Adverse Drug Events

Only adverse events occurring in at least 5% of participants will be analysed for pharmacogenetic associations, because rare-event analyses may have limited statistical power. Adverse drug events were examined in three included studies, making them less commonly studied than non-adherence or PIP/PIMs. Safety events will be captured prospectively using standardised adverse-event forms aligned with WHO Toxicity Grading Scales and linked to pharmacokinetic and pharmacogenetic data. Expected adverse events in the MDR-TB treatment cohort include hepatotoxicity, QT interval prolongation, skin reactions, gastrointestinal reactions, neurological adverse events and general drug intolerance. In a USA latent tuberculosis treatment study, 13.4% of incarcerated patients receiving rifampicin and pyrazinamide experienced adverse drug events, mainly hepatotoxicity. In a Taiwan prison isoniazid study, 12% of inmates had adverse events causing treatment discontinuation, with hepatotoxicity most common. Older age, abnormal baseline aspartate aminotransferase, and excess alcohol use were associated with hepatotoxicity in latent tuberculosis treatment. Hepatitis C virus infection was identified as an…