Understanding What Medication Cannot Be Taken With Omeprazole

According to the U.S. Food and Drug Administration (FDA), omeprazole is contraindicated for patients taking rilpivirine-containing products due to significantly reduced drug exposure. This is just one example of the critical interactions to be aware of when considering what medication cannot be taken with omeprazole, as it can affect how other drugs are absorbed or processed by the body. Understanding these interactions is essential for patient safety and treatment efficacy.

Quick Summary

This article explores significant drug interactions with omeprazole, detailing how the medication's effects on stomach acid and liver enzymes can impact drugs like clopidogrel, certain HIV treatments, and warfarin. It highlights which medications are contraindicated or require dose adjustments and explains the underlying pharmacological mechanisms to promote safer medication management.

Key Points

• Clopidogrel is contraindicated with omeprazole: Omeprazole reduces the effectiveness of this antiplatelet drug by inhibiting the CYP2C19 enzyme.

• Certain HIV medications are poorly absorbed: Drugs like rilpivirine, atazanavir, and nelfinavir need stomach acid for absorption, which omeprazole reduces.

• Warfarin effects can be dangerously increased: The combination raises the risk of serious bleeding due to omeprazole's impact on warfarin metabolism.

• High-dose methotrexate can lead to toxicity: Concomitant use with omeprazole can prolong and elevate methotrexate levels, increasing the risk of toxicity.

• Certain antifungal drugs lose efficacy: The absorption of itraconazole and posaconazole is significantly reduced by omeprazole's acid-suppressing effects.

• Digoxin levels can become toxic: Omeprazole may increase digoxin levels in the blood, potentially causing toxicity in individuals with heart conditions.

• St. John's wort can reduce omeprazole effectiveness: This herbal supplement can decrease the concentration of omeprazole in the body, rendering it less effective.

• Always consult your doctor before combining medications: Never start or stop a medication without professional medical advice, especially when taking omeprazole.

Omeprazole, a proton pump inhibitor (PPI), is widely prescribed to treat conditions like gastroesophageal reflux disease (GERD) and peptic ulcers. While generally safe, its mechanism of action—namely, suppressing stomach acid and affecting liver enzymes—can lead to clinically significant interactions with numerous other medications. Being aware of what medication cannot be taken with omeprazole is vital for both prescribers and patients to prevent adverse effects and ensure treatment is effective.

Drug Interactions Caused by Changes in Gastric pH

Omeprazole works by blocking the enzyme system that produces stomach acid, thereby raising the gastric pH. This can impact the absorption of medications that require an acidic environment to dissolve properly, potentially diminishing their therapeutic effect.

• Certain Antiretrovirals (HIV Medications): Drugs like atazanavir, nelfinavir, and rilpivirine need an acidic environment for absorption. Combining them with omeprazole can lead to significantly decreased plasma concentrations, risking viral resistance and treatment failure. Rilpivirine is contraindicated with omeprazole.
• Some Antifungal Agents: Oral antifungals such as itraconazole and posaconazole depend on low gastric pH for absorption. Omeprazole can reduce their bioavailability and effectiveness, so alternatives to omeprazole are often preferred.
• Oral Iron Supplements: Omeprazole can impair the absorption of oral iron supplements by hindering the conversion of ferric to ferrous iron. Higher iron doses or alternative methods may be needed.
• Mycophenolate Mofetil (MMF): Used to prevent organ rejection, MMF absorption can be reduced by omeprazole, increasing the risk of rejection. Monitoring drug levels is crucial.

Interactions Caused by Liver Enzyme Inhibition

Omeprazole inhibits Cytochrome P450 2C19 (CYP2C19), a liver enzyme metabolizing many drugs. This inhibition can alter the metabolism of other medications, potentially leading to decreased effects or increased toxicity.

Critical Medications Affected by Omeprazole's Enzyme Inhibition

• Clopidogrel: This antiplatelet drug is a prodrug requiring CYP2C19 for activation. Omeprazole inhibits this process, reducing clopidogrel's antiplatelet effect and increasing cardiovascular risk. Regulatory bodies advise against their co-use, suggesting alternative PPIs.
• Warfarin: This blood thinner has a narrow therapeutic index. Omeprazole can inhibit its metabolism, increasing blood levels and bleeding risk. Close INR monitoring is necessary if the combination is unavoidable.
• Diazepam: Metabolized by CYP2C19, diazepam clearance is impaired by omeprazole. This can prolong sedation and increase side effects like confusion. Alternative benzodiazepines are safer.
• Phenytoin: This anti-seizure medication's metabolism is affected by omeprazole, leading to increased phenytoin concentrations and side effect risk. Monitoring levels and adjusting dosage is essential.
• Cilostazol: Used for peripheral artery disease, cilostazol metabolism can be inhibited by omeprazole, potentially increasing side effects. Co-administration may be avoided or dosages adjusted.
• Citalopram: Metabolized by CYP2C19, citalopram levels can increase with omeprazole. This raises the risk of heart rhythm problems and serotonin syndrome.

A Summary of Key Omeprazole Drug Interactions

Medication Class/Drug	Interaction with Omeprazole	Mechanism of Action	Clinical Ramifications
Clopidogrel (Plavix)	Reduced effectiveness	Omeprazole inhibits CYP2C19, reducing the conversion of clopidogrel to its active metabolite.	Increased risk of cardiovascular events, stroke, or stent thrombosis. Consider alternative PPI (pantoprazole).
HIV Medications (Atazanavir, Rilpivirine)	Reduced absorption	Omeprazole raises gastric pH, which is needed for the absorption of these drugs.	Potential for viral resistance and treatment failure. Avoid co-administration.
Warfarin (Coumadin)	Increased blood thinning effect	Omeprazole inhibits warfarin's metabolism via liver enzymes.	Increased risk of serious bleeding. Requires frequent INR monitoring and dose adjustments.
Methotrexate (High Dose)	Increased toxicity	Omeprazole may elevate and prolong serum methotrexate levels.	Potential for methotrexate toxicities. Temporary withdrawal of omeprazole may be necessary.
Digoxin (Lanoxin)	Increased toxicity	Omeprazole can increase digoxin absorption and impair its clearance.	Elevated digoxin levels can cause toxicity. Monitor digoxin levels and adjust dose if needed.
Antifungals (Itraconazole, Posaconazole)	Reduced effectiveness	Omeprazole raises gastric pH, needed for absorption.	May lead to treatment failure. Avoid use together or consider alternatives.
Diazepam (Valium)	Increased sedation/side effects	Omeprazole inhibits the CYP2C19 enzyme that metabolizes diazepam.	Increased plasma levels and prolonged effects, including confusion. Alternative benzodiazepines may be safer.

What to Do When an Interaction Occurs

If you are taking omeprazole and a potentially interacting medication, or if you need to start one, your healthcare provider will determine the best course of action. This might involve switching the PPI, adjusting the dosage, timing the doses, or using alternative treatments {Link: Dr.Oracle.ai https://www.droracle.ai/articles/15530/what-are-the-potential-drug-interactions-with-omeprazole-proton-pump-inhibitor}.

Conclusion

Omeprazole is an effective medication for acid-related conditions, but understanding its drug interactions is crucial {Link: Dr.Oracle.ai https://www.droracle.ai/articles/15530/what-are-the-potential-drug-interactions-with-omeprazole-proton-pump-inhibitor}. Interactions occur by altering gastric pH, affecting absorption of drugs like certain HIV medications and antifungals, and inhibiting liver enzymes, impacting metabolism of medications like clopidogrel, warfarin, and diazepam. These can lead to reduced effectiveness or dangerous drug buildup. Always inform your healthcare provider about all medications and supplements to ensure a safe treatment plan and never stop or start a new medication without consulting a professional.

A comprehensive list of potential omeprazole interactions is available on reputable medical websites such as the Mayo Clinic.

References

• Mayo Clinic. "Omeprazole (oral route) - Side effects & dosage." Accessed October 5, 2025. [https://www.mayoclinic.org/drugs-supplements/omeprazole-oral-route/description/drg-20066836]
• Dai, Y., et al. "Pharmacokinetic drug interaction profile of omeprazole with adverse consequences." International Journal of Clinical Pharmacology and Therapeutics, 2013. [https://pmc.ncbi.nlm.nih.gov/articles/PMC3671798/]
• RxList. "Prilosec (Omeprazole): Side Effects, Uses, Dosage, Interactions." Accessed October 5, 2025. [https://www.rxlist.com/prilosec-drug.htm]
• Ro.co. "Does Omeprazole Have Serious Drug Interactions?" Accessed October 5, 2025. [https://ro.co/health-guide/omeprazole-drug-interactions/]
• GoodRx. "The 10 Omeprazole Interactions Everyone Should Know." Accessed October 5, 2025. [https://www.goodrx.com/omeprazole/interactions]
• Drugs.com. "Omeprazole: Package Insert / Prescribing Information." Accessed October 5, 2025. [https://www.drugs.com/pro/omeprazole.html]
• FDA. "PLAVIX® (clopidogrel tablets) for oral use." Accessed October 5, 2025. [https://www.accessdata.fda.gov/drugsatfda_docs/label/2022/020839s078lbl.pdf]
• Specialist Pharmacy Service (SPS) NHS. "Using clopidogrel with proton pump inhibitors (PPIs)." Accessed October 5, 2025. [https://www.sps.nhs.uk/articles/using-clopidogrel-with-proton-pump-inhibitors-ppis/]
• Dr.Oracle.ai. "What are the potential drug interactions with omeprazole?" Accessed October 5, 2025. [https://www.droracle.ai/articles/15530/what-are-the-potential-drug-interactions-with-omeprazole-proton-pump-inhibitor]
• JAMA Network. "Navigating Drug Interactions with Proton Pump Inhibitors." Accessed October 5, 2025. [https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2820904]
• Dai, Y., et al. "Pharmacokinetic drug interaction profile of omeprazole with adverse consequences." International Journal of Clinical Pharmacology and Therapeutics, 2013. [https://pmc.ncbi.nlm.nih.gov/articles/PMC3671798/]
• Dai, Y., et al. "Pharmacokinetic drug interaction profile of omeprazole with adverse consequences." International Journal of Clinical Pharmacology and Therapeutics, 2013. [https://pmc.ncbi.nlm.nih.gov/articles/PMC3671798/]

Frequently Asked Questions

Can I take omeprazole and clopidogrel together?

No, co-administration of omeprazole with clopidogrel is generally not recommended, as omeprazole can significantly reduce clopidogrel's effectiveness, which can increase your risk of a heart attack or stroke. Your doctor may prescribe a different proton pump inhibitor (PPI) or an alternative medication.

Why can't I take certain HIV medications with omeprazole?

Certain HIV medications, such as rilpivirine, atazanavir, and nelfinavir, require an acidic stomach environment to be properly absorbed. Omeprazole raises the stomach's pH, which can prevent these drugs from being adequately absorbed, potentially leading to treatment failure and viral resistance.

What is the risk of taking warfarin with omeprazole?

The combination of warfarin and omeprazole can increase the anticoagulant effect of warfarin, raising the risk of serious bleeding. This happens because omeprazole inhibits liver enzymes that metabolize warfarin. If co-administration is necessary, your doctor will closely monitor your blood (INR).

Can omeprazole affect my antifungal medication?

Yes, omeprazole can reduce the absorption and effectiveness of certain oral antifungal drugs like itraconazole and posaconazole, which depend on stomach acid for absorption. Your doctor may advise against this combination or suggest alternatives.

What effect does omeprazole have on diazepam?

Omeprazole can increase the concentration of diazepam in your blood by inhibiting its metabolism, leading to a higher risk of side effects like excessive sedation, confusion, and ataxia. Your doctor may need to adjust your diazepam dose or switch you to a different medication.

Is it safe to take iron supplements with omeprazole?

Omeprazole can decrease the absorption of oral iron supplements by reducing stomach acid. This might require you to take a higher dose of iron for a longer period or switch to intravenous iron therapy.

Does St. John's wort interact with omeprazole?

Yes, St. John's wort can increase the rate at which omeprazole is broken down and eliminated from your body, reducing its effectiveness. This combination should be avoided.