Bedaquiline

What is bedaquiline? How does it work?

Bedaquiline is the active substance in a TB drug which is also sometimes known by the trade name of Sirturo. Bedaquiline works by blocking an enzyme inside the Mycobacterium tuberculosis bacteria called ATP synthase. This enzyme is used by the bacteria to generate energy. Without the ability to generate energy, the TB bacteria die and the patient’s condition can start to improve.

When is bedaquiline used?

Bedaquiline is used in combination with other TB drugs to treat pulmonary TB in adults when they have multi drug resistant TB (MDR-TB). MDR-TBis when the TB bacteria that a person is infected with, are resistant to two of the main TB drugs isoniazid (INH) and rifampicin (RMP). This means that the drugs don’t work It should only be used when effective TB treatment cannot otherwise be provided. It is also sometimes used when other drugs cannot be used because of their side effects.

It should be always be used in combination with at least 3 other TB drugs which drug susceptibility testing has shown that the patient is susceptible to. If drug susceptibility testing is not available then bedaquiline should be used with at least 4 other drugs to which the patient is likely to be susceptible.

It should also not be used for the treatment of:

• Latent TB infections due to Mycobacterium tuberculosis
• Drug sensitive tuberculosis
• Extrapulmonary tuberculosis
• Ethambutol (E/Emb)
• Infections caused by non tuberculosis mycobacteria.

The safety and efficacy of the drug in the treatment of HIV positive patients with MDR-TB has also not yet been established.

What is the recommended dose of bedaquiline?

The recommended dose is 400 mg a day for two weeks and then 200 mg taken three times a week (with at least 48 hours between doses) for the next 22 weeks. Bedaquiline is available as 100 mg tablets, and the tablets should be swallowed whole with water and taken with food.

In the EU bedaquiline should only be obtainable with a prescription. Treatment should also be started and monitored by a doctor experienced in the treatment of MDR-TB. It is also recommended that patients are directly observed by a health care professional when taking the drug.

You should not drink alcohol when taking bedaquiline, and it is essential that the entire course of treatment is completed.

What clinical trials of bedaquiline have taken place?

There have been only a limited number of clinical trials carried out with bedaquiline. Two early phase 2 studies of the drug took place and the results of these trials were presented at the Union World TB conferences in 2010 and 2011.2

In addition there has been one major placebo controlled double-blind randomized trial of adults with pulmonary multi drug resistant TB in which patients had the drug for 24 weeks. A placebo is a dummy treatment. Bedaquiline was compared with a placebo when added to combination treatment with other standard TB medicines. The other TB drugs were:

• ethionamide
• kanamycin
• pyrazinamide
• ofloxacin
• cycloserine/terizidone or an available alternative.

The study showed that after 24 weeks 79% of the patients given bedaquiline were sputum smear negative, compared with 58% of patients given placebo. The average time it took to become smear negative was also shorter for patients in the bedaquiline group than for those in the placebo group (83 days versus 125 days).

What are the side effects of bedaquiline?

The most common side effects are headache, dizziness, feeling sick, being sick, joint pain and increases in liver enzymes. Side effects can be experienced by more than one in ten people.

Another potentially significant side effect is that QTc prolongation was noticed during treatment. A prolonged QT interval means some alterations in the heart’s electrical activity. There were also a higher number of reported deaths in the bedaquiline group, although these were not necessarily caused by bedaquiline.

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