Darunavir/Ritonavir + Pravastatin = Precautionary

Effect on Concentration

Darunavir/Ritonavir
Unknown
Applies within class?
No
Pravastatin
Increase
Applies within class?
No

Pharmacologic Effects

Darunavir/Ritonavir
Effect
N/A
Applies within class?
No
Pravastatin
Effect
N/A
Applies within class?
No

Interaction History

N/A

Last Updated 13-Jul-2018

Summary

Potential Increases in pravastatin are not necessarily the result of a drug interaction, but rather result from genotypic differences in SLCO1B1 haplotype. Cautious monitoring is warranted, but clinical significance is unknown.

Sources

Pravastatin vs ritonavir ^

Study Design

Study Results

Study Conclusions

References

M Mascolini. Pravastatin levels 81% higher with darunavir/ritonavir. 8th International Workshop On Clinical Pharmacology Of Hiv Therapy. Budapest, Hungary. ; 2007.

Influence of SLCO1B1 Polymorphisms on the Drug‐Drug Interaction Between Darunavir/Ritonavir and Pravastatin. ^

Study Design

The authors investigated whether SLCO1B1 polymorphisms contribute to variability in pravastatin pharmacokinetics when pravastatin is administered alone versus with darunavir/ritonavir. HIV-negative healthy participants were prospectively enrolled on the basis of SLCO1B1 diplotype: group 1 (*1A/*1A, n = 9); group 2 (*1A/*1B, n = 10; or *1B/*1B, n = 2); and group 3 (*1A/*15, n = 1; *1B/*15, n = 5; or *1B/*17, n = 1). Participants received pravastatin (40 mg) daily on days 1 through 4, washout on days 5 through 11, darunavir/ritonavir (600/100 mg) twice daily on days 12 through 18, with pravastatin 40 mg added back on days 15 through 18. Pharmacokinetic studies were conducted on day 4 (pravastatin alone) and day 18 (pravastatin + darunavir/ritonavir).

Study Results

Pravastatin area under the plasma concentration-time curve (AUC(tau)) was 21% higher during administration with darunavir/ritonavir compared with pravastatin alone; however, this difference was not statistically significant (P = .11). Group 3 variants had 96% higher pravastatin AUC(tau) on day 4 and 113% higher pravastatin AUC(tau) on day 18 compared with group 1. The relative change in pravastatin pharmacokinetics was largest in group 3 but did not differ significantly between diplotype groups.

Study Conclusions

In sum, the influence of SLCO1B1*15 and *17 haplotypes on pravastatin pharmacokinetics was maintained in the presence of darunavir/ritonavir. Because OATP1B1 inhibition would be expected to be greater in carriers of normal or high-functioning SLCO1B1 haplotypes, these findings suggest that darunavir/ritonavir is not a potent inhibitor of OATP1B1-mediated pravastatin transport in vivo.

References

Aquilante CL, Kiser JJ, Anderson PL, Christians U, Kosminski LA, Daily EB, Sidhom MS. Influence of slco1b1 polymorphisms on the drug‐drug interaction between darunavir/ritonavir and pravastatin. Journal Of Clinical Pharmacology. 2012; 11: 1725-38.