arnings and Precautions (5.1) and Drug Interactions (7.2, 7.3)].PREVYMIS is contraindicated with pitavastatin and simvastatin when co-administered with cyclosporine. Concomitant administration of PREVYMIS in combination with cyclosporine may result in significantly increased pitavastatin or simvastatin concentrations, which may lead to myopathy or rhabdomyolysis [see Warnings and Precautions (5.1) and Drug Interactions (7.2, 7.3)].
5.1 Risk Of Adverse Reactions Or Reduced Therapeutic Effect Due To Drug Interactions
The concomitant use of PREVYMIS and 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 [see Contraindications (4) and Drug Interactions (7.1, 7.2, 7.3)].See Table 3 for steps to prevent or manage these possible or known significant drug interactions, including dosing recommendations. Consider the potential for drug interactions prior to and during PREVYMIS therapy; review concomitant medications during PREVYMIS therapy; and monitor for adverse reactions associated with PREVYMIS and concomitant medications.
6.1 Clinical Trials Experience
Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.
7.1 Potential For Other Drugs To Affect Prevymis
Letermovir is a substrate of organic anion-transporting polypeptide 1B1/3 (OATP1B1/3) transporters. Co-administration of PREVYMIS with drugs that are inhibitors of OATP1B1/3 transporters may result in increases in letermovir plasma concentrations (Table 3).
7.2 Potential For Prevymis To Affect Other Drugs
Co-administration of PREVYMIS with midazolam results in increased midazolam plasma concentrations, indicating that letermovir is a moderate inhibitor of CYP3A [see Clinical Pharmacology (12.3)]. Co-administration of PREVYMIS with drugs that are CYP3A substrates may result in clinically relevant increases in the plasma concentrations of co-administered CYP3A substrates (Table 3) [see Contraindications (4) and Warnings and Precautions (5.1)].Letermovir is an inhibitor of OATP1B1/3 transporters. Co-administration of PREVYMIS with drugs that are substrates of OATP1B1/3 transporters may result in a clinically relevant increase in plasma concentrations of co-administered OATP1B1/3 substrates (Table3).The magnitude of CYP3A- and OATP1B1/3-mediated drug interactions on co-administered drugs may be different when PREVYMIS is co-administered with cyclosporine. See the prescribing information for cyclosporine for information on drug interactions with cyclosporine.
7.3 Established And Other Potentially Significant Drug Interactions
If dose adjustments of concomitant medications are made due to treatment with PREVYMIS, doses should be readjusted after treatment with PREVYMIS is completed.Table 3 provides a listing of established or potentially clinically significant drug interactions. The drug interactions described are based on studies conducted with PREVYMIS or are predicted drug interactions that may occur with PREVYMIS [see Contraindications (4), Warnings and Precautions (5.1), and Clinical Pharmacology (12.3)].Table 3: Potentially Significant Drug Interactions: Alterati |
