Schedule H

Oral, Intravenous (IV)

• Tablet: 25 mg, 50 mg

• Injection: 20 mg/mL ampoule (for IV/IM administration)

INDICATIONS + DOSING — FOR CLINICIAN USE ONLY

Primary Indications (Approved / Standard in India)

1. Moderate to Severe Hypertension (Adjunctive Therapy)

⚠️ Not recommended as monotherapy — must be combined with beta-blocker (to prevent reflex tachycardia) and diuretic (to prevent fluid retention)

Parameter Dose

Starting dose 25 mg orally twice daily

Titration Increase by 25 mg/dose every 2–5 days based on BP response

Usual maintenance dose 50–100 mg/day in 2–4 divided doses

Maximum dose 200 mg/day

Clinical Notes:

• Always combine with beta-blocker and diuretic

• Monotherapy causes reflex tachycardia and sodium/water retention

• Reserve for resistant hypertension or when first-line agents contraindicated

1. Hypertensive Emergency in Pregnancy (Severe Pre-eclampsia / Eclampsia)

Specialist use in obstetric ICU/inpatient setting only

IV Bolus Regimen:

Parameter Dose

Starting dose 5 mg IV bolus over 2 minutes

Titration May repeat 5–10 mg IV every 20–30 minutes based on BP response

Usual maintenance dose Not applicable (acute use)

Maximum dose 20 mg per single dose; cumulative 30–40 mg per episode

Continuous IV Infusion (Alternative):

Parameter Dose

Starting dose 0.5–1 mg/hour IV infusion

Titration Increase by 0.5–1 mg/hour every 15–20 minutes

Usual maintenance dose 2–5 mg/hour

Maximum dose 10 mg/hour

Clinical Notes:

• Target: Reduce MAP by ≤25% in first 1–2 hours

• Monitor maternal BP, pulse, urine output, and fetal heart rate continuously

• Preferred IV agent in pregnancy-related hypertensive emergencies per AIIMS/FOGSI protocols

• Have labetalol IV available as alternative if hydralazine ineffective

Secondary Indications – Adults (Off-label)

Indication Dose Duration Supervision Evidence Basis

Heart Failure with Reduced Ejection Fraction (HFrEF) (OFF-LABEL) 25–75 mg orally three to four times daily (in fixed combination with isosorbide dinitrate) Long-term Specialist only (Cardiologist) A-HeFT trial; Indian Heart Failure Society expert consensus; particularly beneficial in ACEi/ARB-intolerant patients

Notes:

• Use fixed-dose combination with isosorbide dinitrate (H-ISDN)

• Consider in patients intolerant to ACE inhibitors/ARBs or with advanced CKD

• Evidence strongest in Black populations but applicable in Indian practice per specialist consensus

PAEDIATRIC DOSING (Specialist Only)

⚠️ Not recommended below 1 month of age except under specialist supervision in NICU/PICU settings

Primary Indication: Severe/Symptomatic Hypertension, Hypertensive Emergency

Oral Dosing (Children ≥1 month):

Parameter Dose

Starting dose 0.25 mg/kg/dose orally twice daily

Titration Increase every 3–5 days based on BP response

Usual maintenance dose 0.75–1 mg/kg/day in 2–4 divided doses

Maximum dose 7.5 mg/kg/day OR 200 mg/day (whichever is lower)

IV Dosing (Neonates and Children — Hospital/ICU Setting):

Neonates 0.1–0.2 mg/kg IV slowly over 10 minutes May repeat every 4–6 hours as needed 0.5 mg/kg/dose

Infants & Children 0.1–0.2 mg/kg IV slowly over 10 minutes May repeat every 4–6 hours 0.5 mg/kg/dose or 20 mg (whichever is lower)

Safety Monitoring:

• Continuous BP and heart rate monitoring during IV administration

• Monitor renal function and electrolytes

• Watch for reflex tachycardia; consider concurrent beta-blocker if persistent

Secondary Indications – Paediatrics (Off-label)

Not established beyond above indications.

Mild-Moderate Impairment No specific dose adjustment required; use with caution

Severe Impairment (eGFR <30) Use cautiously; increased risk of fluid retention and drug accumulation

End-Stage Renal Disease / Dialysis Monitor closely for accumulation; hydralazine is not significantly dialysed

Additional Notes:

• Long-term use increases risk of drug-induced lupus in renal impairment

• Monitor for fluid overload and lupus-like symptoms

• Known hypersensitivity to hydralazine or any excipient

• Mitral valvular rheumatic heart disease (causes increased pulmonary pressure)

• Cor pulmonale

• Dissecting aortic aneurysm

• High-output cardiac states (e.g., thyrotoxicosis, arteriovenous shunts)

• Systemic lupus erythematosus (drug-induced lupus risk)

• Severe tachycardia or tachyarrhythmias (when beta-blocker cannot be given concurrently)

• Coronary artery disease (risk of angina from reflex tachycardia — always combine with beta-blocker)

• Cerebrovascular disease (avoid rapid BP drops; risk of stroke/TIA)

• Pre-existing tachycardia

• Renal impairment (increased accumulation risk)

• Slow acetylators (higher risk of lupus-like syndrome)

• Elderly patients (orthostatic hypotension, falls)

• Concurrent use of other antihypertensives (additive hypotension)

• Pulmonary hypertension

Parameter Information

Overall Safety Considered safe; one of the preferred agents for hypertensive emergencies in pregnancy

Preferred Use IV hydralazine is first-line for acute severe hypertension in pre-eclampsia/eclampsia (AIIMS/FOGSI protocols)

Alternatives Labetalol IV, Nifedipine oral (for non-emergency)

When to Use Acute BP lowering when SBP ≥160 or DBP ≥110 mmHg

Monitoring Maternal BP every 5 minutes during IV; continuous fetal heart rate monitoring; urine output

Parameter Information

Compatibility Compatible with breastfeeding at standard doses

Preferred Alternative Methyldopa preferred for chronic hypertension during lactation

Expected Drug Level in Milk Low

Infant Monitoring Feeding pattern, weight gain, signs of hypotension (lethargy, poor feeding)

Parameter Recommendation

Starting dose 10–25 mg orally twice daily

Titration Increase slowly every 5–7 days; use longer titration intervals

Increased Risks Postural hypotension, falls, reflex tachycardia, confusion

Additional Precautions Avoid monotherapy; ensure concurrent beta-blocker; monitor standing BP

Interacting Drug Effect Management

MAO inhibitors Severe enhanced hypotensive effect Avoid combination

Diazoxide Profound hypotension Avoid concurrent use

Other potent antihypertensives (IV nitroprusside, high-dose nitrates) Additive severe hypotension Use with extreme caution; reduce doses

Epinephrine / Adrenaline Paradoxical hypertensive response possible Use with caution in emergency settings

Interacting Drug Effect Management

Beta-blockers Beneficial combination (prevents reflex tachycardia) Should be co-prescribed; monitor for excessive bradycardia

Diuretics Additive hypotension (beneficial); prevents fluid retention Recommended combination; monitor electrolytes

NSAIDs May reduce antihypertensive effect Monitor BP; avoid long-term NSAID use

CNS depressants (benzodiazepines, opioids) Increased orthostatic hypotension Monitor; counsel patient on falls risk

Alcohol Enhanced hypotensive effect Advise moderation

Antidiabetics May enhance hypoglycaemic effect Monitor blood glucose

• Headache (very common, dose-related)

• Reflex tachycardia, palpitations

• Flushing

• Nasal congestion

• Nausea, vomiting, diarrhoea

• Fluid retention, peripheral oedema

• Dizziness

• Anorexia

Adverse Effect Clinical Action

Drug-induced lupus-like syndrome (dose- and duration-dependent; more common at >200 mg/day or >6 months use) Discontinue immediately; usually reversible; ANA-positive with arthralgia, fever, rash, serositis

Peripheral neuropathy (pyridoxine deficiency) Consider pyridoxine supplementation; discontinue if severe

Severe hypotension Supportive care; IV fluids; reduce dose or discontinue

Hepatotoxicity Monitor LFTs; discontinue if significant elevation

Agranulocytosis (rare) Discontinue immediately; haematology referral

Angina / Myocardial ischaemia (in CAD patients without beta-blocker cover) Ensure beta-blocker coverage; reduce dose

Long-term (if therapy >6 months) ANA titre every 6 months; CBC; LFTs; symptoms of lupus (arthralgia, rash, fever, serositis)

During IV use Continuous BP monitoring every 5 minutes; maternal and fetal heart rate (in pregnancy); urine output

• Apresol™

• Nepresol™

• Hydrazide™

• Hypres™

• Available in combination with isosorbide dinitrate: BiDil™ (limited availability)

Regulatory: Not listed under NLEM 2022; not under NPPA price control

1. Never use as monotherapy — reflex tachycardia and fluid retention limit efficacy; always combine with beta-blocker + diuretic

1. Preferred in pregnancy — IV hydralazine is first-line for acute severe hypertension in eclampsia/pre-eclampsia per Indian protocols; labetalol IV is alternative

1. Lupus risk threshold — risk increases significantly at doses >100 mg/day used for >6 months; monitor ANA and symptoms; more common in slow acetylators

1. Coronary artery disease — avoid unless patient is on beta-blocker; reflex tachycardia can precipitate angina or ischaemia

1. HFrEF combination — hydralazine + isosorbide dinitrate (H-ISDN) is useful in patients intolerant to ACE inhibitors/ARBs or with advanced CKD

1. Response latency — IV onset is 10–20 minutes; avoid stacking doses too rapidly; allow adequate time between boluses

hypertension; vasodilator; pregnancy-safe; eclampsia; pre-eclampsia; resistant-hypertension; HFrEF; drug-induced-lupus; Schedule-H; paediatric-specialist

RxIndia v1.0 — 15 May 2025

• CDSCO Product Information

• Indian Pharmacopoeia (IP)

• API Textbook of Medicine

• AIIMS Obstetric Hypertensive Emergency Protocol

• ICMR Guidelines: Hypertension Treatment

• FOGSI Good Clinical Practice Recommendations — Hypertensive Disorders of Pregnancy

• IAP Drug Formulary (Paediatric Dosing)

• Goodman & Gilman's The Pharmacological Basis of Therapeutics

• Harrison's Principles of Internal Medicine

• A-HeFT Trial (off-label HFrEF evidence)

• Indian Heart Failure Society Expert Consensus