Drug News—July 2024

NEW PRODUCTS Abrysvo: new RSV vaccinerespiratory syncytial virus (RSV) stabilized prefusion F subunit vaccine; lyophilized powder for solution, 120 µg RSV stabilized prefusion F protein per 0.5 mL, reconstituted solution for intramuscular (IM) injection, Pfizer.INDICATIONS 1. Active immunization of pregnant individuals from 32–36 weeks gestational age for the prevention of lower respiratory tract disease (LRTD) and severe LRTD caused by RSV in infants from birth through six months of age. 2. Active immunization of individuals ≥ 60 years of age to prevent LRTD caused by RSV.ACTION A bivalent formulation containing two recombinant stabilized RSV prefusion F antigens, each representing the two major virus subgroups, RSV A and RSV B. Following intramuscular administration, the prefusion F antigens elicit an immune response, which protects against RSV associated LRTD. Adults 60 years of age and older are protected by active immunization. In pregnant individuals, the neutralizing antibodies are passively transferred from mother to infant.DOSAGE Pregnant individuals: A single 0.5 mL dose given IM in the third trimester of pregnancy (from 32–36 weeks gestation). Individuals ≥ 60 years of age: A single 0.5 mL dose given IM.ADMINISTRATION The lyophilized vaccine must be reconstituted using the accompanying vial adapter and sterile water diluent provided in the prefilled syringe (consult product monograph for details). Inject IM into the deltoid muscle.ADVERSE EFFECTS (in pregnant individuals and older adults) MOST COMMON: Headache, myalgia and vaccination site pain, redness and swelling. MOST SERIOUS: Very rare cases of hypersensitivity reactions. Possibility of syncope (fainting), as seen with administration of other injectable vaccines.STORAGE/STABILITY Store under refrigeration (2°C–8°C) in the original carton to protect from light. After reconstitution, administer immediately (within 4 hours). Keep reconstituted vaccine between 15°C–30°C; do refrigerate or freeze.COMMENTS Arexvy (RSV vaccine, recombinant, AS01E adjuvanted) was the first RSV vaccine in Canada, marketed by GlaxoSmithKline in the fall of 2023. It is indicated in adults ≥ 60 years of age to prevent LRTD caused by RSV.Myalepta for leptin deficiencymetreleptin for injection, powder for solution; 3 mg, 5.8 mg and 11.3 mg vials, Medison Pharma Canada.INDICATIONS An adjunct to diet as a replacement therapy to treat the complications of leptin deficiency in patients with lipodystrophy (LD). Intended for patients with confirmed congenital generalized LD (Berardinelli-Seip syndrome) or acquired generalized LD (Lawrence syndrome) in adults and children ≥ 2 years of age. Also intended for patients with confirmed familial partial LD or acquired partial LD (Barraquer-Simons syndrome), in adults and children ≥ 12 years of age with persistent significant metabolic disease for whom standard treatments have failed to achieve adequate metabolic control.ACTION A recombinant human leptin analog. Metreleptin mimics the physiological effects of leptin by binding to and activating the human leptin receptor. It improves metabolic abnormalities (e.g., blood glucose/A1C, triglycerides).DOSAGE Recommended daily dose is based on actual body weight (see Table 1 in product monograph for details).ADMINISTRATION Following reconstitution (see product monograph instructions), administer subcutaneously once daily at the same time every day. Can be administered any time of day without regard to the timing of meals. Inject subcutaneously (SC) into the abdomen, thigh or upper arm. Patients and caregivers can be trained on the proper SC injection technique. Care must be taken to avoid intramuscular injection in patients with minimal SC adipose tissue.ADVERSE EFFECTS MOST COMMON: Decrease in weight, hypoglycemia and fatigue. Mild to moderate injection site reactions may occur. MOST SERIOUS: Abdominal pain, pancreatitis, pneumonia, sepsis, worsening underlying liver disease, cardiac failure, cellulitis, autoimmune diseases with cases of progression of autoimmune hepatitis and membranoproliferative glomerulonephritis. Development of anti-metreleptin antibodies, which could lead to inhibition of endogenous leptin action and loss of metreleptin efficacy. Potential for development of T-cell lymphoma. Hypersensitivity reactions (e.g. anaphylaxis, urticaria, generalized rash).DRUG INTERACTIONS Increased risk of hypoglycemia when used with insulin or other antidiabetic medication (e.g., sulfonylureas). Large dose reductions of baseline insulin requirements may be needed in the first two weeks of treatment. Dose adjustments of other antidiabetic medications may also be needed to minimize the risk of hypoglycemia. Possible reduction in the efficacy of hormonal contraceptives; consider using an additional nonhormonal contraceptive during metreleptin treatment. May have an effect on CYP450 enzymes; dose adjustments may be required for CYP450 substrates with a narrow therapeutic index (e.g., warfarin, cyclosporine).STORAGE Store the refrigerator (2°C–8°C), protect from light.Truqap for breast cancercapivasertib 160 mg and 200 mg tablets, AstraZeneca.INDICATIONS Treatment of hormone receptor (HR) positive, human epidermal growth factor receptor 2 (HER2) negative locally advanced or metastatic breast cancer, in combination with fulvestrant. Intended for adult females with one or more PIK3CA/AKT1/PTEN alterations, who have had progression on at least one endocrine-based regimen in the metastatic setting or recurrence on or within 12 months of completing adjuvant therapy.ACTION Inhibits the kinase activity of all three isoforms of serine/threonine kinase AKT (AKT1, AKT2 and AKT3). Reduces growth of diverse tumourmodels with and without genetic alterations in PIK3CA, AKT1 and/or PTEN, including estrogen receptor-positive (ER+) breast cancer tumour models. The combination of capivasertib and fulvestrant reduces the growth of ER+ breast cancer models with and without alterations in PIK3CA, PTEN or AKT.DOSAGE Weekly dosage regimen is capivasertib 400 mg (two 200 mg tablets) twice daily, approximately 12 hours apart, for four days followed by three days off treatment. Management of severe adverse drug reactions may require temporary dosing interruption, reduction and/or discontinuation; consult product monograph for details.ADMINISTRATION Can be taken with or without food. Swallow tablets whole with water; do not chew, crush, dissolve or divide.ADVERSE EFFECTS MOST COMMON: Diarrhea, cutaneous adverse reactions, nausea, fatigue, stomatitis, vomiting, hyperglycemia, headache, decreased appetite, urinary tract infection, pyrexia, dysgeusia, dyspepsia. MOST SERIOUS: Cutaneous adverse reactions, including drug reaction with eosinophilia and systemic symptoms (DRESS), erythema multiforme and palmar-plantar erythrodysesthesia. Also, severe diarrhea (associated with dehydration and acute kidney injury), vomiting, hyperglycemia (including diabetic ketoacidosis), anemia, stomatitis, hypokalemia.DRUG INTERACTIONS Strong and moderate CYP3A4 inhibitors increase capivasertib concentrations; avoid combination or reduce capivasertib dose to 320 mg twice daily when used concomitantly with strong or moderate CYP3A4 inhibitors. Avoid grapefruit, star fruit, pomegranate, Seville oranges and their juices. Avoid St. John’s wort. Strong CYP3A4 inducers decrease capivasertib concentrations which may reduce efficacy. Avoid use with strong CYP3A4 inducers; avoid moderate CYP3A4 inducers or use with caution. Consult product monograph for further potential drug interactions.Velsipity for ulcerative colitisetrasimod 2 mg tablets (as etrasimod L-arginine), Pfizer.INDICATIONS Treatment of moderately to severely active ulcerative colitis in adults with an inadequate response, loss of response, or intolerance to conventional therapy or an advanced treatment.ACTION A sphingosine 1-phosphate (S1P) receptor modulator. Partially and reversibly blocks lymphocyte egress from lymphoid organs, reducing the number of lymphocytes in peripheral blood and lowering the number of activated lymphocytes in tissue. Mechanism of its therapeutic effects in ulcerative colitis is unknown but may involve the reduction of lymphocyte migration into sites of inflammation.DOSAGE 2 mg orally once daily. No dose adjustment is needed in renal impairment or mild to moderate hepatic impairment; not recommended in severe hepatic impairment. Risk of transient decreases in heart rate when etrasimod is started; four-hour monitoring for bradycardia is recommended after the first dose in patients with resting heart rate < 50 bpm, first-degree or second-degree atrioventricular block, or a history of myocardial infarction or heart failure (see product monograph for details).ADMINISTRATION May be taken with or without food. Swallow tablets whole.ADVERSE EFFECTS MOST COMMON: Lymphopenia, headache, dizziness, arthralgia. Elevated liver enzymes and elevated blood pressure may occur. MOST SERIOUS: Bradyarrhythmia, increased risk of infections (including herpes infections, cryptococcal infections, progressive multifocal leukoencephalopathy), cases of malignancy (including cutaneous malignancies), hepatic injury, macular edema. Before starting treatment, patients should have a cardiac evaluation, liver function tests, complete blood count, ophthalmic assessment, medication review (for drugs that slow heart rate or atrioventricular conduction, or cause immunosuppression) and vaccination review (to ensure immunizations are current); consult product monograph for details. May cause fetal harm. Exclude pregnancy before starting treatment; females of childbearing potential must use effective contraception.DRUG INTERACTIONS Not recommended in combination with agents that are both moderate CYP2C9 and moderate or strong CYP3A4 inhibitors (e.g., fluconazole). Not recommended in combination with agents that are both moderate CYP2C8 or CYP2C9 and strong CYP3A4 inducers (e.g., rifampin). Avoid live attenuated vaccines during etrasimod treatment and for two weeks after discontinuation. Contraindicated in patients with increased risk of opportunistic infections, including those who are immunocompromised due to treatment (e.g., antineoplastic, immunosuppressive or immunomodulating therapies). Consult with a cardiologist before adding antiarrhythmic or QT-prolonging drugs.COMMENTS Etrasimod is the second oral S1P receptor modulator to be marketed for ulcerative colitis in Canada, following ozanimod (Zeposia). Zeposia is also indicated for the treatment relapsing remitting multiple sclerosis, to decrease the frequency of clinical exacerbations.Other new products Dopteletavatrombopag 20 mg tablets (as maleate), SOBI Canada.INDICATIONS Treatment of severe thrombocytopenia in adults with chronic liver disease who are scheduled to undergo an invasive procedure. Treatment of thrombocytopenia in adults with chronic immune thrombocytopenia and an insufficient response to a previous treatment.DOSAGE Chronic liver disease patients scheduled to undergo a procedure: Start avatrombopag dosing with food 10–13 days before the scheduled procedure. The recommended daily dose is based on the patient’s platelet count prior to the scheduled procedure. For patients with a platelet count < 40 x 109/L, give 60 mg (3 tabs) once daily for five days. For patients with a platelet count 40 to < 50 x 109/L, give 40 mg (2 tabs) once daily for five days. Chronic immune thrombocytopenia: For most patients, start with avatrombopag 20 mg (1 tablet) once daily with food. In patients taking moderate or strong dual inducers of CYP2C9 and CYP3A4 (e.g., carbamazepine, enzalutamide, phenytoin, rifampin), start with 40 mg (2 tablets) once daily. In patients taking moderate or strong dual inhibitors of CYP2C9 and CYP3A4 (e.g., fluconazole, itraconazole, ritonavir), start with 20 mg (1 tablet) three times a week. Dose adjustments are based on platelet count response (consult product monograph for details). Use the lowest dose needed to achieve and maintain a platelet count ≥ 50 x109/L, as necessary, to reduce the risk for bleeding.Ondexxyaandexanet alfa for injection; powder for solution for intravenous infusion, 200 mg per single-use vial, AstraZeneca. Available to hospitals through the Canadian Pharmaceutical Distribution Network.INDICATIONS For rapid reversal of anticoagulation due to life-threatening or uncontrolled bleeding in adults treated with FXa inhibitors (rivaroxaban or apixaban). Issued market authorization with conditions, pending the results of trials to verify the drug’s clinical benefit.DOSAGE Dose is based on FXa inhibitor (rivaroxaban or apixaban) dose and timing of the last dose (consult product monograph for details).Tecentriq SCatezolizumab 125 mg/mL solution for SC injection; 1875 mg/15 mL single-use vial of ready-to-use solution, Hoffmann-La Roche.INDICATIONS Treatment of extensive-stage small cell lung cancer, nonsmall cell lung cancer, unresectable or metastatic hepatocellular carcinoma, and unresectable locally advanced or metastatic triple-negative breast cancer. Can be used first line for several indications; see product monograph for details. Patients currently receiving intravenous Tecentriq may transition to Tecentriq SC.DOSAGE 1875 mg (15 mL) administered SC every three weeks; consult product monograph for regimen details.ADMINISTRATION Remove from the refrigerator and allow the solution to reach room temperature prior to administration. Administer SC in the thigh over approximately seven minutes; use of a SC infusion set (e.g., winged/butterfly) is recommended. Do not administer the remaining residual volume in the tubing to the patient. Alternate injection sites between the left and right thigh.COMMENTS Tecentriq SC contains recombinant human hyaluronidase 2,000 U/mL, an enzyme used to increase the dispersion and absorption of co-administered drugs when administered subcutaneously. Tecentriq continues to be marketed in the original intravenous (IV) formulation (atezolizumab 60 mg/mL for injection, concentrate for solution for infusion; 1200 mg/20 mL and 840 mg/14 mL single-use vials). Check product labels to ensure that the correct formulation (IV or SC) is being administered.New indications Cosentyxsecukinumab injection, Novartis.NEW INDICATION Treatment of moderate to severe hidradenitis suppurativa (acne inversa) in adults who have responded inadequately to conventional systemic hidradenitis suppurativa therapy. (Also approved earlier for use in thelso approved earlier for use in the treatment of moderate to severe plaque psoriasis, active psoriatic arthritis, active ankylosing spondylitis, active nonradiographic axial spondyloarthritis and juvenile idiopathic arthritis.)DOSAGE Moderate to severe hidradenitis suppurativa: 300 mg SC at Weeks 0, 1, 2, 3 and 4, followed by monthly maintenance dosing (every 4 weeks). Based on clinical response, the maintenance dose can be increased to 300 mg every 2 weeks.Keytrudapembrolizumab solution for infusion, Merck.NEW INDICATION Treatment of locally advanced unresectable or metastatic biliary tract carcinoma in adults, in combination with gemcitabine-based chemotherapy. (Also approved earlier for numerous other indications; consult product monograph for details.)DOSAGE Biliary tract carcinoma: 200 mg every three weeks or 400 mg every six weeks, administered as an intravenous infusion over 30 minutes.Quliptaatogepant tablets, AbbVie.REVISED INDICATION Now indicated for the prevention of migraine in adults who have at least four migraine days per month. (Original stated indication was for the prevention of episodic migraine [< 15 migraine days per month] in adults.)DOSAGE Episodic migraine: Recommended dosage is 10 mg, 30 mg or 60 mg orally once daily (maximum 60 mg daily). Chronic migraine: Recommended dose is 60 mg orally once daily. Can be administered with or without food.Xeljanztofacitinib tablets, Pfizer.NEW INDICATIONS Treatment of active ankylosing spondylitis in adults who have responded inadequately to a biologic disease-modifying antirheumatic drug or when use of those therapies is inadvisable. Treatment of active polyarticular juvenile idiopathic arthritis and juvenile psoriatic arthritis in children weighing ≥ 40 kg; intended for patients who have responded inadequately or are intolerant to tumour necrosis factor (TNF) inhibitors or when use of those therapies is inadvisable. (Also approved earlier for the treatment of rheumatoid arthritis, psoriatic arthritis and ulcerative colitis in adults.)DOSAGE Ankylosing spondylitis: 5 mg twice daily. Polyarticular juvenile idiopathic arthritis and juvenile psoriatic arthritis: 5 mg twice daily, as monotherapy or in combination with methotrexate.Xtandienzalutamide capsules, Astellas.NEW INDICATION Treatment of nonmetastatic castration-sensitive prostate cancer in patients with biochemical recurrence at high risk of metastasis. (Also approved earlier for prostate cancer in other situations; consult product monograph for details.)DOSAGE 160 mg (four 40 mg capsules) once daily, with or without food.Zoladex LAgoserelin implant (as goserelin acetate), TerSera Canada.NEW INDICATION Management of estrogen receptor (ER)-positive early breast cancer in pre- and perimenopausal women with a high risk of recurrence or advanced breast cancer. (Also indicated for use in the treatment of prostate cancer and for hormonal management of endometriosis.)DOSAGE ER-positive early breast cancer in pre- and perimenopausal women: One implant (10.8 mg goserelin) given by deep SC injection into the anterior abdominal wall every 12 weeks.New dosage guidelinesVfend (voriconazole tablets and oral suspension), Pfizer. The loading dose for the treatment of candidemia and invasive candidiasis in patients weighing < 40 kg has been reduced from 400 mg (two 200 mg tablets or 10 mL of suspension) twice daily 12 hours apart to 200 mg (one 200 mg tablet or 5 mL of suspension) twice daily, 12 hours apart.New genericsGlatiramer Acetate Injection (glatiramer acetate 20 mg/mL); prefilled single-use glass syringes, Viatris. Generic alternative to Copaxone.Health Canada advisories Iodinated contrast media: hypothyroidismA Health Canada safety review concluded that there is a rare risk of hypothyroidism with the use of iodinated contrast media in certain patients, mostly infants. Iodine in the contrast media may affect the production of thyroid hormone. The safety review included the following products available in Canada: Gastrografin, Ultravist, Sinografin, Isovue, Cholografin meglumine, Telebrix, Optiray, Conray, Visipaque and Omnipaque. Product monographs are being updated to include this risk.Neulasta: no link to SJS or TENA Health Canada safety review did not find sufficient evidence to support a link between the use of pegfilgrastim (Neulasta, biosimilars) and the risk of Stevens-Johnson syndrome (SJS), a serious disorder of the skin and mucous membranes, or toxic epidermal necrolysis (TEN), a severe form of SJS. The safety review was triggered by cases of SJS and TEN reported by the manufacturer of Neulasta in 2023. Neulasta has been authorized for sale in Canada since 2004 for the treatment of neutropenia caused by chemotherapy. Biosimilars of pegfilgrastim (Fulphila, Lapelga, Nyvepria, Ziextenzo) have been marketed in Canada since 2019.Nexavar: risk of tumour lysis syndromeA Health Canada safety review found a possible link between the use of Nexavar (sorafenib) and the risk of tumour lysis syndrome, a potentially life-threatening condition that can occur when cancer cells killed by sorafenib release salts and proteins into the blood. When the kidneys cannot remove these substances from the blood quickly enough, it can lead to damage to the kidneys, heart and brain. The product monograph is being updated to include this risk.Lu-Ann Murdoch 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.