What are the guidelines for using Metamizol (Dipyrone) for pain or fever management?

Metamizol (Dipyrone) for Pain and Fever Management

Primary Recommendation

Metamizole should be reserved exclusively for short-term postoperative pain management in a hospital setting due to the risk of agranulocytosis, and should not be used as a first-line agent for routine pain or fever control. 1, 2

Dosing Guidelines

Pediatric Dosing

• Intravenous/Intraoperative: 10-15 mg/kg every 8 hours 1, 2
• Oral: 10 mg/kg every 8 hours 1, 2
• Continuous infusion: 2.5 mg/kg/hour following an intraoperative loading dose 1, 2

Clinical Context

• The European Society for Paediatric Anaesthesiology (2024) positions metamizole as a first-line rescue analgesic in institutions where it is available, but emphasizes this is only for short-term postoperative use 1
• Metamizole can be used for breakthrough pain management on the ward when NSAIDs and paracetamol are insufficient 1

Critical Safety Concerns

Agranulocytosis Risk

• Incidence: Ranges from 0.96 cases per million per year to 1:1602 per patient receiving metamizole 3, 4
• Risk factors: Female gender, older age, duration of intake (dose-independent but time-dependent) 3
• Pediatric risk: Probably lower than adults but still present 3, 5
• Re-exposure: Patients with past exposure may develop rapid-onset agranulocytosis upon re-exposure 3

Clinical Presentation of Agranulocytosis

• Fever, sore throat, fatigue, mucosal inflammation or ulceration 3, 6
• Neutrophil count < 500/µL defines agranulocytosis 3, 5

Immediate Management if Agranulocytosis Suspected

1. Stop metamizole immediately upon suspicion 3, 6
2. Check complete blood count urgently 3
3. Initiate broad-spectrum antibiotics empirically if infection present (e.g., piperacillin/tazobactam) 7, 6
4. Consider G-CSF therapy only in patients with poor prognostic factors 3, 6
5. Monitor closely until neutrophil count normalizes 3
6. Permanent contraindication: Never re-expose patient to metamizole 3

Contraindications and Restrictions

Absolute Restrictions

• Not for chronic pain management 1, 2
• Not for outpatient use 1, 2
• Not as first-line antipyretic in children given alternative options 5
• Avoid in cancer pain except specific situations due to serious, unpredictable side effects 1

Duration Limits

• Maximum use: Short-term postoperative period only (typically 2-5 days) 1, 2
• Risk of agranulocytosis increases with duration of intake 3

Position in Analgesic Hierarchy

When to Consider Metamizole

Metamizole should only be considered when:

• Patient is in a hospital setting with monitoring capability 1, 2
• Postoperative pain requires multimodal analgesia 1
• NSAIDs and paracetamol are insufficient or contraindicated 1
• Before escalating to stronger opioids for breakthrough pain 1

Preferred Alternatives

• First-line for mild-moderate pain: Paracetamol (acetaminophen) 1
• For inflammatory/bone pain: NSAIDs 1
• For moderate pain: Weak opioids (codeine, tramadol) 1
• For severe pain: Strong opioids (morphine) 1

Common Pitfalls to Avoid

1. Using metamizole for routine fever in children - This is inappropriate given safer alternatives like paracetamol and ibuprofen 5
2. Prescribing for outpatient/chronic use - Agranulocytosis risk increases with duration and requires hospital monitoring 1, 2, 3
3. Failing to educate patients about warning signs - Patients must know to report fever, sore throat, or mouth ulcers immediately 3, 6
4. Not checking baseline and monitoring blood counts - While routine monitoring isn't standard, awareness of symptoms is critical 3
5. Re-prescribing to patients with prior metamizole exposure - This can cause rapid-onset agranulocytosis 3

Geographic Considerations

Metamizole availability and acceptance varies significantly by region. It was withdrawn in several countries (including the Netherlands in 1989, though reintroduced in 2013 for specific indications) due to agranulocytosis concerns 7. The 2024 ESPA guidelines acknowledge this by consistently stating "if available" when recommending metamizole 1.