Doravirine

Brand Names: Pifeltro

Drug Class: Human Immunodeficiency Virus 1 Non-Nucleoside Analog Reverse Transcriptase Inhibitor

Overview

11 DESCRIPTION PIFELTRO is a film-coated tablet containing doravirine for oral administration. Doravirine is an HIV-1 non-nucleoside reverse transcriptase inhibitor (NNRTI). Each tablet contains 100 mg of doravirine as the active ingredient. The tablets include the following inactive ingredients: colloidal silicon dioxide, croscarmellose sodium, hypromellose acetate succinate, lactose...

Mechanism of Action

12 CLINICAL PHARMACOLOGY 12.1 Mechanism of Action Doravirine is an antiretroviral drug [see Microbiology (12.4) ]. 12.2 Pharmacodynamics In a Phase 2 trial evaluating doravirine over a dose range of 0.25 to 2 times the recommended dose of PIFELTRO, (in combination with FTC/TDF) in participants living with HIV with no antiretroviral treatment history, no exposure-response relationship for efficacy was identified for doravirine. Cardiac Electrophysiology At a doravirine dose of 1200 mg, which provides approximately 4 times the peak concentration observed following the recommended dose of PIFELTRO, doravirine does not prolong the QT interval to any clinically relevant extent. 12.

Indications

  • 1 INDICATIONS AND USAGE PIFELTRO ® is indicated in combination with other antiretroviral agents for the treatment of HIV-1 infection in adults and pediatric patients weighing at least 35 kg: with no prior antiretroviral treatment history; OR to replace the current antiretroviral regimen in those who are virologically-suppressed (HIV-1 RNA less than 50 copies per mL) on a stable antiretroviral regimen with no history of treatment failure and no known substitutions associated with resistance to doravirine [see Clinical Studies (14) ] .

Common Doses

  • 100 mg

Dosage

2 DOSAGE AND ADMINISTRATION Recommended dosage: One tablet taken orally once daily with or without food in adults and pediatric patients weighing at least 35 kg. ( 2.1 ) Dosage adjustment with rifabutin: One tablet taken twice daily (approximately 12 hours apart). ( 2.2 ) 2.1 Recommended Dosage The recommended dosage regimen of PIFELTRO in adults and pediatric patients weighing at least 35 kg is one 100 mg tablet taken orally once daily with or without food [see Clinical Pharmacology (12.3) ] . 2.

Contraindications

  • 4 CONTRAINDICATIONS 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: the anticonvulsants carbamazepine, oxcarbazepine, phenobarbital, phenytoin the androgen receptor inhibitor enzalutamide the antimycobacterials rifampin, rifapentine the cytotoxic...

Side Effects

  • 6 ADVERSE REACTIONS 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.

Interactions

  • 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 Pharmacology (12.3) ] . Co-administration of PIFELTRO and drugs that are inhibitors of CYP3A may result in increased plasma concentrations of doravirine.