What are the guidelines for using Normaxin (metamizole)?

Guidelines for Using Metamizole (Normaxin)

Metamizole (Normaxin) is banned in many developed countries due to the risk of serious adverse effects, particularly agranulocytosis, and should only be used under strict medical supervision when safer alternatives are not effective or available.

Indications and Usage

• Metamizole is indicated for short-term treatment of severe pain of different etiology, spastic conditions (especially affecting the digestive tract), and fever refractory to other treatments 1, 2
• It can be used for post-surgical pain, cancer pain, post-traumatic pain, pain from myocardial infarction, craniocerebral trauma, and pain during invasive diagnostic interventions 1
• Its spasmolytic effect combined with analgesic activity makes it particularly useful for various colic attacks 1, 2

Dosing Considerations

• Metamizole is a prodrug that converts to active metabolites (4-methylaninoantipyrine and 4-aminoantipyrine) after absorption 1
• Dosing should be adjusted in patients with renal impairment due to increased risk of toxicity 3
• The drug should be administered at the lowest effective dose for the shortest duration possible to minimize adverse effects 2

Contraindications

• Severe renal disease - metamizole causes the most significant oxidative damage to kidney tissue compared to other organs 3
• Known hypersensitivity to metamizole or other pyrazolone derivatives 2
• Patients with bone marrow suppression or history of agranulocytosis 4
• Pregnancy - although animal studies show no teratogenic effects, it is not recommended for pregnant women 2

Major Adverse Effects

• Agranulocytosis: The most serious adverse effect that led to its withdrawal from markets in many countries including the United States 5, 4
• Renal toxicity: Severe damage to kidney tissue with increased BUN and creatinine levels 3
• Hepatotoxicity: Moderate damage to liver tissue with elevated ALT and AST levels 3
• Cardiac effects: Mild damage to heart tissue has been observed in experimental studies 3
• Effects on platelet aggregation: Similar to aspirin, metamizole has significant effects on platelet aggregation 1

Monitoring Recommendations

• Complete blood count should be monitored regularly to detect early signs of agranulocytosis 4
• Renal function tests (BUN, creatinine) should be monitored, especially in patients with pre-existing kidney disease 3
• Liver function tests (ALT, AST) should be monitored in patients with pre-existing liver disease 3
• Patients should be educated about signs of agranulocytosis (fever, sore throat, mouth ulcers) and instructed to seek immediate medical attention if these occur 4

Special Populations

• Elderly: Use with caution due to increased risk of adverse effects, particularly renal toxicity 3
• Children: Can be used as an antipyretic in children, but safety profile is less established than other alternatives 1
• Patients with renal impairment: Should be avoided or used with extreme caution with dose adjustments and close monitoring 3
• Patients with hepatic impairment: Use with caution and monitor liver function 3

Drug Interactions

• Minimal drug interactions have been reported, but caution is advised when co-administered with:
  • Cyclosporine: Regular monitoring of cyclosporine blood levels is recommended 1
  • Other drugs affecting bone marrow function: Increased risk of myelotoxicity 2
  • Morphine: Co-administration produces superadditive antinociceptive effects 2

Regulatory Status

• Banned or severely restricted in many developed countries including the United States, United Kingdom, Japan, Australia, and others 5
• Still available in some European countries and widely used in Latin American countries 5, 4
• In countries where it is permitted, it is often restricted to parenteral preparations for strictly defined indications 5

Patient Education

• Patients should be informed about the risk of agranulocytosis and instructed to discontinue the medication and seek medical attention if signs of infection develop 4
• Latino immigrants in countries where metamizole is banned should be specifically counseled about the risks, as cross-border transfer and use of this medication is common 4
• Patients should be advised not to use metamizole as an over-the-counter medication without medical supervision, even if it is available as such in their country of origin 5, 4