Can omeprazole cause pruritus in a patient with a complex medical history, including autoimmune or inflammatory conditions, and currently taking prednisone?

Can Omeprazole Cause Pruritus?

Yes, omeprazole can cause pruritus, and this is documented both in the FDA drug label and in multiple case reports of hypersensitivity reactions. 1

Evidence from FDA Drug Label

The FDA-approved prescribing information for omeprazole explicitly lists pruritus as a postmarketing adverse reaction. 1 Additional dermatologic reactions reported include:

• Rash (2% incidence in clinical trials) 1
• Pruritus (postmarketing reports) 1
• Severe skin reactions including Stevens-Johnson syndrome, toxic epidermal necrolysis, and erythema multiforme 1
• Urticaria and skin inflammation 1

Mechanism and Clinical Presentation

Pruritus from omeprazole can occur through two distinct mechanisms:

• Immediate hypersensitivity reactions: Urticaria, angioedema, and pruritus occurring within hours of administration, confirmed by positive intradermal skin testing 2, 3
• Delayed hypersensitivity reactions: Persistent pruritic eruptions developing after prolonged use (months to years), presenting as prurigo or fixed drug eruptions 4, 5

One documented case showed a patient developed persistent prurigo after more than 10 years of omeprazole use, with complete resolution after drug discontinuation and recurrence upon rechallenge. 4

Cross-Reactivity with Other Proton Pump Inhibitors

Clinical cross-reactivity occurs with other proton pump inhibitors (PPIs), including pantoprazole and lansoprazole. 4, 3 This suggests a class effect rather than a reaction to specific excipients. If omeprazole-induced pruritus is confirmed, avoid all PPIs unless desensitization is performed. 3

Management Algorithm

If pruritus develops in a patient taking omeprazole:

1. Discontinue omeprazole immediately and observe for symptom resolution over 1-2 weeks 4, 5

2. Assess severity of skin involvement:

   • For mild pruritus without rash: Apply topical emollients and moderate-potency corticosteroids 6
   • For pruritus with rash covering <10% body surface area: Use topical emollients and mild-to-moderate potency topical corticosteroids 7
   • For extensive rash or systemic symptoms: Consider systemic corticosteroids (prednisone 0.5-1 mg/kg/day) 7

3. Add oral antihistamines such as fexofenadine 180 mg or cetirizine 10 mg daily for symptomatic relief 7, 6

4. Switch to alternative acid suppression therapy:

   • H2-receptor antagonists (ranitidine, famotidine) are structurally unrelated and safe alternatives 7
   • Avoid other PPIs due to cross-reactivity 4

5. If PPI therapy is absolutely necessary, refer to allergy/immunology for desensitization protocol, which has been successfully performed starting at 0.001 mg and escalating to full dose over 5.6 hours 3

Special Considerations for Patients on Prednisone

In your patient already taking prednisone, the systemic corticosteroid may mask or reduce the severity of pruritus. 7 However:

• Do not assume prednisone eliminates the need for topical therapy 8
• Add high-lipid content emollients (preferred in elderly patients) and moderate-potency topical corticosteroids 6
• Consider topical menthol 0.5% for additional symptomatic relief 6

Critical Pitfalls to Avoid

• Do not rechallenge with omeprazole outside a monitored hospital setting, as life-threatening anaphylaxis has been reported 2, 3
• Do not assume the reaction is unrelated to omeprazole if the patient has been taking it for years without prior issues—delayed hypersensitivity can develop after prolonged exposure 4
• Do not switch to another PPI without allergy testing, as cross-reactivity is common 4, 3
• Monitor for progression to severe cutaneous adverse reactions (SCARs) including toxic epidermal necrolysis, which has been reported with omeprazole and carries high mortality 1, 9