Summary

Rifampin significantly reduces bupropion plasma concentrations through CYP2B6 enzyme induction, potentially leading to decreased antidepressant efficacy. This interaction requires careful monitoring and possible dose adjustments when these medications are used concurrently.

Introduction

Bupropion is an atypical antidepressant and smoking cessation aid that belongs to the aminoketone class, primarily used for treating major depressive disorder and seasonal affective disorder. Rifampin is a potent antibiotic from the rifamycin family, commonly prescribed for tuberculosis treatment and other mycobacterial infections. Both medications are frequently prescribed, making their potential interaction clinically relevant for healthcare providers managing patients with concurrent depression and infectious diseases.

Mechanism of Interaction

The interaction between bupropion and rifampin occurs through hepatic enzyme induction. Rifampin is a potent inducer of cytochrome P450 enzymes, particularly CYP2B6, which is the primary enzyme responsible for bupropion metabolism. When rifampin induces CYP2B6, it significantly increases the metabolic clearance of bupropion, leading to reduced plasma concentrations and potentially diminished therapeutic effects. This induction effect typically develops within 1-2 weeks of rifampin initiation and can persist for several weeks after rifampin discontinuation.

Risks and Symptoms

The primary clinical risk of this interaction is reduced bupropion efficacy, which may result in inadequate treatment of depression or failure of smoking cessation attempts. Patients may experience return of depressive symptoms, decreased mood stabilization, or reduced success in quit-smoking efforts. The interaction is considered clinically significant due to the substantial reduction in bupropion exposure (up to 87% decrease in AUC). Additionally, patients may be at risk for treatment failure if the interaction is not recognized and managed appropriately.

Management and Precautions

When concurrent use is necessary, consider increasing bupropion dose by up to 2-fold while monitoring for therapeutic response and adverse effects. Close clinical monitoring is essential, including assessment of depressive symptoms and smoking cessation progress. Alternative antibiotics should be considered when possible for patients on stable bupropion therapy. If rifampin is discontinued, bupropion doses may need to be reduced to prevent toxicity as enzyme induction effects wane. Patients should be counseled about potential reduced effectiveness and advised to report any worsening of symptoms. Regular follow-up appointments are recommended to assess treatment response and adjust therapy as needed.

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.

Rifampin interactions with food and lifestyle

Rifampin should be taken on an empty stomach, at least 1 hour before or 2 hours after meals, as food can significantly reduce its absorption and effectiveness. Alcohol consumption should be avoided or limited while taking rifampin, as both rifampin and alcohol can cause liver toxicity, and the combination may increase the risk of hepatotoxicity. Patients should be counseled to take rifampin consistently either with or without food (preferably without) to maintain consistent blood levels.