OBJECT DRUGS
PRECIPITANT DRUGS
Enzyme Inducers:
- Barbiturates
- Bosentan (Tracleer)
- Carbamazepine (Tegretol, etc.)
- Dabrafenib (Tafinlar)
- Dexamethasone (Decadron, etc.)
- Efavirenz (Sustiva)
- Lumacaftor (Orkambi)
- Oxcarbazepine (Trileptal, etc.)
- Phenytoin (Dilantin, etc.)
- Primidone (Mysoline)
- Rifabutin (Mycobutin)
- Rifampin (Rifadin, etc.)
- Rifapentine (Priftin)
- St. John's wort
Comment:
Bedaquiline is metabolized by CYP3A4, and enzyme inducers may substantially reduce serum bedaquiline concentrations. In one study, 3 weeks of rifampin therapy reduced bedaquiline AUC by about 50%. The product information for bedaquiline states that enzyme inducers should not be administered with bedaquiline. Although nevirapine (Viramune) is a CYP3A4 inducer, the manufacturer reports that 4 weeks of nevirapine 400 mg daily did not have a clinically relevant effect on bedaquiline exposure.
Class 2: Use only if Benefit Felt to Outweigh Risk
- Use Alternative:
- Anticonvulsants: In patients on bedaquiline it would be desirable to use anticonvulsants that are not enzyme inducers, but in many cases it may not be reasonable to change the patient's anticonvulsant regimen.
- HIV Medications: Since most antiviral medications are either inducers or inhibitors of CYP3A4, it may not be possible to avoid these interactions in most cases.
- St. John's wort: Given the questionable benefit of St. John's wort, it would be prudent to avoid giving it with bedaquiline.
- Monitor: Monitor for altered bedaquiline effect if enzyme inducers are initiated, discontinued, or changed in dosage. Adjustments in bedaquiline dosage may be necessary. Keep in mind that enzyme induction is usually gradual and may take days to weeks for onset and offset, depending on the specific inducer.