Bedaquiline is a substrate of CYP 3A4 but is not an inhibitor or inducer of this or other CYP encymes.

Bedaquiline is a diarylquinoline antimycobacterial drug.

Bedaquiline is indicated for treatment of pulmonary multidrug-resistant tuberculosis and is used in combination with other antitubercular agents. It is administered orally. Bedaquiline has a very long half-life of about 5 months (SmPC, DrugBank).

Bedaquiline is metabolized by CYP 3A4 to form its main metabolite, N-monodesmethyl bedaquiline. These are highly bound to plasma proteins and are widely distributed to peripheral tissues. The accumulation and slow-release form various tissues is the proposed explanation for the long half-life of drug and main metabolite (SmPC) Both in vitro and in vivo experiments on the effects of bedaquiline on CYP enzymes indicates low potential for inhibition, and in vitro testing shows no significant inhibition on CYP1A2, CYP2A6, CYP2C8/9/10, CYP2C19, CYP2D6, CYP2E1, CYP3A4, CYP3A4/5 and CYP4A (EMA, FDA label, Cao 2017) According to the initial marketing documents (EMA, public assessment report), in vitro assays indicate a potential for CYP enzyme induction when tested against other CYP inducers such as ketoconazole and lopinavir/ritonavir. It is suggested that further studies should be conducted. However, this potential has not been observed in other studies (van Heeswijk 2014). According to the FDA, bedaquiline does not induce CYP3A4, CYP1A2, CYP2C9, or CYP2C19 (FDA label). No CYP-related interactions are listed in drug-drug interaction databases.

South Africa: Used uneventfully in one patient with acute porphyria.