Summary

The interaction between methotrexate and tetracycline is generally considered minor to moderate, with tetracycline potentially increasing methotrexate levels through reduced renal clearance. While not contraindicated, this combination requires careful monitoring for signs of methotrexate toxicity, particularly in patients with compromised kidney function.

Introduction

Methotrexate is an antimetabolite and antifolate drug primarily used as a chemotherapy agent for various cancers and as an immunosuppressant for autoimmune conditions like rheumatoid arthritis and psoriasis. It works by inhibiting dihydrofolate reductase, blocking DNA synthesis and cell division. Tetracycline is a broad-spectrum antibiotic belonging to the tetracycline class, commonly prescribed for bacterial infections including respiratory tract infections, acne, and certain sexually transmitted infections. It functions by inhibiting bacterial protein synthesis through binding to the 30S ribosomal subunit.

Mechanism of Interaction

The interaction between methotrexate and tetracycline occurs primarily through interference with methotrexate's renal elimination. Tetracycline can compete with methotrexate for active tubular secretion in the kidneys, potentially reducing methotrexate clearance and leading to elevated plasma concentrations. Additionally, tetracycline may interfere with the enterohepatic circulation of methotrexate by altering gut bacteria that normally cleave methotrexate metabolites, potentially prolonging methotrexate exposure. This mechanism is similar to other antibiotics that can affect methotrexate pharmacokinetics.

Risks and Symptoms

The primary clinical risk of this interaction is increased methotrexate toxicity, which can manifest as bone marrow suppression (leucopenia, thrombocytopenia, anemia), gastrointestinal toxicity (mucositis, diarrhea, nausea), hepatotoxicity, and nephrotoxicity. Patients at higher risk include those with pre-existing kidney dysfunction, elderly patients, those receiving high-dose methotrexate therapy, or patients with dehydration. The interaction significance is generally rated as moderate, meaning it may require dosage adjustments or increased monitoring but is not typically contraindicated when clinically necessary.

Management and Precautions

Clinical management involves enhanced monitoring of methotrexate levels and toxicity markers when tetracycline is co-administered. Key monitoring parameters include complete blood count, liver function tests, kidney function (creatinine, BUN), and clinical assessment for signs of methotrexate toxicity. Consider temporary methotrexate dose reduction or increased monitoring frequency during tetracycline therapy. Ensure adequate hydration and consider leucovorin rescue if signs of toxicity develop. Alternative antibiotics with less interaction potential may be preferred when clinically appropriate. Healthcare providers should maintain close communication with patients regarding symptoms of methotrexate toxicity and ensure proper timing of laboratory monitoring.

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.

Tetracycline interactions with food and lifestyle

Tetracycline should be taken on an empty stomach, at least 1 hour before or 2 hours after meals, as food significantly reduces absorption. Avoid dairy products (milk, cheese, yogurt), calcium supplements, iron supplements, magnesium-containing antacids, and aluminum-containing antacids within 2-3 hours of taking tetracycline, as these can form chelation complexes that dramatically reduce drug absorption. Avoid alcohol consumption during tetracycline treatment as it may increase the risk of liver toxicity and reduce the effectiveness of the antibiotic.