hese highlights do not include all the information needed to use SIRTURO � safely and effectively. See full prescribing information for SIRTURO.
SIRTURO � (bedaquiline) tablets, for oral use
Initial U.S. Approval 2012
WARNINGS: INCREASED MORTALITY; QT PROLONGATION See full prescribing information for complete boxed warning.
Increased Mortality
An increased risk of death was seen in the SIRTURO treatment group (9/79, 11.4%) compared to the placebo treatment group (2/81, 2.5%) in one placebo-controlled trial. Only use SIRTURO when an effective treatment regimen cannot otherwise be provided. (5.1)
QT Prolongation
QT prolongation can occur with SIRTURO. Use with drugs that prolong the QT interval may cause additive QT prolongation. Monitor ECGs. Discontinue SIRTURO if significant ventricular arrhythmia or QTcF interval >500 ms develops. (5.2)
INDICATIONS AND USAGE
SIRTURO is a diarylquinoline antimycobacterial drug indicated as part of combination therapy in adults (18 years and older) with pulmonary multi-drug resistant tuberculosis (MDR-TB). Reserve SIRTURO for use when an effective treatment regimen cannot otherwise be provided. Administer SIRTURO by directly observed therapy (DOT). (1, 2.1)
This indication is approved under accelerated approval based on time to sputum culture conversion. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials. (1, 14)
Limitations of Use: Do not use SIRTURO for the treatment of latent, extra-pulmonary or drug-sensitive tuberculosis or for the treatment of infections caused by non-tuberculous mycobacteria (1). Safety and efficacy of SIRTURO in HIV-infected patients with MDR-TB have not been established, as clinical data are limited (14).
DOSAGE AND ADMINISTRATION
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 MDR-TB isolate has been shown to be susceptible in vitro. If in vitro testing results are unavailable, may initiate SIRTURO in combination with at least 4 other drugs to which patient's MDR-TB isolate is likely to be susceptible (2.3)
Recommended dosage: 400 mg once daily for 2 weeks followed by 200 mg 3 times per week (with at least 48 hours between doses) for 22 weeks (2.3)
Swallow SIRTURO tablets whole with water and take with food. (2.3)
DOSAGE FORMS AND STRENGTHS
Tablets: 100 mg (3)
CONTRAINDICATIONS
None. (4)
WARNINGS AND PRECAUTIONS
QT prolongation can occur with SIRTURO. Monitor ECGs and discontinue SIRTURO if significant ventricular arrhythmia or QTcF interval > 500 ms develops. (5.2)
Hepatotoxicity may occur with use of SIRTURO. Monitor liver-related laboratory tests. Discontinue if evidence of liver injury. (5.3)
ADVERSE REACTIONS
The most common adverse reactions reported in 10% or more of patients treated with SIRTURO were nausea, arthralgia, headache, hemoptysis and chest pain. (6.1)
To report SUSPECTED ADVERSE REACTIONS, contact Janssen Therapeutics, Division of Janssen Products, LP at 1-800-JANSSEN (1-800-526-7736) or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.
DRUG INTERACTIONS
Avoid use of strong and moderate CYP3A4 inducers with SIRTURO. (7.1, 7.3)
Avoid use for more than 14 consecutive days of systemic strong CYP3A4 inhibitors with SIRTURO unless the benefit outweighs the risk. Monitor for SIRTURO-related adverse reactions. (7.1)
USE IN SPECIFIC POPULATIONS
Use with caution in patients with severe hepatic impairment and only when the benefits outweigh the risks. Monitor for SIRTURO-related adverse reactions. (8.6)
Use with caution in patients with severe renal impairment. (8.7)
See 17 for PATIENT COUNSELING INFORMATION and Medication Guide.
Revised: 1/2017
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FULL PRESCRIBING INFORMATION: CONTENTS*
Table of Contents
1 INDICATIONS AND USAGE
SIRTURO is a diarylquinoline antimycobacterial drug indicated as part of combination therapy in the treatment of adults (18 years and older) with pulmonary multi-drug resistant ...
2 DOSAGE AND ADMINISTRATION
2.1 Important Administration Instructions - Administer SIRTURO by directly observed therapy (DOT). Use SIRTURO only in combination with other ...
3 DOSAGE FORMS AND STRENGTHS
SIRTURO tablets, 100 mg are uncoated white to almost white round biconvex with debossing of "T" over "207" on one side and "100" on the other side.
4 CONTRAINDICATIONS
None.
5 WARNINGS AND PRECAUTIONS
5.1 Increased Mortality - An increased risk of death was seen in the SIRTURO treatment group (9/79, 11.4%) compared to the placebo treatment group (2/81, 2.5%) in one ...
6 ADVERSE REACTIONS
The following serious adverse reactions are discussed elsewhere in the labeling: Increased mortality [see Warnings and Precautions (5.1)] QT Prolongation [see Warnings and ...
7 DRUG INTERACTIONS
7.1 CYP3A4 Inducers/Inhibitors - Bedaquiline exposure may be reduced during co-administration with inducers of CYP3A4 and increased during co-administration with ...
8 USE IN SPECIFIC POPULATIONS
8.1 Pregnancy - Pregnancy Category B - Reproduction studies performed in rats and rabbits have revealed no evidence of harm to the fetus due to ...
10 OVERDOSAGE
There is no experience with the treatment of acute overdose with SIRTURO. Take general measures to support basic vital functions including monitoring of vital signs and ECG (QT interval ...
11 DESCRIPTION
SIRTURO (bedaquiline) for oral administration is available as 100 mg strength tablets. Each tablet contains 120.89 mg of bedaquiline fumarate drug substance, which is equivalent to 100 mg ...
12 CLINICAL PHARMACOLOGY
12.1 Mechanism of Action - Bedaquiline is a diarylquinoline antimycobacterial drug [see Microbiology (12.4)]. 12.2 Pharmacodynamics ...
13 NON-CLINICAL TOXICOLOGY
13.1 Carcinogenesis, Mutagenesis, and Impairment of Fertility - Bedaquiline was not carcinogenic in rats up to the maximum tolerated dose of 10 mg/kg/day. Exposures ...
14 CLINICAL STUDIES
A placebo-controlled, double-blind, randomized trial (Study 1) was conducted in patients with newly diagnosed sputum smear-positive MDR pulmonary M. tuberculosis. All patients received a ...
15 REFERENCES
Clinical and Laboratory Standards Institute (CLSI). Susceptibility Testing of Mycobacteria, Nocardiaceae, and other Aerobic Actinomycetes; Approved Standard � Second Edition. CLSI ...
16 HOW SUPPLIED/STORAGE AND HANDLING
How supplied SIRTURO is supplied as uncoated white to almost white round biconvex 100 mg tablets with debossing of "T" over "207" on one side and "100" on the other ...
17 PATIENT COUNSELING INFORMATION
Advise the patient to read the FDA-approved patient labeling (Medication Guide). Serious Adverse Reactions Advise patients that the following serious side effects ...
SPL UNCLASSIFIED SECTION
Product of India - Finished Product Manufactured by: Recipharm Pharmaservices Pvt. Ltd., Bangalore, India - Manufactured for: Janssen Therapeutics, Division of Janssen Products ...
MEDICATION GUIDE
MEDICATION GUIDE - SIRTURO� (ser toor' oh) (bedaquiline) Tablets, for oral use - Read this Medication Guide before you ...
PRINCIPAL DISPLAY PANEL - 100 mg Tablet Bottle Label
NDC 59676-701-01 Sirturo� (bedaquiline) tablets - 100 mg Dispense Medication Guide - to each patient Attention Pharmacist: Dispense in original - container. Tablets dispensed ...
INGREDIENTS AND APPEARANCE
Product Information
