Summary

The interaction between methotrexate and lansoprazole is generally considered minor to moderate in clinical significance. Lansoprazole may potentially reduce methotrexate elimination by affecting renal clearance, though this interaction is less well-documented compared to other proton pump inhibitors.

Introduction

Methotrexate is an antimetabolite medication primarily used as a disease-modifying antirheumatic drug (DMARD) for rheumatoid arthritis and psoriasis, and as a chemotherapy agent for various cancers. It works by inhibiting dihydrofolate reductase, interfering with DNA synthesis and cell division. Lansoprazole belongs to the proton pump inhibitor (PPI) class of medications, commonly prescribed for gastroesophageal reflux disease (GERD), peptic ulcers, and other acid-related disorders. It reduces stomach acid production by irreversibly blocking the H+/K+-ATPase enzyme in gastric parietal cells.

Mechanism of Interaction

The potential interaction between methotrexate and lansoprazole may occur through effects on renal elimination pathways. Methotrexate is primarily eliminated unchanged through the kidneys via glomerular filtration and active tubular secretion. Some proton pump inhibitors have been reported to potentially interfere with renal organic anion transporters, which could theoretically reduce methotrexate clearance. However, the specific mechanism and clinical significance of lansoprazole's effect on methotrexate elimination is not as well-established as with some other PPIs, and the interaction appears to be less pronounced than with omeprazole.

Risks and Symptoms

The primary clinical risk of this interaction is the potential for increased methotrexate plasma concentrations, which could lead to enhanced toxicity. Methotrexate toxicity can manifest as bone marrow suppression (leucopenia, thrombocytopenia, anemia), gastrointestinal effects (mucositis, nausea, diarrhea), hepatotoxicity, and nephrotoxicity. However, clinically significant interactions between lansoprazole and methotrexate appear to be relatively uncommon compared to other PPI-methotrexate combinations. The risk may be higher in patients with pre-existing renal impairment, elderly patients, or those receiving high-dose methotrexate therapy.

Management and Precautions

When methotrexate and lansoprazole are used concurrently, healthcare providers should implement appropriate monitoring strategies. Regular monitoring of complete blood count, liver function tests, and renal function is recommended, particularly during the initial weeks of combination therapy. Patients should be educated about signs and symptoms of methotrexate toxicity and advised to report any unusual symptoms promptly. Consider more frequent laboratory monitoring in high-risk patients or those receiving higher methotrexate doses. If clinically significant toxicity occurs, temporary discontinuation of one or both medications may be necessary. Alternative acid suppression therapy or methotrexate dosing adjustments should be considered based on individual patient factors and clinical response.

Methotrexate interactions with food and lifestyle

Alcohol consumption should be avoided or strictly limited while taking methotrexate due to increased risk of liver toxicity and hepatotoxicity. Both methotrexate and alcohol can cause liver damage, and their combination significantly increases this risk. Patients should also maintain adequate hydration and avoid excessive sun exposure, as methotrexate can increase photosensitivity. Folic acid supplementation is commonly recommended to reduce certain side effects, though this should be discussed with a healthcare provider as timing and dosing are important.

Lansoprazole interactions with food and lifestyle

Lansoprazole should be taken on an empty stomach, preferably 30-60 minutes before meals, as food can significantly reduce its absorption and effectiveness. Alcohol consumption should be limited or avoided while taking lansoprazole, as alcohol can increase stomach acid production and counteract the medication's acid-reducing effects. Additionally, alcohol may worsen gastroesophageal reflux disease (GERD) symptoms that lansoprazole is intended to treat.