Pharmacology · Non-opioid analgesic antipyretics
Metamizole !
A strong analgesic and antipyretic that also relaxes smooth muscle. Its serious risk is agranulocytosis, unrelated to the dose.
Updated 2026-11-01
Also called: dipyrone, metamizole sodium
Mechanism of action
The mechanism of metamizole is not fully understood. It is a prodrug hydrolysed in the gut to 4-methylaminoantipyrine, its main active metabolite, which is then turned into 4-aminoantipyrine. These metabolites reduce prostaglandin E2-induced hyperalgesia; proposed pathways include cGMP activation with opening of ATP-sensitive potassium channels and activation of CB1 cannabinoid receptors. It has little anti-inflammatory or antiplatelet effect and relaxes smooth muscle.
- Hydrolysed to 4-methylaminoantipyrine, its active metabolite
- The metabolites reduce prostaglandin E2-driven hyperalgesia
- The thermal set point falls and smooth muscle relaxes
- Relief of severe pain, colic and fever
Pharmacokinetics
- Absorption
- By mouth it is quickly hydrolysed to 4-methylaminoantipyrine; the parent drug is barely detectable in the blood.
- Metabolism
- Liver: 4-methylaminoantipyrine is demethylated (mainly by CYP3A4) to 4-aminoantipyrine, which is then acetylated; another route oxidises it to 4-formylaminoantipyrine.
- Elimination
- Kidney, as metabolites.
- Half-life
- That of the active metabolite, 4-methylaminoantipyrine, is about 2.6 to 3.5 hours.
Indications
- Severe acute pain after surgery or trauma when other analgesics are not enough
- Colicky pain, such as renal colic
- Cancer pain
- High fever that does not respond to other treatments
Adverse effects
Common
- Effects on blood cells, above all white cells
- Symptoms of liver injury: fatigue, nausea, poor appetite and right upper abdominal discomfort
Contraindications
- Previous agranulocytosis from metamizole or other pyrazolones or pyrazolidines
- Bone marrow disorders or diseases that affect how blood cells are made or work
- Last trimester of pregnancy
- Breastfeeding
Key interactions
- Antibiotics
- Can mask the first symptoms of agranulocytosis, as can metamizole's own antipyretic effect.
What is monitored
- Fever, chills, sore throat and mucosal sores during treatment and shortly after stopping it
- Full blood count with differential at once if those symptoms appear
- Signs of liver injury: jaundice, dark urine, malaise and nausea
Administration and safety
- Given by mouth, rectally or by injection; if agranulocytosis is suspected the drug is stopped while blood count results are awaited.
- Before giving it, ask about previous reactions to metamizole or other pyrazolones.
Nursing care
- Explain the symptoms of agranulocytosis (fever, chills, sore throat, sores in the mouth or genital area) and that the patient must stop it and seek care at once if they appear.
- Remember that when it is used for fever, an early symptom of agranulocytosis can go unnoticed.
- Check skin and eyes for jaundice and ask about dark urine.
- Record any reaction in the medical record: someone who had agranulocytosis must not receive it again.
Pregnancy and breastfeeding
Evidence on use in pregnancy is scarce; it is not used in the last trimester because of effects on the fetal kidneys and circulation, nor during breastfeeding.
Test yourself
Think of the answer, then tap the question to see it.
What is special about the agranulocytosis risk of metamizole?
It does not depend on the dose, it can appear at any time during treatment or shortly after stopping, and also in people who took it before without problems.
Why can metamizole hide its own most serious adverse effect?
Because it lowers fever, one of the first signs of agranulocytosis; concurrent antibiotics can also mask it.
At what stage of pregnancy is metamizole not used, and why?
In the last trimester, because of evidence of effects on the fetal kidneys and circulation.
What is 4-methylaminoantipyrine?
The main active metabolite of metamizole, formed by rapid hydrolysis in the gut.
Related drugs
← Back to the class: Non-opioid analgesic antipyretics
Educational content on how drugs work; not a prescribing guide and no substitute for a health professional's advice. No doses are given.
Sources: Metamizole-containing medicinal products - referral (European Medicines Agency, 2024); Metamizole containing medicinal products - referral (European Medicines Agency, 2019); Metamizole (PubChem (NCBI), 2026); ATCDDD - ATC/DDD Index (WHO Collaborating Centre for Drug Statistics Methodology, 2026).
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