What are the recommendations for a patient taking bupropion (Wellbutrin) 150mg every 24 hours and hydralazine 25mg?

Initial Consultation: Bupropion 150mg Daily and Hydralazine 25mg

This medication regimen requires immediate dose optimization: bupropion 150mg once daily is appropriate for initial dosing but hydralazine 25mg as a single daily dose is subtherapeutic and not evidence-based for any indication. 1, 2

Critical Dosing Issues

Hydralazine Underdosing

• Hydralazine 25mg once daily has no established therapeutic role 1, 2
• For heart failure with reduced ejection fraction (HFrEF), the evidence-based starting dose is 25-50mg three to four times daily (75-200mg total daily), always combined with isosorbide dinitrate 1, 2
• For hypertension management, standard dosing is 25-50mg two to four times daily 3
• The fixed-dose combination (hydralazine/isosorbide dinitrate) starts at 37.5mg hydralazine three times daily, targeting 75mg three times daily 1, 2

Bupropion Dosing Assessment

• Bupropion 150mg once daily (24-hour formulation) is the appropriate starting dose 4
• After 4 days for major depressive disorder or 7 days for seasonal affective disorder, consider increasing to the target dose of 300mg once daily 4
• The extended-release formulation should be taken in the morning and swallowed whole 4

Cardiovascular Safety Considerations

Bupropion and Blood Pressure

• Bupropion can cause dose-dependent increases in blood pressure, particularly supine blood pressure 5
• In patients with preexisting hypertension, bupropion has caused exacerbation requiring discontinuation in some cases 5
• Monitor blood pressure closely, especially during dose titration 3, 5

Hydralazine Cardiovascular Effects

• Hydralazine causes vasodilation and can lead to symptomatic hypotension, particularly when underdosed or improperly scheduled 3, 2
• Blood pressure response to hydralazine is unpredictable, requiring careful monitoring 3, 2
• When used for heart failure, hydralazine must be combined with isosorbide dinitrate to achieve mortality benefit (43% relative risk reduction, NNT=25 over 10 months) 2

Immediate Management Algorithm

Step 1: Clarify the indication for hydralazine

• If prescribed for HFrEF: Switch to fixed-dose combination hydralazine 37.5mg/isosorbide dinitrate 20mg three times daily 1, 2
• If prescribed for hypertension: Increase to 25mg three to four times daily or consider alternative antihypertensive given bupropion's hypertensive effects 3
• If indication unclear: Discontinue and reassess need, as 25mg once daily serves no therapeutic purpose 1, 2

Step 2: Monitor blood pressure closely

• Baseline blood pressure before any dose adjustments 5
• Weekly blood pressure checks during first month, especially if increasing bupropion to 300mg 4, 5
• Watch for paradoxical hypertension from bupropion opposing inadequate hydralazine dosing 5

Step 3: Assess bupropion response and titration need

• After 4-7 days at 150mg, evaluate tolerability and therapeutic response 4
• If well-tolerated and blood pressure controlled, increase to 300mg once daily 4
• Hold at 150mg if blood pressure elevation occurs 5

Critical Drug Interaction Concerns

Seizure Risk

• Bupropion lowers seizure threshold in a dose-dependent manner 4, 6
• Risk increases with doses above 300mg daily or rapid dose escalation 4
• Never crush, divide, or chew extended-release tablets as this increases seizure risk 4

Metabolic Considerations

• Bupropion is extensively metabolized by CYP2B6 to hydroxybupropion (primary active metabolite) 6, 7
• Bupropion inhibits CYP2D6, potentially affecting other medications metabolized by this pathway 6, 7
• Carbamazepine dramatically reduces bupropion levels (90% decrease in AUC), but this is not relevant unless anticonvulsants are added 8

Common Pitfalls to Avoid

Pitfall 1: Accepting subtherapeutic hydralazine dosing

• Single daily dosing of hydralazine has no evidence base and wastes the medication's therapeutic potential 1, 2
• Always verify the indication and prescribe appropriate frequency (three to four times daily) 1, 2

Pitfall 2: Ignoring the bupropion-hypertension interaction

• Bupropion can raise blood pressure, particularly in patients with baseline hypertension 5
• This effect may counteract hydralazine's antihypertensive action if hydralazine is underdosed 5

Pitfall 3: Prescribing hydralazine without isosorbide dinitrate for heart failure

• Hydralazine monotherapy provides no mortality benefit in HFrEF 2
• The combination reduces mortality by 43% (NNT=25 over 10 months) 2

Pitfall 4: Rapid bupropion dose escalation

• Gradual titration minimizes seizure risk 4
• Wait minimum 4 days before increasing from 150mg to 300mg 4

Adverse Effect Monitoring

Bupropion-Specific

• Neuropsychiatric: insomnia (dose second dose before 3 PM if splitting), nervousness, headache 3, 4
• Cardiovascular: hypertension, tachycardia (less common than with tricyclics) 5
• Seizures: rare but serious, dose-dependent risk 4
• Notably low rates of sexual dysfunction and weight gain compared to SSRIs 9

Hydralazine-Specific

• Symptomatic hypotension, dizziness (often improves with time) 3
• Drug-induced lupus syndrome: arthralgia, joint swelling, pericarditis, pleuritis, rash, fever (check ANA if suspected, discontinue immediately) 3
• Reflex tachycardia when used without beta-blocker 3