Atazanavir and Cobicistat

EVOTAZ is a two-drug combination of atazanavir, a human immunodeficiency virus (HIV-1) protease inhibitor, and cobicistat, a CYP3A inhibitor indicated for use in combination with other antiretroviral agents for the treatment of HIV‑1 infection in adults and pediatric patients weighing at least 35 kg. Limitations of Use Use of EVOTAZ in treatment-experienced patients should be guided by the number of baseline primary protease inhibitor resistance substitutions.

EVOTAZ is a fixed-dose tablet consisting of the HIV-1 antiretroviral drug, atazanavir and the CYP3A inhibitor, cobicistat.

• Pretreatment testing: Renal laboratory testing should be performed in all patients prior to initiation of EVOTAZ and continued during treatment with EVOTAZ. Hepatic testing should be performed in patients with underlying liver disease prior to initiation of EVOTAZ and continued during treatment with EVOTAZ. • Recommended dosage: One tablet once daily, taken orally with food in adults and pediatric patients weighing at least 35 kg. • Renal impairment: EVOTAZ is not recommended for use in treatment-experienced patients with end-stage renal disease managed with hemodialysis. • Hepatic impairment: EVOTAZ is not recommended in patients with any degree of hepatic impairment.

The concomitant use of EVOTAZ and the following drugs in Table 1, are contraindicated due to the potential for serious and/or life-threatening events or loss of therapeutic effect. EVOTAZ 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. • when coadministered with drugs that strongly induce CYP3A4, which may lead to lower exposure of EVOTAZ resulting in potential loss of efficacy and development of possible resistance (Table 5).

• Cardiac conduction abnormalities: PR interval prolongation may occur in some patients. Consider ECG monitoring in patients with preexisting conduction system disease or when administered with other drugs that may prolong the PR interval. • Severe skin reactions: Discontinue if severe rash develops. • Assess creatinine clearance (CLcr) before initiating treatment. Consider alternative medications that do not require dosage adjustments in patients with renal impairment. • When cobicistat, a component of EVOTAZ, is used in combination with a tenofovir disoproxil fumarate (tenofovir DF)-containing regimen, cases of acute renal failure and Fanconi syndrome have been reported. • When used with tenofovir DF, assess urine glucose and urine protein at baseline and monitor CLcr, urine glucose, and urine protein. Monitor serum phosphorus in patients with or at risk for renal impairment.

The following adverse reactions are discussed in greater detail in other sections of the labeling: • cardiac conduction abnormalities • rash • effects on serum creatinine • new onset or worsening renal impairment when used with tenofovir DF • chronic kidney disease • nephrolithiasis and cholelithiasis • hepatotoxicity • hyperbilirubinemia For additional safety information about atazanavir and cobicistat, consult the full prescribing information for these individual products. Most common adverse reactions seen with atazanavir coadministered with cobicistat (greater than 5%, Grades 2-4) are jaundice and rash.

Coadministration of EVOTAZ can alter the concentration of other drugs and other drugs may alter the concentration of EVOTAZ, which may result in known or potentially significant drug interactions. The potential drug-drug interactions must be considered prior to and during therapy.

Store EVOTAZ tablets at 25°C (77°F), excursions permitted between 15°C and 30°C (59°F and 86°F).