Introduction to Omeprazole
Omeprazole, often known by the brand name Prilosec, is a widely used proton pump inhibitor (PPI) [1.6.9]. It works by decreasing the amount of acid produced in the stomach [1.6.9]. Doctors prescribe it to treat conditions such as gastroesophageal reflux disease (GERD), stomach and duodenal ulcers, Zollinger-Ellison syndrome, and to eradicate Helicobacter pylori bacteria in conjunction with antibiotics [1.6.1, 1.6.9]. While generally considered safe for short-term use, its widespread prescription—making up 44% of PPI use globally—means that the potential for drug interactions is a significant concern [1.6.1].
How Omeprazole Causes Drug Interactions
Omeprazole can interfere with other drugs in two primary ways:
- Altering Stomach pH: By reducing stomach acid, omeprazole can decrease the absorption of drugs that require an acidic environment to dissolve and work properly. This includes certain antifungals and HIV medications [1.2.1, 1.2.4]. Conversely, it can increase the absorption of other drugs like digoxin [1.2.4].
- Inhibiting Liver Enzymes: Omeprazole is metabolized by and can inhibit liver enzymes, particularly CYP2C19 and to a lesser extent, CYP3A4 [1.2.1, 1.3.4]. Many other drugs rely on these same enzymes for their metabolism. By inhibiting these enzymes, omeprazole can slow down the breakdown of other medications, leading to higher, potentially toxic levels in the blood. It can also prevent the activation of prodrugs, which need to be metabolized to become effective [1.3.5].
Major Drug Interactions to Avoid
Certain medications have highly significant interactions with omeprazole, and a healthcare provider may recommend avoiding the combination altogether. Always consult your doctor before starting or stopping any medication.
Clopidogrel (Plavix)
This is one of the most well-documented and critical interactions. Clopidogrel is an antiplatelet medication used to prevent heart attacks and strokes [1.3.4]. It's a prodrug that requires activation by the CYP2C19 enzyme [1.3.5].
- Interaction: Omeprazole significantly inhibits CYP2C19, which can reduce the conversion of clopidogrel to its active form. This reduces its antiplatelet effect, potentially leaving the patient less protected against blood clots [1.3.3, 1.3.6].
- Management: The U.S. Food and Drug Administration (FDA) advises against the concurrent use of omeprazole and clopidogrel [1.3.3, 1.3.5]. Taking the doses 12 hours apart does not reduce this interaction [1.3.3]. Alternative PPIs like pantoprazole or rabeprazole, which have less effect on CYP2C19, may be considered [1.2.1, 1.3.5].
Methotrexate
Used to treat cancer and autoimmune diseases like rheumatoid arthritis, methotrexate's toxicity is a major concern [1.4.2, 1.4.3].
- Interaction: Omeprazole can reduce the kidneys' ability to clear methotrexate from the body, leading to elevated and prolonged levels of the drug in the blood [1.4.1, 1.4.3]. This increases the risk of serious side effects, including bone marrow suppression, kidney damage, and liver toxicity [1.4.3, 1.4.5].
- Management: The risk is highest with high-dose methotrexate therapy [1.4.4]. Close monitoring is essential, and a temporary withdrawal of the PPI may be necessary [1.4.4]. An H2-receptor antagonist (like famotidine) is a recommended alternative [1.2.1].
Certain HIV Medications
Omeprazole can significantly decrease the effectiveness of certain antiretroviral drugs used to treat HIV.
- Interaction: By increasing stomach pH, omeprazole reduces the absorption of drugs like atazanavir and rilpivirine, leading to lower blood levels and potential treatment failure [1.2.1].
- Management: Co-administration is generally not recommended. Alternative acid-suppressing therapies, such as an H2 antagonist administered at a specific time, may be an option for rilpivirine [1.2.1].
Antifungal Agents (Azoles)
- Interaction: The absorption of antifungals like itraconazole and ketoconazole is dependent on an acidic stomach environment. Omeprazole reduces their absorption, potentially making them less effective at treating fungal infections [1.2.3, 1.2.4].
- Management: It is often recommended to avoid using PPIs with these agents. One strategy to counteract this effect is to take the antifungal with an acidic beverage like a cola [1.2.1].
Comparison of Key Omeprazole Interactions
| Interacting Drug | Mechanism of Interaction | Potential Consequence | Management Strategy |
|---|---|---|---|
| Clopidogrel | Inhibition of CYP2C19 enzyme, reducing drug activation [1.3.5] | Decreased antiplatelet effect, increased risk of cardiovascular events [1.3.3] | Avoid combination; use alternative PPI like pantoprazole [1.3.5] |
| Methotrexate | Decreased renal clearance [1.4.3] | Increased methotrexate levels and risk of toxicity [1.4.1] | Avoid if possible, especially with high doses; monitor levels; consider H2 antagonists [1.2.1, 1.4.4] |
| Warfarin | Decreased elimination by the liver [1.2.4] | Increased anticoagulant effect, higher risk of bleeding [1.2.3] | Monitor INR closely and adjust warfarin dose as needed [1.2.3] |
| Citalopram | Inhibition of CYP2C19 enzyme, reducing drug metabolism [1.2.2] | Increased citalopram levels, risk of side effects like QT prolongation | Dose adjustment and cardiac monitoring may be required |
| Atazanavir/Rilpivirine | Decreased absorption due to higher stomach pH [1.2.1] | Reduced antiviral effectiveness, risk of viral resistance [1.2.1] | Avoid combination; use alternative acid reducers if necessary [1.2.1] |
| St. John's Wort | Induces enzymes (CYP2C19/CYP3A) that metabolize omeprazole [1.2.1] | Decreased omeprazole effectiveness [1.5.2] | Avoid combination [1.5.2] |
Other Notable Interactions
Moderate Interactions
- Warfarin: Omeprazole can decrease the liver's clearance of this blood thinner, potentially increasing its effects and the risk of bleeding. Close monitoring is essential [1.2.3, 1.2.4].
- Diazepam (Valium) & Citalopram (Celexa): Omeprazole can inhibit the metabolism of these drugs, leading to higher concentrations and increased risk of side effects [1.2.1, 1.2.2].
- Phenytoin: An epilepsy medicine whose breakdown can be slowed by omeprazole, increasing its levels [1.2.3].
- Tacrolimus: An immunosuppressant used in transplant patients. Omeprazole can increase its levels, especially in certain genetic subtypes [1.2.1].
- Digoxin: A heart medication. Omeprazole can increase its absorption, raising the risk of toxicity [1.2.4].
Supplement and Food Interactions
- St. John's Wort: This herbal supplement can speed up the elimination of omeprazole, making it less effective. It should not be taken with omeprazole [1.5.2].
- Vitamin B12: Long-term use of omeprazole (typically over two years) can interfere with the absorption of vitamin B12 from food, potentially leading to a deficiency [1.5.4].
- Iron Supplements: Omeprazole can decrease the absorption of oral iron supplements [1.2.1].
- Grape Juice: Consuming grape juice can reduce the effectiveness of omeprazole by activating enzymes that break it down more quickly [1.5.1].
- Food: Omeprazole should ideally be taken on an empty stomach, about 30-60 minutes before a meal, as food can reduce its absorption and effectiveness [1.4.3, 1.5.5].
Conclusion
Omeprazole is a highly effective medication for acid-related conditions, but its potential for drug interactions is significant. By altering stomach acidity and affecting liver enzymes, it can change the way the body processes a wide range of other drugs and supplements. The most critical interactions to be aware of are with clopidogrel and high-dose methotrexate. It is imperative for patients to provide their healthcare provider with a complete list of all medications, over-the-counter drugs, and herbal supplements they are taking. Never make changes to your medication regimen without professional medical advice. For more detailed information, you can consult authoritative sources such as the National Institutes of Health [1.2.1].
