Overview
11 DESCRIPTION SIRTURO ® contains bedaquiline fumarate, a diarylquinoline antimycobacterial drug for oral administration. Each SIRTURO 20 mg tablet contains 20 mg of bedaquiline (equivalent to 24.18 mg of bedaquiline fumarate). Each SIRTURO 100 mg tablet contains 100 mg of bedaquiline (equivalent to 120.89 mg of bedaquiline fumarate).
Mechanism of Action
12 CLINICAL PHARMACOLOGY 12.1 Mechanism of Action Bedaquiline is a diarylquinoline antimycobacterial drug [see Microbiology (12.4) ] . 12.2 Pharmacodynamics Bedaquiline has activity against M. tuberculosis . The major metabolite, M2 is not thought to contribute significantly to clinical efficacy given its lower average exposure (23% to 31%) in humans and lower antimycobacterial activity (3-fold to 6-fold lower) compared to the parent compound. However, M2 plasma concentrations are correlated with QTc prolongation. Cardiac Electrophysiology In Study 1, the largest mean increase in QTc during the 24 weeks of SIRTURO treatment was 16 ms compared to 6 ms with placebo treatment (at Week 18).
Indications
- 1 INDICATIONS AND USAGE SIRTURO is a diarylquinoline antimycobacterial drug indicated as part of combination therapy in the treatment of adult and pediatric patients (2 years and older and weighing at least 8 kg) with pulmonary tuberculosis (TB) due to Mycobacterium tuberculosis resistant to at least rifampin and isoniazid. SIRTURO is a diarylquinoline antimycobacterial drug indicated as part of combination therapy in adult and pediatric patients (2 years and older and weighing at least 8 kg) with pulmonary tuberculosis (TB) due to Mycobacterium tuberculosis resistant to at least rifampin and...
Common Doses
- 400 mg
- 100 mg
- 20 mg
- 200 mg
Dosage
2 DOSAGE AND ADMINISTRATION Administer SIRTURO by directly observed therapy (DOT). ( 2.1 ) Emphasize need for compliance with full course of therapy. ( 2.1 ) Prior to administration, obtain ECG, liver enzymes and electrolytes. Obtain susceptibility information for the background regimen against Mycobacterium tuberculosis isolate if possible. ( 2.2 ) Only use SIRTURO in combination with at least 3 other drugs to which the patient's TB isolate has been shown to be susceptible in vitro.
Black Box Warning
WARNING: QTc PROLONGATION QTc prolongation can occur with SIRTURO. Use with drugs that prolong the QTc interval may cause additive QTc prolongation. Monitor ECGs. Discontinue SIRTURO if significant ventricular arrhythmia or QTc interval greater than 500 ms develops [see Warnings and Precautions (5.1) ] . WARNING: QTc PROLONGATION See full prescribing information for complete boxed warning. QTc Prolongation QTc prolongation can occur with SIRTURO. Use with drugs that prolong the QTc interval may cause additive QTc prolongation. Monitor ECGs.
Contraindications
- 4 CONTRAINDICATIONS None. None. ( 4 )
Side Effects
- 6 ADVERSE REACTIONS The following serious adverse reactions are discussed elsewhere in the labeling: QTc Prolongation [see Warnings and Precautions (5.1) and Clinical Pharmacology (12.2) ] Mortality Imbalance in Clinical Trials [see Warnings and Precautions (5.2) ] Hepatotoxicity [see Warnings and Precautions (5.4) ] Drug Interactions [see Warnings and Precautions (5.5) ] The most common adverse reactions reported in 10% or more adult patients treated with SIRTURO in Study 1 were nausea, arthralgia, headache, hemoptysis and chest pain. ( 6.
Interactions
- 7 DRUG INTERACTIONS Avoid use of strong and moderate CYP3A4 inducers with SIRTURO. ( 7.1 ) Closely monitor patient safety (e.g., liver function) when SIRTURO is coadministered with CYP3A4 inhibitors. ( 5.4 , 7.1 ) 7.1 Effect of Other Drugs on SIRTURO Strong and Moderate CYP3A4 Inducers Coadministration of SIRTURO with moderate or strong CYP3A4 inducers may decrease systemic exposure of bedaquiline. Avoid coadministration of SIRTURO with strong or moderate CYP3A4 inducers [see Clinical Pharmacology (12.3) ] .