Protease inhibitors (PIs) and nonnucleoside reverse transcriptase inhibitors (NNRTIs) can affect hepatic metabolism of HMG-coenzyme A reductase inhibitors (statins). ARVs generally do not affect the metabolism of other classes of lipid-lowering agents.
Most PIs inhibit the metabolism of most statins and can significantly increase serum statin levels, thus increasing the risk of toxicity, including myopathy and rhabdomyolysis.
The degree to which statin metabolism is affected by PIs varies according to the statin as well as the specific PI. Unfortunately, many specific interactions have not been studied.
In general, the potential for inhibition of statin metabolism is as follows: simvastatin and lovastatin > atorvastatin and rosuvastatin >> pravastatin.
Interactions of PIs with fluvastatin and pitavastatin have not been studied thoroughly.
NNRTI effects vary according to the specific NNRTI.
|Efavirenz generally induces statin metabolism, resulting in lower serum statin levels.|
|Nevirapine has not been studied well in combination with statins, but its interactions with statins would be expected to be similar to those of efavirenz.|
|Etravirine has not been studied thoroughly in combination with statins. Its interactions are expected to depend on the specific statin.|
|Rilpivirine has not been studied thoroughly in combination with statins.|
|Delavirdine inhibits hepatic cytochrome P450 metabolism. Thus, delavirdine increases statin levels and the risk of statin-related adverse effects.|
Medical providers should consult information on drug interactions before prescribing statins for patients taking PIs or NNRTIs, as dosage adjustments are frequently required and some combinations are contraindicated.
Other classes of antiretrovirals (NRTIs, fusion inhibitors, chemokine coreceptor antagonists, and integrase inhibitors) do not have recognized interactions with statins. Other types of lipid-lowering medications are not metabolized by hepatic cytochrome P450 and generally are not affected by ARVs (an exception to this is gemfibrozil, whose levels are decreased by lopinavir/ritonavir, by an unknown mechanism).
Note on cobicistat: The pharmacokinetic enhancer cobicistat is expected to have interactions with statins that are similar to those of ritonavir; however, these have not been well studied.