Bedaquiline

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 isoniazid. …

• Administer SIRTURO by directly observed therapy (DOT)
• Emphasize need for compliance with full course of therapy
• Prior to administration, obtain ECG, liver enzymes and electrolytes
• Obtain susceptibility information for the background regimen against Mycobacterium tuberculosis isolate if possible
• 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
• If in vitro testing results are unavailable, may initiate SIRTURO in combination with at least 4 other drugs to which patient's TB isolate is likely to be susceptible
• Recommended dosage in adult patients: 400 mg (4 of the 100 mg tablets OR 20 of the 20 mg tablets) once daily for 2 weeks followed by 200 mg (2 of the 100 mg tablets OR 10 of the 20 mg tablets) 3 times per week (with at least 48 hours between doses) for 22 weeks
• Recommended dosage
• In pediatric patients (2 years and older and weighing at least 8 kg) is based on body weight
• Take SIRTURO tablets with food
• See full prescribing information for the different methods of administration of SIRTURO 20 mg tablet and administration of the 100 mg tablet
• Important Administration Instructions Administer SIRTURO by directly observed therapy (DOT)
• Only use SIRTURO in combination with at least three other drugs to which the patient's TB isolate has been shown to be susceptible in vitro. …

SIRTURO 20 mg tablet: uncoated, white to almost white oblong functionally scored tablet, with a score line on both sides, debossed with "2" and "0" on one side and plain on the other side. SIRTURO 100 mg tablet: uncoated, white to almost white round biconvex tablet with debossing of "T" over "207" on one side and "100" on the other side. …

• The safety and effectiveness of SIRTURO have been established
• In pediatric patients 2 years and older weighing at least 8 kg
• The use of SIRTURO in this pediatric population is supported by evidence from the study of SIRTURO
• In adults together with additional pharmacokinetic and safety data from the single-arm, open-label, multi-cohort trial that enrolled 45
• Pediatric patients 2 years to less than 18 years of age with confirmed or probable pulmonary TB caused by M. …

Clinical studies of SIRTURO did not include sufficient numbers of patients 65 years of age and older to determine whether they respond differently from younger adult patients [see Clinical Pharmacology (12.3) ] .

• Advise patients to read the FDA-approved patient labeling (Medication Guide)
• Serious Adverse Reactions Advise patients that the following serious side effects can occur with SIRTURO: heart rhythm abnormalities, death and/or hepatitis
• In addition, advise patients about other potential side effects: nausea, vomiting, joint pain, increased transaminases, dizziness, headache, myalgia, diarrhea, increased blood amylase, hemoptysis, chest pain, anorexia, rash, and/or abdominal pain
• Additional testing may be needed to monitor or reduce the likelihood of adverse effects
• Compliance with Treatment Advise patients to take SIRTURO in combination with other antimycobacterial drugs as prescribed. …

• None
• None

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) ] . CYP3A4 Inhibitors Coadministration of SIRTURO with CYP3A4 inhibitors increases the systemic exposure of bedaquiline which may increase the risk of adverse reactions. …

A mortality imbalance was seen in clinical trials in SIRTURO-treated patients with pulmonary TB due to Mycobacterium tuberculosis resistant to at least rifampin. ( 5.2 ) Hepatotoxicity may occur with use of SIRTURO. Monitor liver-related laboratory tests. Discontinue SIRTURO if evidence of liver injury occurs. ( 5.4 ) 5.1 QTc Prolongation SIRTURO prolongs the QTc interval [see Clinical Pharmacology (12.2) ] . Use with drugs that prolong the QTc interval may cause additive QTc prolongation [see Adverse Reactions (6) ] . …

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. …

8.1 Pregnancy Risk Summary Available data from published literature of SIRTURO use in pregnant women are insufficient to evaluate a drug-associated risk of major birth defects, miscarriage, or adverse maternal or fetal outcomes. There are risks associated with active TB during pregnancy (see Clinical Considerations ) . …

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 (QTc interval) in case of deliberate or accidental overdose. It is advisable to contact a poison control center to obtain the latest recommendations for the management of an overdose. Since bedaquiline is highly protein-bound, dialysis is not likely to significantly remove bedaquiline from plasma.

SIRTURO 20 mg Tablet Store in original container. Bottle contains desiccant. Do not discard desiccant. Protect from light and moisture. Keep the container tightly closed. …

Take it when you remember, unless it is nearly time for the next dose. Then skip the missed one. Never take two doses at once to make up for it. Check your leaflet, as some medicines are different.