Bedaquiline

QT prolongation remained a uniquely strong bedaquiline signal compared with delamanid and pretomanid. For bedaquiline, cytotoxic metabolite generation through the CYP2E1/NF-kB pathway has been implicated in hepatotoxicity. Bedaquiline's adverse event profile is mainly characterized by cardiovascular and hepatic involvement. An early phase II trial led the FDA to place a black box warning on bedaquiline because of higher mortality in the bedaquiline arm, although later cohort data found lower all-cause mortality than controls. Bedaquiline and delamanid shared several signals, including peripheral neuropathy, hypokalaemia, respiratory failure, seizures, and gastrointestinal or constitutional symptoms.