What are the indications, oral and intravenous dosing regimens, contraindications, side effects, drug interactions, and monitoring recommendations for hydralazine in adults?

Hydralazine: Clinical Overview

Primary Indications

Hydralazine is indicated for heart failure (particularly in African American patients as adjunct to ACE inhibitors/beta-blockers), hypertension (as third-line therapy), hypertensive crisis, and pregnancy-induced hypertension. 1, 2, 3

• In heart failure, the combination of hydralazine with isosorbide dinitrate is specifically recommended for African American patients who remain symptomatic despite optimal therapy with ACE inhibitors and beta-blockers, based on demonstrated mortality benefit 1
• For hypertension, hydralazine should NOT be used as monotherapy or first-line treatment—it requires combination with beta-blockers and diuretics 4, 3
• The drug should never substitute for ACE inhibitors in patients tolerating them without difficulty 1

Dosing Regimens

Oral Dosing

• Standard dosing: 200-300 mg daily in divided doses 2, 5
• Twice-daily dosing (every 12 hours) is as effective as four times daily, despite the drug's short half-life 5
• Administration with food increases plasma levels 2

Intravenous Dosing

• Acute setting: 20-40 mg IV bolus, repeated as necessary 6
• Blood pressure begins falling within minutes, with maximal decrease at 10-80 minutes 6
• Patients with renal impairment require lower doses 6
• Transfer to oral therapy within 24-48 hours 6
• Critical pitfall: Do NOT add to infusion solutions; use immediately after opening vial and discard if discolored 6

Contraindications and Precautions

Absolute Cautions

• Coronary artery disease: Hydralazine causes myocardial stimulation leading to anginal attacks, ECG ischemic changes, and has been implicated in myocardial infarction 2
• Mitral valvular disease (may increase pulmonary artery pressure) 2
• Cerebrovascular accidents (use with extreme caution) 2

Relative Contraindications

• Advanced renal damage (though improved renal function has been noted in some cases) 2
• Increased intracranial pressure (lowering BP may worsen cerebral ischemia) 6

Side Effects Profile

Cardiovascular Effects

• Reflex tachycardia is the primary cardiac effect, NOT bradycardia—this occurs due to baroreceptor-mediated compensation for arterial vasodilation 4
• Sodium and water retention from reduced renal perfusion 4, 3
• Postural hypotension (less common than with ganglionic blockers) 2

Drug-Induced Lupus

• Occurs at doses above 150-200 mg daily, particularly in slow acetylators 7, 8
• Monitor with antinuclear antibody titers before and periodically during therapy 2
• Symptoms include arthralgia, fever, chest pain, and malaise 2

Hematologic Effects

• Blood dyscrasias: anemia, leukopenia, agranulocytosis, purpura 2
• Requires complete blood counts before and during prolonged therapy 2

Neurologic Effects

• Peripheral neuritis (paresthesia, numbness, tingling) from antipyridoxine effect 2
• Add pyridoxine if symptoms develop 2

Other Common Effects

• Headache and gastrointestinal complaints (frequent, often dose-limiting) 1
• Myocardial ischemia in susceptible patients 2

Critical Drug Interactions

• MAO inhibitors: Use with extreme caution 2
• Diazoxide: Profound hypotensive episodes when combined—requires continuous monitoring for several hours 2
• Epinephrine: Reduced pressor response 2
• Beta-blockers blunt the chronotropic effect, which is therapeutically desirable 4

Monitoring Requirements

Baseline Assessment

• Complete blood count 2
• Antinuclear antibody titer 2
• Renal function 2
• Cardiac evaluation if coronary disease suspected 2

Ongoing Monitoring

• Blood pressure frequently during IV administration (check within minutes and continue monitoring) 6, 9
• Periodic CBC and ANA titers during prolonged therapy, even if asymptomatic 2
• Immediate testing if patient develops arthralgia, fever, chest pain, or unexplained symptoms 2
• Heart rate monitoring (expect increase, not decrease) 4

Essential Clinical Algorithm

Step 1: Confirm appropriate indication (heart failure in African Americans on optimal therapy, or hypertension requiring third-line agent) 1

Step 2: Rule out coronary artery disease, mitral valve disease, and cerebrovascular disease 2

Step 3: Initiate ONLY in combination with beta-blocker (to prevent reflex tachycardia) and diuretic (to prevent fluid retention) 4, 3

Step 4: Start oral dosing at lower end of range, given twice daily with food 2, 5

Step 5: Keep total daily dose below 150-200 mg to minimize lupus risk 7

Step 6: Monitor CBC and ANA at baseline and periodically; discontinue if blood dyscrasias develop 2

Step 7: Add pyridoxine if peripheral neuritis symptoms emerge 2

Common Pitfalls to Avoid

• Never confuse hydralazine's reflex tachycardia with bradycardia-inducing antihypertensives—the mechanisms are entirely opposite 4
• Never use as monotherapy or substitute for ACE inhibitors in tolerant patients 1
• Never add IV hydralazine to infusion solutions 6
• Never ignore slow acetylator status—these patients have better BP control but significantly more side effects 8
• Never use in hypertensive emergencies as first-line due to unpredictable response and prolonged duration 4