Tipranavir + Atorvastatin = Precautionary

Effect on Concentration

Tipranavir
Unknown
Applies within class?
No
Atorvastatin
Increase
Applies within class?
No

Pharmacologic Effects

Tipranavir
Effect
N/A
Applies within class?
No
Atorvastatin
Effect
N/A
Applies within class?
No

Interaction History

N/A

Last Updated 10-Jul-2018

Summary

Sources

Differential effects of tipranavir plus ritonavir on atorvastatin or rosuvastatin pharmacokinetics in healthy volunteers ^

Study Design

The manufacturer has performed pharmacokinetic studies on multiple protease inhibitors and their effect on atorvastatin. Combining atorvastatin (10mg x 1) with tipranavir/ritonavir (500mg BID/200mg BID x 7 days), resulted in an increase in the atorvastatin exposure (AUC) by 9.4-fold. The combination of atorvastatin with saquinavir/ritonavir (not a clinically used dose, but atorvastatin exposure is expected to be even larger clinically) and darunavir/ritonavir caused an almost 4-fold increase in the AUC of atorvastatin. Atorvastatin with fosamprenavir +/- ritonavir caused an approximately 2.5 fold increase in atorvastatin AUC. Nelfinavir co-administered with atorvastatin caused an increase in atorvastatin AUC by 74%. Pham et al. report that coadministration with ritonavir-boosted tipranavir led to a nine-fold increase in the atorvastatin AUC coupled with concomitant decreases in the metabolite AUC (decreases of 89 and 82 %, respectively, for the ortho-hydroxy and parahydroxy metabolites). In addition, this drug combination was not well tolerated, with occurrence of mild gastrointestinal disturbance, headache and mild reversible liver enzyme elevations (grade 1 and 2).

Study Results

When atorvastatin is administered concomitantly with protease inhibitors used to treat HIV, it is recommended to use the lowest possible dose of atorvastatin. The FDA suggests doses of no higher than 20 mg of atorvastatin when given with early protease inhibitors including lopinavir/ritonavir and fosamprenavir. Similarly, utilizing statin drugs that are not metabolized by CYP3A, including rosuvastatin, pitavastatin, or pravastatin may also be considered.

Study Conclusions

When statin drugs are utilized with HIV protease inhibitors, it is best to start with the lowest possible dose, and slowly increase the dose to maximum effect. Careful monitoring of muscle related adverse events is recommended, and liver function tests, creatine phospokinase (CPK) and renal function should be considered. ** Please note: specific drug interactions between other statin drugs and HIV protease inhibitors have been reviewed, and the investigator is encouraged to seek the monograph for the specific drugs being considered, as further data may be available.

References

Pham PA. Differential effects of tipranavir plus ritonavir on atorvastatin or rosuvastatin pharmacokinetics in healthy volunteers. Antimicrobial Agents And Chemotherapy . 2009; 10: 4385-4392.