Metamizole or Dipyrone is a pain reliever medicine. It is used to treat severe post-traumatic or postoperative pain when treatment with other non-opioid medications did not work. Metamizole is banned in many countries (including the US) because it can cause agranulocytosis (a severe reduction in the number of white blood cells in the blood) which can lead to the number of infections that can be fatal.

Dipiriona – Qué es

Metamizole, or dipyrone, is an analgesic, soothing, and fever reliever. Like acetaminophen, it has minimal anti-inflammatory effects. It is usually administered orally or by injection.

Although it is still available without a prescription in some countries, it is now prescribed or banned in most developed countries, due to its potential for adverse events, including agranulocytosis. It is in the ampyrone sulfonate family of drugs.

It was first used medically in Germany in 1922 under the brand name “Novalgin” and for many years it was available without a prescription in most countries, until its toxicity became apparent. Metamizole is marketed under various trade names.

Dipyrone – History

Ludwig Knorr was a student of Emil Fischer who won the Nobel Prize for his work on purines and sugars, which included the discovery of phenylhydrazine. In the 1880s, Knorr was trying to make quinolone derivatives from phenylhydrazine, and instead produced a pyrazole derivative, which after methylation, turned it into phenazone, also called antipyrine, which has been called “the mother ”of all modern antipyretic painkillers. Sales of that drug exploded, and in the 1890s chemists at Teerfarbenfabrik Meister, Lucius & Co. (a precursor to Hoechst AG that is now Sanofi), manufactured another derivative called pyramidon that was three times more active than antipyrine.

In 1893, a derivative of antipyrine, aminopyrine, was manufactured by Friedrich Stolz in Hoechst. However, later, the chemists at Hoechst made a derivative, melubrine (antipyrine sodium aminomethanesulfonate), which was introduced in 1913 and yet metamizole was subsequently synthesized; metamizole is a methyl derivative of melubrine and is also a more soluble prodrug of pyramidon. Metamizole was first marketed in Germany as “Novalgin” in 1922.

Dipyrone – Uses

Medical uses

It is used primarily for perioperative pain, acute injury, colic, cancer pain, other acute / chronic forms of pain, and high fever that does not respond to other agents.

Special populations

Its use in pregnancy is discouraged, although studies with animals are reassuring, having a risk of birth defects; Its use in the elderly or people with hepatic / renal impairment is not recommended, but if these groups of people must be treated, a lower dose is recommended and caution is advised.

Dipyrone – Precautions and Contraindications

Previous hypersensitivity (such as agranulocytosis or anaphylaxis) to metamizole or any of the excipients (for example, lactose) in the preparation used, acute porphyria, altered hematopoiesis (as due to treatment with chemotherapy agents), third trimester of pregnancy (possibility of effects adverse events) in the newborn), breastfeeding, children with a body weight less than 16 kg.

Although it is banned in most countries in the world, this drug is still used in many countries in Europe. That’s because research has shown that this very rare drug causes agranulocytosis. This meta-analysis showed that patients taking Metamizole were not at increased risk of serious side effects.

Another study conducted in Poland showed that this drug is completely safe if used for a short period of time and in a hospital setting. However, if you notice cold or flu symptoms, stop treatment immediately and contact your doctor.

It presents contraindications in the following cases:

  • Glucose-6-phosphate dehydrogenase deficiency
  • Severe liver failure
  • Severe kidney failure
  • Acute intermittent porphyria
  • The pregnancy
  • Patients under 18 years of age

Metamizole, pregnancy and lactation

Metamizole is contraindicated in pregnant women and nursing mothers. It passes into breast milk and can harm your baby.


There have been reports that a patient took 15 grams of Metamizole but has not experienced any serious side effects. Overdose is generally rare, but when it does occur, it is manifested by the following symptoms:

  • Nausea
  • Throwing up
  • Seizures
  • Dizziness
  • Coma
  • Mydriasis
  • Hepatic injury
  • Kidney damage

Dipirona – Administration

The recommended dose is 500 mg (one tablet) 3-4 times a day. The maximum daily dose is 4000 mg (8 tablets).

Dipyrone – Interactions

  • Drug (s) Interaction / Theoretical Potential Reason for Interaction
  • Cyclosporine Decreased serum levels of cyclosporine.
  • Additive hypothermia may occur with chlorpromazine (low body temperature).
  • Oral anticoagulants (anticoagulants), lithium, captopril, may interact with metamizole, since other pyrazolones are known to interact adversely with these substances.


It is considered quite safe in overdose, but supportive measures are generally recommended in these cases, as well as measures to limit absorption (such as activated charcoal) and accelerate excretion (such as hemodialysis).


It is a sulfonic acid and comes in the form of calcium, sodium and magnesium salts. Its sodium salt monohydrate form is a white / almost crystalline powder that is unstable in the presence of light, highly soluble in water and ethanol but practically insoluble in dichloromethane.


Although it is believed that inhibition of brain and spinal cord prostaglandin (fat-like molecules that are involved in inflammation, pain and fever) could be involved. Recently, researchers discovered another potential mechanism that implies that metamizole is a prodrug. In this proposal, not yet verified by other researchers, metamizole is broken down into other chemicals that are the actual active agents.

The result is a pair of conjugates of arachidonic acid with cannabinoids and NSAIDs [clarification needed] (although not in the strict chemical meaning of the word) of the degradation products of metamizole. Despite this, animal studies have found that the CB1 cannabinoid receptor is not involved in metamizole-induced analgesia. Although it seems to inhibit fevers caused by prostaglandins, especially prostaglandin E2.

Metamizole can increase the effect of the following medicines that increase the risk of toxicity:

Blood thinners, such as warfarin, acenocoumarol, heparin, and other antibiotics (penicillin and sulfonamides); Corticosteroids and medicines used to treat diabetes, antiplatelets (eg clopidogrel) and antihypertensives (eg diuretics and ACE inhibitors).

Medicines that can increase the levels of Metamizole in the blood and cause adverse effects are:

  • Sedatives
  • Hypnotics
  • Metamizole can reduce the effects of cyclosporine.

It should not be administered simultaneously with alcoholic beverages.

Dipyrone – Adverse Reactions

Metamizole can cause the following adverse reactions:

  • Abdominal discomfort
  • Maculopapular rash
  • Stevens-Johnson syndrome
  • Lyell’s syndrome
  • Agranulocytosis (sore throat, swollen mouth, pain when swallowing, fever, and cough)
  • Hypotension
  • Broncoespasmo
  • Arrhythmia
  • Allergic reactions

Society and Culture

Metamizole legal status by country as of April 2014 Gray: No data; probably without a prescription if the country is undeveloped, otherwise probably prohibited. Light Blue – Over the counter with limited restrictions. Blue – By prescription only, with fairly limited restrictions on use. Orange – By prescription only, with extensive restrictions on use. Red: complete ban.

Metamizole is banned in several countries, available by prescription in others (sometimes with strong warnings, sometimes without), and available without a prescription in others.

Samantha Robson
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Dr. Samantha Robson ( CRN: 0510146-5) is a nutritionist and website content reviewer related to her area of ​​expertise. With a postgraduate degree in Nutrition from The University of Arizona, she is a specialist in Sports Nutrition from Oxford University and is also a member of the International Society of Sports Nutrition.

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