Hydralazine

Generic Name: Hydralazine Hydrochloride

Brand Names: Apresoline

Hydralazine is a vasodilator used to treat high blood pressure and heart failure, often combined with nitrates.

CardiovascularVasodilator

Drug Class

Direct-Acting Arteriolar Vasodilator

Pregnancy

Category C — No teratogenicity has been demonstrated in humans, and hydralazine has a long track record of use for severe hypertension and preeclampsia in pregnancy. It remains a guideline-recommended option for acute severe hypertension during pregnancy, typically given intravenously under close monitoring.

Available Forms

Oral tablet (10 mg, 25 mg, 50 mg, 100 mg), IV / IM injection (20 mg/mL), Combination tablet with isosorbide dinitrate (BiDil: 37.5 mg/20 mg)

What It's Used For

Hypertension treatment
Heart failure in African American patients (with isosorbide dinitrate)
Hypertensive emergencies
Alternative for patients intolerant to ACE inhibitors or ARBs

Dosage Quick Reference

These are general dosage guidelines. Your doctor will determine the appropriate dose for your specific situation.

Condition	Starting Dose	Maintenance Dose
Essential hypertension (oral)	10 mg orally four times daily for 2–4 days	Increase to 25 mg four times daily; usual maintenance 50–100 mg/day in divided doses; max 300 mg/day
Heart failure (with isosorbide dinitrate, self-identified African American patients)	37.5 mg/20 mg three times daily	Titrate to 75 mg/40 mg three times daily as tolerated
Severe hypertension / hypertensive emergency (IV)	5–10 mg IV bolus over 1–2 minutes	Repeat every 20–30 minutes as needed; max 20 mg per dose
Hypertension in pregnancy (IV)	5 mg IV bolus	Repeat 5–10 mg every 20–40 minutes as needed

Side Effects

Common Side Effects:

Headache
Rapid heartbeat (palpitations)
Nausea and vomiting
Diarrhea
Loss of appetite
Dizziness
Nasal congestion

Serious Side Effects (seek immediate medical attention):

Symptoms of lupus-like syndrome (joint pain, fever, rash, fatigue)
Chest pain (angina)
Numbness or tingling in hands or feet (peripheral neuropathy)
Severe hypotension
Signs of heart failure (swelling, shortness of breath)

Drug Interactions

Hydralazine vasodilation produces strong reflex sympathetic activation, which drives most of its interaction profile.

Other antihypertensives (beta-blockers, diuretics, nitrates): Often combined intentionally — beta-blockers blunt reflex tachycardia and diuretics counteract fluid retention. Monitor for additive hypotension during titration.
MAO inhibitors: May markedly potentiate the hypotensive response. Use with caution and at reduced doses.
NSAIDs: Blunt the antihypertensive effect of hydralazine and may cause sodium and fluid retention. Use the lowest effective NSAID dose.
Potent peripheral vasodilators (e.g., minoxidil, sildenafil): Risk of severe hypotension when combined.
Diazoxide: Concomitant use can cause profound hypotension; avoid the combination.
Drugs that prolong QT or cause sympathomimetic effects (e.g., epinephrine): Reflex tachycardia from hydralazine may amplify these effects, particularly in patients with coronary disease.

Additional Information

Hydralazine is a direct-acting arterial vasodilator used primarily in the treatment of hypertension and heart failure. By relaxing vascular smooth muscle in arterioles, it reduces peripheral vascular resistance and afterload, making it valuable for managing both conditions, particularly when combined with other agents such as nitrates in heart failure therapy.

Mechanism of Action

Hydralazine causes direct relaxation of arteriolar smooth muscle through a mechanism that is not completely understood but involves interference with calcium movements and alterations in cellular calcium metabolism. Unlike many other vasodilators, hydralazine primarily affects arterioles rather than veins, causing a reduction in peripheral vascular resistance without significant venodilation. This selective arteriolar effect results in decreased blood pressure and reduced cardiac afterload.

The blood pressure reduction triggers baroreceptor-mediated reflex responses including increased heart rate, cardiac output, and renin release. These compensatory mechanisms can limit the antihypertensive effect of hydralazine when used alone, which is why it is typically used in combination with beta-blockers (to control reflex tachycardia) and diuretics (to counteract sodium retention).

Available Formulations

Hydralazine is available in oral and injectable formulations. Oral tablets come in 10 mg, 25 mg, 50 mg, and 100 mg strengths. An injectable solution (20 mg/mL) is available for intravenous or intramuscular administration in acute hypertensive emergencies or when oral administration is not possible. A fixed-dose combination with isosorbide dinitrate (BiDil) is specifically approved for heart failure in African American patients.

FDA-Approved Indications

Hydralazine is FDA-approved for essential hypertension (oral formulation), severe essential hypertension when rapid blood pressure reduction is required (parenteral), and in combination with isosorbide dinitrate for heart failure in African American patients who remain symptomatic despite optimal therapy with ACE inhibitors and beta-blockers. The combination with nitrates leverages complementary mechanisms to improve outcomes in heart failure.

Dosing Guidelines

For hypertension, the usual starting dose is 10 mg orally four times daily for the first 2-4 days, then increased to 25 mg four times daily for the rest of the first week. Subsequent dosing is individualized based on response, with a usual maintenance dose of 50 mg four times daily. For hypertensive emergencies, 10-20 mg may be given IV, repeated as needed. For heart failure (as BiDil), the combination tablet is given three times daily.

Role in Heart Failure

The A-HeFT trial demonstrated that the combination of hydralazine and isosorbide dinitrate significantly reduces mortality and hospitalizations in African American patients with heart failure when added to standard therapy. This benefit appears related to enhanced nitric oxide bioavailability and neurohormonal modulation. The combination is recommended by heart failure guidelines for this population and may also be considered in patients of any race who cannot tolerate ACE inhibitors or ARBs.

Important Safety Considerations

Drug-induced lupus erythematosus is a significant concern with hydralazine, particularly with doses exceeding 200 mg daily or with prolonged therapy. Symptoms include arthralgia, myalgia, fever, and skin rash. Testing for antinuclear antibodies is recommended with prolonged use. The condition typically resolves after discontinuation. Hydralazine should be used with caution in patients with coronary artery disease due to reflex tachycardia, and in patients with rheumatic mitral valve disease due to increased pulmonary pressure.

Drug Interactions

NSAIDs may reduce the antihypertensive effect of hydralazine. Beta-blockers are often used together intentionally to counteract reflex tachycardia. Diuretics may be needed to manage fluid retention that can occur with hydralazine therapy. MAO inhibitors should be used with caution due to potential for enhanced hypotensive effects. The medication may enhance the hypotensive effects of other antihypertensive agents.

Special Populations

Hydralazine metabolism is affected by acetylator phenotype; slow acetylators may require lower doses and are at higher risk for lupus-like syndrome. Renal impairment may require dosage adjustment due to reduced clearance. Use during pregnancy is considered relatively safe and hydralazine is often used for hypertensive emergencies in pregnancy. Dose reduction may be needed in elderly patients due to increased sensitivity.

Learn more at MedlinePlus

Frequently Asked Questions

Hydralazine triggers two compensatory responses that limit its effectiveness: reflex tachycardia (which can worsen angina) and sodium-water retention (which raises blood pressure back up). Adding a beta-blocker controls the heart rate response, and a diuretic prevents fluid retention. This "triple therapy" makes hydralazine far more effective and better tolerated.

Hydralazine can trigger a lupus-like syndrome — typically with fever, joint pain, rash, fatigue, and pleuritic chest pain — usually after months to years of treatment. Risk rises with daily doses above 200 mg, slow acetylator status, and female sex. Most cases resolve within weeks of stopping the drug. Report new joint pain, rash, or unexplained fevers to your doctor; a positive anti-histone antibody test supports the diagnosis.

The A-HeFT trial showed that adding hydralazine plus isosorbide dinitrate to standard therapy reduced mortality and heart failure hospitalizations in self-identified African American patients with HFrEF. Current guidelines recommend the combination for this group when symptoms persist on optimal ACE inhibitor/ARB/ARNI, beta-blocker, and aldosterone antagonist therapy. Other patients may also benefit when ACE inhibitors and ARBs are not tolerated.

Hydralazine has a short half-life (about 3–7 hours), so it requires dosing 2 to 4 times daily for sustained blood pressure control. Missing doses can cause significant blood pressure swings. If adherence is difficult, ask your doctor whether a longer-acting alternative would suit you.

Yes — headaches occur in up to 1 in 5 patients, especially when the dose is escalated. They usually result from vasodilation and improve over the first few weeks. Slow titration, splitting doses, and treating headaches with acetaminophen often help. Persistent or severe headaches warrant a call to your physician.

Questions to Ask Your Doctor

Consider discussing these topics at your next appointment:

✓Will I need a beta-blocker or diuretic added to hydralazine to manage side effects?
✓How often should we check labs (ANA, complete blood count) given the lupus-like syndrome risk?
✓What signs of fluid retention or angina should I report between visits?
✓If I struggle with multiple daily doses, is there a longer-acting alternative that would work for me?

Schedule an Appointment

Related Health Conditions

This medication is commonly used to treat or manage the following conditions:

Coronary Artery Disease (CAD)

Coronary Artery Disease (CAD) results from plaque buildup in coronary arteries (atherosclerosis), restricting blood flow and potentially causing angina, heart attack, or heart failure, influenced by factors like high blood pressure and cholesterol.

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Heart Failure Due to Coronary Artery Disease

Heart failure stemming from coronary artery disease arises from narrowed arteries restricting blood flow, weakening or stiffening the heart muscle and reducing its pumping efficiency.

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Osteoarthritis

Osteoarthritis, a common degenerative joint disease, causes pain, stiffness, and reduced motion due to cartilage breakdown from aging, genetics, obesity, injuries, or repetitive stress.

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Portal Hypertension

Portal hypertension, an elevated pressure in the portal vein due to blockage often from cirrhosis or other pre-hepatic causes, can lead to serious complications like bleeding and ascites.

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Secondary Pulmonary Hypertension

Secondary pulmonary hypertension, unlike its primary form, arises from underlying conditions such as heart/lung disease, blood clots, or connective tissue disorders, increasing lung artery pressure.

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Medical Disclaimer: This information is for educational purposes only and should not be considered medical advice. Always consult with your healthcare provider before starting, stopping, or changing any medication. Your doctor can provide personalized recommendations based on your specific health condition and medical history.