Summary

The combination of methotrexate and furosemide can lead to increased methotrexate toxicity due to reduced renal clearance. This interaction requires careful monitoring and potential dose adjustments to prevent serious adverse effects.

Introduction

Methotrexate is an antimetabolite medication primarily used as a chemotherapy agent for various cancers and as an immunosuppressant for autoimmune conditions like rheumatoid arthritis and psoriasis. It belongs to the folate antagonist class of drugs. Furosemide is a potent loop diuretic commonly prescribed for treating fluid retention (edema) and high blood pressure. It works by blocking sodium and chloride reabsorption in the kidneys, promoting increased urine production.

Mechanism of Interaction

The interaction between methotrexate and furosemide occurs through multiple mechanisms. Furosemide can reduce renal blood flow and glomerular filtration rate, leading to decreased methotrexate clearance from the body. Additionally, both drugs compete for active tubular secretion in the kidneys through organic anion transporters. Furosemide may also cause dehydration and electrolyte imbalances, which can further impair kidney function and methotrexate elimination. This results in elevated methotrexate plasma concentrations and prolonged exposure to the drug.

Risks and Symptoms

The primary risk of this interaction is methotrexate toxicity, which can manifest as severe bone marrow suppression, mucositis, hepatotoxicity, and nephrotoxicity. Patients may experience symptoms including severe fatigue, increased infection risk due to low white blood cell counts, bleeding due to low platelet counts, mouth sores, nausea, vomiting, and potential liver or kidney damage. The interaction is considered clinically significant and can be life-threatening if not properly managed. Elderly patients and those with pre-existing kidney disease are at particularly high risk.

Management and Precautions

When concurrent use is necessary, close monitoring is essential. Methotrexate levels should be measured more frequently, and complete blood counts, liver function tests, and kidney function should be monitored closely. Consider reducing the methotrexate dose and ensure adequate hydration. Leucovorin rescue may be necessary if methotrexate levels become dangerously elevated. Alternative diuretics with less interaction potential should be considered when possible. Patients should be educated about signs of methotrexate toxicity and instructed to seek immediate medical attention if symptoms occur. Healthcare providers should verify kidney function before initiating this combination and maintain regular follow-up.

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.

Furosemide interactions with food and lifestyle

Furosemide should be taken with food or milk to reduce stomach upset. Alcohol consumption should be limited as it can increase the risk of dehydration and low blood pressure when combined with furosemide. Patients should maintain adequate fluid intake unless specifically restricted by their healthcare provider, as furosemide can cause dehydration. Salt substitutes containing potassium should be used cautiously, as furosemide can affect potassium levels. Excessive sun exposure should be avoided as furosemide may increase sensitivity to sunlight.