PREVYMIS INJECTION Dosage & Rx Info

Prevymis Injection Generic Name & Formulations

Legal Class

General Description

Letermovir 240mg/12mL, 480mg/24mL; soln for IV infusion after dilution; contains hydroxypropyl betadex; preservative-free.

Pharmacological Class

CMV DNA terminase complex inhibitor.

How Supplied

Tabs—14, 28; Single-dose vial—1

Manufacturer

Merck & Co., Inc.

Generic Availability

Mechanism of Action

Letermovir inhibits the CMV DNA terminase complex (pUL51, pUL56, and pUL89) which is required for viral DNA processing and packaging.

Prevymis Injection Indications

Indications

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

Prevymis Injection Dosage and Administration

Adult

Give as IV infusion over 1hr; do not give as IV bolus. HSCT: Start between Days 0 and 28 post-HSCT (before or after engraftment) and continue through Day 100 post-HSCT; may be continued through Day 200 post-HSCT in those at risk for late CMV infection/disease. Kidney transplant: Start between Days 0 and 7 post-transplant and continue through Day 200 post-transplant. 480mg once daily. Concomitant cyclosporine: reduce to 240mg once daily. Switch to oral therapy as soon as able to take oral meds.

Children

<18yrs: not established.

Prevymis Injection Contraindications

Contraindications

Concomitant pimozide, ergot alkaloids. Concomitant pitavastatin, simvastatin when co-administered with cyclosporine.

Prevymis Injection Boxed Warnings

Not Applicable

Prevymis Injection Warnings/Precautions

Warnings/Precautions

Monitor for CMV reactivation after therapy completion. Renal impairment (CrCl <50mL/min): closely monitor serum creatinine (in IV use). Severe hepatic impairment (Child-Pugh C): not recommended. Pregnancy. Nursing mothers.

Prevymis Injection Pharmacokinetics

Absorption

Bioavailability in HSCT recipients: 35% (for 480 mg oral once daily without cyclosporine); 85% (for 240 mg oral once daily with cyclosporine).

Bioavailability in kidney transplant recipients: 56% (for 480 mg oral once daily with cyclosporine).

Median Tmax: 1.5–3.0 hours.

Distribution

Mean steady-state volume of distribution: 45.5 L following IV administration in HSCT recipients.

Plasma protein bound: 99% bound (across the concentration range of 0.2–50 mg/L).

Metabolism

In vitro metabolism: UGT1A1/1A3 (minor).

Elimination

Fecal (93%), renal (<2%). Half-life: 12 hours.

Prevymis Injection Interactions

Interactions

See Contraindications. Specific interactions with cyclosporine: see full labeling. Concomitant inducers of P-gp and/or UGT, nafcillin, carbamazepine, phenobarbital, phenytoin, rifabutin, rifampin, thioridazine, bosentan, St. John's wort, efavirenz, etravirine, nevirapine, pitavastatin, simvastatin, modafinil: not recommended. May be potentiated by OATP1B1/3 inhibitors. Potentiates CYP3A substrates (eg, midazolam, alfentanil, fentanyl, quinidine), OATP1B1/3 substrates: see full labeling for dose adjustment. Concomitant amiodarone, voriconazole, sirolimus, tacrolimus, omeprazole, pantoprazole: monitor frequently and adjust dose if necessary. Monitor INR with warfarin. Concomitant glyburide, repaglinide, rosiglitazone: monitor glucose levels; avoid repaglinide if co-administered with cyclosporine. Concomitant atorvastatin (max 20mg daily): monitor closely; avoid if co-administered with cyclosporine. Concomitant fluvastatin, lovastatin, pravastatin, rosuvastatin: monitor and reduce statin dose if necessary; avoid lovastatin if co-administered with cyclosporine.

Prevymis Injection Adverse Reactions

Adverse Reactions

Nausea, diarrhea, vomiting, peripheral edema, cough, headache, fatigue, abdominal pain, lab abnormalities.

Prevymis Injection Clinical Trials

See Literature

Prevymis Injection Note