Drug News A review of new launches, new indications, new dosage forms and Health Canada advisories

New Products

Kerendia for reducing cardiorenal risk finerenone 10 mg and 20 mg tablets, Bayer.

INDICATIONS An adjunct to standard therapy in adults with chronic kidney disease and type 2 diabetes. Used to reduce the risk of end-stage kidney disease and a sustained decrease in estimated glomerular filtration rate, and the risk of cardiovascular death, nonfatal myocardial infarction and hospitalization for heart failure.

within the first four weeks. The drug should not be started in patients with a serum potassium > 5.0 mmol/L or if the eGFR is < 25 mL/min/1.73m2. Take tablet at approximately the same time each day, with a glass of water, with or without food.

ADVERSE EFFECTS MOST COMMON: Hyperkalemia and decreased GFR. Hyperuricemia, hyponatremia, hypotension and pruritus have been reported. MOST SERIOUS: Hyperkalemia leading to hospitalization.

are candidates for systemic therapy or phototherapy.

ACTION A tyrosine kinase 2 (TYK2) inhibitor. Inhibits receptor-mediated activation of TYK2, which inhibits the release of proinflammatory cytokines and chemokines.

ACTION A nonsteroidal, selective mineralocorticoid receptor antagonist. Blocks the binding of aldosterone to mineralocorticoid receptors. Mechanisms by which finerenone helps to reduce renal and cardiovascular events are not completely understood, but may involve attenuation of inflammation and fibrosis (which are thought to be mediated by overactivation of mineralocorticoid receptors) and counteracting sodium retention in the kidneys and hypertrophic processes in the kidneys, heart and blood vessels. Has no significant affinity for androgen, progesterone, estrogen or glucocorticoid receptors; therefore, it is unlikely to cause sex hormone-related adverse events (e.g., gynecomastia).

DOSAGE Patients should be adequately treated with standard of care therapy before starting finerenone. Starting dose is 20 mg once daily if eGFR (estimated glomerular filtration rate) ≥ 60 mL/min/1.73m2, or 10 mg once daily if eGFR ≥ 25 to < 60 mL/ min/1.73m2. Should only be initiated when serum potassium is ≤ 4.8 mmol/L, but may be considered if serum potassium is > 4.8 to 5.0 mmol/L, provided that there is additional serum potassium monitoring

DRUG INTERACTIONS Contraindicated in patients receiving concomitant treatment with strong CYP3A4 inhibitors (e.g., itraconazole, ketoconazole, ritonavir, nelfinavir, cobicistat, clarithromycin). Use with weak CYP3A4 inhibitors (e.g., amiodarone, fluvoxamine) or moderate CYP3A4 inhibitors (e.g., erythromycin, verapamil) is expected to increase finerenone exposure; consider additional serum potassium monitoring, especially when starting or changing the dose of finerenone or the CYP3A4 inhibitor. Avoid concomitant use of moderate CYP3A4 inducers (e.g., efavirenz, phenobarbital) or strong CYP3A4 inducers (e.g., rifampin, carbamazepine, phenytoin, St John’s wort) as these agents are expected to markedly decrease finerenone plasma concentrations and result in reduced therapeutic effect. Avoid intake of grapefruit or grapefruit juice as this is expected to increase finerenone plasma concentrations.

Risk of hyperkalemia is increased if used concomitantly with medications that increase serum potassium. Avoid concomitant use with potassium-sparing diuretics (e.g., amiloride, triamterene), or other mineralocorticoid receptor antagonists (e.g., eplerenone, spironolactone). Use with caution and monitor serum potassium when taken concomitantly with potassium supplements, trimethoprim or trimethoprim–sulfamethoxazole; temporary discontinuation of finerenone may be necessary.

Sotyktu for psoriasis deucravacitinib 6 mg tablets, Bristol-Myers Squibb.

INDICATIONS Treatment of moderate to severe plaque psoriasis in adults who

DOSAGE 6 mg orally once daily. No dosage adjustment is required in patients with mild, moderate or severe renal impairment or mild or moderate hepatic impairment. Not recommended in severe hepatic impairment.

ADMINISTRATION Can be administered with or without food. Swallow tablets whole; do not crush, cut or chew.

ADVERSE EFFECTS MOST COMMON: Upper respiratory tract infection (~19%), acneiform rash, herpes simplex infections, oral ulcers, folliculitis (all < 5%). Increases in creatine phosphokinase and liver transaminases (ALT, AST) have been reported.

MOST SERIOUS: Serious infections (< 1%). Should not be started in patients with any clinically important active infection until the infection resolves or is adequately treated. Consider risks and benefits before prescribing deucravacitinib in patients with a chronic infection or a history of recurrent infection. Evaluate patients for tuberculosis infection prior to initiating treatment. DRUG INTERACTIONS Avoid use of live vaccines. Consider completing all ageappropriate immunizations before starting deucravacitinib therapy. Safety and efficacy of combining deucravacitinib with immunosuppressants, including biologics, has not been evaluated in patients with psoriasis. Not recommended for use in combination with other potent immunosuppressants, due to the increased risk of infection during treatment.

COMMENTS First tyrosine kinase 2 inhibitor for psoriasis to be marketed in Canada.

Tabrecta for nonsmall cell lung cancer

capmatinib 150 mg and 200 mg tablets (as capmatinib hydrochloride), Novartis.

INDICATIONS Treatment of locally advanced unresectable or metastatic nonsmall cell lung cancer in adults harbouring mesenchymal-epithelial transition (MET) exon 14 skipping alterations. Issued market authorization with conditions, pending the results of trials to verify the drug’s clinical benefit.

ACTION An inhibitor of the MET receptor tyrosine kinase, which leads to inhibition of the proliferation and survival of METdependent cancer cells.

DOSAGE 400 mg twice daily, with or without food. Continue until disease progression or unacceptable toxicity occurs. Dose reduction or modification may be required to manage adverse reactions.

ADVERSE EFFECTS MOST COMMON: Peripheral edema, nausea, fatigue, vomiting, dyspnea, decreased appetite. Risk of photosensitivity reactions; advise patients to limit direct ultraviolet exposure during treatment and to use sunscreen/protective clothing. MOST

SERIOUS: Dyspnea, pneumonia, pleural effusion, vomiting, interstitial lung disease/ pneumonitis, hepatotoxicity (alanine aminotransferase [ALT] and/or aspartate aminotransferase [AST] elevations). Liver function tests (ALT, AST, total bilirubin) should be performed before starting treatment, every two weeks during the first three months of treatment, then once a month or as clinically indicated. Elevations in amylase and lipase (acute pancreatitis may occur); monitor amylase and lipase at baseline and regularly during treatment. Some deaths have been reported (from hepatitis, treatment-related pneumonitis).

DRUG INTERACTIONS A substrate of CYP3A4. Coadministration with a strong CYP3A inhibitor (e.g., clarithromycin, indinavir, itraconazole, lopinavir/ritonavir, verapamil) may increase the incidence and severity of capmatinib adverse reactions. Coadministration with a strong or moderate CYP3A inducer (e.g., carbamazepine, phenobarbital, phenytoin, rifampin, St. John’s wort) may decrease capmatinib antitumour activity. Capmatinib is a moderate inhibitor of CYP1A2 and an inhibitor of transporters P-gp and BCRP. Coadministration with a CYP1A2, P-gp or BCRP substrate may increase the incidence and severity of adverse drug reactions of these substrates.

Ubrelvy for acute migraine ubrogepant 50 mg and 100 mg tablets, AbbVie.

INDICATIONS Acute treatment of migraine, with or without aura, in adults.

ACTION A calcitonin gene-related peptide (CGRP) antagonist. CGRP is released from sensory nerve endings during a migraine attack. Ubrogepant may relieve migraine by blocking CGRP-induced neurogenic vasodilation, halting the cascade of CGRPinduced neurogenic inflammation, and/or inhibiting the central relay of pain signals from the trigeminal nerve to the caudal trigeminal nucleus.

DOSAGE 50 mg or 100 mg, taken with or without food. If needed, a second dose may be taken at least two hours after the initial dose. Maximum daily dose is 200 mg. Limit doses to 50 mg (initial and optional second dose) in patients with severe hepatic impairment (Child-Pugh Class C) or severe renal impairment (CrCl 15–29 mL/min). The safety of taking more than 16 doses in a 30-day period has not been established.

ADVERSE EFFECTS MOST COMMON: Nausea, somnolence, and dry mouth (all < 5%).

MOST SERIOUS: Hypersensitivity (e.g., rash, urticaria, facial edema, dyspnea).

DRUG INTERACTIONS Metabolized primarily by CYP3A4. Contraindicated with strong CYP3A4 inhibitors (e.g., ketoconazole, itraconazole, clarithromycin). Patients using moderate CYP3A4 inhibitors (e.g., ciprofloxacin, fluconazole, fluvoxamine, verapamil, grapefruit juice) should use only a single 50 mg dose of ubrogepant and avoid taking a second dose within 24 hours. Avoid use with strong CYP3A4 inducers (e.g., phenytoin, rifampin, St. John’s wort), as loss of ubrogepant efficacy is expected. Consider using the 100 mg dose of ubrogepant if co-administered with weak or moderate CYP3A4 inducers (e.g., modafinil, bosentan, efavirenz, primidone).

COMMENTS First oral CGRP antagonist to be marketed in Canada.

Other New Products

Kirsty insulin aspart solution for subcutaneous injection 100 units/mL; 3 mL disposable prefilled pen, BGP Pharma/Viatris.

INDICATIONS 1. Treatment of patients with diabetes who require insulin for the control of hyperglycemia. Should normally be used in regimens together with an intermediate or long-acting insulin.

2. Kirsty 10 mL vials (approved, but not yet marketed in Canada) may also be used for continuous subcutaneous insulin infusion (CSII) in pump systems that are licensed in Canada for insulin infusion.

DOSAGE Individualized; consult product monograph for details.

COMMENTS Second biosimilar to NovoRapid (Novo Nordisk) to be marketed in Canada, following Trurapi (Sanofi-Aventis).

Koselugo selumetinib 10 mg and 25 mg capsules, AstraZeneca.

INDICATIONS Treatment of neurofibromatosis type 1 (NF1) in children two years of age or older who have symptomatic, inoperable plexiform neurofibromas.

DOSAGE 25 mg/m2, taken orally twice daily (about every 12 hours). Doses should be rounded to the nearest achievable 5 mg or 10 mg dose (up to a maximum single dose of 50 mg). Different strengths of capsules can be combined to provide the required dose.

ADMINISTRATION Take on an empty stomach with no food or drink other than water. Do not consume food within two hours before dosing and one hour after dosing. Swallow capsules whole with water; do not chew, dissolve or open capsules. Should not be administered to children who are unable to swallow a whole capsule.

Livtencity

maribavir 200 mg tablets, Takeda.

INDICATIONS An antiviral for the treatment of adults with post-transplant cytomegalovirus infection/disease. Intended for patients who are refractory (with or without genotypic resistance) to one or more prior antiviral therapies. DOSAGE 400 mg (two 200 mg tablets) twice daily, with or without food.

Semglee insulin glargine (rDNA origin) solution for SC injection 100 units/mL; 3 mL disposable prefilled pen, BGP Pharma/Viatris.

INDICATIONS Once-daily SC administration in the treatment of patients > 17 years of age with type 1 or type 2 diabetes who require basal (long-acting) insulin for the control of hyperglycemia. Also indicated in the treatment of children (> 6 years of age) with type 1 diabetes who require basal (long-acting) insulin for the control of hyperglycemia.

DOSAGE Individualized; consult product monograph for details.

COMMENTS Second biosimilar to Lantus (Sanofi-Aventis) to be marketed in Canada, following Basaglar (Eli Lilly).

Tavneos avacopan 10 mg capsules, Otsuka Canada.

INDICATIONS Adjunctive treatment of adults with severe active antineutrophil cytoplasmic autoantibody (ANCA)associated vasculitis (granulomatosis with polyangiitis [GPA] and microscopic polyangiitis [MPA]). Intended for use in combination with standard background therapy, including glucocorticoids.

DOSAGE 30 mg (3 x 10 mg capsules) twice daily (morning and evening), with food. Swallow capsules whole with water; do not open, crush or chew.

New Dosage Forms

• Lapelga Pre-Filled Autoinjector 6 mg/0.6 mL (pegfilgrastim preservative-free solution) Apotex, is now available, in addition to the original 6 mg/0.6 mL prefilled syringe.

• Nucala (mepolizumab solution for subcutaneous injection), GlaxoSmithKline. New single-use prefilled syringe containing 40 mg/ 0.4 mL (for use in children aged 6–11 years of age with severe eosinophilic asthma) joins the existing 100 mg/mL single-use prefilled syringe, 100 mg/mL prefilled single-use autoinjector and lyophilized powder for solution (100 mg vial).

• Skyrizi (risankizumab injection), AbbVie. New 600 mg/10 mL vial for intravenous (IV) use is now available (for induction treatment of Crohn’s disease in adults). Also, a new 360 mg/2.4 mL (150 mg/mL) prefilled cartridge for subcutaneous use using the Skyrizi on-body injector (for maintenance treatment of Crohn’s disease in adults), joins the existing 150 mg/1 mL prefilled pen or syringe and the 75 mg/0.83 mL (90 mg/mL) prefilled syringe for subcutaneous use (for treatment of moderate to severe plaque psoriasis and active psoriatic arthritis). See also New indications

NEW GENERICS

• Jamp-Apremilast (apremilast 10 mg and 30 mg tablets), Jamp Pharma. Generic alternative to Otezla.

• pms-Apremilast (apremilast 30 mg tablets), Pharmascience. Generic alternative to Otezla.

• pms-Tofacitinib (tofacitinib 5 mg tablets), Pharmascience. Generic alternative to Xeljanz.

New Indications

Abevmy bevacizumab for injection, BGP Pharma/Viatris.

NEW INDICATION Treatment of first recurrence platinum-sensitive epithelial ovarian, fallopian tube or primary peritoneal cancer, in combination with carboplatin and gemcitabine. Patients should not have received prior VEGFtargeted therapy. (Also approved earlier for use in the treatment of metastatic colorectal cancer, locally-advanced, metastatic or recurrent nonsmall cell lung cancer, platinum-resistant recurrent epithelial ovarian, fallopian tube and primary peritoneal cancer, and malignant glioma/glioblastoma.)

DOSAGE Platinum-sensitive recurrent epithelial ovarian, fallopian tube and primary peritoneal cancer: 15 mg/kg by IV infusion every three weeks. Administered in combination with carboplatin and gemcitabine for six cycles (up to 10 cycles), followed by continued use of bevacizumab as a single agent until disease progression.

Abrilada adalimumab SC injection, Pfizer.

NEW INDICATION Inducing and maintaining clinical remission in children five years of age or older with moderately to severely active ulcerative colitis. Intended for patients who have had an inadequate response to conventional therapy, including corticosteroids and/ or azathioprine or 6-mercaptopurine, or who are intolerant to such therapies. (Also approved earlier for several other therapeutic uses; consult product monograph for details.)

DOSAGE Pediatric ulcerative colitis: Induction and maintenance doses are based on body weight; consult product monograph for details. Administer by SC injection.

Beovu brolucizumab solution for intravitreal injection, Novartis.

NEW INDICATION Treatment of diabetic macular edema. (Originally indicated only for use in the treatment of neovascular [wet] age-related macular degeneration.)

DOSAGE Diabetic macular edema: 6 mg (0.05 mL) administered by intravitreal injection every six weeks for the first five doses. Thereafter, treatment intervals (e.g., every 8 or 12 weeks) are based on disease activity as assessed by visual acuity and/ or anatomical parameters.

Comirnaty Original & Omicron BA.4/BA.5 COVID-19 mRNA vaccine, bivalent (original and Omicron BA.4/BA.5), Pfizer.

NEW INDICATION Now indicated as a booster in children five years through < 12 years of age. (Originally indicated as a booster in individuals 12 years of age or older only.)

DOSAGE Booster in children five years through < 12 years of age: 0.2 mL administered intramuscularly at least six months after completing the primary twodose series with Comirnaty (COVID-19 vaccine, mRNA).

Ivozfo fosfomycin for injection, Verity Pharmaceuticals.

REMOVED INDICATIONS No longer indicated for the treatment of osteomyelitis or nosocomial lower respiratory tract infections in adults or children (including neonates).

NEW INDICATIONS Treatment of the following infections in adults and children, including neonates: bone and joint infections, complicated intra-abdominal infections, complicated skin and soft tissue infections, hospital-acquired pneumonia, including ventilator- associated pneumonia, and infective endocarditis. (Also approved earlier for use in the treatment of bacterial meningitis, bacteremia and complicated urinary tract infections.)

DOSAGE Varies according to the indication, severity and site of the infection, susceptibility of the pathogen(s) to fosfomycin and renal function. Dosage also varies according to age and body weight in children. Consult product monograph for details.

Nuvaxovid

COVID-19 vaccine (recombinant protein, adjuvanted), Novavax/Innomar Strategies.

NEW INDICATION Now approved for active immunization to prevent COVID-19 in adolescents 12 through 17 years of age.

(Originally indicated only for use in adults.)

DOSAGE Individuals ≥ 12 years of age: Primary series of two 0.5 mL doses, with the second dose administered three weeks after the first dose. Administer by intramuscular injection, preferably in the deltoid muscle of the upper arm.

NEW INDICATION A first booster dose in adults (≥ 18 years of age).

DOSAGE First booster dose in adults: 0.5 mL administered intramuscularly approximately six months after receiving the second dose of the primary two-dose series.

Polivy polatuzumab vedotin for injection, Hoffmann-La Roche.

NEW INDICATION Treatment of adults with previously untreated large B-cell lymphoma (LBCL), including diffuse large B-cell lymphoma (DLBCL) not otherwise specified (NOS), high grade B-cell lymphoma, Epstein-Barr virus-positive (EBV+) DLBCL NOS, and T-cell/histiocyte rich LBCL. Used in in combination with rituximab, cyclophosphamide, doxorubicin and prednisone. (Also approved earlier [with conditions] for the treatment of relapsed or refractory DLBCL NOS in adults who are not eligible for autologous stem cell transplant and have received at least one prior therapy. Used in combination with bendamustine and rituximab.)

DOSAGE Adults with previously untreated LBCL: 1.8 mg/kg given as an IV infusion every 21 days for six cycles (in combination with rituximab, cyclophosphamide, doxorubicin and prednisone); see product monograph for details.

Skyrizi risankizumab injection, AbbVie.

NEW INDICATION Treatment of moderately to severely active Crohn’s disease in adults who have had an inadequate response, intolerance or demonstrated dependence to corticosteroids; or an inadequate response, intolerance or loss of response to immunomodulators or biologic therapies. (Also approved earlier for use in adults for the treatment of moderate to severe plaque psoriasis and active psoriatic arthritis.)

DOSAGE Moderately to severely active Crohn’s disease in adults: 600 mg administered by IV infusion at Weeks 0, 4 and 8, followed by 360 mg administered by subcutaneous injection at Week 12, and every eight weeks thereafter. See also New dosage forms

Ultomiris ravulizumab for injection, Alexion/Innomar Strategies.

EXPANDED INDICATION Treatment of adults and children (1 month of age or older) with paroxysmal nocturnal hemoglobinuria. (Originally indicated for adults only.)

NEW INDICATION Treatment of adults and children (1 month of age or older) with atypical hemolytic uremic syndrome, to inhibit complement-mediated thrombotic microangiopathy.

DOSAGE Based on body weight; consult product monograph for details. Administer as an IV infusion.

Xeomin incobotulinumtoxinA for injection, Merz Pharma Canada.

NEW INDICATION Treatment of chronic sialorrhea associated with neurological disorders in children (age 2–17 years weighing ≥ 12 kg). (Also approved earlier for use in the treatment of chronic sialorrhea associated with neurological disorders in adults, hypertonicity disorders of the 7th nerve [e.g., blepharospasm, including benign essential blepharospasm and hemifacial spasm in adults], cervical dystonia [spasmodic torticollis] in adults, and spasticity of the upper limb in adults.)

DOSAGE Chronic sialorrhea associated with neurological disorders in children: Dosage varies according to body weight; consult product monograph for details. Injected into the parotid and submandibular glands, on both sides.

Health Canada Advisories

Pfizer COVID-19 vaccine: avoid med errors

Health Canada has announced that the bivalent vaccine Comirnaty Original & Omicron BA.4/BA.5 (DIN 02533197) for use in children five to < 12 years of age will initially be supplied in vials and cartons with English-only labels with the name “Pfizer-BioNTech COVID-19 Vaccine, Bivalent Original and Omicron BA.4/BA.5.” This product has the same orange cap and label border as monovalent Comirnaty (COVID-19 Vaccine, mRNA), 10 µg/0.2 mL (DIN 02522454). Healthcare providers must pay careful attention to the vial and carton label to avoid medication errors.

Evusheld: risk of prophylaxis/treatment failure

Health Canada is warning that Evusheld (tixagevimab and cilgavimab for injection) may not be effective against certain SARS-CoV-2 Omicron subvariants when used for prophylaxis or treatment of COVID-19. Healthcare providers should consider local epidemiology and individual exposure to circulating SARS-CoV-2 viral variants when making decisions regarding the use of Evusheld. Patients who receive Evusheld should be warned about the potential lack of effectiveness against certain SARS-CoV-2 viral variants and instructed to seek medical advice if signs or symptoms of COVID-19 occur, persist or worsen.

Ocaliva: new contraindication

Health Canada has announced that Ocalvia (obeticholic acid) is now contraindicated for primary biliary cholangitis patients with advanced disease, such as those with Child-Pugh Class B or C decompensated cirrhosis or a prior decompensation event, as well as for patients with compensated cirrhosis who have evidence of portal hypertension.

Lu-Ann Murdoch, RPh, BScPhm, ACPR, is a consulting clinical editor for Pharmacy Practice + Business and drug information consultant for Pharmacist’s Letter

Further details about these advisories and safety reviews can be obtained from the MedEffect Canada website: https://www.canada.ca/en/health-canada/ services/drugs-health-products/medeffect-canada. html and https://www.canada.ca/en/health-canada/ services/drugs-health-products/medeffect-canada/ safety-reviews.html