Bedaquiline
Indications
Bedaquiline is used for:
Multidrug Resistant Pulmonary Tuberculosis
Diarylquinoline antimycobacterial indicated as part of combination therapy for pulmonary multidrug resistant tuberculosis (MDR-TB); reserve bedaquiline for when an effective treatment TB regimen cannot otherwise be provided
Adult Dose
Multidrug Resistant Pulmonary Tuberculosis
Weeks 1-2: 400 mg PO qDay for 2 weeks, THEN
Weeks 3-24: 200 mg 3 times/week with at least 48 hr between doses
Use in combination with at least 4 other drugs to which the patient's MDR-TB isolate is likely to be susceptible; reserve bedaquiline for when an effective treatment TB regimen cannot otherwise be provided
Hepatic impairment
Mild or moderate (Child-Pugh A or B): No dosage adjustment required
Severe (Child-Pugh C): Not studied; use only if benefits outweigh risks
Child Dose
Multidrug Resistant Pulmonary Tuberculosis
<12 years: Safety and efficacy not established
>12 years with weight >30 kg
Weeks 1-2: 400 mg PO qDay for 2 weeks, THEN
Weeks 3-24: 200 mg 3 times/week with at least 48 hr between doses
Use in combination with at least 4 other drugs to which the patient's MDR-TB isolate is likely to be susceptible; reserve bedaquiline for when an effective treatment TB regimen cannot otherwise be provided
Renal Dose
Renal impairment
Mild-to-moderate: No dosage adjustment required
Severe or end-stage renal disease requiring hemodialysis or peritoneal dialysis: Use with caution; if used, monitor for adverse reactions of bedaquiline
Administration
Contra Indications
Precautions
Increased risk of death in bedaquiline treatment group
Administered by directly observed therapy (DOT)
Potential for development of resistance to bedaquiline in M tuberculosis exists; must only be used in an appropriate combination regimen fo treatment of pulmonary MDR-TB to reduce risk of developing resistance
Hepatotoxicity
Hepatic-related adverse effects increased when bedaquiline added to multidrug regimen; avoid alcohol and other hepatotoxic drugs, especially in patients with hepatic impairment
Monitor symptoms (eg, fatigue, anorexia, nausea, jaundice, dark urine, liver tenderness, hepatomegaly) and laboratory tests (ALT, AST, alkaline phosphatase, and bilirubin) at baseline, monthly while on treatment, and as needed; test for viral hepatitis and discontinue other hepatotoxic medications if evidence of new or worsening liver dysfunction occurs
Monitor ALT, AST, Alkaline phosphatase, and bilirubin at baseline, and monthly while on treatment
Pregnancy-Lactation
Pregnancy
Available data from published literature of use in pregnant women are insufficient to evaluate a drug-associated risk of major birth defects, miscarriage, or adverse maternal or fetal outcomes
Clinical considerations
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
Animal studies
Reproduction studies in rats and rabbits revealed no evidence of harm to fetuses of pregnant rats and rabbits during organogenesis at exposures up to 6x the clinical dose based on AUC comparisons
Lactation
No data are available regarding presence in human milk
Monitor infants exposed for signs of bedaquiline-related adverse reactions (eg, hepatotoxicity)
Animal studies
Bedaquiline concentrations in rat milk were 6-fold to 12-fold higher than the maximum concentration observed in maternal plasma at exposures 1-2x the clinical exposure (based on AUC comparisons)
Interactions
May prolong QT interval; assess thoroughly and if possible, avoid coadministration with other drugs that prolong QT interval
Metabolized by CYP3A4; avoid strong CYP3A4 inducers (eg, rifampin, rifapentine, rifabutin) and antiretroviral drugs that are moderate inducers (eg, efavirenz) that may reduce bedaquiline’s effect
Coadministration with CYP3A4 inhibitors may increase systemic exposure and result in adverse effects; avoid coadministration with strong CYP3A4 inhibitors >14 consecutive days, unless the benefit of treatment outweighs the risk
Use bedaquiline with caution when coadministered with lopinavir/ritonavir and only if the benefit outweighs the risk
There are no clinical data on the combined use of antiretroviral agents and bedaquiline in HIV/MDR-TB coinfected patients and only limited clinical data on use in HIV/MDR-TB coinfected patients not receiving antiretroviral therapy
Adverse Effects
Side effects of Bedaquiline :
>10%
Adults
Nausea (38%)
Arthralgia (33%)
Headache (28%)
Chest pain (11%)
Pediatrics
Arthralgia (40%)
Nausea (13%)
Abdominal pain (13%)
1-10%
Adults
Anorexia (9%)
Rash (8%)
Adults or children
Transaminases increased (9%)
Blood amylase increased (3%)
Frequency Not Defined
QT prolongation