What should you not mix with omeprazole?

Omeprazole, one of the most widely prescribed medications worldwide, is used to treat conditions like GERD and peptic ulcers. However, taking it alongside certain other medications can lead to dangerous interactions, significantly impacting their effectiveness or causing serious health risks. Understanding what you should not mix with omeprazole is vital for preventing adverse effects and ensuring your treatment is safe.

Quick Summary

This guide details important drug-drug interactions involving omeprazole, including those with blood thinners like clopidogrel and warfarin, HIV medications, antifungals, and more, for enhanced patient safety.

Key Points

• Blood Thinners: Avoid combining omeprazole with antiplatelets like clopidogrel or anticoagulants like warfarin, as this can increase your risk of bleeding or reduce their effectiveness.

• HIV Medications: Do not mix omeprazole with certain HIV antiretrovirals, including atazanavir, nelfinavir, and rilpivirine, as it can drastically decrease their absorption and lead to treatment failure.

• Cancer & Immunosuppressants: Omeprazole can increase the toxicity of methotrexate and raise blood levels of tacrolimus and mycophenolate mofetil, requiring careful monitoring.

• Antifungals: The absorption of certain oral antifungals, such as itraconazole and posaconazole capsules, can be compromised by omeprazole due to reduced stomach acid.

• Nutrient Deficiencies: Long-term omeprazole use is associated with reduced absorption of Vitamin B12 and iron, potentially leading to deficiencies.

• Herbal Supplements: The herbal remedy St. John's wort can decrease omeprazole's effectiveness and should be avoided.

• Altered Drug Metabolism: Omeprazole inhibits a liver enzyme (CYP2C19), affecting how your body processes many other medications, including certain antidepressants and benzodiazepines.

Understanding How Omeprazole Can Cause Drug Interactions

Omeprazole belongs to a class of drugs called proton pump inhibitors (PPIs) that work by reducing stomach acid. This primary action can cause two main types of interactions with other substances:

• Altered Absorption: By decreasing stomach acid, omeprazole can hinder the absorption of medications or nutrients that require an acidic environment to dissolve properly.
• Altered Metabolism: Omeprazole is metabolized in the liver by specific enzymes, particularly CYP2C19. It can inhibit this enzyme, which can affect the metabolism and clearance of other drugs that also use this pathway, leading to either increased drug levels (toxicity) or decreased drug levels (reduced effectiveness).

Serious Drug Interactions to Avoid with Omeprazole

Certain medications should not be mixed with omeprazole or require close medical supervision and dosage adjustment due to the potential for significant harm.

Antiplatelet Drugs and Blood Thinners

Omeprazole can interfere with blood-thinning medications, creating a serious risk.

• Clopidogrel (Plavix): This antiplatelet drug is a prodrug, meaning it requires activation by the CYP2C19 enzyme to become effective. Omeprazole inhibits this enzyme, which can reduce clopidogrel's antiplatelet effect and increase the risk of blood clots and cardiovascular events. The FDA has issued a warning about this interaction.
• Warfarin (Coumadin, Jantoven): Omeprazole can increase the levels of warfarin in the body, which can lead to a dangerously increased risk of bleeding. Patients on both medications need frequent monitoring of their International Normalized Ratio (INR).

HIV Medications

Several antiretroviral drugs used to treat HIV are affected by omeprazole.

• Atazanavir, Nelfinavir, and Rilpivirine: These medications rely on stomach acid for proper absorption. By reducing gastric acid, omeprazole can significantly decrease the blood levels of these drugs, potentially leading to treatment failure and viral resistance. Concomitant use is generally not recommended.

Cancer and Immunosuppressant Drugs

• Methotrexate: High-dose methotrexate, a drug used for cancer and autoimmune conditions, can become toxic when mixed with omeprazole. Omeprazole can block the renal elimination of methotrexate, causing its levels to rise to dangerous concentrations in the body. Close monitoring is necessary.
• Tacrolimus: This immunosuppressant, used to prevent organ rejection, is metabolized by an enzyme also inhibited by omeprazole. Coadministration can cause increased tacrolimus levels, requiring careful monitoring.
• Mycophenolate mofetil: The absorption of this immunosuppressant can be reduced by omeprazole, potentially decreasing its effectiveness.

Antifungal Medications

Certain antifungals are dependent on an acidic stomach environment for proper absorption.

• Itraconazole and Posaconazole (capsules): Omeprazole can drastically lower the absorption of these oral antifungals, rendering them ineffective. Separating doses or using an alternative acid suppressant may be necessary. Itraconazole oral solution may be less affected.

Certain Antidepressants

• Citalopram (Celexa): Omeprazole can increase citalopram levels by affecting its metabolism, which can increase the risk of heart rhythm problems (prolonged QT interval) and potentially lead to serotonin syndrome. Dose adjustments may be required.

Benzodiazepines

• Diazepam (Valium): Omeprazole can decrease the clearance of diazepam from the body, causing an increase in its levels and increasing the risk of side effects like confusion and ataxia. Other benzodiazepines like oxazepam or lorazepam may be safer alternatives.

Foods, Herbs, and Vitamins to Watch For

Beyond prescription drugs, other items can interact with omeprazole.

Herbal Supplements

• St. John's Wort: This herbal remedy, often used for depression, can reduce the effectiveness of omeprazole by inducing the enzyme that metabolizes it.

Nutrients

• Iron: Long-term omeprazole use can hinder the absorption of non-heme iron (from plant-based sources) due to reduced stomach acid. This can lead to iron deficiency and requires careful management.
• Vitamin B12: Similar to iron, the absorption of vitamin B12 is dependent on stomach acid. Chronic omeprazole use, especially for more than a year, has been linked to vitamin B12 deficiency.

Lifestyle and Dietary Considerations

• Alcohol: While not directly interacting with the drug's mechanism, alcohol increases stomach acid production, which can counteract omeprazole's effects and worsen symptoms like heartburn.
• Foods: For people with acid reflux or GERD, certain foods like spicy, fatty, or acidic foods can worsen symptoms, even while on omeprazole.

Comparison of Omeprazole and Other PPIs for Select Interactions

Some PPIs have different metabolic pathways and may be safer alternatives in certain situations. It is essential to discuss these alternatives with a healthcare provider.

Interacting Medication	Risk with Omeprazole	Potential Alternative PPI (consult physician)	Why an Alternative is Needed
Clopidogrel	Reduced antiplatelet effect via CYP2C19 inhibition; increased risk of blood clots.	Pantoprazole or Rabeprazole.	Less inhibitory effect on CYP2C19.
Warfarin	Increased warfarin levels, boosting bleeding risk.	Pantoprazole or Rabeprazole.	Less inhibitory effect on CYP2C19.
Atazanavir	Decreased absorption and effectiveness; potential viral resistance.	Generally, PPIs are not recommended. Famotidine (H2 blocker) may be used with careful timing.	Dependent on acidic stomach environment for absorption.
Methotrexate	Increased methotrexate toxicity via renal elimination inhibition.	H2 antagonists (like ranitidine) may be safer; requires careful monitoring.	Omeprazole blocks renal excretion.
Diazepam	Increased diazepam levels and toxicity via CYP2C19 inhibition.	Pantoprazole or Rabeprazole.	Less inhibitory effect on CYP2C19.
Itraconazole	Decreased absorption and effectiveness.	Consider alternative antifungal or formulation (e.g., oral solution).	Absorption is pH-dependent.

How to Manage Medication and Substance Interactions

1. Always Consult a Healthcare Provider: Before starting or stopping any medication, including over-the-counter omeprazole, discuss all other drugs, supplements, and vitamins you take with your doctor or pharmacist. They can perform a comprehensive medication review.
2. Report Side Effects: If you experience any unusual symptoms like bleeding, bruising, or dizziness while taking omeprazole with other medications, inform your doctor immediately.
3. Monitor Closely: For unavoidable combinations, such as warfarin and omeprazole, a physician will schedule frequent monitoring of blood tests like INR.
4. Consider Alternatives: As shown in the table above, sometimes a different PPI or another class of acid-reducing medication (like an H2 blocker) can be used to avoid a problematic interaction.
5. Time Your Doses: Some interactions can be minimized by separating the administration times of the two medications. Consult your pharmacist for specific advice.

Conclusion

While omeprazole is a highly effective medication for treating acid-related digestive problems, it is not without risks, particularly concerning drug-drug interactions. By affecting critical metabolic enzymes and altering stomach acidity, omeprazole can dangerously impact the effectiveness of blood thinners, HIV drugs, and antifungals, as well as lead to long-term nutrient deficiencies. Responsible medication management starts with a full understanding of these potential risks. Always consult your healthcare provider about what you should not mix with omeprazole to ensure both your safety and the efficacy of your treatment plan.

National Center for Biotechnology Information: Pharmacokinetic drug interaction profile of omeprazole

Disclaimer: The information provided in this article is for educational purposes only and is not a substitute for professional medical advice. Always consult with a qualified healthcare provider before making any decisions about your treatment.

Frequently Asked Questions

Is it safe to take omeprazole with clopidogrel (Plavix)?

Co-administration of omeprazole with clopidogrel is not recommended. Omeprazole can inhibit the enzyme needed to activate clopidogrel, reducing its effectiveness and potentially increasing the risk of blood clots. Your doctor may suggest an alternative PPI with a lower interaction risk, such as pantoprazole.

Can I take alcohol with omeprazole?

It is generally best to avoid alcohol while taking omeprazole. While alcohol doesn't directly affect how the medication works, it can increase stomach acid production and worsen the very symptoms (like heartburn) that omeprazole is meant to treat.

What foods or drinks should I avoid while on omeprazole?

While there are no specific food interactions, you should avoid foods and drinks that aggravate your acid reflux or heartburn symptoms. These can include spicy, fatty, and acidic foods, as well as caffeine, soda, and chocolate.

Does omeprazole interact with warfarin (Coumadin)?

Yes, omeprazole can increase the blood levels of warfarin, which can significantly raise the risk of serious bleeding. Patients taking this combination require close and frequent monitoring of their INR.

Is it okay to take omeprazole with vitamin supplements?

Omeprazole can interfere with the absorption of certain nutrients, including Vitamin B12 and iron, especially with long-term use. While it's fine to take a general multivitamin, if you have or are at risk for deficiencies, your doctor may need to monitor your levels or recommend specific supplementation.

What is the interaction between omeprazole and methotrexate?

Combining omeprazole with methotrexate, especially high-dose therapy, can increase methotrexate levels in the body, leading to toxic effects. This is because omeprazole can block the renal elimination of methotrexate. A doctor must closely monitor this combination.

Can I use over-the-counter omeprazole if I take other medications?

Even over-the-counter versions of omeprazole carry the same interaction risks as prescription versions. It is crucial to inform your pharmacist and doctor about all medications, including OTCs, to screen for potential interactions before starting treatment.

What is the effect of St. John's wort with omeprazole?

You should not take St. John's wort while on omeprazole. It can decrease the effectiveness of omeprazole by inducing the liver enzymes that break it down, causing lower drug concentrations in your body.