SIRTURO

Pharmacokinetics (PK) parameters The pharmacokinetic properties of bedaquiline are summarized in Table 5 as mean (SD) in adult patients.

Table 5Model-Derived Pharmacokinetic Parameters of Bedaquiline and M2 (mean [SD]) after Multiple Doses of SIRTURO at the Recommended Dosing Regimen Pharmacokinetic Parameters Bedaquiline SD=Standard Deviation

AbsorptionFood effect High fat meal (22 grams of fat, 558 total Kcal) increased C max and AUC by 2-fold. SIRTURO should be taken with food to enhance i...

14.1 SIRTURO Use in Adult Patients With Pulmonary Tuberculosis

Study 1(NCT00449644, Stage 2) was a placebo-controlled, double-blind, randomized trial conducted in patients with newly diagnosed sputum smear-positive pulmonary TB due to M. tuberculosis resistant to at least rifampin and isoniazid. Patients were randomized to receive a combination of SIRTURO or placebo with five other antimycobacterial drugs (i.e., ethionamide, kanamycin, pyrazinamide, ofloxacin, and cycloserine/terizidone or available alternative) for a total duration of 18 to 24 months or at least 12 months after the first con...

The following serious adverse reactions are discussed elsewhere in the labeling: QTc Prolongation [see Warnings and Precautions (5.1) and Clinical Pharmacology (12.2) ] Mortality Imbalance in Clinical Trials [see Warnings and Precautions (5.2) ] Hepatotoxicity [see Warnings and Precautions (5.4) ] Drug Interactions [see Warnings and Precautions (5.5) ] The most common adverse reactions reported in 10% or more adult patients treated with SIRTURO in Study 1 were nausea, arthralgia, headache, hemop...

None. None. ( 4 )

A mortality imbalance was seen in clinical trials in SIRTURO-treated patients with pulmonary TB due to Mycobacterium tuberculosis resistant to at least rifampin. ( 5.2 ) Hepatotoxicity may occur with use of SIRTURO. Monitor liver-related laboratory tests. Discontinue SIRTURO if evidence of liver injury occurs. ( 5.4 ) 5.1 QTc Prolongation SIRTURO prolongs the QTc interval [see Clinical Pharmacology (12.2) ] . Use with drugs that prolong the QTc interval may cause additive QTc prolongation [see A...

7 DRUG INTERACTIONS Avoid use of strong and moderate CYP3A4 inducers with SIRTURO. ( 7.1 ) Closely monitor patient safety (e.g., liver function) when SIRTURO is coadministered with CYP3A4 inhibitors. ( 5.4 , 7.1 ) 7.1 Effect of Other Drugs on SIRTURO Strong and Moderate CYP3A4 Inducers Coadministration of SIRTURO with moderate or strong CYP3A4 inducers may decrease systemic exposure of bedaquiline...