What are appropriate alternatives to paracetamol (acetaminophen) for a patient with a confirmed allergy when treating mild‑to‑moderate pain or fever?

Alternative to Paracetamol in Confirmed Allergy

For patients with confirmed paracetamol allergy, NSAIDs (specifically ibuprofen or naproxen) are the first-line alternatives for mild-to-moderate pain and fever, with ibuprofen preferred due to its superior safety profile at over-the-counter doses. 1, 2

First-Line Alternative: NSAIDs

Ibuprofen as Primary Choice

• Ibuprofen 400-600 mg every 6-8 hours (maximum 2400 mg/day) is the preferred alternative due to its well-established safety profile at OTC doses and comparable efficacy to paracetamol 1, 2
• Ibuprofen has a good safety profile at low doses (800-1200 mg/day) comparable to paracetamol, with lower gastrointestinal, cardiovascular, and renal risks compared to other NSAIDs 2
• The short plasma half-life and lack of toxic metabolites contribute to ibuprofen's favorable safety profile 2

Naproxen as Alternative NSAID

• Naproxen 250-500 mg every 8-12 hours can be used when longer duration of action is desired 3
• Naproxen has demonstrated superior efficacy to codeine-acetaminophen combinations (NNT 2.7 vs 4.4) 1

Critical Safety Considerations Before Prescribing NSAIDs

Absolute Contraindications

• Do not prescribe NSAIDs if the patient has: 1, 3
  • History of gastroduodenal ulcers or GI bleeding
  • Severe renal impairment (eGFR <30 ml/min)
  • Congestive heart failure
  • Recent cardiovascular events
  • Aspirin-sensitive asthma
  • Third trimester pregnancy

High-Risk Populations Requiring Caution

• Elderly patients (≥65 years): Use lowest effective dose for shortest duration due to increased risk of GI, renal, and cardiovascular adverse effects 1
• Patients on anticoagulants or corticosteroids: Significantly increased bleeding risk 3
• Hypertension or cardiovascular disease: Monitor blood pressure and consider cardioprotective strategies 1

Alternative Options When NSAIDs Are Contraindicated

COX-2 Selective Inhibitors

• Celecoxib 200 mg once or twice daily provides comparable analgesia to non-selective NSAIDs with reduced GI toxicity 1
• Critical caveat: COX-2 inhibitors still carry renal toxicity risk and potential cardiovascular risks, particularly rofecoxib (now withdrawn) 1
• Consider only when patient has GI ulcer history but NSAIDs are otherwise appropriate 1

Weak Opioids for Moderate Pain

• Codeine 30-60 mg every 4-6 hours (combined with aspirin if not allergic) for moderate pain when NSAIDs contraindicated 1
• Tramadol 50-100 mg every 6 hours (maximum 400 mg/day) as alternative weak opioid 1
• Important limitation: Codeine has inferior efficacy compared to NSAIDs (NNT 4.4 vs 2.7), CNS depressant effects, and variable metabolism due to CYP2D6 polymorphisms 1

Topical Analgesics

• Topical NSAIDs (diclofenac gel, ibuprofen gel) for localized musculoskeletal pain provide effective analgesia with minimal systemic absorption 1
• Capsaicin cream or methyl salicylate for localized joint pain 1

Dosing Algorithm by Clinical Scenario

Mild Pain or Fever (NRS <3/10)

1. First choice: Ibuprofen 400 mg every 6-8 hours 1, 2
2. If GI risk factors present: Topical NSAIDs for localized pain 1
3. If NSAIDs contraindicated: Consider aspirin 500-1000 mg every 4-6 hours (if no aspirin allergy) 1

Moderate Pain (NRS 3-6/10)

1. First choice: Ibuprofen 600 mg every 6-8 hours or naproxen 500 mg every 12 hours 1
2. If NSAIDs contraindicated: Codeine 30-60 mg or tramadol 50-100 mg every 6 hours 1
3. If elderly or fall risk: Avoid opioids; use topical NSAIDs instead 4

Severe Pain (NRS >6/10)

1. First choice: Strong opioids (morphine 5-10 mg oral every 4 hours or hydromorphone 1-2 mg) with ibuprofen 400-600 mg if not contraindicated 1
2. Alternative: Fentanyl IV 1 mcg/kg for acute severe pain in emergency settings 1

Common Pitfalls to Avoid

• Never assume paracetamol allergy includes aspirin or NSAIDs – these are chemically distinct classes with different allergenic profiles 1
• Do not use NSAIDs long-term (>10 days) without gastroprotection in patients with risk factors 1, 3
• Avoid combining multiple NSAIDs – this increases toxicity without improving efficacy 3
• Do not prescribe codeine-paracetamol combinations to paracetamol-allergic patients (obviously contains paracetamol) 1
• Screen for concurrent aspirin use if prescribing ibuprofen, as ibuprofen may interfere with aspirin's antiplatelet effects 2

Gastroprotection Strategy When NSAIDs Required Long-Term

• Proton pump inhibitor (omeprazole 20 mg daily) or COX-2 selective inhibitor for patients with GI risk factors requiring prolonged NSAID therapy 1
• Risk factors include: age >65, history of peptic ulcer, concurrent corticosteroids/anticoagulants, high-dose or multiple NSAID use 1