Bedaquiline

Bedaquiline is an antimycobacterial drug of the diarylquinoline class used to treat multidrug-resistant tuberculosis (MDR-TB). It is prescribed as part of combination regimens for adults and certain pediatric patients when the TB strain is resistant to first-line medicines or when standard therapy cannot be used.

Mechanism of action: Bedaquiline inhibits the mycobacterial ATP synthase (AtpE), an essential enzyme for energy production, thereby reducing ATP generation and killing Mycobacterium tuberculosis. It has bactericidal activity and is active against replicating and nonreplicating bacilli, contributing to its use in MDR-TB.

Development and approval: Developed by Janssen Pharmaceuticals as a new antituberculosis drug. It received regulatory approval in several regions starting in 2012 for MDR-TB in adults, with later approvals expanding to pediatric use and other indications. It is reserved for use in combination regimens due to potential safety concerns.

Dosing and administration: The recommended regimen typically starts with 400 mg once daily for 14 days, followed by 200 mg three times weekly for 22 weeks, in combination with other anti-TB drugs. Treatment duration is usually about six months, integrated into a broader MDR-TB regimen and adjusted for drug interactions and tolerability.

Safety and adverse effects: Bedaquiline carries a boxed warning for QT interval prolongation and an increased risk of death when used in certain populations. Other adverse effects include nausea, arthralgia, headaches, and hepatotoxicity. It interacts with drugs that affect the cytochrome P450 system, particularly CYP3A4 inhibitors or inducers, and requires regular ECG monitoring and liver function tests.

Pharmacokinetics: It is highly lipophilic with a long terminal half-life and extensive tissue distribution. It is predominantly metabolized by CYP3A4 and eliminated mainly in feces.