bed- AK-wi-leen

Therapeutic Classification: antituberculars

Pharmacologic Classification: diarylquinolines

• Multi-drug resistant pulmonary tuberculosis in adults, when other treatment regimens cannot be provided (in combination with 3 other drugs).
• Not to be used for latent, extra-pulmonary or other-drug sensitive tuberculosis.

• Inhibits bacterial adenosine 5–triphosphate (ATP) synthase which is required for mycobacterial energy production.

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

Absorption: Absorption following oral administration is doubled by food.

Distribution: Unknown.

Protein Binding: >99.9%.

Metabolism/Excretion: Mostly metabolized (CYP3A4 enzyme system) and eliminated in feces, negligible renal excretion.

Half-life: 5.5 mo (terminal elimination half-life).

(blood levels)

Contraindicated in:

• Concurrent use of strong CYP3A4 inducers
• Concurrent use of strong CYP3A4 inhibitors for >14 days.

Use Cautiously in:

• Electrolyte abnormalities (correct prior to use)
• Severe hepatic or renal impairment
• Concurrent use of other drugs that prolong the QT interval, history of torsades de pointes, prolonged QT interval, hypothyroidism, bradyarrhythmias, and decompensated HF (↑ risk of QT prolongation and serious arrhythmias)
• OB: Safety not established in pregnancy
• Lactation: Safety not established during breastfeeding
• Pedi: Children <5 yr (safety and effectiveness not established).

Neuro: headache.

Resp: hemoptysis.

CV: chest pain, QT interval prolongation.

GI: nausea, anorexia, HEPATOTOXICITY.

Derm: rash.

MS: arthralgia.

Drug-Drug:

• Strong CYP3A4 inducers, including rifampin, rifapentine and rifabutin and moderate CYP3A4 inducers, including efavirenz can ↓ levels and effectiveness and should be avoided.
• Strong CYP3A4 inhibitors including ketoconazole can ↑ levels and the risk of toxicity; avoid use for more than 14 consecutive days if possible.
• Concurrent use of lopinavir/ritonavir may ↑ blood levels and risk of adverse reactions.
• Concurrent use of other drugs that prolong the QT interval including fluoroquinolones, macrolides and clofazimine) may ↑ risk of serious arrhythmias.
• Concurrent use of alcohol or hepatotoxic drugs may ↑ risk of adverse hepatic events.

• 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.

• Tablets: 20 mg; 100 mg;

• Obtain ECG prior to starting therapy and at least 2, 12 and 24 wks after starting therapy to monitor for QT prolongation of >500 msec, clinically significant ventricular arrhythmias, or if syncope occurs.

• Monitor serum potassium, calcium, and magnesium at baseline and if QT interval prolongation is detected. 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, repeat test within 48 hr and test for viral hepatitis and other hepatotoxic medications. If symptoms of liver dysfunction (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 upper limit of normal, or if AST and ALT ↑ >8 time upper limits of normal, or if AST and ALT ↑ >5 times upper limit of normal and persist beyond 2 wks, discontinue bedaquiline.
  • Test patient for viral hepatitis prior to starting therapy.

• Only administer by direct observation therapy (DOT).
• 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 (maximum 5 tablets/5 mL) and administered or dispersed in water and mixed with a at least 5 mL of beverage (water, milk products, apple juice, orange juice, cranberry juice, carbonated beverage) or 1 tsp of soft food (yogurt, apple sauce, 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 non-carbonated 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 hrs between doses for a total of 600 mg/wk.

• Instruct patient to take bedaquiline as directed for the complete 24 wk course of therapy. Do not stop without discussing with health care professional. If a dose is missed during first 2 wks, skip dose and return to usual schedule. If a dose is missed wks 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 professional. If any medications are stopped may decrease effectiveness of therapy and may increase 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 professional if signs and symptoms of QT 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 professional of all Rx or OTC medications, vitamins, or herbal products being taken and to consult with health care professional before taking other medications or alcohol.
• Rep: Advise females of reproductive potential to notify health care professional if pregnancy is planned or suspected or if breastfeeding. Monitor infants exposed to bedaquiline through breast milk for signs of bedaquiline-related adverse reactions, (hepatotoxicity: yellowing of eyes, changes in color of urine or stool).

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

Sirturo

NDC Code^*

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