Is it appropriate to prescribe hydralazine (direct vasodilator) for a patient?

Hydralazine Prescription Decision

Hydralazine should be prescribed in specific clinical contexts only: as combination therapy with isosorbide dinitrate for heart failure with reduced ejection fraction (particularly in African American patients), as IV therapy for severe hypertension in pregnancy, or as a last-resort agent for resistant hypertension when combined with beta-blockers and diuretics—but it should NOT be used as monotherapy for chronic hypertension or as first-line therapy for most hypertensive emergencies. 1, 2

Heart Failure with Reduced Ejection Fraction (HFrEF)

Primary Indication: African American Patients

• Prescribe hydralazine combined with isosorbide dinitrate (Class I recommendation) for self-identified African American patients with NYHA class III-IV HFrEF who remain symptomatic despite optimal therapy with ACE inhibitors, beta-blockers, and aldosterone antagonists. 1
• This combination demonstrates remarkable mortality benefit: 43% relative risk reduction with a number needed to treat (NNT) of only 7 over 36 months, and 33% reduction in heart failure hospitalizations. 1, 3
• Start with 37.5 mg hydralazine plus 20 mg isosorbide dinitrate three times daily, titrating to target dose of 75 mg plus 40 mg three times daily. 1, 2

Alternative Indication: ACE Inhibitor/ARB Intolerance

• Consider hydralazine-isosorbide dinitrate combination (Class IIa recommendation) for patients with current or prior symptomatic HFrEF who cannot tolerate ACE inhibitors or ARBs due to drug intolerance, hypotension, or renal insufficiency. 1
• Evidence is weaker in this population, but the combination remains a reasonable therapeutic option when standard neurohumoral antagonists cannot be used. 1, 3

Critical Contraindication in Heart Failure

• Never prescribe hydralazine without a nitrate in HFrEF—this is associated with harm (Class III recommendation). 3
• The combination should not substitute for ACE inhibitor/ARB therapy in patients tolerating these medications without difficulty. 1

Hypertensive Emergencies

Pregnancy-Specific Use

• Prescribe IV hydralazine for severe hypertension in pregnancy, starting with 5 mg IV bolus, then 10 mg every 20-30 minutes to a maximum of 25 mg per episode. 2
• Onset of action occurs within 10-30 minutes with duration of 1-4 hours. 2
• Monitor for side effects that may mimic worsening preeclampsia and watch for fetal distress from abrupt maternal hypotension. 2

Non-Obstetric Hypertensive Emergencies

• Do NOT use hydralazine as first-line therapy for most hypertensive emergencies due to unpredictable blood pressure response and prolonged duration of action (2-4 hours). 1, 2, 4
• If used, administer 10 mg via slow IV infusion (maximum initial dose 20 mg), repeating every 4-6 hours as needed. 1
• Preferred alternatives include nicardipine (initial 5 mg/h) or clevidipine (initial 1-2 mg/h) for more predictable titration. 1, 4

Specific Contraindication: Bradycardia

• Avoid hydralazine in patients with bradycardia, as reflex tachycardia is a common effect that becomes problematic when baseline heart rate is already low. 4
• Choose calcium channel blockers like nicardipine instead, which do not worsen bradycardia. 4

Chronic Hypertension Management

Fifth-Line Agent Only

• Consider hydralazine only as a fifth-line agent for resistant hypertension, and ONLY when combined with both a beta-blocker (to counteract reflex tachycardia) and a diuretic (to counteract sodium/water retention). 2, 3
• Never use hydralazine as monotherapy for chronic hypertension. 3
• Keep total daily doses below 150 mg to avoid drug-induced systemic lupus erythematosus. 3

Absolute Contraindications

• Do not prescribe hydralazine in patients with advanced aortic stenosis due to unpredictable blood pressure effects. 1, 3
• Avoid in patients with reactive airways disease when considering combination with beta-blockers. 1

Critical Monitoring and Adverse Effects

Mandatory Concurrent Therapy

• Always prescribe a beta-blocker with hydralazine to prevent reflex tachycardia. 2, 3
• Always prescribe a diuretic with hydralazine to prevent fluid retention. 2, 3

Monitoring Requirements

• Check blood pressure at 10-30 minutes, 1 hour, and 2-4 hours after each IV dose. 2
• Continuous monitoring required for IV administration to prevent overshoot hypotension. 2
• Monitor for lupus-like syndrome, particularly at cumulative doses >200 mg/day. 2

Common Adverse Effects

• Expect headache, dizziness, palpitations, flushing, and gastrointestinal complaints. 1, 2
• Adherence is generally poor due to high pill burden (three times daily dosing), frequency of administration, and adverse reactions. 1
• Blood dyscrasias (reduction in hemoglobin, leukopenia, agranulocytosis, purpura) require discontinuation if they develop. 5

Drug Interactions

• Use caution with MAO inhibitors. 5
• Profound hypotensive episodes may occur when combined with diazoxide. 5
• Higher plasma levels occur when administered with food. 5

Dosing Algorithms by Indication

Heart Failure (Three Times Daily)

• Initial: 37.5 mg three times daily with isosorbide dinitrate 20 mg three times daily. 1, 2
• Target: 75 mg three times daily with isosorbide dinitrate 40 mg three times daily. 1, 2
• Titrate slowly over 3-4 weeks to enhance tolerance. 1

Chronic Hypertension (Four Times Daily)

• Initial: 0.75 mg/kg/day divided into four doses (pediatric dosing extrapolated). 5
• Maximum: 7.5 mg/kg or 200 mg daily, whichever is lower. 5
• Must be combined with beta-blocker and diuretic. 2, 3

Acute IV Use (Pregnancy)

• 5 mg IV bolus initially, then 10 mg every 20-30 minutes. 2
• Maximum 25 mg per episode, may repeat cycle after several hours. 2

Acute IV Use (Non-Pregnancy)

• 10 mg slow IV infusion (maximum initial dose 20 mg). 1
• Repeat every 4-6 hours as needed. 1