bedaquiline

Absorption: Absorption following oral administration is doubled by food.

Distribution: Unknown.

Protein Binding: >99.9%.

Metabolism/Excretion: Primarily metabolized by the liver via the CYP3A4 isoenzyme; eliminated in feces; negligible renal excretion.

Half-Life: 5.5 mo.

Time/Action Profile ⬆ ⬇

(plasma concentrations)

ROUTE	ONSET	PEAK	DURATION
PO	unknown	5 hr	unknown

Contraind./Precautions ⬆ ⬇

Contraindicated in:

Lactation: Lactation.

Use Cautiously in:

Severe hepatic or renal impairment;
History of torsades de pointes, congenital long QT syndrome, hypothyroidism, bradyarrhythmias, decompensated HF, hypokalemia, hypomagnesemia, or hypocalcemia (↑ risk of QT interval prolongation and serious arrhythmias);
OB: Safety not established in pregnancy;
Pedi: Children <5 yr (safety and effectiveness not established).

Adv. Reactions/Side Effects ⬆ ⬇

CV: chest pain,

QT interval prolongation

Derm: rash

GI: nausea, anorexia, HEPATOTOXICITY

MS: arthralgia

Neuro: headache

Resp: hemoptysis

Interactions ⬆ ⬇

Drug-drug:

Strong CYP3A4 inducers, including rifampin, rifapentine, and rifabutin, and moderate CYP3A4 inducers, including efavirenz, can ↓ levels and effectiveness; avoid concurrent use.
Strong CYP3A4 inhibitors, including ketoconazole, can ↑ levels and risk of toxicity; avoid use for >14 consecutive days, if possible.
Lopinavir/ritonavir may ↑ levels and risk of toxicity.
Other
QT interval prolonging drugs may ↑ risk of QT interval prolongation
.
Alcohol or hepatotoxic drugs may ↑ risk of adverse hepatic events.

Route/Dosage ⬆ ⬇

PO (Adults and Children ≥5 yr and ≥30 kg): 400 mg once daily for 2 wk; then 200 mg 3 times weekly (with ≥48 hr between doses) for 22 wk.
PO (Children ≥5 yr and 15–29 kg): 200 mg once daily for 2 wk; then 100 mg 3 times weekly (with ≥48 hr between doses) for 22 wk.

Availability ⬆ ⬇

Tablets: 20 mg; 100 mg

Assessment ⬆ ⬇

Assess cardiac status (palpitations, chest pain, syncopal episodes) and vital signs.
Obtain an ECG before start of therapy, 2 wk after initiation, during treatment, as clinically indicated, and at the expected time of maximum ↑ in the QTc interval of the concurrently administered QTc prolonging drugs (as applicable). If syncope or palpitations occur, obtain an ECG to detect QTc prolongation. Discontinue therapy if significant ventricular arrhythmia occurs or if QTc interval >500 msec.
Assess and monitor for hepatotoxicity (fatigue, anorexia, nausea or vomiting, jaundice, dark urine, liver tenderness and hepatomegaly, stomach pain, fever, weakness, itching, light-colored bowel movements, dark-colored urine, yellowing of skin or white of eyes).

Lab Test Considerations:

Obtain baseline serum potassium, calcium, and magnesium, and monitor throughout treatment. Correct abnormalities.
- Monitor liver function tests (ALT, AST, alkaline phosphatase, and bilirubin) at baseline, monthly during therapy, and as needed. If serum AST and ALT ↑ to 3 times the upper limit of normal (ULN), repeat test within 48 hr and test for viral hepatitis and discontinue other hepatotoxic medications. If symptoms of liver impairment (clinically significant ↑ serum ALT, AST, or bilirubin and/or symptoms of fatigue, anorexia, nausea, jaundice, dark urine, liver tenderness, and hepatomegaly) occur, re-evaluate. If AST and ALT ↑ accompanied by total bilirubin ↑ >2 times ULN, or if AST and ALT ↑ >8 time ULN, or if AST and ALT ↑ >5 times ULN and persist beyond 2 wk, discontinue bedaquiline.
- Test patient for viral hepatitis prior to starting therapy.

Implementation ⬆ ⬇

Only administer by direct observation therapy.
Must be taken in combination with 3–4 other antitubercular drugs.
PO: Administer with food. Tablets may be split for lower doses.
- Tablets may be dispersed in water and mixed with at least 5 mL of beverage (water, milk products, apple juice, orange juice, cranberry juice, carbonated beverage) or 1 teaspoon of soft food (yogurt, applesauce, mashed banana, porridge) or crushed and mixed with soft food or administered through a feeding tube. Administer immediately after mixing. Rinse with beverage or add more soft food to ensure no tablet residue is left in cup. For feeding tube administration, disperse 5 tablets or less in 50 mL noncarbonated water and mix well. Mixture should be white to almost white with visible particles. Administer via NG tube immediately; rinse and flush with 25 mL additional water.
- Weeks 1–2: Administer 400 mg once daily.
- Weeks 3–24: Administer two 100 mg tablets 3 times/wk with at least 48 hr between doses for a total of 600 mg/wk.

Patient/Family Teaching ⬆ ⬇

Instruct patient to take bedaquiline as directed for the complete 24-wk course of therapy. Do not stop without discussing with health care provider. If a dose is missed during 1st 2 wk, skip dose and return to usual schedule. If a dose is missed during Wk 3–24, take missed dose as soon as remembered; then resume 3 times/wk regimen. Emphasize that bedaquiline is always taken with 3–4 other antitubercular medications and these medications should be continued unless discussed with health care provider. Stopping any medications may ↓ effectiveness of therapy and may ↑ risk of Mycobacterium resistance and disease becoming untreatable in future. Advise patient to read Medication Guide before starting therapy.
Caution patient to avoid alcohol during therapy.
Advise patient to notify health care provider immediately if signs and symptoms of QT interval prolongation (change in heartbeat, dizziness, fainting) or hepatotoxicity (nausea or vomiting, stomach pain, fever, weakness, itching, unusual tiredness, loss of appetite, light-colored bowel movements, dark-colored urine, yellowing of skin or white of eyes) occur.
Advise patient to notify health care provider of all Rx or OTC medications, vitamins, or herbal products being taken and to consult with health care provider before taking other medications.
Rep: Advise women of reproductive potential to notify health care provider if pregnancy is planned or suspected and to avoid breastfeeding during therapy.
Pedi: Advise caregivers to call the doctor if the child has a fast or abnormal heartbeat or dizziness or passes out.

Evaluation/Desired Outcomes ⬆ ⬇

Shortened time to sputum conversion to negativity and resultant decrease in infectiousness of patient and sequelae of tuberculosis.

US Brand Names ⬆ ⬇

Code ⬆

NDC Code

59676- Janssen Products, LP
- 59676-701- SIRTURO
  - 59676-701-01- 188 TABLET in 1 BOTTLE (59676-701-01)

59676- Janssen Products, LP
- 59676-702- SIRTURO
  - 59676-702-60- 60 TABLET in 1 BOTTLE (59676-702-60)

69766- MSN Life Sciences Private Limited
- 69766-058-
  - 69766-058-01- 50 kg in 1 DRUM (69766-058-01)

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Pronunciation ⬇

Classifications ⬆ ⬇

Indications ⬆ ⬇

Action ⬆ ⬇

Pharmacokinetics ⬆ ⬇