EFAVIRENZ, EMTRICITABINE, AND TENOFOVIR DISOPROXIL FUMARATE

AbsorptionPeak efavirenz plasma concentrations of 1.6-9.1 μM were attained by 5 hours following single oral doses of 100 mg to 1600 mg administered to uninfected volunteers. Dose-related increases in C max and AUC were seen for doses up to 1600 mg; the increases were less than proportional suggesting diminished absorption at higher doses. In HIV-1-infected patients at steady state, mean C max , mean C min , and mean AUC were dose proportional following 200 mg, 400 mg, and 600 mg daily doses. Ti...

14.1 Adults Study 006 , a randomized, open-label trial, compared efavirenz tablets (600 mg once daily) + zidovudine (ZDV, 300 mg q12h) + lamivudine (LAM, 150 mg q12h) or efavirenz tablets(600 mg once daily) + indinavir (IDV, 1000 mg q8h) with indinavir (800 mg q8h) + zidovudine (300 mg q12h) + lamivudine (150 mg q12h). Twelve hundred sixty-six patients (mean age 36.5 years [range 18-81], 60% Caucasian, 83% male) were enrolled. All patients were efavirenz-, lamivudine-, NNRTI-, and PI-naive at study entry. The median baseline CD4+ cell count was 320 cells/mm3 and the median baseline HIV-1 RNA l...

The most significant adverse reactions observed in patients treated with efavirenz are:

• psychiatric symptoms [see Warnings and Precautions ( 5.5 )],
• nervous system symptoms [see Warnings and Precautions ( 5.6 )],
• rash [see Warnings and Precautions ( 5.8 )].
• hepatotoxicity [see Warnings and Precautions ( 5.9 )] Most common adverse reactions (>5%, moderate-severe) are impaired concentration, abnormal dreams, rash, dizziness, nausea, headache, fatigue, insomnia, and vomiting.( 6 ) To report SUS...

• Efavirenz is contraindicated in patients with previously demonstrated clinically significant hypersensitivity (e.g., Stevens-Johnson syndrome, erythema multiforme, or toxic skin eruptions) to any of the components of this product.
• Coadministration of efavirenz with elbasvir and grazoprevir is contraindicated [see Warnings and Precautions ( 5.1 ) and Drug Interactions ( 7.1 ) ].
• Patients with...

• QTc prolongation : Consider alternatives to efavirenz in patients taking other medications with a known risk of Torsade de Pointes or in patients at higher risk of Torsade de Pointes. ( 5.2 )
• Do not use as a single agent or add on as a sole agent to a failing regimen. Consider potential for cross resistance when choosing other agents. ( 5.3 )
• Not recommended with ATRIPLA, which contains efavirenz, emtricitabine, and tenofovir disoproxil fumarate, unless needed for dose adjustment when coadm...

7 DRUG INTERACTIONS Coadministration of efavirenz can alter the concentrations of other drugs and other drugs may alter the concentrations of efavirenz. The potential for drug-drug interactions should be considered before and during therapy. ( 7 ) 7.1 Potential for efavirenz to Affect other Drugs Efavirenz has been shown in vivo to induce CYP3A and CYP2B6. Other compounds that are substrates of CY...