Bedaquiline Tablets

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.

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 side. The tablets are packaged in white high density polyethylene (HDPE) bottles with child-resistant polypropylene (PP) closure with induction seal liner. Each bottle contains 188 tablets.

NDC 59676-701-01

Keep out of reach of children.

Dispense in original container. Store tablets dispensed outside the original container in a tight lightresistant container with an expiration date not to exceed 3 months.

Store at 25°C (77°F); excursions permitted to 15–30°C (59–86°F). [See USP Controlled Room Temperature]

Manufactured for: Janssen Therapeutics, Division of Janssen Products, LP Titusville, NJ 08560.Revised: March 2017

The following serious adverse reactions are discussed elsewhere in the labeling:

• Increased mortality [see WARNINGS AND PRECAUTIONS]
• QT Prolongation [see WARNINGS AND PRECAUTIONS and CLINICAL PHARMACOLOGY]
• Hepatotoxicity [see WARNINGS AND PRECAUTIONS]
• Drug Interactions [see WARNINGS AND PRECAUTIONS]

Clinical Studies Experience

Because clinical studies are conducted under widely varying conditions, adverse reaction rates observed in the clinical studies of a drug cannot be directly compared to the rates in the clinical studies of another drug and may not reflect the rates observed in clinical practice.

Use SIRTURO only in combination with other anti-mycobacterial drugs [see DOSAGE AND ADMINISTRATION ]. Refer to the prescribing information of the drugs used in combination with SIRTURO for their respective adverse reactions.

Adverse drug reactions for SIRTURO were identified from the pooled safety data from 335 SIRTURO-exposed patients who received 8 weeks (Study 2) and 24 weeks (Studies 1 and 3) at the proposed dose. Studies 1 and 2 were randomized, double-blind, placebo-controlled trial in newly diagnosed patients with pulmonary MDR-TB. In both treatment arms, patients received SIRTURO or placebo in combination with other drugs used to treat MDR-TB. Study 3 was an open-label, noncomparative study with SIRTURO administered as part of an individualized pulmonary MDR-TB treatment regimen in previously treated patients.

In Study 1, 35% were Black, 17.5% were Hispanic, 12.5% were White, 9.4% were Asian, and 25.6% were of another race. Eight of 79 (10.1%) patients in the SIRTURO group and 16 of 81 (19.8%) patients in the placebo treatment group were HIV-infected. Seven (8.9%) SIRTURO-treated patients and six (7.4%) placebo-treated patients discontinued Study 1 because of an adverse reaction.

Table 1: Select Adverse Reactions from Study 1 That Occurred More Frequently Than Placebo During Treatment with SIRTURO

No additional unique Adverse Reactions were identified from the uncontrolled Study 3.

In both Studies 1 and 2, aminotransferase elevations of at least 3 times the upper limit of normal developed more frequently in the SIRTURO treatment group (11/102 [10.8%] vs 6/105 [5.7%]) than in the placebo treatment group. In Study 3, 22/230 (9.6%) patients had alanine aminotransferase or aspartate aminotransferase greater than or equal to 3 times the upper limit of normal during the overall treatment period.

In Study 1, there was a statistically significant increased mortality risk by Week 120 in the SIRTURO treatment group compared to the placebo treatment group (9/79 (11.4%) versus 2/81 (2.5%), pvalue= 0.03, an exact 95% confidence interval of the difference [1.1%, 18.2%]). Five of the 9 SIRTURO deaths and the 2 placebo deaths were tuberculosis-related. One death occurred during the 24-week SIRTURO treatment period. The median time to death for the remaining eight subjects in the SIRTURO treatment group was 329 days after last intake of SIRTURO. The imbalance in deaths is unexplained; no discernible pattern between death and sputum conversion, relapse, sensitivity to other drugs used to treat tuberculosis, HIV status, and severity of disease was observed.

In the open-label Study 3, 6.9% (16/233) subjects died. The most common cause of death as reported by the investigator was TB (9 subjects). All but one subject who died of TB had not converted or had relapsed. The causes of death in the remaining subjects varied.

Read the entire FDA prescribing information for Sirturo (Bedaquiline Tablets)