What is a suitable substitute for paracetamol (acetaminophen) in a patient with a paracetamol allergy for managing fever?

Alternative Antipyretic for Paracetamol Allergy

Ibuprofen is the optimal first-line substitute for fever management in patients with paracetamol allergy, as it provides superior fever reduction with longer duration of action compared to paracetamol. 1

Primary Recommendation: Ibuprofen

• Ibuprofen should be administered as the first-choice alternative antipyretic for patients allergic to paracetamol. 1
• Dosing for adults: 400-600 mg IV or oral every 6-8 hours as needed for fever control 2
• Ibuprofen demonstrates equivalent efficacy to paracetamol in reducing fever within 30 minutes of administration, with sustained effect 2
• Both IV ibuprofen 400 mg and IV paracetamol 1000 mg achieve significant fever reduction without superiority of either agent, making ibuprofen an excellent substitute 2

Alternative NSAID Options if Ibuprofen is Contraindicated

• If ibuprofen is not tolerated or contraindicated, consider structurally distinct NSAIDs such as meloxicam or nabumetone, which may have reduced cross-reactivity risk. 1
• Cross-reactivity within the same NSAID chemical class can occur but is not universal 1
• Avoid all NSAIDs in the same class if the patient has a history of severe cutaneous reactions (Stevens-Johnson syndrome, toxic epidermal necrolysis, DRESS syndrome) to any NSAID 1

Critical Contraindications and Dose Adjustments

• Reduce ibuprofen dose in patients with impaired renal function 1
• Avoid ibuprofen entirely in patients taking low-dose aspirin for cardioprotection, as ibuprofen antagonizes aspirin's irreversible platelet inhibition 1, 3
• Do not use NSAIDs in patients with active upper GI bleeding, severe renal impairment, or decompensated cardiovascular disease 3
• Avoid NSAIDs in patients with severe COVID-19 manifestations (kidney, cardiac, or gastrointestinal injury) 4, 3

Special Populations Requiring Specialist Consultation

• Patients with mastocytosis require specialist consultation before any NSAID use, as they may exhibit NSAID hypersensitivity through mast cell degranulation 1, 3
• Patients with documented severe cutaneous reactions to NSAIDs must avoid all NSAIDs in that chemical class 1, 3

Adjunctive Non-Pharmacological Measures

• Maintain adequate hydration (no more than 2 liters per day in adults) 1, 4
• Physical cooling methods such as tepid sponging may be considered as adjunctive therapy, though evidence from randomized trials is limited and these methods cause patient discomfort 1, 4
• Reduce excessive environmental stimuli and lower ambient temperature during warmer months 4

Escalation Strategy if NSAIDs are Contraindicated

• If both paracetamol (due to allergy) and NSAIDs (due to contraindications) cannot be used, consider short-term opioid-based symptomatic relief with codeine or morphine for distressing fever. 3
• This approach should be conservative, time-limited, and recognized as off-label use for fever suppression 3
• In severe cases where fever poses risk of secondary organ injury, initiate automated feedback-controlled temperature management devices rather than relying solely on pharmacological agents 3

Common Pitfalls to Avoid

• Do not use antipyretics with the sole aim of reducing body temperature—treat fever only when it causes distressing symptoms 3
• Never substitute aspirin for paracetamol in children with febrile conditions due to Reye's syndrome risk 5
• Avoid indiscriminate use of steroids or antihistamines for febrile transfusion reactions; tailor treatment to specific symptoms (IV paracetamol for febrile reactions, antihistamines for allergic reactions) 6