OBJECT DRUGS
HMG-CoA Reductase Inhibitors:
- Atorvastatin (Lipitor)
- Lovastatin (Mevacor, etc.)
- Simvastatin (Zocor)
PRECIPITANT DRUGS
Enzyme Inducers:
- Barbiturates
- Bosentan (Tracleer)
- Carbamazepine (Tegretol, etc.)
- Dabrafenib (Tafinlar)
- Dexamethasone (Decadron, etc.)
- Efavirenz (Sustiva)
- Etravirine (Intelence)
- Lumacaftor (Orkambi)
- Nevirapine (Viramune, etc.)
- Oxcarbazepine (Trileptal, etc.)
- Phenytoin (Dilantin, etc.)
- Primidone (Mysoline)
- Rifabutin (Mycobutin)
- Rifampin (Rifadin, etc.)
- Rifapentine (Priftin)
- St. John's wort
Comment:
Atorvastatin, lovastatin, and simvastatin are metabolized by CYP3A4 and enzyme inducers may substantially lower their serum concentrations. The magnitude of the effect may be sufficient to reduce the efficacy of the statin. For example, the potent inducer rifampin can lower simvastatin serum concentrations to less than 10% of normal, while even the modest enzyme inducer St. John's wort can lower simvastatin serum concentrations to about one-third of normal. Although little is known about the effects of enzyme inducers on fluvastatin (Lescol), it is metabolized primarily by CYP2C9 and is likely to interact with enzyme inducers as well. Rosuvastatin (Crestor) has minimal CYP2C9 metabolism and will be unlikely to be affected by enzyme inducers.
Class 3: Assess Risk & Take Action if Necessary
- Consider Alternative: If possible, select an alternative to the CYP3A4 inducer for patients receiving concomitant atorvastatin, lovastatin, or simvastatin.
- HMG-CoA Reductase Inhibitors: Pravastatin (Pravachol) is not metabolized by cytochrome P450 isozymes, and theoretically would not be affected by enzyme induction. Nonetheless, there is conflicting evidence on the effect of rifampin on pravastatin, with both increases and decreases in plasma pravastatin being reported. Rifampin appears to modestly increase pitavastatin (Livalo) plasma concentrations, perhaps through inhibition of OATP1B1.
- Monitor: If atorvastatin, lovastatin, or simvastatin is used with an enzyme inducer, monitor for impairment of cholesterol-lowering effect. Keep in mind that enzyme induction is usually gradual and may take days to weeks for onset and offset, depending on the specific inducer.