Pharmacology and relevant drug interactions of metamizole

Abstract

Metamizole is a frequently prescribed analgesic because of its favourable benefit/risk ratio compared with classic NSAIDs. However, increasing research shows that metamizole displays several drug interactions that are relevant to clinical practice. We reviewed the literature to summarize the pharmacology and most clinically relevant drug interactions of metamizole. Metamizole has a fast analgesic effect but a short half-life and duration of action. The exact mechanism of action of metamizole is currently not fully known. Studies showed that metamizole appears to be a moderate to strong inductor of the enzymes CYP3A4, CYP2B6 and CYP2C19; a weak inductor of CYP2C9; and a moderate inhibitor of CYP1A2. Furthermore, metamizole inhibits the effect of acetylsalicylic acid when taken simultaneously. Metamizole should be cautiously used together with other drugs that can cause agranulocytosis. If metamizole is prescribed in a high dosage (1000 mg three or four times daily) for more than 1 day, these pharmacokinetic and dynamic interactions should be taken into account.

Keywords: CYP; acetylsalicylic acid; dipyrone; interactions; metamizole; pharmacology.

FIGURE 1

Interaction between metamizole and acetylsalicylic acid in the COX‐1 enzyme of the thrombocyte. (A) Arachnidonic acid binds to the active core of the COX‐1 enzyme and is converted to prostaglandins. (B) Acetylsalicylic acid (ASA) prevents the binding of arachnidonic acid by binding to the protein serine 530. (C) Metamizole binds to the same serine 530, preventing the binding of acetylsalicylic acid and arachnidonic acid. Adapted from Catella‐Lawson et al.