Products
Bedaquiline was approved in the United States in 2012 and in the EU in 2014 in tablet form (Sirturo).
Structure and properties
Bedaquiline (C32H31BrN2O2, Mr = 555.5 g/mol) is a diarylquinoline. It is present in the drug as bedaquiline fumarate, a white powder that is practically insoluble in water.
Effects
Bedaquiline (ATC J04AK05) has bactericidal (antifungal) properties against dividing and nondividing tuberculosis bacteria. The effects are based on inhibition of mycobacterial ATP synthase, which is important for energy production. This prevents the formation of the energy carrier ATP. Bedaquiline and the M2 metabolite have a long half-life of 5.5 months.
Indications
In combination with other tuberculostatics for the treatment of multidrug-resistant pulmonary tuberculosis (MDR-TB) with the causative agent .
Dosage
According to the SmPC. Tablets are taken with a meal. Once daily for the first two weeks, then only three times per week. Bedaquiline must be combined with at least three other tuberculostatics. Treatment lasts for 24 weeks.
Contraindications
- Hypersensitivity
For complete precautions, see the drug label.
Interactions
Bedaquiline is a substrate of CYP3A4 and corresponding drug-drug interactions are possible. Hepatotoxic drugs and alcohol should be avoided during treatment. Interactions may also occur with agents that prolong the QT interval.
Adverse effects
The most common potential adverse effects include nausea, joint pain, headache, vomiting, and dizziness. Bedaquiline prolongs the QT interval and has liver-toxic properties. More deaths occurred in the verum group than in the control group in the main clinical trial.
