Frequently Asked Questions on bedaquiline
Why is the introduction of bedaquiline significant?
The last time a drug was introduced specifically for the treatment of TB was in the late 1960s. That drug was rifampicin. Since then, resistance to rifampicin has been increasingly reported in the world. This is a major concern given that it remains among the most effective anti-TB drugs available today.
Bedaquiline has been released specifically to treat TB patients with bacteria that are resistant to rifampicin as well as to isoniazid, another core anti-TB drug, and thus suffer from multidrug-resistant tuberculosis (MDR-TB).
While bedaquiline has shown beneficial effect in studies including two Phase IIb trials, Phase III trials have not been completed. However, given the serious threat posed by MDR-TB both to the individual patient and to the community, some regulatory authorities have used an accelerated procedure for the approval of bedaquiline in order to ensure that eligible patients may benefit from this new drug when used under defined conditions. In order to guide countries on the use of bedaquiline in the treatment of MDR-TB, WHO is issuing interim guidance which will be reviewed in 2015 or before based on the results of further research(1).
What is bedaquiline and how does the drug work?
Bedaquiline is a bactericidal drug which belongs to a new class of antibiotics (diarylquinolines). Although the drug is active against many different bacteria, it has been registered specifically for the treatment of MDR-TB(2). The drug is unique among the anti-tuberculosis drugs currently used in that it interferes with the function of an enzyme required by the tuberculosis bacterium to produce energy and to replicate. The drug has been tested for the treatment of MDR-TB in addition to conventional treatment regimens including several drugs.
Should all TB patients now be treated with bedaquiline?
No. Up to now, bedaquiline has only been approved for use in patients who have MDR-TB and when options to treat this condition using existing drugs have been exhausted. The drug is to be given in addition to the multidrug treatment regimen recommended by WHO. Given the limited experience on its use, bedaquiline is recommended for use in adults affected with pulmonary (lung) MDR-TB. Special caution is needed when the drug is used in the elderly, in pregnant women, and in persons living with HIV who are taking antiretroviral medication (see cautions on the use of specific anti-retroviral drugs below). Bedaquiline should not be used to treat latent TB infection.
What are the conditions under which bedaquiline should be introduced?
Programmes introducing bedaquiline in their national MDR-TB regimens should take measures to ensure its proper use. It is important that all efforts are made to avoid bacterial resistance to this new drug as a result of misuse. In the interim guidance, WHO recommends that bedaquiline is used in line with existing guidance on the combination treatment of MDR-TB, that the response to treatment is monitored closely, that patients are well informed of both the expected benefits and possible harms of the drug, and that particular attention is given to detect and report any adverse events that develop. As with all other TB drugs, bedaquiline should not be used alone but as part of a combination therapy, and never added alone to a failing regimen.
What are the side-effects of bedaquiline? Are there any special measures that need to be taken when bedaquiline is introduced?
Bedaquiline has been reported to disturb the function of the heart and liver in particular. Interactions with other drugs, especially lopinavir and efavirenz (used in the treatment of HIV), ketoconazole, as well as other drugs used in the treatment of MDR-TB (eg moxifloxacin, clofazimine) may be expected. More deaths were reported among patients taking bedaquiline during the studies carried out to investigate the drug, although it is not clear whether this was due to the drug. For all these reasons, it is important that patients are closely monitored and that adverse events are systematically reported (“active pharmacovigilance”), particularly those that are serious and life-threatening. Clinical monitoring of symptoms, performance of special tests at appropriate intervals, and engagement of the patient to report untoward consequences of treatment to the appropriate pharmacovigilance institution are the cornerstones for the effective management of side effects in a timely fashion.
What support will WHO provide to countries who wish to introduce bedaquiline?
In addition to the WHO interim policy, a guide on clinical management of patients will be released in the coming months. WHO will work on other programmatic planning and implementation tools. WHO will monitor closely the new developments concerning this drug and modify the interim policy accordingly. The Organization is also available to advise programmes on practical implementation issues and on how to monitor the use of the drug for effectiveness and harms. WHO is collaborating with other partners to enable support for rational introduction.
How long is the treatment with bedaquiline? What is the dose?
Bedaquiline should be given for a maximum of six months on top of the WHO recommended combination treatment regimen. The manufacturer recommends 400 mg daily (4 tablets) for 2 weeks followed by 200 mg 3 times per week for the remaining 22 weeks. For more information on dosage and conditions for use please see the references at the end (2).
Can bedaquiline be used to shorten treatment of MDR-TB?
No, there is no evidence as yet that this drug can reduce treatment duration. Moreover there is no experience of the use of this drug in short MDR-TB treatment regimens. While bedaquiline is expected to improve the likelihood of a successful outcome for individual patients, its overall impact on public health and transmission of MDR-TB in countries cannot as yet be established.
Will there be other new drugs to treat TB?
The development of new drugs requires substantial investment and research usually lasting many years. Other new drugs are presently being investigated and it is expected that some may be released within the next few years. (3)
- The use of bedaquiline in the treatment of multidrug-resistant tuberculosis. Interim policy guidance (WHO/HTM/TB/2013.6). Geneva, World Health Organization. 2013.
- BRIEFING PACKAGE Division of Anti-Infective Products Office of Antimicrobial Products CDER, FDA. SirturoTM (bedaquiline 100 mg tablets) For the treatment of adults (≥ 18 years) as part of combination therapy of pulmonary multi-drug resistant tuberculosis (MDRTB). Applicant: Janssen Research and Development, L.L.C FDA Anti-Infective Drugs Advisory Committee Meeting Silver Spring, MD Date: November 28, 2012 [Internet]. [cited 2013 Feb 21]. Available from: http://www.fda.gov/downloads/AdvisoryCommittees/CommitteesMeetingMaterials/Drugs/Anti-InfectiveDrugsAdvisoryCommittee/UCM329258.pdf
- Global tuberculosis report 2012 (WHO/HTM/TB/2012.6). Geneva, World Health Organization. 2012.