Bedaquiline , sold under the trademark Sirturo , is a drug used to treat active tuberculosis. It is specifically used to treat drug-resistant TB (MDR-TB) when other treatments can not be used. It should be used in conjunction with at least three other drugs for tuberculosis. It is used by mouth.
Common side effects include nausea, joint pain, headache, and chest pain. Serious side effects include QT prolongation, liver dysfunction, and an increased risk of death. While the danger during pregnancy has not been found, it has not been well studied in this population. This is a class of antimicrobacterial drug diarylquinoline. It works by blocking the ability of M. tuberculosis to make adenosine 5'-triphosphate (ATP).
Bedaquiline is approved for medical use in the United States in 2012. This is the List of Essential Medicines of the World Health Organization, the most effective and safe medicines needed in the health system. The cost for six months is about $ 900 USD in low-income countries, $ 3,000 USD in middle-income countries, and $ 30,000 USD in high-income countries.
Video Bedaquiline
Medical use
Its use is officially approved (December 2012) by the US Food and Drug Administration (FDA) for use in the treatment of tuberculosis (TB), as part of the Fast Track accelerated approval, for use only in cases of drug-resistant TB, and more resistant drug-resistant tuberculosis extensively.
In 2013 Both the World Health Organization (WHO) and the Centers for Disease Control (CDC) USA have recommended (temporarily) that bedaquiline is provided for patients with drug-resistant TB when the recommended regimen can not be designed.
Clinical test
Bedaquiline has been studied in phase IIb studies for the treatment of multi-drug resistant tuberculosis while phase III studies are currently underway. It has been shown to increase the rate of recovery of smear-positive smear-positive TB, albeit with some concern for increased mortality (more detailed in the Adverse effects section).
A small study also examined its use as a rescue therapy for non-tuberculosis mycobacterial infections.
This is a component of a combination of experimental BPaMZ treatment (bedaquiline pretomanid moxifloxacin pyrazinamide).
Maps Bedaquiline
Side effects
The most common side effects of bedaquiline in the study were nausea, joint and chest pain, and headache. The drug also has a black box warning for an increased risk of death and arrhythmia, as it can extend QT intervals by blocking the hERG channels. All patients in bedaquiline should monitor with baseline and recurrent EKG. If a patient has QTcF of & gt; 500ms or significant ventricular arrhythmias, bedaquiline and other QT extension drugs should be discontinued.
There is a great controversy over approval for the drug, as one of the largest studies to date has more deaths in the group receiving the difference that those who received the placebo. 10 deaths occurred in the bedaquiline group of 79, while 2 occurred in the placebo group, out of 81. Of the 10 deaths in bedaquiline, 1 was due to motor vehicle accidents, 5 were assessed as a result of progression of underlying tuberculosis. and 3 well after the patient stopped receiving bedaquiline. However, there are still significant concerns for higher mortality in bedaquiline-treated patients, leading to recommendations to limit their use to situations in which 4 drug regimens can not be established, limiting use with other drugs that prolong QT interval and placement of box warning black protruding.
Drug interactions
Bedaquiline should not be administered along with other drugs that are strong inducers or inhibitors of CYP3A4, the liver enzyme responsible for drug oxidative metabolism. Co-administration with rifampicin, a potent CYP3A4 inducer, resulted in a 52% reduction in drug AUC. It reduces the body's exposure to the drug and decreases its antibacterial effect. Co-administration with ketoconazole, a potent CYP3A4 inhibitor, resulted in a 22% increase in AUC, and potentially increased rates of adverse events.
Because bedaquiline can also prolong the QT interval, the use of other QT-extending drugs should be avoided. Other drugs for tuberculosis that can prolong the QT interval include fluoroquinolones and clofazimine.
Action mode
Bedaquiline blocks the proton pump for ATP synthase mycobacteria. ATP production is required for cellular energy production and its loss leads to cell death, even in dormant or non-triggered mycobacteria. This is the first member of a new class of drugs called diarylquinolines. Bedaquiline is bactericidal.
Resistance
The specific part of the synthase of ATP influenced by bedaquiline is the subunit c encoded by the atpE gene. Mutations in atpE can cause resistance. Mutations in the drug release pump have also been associated with resistance.
History
Bedaquiline was described for the first time in 2004 at the Interscience Conference at the meeting of Antimicrobial Agents and Chemotherapy (ICAAC), after which the drug has been developed for more than seven years. Discovered by a team led by Koen Andries at Janssen Pharmaceutica.
Bedaquiline is approved for medical use in the United States by 2012.
Manufactured by Johnson & amp; Johnson (J & J), who requested an accelerated drug approval, a type of temporary agreement for a disease that has no viable treatment option. By getting approval for drugs that treat neglected diseases, J & amp; J can now request an accelerated FDA review of future drugs.
When approved by the FDA on December 28, 2012, it is the first new drug for tuberculosis in more than forty years.
References
Source of the article : Wikipedia
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