The 3 HP regimen for tuberculosis preventive treatment: safety, dosage and related concerns during its large-scale implementation in countries like India

Abstract

The 3-month once-weekly isoniazid-rifapentine (3 HP) regimen for tuberculosis preventive treatment recommended by WHO is being rolled in countries including India. It has higher completion rates and lower risk of hepatotoxicity than isoniazid preventive treatment, but trials also showed higher frequency of systemic drug reactions (SDRs) including flu-like syndromes and dizziness, and also uncommon Grade 3 or 4 adverse events like hypotension, syncope, bronchospasm. Low BMI is a risk factor for SDRs. Available data on safety of 3 HP in the Asian region is limited, heterogeneous, but points to a higher frequency of SDRs suggesting a need for caution in its large-scale implementation. 19% (118/614) of household contacts initiated on 3 HP in Delhi reported dizziness. Multiple lines of evidence including pharmacokinetic data suggest that the SDRs may be related to isoniazid and its plasma concentration. WHO and national guidelines for the 3 HP regimen currently recommend a fixed dose of once-weekly 900 mg isoniazid in adults regardless of body weight that poses a risk of SDRs for lower weight adults, amplified by the acetylator status and the lack of co-administration of pyridoxine. Weight based dosing, co-administration of pyridoxine and pharmacovigilance studies should accompany the roll out of 3 HP to ensure its safe and successful implementation.