Minor
Hypericum perforatum × Paracetamol
Antidepressants. Other antidepressants of herbal origin×Anilides. Analgesics and antipyretics
Mechanism
St John's wort is a CYP3A4 inducer and a weak CYP2E1 inducer. It may theoretically increase formation of paracetamol's hepatotoxic metabolite NAPQI on long-term combination, but clinical cases are rare.
Symptoms
Fatigue, nausea, jaundice, elevated liver enzymes. Symptoms possible on long-term combination (over 1 month) and high paracetamol dose (over 3 g/day).
Management
For short paracetamol courses (3–7 days), no specific adjustment needed. On long-term combination (St John's wort as phytotherapy for depression), cap paracetamol at 2 g/day. St John's wort has many interactions via CYP3A4 induction (contraceptives, warfarin, SSRIs) — reconsider its use.