Summary

The interaction between doxepin and lansoprazole is generally considered minor to moderate in clinical significance. Lansoprazole may potentially increase doxepin plasma concentrations by inhibiting its metabolism, though this interaction is not commonly reported as clinically significant in most patients.

Introduction

Doxepin is a tricyclic antidepressant (TCA) primarily used to treat depression, anxiety disorders, and chronic insomnia. It works by blocking the reuptake of norepinephrine and serotonin neurotransmitters. Lansoprazole is a proton pump inhibitor (PPI) commonly prescribed to treat gastroesophageal reflux disease (GERD), peptic ulcers, and other acid-related gastrointestinal conditions by reducing stomach acid production through irreversible inhibition of the H+/K+-ATPase enzyme system.

Mechanism of Interaction

The potential interaction between doxepin and lansoprazole occurs through hepatic enzyme inhibition. Lansoprazole can inhibit certain cytochrome P450 enzymes, particularly CYP2C19 and to a lesser extent CYP3A4, which are involved in the metabolism of doxepin. This inhibition may lead to decreased clearance of doxepin, potentially resulting in increased plasma concentrations and prolonged half-life of the tricyclic antidepressant.

Risks and Symptoms

The primary clinical risk of this interaction is the potential for enhanced doxepin effects, including increased sedation, anticholinergic side effects (dry mouth, constipation, urinary retention), and cardiovascular effects such as orthostatic hypotension or cardiac conduction abnormalities. Elderly patients may be at higher risk due to age-related changes in drug metabolism and increased sensitivity to anticholinergic effects. However, clinically significant interactions are relatively uncommon, and many patients tolerate this combination well.

Management and Precautions

Monitor patients for signs of increased doxepin toxicity, particularly during the first few weeks of concurrent therapy or after lansoprazole dose increases. Watch for excessive sedation, confusion, anticholinergic symptoms, or cardiovascular effects. Consider starting with lower doxepin doses if initiating both medications simultaneously. Regular assessment of therapeutic response and side effects is recommended. If significant adverse effects occur, consider dose reduction of doxepin or alternative acid suppression therapy. Patients should be counseled about potential increased drowsiness and advised to avoid driving or operating machinery until effects are known.

Doxepin interactions with food and lifestyle

Alcohol: Avoid alcohol while taking doxepin as it can increase drowsiness, dizziness, and impair thinking and motor skills. The combination may also increase the risk of respiratory depression. Grapefruit: Grapefruit and grapefruit juice may increase doxepin levels in the blood by inhibiting CYP3A4 metabolism, potentially leading to increased side effects. Driving and Operating Machinery: Doxepin may cause drowsiness, dizziness, and blurred vision. Patients should avoid driving or operating heavy machinery until they know how the medication affects them. Sun Exposure: Doxepin may increase sensitivity to sunlight (photosensitivity). Use sunscreen and protective clothing when outdoors to prevent sunburn and skin reactions.

Lansoprazole interactions with food and lifestyle

Lansoprazole should be taken on an empty stomach, preferably 30-60 minutes before meals, as food can significantly reduce its absorption and effectiveness. Alcohol consumption should be limited or avoided while taking lansoprazole, as alcohol can increase stomach acid production and counteract the medication's acid-reducing effects. Additionally, alcohol may worsen gastroesophageal reflux disease (GERD) symptoms that lansoprazole is intended to treat.