Sirturo Bedaquiline Fumarate Tablets

1. Indications and Usage
Multidrug-Resistant Tuberculosis (MDR-TB):
Indicated as part of an all-oral combination treatment regimen for the treatment of pulmonary tuberculosis in adults (≥18 years) with multidrug-resistant tuberculosis (MDR-TB) or rifampicin-resistant tuberculosis (RR-TB), when an effective treatment regimen cannot otherwise be provided.
Note: Safety and efficacy have not been established for treating latent tuberculosis infection or drug-susceptible active tuberculosis.
2. Dosage and Administration
Route of Administration:
For Oral Use ONLY. Must be taken with food to enhance bioavailability.
Recommended Dosage (24-Week Course):
Loading Phase (Weeks 1–2): 400 mg once daily for 2 weeks.
Maintenance Phase (Weeks 3–24): 200 mg three times per week (e.g., Monday, Wednesday, Friday) for 22 weeks. Each dose should be administered at least 48 hours apart.
Missed Dose:
If a dose is missed during the first 2 weeks, do not make up for it. From Week 3 onward, patients should take the missed dose as soon as possible and then resume the normal schedule.
3. Mechanism of Action
ATP Synthase Inhibition:
Bedaquiline is a diarylquinoline antibiotic that specifically targets the mycobacterial adenosine triphosphate (ATP) synthase enzyme (a proton pump).
Energy Deprivation:
By inhibiting this enzyme, it blocks the synthesis of ATP, effectively cutting off the energy supply of the bacteria. This leads to bacterial death, including against non-replicating (dormant) organisms.
4. Safety and Warnings
QTc Interval Prolongation:
Bedaquiline can prolong the QT interval. ECG monitoring is required at baseline, at least once every 2 weeks during treatment, and periodically until 24 weeks after treatment cessation. Concomitant use with other QT-prolonging drugs requires caution.
Hepatotoxicity:
Elevated liver enzymes and hepatotoxicity have been reported. Liver function tests (ALT, AST, Bilirubin) should be monitored regularly.
Increased Mortality Risk:
Clinical trials observed a higher mortality rate in the bedaquiline group compared to placebo (though this was likely confounded by baseline disease severity). It should only be used when effective alternatives are not available.
5. Adverse Reactions
Most Common:
Gastrointestinal: Nausea, vomiting, abdominal pain.
Musculoskeletal: Arthralgia (joint pain), myalgia.
Cardiac: QTc interval prolongation.
Others: Headache, dizziness, increased serum amylase, rash.
6. Drug Interactions
Metabolic Pathway (CYP3A4):
Bedaquiline is primarily metabolized by the cytochrome P450 enzyme CYP3A4.
Contraindicated/Avoided Combinations:
Strong CYP3A4 Inducers: Avoid concomitant use with Rifamycins (Rifampin, Rifabutin, Rifapentine) or Efavirenz, as they significantly reduce Bedaquiline exposure.
Strong CYP3A4 Inhibitors: Avoid concomitant use with strong inhibitors (e.g., Ketoconazole, Clarithromycin) for more than 14 days unless the benefit outweighs the risk, as they increase toxicity.
7. Pharmaceutical Information
Chemical Composition:
Active Ingredient: Bedaquiline Fumarate.
Appearance: White to off-white film-coated tablets.
Storage: Store at controlled room temperature (15°C–30°C) in the original package.