PIFELTRO

Doravirine pharmacokinetics are similar in healthy participants and participants living with HIV. Doravirine pharmacokinetics are provided in Table 7.

Table 7Pharmacokinetic Properties of Doravirine Parameter Doravirine Abbreviations: AUC=area under the time concentration curve; C max =maximum concentration; C 24 =concentration at 24 hours; T max time to C max ; V dss = volume of distribution at steady state, t 1/2 =elimination half-life; CL/F=apparent clearance; CL renal =apparent renal clear...

14.1 Clinical Trial Results in Adults with No Antiretroviral Treatment History The efficacy of PIFELTRO is based on the analyses of 96-week data from two randomized, multicenter, double-blind, active controlled Phase 3 trials (DRIVE-FORWARD, NCT02275780 and DRIVE-AHEAD, NCT02403674) in participants living with HIV with no antiretroviral treatment history (n=1494). In DRIVE-FORWARD, 766 participants were randomized and received at least 1 dose of either PIFELTRO once daily or darunavir 800 mg + ritonavir 100 mg (DRV+r) once daily each in combination with emtricitabine/tenofovir DF (FTC/TDF) or ...

The following adverse reactions are discussed in other sections of the labeling: Immune Reconstitution Syndrome [see Warnings and Precautions (5.3) ] Most common adverse reactions (incidence greater than or equal to 5%, all grades) are nausea, dizziness, headache, fatigue, diarrhea, abdominal pain, and abnormal dreams. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Merck Sharp & Dohme LLC at 1-877-888-4231 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch . 6.1 Clinical Trials Experience ...

PIFELTRO is contraindicated when co-administered with drugs that are strong cytochrome P450 (CYP)3A enzyme inducers as significant decreases in doravirine plasma concentrations may occur, which may decrease the effectiveness of PIFELTRO [see Warnings and Precautions (5.2) , Drug Interactions (7.1) , and Clinical Pharmacology (12.3) ] . These drugs include, but are not limited to, the following: th...

Severe skin reactions, including Stevens-Johnson syndrome (SJS)/toxic epidermal necrolysis (TEN), have been reported during the postmarketing experience with doravirine-containing regimens. Discontinue PIFELTRO, and other medications known to be associated with severe skin reactions, immediately if a painful rash with mucosal involvement or a progressive severe rash develops, and closely monitor clinical status. ( 5.1 ) Monitor for Immune Reconstitution Syndrome. ( 5.3 ) 5.1 Severe Skin Reaction...

7 DRUG INTERACTIONS Consult the full prescribing information prior to and during treatment for important potential drug-drug interactions. ( 4 , 5.2 , 7 ) 7.1 Effect of Other Drugs on PIFELTRO Co-administration of PIFELTRO with a CYP3A inducer decreases doravirine plasma concentrations, which may reduce PIFELTRO efficacy [see Contraindications (4) , Warnings and Precautions (5.2) , and Clinical Ph...