Metamizole in Pain Therapy in the General Practitioner and Pediatric Office
Metamizole is a pyrazole analgesic-antipyretic with spasmolytic effects, indicated for the treatment of post-traumatic or postoperative pain, visceral colic, cancer pain, and high fever unresponsive to other treatments. The advantage of this drug is its good tolerance without serious adverse effects on the gastrointestinal system, no impact on platelet aggregation, and usability in adults and children of all ages.
Mechanism of Action
Similar to other analgesics, the mechanism of action of metamizole has not yet been fully elucidated. After oral administration, it is hydrolyzed into active metabolites. It leads to the inhibition of cyclooxygenase (COX-1 and COX-2) and possible interaction with cannabinoid receptors (CB1).
Indications and Efficacy
Metamizole is indicated for the treatment of acute severe postoperative and post-traumatic pain, painful colics, cancer pain, other acute or chronic severe pain if other treatments are contraindicated, and high fever unresponsive to other treatments.
In the Oxford League Table of Analgesic Efficacy, metamizole ranks high in analgesic therapy. Drugs are ranked according to the NNT (number needed to treat) value − this parameter indicates the number of patients who need to take a certain dose of the drug for at least one of them to achieve a 50% reduction in pain within 4–5 hours. The lower this value, the higher the probability of the drug's effect. Metamizole at a dose of 500 mg is in the top third of the ranking with an NNT of 2.4, and at a dose of 1000 mg, it ranks top along with etoricoxib with an NNT of 1.6.
Dosage Forms and Dosing
Metamizole is available in two dosage forms: tablets (500 mg) and oral drops with raspberry flavor (20, 50, and 100 ml), with 1 ml of the drug (20 drops) corresponding to 500 mg of the active substance. It is suitable for children of all ages, adolescents, and adults. The single dose is 500 mg, and up to 8 tablets daily (4 g) can be used for a short period. In children, the dose should follow body weight: the single dose is 4 drops per 10 kg, and the daily dose is 16 drops per 10 kg. The duration of treatment depends on the type and severity of the condition. Long-term administration requires regular monitoring of the blood count, including the differential leukocyte count.
Options for Combination Therapy
To achieve optimal analgesic effect, metamizole can be combined with other analgesics and co-analgesics. Short-term concurrent administration with nonsteroidal anti-inflammatory drugs (NSAIDs) is possible to utilize the additive effect, and with paracetamol. The combination of metamizole with strong and weak opioid analgesics is effective, as well as with gabapentinoids and some classes of antidepressants (tricyclic, SSRIs, atypical).
Due to drug interactions, metamizole should not be administered concurrently with chlorpromazine due to the possible development of hypotermia, with methotrexate due to the increased risk of hematopoietic disorders, and with cyclosporine due to the decline in its levels.
Safety Profile
Generally, it is a safe drug with good tolerance. Compared to NSAIDs and opioids, the great advantage of metamizole is the lower incidence of adverse effects, especially gastrointestinal. The main adverse effects of metamizole are related to hypersensitivity reactions (anaphylactic reaction, skin reactions, hypotensive reaction) and hematological risks, the most feared of which is agranulocytosis. However, these occur very rarely. In the Czech Republic, no case of agranulocytosis has been reported since the drug's registration despite the consumption of 10 million defined daily doses of drugs containing metamizole.
The risk of death from adverse effects is as low for metamizole as it is for paracetamol (20–25 deaths per 100 million exposed individuals) and approximately 20 times lower than for diclofenac. Nevertheless, metamizole should not be the first-choice analgesic and its use requires a prescription.
The administration of metamizole is not recommended in the first and third trimesters of pregnancy (ideally throughout pregnancy) and is contraindicated in patients with hypersensitivity to pyrazolone derivatives, allergic asthma, allergy to NSAIDs and paracetamol, hematopoiesis disorders, and porphyria. The dose should be reduced in older or weakened individuals and in patients with reduced creatinine clearance.
Conclusion
Metamizole is an effective non-opioid analgesic that finds wide application in the treatment of acute and chronic pain of various etiologies, including visceral colicky pain due to its spasmolytic effect. It can be administered to children without age restrictions, adolescents, and adults. Its advantages include minimal adverse effects, the absence of serious adverse effects on the gastrointestinal tract, the potential for combination with other analgesics to achieve optimal analgesic effect, even distribution in body compartments, and the possibility of pain therapy in patients on anticoagulant treatment, such as warfarin.
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Sources:
1. Lejčko J. Metamizole in pain treatment. Presentation. Center for Pain Treatment KARIM LF UK and FN Plzeň.
2. Šimíček M. Oxford analgesics league and acute pain therapy from the pharmacist's perspective. Practical pharmacy 2015; 5 (2): 54–58.
3. SPC Metamizole Stada. Available at: www.sukl.cz/modules/medication/detail.php?code=0205930&tab=texts
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