SIRTURO Dosage & Rx Info | Uses, Side Effects

Sirturo Generic Name & Formulations

Legal Class

General Description

Bedaquiline 20mg+, 100mg; tabs; +scored.

Pharmacological Class

Diarylquinoline.

How Supplied

Tabs 20mg—60; 100mg—188

Manufacturer

Janssen Therapeutics

Generic Availability

Mechanism of Action

Sirturo inhibits mycobacterial ATP (adenosine 5'-triphosphate) synthase, by binding to subunit c of the enzyme that is essential for the generation of energy in M. tuberculosis.

Sirturo Indications

Indications

As part of combination therapy in pulmonary multi-drug resistant tuberculosis (MDR-TB). Reserve for use when an effective treatment regimen cannot otherwise be provided.

Limitations of Use

Not for treating latent infection, drug-sensitive or extra-pulmonary tuberculosis, or non-tuberculous mycobacterial infections. The safety and efficacy for use in HIV-infected patients have not been established.

Sirturo Dosage and Administration

Adult

Administer by directly observed therapy. Only use in combination with ≥3 other drugs to which the MDR-TB isolate is susceptible. Swallow whole with water. Take with food. 400mg once daily for 2 weeks followed by 200mg three times weekly (≥48hrs between doses) for 22 weeks. Methods of administration of 20mg tabs: see full labeling.

Children

<5yrs and/or <15kg: not established. Swallow whole with water. Take with food. ≥5yrs (15–<30kg): 200mg once daily for 2 weeks followed by 100mg three times weekly (≥48hrs between doses) for 22 weeks; (≥30kg): use Adult dose. Methods of administration of 20mg tabs: see full labeling.

Sirturo Contraindications

Not Applicable

Sirturo Boxed Warnings

Boxed Warning

Increased mortality. QT prolongation.

Sirturo Warnings/Precautions

Warnings/Precautions

Increased risk of mortality. Increased risk of QT prolongation in patients with history of Torsade de Pointes, congenital long QT syndrome, hypothyroidism, bradyarrhythmias, uncompensated heart failure, electrolyte abnormalities; monitor closely. Obtain ECG prior to therapy, and at least 2, 12, and 24 weeks after starting. Correct any electrolyte abnormalities at baseline and monitor if QT prolongation is detected. Discontinue Sirturo and all other QT prolonging drugs if ventricular arrhythmia or QTcF interval >500ms develops. Monitor ALT/AST, phosphatase, bilirubin at baseline, monthly during treatment, and as needed. Test for viral hepatitis and discontinue other hepatotoxic drugs if new or worsening liver dysfunction occurs. Discontinue if aminotransferase elevation with total bilirubin >2×ULN, aminotransferase elevation >8×ULN, or >5×ULN that persists >2 weeks. Severe hepatic or severe renal impairment/ESRD; monitor. Pregnancy. Nursing mothers: not recommended (during and for 27.5 months after the last dose).

Sirturo Pharmacokinetics

Absorption

Maximum plasma concentration: ~5 hours post-dose. Administration with a standard meal containing ~22g of fat (558 total Kcal) increased the relative bioavailability by ~2-fold vs under fasted conditions.

Distribution

Plasma protein bound: >99.9%. Volume of distribution: ~164 L.

Metabolism

CYP3A4.

Elimination

Fecal, renal (<0.001%). Half-life: ~5.5 months.

Sirturo Interactions

Interactions

Avoid concomitant strong CYP3A4 inducers (eg, rifampin, rifapentine, rifabutin) or moderate CYP3A inducers (eg, efavirenz). Avoid concomitant strong CYP3A4 inhibitors (eg, ketoconazole, itraconazole) for >14 days; monitor. May increase QT prolongation when concomitant other QT prolonging drugs (eg, fluoroquinolones, macrolides, clofazimine); monitor ECG. Avoid alcohol and other hepatotoxic drugs (esp. in hepatic impairment). Caution with concomitant lopinavir/ritonavir.

Sirturo Adverse Reactions

Adverse Reactions

Nausea, arthralgia, headache, hemoptysis, chest pain, abdominal pain; hepatotoxicity, syncope (obtain ECG).

Sirturo Clinical Trials

See Literature

Sirturo Note