Elvitegravir + Atazanavir = Precautionary

Effect on Concentration

Elvitegravir
Increase
Applies within class?
No
Atazanavir
No change
Applies within class?
No

Pharmacologic Effects

Elvitegravir
Effect
N/A
Applies within class?
No
Atazanavir
Effect
N/A
Applies within class?
No

Interaction History

N/A

Last Updated 18-Jul-2018

Summary

Sources

Boosted Elvitegravir versus Atazanavir ^

Study Design

PK study to determine PK differences between cobicistat boosted elvitegravir alone verusus cobicistat boosted elvitegravir with atazanavir

Study Results

In a pharmacokinetic (PK) study presented in the elvitegravir (EVG) prescribing information1, concomitant administration of EVG 200 mg once daily and ritonavir-boosted atazanavir (ATV/r; 300/100 mg once daily) in healthy subjects (n=33) has resulted in increased EVG AUC, maximum serum concentration (Cmax), and minimum serum concentration.Concomitant administration of a EVG 200 mg once daily modestly decreased AUC and Cmax of ATV. In a separate study1, when a reduced EVG dose (85 mg once daily) was given with ATV/r 300/100 mg once daily in healthy subjects (n=20), the AUC and Cmax of EVG were similar to PKs of EVG 150mg daily administered alone. PKs of ATV were not significantly affected by a reduced EVG dose (85 mg once daily). Another PK trial in healthy subjects (n=10) showed consistent result with the study above.2 Concomitant use of ATV/r (300/100 mg) and EVG 85mg once daily resulted in AUC and Cmax of EVG similar to those when EVG 150mg daily was administered alone. PKs of ATV were modestly decreased when administered with EVG 85 mg once daily. ref population EVG (dose/freq) ATV or ATV/r (dose/ freq) PK parameters [90% CI] of EVG Cmax AUC Cmin 1 n=33 200 mg QD 300/100 mg QD 1.85 [1.69, 2.03] 2.00 [1.85, 2.16] 2.88 [2.53, 3.27] 1 n=20 85 mg QD 0.91 [0.81, 1.02]* 1.07 [0.95, 1.21]* 1.38 [1.18, 1.61]* 2 n=10 0.84 [0.62, 1.15]* 1.17 [0.88, 1.56]* 1.83 [1.17, 2.86]* *Comparison based on EVG 150 mg QD ref population EVG (dose/freq) ATV or ATV/r (dose/ freq) PK parameters [90% CI] of ATV Cmax AUC Cmin 1 n=33 200 mg QD 300/100 mg QD 0.84 [0.78, 0.91] 0.79 [0.74, 0.85] 0.65 [0.59, 0.73] 1 n=20 85 mg QD 0.97 [0.87, 1.08] 0.89 [0.80, 0.99] 0.83 [0.72, 0.95] 2 n=10 0.76 [0.59, 0.98] 0.90 [0.73, 1.12] 0.81 [0.56, 1.17]

Study Conclusions

Based on the study results above and the prescribing information for EVG published, when EVG is combined with ATV/r 300 /100 mg once daily, the EVG dose should be reduced to 85 mg once daily.However, when EVG is administered as the combination product containing elvitegravir/cobicistat/emtricitabine/tenofovir, use of ATV or ATV/r is not recommended due to lack of data and unknown pharmacokinetic effects.

References

Ramanathan S, Wang H, Stondell T, Cheng A, Kearney BP. Pharmacokinetics and drug interaction profile of cobicistat boosted-elvitegravir with atazanavir, rosuvastatin or rifabutin . International Workshop On Clinical Pharmacology Of Hiv Therapy. Barcelona, Spain. 13; April 2012.