What are the risks and considerations for a patient taking Wellbutrin (bupropion) for depression who is also prescribed Tamiflu (oseltamivir) for influenza?

Tamiflu and Wellbutrin: Safe Co-Administration with Monitoring

There is no pharmacokinetic drug interaction between oseltamivir (Tamiflu) and bupropion (Wellbutrin), and these medications can be safely co-administered, though vigilance for neuropsychiatric symptoms is warranted given that both agents have been independently associated with CNS effects. 1

Pharmacokinetic Safety Profile

• Oseltamivir is primarily excreted unchanged via the kidneys through glomerular filtration and tubular secretion, with minimal hepatic metabolism and no involvement of cytochrome P450 enzymes 1
• This renal elimination pathway means oseltamivir does not interact with bupropion's hepatic metabolism, eliminating concerns about altered drug levels or efficacy 1
• The only clinically significant drug interaction with oseltamivir involves probenecid (which reduces oseltamivir clearance by 50%), but this does not apply to bupropion 1

Neuropsychiatric Monitoring Considerations

While no direct interaction exists, both medications carry independent neuropsychiatric warnings that require clinical awareness:

Oseltamivir-Related Neuropsychiatric Effects

• Seizure events have been reported during postmarketing use of oseltamivir, though no epidemiologic studies have established increased seizure risk 2
• Transient neuropsychiatric events (abnormal behavior, delusions, perceptual disturbances, mania, depression) have been reported postmarketing, though these are rare 1, 3
• A case series documented acute exacerbation of psychiatric symptoms in chronic schizophrenia patients treated with oseltamivir, suggesting additional caution in patients with established psychiatric diagnoses 3

Bupropion-Related Seizure Risk

• Bupropion lowers the seizure threshold in a dose-dependent manner, with seizure risk at ≤450 mg/day comparable to other antidepressants (approximately 0.4%), but increasing substantially at higher doses 4, 5, 6
• Seizures can occur even at therapeutic doses (450 mg/day or less) and moderate blood levels in patients without predisposing factors 5
• Doses ≥2.7g in overdose consistently cause seizures, encephalopathy, and cardiovascular effects 6
• Bupropion can precipitate mania in bipolar patients, particularly at doses exceeding 450 mg/day 7

Clinical Management Algorithm

For patients on Wellbutrin who develop influenza:

1. Prescribe oseltamivir at standard dosing: 75 mg orally twice daily for 5 days, initiated within 48 hours of symptom onset 8, 1

2. Continue bupropion without dose adjustment—no pharmacokinetic interaction exists 1

3. Administer oseltamivir with food to minimize gastrointestinal side effects (nausea/vomiting occur in ~10% of patients) 1

4. Monitor specifically for:

   • New-onset confusion, agitation, or behavioral changes during the 5-day oseltamivir course 3
   • Any seizure activity, particularly if bupropion dose is >300 mg/day 4, 5
   • Mood destabilization in patients with bipolar disorder 7

5. Adjust oseltamivir dose to 75 mg once daily if creatinine clearance is 10-30 mL/min 1

High-Risk Patient Considerations

Patients requiring heightened vigilance include:

• Those with pre-existing seizure disorders (both medications independently associated with seizure reports) 2, 4
• Patients with bipolar disorder on bupropion (oseltamivir has precipitated mania in case reports) 3, 7
• Individuals with chronic schizophrenia or other psychotic disorders (oseltamivir may exacerbate psychotic symptoms) 3
• Patients taking bupropion doses approaching or exceeding 450 mg/day (higher seizure threshold lowering) 4, 6, 7

Critical Pitfalls to Avoid

• Do not withhold oseltamivir in high-risk influenza patients (elderly, immunocompromised, chronic medical conditions) due to theoretical neuropsychiatric concerns—the mortality benefit of oseltamivir (OR 0.21 for death within 15 days) far outweighs the rare risk of CNS effects 8
• Do not discontinue bupropion during the 5-day oseltamivir course unless acute psychiatric decompensation occurs—abrupt antidepressant discontinuation carries its own risks 4
• Do not delay oseltamivir initiation while awaiting laboratory confirmation in patients with influenza-like illness during flu season—empiric treatment within 48 hours provides maximum benefit 8

Expected Clinical Outcomes

• Oseltamivir will reduce influenza illness duration by 1-1.5 days when started within 48 hours 8
• Risk of pneumonia decreases by 50% with oseltamivir treatment 8
• Bupropion efficacy for depression remains unchanged (no pharmacokinetic interaction) 1
• The vast majority of patients tolerate this combination without incident, as the reported neuropsychiatric effects of oseltamivir are rare and not definitively causally linked 1, 3