What it is
Metamizole (dipyrone) is an analgesic and antipyretic from the pyrazolone family. It is very effective for severe pain and high fever, but its anti-inflammatory effect is weak: it does not behave like a classic NSAID.
In Spain it requires a prescription. It is not a first-line medicine: it is kept for when paracetamol or NSAIDs are not enough or cannot be used, and the Spanish medicines agency (AEMPS) has stressed that courses must be short because of the risk of agranulocytosis. It is not marketed in the UK, the US or much of northern Europe precisely because of that risk.
Mechanism of action
Its mechanism is not fully understood. It is attributed to:
- Inhibition of prostaglandin synthesis, mainly in the central nervous system
- An effect on the hypothalamic centre that regulates temperature (hence its strong antipyretic effect)
- Activation of central pathways that modulate pain; it also relaxes smooth muscle, which helps in colicky pain
At the counter
When to recommend it
- Severe acute pain (colic, post-operative) prescribed by the doctor
- High fever not responding to paracetamol or ibuprofen, on prescription
- Patients who cannot take NSAIDs because of gastrointestinal risk, if the doctor prescribes it
- Short courses: the prescription sets the duration, and it is worth reminding the patient
When not to
- Allergy or hypersensitivity to pyrazolones, or analgesic-induced asthma
- History of agranulocytosis or bone marrow disorders
- First and third trimester of pregnancy, and breastfeeding
- Glucose-6-phosphate dehydrogenase deficiency or acute porphyria
Warnings
- Important Agranulocytosis: rare but serious and unpredictable. Warn the patient about the symptoms —fever, sore throat, mouth ulcers— and that if they appear they must stop it and get checked straight away.
- Important Potentially serious allergic reactions (angioedema, anaphylaxis), with cross-reactivity in patients sensitive to other analgesics. Always ask about previous reactions.
- Caution The AEMPS recommends short courses and, if treatment is prolonged, blood count monitoring. A patient who takes it 'all the time' deserves a conversation with their doctor.
- Caution It can lower blood pressure, especially at high doses or in patients who are dehydrated or have a high fever.
Pharmacokinetics
- Absorption
- Rapid and almost complete absorption after oral administration. Bioavailability above 85%. Onset of action at 30–60 minutes, peak effect at 2–3 hours.
- Distribution
- Widely distributed in body tissues. Plasma protein binding of 55–60%. It crosses the placenta and is excreted in breast milk.
- Metabolism
- Extensive hepatic metabolism. It is rapidly converted into active metabolites (4-methylaminoantipyrine and its derivatives) that keep the analgesic activity.
- Elimination
- Mainly renal, as metabolites. Half-life of 2–3 hours for the parent compound, but the active metabolites can remain for 10–20 hours.
Metamizole vs ibuprofen
| Aspect | Metamizole | Ibuprofen |
|---|---|---|
| Analgesic potency | High | Moderate to high |
| Antipyretic action | Very strong | Good |
| Anti-inflammatory effect | Weak | Real |
| Gastrointestinal risk | Lower | Higher |
| Characteristic risk | Agranulocytosis (rare, serious) | Ulcer, kidney, blood pressure |
| Access in Spain | Prescription only | 400 mg without prescription |
Metamizole is not 'a stronger ibuprofen': it has a different risk profile. It is used on prescription, in short courses, and with the agranulocytosis warning always said out loud.
Self-assessment
Three questions. When you check your answers you will see the explanation for each one.
-
These are the symptoms through which agranulocytosis shows up, a rare but serious reaction. Patients do not associate them with the painkiller, so they have to be told.
-
Taken orally it starts to work in 30–60 minutes and reaches its maximum at 2–3 hours. It is not instant, but it is fast for an oral medicine.
-
Allergy to pyrazolones and previous agranulocytosis are clear contraindications. Severe pain and NSAID intolerance are precisely the situations in which a doctor may prescribe it.
Training content. It does not replace the summary of product characteristics or clinical judgement.