Wellbutrin and Zofran: Concurrent Use Guidelines
Wellbutrin (bupropion) and Zofran (ondansetron) can be used together safely in most patients, with no direct pharmacokinetic interaction between these medications, though monitoring for neuropsychiatric effects and seizure risk with bupropion remains essential regardless of concurrent ondansetron use. 1
Key Safety Considerations
No Direct Drug-Drug Interaction
- Bupropion is primarily metabolized by CYP2B6 and inhibits CYP2D6, while ondansetron is metabolized by CYP3A4, CYP1A2, and CYP2D6 2
- These medications work through distinct mechanisms: bupropion is a dopamine-norepinephrine reuptake inhibitor, while ondansetron is a 5-HT3 receptor antagonist 2, 3
- No formal contraindication exists for concurrent use in current guidelines 1
Bupropion-Specific Precautions (Apply Regardless of Ondansetron Use)
Absolute Contraindications for Bupropion:
- Seizure disorders or conditions that lower seizure threshold (brain metastases, stroke history) 1, 4
- Current use of MAO inhibitors or within 14 days of discontinuation 1, 4
- Uncontrolled hypertension 1
Dose Adjustments Required:
- Moderate to severe hepatic impairment: maximum 150 mg daily 1, 4
- Moderate to severe renal impairment: reduce total daily dose by 50% 1, 4
- Maximum dose should never exceed 450 mg/day to minimize seizure risk (0.1% at therapeutic doses) 1, 4, 5
Monitoring Requirements
Neuropsychiatric Monitoring:
- Monitor for depression, suicidal ideation/behavior, especially in patients under 24 years old 1
- Black box warning exists for suicidal behavior risk in young adults with depression 1
- Recent large trials (EAGLES, n=8,144) showed no significant increase in neuropsychiatric adverse events compared to placebo 1
Cardiovascular Monitoring:
- Monitor blood pressure regularly, as bupropion can cause modest increases in systolic and diastolic blood pressure, particularly in first 8 weeks 1, 4
- Avoid in patients with uncontrolled hypertension 1
Clinical Scenarios Where Combination is Appropriate
Cancer Patients
- Bupropion is recommended for smoking cessation in cancer patients (150 mg twice daily for 7-12 weeks) 1
- Ondansetron is standard antiemetic therapy during chemotherapy 6
- The combination is commonly used in oncology settings without reported safety concerns 1
Depression with Nausea
- Bupropion is effective for major depressive disorder at 150 mg twice daily (SR formulation) or 300 mg once daily (XL formulation) 4, 2, 3
- Ondansetron may be used for nausea management without compromising bupropion efficacy 6
Obesity Management with Nausea
- Naltrexone-bupropion ER (16 mg/180 mg twice daily) is FDA-approved for weight management 1
- Ondansetron can be used concurrently for nausea management if needed 1
Important Clinical Caveat
One theoretical concern exists with SSRIs (not bupropion) and ondansetron: A 1995 case series reported that fluoxetine (an SSRI/5-HT reuptake inhibitor) may reduce ondansetron's antiemetic efficacy by increasing synaptic serotonin that competes with ondansetron at 5-HT3 receptors 6. However, this concern does NOT apply to bupropion, which works through dopamine-norepinephrine reuptake inhibition, not serotonin 2, 3.
Practical Dosing When Using Both Medications
Bupropion SR (most common formulation):
- Start 150 mg once daily for 3 days, then increase to 150 mg twice daily 4
- For smoking cessation: begin 1-2 weeks before quit date 1, 4
- Administer second dose before 3 PM to minimize insomnia 4
Ondansetron:
- Dose per standard protocols for indication (typically 8 mg every 8-12 hours for chemotherapy-induced nausea)
- No dose adjustment needed when combined with bupropion