SIRTURO

Clinical safety rating: caution

Comprehensive clinical and safety monograph for SIRTURO (SIRTURO).

How it works

Diarylquinoline that inhibits mycobacterial ATP synthase, specifically targeting subunit c (atpE), leading to uncoupling of ATP hydrolysis and bacterial cell death.

What the body does with it

Metabolism	Primarily metabolized by CYP3A4; also a substrate of P-glycoprotein.
Excretion	Fecal: approximately 86% (mainly as unchanged drug and metabolites); Renal: less than 1% as unchanged drug; Biliary: significant, with enterohepatic recirculation.
Half-life	Terminal elimination half-life is approximately 5.5 months (173 days) due to slow release from tissues, supporting once-weekly dosing after the initial 2-week daily phase.
Protein binding	Approximately 99.9% bound to human serum proteins, primarily albumin.
Volume of Distribution	Extensive, with a mean Vd/F of 170 L (approx. 2.4 L/kg in adults), indicating wide distribution into tissues, including lung and macrophages.
Bioavailability	Oral: approximately 70% under fed conditions; absorption is significantly increased with high-fat food (about 2-fold increase in AUC).
Onset of Action	Oral: Bactericidal activity begins within days, with measurable colony-forming unit reductions in sputum by 2 weeks of therapy.
Duration of Action	Sustained bactericidal effect persists for weeks due to long half-life; clinical duration influenced by total treatment duration (typically 6 months as part of combination regimen).

Classification & Brands

Dosing & administration

For pulmonary multidrug-resistant tuberculosis: 400 mg orally twice daily for 2 weeks, then 200 mg three times weekly for 22 weeks (total 24 weeks). Administered with food.

Dosage form	TABLET
Renal impairment	No dose adjustment required for mild to moderate renal impairment. Not studied in severe renal impairment (CrCl < 30 mL/min) or on dialysis; use with caution.
Liver impairment	Child-Pugh A: No adjustment. Child-Pugh B: Use with caution; no specific dose recommendation. Child-Pugh C: Contraindicated.
Pediatric use	Approved for children ≥5 years and weighing ≥15 kg. Weight-based dosing: 15-30 kg: 200 mg once daily for 2 weeks, then 100 mg three times weekly for 22 weeks; 31-54 kg: 300 mg once daily for 2 weeks, then 150 mg three times weekly for 22 weeks; ≥55 kg: 400 mg once daily for 2 weeks, then 200 mg three times weekly for 22 weeks.
Geriatric use	No specific dose adjustment; use standard adult dosing with monitoring for QT prolongation, hepatotoxicity, and electrolyte disturbances due to age-related comorbidities and polypharmacy.

Use during pregnancy

1st trimester	Consult provider
2nd trimester	Consult provider
3rd trimester	Consult provider

Clinical note

Comprehensive clinical and safety monograph for SIRTURO (SIRTURO).

Breastfeeding	No human data. M/P ratio unknown. Bedaquiline and its metabolites are excreted in rat milk. Due to potential for adverse reactions in nursing infants, breastfeeding is not recommended during therapy.
Teratogenic Risk	First trimester: Limited human data. Animal studies show embryo-fetal toxicity including skeletal variations and reduced fetal weight at exposures below human therapeutic levels. Second and third trimesters: No specific data; potential for fetal harm based on animal findings. Use only if benefit outweighs risk.

Warnings & precautions

■ FDA Black Box Warning

Increased mortality observed in clinical trials; use only when no other effective treatment regimen is available.

Side Effect Profile

Serious Effects

Absolute Contraindications

Known hypersensitivity to bedaquiline; concomitant use with strong CYP3A4 inducers; use in patients with clinically significant QT prolongation or history of torsade de pointes.

Clinical Precautions

Precautions

Hepatotoxicity, QT prolongation, increased mortality, pancreatitis, hemoptysis, and potential for drug interactions with strong CYP3A4 inducers or inhibitors.

Clinical Tips & Counseling

Drug interactions

Loading safety data…

SIRTURO

Clinical safety rating: caution

Comprehensive clinical and safety monograph for SIRTURO (SIRTURO).

How it works

Diarylquinoline that inhibits mycobacterial ATP synthase, specifically targeting subunit c (atpE), leading to uncoupling of ATP hydrolysis and bacterial cell death.

What the body does with it

Metabolism	Primarily metabolized by CYP3A4; also a substrate of P-glycoprotein.
Excretion	Fecal: approximately 86% (mainly as unchanged drug and metabolites); Renal: less than 1% as unchanged drug; Biliary: significant, with enterohepatic recirculation.
Half-life	Terminal elimination half-life is approximately 5.5 months (173 days) due to slow release from tissues, supporting once-weekly dosing after the initial 2-week daily phase.
Protein binding	Approximately 99.9% bound to human serum proteins, primarily albumin.
Volume of Distribution	Extensive, with a mean Vd/F of 170 L (approx. 2.4 L/kg in adults), indicating wide distribution into tissues, including lung and macrophages.
Bioavailability	Oral: approximately 70% under fed conditions; absorption is significantly increased with high-fat food (about 2-fold increase in AUC).
Onset of Action	Oral: Bactericidal activity begins within days, with measurable colony-forming unit reductions in sputum by 2 weeks of therapy.
Duration of Action	Sustained bactericidal effect persists for weeks due to long half-life; clinical duration influenced by total treatment duration (typically 6 months as part of combination regimen).

Classification & Brands

Dosing & administration

For pulmonary multidrug-resistant tuberculosis: 400 mg orally twice daily for 2 weeks, then 200 mg three times weekly for 22 weeks (total 24 weeks). Administered with food.

Dosage form	TABLET
Renal impairment	No dose adjustment required for mild to moderate renal impairment. Not studied in severe renal impairment (CrCl < 30 mL/min) or on dialysis; use with caution.
Liver impairment	Child-Pugh A: No adjustment. Child-Pugh B: Use with caution; no specific dose recommendation. Child-Pugh C: Contraindicated.
Pediatric use	Approved for children ≥5 years and weighing ≥15 kg. Weight-based dosing: 15-30 kg: 200 mg once daily for 2 weeks, then 100 mg three times weekly for 22 weeks; 31-54 kg: 300 mg once daily for 2 weeks, then 150 mg three times weekly for 22 weeks; ≥55 kg: 400 mg once daily for 2 weeks, then 200 mg three times weekly for 22 weeks.
Geriatric use	No specific dose adjustment; use standard adult dosing with monitoring for QT prolongation, hepatotoxicity, and electrolyte disturbances due to age-related comorbidities and polypharmacy.

Use during pregnancy

1st trimester	Consult provider
2nd trimester	Consult provider
3rd trimester	Consult provider

Clinical note

Comprehensive clinical and safety monograph for SIRTURO (SIRTURO).

Breastfeeding	No human data. M/P ratio unknown. Bedaquiline and its metabolites are excreted in rat milk. Due to potential for adverse reactions in nursing infants, breastfeeding is not recommended during therapy.
Teratogenic Risk	First trimester: Limited human data. Animal studies show embryo-fetal toxicity including skeletal variations and reduced fetal weight at exposures below human therapeutic levels. Second and third trimesters: No specific data; potential for fetal harm based on animal findings. Use only if benefit outweighs risk.

Warnings & precautions

■ FDA Black Box Warning

Increased mortality observed in clinical trials; use only when no other effective treatment regimen is available.

Side Effect Profile

Serious Effects

Absolute Contraindications

Known hypersensitivity to bedaquiline; concomitant use with strong CYP3A4 inducers; use in patients with clinically significant QT prolongation or history of torsade de pointes.

Clinical Precautions

Precautions

Hepatotoxicity, QT prolongation, increased mortality, pancreatitis, hemoptysis, and potential for drug interactions with strong CYP3A4 inducers or inhibitors.

Clinical Tips & Counseling

Drug interactions

Loading safety data…