Pharmacological Class:
Diarylquinoline.
Active Ingredient(s):
Bedaquiline 100mg; tabs.
Company
Janssen Therapeutics
Indication(s):
As part of combination therapy in pulmonary multi-drug resistant tuberculosis (MDR-TB) only when an effective treatment regimen cannot otherwise be provided.
Limitations of use: the safety and efficacy for treatment of latent infection, drug-sensitive, or extra-pulmonary tuberculosis (eg, CNS) has not been established.
Pharmacology:
Bedaquiline inhibits mycobacterial ATP (adenosine 5’-triphosphate) synthase, an enzyme that is essential for the generation of energy in Mycobacterium tuberculosis.
Clinical Trials:
Study 1 was a placebo-controlled trial conducted in newly diagnosed patients with MDR pulmonary Mycobacterium tuberculosis. Patients were randomized to either Sirturo plus other drugs used to treat MDR-TB or placebo plus other drugs used to treat MDR-TB. The other drugs consisted of a combination of 5 other antimycobacterials. The Sirturo dose was given as 400mg once daily for the first 2 weeks and then 200mg was given three times weekly for the following 22 weeks.
Time to sputum culture conversion was: the interval in days between the first dose of study drug and the date of the first of two consecutive negative sputum cultures collected at least 25 days apart during therapy. In this ongoing trial, the Sirturo group had a decreased time to culture conversion and improved culture conversion rates vs. placebo at Week 24. Median time to culture conversion was 83 days for Sirturo vs. 125 days for placebo.
Study 2 was similarly designed to Study 1 except that Sirturo or placebo was given for 8 weeks vs. 24 weeks. The Sirturo group had a decreased time to culture conversion and improved culture conversion rates vs. placebo at Week 8. At Weeks 8 and 24, the differences in culture conversion proportions were 38.9% (95% CI: [12.3%, 63.1%] and P=0.004), 15.7% (95% CI: [-11.9%, 41.9%] and P= 0.32), respectively.
Legal Classification:
Rx
Adults:
Administer by directly observed therapy and in combination with ≥3 other drugs to which the isolate is susceptible. Swallow whole with water. Take with food. ≥18 years: 400mg once daily for 2 weeks followed by 200mg three times weekly for 22 weeks.
Children:
<18 years: not established.
Warnings/Precautions:
Increased risk of mortality. Increased risk of QT prolongation in patients with history of Torsade de Pointes, congenital long QT syndrome, hypothyroidism, bradyarrhythmias, uncompensated heart failure, electrolyte abnormalities; monitor closely. Obtain ECG prior to therapy, and at least 2, 12, and 24 weeks after starting. Correct any electrolyte abnormalities at baseline and monitor if QT prolongation is detected. Discontinue Sirturo and all other QT prolonging drugs if ventricular arrhythmia or QTcF interval >500ms develops. Monitor ALT/AST, phosphatase, bilirubin at baseline, monthly during treatment, and as needed. Test for viral hepatitis and discontinue other hepatotoxic drugs if serum aminotransferases >3XULN (repeat testing within 48 hours). Discontinue if aminotransferase elevation with total bilirubin >2XULN, aminotransferase elevation >8XULN, or aminotransferase elevations persist >2 weeks. Severe hepatic or severe renal impairment/ESRD. Pregnancy (Category B). Nursing mothers: not recommended.
Interaction(s)
Avoid concomitant use with strong CYP3A4 inducers (eg, rifampin, rifapentine, rifabutin). Avoid concomitant use with strong CYP3A4 inhibitors (eg, ketoconazole) for >14 days; monitor. Additive QT prolongation with other drugs that prolong the QT interval (eg, fluoroquinolones, macrolides, clofazimine). Avoid alcohol and other hepatotoxic drugs. Sirturo exposure increased with Kaletra (caution).
Adverse Reaction(s)
Nausea, arthralgia, headache, hemoptysis, chest pain; arrhythmias, syncope (obtain ECG), hepatic dysfunction, QT prolongation.
How Supplied:
Tabs—188
LAST UPDATED:
6/28/2013
