Summary

The interaction between methotrexate and azithromycin is generally considered low to moderate risk. While azithromycin may theoretically increase methotrexate levels through competition for renal elimination, clinically significant interactions are uncommon with short-term azithromycin use.

Introduction

Methotrexate is an antimetabolite and immunosuppressive agent primarily used to treat rheumatoid arthritis, psoriasis, and certain cancers. It works by inhibiting dihydrofolate reductase, interfering with DNA synthesis and cell division. Azithromycin is a macrolide antibiotic commonly prescribed for respiratory tract infections, skin infections, and sexually transmitted diseases. It works by binding to the 50S ribosomal subunit, inhibiting bacterial protein synthesis.

Mechanism of Interaction

The potential interaction between methotrexate and azithromycin primarily involves competition for renal tubular secretion. Both drugs are eliminated through the kidneys via organic anion transporters. Azithromycin may theoretically compete with methotrexate for these transporters, potentially reducing methotrexate clearance and increasing plasma concentrations. However, this mechanism is less pronounced with azithromycin compared to other antibiotics like trimethoprim-sulfamethoxazole or penicillins.

Risks and Symptoms

The main clinical risk of this interaction is potential methotrexate toxicity, which can manifest as bone marrow suppression, hepatotoxicity, nephrotoxicity, and gastrointestinal toxicity. Symptoms may include fatigue, bruising, bleeding, nausea, vomiting, mouth sores, and elevated liver enzymes. However, the risk is generally low with short-term azithromycin courses (3-5 days) commonly used for acute infections. The risk may be higher in patients with pre-existing kidney disease, elderly patients, or those on higher methotrexate doses.

Management and Precautions

When co-administering methotrexate and azithromycin, monitor patients for signs of methotrexate toxicity, especially during and immediately after antibiotic treatment. Consider checking complete blood count, liver function tests, and creatinine if prolonged azithromycin use is required or if the patient has risk factors. Ensure adequate hydration and continue folic acid supplementation as prescribed. Educate patients to report symptoms such as unusual fatigue, bruising, mouth sores, or persistent nausea. For high-risk patients or prolonged antibiotic courses, consider alternative antibiotics with lower interaction potential or temporary methotrexate dose reduction under medical supervision.

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.

Azithromycin interactions with food and lifestyle

Azithromycin can be taken with or without food. However, taking azithromycin with food may help reduce stomach upset in some patients. Antacids containing aluminum or magnesium should be avoided within 2 hours before or after taking azithromycin, as they may decrease the absorption of the medication. No significant interactions with alcohol have been established, but patients should use alcohol cautiously while taking any antibiotic due to potential effects on immune function and healing.