Analgesic and antipyretic (pyrazolone)
Metamizole (dipyrone) is an analgesic and antipyretic used for moderate to severe acute pain and high fever when other medicines are not effective. It is effective, but can cause a severe decrease in white blood cells (agranulocytosis), so it should only be used when the benefit justifies the risk and under medical supervision.
Also known as: dipirona, dipyrone, metamizol magnésico, Nolotil
Prontuário Terapêutico INFARMED (section 2.10) + Levy M. Clin Pharmacokinet 1995 (PMID 7758252)
Metamizole may reduce the antiplatelet effect of low-dose acetylsalicylic acid.
Metamizole, like some NSAIDs, can interfere with the irreversible acetylation of platelet COX-1 by aspirin and reduce its antiplatelet effect, especially when taken before aspirin; additionally, metamizole is associated with agranulocytosis, although rare. The combination should be weighed: prefer paracetamol for occasional analgesia in patients taking low-dose aspirin, separate administration when possible and instruct the patient about bleeding signs or signs of infection (fever, pharyngitis) that may indicate agranulocytosis.
Aspirin + metamizole: metamizole can interfere with the antiplatelet effect of aspirin and adds haematological risk (agranulocytosis). Monitor.
Metamizole interferes with aspirin COX-1 platelet inhibition, which may reduce cardioprotection.
Patient cardiovascular risk and adherence to antiplatelet therapy.
New ischaemic event while on aspirin requires review of the antithrombotic strategy.
Avoid coadministration when aspirin is used for cardiovascular prevention.
EMA (Article 31 referral) — Metamizole: https://www.ema.europa.eu/en/medicines/human/referrals/metamizole-containing-medicinal-products ; approved Aspirin label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=3ba0a9f2-062a-401e-82eb-54383a822366 — with additional references: Prontuário Terapêutico do INFARMED (11th ed., 2012) and national Analgin 500 mg SmPC (HALMED)
Metamizole may potentiate the effect of oral anticoagulants, increasing bleeding risk.
Metamizole (dipyrone) can increase the effect of warfarin through a pharmacokinetic interaction (metabolism inhibition, with INR elevation) and its own antiplatelet effect; cases of severe bleeding, including gastrointestinal bleeding, have been described. The EMA, in its metamizole review, mentions the need for INR monitoring in anticoagulated patients. Whenever possible, use alternative analgesics (paracetamol at controlled doses); if metamizole is used, monitor the INR frequently and alert for bleeding signs.
Metamizole can potentiate warfarin (pharmacokinetic interaction and antiplatelet effect). Monitor the INR and watch for bleeding; prefer paracetamol as first-line analgesic.
Mechanism not fully established; metamizole may enhance coumarin anticoagulants and increase gastrointestinal bleeding risk.
INR, bruising, bleeding and fall in haemoglobin.
INR above target or active bleeding require anticoagulant adjustment.
Monitor INR and signs of bleeding; where possible prefer paracetamol as analgesic.
EMA — Metamizole (Article 31 referral): https://www.ema.europa.eu/en/medicines/human/referrals/metamizole-containing-medicinal-products ; approved Warfarin label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=541c9a70-adaf-4ef3-94ba-ad4e70dfa057 — with additional references: Prontuário Terapêutico do INFARMED (11th ed., 2012) and national Analgin 500 mg SmPC (HALMED)
Alcohol enhances the effect of metamizole and may increase the risk of CNS depression.
Advise avoiding alcohol consumption during metamizole treatment.
National Analgin 500 mg SmPC (HALMED) — metamizole interaction with alcohol ; EMA — Metamizole (Article 31 referral): https://www.ema.europa.eu/en/medicines/human/referrals/metamizole-containing-medicinal-products
Recurrent and potentially fatal risk of agranulocytosis after previous exposure.
Contraindicated; warn about signs of infection requiring an immediate blood count.
National Analgin 500 mg SmPC (HALMED) ; EMA — Metamizole (Article 31 referral): https://www.ema.europa.eu/en/medicines/human/referrals/metamizole-containing-medicinal-products
Metamizole is contraindicated in the third trimester (risk of fetal renal toxicity and premature closure of the ductus arteriosus).
Contraindicated in the third trimester; in the first two trimesters avoid unless short-term use is needed.
Excreted in milk; avoid while breastfeeding.
Advise effective contraception.
EMA — Metamizole (Article 31 referral), 3rd-trimester contraindication: https://www.ema.europa.eu/en/medicines/human/referrals/metamizole-containing-medicinal-products
Clinical and educational support tool. The information does not replace a medical prescription or the opinion of a qualified healthcare professional.
Non-opioid analgesic and antipyretic (pyrazolone), with spasmolytic effect, used for acute moderate to severe pain and high fever when other drugs are not suitable. No relevant anti-inflammatory effect. Associated with a rare but serious risk of agranulocytosis — use the lowest effective dose for the shortest duration, and discontinue if signs of infection appear (fever, sore throat, stomatitis).
Metamizole is a prodrug: it hydrolyses rapidly (non-enzymatically) to the active metabolite 4-methylaminoantipyrine (MAA), responsible for the analgesic/antipyretic effect. The analgesic mechanism involves inhibition of prostaglandin synthesis in the CNS and modulation of central pathways (endocannabinoid system and TRPA1 receptors); it does not relevantly inhibit peripheral COX (no anti-inflammatory/antiplatelet effect).
Rapidly absorbed orally: MAA (the active metabolite) reaches peak plasma concentrations in about 1-2 hours, with oral bioavailability of approximately 85% (tablets). IV/IM administration produces faster peaks. Onset of oral analgesia occurs within 30-60 minutes.
MAA is subsequently metabolised by oxidation and N-demethylation to 4-aminoantipyrine (AA) and 4-formylaminoantipyrine (FAA), also active metabolites excreted renally; a fraction is acetylated (N-acetyl-AA). Metamizole-associated agranulocytosis is idiosyncratic (not dose-dependent), probably immune-mediated.
Elimination half-life of the active metabolite MAA of approximately 3 hours (2.6-3.7 h); the AA and FAA metabolites have half-lives of about 3.5-5 hours. In patients with liver cirrhosis the half-life of MAA may quadruple. Elimination is essentially renal (metabolites).
Medicines from the same therapeutic group (ATC classification) or the same pharmacological class.
