Hydralazine is a long-standing prescription medicine used to lower blood pressure by relaxing the small arteries (arterioles). Because it targets resistance vessels, it reduces afterload and can improve forward blood flow from the heart. Clinicians use hydralazine in several settings: as an add-on for difficult-to-control hypertension, as part of a fixed-dose combination with isosorbide dinitrate in heart failure with reduced ejection fraction, and as an intravenous option for acute, severe hypertension—including during pregnancy under expert supervision. Like all vasodilators, it can cause reflex fast heart rate and fluid retention, so it’s often paired with a beta-blocker and a diuretic. A rare but important risk is drug-induced lupus with sustained higher doses. This guide explains how hydralazine works, when it helps, how to take it safely, what to expect, and who should avoid it.
Essential Insights
- Lowers blood pressure by directly relaxing arterioles, reducing afterload and improving cardiac output.
- In heart failure with reduced ejection fraction, the hydralazine–isosorbide dinitrate combination can improve symptoms and outcomes when appropriately prescribed.
- Rare risk of drug-induced lupus increases with prolonged high doses; monitor symptoms such as joint pain, fever, or rash.
- Typical oral maintenance 100–200 mg/day in divided doses (maximum 300 mg/day) as directed by a clinician.
- Avoid use in people with active coronary artery disease or rheumatic mitral valve disease unless a specialist advises otherwise.
Table of Contents
- What hydralazine is and how it works
- Does hydralazine work and who benefits?
- Dosing and how to take it safely
- Variables that change response and examples
- Common mistakes, risks, and who should avoid
- Evidence at a glance: clinical and guideline summary
What hydralazine is and how it works
Hydralazine is a direct vasodilator that preferentially relaxes arteriolar smooth muscle. By reducing peripheral vascular resistance, it lowers diastolic pressure more than systolic and decreases afterload, allowing the left ventricle to eject more blood with less effort. The result is a fall in blood pressure and, in some settings, improved stroke volume and cardiac output.
Mechanism, in plain terms. Vascular smooth muscle contracts when calcium enters the cells and interacts with contractile proteins. Hydralazine interferes with intracellular calcium handling and downstream signaling that maintain vascular tone. The drug binds within vascular tissue, so its blood-pressure effect can outlast the measured plasma half-life.
What that means clinically.
- Arteriolar selectivity minimizes venous pooling and orthostatic symptoms compared with mixed vasodilators.
- Reflex responses—faster heart rate and activation of the renin–angiotensin–aldosterone system—can offset part of the blood-pressure drop. That’s why clinicians usually pair hydralazine with a beta-blocker (to blunt tachycardia) and a diuretic (to limit fluid retention), especially when used chronically for hypertension.
- Afterload reduction is the reason hydralazine can help in heart failure when combined with a nitrate (isosorbide dinitrate). The nitrate reduces preload and improves coronary perfusion; hydralazine reduces afterload—together, they decrease wall stress and improve symptoms.
Formulations.
- Oral tablets: 10 mg, 25 mg, 50 mg, and 100 mg strengths are common.
- Injection: intravenous or intramuscular hydralazine is used in hospitals for urgent blood-pressure control when oral therapy isn’t possible, including certain pregnancy-related hypertensive crises.
Onset and duration. Oral onset often appears within 30–90 minutes; peak effect in 2–4 hours; duration 2–6 hours (sometimes longer due to tissue binding). Intravenous dosing has a quicker onset (minutes), but the magnitude and duration are variable, so careful monitoring is essential.
Metabolism and genetics. Hydralazine is primarily acetylated in the liver by N-acetyltransferase 2 (NAT2). “Slow acetylators” can have higher exposure, greater blood-pressure response, and increased risk of some adverse effects, including drug-induced lupus, especially at sustained higher daily doses.
Where it fits. Hydralazine isn’t usually a first-line antihypertensive; it’s more often an add-on for resistant hypertension or used when specific comorbidities or contraindications to other agents exist. In heart failure with reduced ejection fraction (HFrEF), the hydralazine–isosorbide dinitrate (H-ISDN) combination is an option alongside guideline-directed therapies.
Does hydralazine work and who benefits?
Hydralazine does lower blood pressure effectively, particularly as part of combination therapy. Its benefits are clearest when the treatment goal is targeted afterload reduction or when specific clinical scenarios favor its pharmacology.
Who benefits in hypertension.
- Resistant hypertension: Patients already on multiple drugs (commonly a renin–angiotensin blocker, calcium-channel blocker, and thiazide-type diuretic) may benefit from add-on hydralazine. Its arteriolar selectivity can yield incremental drops in diastolic pressure.
- Hypertension with chronic kidney disease: Because hydralazine can maintain or increase renal blood flow, it’s sometimes chosen when other options are limited. Still, clinicians must watch for fluid retention and pair it appropriately (often with a loop diuretic in advanced CKD).
- Hospital settings: As an IV option, hydralazine is used for acute, severe hypertension when oral therapy isn’t feasible and rapid reduction is required under monitoring.
Who benefits in heart failure.
- HFrEF on guideline-directed therapy: Adding hydralazine plus isosorbide dinitrate can improve symptoms and exercise tolerance, and in selected populations (notably in self-identified Black patients in a key trial), reduce hospitalization risk and improve survival when titrated to target doses.
- ACE inhibitor/ARB/ARNI intolerance: For patients who cannot take renin–angiotensin inhibitors due to cough, angioedema, renal artery stenosis, or advanced kidney disease, the H-ISDN combination is a reasonable alternative for afterload reduction.
Pregnancy-related severe hypertension.
In skilled hands and appropriate settings, IV hydralazine is among the agents used to treat acute-onset severe hypertension in pregnancy and the postpartum period. Its role is alongside other first-line options such as IV labetalol or immediate-release oral nifedipine. Choice depends on clinical context, access, and clinician experience. Because blood-pressure response to IV hydralazine can be unpredictable, careful bedside monitoring is essential.
Limitations.
- Tolerance and counter-regulation: Sympathetic activation may limit sustained blood-pressure reductions unless hydralazine is combined with a beta-blocker and a diuretic.
- Dosing frequency: Traditional regimens use multiple daily doses (3–4 times daily), which can challenge adherence.
- Adverse-effect profile: Headache, flushing, palpitations, and edema are not uncommon; rare immune-mediated effects require awareness.
Bottom line. Hydralazine works best when its pharmacology is matched to the goal: add-on afterload reduction in resistant hypertension, paired vasodilation in HFrEF (with a nitrate), or carefully monitored IV use for acute severe hypertension—especially in obstetric settings—when clinicians need an immediate effect.
Dosing and how to take it safely
Always follow your clinician’s instructions. The ranges below describe commonly used regimens and typical limits, but individual plans vary based on response, comorbidities, and concurrent medications.
Oral dosing for chronic hypertension (adults).
- Start: 10 mg four times daily for 2–4 days.
- Titrate: Increase to 25 mg four times daily for the remainder of week 1.
- Maintenance: 50 mg four times daily; many patients can be maintained at 100–200 mg/day divided (e.g., 25–50 mg 3–4 times daily).
- Maximum: 300 mg/day (divided doses).
- Adherence-friendly alternatives: Some clinicians consolidate to 25–100 mg twice to three times daily after stabilization, balancing control and practicality.
Pediatric oral dosing (specialist settings).
- Commonly 0.75 mg/kg/day in four divided doses; gradual titration up to 7.5 mg/kg/day or 200 mg/day (whichever is lower), with careful monitoring. Pediatric use should be managed by clinicians experienced in pediatric hypertension.
Intravenous (IV) or intramuscular (IM) dosing (inpatient use).
- Typical IV bolus doses are 5–20 mg, with reassessment and repeat dosing at measured intervals based on response and protocols. Some labels describe 20–40 mg IV/IM in urgent-care contexts, repeated as needed. Because response can be variable and prolonged, continuous bedside monitoring is required.
- In obstetric hypertensive emergencies, hospitals use protocolized IV dosing (for example, 5–10 mg IV, reassess in 20–30 minutes) with maternal–fetal monitoring and team-based care.
Heart failure (H-ISDN combination).
- Fixed-dose product (e.g., 20 mg isosorbide dinitrate/37.5 mg hydralazine): 1 tablet three times daily, titrating toward 2 tablets three times daily as tolerated (target 40 mg ISDN/75 mg hydralazine three times daily).
- Separate tablets: Some clinicians titrate hydralazine 25–75 mg three to four times daily with isosorbide dinitrate 20–40 mg three times daily, individualized to blood pressure and symptoms.
Renal or hepatic considerations.
- Metabolism is hepatic; metabolites are renally excreted. In advanced renal impairment, start low and titrate cautiously (exposure can increase). Clinicians may widen dosing intervals or lower maintenance doses in severe impairment.
- In hepatic impairment, start low due to reduced first-pass metabolism and higher exposure.
What to pair with hydralazine.
- For chronic hypertension: Combine with a beta-blocker (to blunt tachycardia) and a diuretic (to counter fluid retention).
- In HFrEF: Hydralazine is paired with a nitrate; do not combine nitrates with PDE-5 inhibitors (e.g., sildenafil, tadalafil) due to the risk of dangerous hypotension.
Practical tips for safe use.
- Take at regular intervals with or without food; consistency helps maintain levels.
- Do not stop abruptly; sudden withdrawal may worsen blood pressure.
- Track blood pressure and heart rate at home if your clinician recommends it—especially during dose changes.
- Report headache, palpitations, ankle swelling, joint pain, unexplained fever, or rash promptly.
- If doses are missed, take the next scheduled dose; do not double up unless your clinician directs you.
When to call urgently.
- Chest pain, severe dizziness/fainting, new neurologic symptoms, or shortness of breath warrant immediate medical evaluation.
Variables that change response and examples
Hydralazine’s effect varies widely among individuals. Knowing what shifts the response helps clinicians tailor therapy and anticipate side effects.
1) Acetylator status (NAT2).
- Slow acetylators: Higher plasma levels at a given dose, more potent blood-pressure lowering, and higher risk of immune-mediated adverse effects (notably drug-induced lupus) with sustained higher daily doses.
- Fast acetylators: Lower exposure; may require higher or more frequent dosing to achieve the same effect.
2) Sympathetic and RAAS activation.
Hydralazine can trigger reflex tachycardia and renin release. Pairing with a beta-blocker and diuretic is often necessary to maintain the antihypertensive effect and minimize edema.
3) Kidney function.
- Advanced CKD: Hydralazine may be attractive because it can maintain renal blood flow; however, fluid retention risk is higher. In stage 4–5 CKD, clinicians often choose lower starting doses and titrate slowly with close monitoring, usually alongside a loop diuretic.
4) Heart rate and ischemia risk.
- In coronary artery disease, reflex tachycardia can precipitate angina. If hydralazine is used, a beta-blocker is essential; in many cases, other agents are preferred.
- In aortic dissection (or suspected), hydralazine can increase shear stress—avoid; use agents that both lower blood pressure and reduce dP/dt (e.g., IV beta-blockers) under specialist care.
5) Pregnancy.
- IV hydralazine is one of several first-line treatments for acute severe hypertension in pregnancy/postpartum within standardized hospital protocols. Choice among hydralazine, labetalol, and nifedipine depends on the scenario, timing, and resources.
- For chronic hypertension during pregnancy, clinicians typically favor other oral agents with more predictable profiles; hydralazine is not commonly used as daily monotherapy.
6) Concomitant drugs.
- With nitrates (in HFrEF), hydralazine complements preload reduction.
- With PDE-5 inhibitors: The combination of nitrates and PDE-5 inhibitors is contraindicated; if you are on an H-ISDN combination, avoid PDE-5 inhibitors.
- With other antihypertensives: Additive hypotension can occur; careful titration prevents overshoot.
7) Age.
- Older adults may need lower starting doses due to slower clearance and higher sensitivity to dizziness or orthostatic symptoms.
- Children require weight-based dosing and specialist oversight.
Examples of tailoring.
- Resistant hypertension in CKD stage 4: Start hydralazine 10–25 mg two to three times daily with a loop diuretic and a beta-blocker, titrating every 3–7 days as tolerated.
- HFrEF patient intolerant to ACE inhibitors: Initiate fixed-dose H-ISDN 20/37.5 mg three times daily and up-titrate to 40/75 mg three times daily if tolerated, watching for headache and hypotension.
- Acute severe hypertension postpartum: IV hydralazine 5–10 mg in a monitored setting with reassessment in 20–30 minutes, per protocol, until targets are met or an alternative is chosen.
Common mistakes, risks, and who should avoid
Common mistakes.
- Using hydralazine alone for chronic hypertension without a beta-blocker and diuretic: reflex tachycardia and fluid retention can undermine control.
- Escalating too fast: Rapid titration raises the risk of headache, flushing, and hypotension.
- Skipping doses: Because effect duration is modest, missed doses can cause rebound hypertension; set reminders and simplify regimens when possible.
- Overlooking drug interactions: In H-ISDN therapy, patients must avoid PDE-5 inhibitors due to life-threatening hypotension with nitrates.
- Missing early clues of immune reactions: Unexplained fever, joint pains, or a new rash during sustained therapy—especially at higher daily doses—warrants prompt evaluation.
Side effects to expect vs. to report.
- Common: Headache, flushing, palpitations, nasal congestion, nausea, and ankle swelling. These often ease with dose adjustment or after a few days.
- Serious (seek care): Chest pain, fainting, severe dizziness, shortness of breath, or neurologic symptoms.
- Drug-induced lupus (rare): Symptoms may include joint pain, muscle aches, fever, fatigue, and rash; lab tests often show antinuclear antibodies (ANA) or anti-histone antibodies. Risk rises with prolonged exposure to ≥200 mg/day and in slow acetylators, but it can occur at lower doses. Symptoms usually resolve after stopping the drug under medical guidance.
Who should avoid or use extreme caution.
- Allergy to hydralazine.
- Coronary artery disease or hypertrophic cardiomyopathy with angina: risk of worsening ischemia from reflex tachycardia—avoid or use with a beta-blocker and specialist input.
- Rheumatic mitral valve disease: hydralazine-induced increases in cardiac output may worsen hemodynamics.
- Aortic dissection (suspected or confirmed): avoid due to rising shear stress.
- Severe tachycardia at baseline: hydralazine may exacerbate rate.
- Advanced renal or hepatic impairment: start low, go slow; consider alternatives if intolerance occurs.
- Concomitant nitrates plus PDE-5 inhibitors: if you are on hydralazine–isosorbide dinitrate, do not use PDE-5 inhibitors.
Monitoring checklist for clinicians.
- Blood pressure and heart rate at baseline and during titration.
- Fluid status (edema, weight).
- Consider periodic labs if prolonged high-dose therapy: complete blood count and ANA per local practice, especially if symptoms suggest immune effects.
Patient safety habits.
- Keep an updated medication list (including over-the-counter drugs and supplements).
- Use a home BP log if instructed.
- Have a plan for missed doses and refills before they run out.
Evidence at a glance: clinical and guideline summary
Hypertension (chronic). Hydralazine consistently lowers diastolic and systolic pressures when added to multi-drug regimens. Because of counter-regulatory responses and adherence challenges, it is rarely first-line but remains a useful add-on for resistant cases. Labeling supports stepwise dose escalation from 10 mg four times daily to 25 mg four times daily in week 1, then 50 mg four times daily, with a maximum 300 mg/day—tailored to response and tolerability.
Hypertensive emergencies and pregnancy. In acute severe hypertension during pregnancy or postpartum, hospital protocols list IV hydralazine—alongside IV labetalol or immediate-release nifedipine—as a first-line agent. Treatment aims to lower severe pressures promptly (often within 30–60 minutes) to reduce the risk of maternal stroke, while avoiding precipitous hypotension that could compromise uteroplacental perfusion. Because IV hydralazine’s response can be variable and prolonged, obstetric and anesthesia teams titrate doses carefully and monitor both mother and fetus.
Heart failure with reduced ejection fraction (HFrEF). The hydralazine–isosorbide dinitrate (H-ISDN) combination provides dual vasodilation—reduced preload (nitrate) and afterload (hydralazine). Fixed-dose products initiate at 20/37.5 mg three times daily and titrate toward 40/75 mg three times daily as tolerated. Trials and labeling support improved quality of life and, in selected populations on background therapy, reductions in heart-failure hospitalizations and mortality. Headache and dizziness are common and may limit rapid up-titration; clinicians titrate over days to weeks.
Safety signals.
- Drug-induced lupus: rare, dose- and duration-related; resolve in most patients after discontinuation. Consider risk higher with ≥200 mg/day for months and in slow acetylators; monitor for fevers, arthralgias, and rashes.
- Peripheral neuritis: uncommon, possibly linked to antipyridoxine effect; symptoms include paresthesias and numbness.
- Ischemia risk: Reflex tachycardia may trigger angina; combination with a beta-blocker mitigates this.
- Hypotension and syncope: especially during titration or when combined with other vasodilators.
Clinical takeaways for practice.
- Use hydralazine purposefully: afterload reduction in resistant hypertension (with a beta-blocker and diuretic), H-ISDN in HFrEF, or IV dosing in acute severe hypertension under monitoring.
- Start low, go slow, and simplify dosing schedules to support adherence.
- Anticipate and manage reflex responses and fluid retention; pair with appropriate agents.
- Maintain a high index of suspicion for immune-mediated effects with prolonged high-dose therapy.
References
- Hydralazine – StatPearls – NCBI Bookshelf 2023 (Overview, dosing, adverse effects)
- DailyMed – HYDRALAZINE HYDROCHLORIDE tablet 2011 (Labeling, oral dosing, safety)
- DailyMed – HYDRALAZINE HYDROCHLORIDE injection 2022 (Labeling, IV dosing, warnings)
- DailyMed – BIDIL- hydralazine hydrochloride and isosorbide dinitrate tablet, film coated 2021 (Labeling, H-ISDN dosing, precautions)
- Hypertension in Pregnancy and Postpartum 2025 (Review, obstetric hypertension standards)
Medical Disclaimer
This article provides general educational information about hydralazine and related therapies. It is not a substitute for personalized medical advice, diagnosis, or treatment. Medications, doses, and monitoring must be selected by a qualified clinician who knows your health history. If you have questions about starting, stopping, or changing any medicine—or experience concerning symptoms—seek medical care promptly. If you think you are experiencing a medical emergency, call your local emergency number immediately.
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