Coadministration of Reyataz with efavirenz is not recommended. If the coadministration of Reyataz with an NNRTI is required, an increase in the dose of both Reyataz and ritonavir to 400 mg and 200 mg, respectively, in combination with efavirenz could be considered with close clinical monitoring. Coadministration of efavirenz (600 mg, once daily, with food) with atazanavir/ritonavir (400 mg/100 mg, once daily, with food) was studied in healthy volunteers. When compared to Reyataz 300 mg/ritonavir 100 mg once daily in the evening without efavirenz, atazanavir AUC was unchanged, Cmax increased 17% and Cmin decreased 42%. This decrease in atazanavir Cmin might negatively impact the efficacy of atazanavir. Coadministration of efavirenz (600 mg, once daily, with food) with atazanavir/ritonavir (400 mg/200 mg, once daily, with food) was studied in healthy volunteers. When compared to Reyataz 300 mg/ritonavir 100 mg once daily in the evening without efavirenz and based on historical comparison, atazanavir AUC, Cmax and Cmin were unchanged. The mechanism of efavirenz/atazanavir interaction is CYP3A4 induction. 

Efavirenz decreases atazanavir exposure. In treatment-naive adult patients: if Reyataz is combined with efavirenz, Reyataz 400 mg (two 200-mg capsules) should be administered with ritonavir 100 mg simultaneously once daily with food, and efavirenz 600 mg should be administered once daily on an empty stomach, preferably at bedtime. In treatment-experienced adult patients: coadministration of Reyataz with efavirenz in treatment-experienced patients is not recommended due to decreased atazanavir exposure. Coadministration of efavirenz (600 mg, once daily) with atazanavir (400 mg, once daily) was studied in 27 healthy volunteers. Atazanavir Cmax, AUC and Cmin decreased 59%, 74% and 93%, respectively. Coadministration of efavirenz (600 mg, once daily) with atazanavir/ritonavir (300 mg/100 mg, once daily, 2 hours before efavirenz) was studied in 13 healthy volunteers. Cmax, AUC and Cmin increased 14%, 39% and 48%, respectively. Coadministration of efavirenz (600 mg, once daily, with food) with atazanavir/ritonavir (400 mg/100 mg, once daily, with food) was studied in 14 healthy volunteers. Atazanavir AUC was unchanged, Cmax increased 17% and Cmin decreased 42%.

Coadministration of atazanavir (400 mg once daily) and efavirenz (600 mg once daily) to 27 subjects resulted in a 59% decrease in atazanavir Cmax, a 74% decrease in AUC and a 93% decrease in Cmin. A study in 13 patients showed that boosting atazanavir with ritonavir (300/100 mg once daily) with co-administered efavirenz (600 mg once daily) increased Cmax, AUC and Cmin by 14%, 39% and 48%, respectively, compared to unboosted atazanavir (400 mg once daily) without efavirenz. Coadministration of atazanavir/ritonavir (400/100 mg once daily) and efavirenz (600 mg once daily) had no effect on atazanavir AUC, increased atazanavir Cmax by 17% and decreased Cmin by 42% (n=14). When co-administered with efavirenz in treatment naïve patients, the recommended dose of atazanavir is 400 mg with ritonavir 100 mg (together once daily with food) and efavirenz 600 mg (once daily on an empty stomach, preferably at bedtime). Coadministration of efavirenz and atazanavir in treatment-experienced patients is not recommended.

Comparison of switching from atazanavir alone (400 mg) to coadministration of 600 mg atazanavir and 600 mg efavirenz versus 300 mg atazanavir, 100 mg ritonavir and 600 mg efavirenz showed atazanavir AUC was decreased (21%) when given without ritonavir but maintained (increased 39%) when boosted with ritonavir. 

Coadministration of atazanavir (400 mg once daily) and efavirenz (600 mg once daily) to healthy subjects (n=27) resulted in decreases in atazanavir Cmax (3369 to 1375 ng/ml, 59%) and AUC (20656 to 5462 ng/ml.h, 74%). Mean efavirenz pharmacokinetic parameters were similar to literature values in HIV+ patients.