PREVYMIS

The pharmacokinetic properties of letermovir are displayed in Table 12.

Table 12Absorption, Distribution, Metabolism, Elimination (ADME), and Pharmacokinetic Properties of PREVYMIS Values were obtained in studies of healthy adult subjects unless otherwise indicated. Pharmacokinetics in Adult HSCT Recipients Treatment Regimen Steady-state median (90% prediction interval) AUC (ng∙hr/mL) of PREVYMIS 480 mg oral once daily, no cyclosporine 34,400 (16,900, 73,700) 480 mg IV once daily, no cyclospor...

14.1 Overview of Clinical Studies An overview of the trials contributing to the assessment of efficacy and safety of PREVYMIS in HSCT and kidney transplant recipients is provided in Table 17.

Table 17Trials Conducted with PREVYMIS Trial (NCT Number) Population Trial Arms (N) N represents the number of subjects treated. Duration of Prophylaxis Post-Transplant Efficacy Endpoint P001 (NCT02137772) Adult allogeneic HSCT recipients [R+] PREVYMIS (373) Placebo (192) Through Week 14 Clinically significant CMV infection through Week 24 post-HSCT P040 (NCT03930615) Adult allogeneic HSCT recipients [R...

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 pediat...

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)...

Risk of Adverse Reactions or Reduced Therapeutic Effect Due to Drug Interactions: The concomitant use of PREVYMIS with certain drugs may result in potentially significant drug interactions, some of which may lead to adverse reactions (PREVYMIS or concomitant drugs) or reduced therapeutic effect of PREVYMIS or the concomitant drug. Consult the full prescribing information for contraindications and dosage recommendations for concomitant drugs. ( 4 , 5.1 , 7.1 , 7.2 , 7.3 ) Risks Associated with Hy...

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 t...