Nevirapine + Simvastatin = Precautionary

Effect on Concentration

Nevirapine
No change
Applies within class?
No
Simvastatin
Decrease
Applies within class?
No

Pharmacologic Effects

Nevirapine
Effect
N/A
Applies within class?
No
Simvastatin
Effect
N/A
Applies within class?
No

Interaction History

N/A

Last Updated 01-Aug-2018

Summary

Sources

NNRTIs versus Statins ^

Study Design

Both lovastatin and simvastatin are CYP3A4 substrates and are especially sensitive to CYP3A4 inhibition; Efavirenz or Nevirapine may decrease concentrations. While the interaction between lovastatin and efavirenz has not been directly studied, information can be extrapolated from results from interaction studies between efavirenz and other statin drugs. 52 (42 for statistical PK analysis) healthy HIV-seronegative subjects were given simvastatin 40mg, atorvastatin 10mg and pravastatin 40mg daily on days 1-3 and days 15-18 while efavirenz 600mg daily was given on days 4-18.

Study Results

EFV significantly reduced the simvastatin median AUC0-24h by 58%, atorvastatin by 42.7%, and pravastatin by 40.4%. None of the statins affected the non-steady-state PK of EFV.

Study Conclusions

The authors suggested that some patients taking EFV may require higher titrations of simvastatin but only with increased monitoring of toxicities. Because etravirine is a modest inducer of CYP3A, simvastatin may also require higher doses to ensure similar efficacy. Dose adjustments of these statins may be necessary, based upon clinical monitoring of both safety and efficacy.

References

Gerber JG. Effect of efavirenz on the pharmacokinetics of simvastatin, atorvastatin, and pravastatin: results of aids clinical trials group 5108 study. Jaids: Journal Of The Acquired Immunodeficiency Syndrome. 2005; : 307-312.