Major
Haloperidol × Rifampicin
First-generation antipsychotics. Butyrophenone derivatives×Antituberculous antibiotic
Mechanism
Rifampicin strongly induces CYP3A4 – the main haloperidol metabolic route. Haloperidol plasma levels fall by 70%; antipsychotic effect weakens.
Symptoms
Return of positive symptoms: hallucinations, delusions, agitation. In schizophrenia: risk of acute relapse.
Management
During anti-TB therapy, increase haloperidol 2- to 3-fold with clinical monitoring. Alternative antipsychotics without CYP3A4 dependence: olanzapine or aripiprazole.