Indications for SIRTURO:
As part of combination therapy in pulmonary multi-drug resistant tuberculosis (MDR-TB) only 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.
Administer by directly observed therapy and in combination with ≥3 other drugs to which the isolate is susceptible. Swallow whole with water. Take with food. ≥12yrs (≥30kg): 400mg once daily for 2 weeks followed by 200mg three times weekly (≥48hrs between doses) for 22 weeks.
<12yrs and/or <30kg: not established.
Increased mortality. QT prolongation.
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: monitor infants.
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. Additive QT prolongation with other drugs that prolong the QT interval (eg, fluoroquinolones, macrolides, clofazimine); monitor ECG. Avoid alcohol and other hepatotoxic drugs. Caution with concomitant lopinavir/ritonavir.
Nausea, arthralgia, headache, hemoptysis, chest pain, abdominal pain; hepatotoxicity, syncope (obtain ECG).