Bedaquiline

Bedaquiline is a prescription medication used for the treatment of multidrug-resistant pulmonary tuberculosis.

• Bedaquiline is available under the following different brand names: Sirturo

Adult and pediatric dosage

Tablet

• 20mg (functionally scored)
• 100mg

Multidrug-Resistant Pulmonary Tuberculosis

Adult dosage

• Weeks 1-2: 400 mg orally every day for 2 weeks, THEN
• Weeks 3-24: 200 mg 3 times/week with at least 48 hours  between doses

Pediatric dosage

• Children below 5 years: Safety and efficacy not established
• Children above 5 years
  • Weight above 30 kg
    • Weeks 1-2: 400 mg orally every day for 2 weeks, THEN
    • Weeks 3-24: 200 mg 3 times/week with at least 48 hours between doses
  • Weight 15 to 29 kg
    • Weeks 1-2: 200 mg orally every day for 2 weeks, THEN
    • Weeks 3-24: 100 mg 3 times/week with at least 48 hours between doses

Dosage Considerations – Should be Given as Follows: 

• See “Dosages”

Common side effects of the Bedaquiline include:

• nausea,
• stomach pain,
• coughing up blood,
• headache,
• skin rash, and
• joint pain

Serious side effects of the Bedaquiline include:

• hives,
• difficulty breathing,
• swelling of the face, lips, tongue, or throat,
• fast or pounding heartbeats,
• fluttering in the chest,
• shortness of breath,
• sudden dizziness,
• chest pain,
• coughing up blood,
• vomit that looks like coffee grounds,
• loss of appetite,
• stomach pain (upper right side),
• tiredness,
• dark urine,
• clay-colored stools, and
• yellowing of the skin or eyes (jaundice)

Rare side effects of the Bedaquiline include:

• none 

This is not a complete list of side effects and other serious side effects or health problems that may occur as a result of the use of this drug. Call your doctor for medical advice about serious side effects or adverse reactions. You may report side effects or health problems to FDA at 1-800-FDA-1088.

If your medical doctor is using this medicine to treat your pain, your doctor or pharmacist may already be aware of any possible drug interactions and may be monitoring you for them. Do not start, stop, or change the dosage of any medicine before checking with your doctor, health care provider, or pharmacist first.

• Bedaquiline has severe interactions with the following drug:
  • lefamulin
• Bedaquiline has serious interactions with at least 102 other drugs.
• Bedaquiline has moderate interactions with at least 126 other drugs.
• Bedaquiline has minor interactions with no other drugs.

This information does not contain all possible interactions or adverse effects. Visit the RxList Drug Interaction Checker for any drug interactions. Therefore, before using this product, tell your doctor or pharmacist about all the products you use. Keep a list of all your medications with you and share this information with your doctor and pharmacist. Check with your health care professional or doctor for additional medical advice, or if you have health questions or concerns.

Contraindications

• None

Effects of drug abuse

• None

Short-Term Effects

• See “What Are Side Effects Associated with Using Bedaquiline?”

Long-Term Effects

• See “What Are Side Effects Associated with Using Bedaquiline?”

Cautions

• Increased risk of death in the bedaquiline treatment group
• Administered by directly observed therapy (DOT)
• The potential for development of resistance to bedaquiline in M tuberculosis exists; must only be used in an appropriate combination regimen for treatment of pulmonary MDR-TB to reduce the risk of developing resistance
• Hepatotoxicity
  • Hepatic-related adverse effects increased when bedaquiline was added to the 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
  • Discontinue if
    • Aminotransferase increases are accompanied by total bilirubin elevation of more than 2x ULN
    • Aminotransferase elevations of more than 8x ULN
    • Aminotransferase elevations persist beyond 2 weeks
• QT prolongation
  • Prolongs QT interval; obtain ECG before initiating treatment and at least 2, 12, and 24 weeks after starting treatment
  • Obtain baseline serum levels for potassium, calcium, and magnesium and correct if abnormal; follow-up electrolyte monitoring if QT prolongation detected
  • Increased risk for QT prolongation with
  • Coadministration with QT-prolonging drugs (eg, fluoroquinolones, macrolides, clofazimine)
  • History of Torsade de Pointes, congenital long-QT syndrome, uncompensated heart failure, or hypothyroidism with bradyarrhythmias
  • Discontinue bedaquiline and other QT-prolonging drugs if the following develops
  • Clinically significant ventricular arrhythmia
  • QTcF interval of more than 500 ms
  • Monitor ECG to confirm QT interval returned to baseline
  • If syncope occurs, obtain ECG
• Drug interaction overview
  • 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 for more than 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 co-infected patients and only limited clinical data on use in HIV/MDR-TB co-infected patients not receiving antiretroviral therapy

Pregnancy and Lactation

• Available data from published literature on 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, cesarean delivery, preterm birth, low birth weight, birth asphyxia, and perinatal infant death
• Lactation
  • No data are available regarding the presence of human milk
  • Monitor infants exposed for signs of bedaquiline-related adverse reactions (eg, hepatotoxicity)