Contraindications of Omeprazole
Omeprazole is absolutely contraindicated in patients with known hypersensitivity to omeprazole or any substituted benzimidazole, and in patients receiving rilpivirine-containing products. 1
Absolute Contraindications
Hypersensitivity Reactions
Known hypersensitivity to omeprazole or any substituted benzimidazole is an absolute contraindication. 1 This includes patients who have experienced:
Cross-reactivity between different proton pump inhibitors has been documented, meaning patients with hypersensitivity to omeprazole may also react to pantoprazole and other PPIs. 4 If a patient has experienced neutropenia or allergic reactions to one PPI, close monitoring is required if switching to another PPI, as immune-mediated cross-reactivity can occur. 4
Drug-Drug Interactions
Omeprazole is absolutely contraindicated in patients taking rilpivirine-containing products (EDURANT, COMPLERA) used to treat HIV-1. 1 This is because PPIs significantly reduce the absorption and efficacy of rilpivirine. 1
While not an absolute contraindication, omeprazole significantly reduces the antiplatelet effects of clopidogrel through CYP2C19 inhibition. 5 In patients requiring dual antiplatelet therapy after acute coronary syndrome or stent placement, if a PPI is needed for gastrointestinal protection, pantoprazole or rabeprazole should be used instead of omeprazole or esomeprazole, as they have the lowest propensity for clinically relevant interactions. 5
Important Clinical Caveats
Combination Antibiotic Therapy
- When omeprazole is used in combination with antibiotics (clarithromycin and amoxicillin) for H. pylori eradication, the contraindications of those antibacterial agents must also be considered. 1
Rechallenge Considerations
Rechallenge with omeprazole in patients with previous hypersensitivity reactions should only be attempted in a hospital setting with immediate access to emergency treatment. 2 One case demonstrated that the allergic reaction was to the drug itself, not the capsule shell, when enteric-coated granules were tested separately. 2
Desensitization protocols exist for patients who require omeprazole despite previous anaphylaxis, starting at 0.001 mg and escalating to full dose over 5.6 hours, but this should only be performed in specialized settings with appropriate monitoring. 3
Drug Interactions Requiring Caution (Not Absolute Contraindications)
Omeprazole significantly affects the pharmacokinetics of multiple medications through CYP450 inhibition, P-glycoprotein inhibition, or gastric acid suppression: 6
- Antiretrovirals: atazanavir, nelfinavir, indinavir (reduced absorption) 6
- Immunosuppressants: tacrolimus, mycophenolate mofetil (altered levels) 6
- Antifungals: itraconazole, posaconazole (reduced absorption) 6
- Other medications: diazepam, carbamazepine, clozapine, methotrexate, digoxin (increased levels) 6
- Iron supplementation (reduced absorption) 6
In these cases, alternative PPIs with different interaction profiles or H2-receptor antagonists should be considered rather than omeprazole. 6