Summary

The interaction between methotrexate and tetracycline is generally considered minor to moderate, with tetracycline potentially affecting methotrexate absorption and elimination. While not contraindicated, this combination requires careful monitoring for signs of methotrexate toxicity, particularly in patients with compromised renal function.

Introduction

Methotrexate is an antifolate medication 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 works by inhibiting bacterial protein synthesis through binding to the 30S ribosomal subunit.

Mechanism of Interaction

The interaction between methotrexate and tetracycline occurs through multiple potential mechanisms. Tetracycline may interfere with methotrexate's renal elimination by competing for active tubular secretion pathways, potentially leading to increased methotrexate plasma concentrations. Additionally, tetracycline can alter gut microbiota, which may affect the enterohepatic circulation of methotrexate and its metabolites. Some studies suggest tetracycline may also interfere with methotrexate's cellular uptake or metabolism, though this mechanism is less well-established.

Risks and Symptoms

The primary clinical risk of this interaction is increased methotrexate toxicity, which can manifest as bone marrow suppression (neutropenia, thrombocytopenia, anemia), gastrointestinal toxicity (mucositis, diarrhea, nausea), hepatotoxicity, and nephrotoxicity. Patients with pre-existing renal impairment are at higher risk due to reduced methotrexate clearance. The interaction significance is generally rated as moderate, meaning clinical monitoring is recommended but the combination is not contraindicated. Severe toxicity is more likely with high-dose methotrexate regimens or in patients with multiple risk factors.

Management and Precautions

When co-administering methotrexate and tetracycline, implement enhanced monitoring protocols including complete blood count, liver function tests, and serum creatinine at baseline and regularly during treatment. Consider more frequent monitoring in high-risk patients (elderly, renal impairment, high methotrexate doses). Ensure adequate hydration and consider leucovorin rescue if signs of methotrexate toxicity develop. Educate patients about early toxicity symptoms including mouth sores, unusual bleeding, persistent nausea, or signs of infection. If possible, consider alternative antibiotics with lower interaction potential, though tetracycline may be continued with appropriate monitoring when clinically necessary.

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.