Darunavir + Pitavastatin = Unknown or no reaction

Effect on Concentration

Darunavir
No change
Applies within class?
No
Pitavastatin
No change
Applies within class?
No

Pharmacologic Effects

Darunavir
Effect
N/A
Applies within class?
No
Pitavastatin
Effect
N/A
Applies within class?
No

Interaction History

N/A

Last Updated 16-Jul-2018

Summary

Sources

Darunavir versus Pitavastatin ^

Study Design

An open-label, parallel-arm, pharmacokinetic (PK) study in HIV-uninfected healthy volunteers was conducted to examine drug-drug interactions between pitavastatin and darunavir/ritonavir (DRV/r) as well as pitavastatin and efavirenz (EFV). Subjects received a pitavastatin dose of 2 mg for 4 days, followed by either EFV 600 mg (n = 14) or DRV/r 800/100 mg (n = 14) daily for 10 days, and pitavastatin 2 mg coadministered with EFV 600 mg or DRV/r 800/100 mg for 4 days. Full PK profiles were determined for pitavastatin and its lactone metabolite on days 4 and 18 and for EFV or DRV on days 14 and 18. There were no washout periods. An additional single-centered, open-label, multi-dose, fixed-sequence study was conducted in HIV seronegative, healthy volunteers. Pitavastatin 4mg was administered once daily on days 1-5 and days 12-16. Darunavir 800mg with ritonavir 100mg was administed on days 6 - 16. PK blood sampling was performed on days 5, 11, and 16. No significiant interaction was concluded if the 90% CI of the GMRs for total exposure and for peak exposure of the two treatments were within the 80-125% range. 28 subjects were enrolled and 27 subjects were available for PK blood sampling. There were no washout periods.

Study Results

In the first study, the GMR for pitavastatin with DRV/r versus alone was 0.91 (90% CI: 0.78 to 1.06) for AUC and 0.93 (90% CI: 0.72 to 1.19) for Cmax.Thus there were no significant PK interactions between Pitavastatin and DRV/r. Also, no significant safety issues or lipid changes were noted. The results from the second study showed a GMR (90% CI) of 0.74 (0.69-0.80) for AUC and 0.96 (0.84-1.09) for Cmax during coadministration with darunavir/ritonavir. For both darunavir and ritonavir, the 90 % CIs for AUC and Cmax were within 80-125% with pitavastatin co-administration. No significant safety issues were reported.

Study Conclusions

The combination of darunavir/ritonavir and pitavastatin do not appear to cause any clinically significant alterations in PK paramaters.

References

Malvestutto CD, Ma Q, Morse GD. Lack of pharmacokinetic interactions between pitavastatin and efavirenz or darunavir/ritonavir. Journal Of Acquired Immunodeficiency Syndromes . 2014; 4: 390-396.