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: Possible clinically significant adverse reactions from greater exposure of concomitant drugs or PREVYMIS; Significant decrease of concomitant drug plasma concentrations which may lead to reduced therapeutic effect of the concomitant drug.
See Table 6 for steps to prevent or manage these known or potentially significant drug interactions, including dosing recommendations [see CONTRAINDICATIONS, Effects of PREVYMIS on Other Drugs and Established and Other Potential Drug Interactions under INTERACTIONS].
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. [See Table 6, Effects of PREVYMIS on Other Drugs and Established and Other Potential Drug Interactions under INTERACTIONS].
The safety and efficacy of letermovir has been established in patients with a negative CMV DNA test result prior to initiation of prophylaxis. CMV DNA was monitored on a weekly basis until post-transplant Week 14, and subsequently bi-weekly until Week 24. In cases of clinically significant CMV DNAemia or disease, letermovir prophylaxis was stopped and standard-of-care pre-emptive therapy (PET) or treatment was initiated. In patients in whom letermovir prophylaxis was initiated and the baseline CMV DNA test was subsequently found to be positive, prophylaxis could be continued if PET criteria has not been met.
Renal Impairment: No dose adjustment of PREVYMIS is required based on renal impairment [see Renal Impairment and Hepatic Impairment under DOSAGE & ADMINISTRATION, and Hepatic Impairment as follows]. There are no data in patients with end-stage renal disease (CrCl less than 10 mL/min), including patients on dialysis.
In patients with moderate or severe renal impairment (CrCl less than 50 mL/min) receiving PREVYMIS concentrate for solution for infusion, accumulation of the intravenous vehicle, hydroxypropyl betadex, could occur. Serum creatinine levels should be closely monitored in these patients.
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 [see Hepatic Impairment under DOSAGE & ADMINISTRATION].
PREVYMIS is not recommended in patients with moderate hepatic impairment combined with moderate or severe renal impairment [see Hepatic Impairment under DOSAGE & ADMINISTRATION].
Use in Children: Safety and efficacy of PREVYMIS in patients below 18 years of age have not been established.
Use in Elderly: Safety and efficacy were similar across older and younger subjects in the Phase 3 trial in HSCT recipients.