FDA APPROVAL

tramadol Fortress

• IV • Opioid agonist

Postsurgical pain

10/09/2020

zolmitriptan microneedle patch Zosano

• Transdermal • Triptan

Acute migraine treatment

10/20/2020

eflapegrastim Spectrum

• SC • Colony stimulating factor

Chemotherapy-induced neutropenia

10/23/2020

REGN-EB3 Regeneron

• IV • Antiviral antibody

Ebola virus infection

10/23/2020

loteprednol etabonate 0.25% Kala

• Ophthalmic • Glucocorticosteroid

Dry eye syndrome

10/30/2020

mannitol dry powder Pharmaxis

• Inhalation • Mucolytic

Cystic fibrosis

10/30/2020

viloxazine Supernus

• Oral • Serotonin norepinephrine modulating agent

Attention deficit hyperactivity disorder (ADHD)

11/06/2020

amphetamine (immediate-release, tamper-resistant) Arbor

• Oral • CNS stimulant

ADHD

11/13/2020

naloxone prefilled syringe US WorldMeds

• IM • Opioid antagonist

Opioid overdose

11/13/2020

samidorphan/olanzapine Alkermes

• Oral • Opioid antagonist/atypical antipsychotic

Bipolar disorder; Schizophrenia

11/13/2020

sutimlimab Sanofi

• IV • Complement inhibitor

Cold agglutinin disease

11/13/2020

IM = intramuscular; IV = intravenous; SC = subcutaneous


RECENT FDA

APPROVALS DRUG NAME MANUFACTURER

DESCRIPTION

New Drugs clascoterone (Winlevi®) Cassiopea

• NDA approval 08/26/2020 • Indicated for the topical treatment of acne vulgaris in patients ≥ 12 years of age • Androgen receptor inhibitor • Topical cream: 1% in a 60 g tube • Recommended dosage is a thin layer (approximately 1 g) applied topically to affected area twice daily • Product availability is expected in early 2021

bupivacaine (Xaracoll®) Innocoll

• 505(b)(2) NDA approval 08/28/2020 • Indicated for use in adults for placement into the surgical site to produce postsurgical analgesia for up to 24 hours following open inguinal hernia repair; safety and efficacy have not been established in other surgical procedures (e.g., orthopedic and boney procedures) • Amide local anesthetic • Resorbable and biodegradable collagen implant: 100 mg bupivacaine per implant (3 implants per package) • Recommended dosage is 300 mg (3 implants); cut each implant in half using aseptic technique prior to placing the dry implants into the surgical site; place 3 halves below the site of mesh placement and 3 halves below the skin closure • Product availability is expected in late 2020

somapacitan-beco (Sogroya®) Novo Nordisk

• BLA approval 08/28/2020 • Indicated for the replacement of endogenous GH in adults with GHD • Human GH analog • Injection: 10 mg/1.5 mL (6.7 mg/mL) prefilled pen • Recommended initial dosages are: » 1.5 mg SC once weekly for treatment-naïve patients and those switching from daily GH therapy » 1 mg SC once weekly in patients ≥ 65 years of age and for those with moderate hepatic impairment » 2 mg SC once weekly in women taking oral estrogen • Titrate dose based on serum IGF-1 level and clinical response; may increase dose every 2 to 4 weeks by 0.5 mg to 1.5 mg; maximum dose is 8 mg once weekly

ANDA = Abbreviated New Drug Application; BLA = Biologics License Application; H = Half; NDA = New Drug Application; Q = Quarter; sBLA = Supplemental Biologics License Application; sNDA = Supplemental New Drug Application; 505(b)(2) = FDA approval pathway that allows for submission of data from studies not conducted by or for the applicant.

6 | OCTOBER 2020


RECENT FDA APPROVALS continued DRUG NAME MANUFACTURER

DESCRIPTION

New Drugs continued azacitidine (Onureg®) Celgene

• NDA approval 09/01/2020; Orphan Drug, Priority Review • Indicated for continued treatment of adults with acute myeloid leukemia (AML) who achieved 1st complete remission (CR) or complete remission with incomplete blood count recovery (CRi) following intensive induction chemotherapy and who are not able to complete intensive curative therapy • Nucleoside metabolic inhibitor • Tablets: 200 mg and 300 mg • Recommended dosage is 300 mg orally once daily on days 1 to 14 of each 28-day cycle; continue until disease progression or unacceptable toxicity; administer an antiemetic before each dose for at least the first 2 cycles; follow appropriate handling and disposal procedures for hazardous drugs • Not a substitute for IV or SC azacitidine (Vidaza®)

tramadol HCl (Qdolo™) Athena Biosciences

• 505(b)(2) NDA approval 09/01/2020 • Indicated for use in adults for the management of pain severe enough to require an opioid analgesic and for which alternative treatments are inadequate; due to the risks of addiction, abuse, and misuse with opioids, reserve for use in patients for whom alternative treatments have not been tolerated or have provided inadequate analgesia • Opioid agonist • Oral solution: 5 mg/mL • Recommended initial dosage is 25 mg per day; may titrate the dose as described in the product labeling as 25 mg (initial) to 50 mg increments every 3 days; maximum 400 mg per day, divided in doses given every 4 to 6 hours • Boxed warnings for addiction, abuse, misuse; medication errors; life-threatening respiratory depression; accidental ingestion; ultra-rapid metabolism in children; neonatal opioid withdrawal syndrome; potential drug interaction with CYP450 isoenzymes; concomitant use with benzodiazepines or other CNS depressants; requirement for Risk Evaluation and Mitigation Strategy (REMS) program • Scheduled IV controlled substance

pralsetinib (Gavreto™) Blueprint/Genentech

• NDA approval 09/04/2020; Accelerated Approval, Assessment Aid, Breakthrough Therapy, Orphan Drug, Priority Review, Real-Time Oncology Review • Indicated for the treatment of adults with metastatic rearranged during transfection (RET) fusion-positive non-small cell lung cancer (NSCLC) as detected by an FDA-approved test; continued approval may require demonstration of benefit in confirmatory clinical trials • Kinase inhibitor of wild-type RET and oncogenic RET fusions and mutations • Capsule: 100 mg • Recommended dosage is 400 mg orally once daily on an empty stomach (no food for ≥ 2 hours before and ≥ 1 hour after) with therapy continued until disease progression or until unacceptable toxicity

ANDA = Abbreviated New Drug Application; BLA = Biologics License Application; H = Half; NDA = New Drug Application; Q = Quarter; sBLA = Supplemental Biologics License Application; sNDA = Supplemental New Drug Application; 505(b)(2) = FDA approval pathway that allows for submission of data from studies not conducted by or for the applicant.

References:

fda.gov

nih.gov

psychiatryonline.org

rarediseases.org

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