Use in Specific Populations

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 tuberculosis during pregnancy. Reproduction studies performed in rats and rabbits have revealed no evidence of harm to the fetus due to oral administration of bedaquiline to pregnant rats and rabbits during organogenesis at exposures up to 6 times the clinical dose based on AUC comparisons.

Clinical Considerations

Disease-associated Maternal and/or Embryo/Fetal Risk

Active tuberculosis in pregnancy is associated with adverse maternal and neonatal outcomes including maternal anemia, caesarean delivery, preterm birth, low birth weight, birth asphyxia, and perinatal infant death.

Lactation

Risk Summary:

There is no information regarding the presence of bedaquiline in human milk. Minimal data are available on the effects of the drug on breastfed infants. No data are available on the effects of the drug on milk production. Bedaquiline is concentrated in the milk of rats. When a drug is present in animal milk, it is likely that the drug will be present in human milk. The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for SIRTURO® and any potential adverse effects on the breastfed infant from SIRTURO® or from the underlying maternal condition.

Clinical Considerations

Monitor infants exposed to bedaquiline through breast milk for signs of bedaquiline-related adverse reactions, such as hepatotoxicity.

Pediatric Use

The safety and effectiveness of SIRTURO have been established in pediatric patients 5 years and older weighing at least 15 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 30 pediatric patients 5 years to less than 18 years of age with confirmed or probable MDR-TB infection who were to be treated with SIRTURO for 24 weeks in combination with a background regimen.

The safety, effectiveness and dosage of SIRTURO in pediatric patients less than 5 years of age and/or weighing less than 15 kg have not been established.

Geriatric Use

There are limited data on the use of SIRTURO® in tuberculosis patients 65 years and older. Because of limited data, differences in outcomes or specific risks with SIRTURO® cannot be ruled out for patients 65 years of age and older.

Race/Ethnicity

In a population pharmacokinetic analysis of MDR-TB patients treated with SIRTURO®, systemic exposure (AUC) to SIRTURO® was found to be 34% lower in Black patients than in patients from other race categories. This lower exposure was not considered to be clinically relevant as no clear relationship between exposure to SIRTURO® and response has been observed in clinical trials of MDR-TB. Furthermore, response rates were comparable in patients of different race categories that completed 24 weeks of SIRTURO® treatment.

Hepatic Impairment

The pharmacokinetics of bedaquiline were assessed after single-dose administration to adult patients with moderate hepatic impairment (Child-Pugh B). Based on these results, no dose adjustment is necessary in patients with mild or moderate hepatic impairment. After single dose administration of 400 mg SIRTURO® in 8 adult patients with moderate hepatic impairment (Child Pugh B), mean exposure to SIRTURO® and and its active metabolite M2 (AUC672h) was approximately 20% lower compared to healthy subjects.

SIRTURO® has not been studied in patients with severe hepatic impairment and should be used with caution in these patients only when the benefits outweigh the risks. Clinical monitoring for SIRTURO®-related adverse reactions is recommended.

Renal Impairment

SIRTURO® has mainly been studied in adult patients with normal renal function. Renal excretion of unchanged SIRTURO® is not substantial (≤0.001%). No dose adjustment is required in patients with mild or moderate renal impairment. In patients with severe renal impairment or end stage renal disease requiring hemodialysis or peritoneal dialysis, SIRTURO® should be used with caution. Monitor adult and pediatric patients for adverse reactions of SIRTURO® when administered to patients with severe renal impairment or end stage renal disease requiring hemodialysis or peritoneal dialysis.

HIV Co-infection

There are limited data on the use of SIRTURO® in HIV co-infected patients.