Overview
11 DESCRIPTION Efavirenz, emtricitabine and tenofovir disoproxil fumarate is a fixed-dose combination tablet containing EFV, FTC, and TDF. EFV is a non-nucleoside reverse transcriptase inhibitor (NNRTI). FTC is a synthetic nucleoside analog of cytidine. TDF, which is converted in vivo to tenofovir, is an acyclic nucleoside phosphonate (nucleotide) analog of adenosine 5′-monophosphate.
Mechanism of Action
12 CLINICAL PHARMACOLOGY 12.1 Mechanism of Action Efavirenz, emtricitabine and tenofovir disoproxil fumarate is a fixed-dose combination of antiviral drugs EFV, FTC, and TDF [see Microbiology (12.4) ]. 12.2 Pharmacodynamics Cardiac Electrophysiology Efavirenz: The effect of EFV on the QTc interval was evaluated in an open-label, positive and placebo-controlled, fixed single sequence 3-period, 3-treatment crossover QT study in 58 healthy subjects enriched for CYP2B6 polymorphisms. The mean C max of EFV in subjects with CYP2B6 *6/*6 genotype following the administration of 600 mg daily dose for 14 days was 2.25-fold the mean C max observed in subjects with CYP2B6 *1/*1 genotype. A positive relationship between EFV concentration and QTc prolongation was observed.
Indications
- 1 INDICATIONS AND USAGE Efavirenz, emtricitabine and tenofovir disoproxil fumarate tablets are indicated as a complete regimen or in combination with other antiretroviral agents for the treatment of HIV-1 infection in adults and pediatric patients weighing at least 40 kg. Efavirenz, emtricitabine and tenofovir disoproxil fumarate tablet is a three-drug combination of efavirenz (EFV), a non-nucleoside reverse transcriptase inhibitor, and emtricitabine (FTC) and tenofovir disoproxil fumarate (TDF), both HIV-1 nucleoside analog reverse transcriptase inhibitors, and is indicated as a complete...
Common Doses
- 50 mL
- 200 mg
- 600 mg
- 300 mg
Dosage
2 DOSAGE AND ADMINISTRATION Testing: Consult Full Prescribing Information for important testing recommendations prior to initiation and during treatment with efavirenz, emtricitabine and tenofovir disoproxil fumarate tablets. (2.1) Recommended dosage in adults and pediatric patients weighing at least 40 kg: One tablet once daily taken orally on an empty stomach, preferably at bedtime. (2.2) Renal impairment: Not recommended in patients with estimated creatinine clearance below 50 mL/min. (2.3) Hepatic impairment: Not recommended in patients with moderate to severe hepatic impairment. (2.
Black Box Warning
WARNING: POSTTREATMENT ACUTE EXACERBATION OF HEPATITIS B Severe acute exacerbations of hepatitis B virus (HBV) have been reported in patients who are coinfected with HIV-1 and HBV and have discontinued products containing emtricitabine (FTC) and/or tenofovir disoproxil fumarate (TDF), which are components of efavirenz, emtricitabine and tenofovir disoproxil fumarate. Closely monitor hepatic function with both clinical and laboratory follow-up for at least several months in patients who are coinfected with HIV-1 and HBV and discontinue efavirenz, emtricitabine and tenofovir disoproxil fumarate.
Contraindications
- 4 CONTRAINDICATIONS Efavirenz, emtricitabine and tenofovir disoproxil fumarate tablets are contraindicated in patients with previously demonstrated clinically significant hypersensitivity (e.g., Stevens-Johnson syndrome, erythema multiforme, or toxic skin eruptions) to efavirenz, a component of efavirenz, emtricitabine and tenofovir disoproxil fumarate tablets [see Warnings and Precautions (5.2) ] . Efavirenz, emtricitabine and tenofovir disoproxil fumarate tablets are contraindicated to be coadministered with voriconazole or elbasvir/grazoprevir [see Drug Interactions (7.
Side Effects
- 6 ADVERSE REACTIONS The following adverse reactions are discussed in other sections of the labeling: Severe Acute Exacerbations of Hepatitis B in Patients Coinfected with HIV-1 and HBV [see Warnings and Precautions (5.1) ] . Rash [see Warnings and Precautions (5.2) ]. Hepatotoxicity [see Warnings and Precautions (5.3) ]. Psychiatric Symptoms [see Warnings and Precautions (5.5) ]. Nervous System Symptoms [see Warnings and Precautions (5.6) ]. New Onset or Worsening Renal Impairment [see Warnings and Precautions (5.7) ]. Embryo-Fetal Toxicity [see Warnings and Precautions (5.8) ].
Interactions
- 7 DRUG INTERACTIONS Consult Full Prescribing Information prior to and during treatment for important potential drug interactions. (4 , 5.4 , 7 ) HIV-1 protease inhibitors: Coadministration of efavirenz, emtricitabine and tenofovir disoproxil fumarate with either lopinavir/ritonavir or darunavir and ritonavir increases tenofovir concentrations. Monitor for evidence of tenofovir toxicity. Coadministration of efavirenz, emtricitabine and tenofovir disoproxil fumarate with either atazanavir or atazanavir and ritonavir is not recommended. (7.3) 7.