PREVYMIS 480 MG — DIN 02469383

What is PREVYMIS?

PREVYMIS 480 MG contains LETERMOVIR : 480 MG. It is listed in the Health Canada Drug Product Database under DIN 02469383, held by MERCK CANADA INC, supplied as TABLET for ORAL administration. Health Canada currently lists it as marketed, status dated 20-Dec-2017. Nexara Health is a licensed Canadian wholesale distributor (DEL 3-002896-A) and can source this product for hospitals, pharmacies and clinics. Availability and lead time are confirmed per order.

What is PREVYMIS used for?

PREVYMIS® (letermovir) is indicated for: • the prophylaxis of cytomegalovirus (CMV) infection in adult CMV-seropositive recipients [R+] of an allogeneic hematopoietic stem cell transplant (HSCT). • the prophylaxis of CMV disease in adult kidney transplant recipients who are at high risk (donor CMV-seropositive [D+]/recipient CMV-seronegative [R-]).

Authorized indication as written in the Health Canada product monograph. For healthcare professionals and licensed purchasers; this is not medical advice.

How is it administered?

PREVYMIS® Tablets: • Administer with or without food. • Swallow tablets whole. Do not divide, crush or chew. PREVYMIS® Injection: • PREVYMIS® injection must be administered through a sterile 0.2 micron or 0.22 micron polyethersulfone (PES) in-line filter. • Do not administer as an IV bolus injection. • Administer by intravenous (IV) infusion upon dilution via a peripheral catheter or central venous line over approximately 60 minutes. PREVYMIS® tablet and injection may be used interchangeably at the discretion of the physician, and no dose adjustment is necessary. Recommended Dosage: Adults: The recommended dosage of PREVYMIS® is 480 mg administered once daily. If PREVYMIS® is co-administered with cyclosporine, the dosage of PREVYMIS® should be decreased to 240 mg once daily. HSCT: PREVYMIS® should be started after HSCT. PREVYMIS® may be started on the day of transplant and no later than 28 days post-HSCT. PREVYMIS® may be started before or after engraftment. Continue PREVYMIS® through 100 days post-HSCT. In patients at risk for late CMV infection and disease, PREVYMIS® may be continued through 200 days post-HSCT. Following completion of PREVYMIS® prophylaxis, monitoring for CMV reactivation in HSCT recipients is recommended. Kidney Transplant: PREVYMIS® should be started on the day of transplant and no later than 7 days post-kidney transplant and continued through 200 days post-transplant. Pediatrics (< 18 years of age): Safety and efficacy of PREVYMIS® have not been established in pediatric patients less than 18 years of age. Geriatrics (≥ 65 years of age): No dose adjustment of PREVYMIS® is required based on age. Dosage Adjustment in Adults: If PREVYMIS® is co-administered with cyclosporine, the dosage of PREVYMIS® should be decreased to 240 mg once daily. • If cyclosporine is initiated after starting PREVYMIS®, the next dose of PREVYMIS® should be decreased to 240 mg once daily. • If cyclosporine is discontinued after starting PREVYMIS®, the next dose of PREVYMIS® should be increased to 480 mg once daily. • If cyclosporine dosing is temporarily interrupted due to high cyclosporine levels, no dose adjustment of PREVYMIS® is needed. Renal Impairment: No dose adjustment of PREVYMIS® is required based on renal impairment. There are no data in patients with end-stage renal disease (CrCl less than 10 mL/min), including patients on dialysis. Hepatic Impairment: No dose adjustment of PREVYMIS® is required based on mild (Child-Pugh Class A) to moderate (Child-Pugh Class B) hepatic impairment. PREVYMIS® is not recommended for patients with severe (Child-Pugh Class C) hepatic impairment. Combined Renal and Hepatic Impairment: PREVYMIS® is not recommended in patients with moderate hepatic impairment combined with moderate or severe renal impairment (CrCl less than 50 mL/min).

Included because it drives pack selection and wastage. Consult the monograph.

Contraindications

PREVYMIS® is contraindicated in patients who are hypersensitive to this drug or to any ingredient in the formulation, including any non-medicinal ingredient, or component of the container. Pimozide: Concomitant administration of PREVYMIS® may result in increased concentrations of pimozide due to inhibition of cytochrome P450 3A (CYP3A) by letermovir, leading to QT prolongation and torsades de pointes. Ergot Alkaloids: Concomitant administration of PREVYMIS® may result in increased concentrations of ergot alkaloids (ergotamine and dihydroergotamine) due to inhibition of CYP3A by letermovir, which may lead to ergotism. Cyclosporine with lovastatin, rosuvastatin or simvastatin: Concomitant administration of PREVYMIS® when used in combination with cyclosporine is contraindicated as it may result in significantly increased lovastatin, rosuvastatin or simvastatin concentrations, which may lead to myopathy or rhabdomyolysis. Cyclosporine with bosentan: Concomitant administration of PREVYMIS® when used in combination with cyclosporine is contraindicated as it may result in significantly increased concentrations of bosentan.

Warnings and precautions

Risk of Adverse Reactions or Reduced Therapeutic Effect Due to Drug Interactions: • The concomitant use of PREVYMIS® and certain drugs may result in known or potentially significant drug interactions, some of which may lead to: o Possible clinically significant adverse reactions from greater exposure of concomitant drugs or PREVYMIS®. o Significant decrease of concomitant drug plasma concentrations which may lead to reduced therapeutic effect of the concomitant drug. PREVYMIS® should be used with caution with drugs that are CYP3A substrates with narrow therapeutic ranges (e.g., alfentanil, fentanyl, and quinidine) as co-administration may result in increases in the plasma concentrations of CYP3A substrates. Close monitoring and/or dose adjustment of co-administered CYP3A substrates is recommended. Co-administration of PREVYMIS® with strong and moderate inducers of transporters (e.g., P-gp) and/or enzymes (e.g. UGTs) is not recommended due to the potential for a decrease in letermovir plasma concentrations. Rifampin co-administration resulted in an initial increase in letermovir plasma concentrations (due to OATP1B1/3 inhibition) that is not clinically significant, followed by clinically relevant decreases in letermovir plasma concentrations with continued rifampin co-administration. This may result in loss of prophylactic efficacy and necessitate initiation of anti-CMV therapy for CMV reactivation and/or disease. Co-administration of PREVYMIS® may result in increases in the plasma concentrations of cyclosporine, tacrolimus, and sirolimus. Close monitoring and/or dose adjustment of cyclosporine, tacrolimus, and sirolimus is recommended when co-administered with PREVYMIS®. Hepatic Insufficiency: PREVYMIS® is not recommended for patients with severe (Child-Pugh Class C) hepatic impairment. Renal Insufficiency: In patients with moderate or severe renal impairment (CrCl less than 50 mL/min) receiving PREVYMIS® injection, accumulation of the IV vehicle, hydroxypropyl betadex, could occur. Serum creatinine levels should be closely monitored in these patients. Combined Renal and Hepatic Insufficiency: PREVYMIS® is not recommended in patients with moderate hepatic impairment combined with moderate or severe renal impairment.