Metamizole or dipyrone is a painkiller, spasm reliever, and fever reliever drug. It is most commonly given by mouth or by intravenous infusion. It belongs to the ampyrone sulfonate family of medicines and was patented in 1922. Metamizole is marketed under various trade names. It was first used medically in Germany under the brand name Novalgin, later becoming widely known in Slavic nations and India under the brand name Analgin. The sale of metamizole is restricted in some jurisdictions following studies in the 1970s which correlated it to severe adverse effects, including agranulocytosis. Other studies have disputed this judgement, instead claiming that it is a safer drug than other painkillers. Metamizole is popular in many countries, where it is typically available as an over-the-counter medication. In the United States, metamizole is known colloquially as "Mexican aspirin".
Medical uses Metamizole, with its analgesic (pain relief), antipyretic (fever reduction), and spasmolytic (relax muscle contractions) properties, is utilized in the management of acute pain, fever, and pain caused by muscle spasms. Metamizole is primarily used for perioperative pain, acute injury, colic, cancer pain, other acute/chronic forms of pain and high fever unresponsive to other agents. Metamizole also effectively manages biliary and intestinal colic-like pain, and reduces the spasm of the smooth muscle of the sphincter of Oddi.
Special populations Its use in pregnancy is advised against, although animal studies are reassuring in that they show minimal risk of birth defects. Its use in the elderly and those with liver or kidney impairment is advised against, but if these groups of people must be treated, a lower dose and caution is usually advised. Its use during lactation is advised against, as it is excreted in breast milk.
Adverse effects While metamizole is a relatively safe medication, it is not entirely devoid of adverse effects. A 2024 review article found that metamizole had a lower risk of causing mild adverse effects than aspirin and paracetamol. Metamizole has a potential of blood-related toxicity (blood dyscrasias), but causes less kidney, cardiovascular, and gastrointestinal toxicity than non-steroidal anti-inflammatory drugs (NSAIDs). Like NSAIDs, it can trigger bronchospasm or anaphylaxis, especially in those with asthma. Serious side effects include agranulocytosis, aplastic anaemia, hypersensitivity reactions (e.g., anaphylaxis and bronchospasm), toxic epidermal necrolysis, and it may provoke acute attacks of porphyria, as it is chemically related to the sulfonamides. The relative risk for agranulocytosis appears to greatly vary according to the country of estimates on said rate and opinion on the risk is strongly divided. Genetics may influence metamizole sensitivity. It is suggested that some populations are more prone to suffer from metamizole induced agranulocytosis than others. As an example, metamizole-related agranulocytosis seems to be an adverse effect more frequent in British population as opposed to Spaniards. An assessment report by the European Medicines Agency remarked that "the potential to induce agranulocytosis may be associated with genetic characteristics of the population studied". A 2015 meta-analysis concluded that on the evidence available "for short-term use in the hospital setting, metamizole seems to be a safe choice when compared to other widely used analgesics", but that the "results were limited by the mediocre overall quality of the reports" analysed. A systematic review from 2016 found that metamizole significantly increased the relative risk of upper gastrointestinal bleeding, by a factor of 1.4–2.7 times; however, none of the studies included in that review accounted for duration of therapy or dose. A study by one of the manufacturers of the drug found the risk of agranulocytosis within the first week of treatment to be a 1.1 in a million, versus 5.9 in a million for diclofenac. Therapeutic effect of metamizole on intestinal colic is attributed to its analgesic properties, with no evidence of interference in small bowel or colon motility. Metamizole has potential for hepatotoxicity.
Contraindications Previous hypersensitivity (e.g., agranulocytosis or anaphylaxis) to metamizole or any of the excipients (e.g., lactose) in the preparation used, acute porphyria, impaired hematopoiesis (such as due to treatment with chemotherapy agents), third trimester of pregnancy (potential for adverse effects in the newborn), lactation, children with a body weight below 16 kg, history of aspirin-induced asthma and other hypersensitivity reactions to analgesics. In 2018, the European Medicines Agency (EMA) reviewed the safety of metamizole and concluded it to be generally safe for the general population. However, they advised against its use in the third trimester of pregnancy or while breastfeeding due to risks of renal impairment or ductus arteriosus to the fetus or infant.
Interactions A clinically severe interaction has been identified between aspirin and metamizole for patients who regularly take aspirin to manage vascular disease: this interaction occurs due to steric hindrance at the active aspirin binding site of COX-1 by metamizole; to manage this interaction, it is recommended to make a delay between the intake of each of these drugs, with aspirin being taken at least 30 minutes before metamizole.
Oral anticoagulants (blood thinners), lithium, captopril, triamterene and antihypertensives may also interact with metamizole, as other pyrazolones are known to interact adversely with these substances.
Overdose Metamizole is fairly safe on overdose, but in these cases supportive measures are usually advised as well as measures to limit absorption (e.g., activated charcoal) and accelerate excretion (e.g., hemodialysis).
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