PREVYMIS

What it is

PREVYMIS contains letermovir. Film-coated tablets are available in 240 mg or 480 mg strengths. A concentrated injection for infusion is supplied in single-dose vials containing 240 mg or 480 mg of letermovir. Letermovir inhibits the CMV DNA terminase complex, which is required for viral replication.

Approved indications

— Prophylaxis of cytomegalovirus (CMV) infection or disease in adult CMV-seropositive recipients of an allogeneic haematopoietic stem cell transplant. — Prophylaxis of CMV disease in adult kidney transplant recipients at high risk (Donor CMV seropositive/Recipient CMV seronegative [D+/R−]).

Dosing overview

The recommended dosage of PREVYMIS is 480 mg administered once daily. For HSCT recipients, PREVYMIS may be started on the day of transplant and no later than 28 days post-HSCT and should be continued through 100 days post-HSCT. In patients at risk for late CMV infection and disease, PREVYMIS may be continued through 200 days post-HSCT. For kidney transplant recipients, 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. If PREVYMIS is co-administered with ciclosporin, the dosage should be decreased to 240 mg once daily; if ciclosporin is initiated after starting PREVYMIS, the next dose should be decreased to 240 mg once daily; if ciclosporin is discontinued, the next dose should be increased to 480 mg once daily.

Key safety warnings

The cardiac adverse event rate was higher in subjects receiving PREVYMIS (13%) compared to subjects receiving placebo (6%), with the most common cardiac adverse events being tachycardia (reported in 4% of PREVYMIS subjects) and atrial fibrillation (reported in 3% of PREVYMIS subjects). The concomitant use of PREVYMIS with certain drugs may result in possible clinically significant adverse reactions from greater exposure of concomitant drugs or PREVYMIS, or a 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 (such as alfentanil, fentanyl, and quinidine) as co-administration may result in increases in the plasma concentrations of CYP3A substrates, and close monitoring and dose adjustment of co-administered CYP3A substrates is recommended. In patients with moderate or severe renal impairment receiving PREVYMIS concentrated injection for infusion, accumulation of the intravenous vehicle, hydroxypropylbetadex, could occur, and serum creatinine levels should be closely monitored in these patients.

Contraindications

PREVYMIS is contraindicated in patients with hypersensitivity to letermovir or any of its inactive ingredients. Concomitant administration of PREVYMIS with pimozide may result in increased concentrations of pimozide due to inhibition of cytochrome P450 (CYP3A) by letermovir, leading to QT prolongation and torsades de pointes. Concomitant administration of PREVYMIS with ergot alkaloids (ergotamine and dihydroergotamine) may result in increased concentrations due to inhibition of CYP3A by letermovir, which may lead to ergotism. Concomitant administration of PREVYMIS in combination with ciclosporin may result in significantly increased pitavastatin or simvastatin concentrations, which may lead to myopathy or rhabdomyolysis.

PBS listing

No PBS listing information is provided in the source documents.

Regulatory history

PREVYMIS letermovir was first listed on the ARTG on 2018-06-22 in four formulations: 480 mg/24 mL concentrated injection for infusion vial (ARTG 289796), 240 mg/12 mL concentrated injection for infusion vial (ARTG 289794), 240 mg film-coated tablet blister pack (ARTG 289795), and 480 mg film-coated tablet blister pack (ARTG 289797). PREVYMIS is subject to additional monitoring in Australia, which will allow quick identification of new safety information.