Lansoprazole, a proton pump inhibitor (PPI), works by reducing the amount of acid produced in the stomach [1.4.3]. It is commonly used to treat conditions like gastroesophageal reflux disease (GERD), stomach ulcers, and erosive esophagitis [1.4.3]. While effective, lansoprazole can interact with numerous other medications, altering their effects and potentially leading to serious health risks. It is essential to inform your doctor about all prescription drugs, over-the-counter medicines, and herbal supplements you are taking [1.4.1].
How Lansoprazole Causes Drug Interactions
Lansoprazole can interfere with other drugs in two primary ways:
1. Altering Stomach pH
By decreasing stomach acid, lansoprazole can affect the absorption of drugs that require an acidic environment to be broken down and absorbed properly [1.3.5]. This can make these medications less effective.
- Antifungals: Medications like ketoconazole and itraconazole require stomach acid for absorption. Lansoprazole can reduce their effectiveness [1.2.1, 1.3.5].
- HIV Medications: Certain HIV drugs, such as atazanavir and rilpivirine, are less effective when taken with PPIs [1.3.2, 1.4.2]. Co-administration with rilpivirine-containing products is contraindicated [1.4.2].
- Iron Salts: The absorption of iron supplements can be reduced in a less acidic stomach environment [1.2.2].
2. Affecting Liver Enzymes
Lansoprazole is metabolized by enzymes in the liver, primarily CYP2C19 [1.5.3]. It can inhibit this enzyme, slowing down the metabolism of other drugs that rely on the same pathway. This can lead to increased concentrations of those drugs in the blood, raising the risk of toxicity and side effects [1.5.3, 1.7.1]. Conversely, some drugs can affect these enzymes and alter the concentration of lansoprazole itself [1.2.1].
Major Drug Interactions with Lansoprazole
Certain medications pose a significant risk when taken with lansoprazole and should either be avoided or used only with close medical supervision.
Methotrexate
Used to treat cancer and autoimmune diseases like rheumatoid arthritis, methotrexate's clearance can be reduced by PPIs like lansoprazole [1.6.1, 1.6.4]. This can lead to elevated and prolonged serum levels of methotrexate, potentially causing toxicity [1.4.2, 1.6.2]. Symptoms of methotrexate toxicity include bone marrow suppression, gastrointestinal issues, and kidney damage [1.6.4]. For patients on high-dose methotrexate, a temporary withdrawal of lansoprazole may be considered [1.4.2].
Warfarin
Warfarin is a blood thinner used to prevent blood clots [1.5.3]. Lansoprazole can inhibit the metabolism of warfarin, potentially increasing its anticoagulant effect and elevating the International Normalized Ratio (INR) [1.5.3]. This heightens the risk of bleeding [1.5.1]. Patients taking both medications require close monitoring of their INR, especially when starting, stopping, or changing the dose of lansoprazole [1.5.5].
Clopidogrel
Clopidogrel is an antiplatelet medication used to prevent heart attacks and strokes [1.7.3]. It is a prodrug that requires activation by the CYP2C19 enzyme [1.7.1]. Since lansoprazole inhibits this enzyme, it can reduce clopidogrel's conversion to its active form, diminishing its antiplatelet effect [1.7.1, 1.7.2]. This interaction may increase the risk of major adverse cardiovascular events (MACEs), such as stent thrombosis or myocardial infarction [1.7.4]. Some studies suggest that lansoprazole has one of the highest risks for increasing MACEs when combined with clopidogrel compared to other PPIs [1.7.4, 1.7.6].
Other Significant Interactions
- Rilpivirine: An HIV medication. Co-administration with PPIs is contraindicated due to a significant decrease in rilpivirine's effectiveness [1.4.2].
- Digoxin: A heart medicine. Lansoprazole can increase digoxin levels in the blood, raising the risk of serious side effects [1.3.1, 1.3.5].
- Tacrolimus: An immunosuppressant used to prevent organ transplant rejection. Lansoprazole can increase blood levels of tacrolimus, which can be dangerous [1.3.2, 1.3.4].
- St. John's Wort: This herbal supplement for depression can decrease the effectiveness of lansoprazole [1.3.1, 1.3.5].
- Rifampin: An antibiotic that can cause lansoprazole to be metabolized faster, reducing its effectiveness [1.3.1].
Comparison of Lansoprazole Interactions
| Medication | Mechanism of Interaction | Potential Consequence | Management Recommendation |
|---|---|---|---|
| Methotrexate | Decreased renal clearance of methotrexate [1.6.4] | Increased risk of methotrexate toxicity [1.6.1] | Avoid or use with close monitoring; consider temporary PPI withdrawal with high-dose methotrexate [1.4.2] |
| Warfarin | Inhibition of CYP2C19, reducing warfarin metabolism [1.5.3] | Increased anticoagulant effect and bleeding risk [1.5.1] | Frequent INR monitoring, especially at initiation or discontinuation of lansoprazole [1.5.5] |
| Clopidogrel | Inhibition of CYP2C19, preventing clopidogrel activation [1.7.1] | Reduced antiplatelet effect, increased risk of cardiovascular events [1.7.4] | Avoid combination; consider alternative acid-suppressing therapy like an H2-receptor antagonist [1.7.5] |
| Rilpivirine | Increased gastric pH reduces absorption | Loss of virologic response | Contraindicated [1.4.2] |
| Ketoconazole | Increased gastric pH reduces absorption [1.3.5] | Decreased antifungal effectiveness [1.3.5] | Monitor effectiveness; consider alternative antifungal or acid-suppressing therapy |
Conclusion
While lansoprazole is a highly effective medication for acid-related stomach issues, its potential for drug interactions is significant. The most critical interactions involve medications like methotrexate, warfarin, and clopidogrel, where the consequences can be severe. Alterations in stomach pH and interference with liver enzymes are the main mechanisms behind these interactions. It is imperative for patients to maintain open communication with their healthcare providers, disclosing all medications and supplements they use to ensure safety and therapeutic effectiveness. Never start, stop, or change the dose of any medication without consulting a doctor first [1.3.7].
For more detailed information on drug interactions, you can consult the Drugs.com Interaction Checker. This is an authoritative source for verifying potential interactions.
