Summary

The interaction between lithium and indomethacin is clinically significant and potentially dangerous. Indomethacin can increase lithium blood levels by reducing its renal clearance, leading to lithium toxicity.

Introduction

Lithium is a mood stabilizer primarily used to treat bipolar disorder and prevent manic episodes. It belongs to the class of antimanic agents and has a narrow therapeutic window. Indomethacin is a nonsteroidal anti-inflammatory drug (NSAID) used to treat pain, inflammation, and fever, commonly prescribed for conditions like arthritis, gout, and headaches.

Mechanism of Interaction

Indomethacin reduces lithium clearance by the kidneys through inhibition of prostaglandin synthesis. NSAIDs like indomethacin decrease renal blood flow and glomerular filtration rate by blocking cyclooxygenase enzymes, which reduces prostaglandin E2 production. This leads to decreased lithium excretion and subsequent accumulation in the blood, potentially increasing lithium levels by 15-60%.

Risks and Symptoms

The primary risk is lithium toxicity, which can manifest as nausea, vomiting, diarrhea, tremor, confusion, drowsiness, and in severe cases, seizures, coma, or death. Even therapeutic doses of indomethacin can push lithium levels into the toxic range. This interaction is considered major and can occur within days of starting indomethacin. Patients with pre-existing kidney disease, dehydration, or those taking other medications affecting renal function are at higher risk.

Management and Precautions

Close monitoring of lithium levels is essential when indomethacin cannot be avoided. Baseline lithium levels should be obtained before starting indomethacin, with follow-up levels checked within 3-5 days and weekly thereafter. Consider alternative pain management options such as acetaminophen or topical preparations. If indomethacin is necessary, lithium dose reduction may be required. Patients should be educated about signs of lithium toxicity and advised to maintain adequate hydration. Healthcare providers should consider the risk-benefit ratio and explore safer alternatives whenever possible.

Lithium interactions with food and lifestyle

Lithium has several important food and lifestyle interactions that require careful monitoring. Sodium intake significantly affects lithium levels - both low sodium diets and sudden increases in sodium intake can alter lithium concentrations and potentially lead to toxicity or reduced effectiveness. Patients should maintain consistent sodium intake and avoid drastic dietary changes. Adequate fluid intake (8-10 glasses of water daily) is essential, as dehydration can increase lithium levels and risk of toxicity. Caffeine intake should be kept consistent, as sudden changes in caffeine consumption can affect lithium levels. Alcohol should be avoided or used with extreme caution, as it can increase the risk of lithium toxicity and may worsen mood symptoms. Patients should also avoid excessive sweating through intense exercise or saunas without proper hydration, as fluid loss can concentrate lithium levels. These interactions are well-documented in major drug databases and clinical guidelines, requiring regular monitoring of lithium blood levels.

Indomethacin interactions with food and lifestyle

Alcohol: Concurrent use of indomethacin with alcohol may increase the risk of gastrointestinal bleeding and ulceration. Patients should avoid or limit alcohol consumption while taking indomethacin. Food: Indomethacin should be taken with food, milk, or antacids to reduce gastrointestinal irritation and minimize the risk of stomach upset, nausea, and potential ulceration. Taking indomethacin on an empty stomach significantly increases the risk of gastrointestinal side effects.