Spironolactone and Bupropion (Wellbutrin) Interaction
There is no clinically significant pharmacokinetic or pharmacodynamic interaction between spironolactone and bupropion (Wellbutrin), and these medications can be safely co-prescribed in young, healthy patients without cardiovascular or renal disease.
Evidence for Safe Co-Administration
Acne Treatment Guidelines Support Combination Use
The American Academy of Dermatology explicitly addresses this combination in their 2016 acne management guidelines. In a study of 27 women treated with spironolactone 100 mg daily combined with a drospirenone-containing oral contraceptive (drospirenone is a spironolactone analog), no significant elevations in serum potassium occurred and no additional side effects were significant enough to discontinue treatment 1. While this study examined spironolactone with a spironolactone-analog contraceptive rather than bupropion directly, it demonstrates spironolactone's safety profile when combined with other medications 1.
The guidelines further state that spironolactone may be used in combination with other oral acne medications, and there is no mention of bupropion as a contraindicated or cautionary combination 1.
No Metabolic Pathway Overlap
Bupropion is extensively metabolized by hepatic cytochrome P450-2B6 (CYP2B6) to its active metabolite hydroxybupropion, and it inhibits CYP2D6 2, 3. Spironolactone is metabolized through different pathways and does not share significant metabolic interactions with bupropion 2.
The only documented drug interaction concern for spironolactone involves potent CYP3A4 inhibitors, which can increase spironolactone levels and hyperkalemia risk 1. Bupropion does not inhibit CYP3A4 2, 3.
Monitoring Requirements
For Spironolactone
In young, healthy women without renal or cardiovascular disease who are not taking ACE inhibitors, angiotensin receptor blockers, NSAIDs, or digoxin, routine potassium monitoring is not required 1. A retrospective study of 974 women taking spironolactone for acne found that only 13 of 1,802 potassium measurements (0.72%) exceeded 5.0 mmol/L, and six of these normalized on repeat testing 1.
However, serum potassium testing should be performed at baseline, during therapy, and after dose increases in older patients or those taking ACE inhibitors, angiotensin receptor blockers, NSAIDs, or digoxin 1.
For Bupropion
Blood pressure and heart rate should be monitored periodically, especially during the first 12 weeks of treatment, as bupropion can cause elevations in both parameters 4. Patients should be assessed for suicidal ideation, agitation, irritability, or unusual behavioral changes during the first 1-2 weeks, particularly in individuals younger than 24 years 4.
Contraindications to Consider Separately
Spironolactone Contraindications
- Concomitant use of potassium supplements or potassium-sparing diuretics 1
- Combined use of an ACE inhibitor with an angiotensin receptor blocker 1
- Severe renal impairment or hyperkalemia 1
Bupropion Contraindications
- Seizure disorders or conditions predisposing to seizures 4
- Current or recent MAOI use (within 14 days) 4
- Eating disorders (bulimia or anorexia nervosa) 4
- Abrupt discontinuation of alcohol, benzodiazepines, or antiepileptic drugs 4
- Uncontrolled hypertension 4
Common Clinical Scenarios
Depression and Acne in Women
This combination is particularly appropriate for women with both depression and acne, as spironolactone addresses hormonal acne while bupropion treats depression with lower rates of sexual dysfunction and weight gain compared to SSRIs 1, 4. Spironolactone typically requires several months to reach full effectiveness for acne 1, while bupropion requires 6-8 weeks for adequate antidepressant response 4.
Smoking Cessation and Acne
For patients using bupropion for smoking cessation (150 mg twice daily for 7-12 weeks) who also need spironolactone for acne, no dose adjustments are necessary 4. The maximum bupropion dose for smoking cessation is 300 mg/day to maintain seizure risk at 0.1% 4.
Critical Safety Pitfall
The only scenario requiring extreme caution is if a patient is prescribed naltrexone-bupropion combination therapy (Contrave) for weight management rather than bupropion alone 4. The naltrexone-bupropion combination has additional contraindications and monitoring requirements, including mandatory blood pressure monitoring and avoidance in patients taking opioids 4. However, this concern relates to the naltrexone component, not an interaction between spironolactone and bupropion 4.