Metamizole – wide possibilities of an analgesic with a unique mechanism of action and different routes of administration
Metamizole is a non-addictive pyrazolone analgesic with antipyretic effects, which differs from other non-opioid analgesics by its spasmolytic action. It is indicated in monotherapy and in combinations for the treatment of severe acute and chronic pain. Its high analgesic efficacy is evidenced by a low number of patients needed to treat to achieve at least 50% pain relief in 4-6 hours. The favorable safety profile of metamizole is supported by more than 100 years of clinical experience.
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Mechanism of action
The mechanism of action of metamizole is not completely elucidated. According to some data, metamizole and its main metabolite (4-N-methylaminoantipyrine) may have combined central and peripheral effects.
Metamizole is not a typical cyclooxygenase (COX) inhibitor, although through its effect on COX, it inhibits peripheral and central prostaglandin synthesis. However, its effects on COX are weak compared to nonsteroidal anti-inflammatory drugs (NSAIDs), which explains the absence of its effect on platelet aggregation and minimal side effects resulting from COX inhibition.
Another possible analgesic mechanism of action of metamizole is the activation of the endogenous opioid and cannabinoid systems. The drug activates the cannabinoid receptor CB1, thereby enhancing the effects of the pain-suppressing pathway.
Metamizole blocks not only prostaglandin-dependent pathways but also prostaglandin-independent pathways (i.e., insensitive to indomethacin), which means its antipyretic mechanism of action differs from other COX inhibitors.
Oral, intramuscular or intravenous administration
Metamizole sodium is available in an injection form for intramuscular or intravenous administration (500 mg in 1 ml of injection solution) and in tablet form for oral administration (500 mg in 1 coated tablet). The product is indicated for the treatment of severe acute or chronic pain and fever unresponsive to other treatment. The pharmacokinetic properties of metamizole are similar for both oral and parenteral administration.
The tablet form is not recommended for children under 15 years of age due to the strength of the product. In the injection form, it is administered to infants, children, and adolescents intravenously or intramuscularly. In adults, oral administration is usually sufficient to achieve satisfactory analgesia. Only where oral administration is not suitable (e.g., with vomiting or swallowing disorders), is parenteral administration recommended, which is associated with a higher risk of anaphylactic/anaphylactoid reactions. Due to observed hypotensive reactions, metamizole must not be administered parenterally to patients with hypotension or hemodynamic instability.
Dosage depends on the intensity of pain or fever and individual response. It is recommended to administer the lowest dose sufficient to control pain and fever.
Effectiveness
An example demonstrating the strong analgesic efficacy of metamizole is the results of a meta-analysis published in 2022. The number of patients needed to treat with metamizole p.o. at a dose of 500 mg to achieve at least 50% relief of tooth pain in 4–6 hours (NNT – number needed to treat) was 2.3, placing it alongside rapidly acting ibuprofen and diclofenac among non-opioid analgesics with the lowest, i.e., most favorable NNT.
Safety profile
Several studies have documented that metamizole has a favorable gastrointestinal, cardiovascular, and cerebrovascular safety profile compared to nonsteroidal antirheumatics. The most serious adverse event, which occurs only rarely, is agranulocytosis. Rare anaphylactic/anaphylactoid reactions, including shock, can occur during any route of administration. Milder forms usually manifest with skin and mucosal symptoms. Due to undesirable effects, the product is not suitable for long-term administration (months).
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Source: Stromer W., Palladini M. Metamizole: a comprehensive approach to its benefit-risk profile. EFSM 2022 Nov 2; 2: 220153, doi: 10.52778/efsm.22.0153.
SmPC Novalgin inj.: https://prehledy.sukl.cz/prehled_leciv.html#/detail-reg/0254042
SmPC Novalgin tbl.: https://prehledy.sukl.cz/prehled_leciv.html#/detail-reg/0254040
MAT-CZ-2400522 – 1.0 – 05/2024
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