Overview
11 DESCRIPTION PREVYMIS contains letermovir, an inhibitor of the CMV DNA terminase complex, and is administered orally or by intravenous infusion. Letermovir has a molecular formula of C 29 H 28 F 4 N 4 O 4 and a molecular weight of 572.55. The chemical name for letermovir is (4 S )-2-{8-Fluoro-2-[4-(3- methoxyphenyl)piperazin-1-yl]-3-[2-methoxy-5-...
Mechanism of Action
12 CLINICAL PHARMACOLOGY 12.1 Mechanism of Action PREVYMIS is an antiviral drug against CMV [see Microbiology (12.4) ] . 12.2 Pharmacodynamics Cardiac Electrophysiology In a thorough QT trial in healthy adult subjects, letermovir at the therapeutic IV dose or at a dose of 2 times the approved IV dose did not prolong QTc to any clinically relevant extent. 12.3 Pharmacokinetics The pharmacokinetic properties of letermovir are displayed in Table 12. Table 12: Absorption, Distribution, Metabolism, Elimination (ADME), and Pharmacokinetic Properties of PREVYMIS Values were obtained in studies of healthy adult subjects unless otherwise indicated.
Indications
- 1 INDICATIONS AND USAGE PREVYMIS is a CMV DNA terminase complex inhibitor indicated for: Prophylaxis of cytomegalovirus (CMV) infection and disease in adult and pediatric patients 6 months of age and older and weighing at least 6 kg who are CMV-seropositive recipients [R+] of an allogeneic hematopoietic stem cell transplant (HSCT). ( 1.1 ) Prophylaxis of CMV disease in adult and pediatric patients 12 years of age and older and weighing at least 40 kg who are kidney transplant recipients at high risk (Donor CMV seropositive/Recipient CMV seronegative [D+/R-]). ( 1.2 ) 1.
Common Doses
- 480 mg
- 240 mg
- 120 mg
- 80 mg
Dosage
2 DOSAGE AND ADMINISTRATION Adult and Pediatric Patients 12 Years of Age and Older and Weighing at least 30 kg Who Are HSCT Recipients or Adult and Pediatric Patients 12 Years of Age and Older and Weighing at least 40 kg Who Are Kidney Transplant Recipients: HSCT : 480 mg administered once daily orally or as an intravenous (IV) infusion over 1 hour through 100 days post-HSCT. In patients at risk for late CMV infection and disease, PREVYMIS may be continued through 200 days post-HSCT. ( 2.1 , 2.
Contraindications
- 4 CONTRAINDICATIONS PREVYMIS is contraindicated in patients receiving pimozide or ergot alkaloids: Pimozide: Concomitant administration of PREVYMIS in patients receiving pimozide may result in increased concentrations of pimozide due to inhibition of cytochrome P450 3A (CYP3A) by letermovir, which may lead to QT prolongation and torsades de pointes [see Warnings and Precautions (5.1) and Drug Interactions (7.2 , 7.3) ] .
Side Effects
- 6 ADVERSE REACTIONS Adult HSCT Patients: Most common adverse events (occurring in at least 10% of subjects in the PREVYMIS group and at a frequency at least 2% greater than placebo) are nausea, diarrhea, vomiting, peripheral edema, cough, headache, fatigue, and abdominal pain. ( 6.1 ) Adult Kidney Transplant Patients: Most common adverse event (occurring in at least 10% of subjects in the PREVYMIS group and at a frequency greater than valganciclovir) is diarrhea. ( 6.1 ) Pediatric Patients: Adverse events in pediatric patients are similar to adults. ( 6.
Interactions
- 7 DRUG INTERACTIONS Dosage Adjustment: If PREVYMIS is co-administered with cyclosporine, the dosage of PREVYMIS should be decreased to 240 mg once daily in adult and pediatric patients 12 years of age and older. ( 2.4 ) If PREVYMIS is co-administered with cyclosporine in pediatric patients less than 12 years of age, dose adjustment may be required. ( 2.6 ) Co-administration of PREVYMIS may alter the plasma concentrations of other drugs and other drugs may alter the plasma concentrations of PREVYMIS.