Detailed View: Safety Labeling Changes Approved By FDA Center for Drug Evaluation and Research (CDER)
BOXED WARNING (edited)
- QT prolongation can occur with SIRTURO. Use with drugs that prolong the QT interval may cause additive QT prolongation. Monitor ECGs. Discontinue SIRTURO if significant ventricular arrhythmia or if QTcF interval prolongation of greater than 500 ms develops [see Warnings and Precautions (5.2)].
WARNINGS AND PRECAUTIONS
- added...SIRTURO has not been studied in patients with ventricular arrhythmias or recent myocardial infarction.
Hepatotoxicity section edited
- More hepatic-related adverse reactions were reported with the use of SIRTURO plus other drugs used to treat tuberculosis compared to other drugs used to treat tuberculosis without the addition of SIRTURO. Alcohol and other hepatotoxic drugs should be avoided while on SIRTURO, especially in patients with impaired hepatic function.
- Monitor symptoms (such as fatigue, anorexia, nausea, jaundice, dark urine, liver tenderness and 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.
Discontinue SIRTURO if:
- aminotransferase elevations are accompanied by total bilirubin elevation greater than two times the upper limit of normal
- aminotransferase elevations are greater than eight times the upper limit of normal
- aminotransferase elevations are greater than five times the upper limit of normal and persist beyond two weeks
Clinical Studies Experience section edited with trial data
CYP3A4 Inducers/Inhibitors section edited
- Bedaquiline exposure may be reduced during co-administration with inducers of CYP3A4 and increased during co-administration with inhibitors of CYP3A4.
- Due to the possibility of a reduction of the therapeutic effect of bedaquiline because of the decrease in systemic exposure, co-administration of strong CYP3A4 inducers, such as rifamycins (i.e., rifampin, rifapentine and rifabutin), or moderate CYP3A4 inducers should be avoided during treatment with SIRTURO [see Clinical Pharmacology (12.3)].
- Due to the potential risk of adverse reactions to bedaquiline because of the increase in systemic exposure, prolonged co-administration of bedaquiline and strong CYP3A4 inhibitors, such as ketoconazole or itraconazole, for more than 14 consecutive days should be avoided unless the benefit outweighs the risk [see Clinical Pharmacology (12.3)]. Appropriate clinical monitoring for SIRTURO-related adverse reactions is recommended.
Other Antimicrobial Medications section edited
- No dose-adjustment of isoniazid or pyrazinamide is required during co-administration with SIRTURO. In a placebo-controlled clinical trial in patients with MDR-TB, no major impact of co-administration of SIRTURO on the pharmacokinetics of ethambutol, kanamycin, pyrazinamide, ofloxacin or cycloserine was observed.
Antiretroviral Medications section edited
- Although clinical data in HIV/MDR-TB co-infected patients on the combined use of lopinavir (400 mg)/ritonavir (100 mg) with SIRTURO are not available, use SIRTURO with caution when co-administered with lopinavir/ritonavir and only if the benefit outweighs the risk [see Clinical Pharmacology (12.3)].
- No dosage adjustment of bedaquiline is required when co-administered with nevirapine [see Clinical Pharmacology (12.3)].
- Concomitant administration of bedaquiline and efavirenz, or other moderate CYP3A inducers, should be avoided [see Warnings and Precautions (5.4)].
QT Interval Prolonging Drugs
- added...Monitor ECGs if SIRTURO is co-administered to patients receiving other drugs that prolong the QTc interval, and discontinue SIRTURO if evidence of serious ventricular arrhythmia or QTcF interval greater than 500 ms. [see Warnings and Precautions (5.2) and Clinical Pharmacology (12.2)].
USE IN SPECIFIC POPULATIONS
Geriatric Use section edited
- Because of limited data, differences in outcomes or specific risks with SIRTURO cannot be ruled out for patients 65 years of age and older.
It is not known if Sirturo is safe and effective in:
- people who have an infection caused by bacteria other than TB