EVOTAZ

Absorption, Distribution, Metabolism, and

ExcretionThe pharmacokinetic (PK) properties of the components of EVOTAZ (atazanavir 300 mg and cobicistat 150 mg) were evaluated in healthy adult participants (Study AI424-511). Results are summarized in Table 6.

Table 6Pharmacokinetic Properties of the Components of EVOTAZ Atazanavir Cobicistat a Following EVOTAZ dosing under fasted conditions. b Values refer to geometric mean ratio (fed / fasted) and (90% confidence interval). c Dosing in mass bala...

14.1 Clinical Trial Results in Treatment-Naive Adult Participants with HIV-1 Study GS-US-216-0114 The safety and efficacy of atazanavir coadministered with cobicistat were evaluated in a randomized, double-blind, active-controlled trial (Study GS-US-216-0114 [NCT01108510]) in treatment-naive participants with HIV-1 infection with baseline estimated creatinine clearance above 70 mL/min (N=692). Participants were randomized in a 1:1 ratio to receive either atazanavir 300 mg coadministered with cobicistat 150 mg once daily or atazanavir 300 mg coadministered with ritonavir 100 mg once daily. All ...

The following adverse reactions are discussed in greater detail in other sections of the labeling:

• cardiac conduction abnormalities [see Warnings and Precautions (5.1) ]
• rash [see Warnings and Precautions (5.2) ]
• effects on serum creatinine [see Warnings and Precautions (5.3) ]
• new onset or worsening renal impairment when used with tenofovir DF [see Warnings and Precautions (5.4) ]
• chronic kidney disease [see Warnings and Precautions (5.5) ]
• nephrolithiasis and cholelithiasis [see Wa...

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 [see Warnings and Precautions (5.8 , 5.9) , Drug Interactions (7) , and Clinical Pharmacology (12.3) ]. EVOTAZ is contraindicated:

• in patients with previously demonstrated clinically significant hypersensitivity (e.g.,...

• 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. ( 5.1 , 6 , 7.3 , 12.2 , 17 )
• Severe skin reactions: Discontinue if severe rash develops. ( 5.2 , 6.1 , 17 )
• Assess creatinine clearance (CLcr) before initiating treatment. Consider alternative medications that do not require dosage adjustments in patients...

7 DRUG INTERACTIONS 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. (4 , 7 , 12.3) 7.1 Potential for EVOTAZ to Affect Other Drugs Atazanavir is an inhibitor of CYP3A ...