Summary

Methotrexate and theophylline can interact through competitive inhibition of renal tubular secretion, potentially leading to increased levels of both drugs. This interaction may result in enhanced toxicity, particularly methotrexate-related adverse effects and theophylline toxicity.

Introduction

Methotrexate is an antimetabolite and antifolate drug primarily used as a disease-modifying antirheumatic drug (DMARD) for rheumatoid arthritis, psoriasis, and certain cancers. It works by inhibiting dihydrofolate reductase, interfering with DNA synthesis and cell division. Theophylline is a methylxanthine bronchodilator used to treat asthma and chronic obstructive pulmonary disease (COPD). It works by inhibiting phosphodiesterase and blocking adenosine receptors, leading to smooth muscle relaxation and bronchodilation.

Mechanism of Interaction

The interaction between methotrexate and theophylline occurs primarily at the level of renal elimination. Both drugs are actively secreted by the organic anion transporters in the proximal renal tubules. When administered concurrently, they compete for the same transport mechanisms, potentially leading to reduced clearance of both medications. This competitive inhibition can result in increased plasma concentrations and prolonged half-lives of both methotrexate and theophylline, increasing the risk of dose-related adverse effects.

Risks and Symptoms

The primary clinical risks include increased methotrexate toxicity, which can manifest as bone marrow suppression, hepatotoxicity, nephrotoxicity, and gastrointestinal toxicity. Elevated theophylline levels may lead to nausea, vomiting, cardiac arrhythmias, seizures, and central nervous system stimulation. Patients with pre-existing kidney disease are at higher risk due to already compromised renal clearance. The interaction is considered moderate in severity and requires careful monitoring when both drugs are used concurrently.

Management and Precautions

Close monitoring is essential when methotrexate and theophylline are used together. Regular monitoring should include complete blood counts, liver function tests, kidney function, and theophylline serum levels. Consider dose adjustments based on clinical response and laboratory values. Maintain adequate hydration and consider leucovorin rescue if methotrexate toxicity develops. Alternative bronchodilators such as beta-2 agonists or anticholinergics may be considered if clinically appropriate. Healthcare providers should educate patients about signs and symptoms of toxicity from both medications and ensure regular follow-up appointments.

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.

Theophylline interactions with food and lifestyle

Theophylline has several important food and lifestyle interactions that patients should be aware of. Caffeine consumption should be limited as both theophylline and caffeine are methylxanthines, and concurrent use can increase the risk of side effects such as nervousness, irritability, and rapid heart rate. High-protein, low-carbohydrate diets may increase theophylline clearance and reduce drug levels, while high-carbohydrate, low-protein diets may decrease clearance and increase drug levels. Charcoal-broiled foods may increase theophylline metabolism and reduce effectiveness. Smoking tobacco significantly increases theophylline clearance, requiring higher doses in smokers, and dose adjustments are needed when patients quit smoking. Alcohol consumption should be limited as it may affect theophylline metabolism. Patients should maintain consistent dietary habits and inform their healthcare provider of any significant dietary changes or smoking status changes, as these may require dose adjustments to maintain therapeutic levels.