Bpal

BPaL is an all-oral tuberculosis regimen consisting of bedaquiline (B), pretomanid (Pa), and linezolid (L). It is used primarily for adults with rifampicin-resistant TB, including multidrug-resistant TB (MDR-TB) and extensively drug-resistant TB (XDR-TB), in settings where other regimens are unsuitable or less feasible.

Clinical evidence for BPaL comes mainly from the Nix-TB trial, which enrolled patients with XDR-TB or MDR-TB with additional resistance. Treatment for six to nine months using BPaL achieved favorable outcomes in the majority of participants, with cure or completion rates around 85–90%. The regimen is notable for being all-oral and avoiding injectable second-line drugs, addressing a key constraint of older regimens.

Adverse events are a major consideration. Linezolid is associated with peripheral neuropathy, anemia, and other myelosuppressive effects, which often require dose adjustments or stopping linezolid. Bedaquiline carries a risk of QT interval prolongation, and pretomanid can cause liver-related and other adverse effects; together, the combination requires careful monitoring for drug interactions and toxicity.

Regulatory status and guidelines: The regimen has received regulatory approvals and policy endorsements. The U.S. FDA approved pretomanid in combination with bedaquiline and linezolid for certain TB cases; the World Health Organization issued policy recommendations in 2020 endorsing BPaL as an all-oral option for adults with rifampicin-resistant TB when other options are limited. The regimen is not universally suitable for all drug-resistant TB patients, and pediatric data are limited.

Implementation considerations: BPaL requires experienced TB programs, access to the three drugs, and close monitoring for adverse events and drug interactions, particularly with HIV co-infection and concurrent therapies. Ongoing research, including dose-optimization studies, aims to reduce linezolid-related toxicity and refine patient selection.