Summary

Bupropion and omeprazole have a potential pharmacokinetic interaction where omeprazole may inhibit the metabolism of bupropion, potentially leading to increased bupropion levels. This interaction is generally considered mild to moderate in clinical significance but requires monitoring for enhanced bupropion effects.

Introduction

Bupropion is an atypical antidepressant and smoking cessation aid that belongs to the aminoketone class, commonly prescribed for major depressive disorder and as a quit-smoking medication under brand names like Wellbutrin and Zyban. Omeprazole is a proton pump inhibitor (PPI) widely used to treat gastroesophageal reflux disease (GERD), peptic ulcers, and other acid-related disorders, available both by prescription and over-the-counter as Prilosec. Both medications are frequently prescribed and may be used concurrently in patients with multiple health conditions.

Mechanism of Interaction

The interaction between bupropion and omeprazole occurs through cytochrome P450 enzyme inhibition. Bupropion is primarily metabolized by the CYP2B6 enzyme system, with some involvement of CYP3A4. Omeprazole is a known inhibitor of CYP2C19 and has some inhibitory effects on CYP3A4 and potentially CYP2B6. When omeprazole inhibits these metabolic pathways, it can reduce the clearance of bupropion, leading to increased plasma concentrations of the parent drug and potentially altered levels of its active metabolites, particularly hydroxybupropion.

Risks and Symptoms

The primary clinical risk of this interaction is the potential for enhanced bupropion effects due to increased drug levels. Patients may experience intensified side effects including increased risk of seizures (bupropion's most serious adverse effect), anxiety, agitation, insomnia, dry mouth, constipation, and tremor. The seizure risk is particularly concerning as it is dose-dependent, and elevated bupropion levels could push patients closer to the seizure threshold. Additionally, patients may experience enhanced therapeutic effects, which could lead to mood changes or increased stimulant-like effects.

Management and Precautions

Healthcare providers should monitor patients closely when initiating omeprazole in those already taking bupropion, or vice versa. Key management strategies include: starting with lower doses when possible, monitoring for signs of bupropion toxicity (especially neurological symptoms like tremor, agitation, or seizure activity), educating patients about potential side effects to watch for, and considering alternative acid-suppressing medications if clinically appropriate. Regular follow-up appointments should assess therapeutic response and adverse effects. If significant side effects occur, dose reduction of bupropion or discontinuation of one medication may be necessary. Patients should be advised not to exceed recommended bupropion doses and to avoid alcohol, which can further lower seizure threshold.

Bupropion interactions with food and lifestyle

Alcohol: Bupropion may lower the seizure threshold, and concurrent alcohol use can further increase seizure risk. Patients should avoid or limit alcohol consumption while taking bupropion. Sudden discontinuation of alcohol in patients with alcohol dependence may also increase seizure risk. Smoking cessation: While bupropion is used for smoking cessation, patients should be aware that nicotine withdrawal itself can affect seizure threshold. Close monitoring is recommended during the quit process. High-fat meals: Taking bupropion with high-fat meals may increase drug absorption and potentially increase side effects. Consider taking with light meals or on an empty stomach as tolerated.

Omeprazole interactions with food and lifestyle

Omeprazole 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 omeprazole, 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 omeprazole is treating. Smoking should be avoided or discontinued, as tobacco use increases stomach acid production and can reduce the effectiveness of omeprazole therapy. Patients should also be aware that omeprazole may interact with certain dietary supplements, particularly those containing magnesium, as long-term use of omeprazole can lead to magnesium deficiency.