Clinical safety rating
safeAnimal studies have demonstrated safety
Hydralazine is a direct-acting vasodilator that relaxes arteriolar smooth muscle, leading to decreased peripheral vascular resistance and blood pressure. Its exact mechanism is unclear but may involve interference with calcium movement and increased cGMP levels.
| Metabolism | Primarily hepatic via acetylation (N-acetyltransferase 2, NAT2). Metabolites include hydralazine pyruvic acid hydrazone and acetylhydralazine. |
| Excretion | Hydralazine is primarily metabolized in the liver via N-acetylation and hydroxylation. Approximately 80-90% of the drug is eliminated in urine as metabolites, with less than 10% excreted unchanged. A small fraction appears in feces via biliary excretion. |
| Half-life | The terminal elimination half-life of hydralazine is approximately 2-4 hours in patients with normal renal function. However, the duration of antihypertensive effect may be longer (6-12 hours) due to tissue binding and slow release from vascular smooth muscle. In renal impairment, half-life may extend to 7-16 hours, necessitating dose adjustment. |
| Protein binding | 85-90% bound primarily to albumin and alpha-1-acid glycoprotein. |
| Volume of Distribution | 1.5-2.0 L/kg. This high Vd indicates extensive tissue binding and accumulation in vascular smooth muscle. |
| Bioavailability | Oral: 10-30% due to extensive first-pass metabolism. Bioavailability is lower in fast acetylators. Bioavailability is 100% for intravenous administration. |
| Onset of Action | Oral: 20-30 minutes. Intravenous: 5-20 minutes. Intramuscular: 10-30 minutes. Onset may be delayed in the presence of food. |
| Duration of Action | Oral: 3-8 hours (up to 12 hours with high doses). Intravenous: 2-6 hours. Duration may be extended in patients with slow acetylation phenotype or renal impairment. |
| Molecular Weight | 196.21 |
10-50 mg orally every 6 hours, titrate to maximum 300 mg/day; 10-20 mg intramuscularly or intravenously every 4-6 hours as needed.
| Renal impairment | GFR 10-50 mL/min: administer every 8-12 hours; GFR <10 mL/min: administer every 12-24 hours. |
| Liver impairment | Child-Pugh A: caution, consider starting at 25% of normal dose; Child-Pugh B: reduce dose by 50%; Child-Pugh C: contraindicated. |
| Pediatric use | 0.75-1 mg/kg/day orally divided every 6-12 hours, maximum 7.5 mg/kg/day; intravenous: 0.1-0.2 mg/kg/dose every 4-6 hours as needed. |
| Geriatric use | Start at 10 mg orally twice daily, increase slowly; monitor for hypotension and reflex tachycardia; maximal dose 200 mg/day. |
| 1st trimester | Use only if potential benefit justifies risk. Limited human data; animal studies suggest risk of teratogenic effects at high doses. |
| 2nd trimester | Monitor for maternal hypotension and fetal distress. May cause fetal tachycardia or thrombocytopenia. |
| 3rd trimester | May cause neonatal thrombocytopenia, tachycardia, or hypotension. Avoid if possible near term due to risk of fetal and neonatal adverse effects. |
Clinical note
Parenteral vasodilator used for acute treatment of severe-range blood pressures (≥160/110 mmHg) in pregnancy and postpartum. Extensively used for decades with no established teratogenicity. IV labetalol and oral/IV nifedipine are now often preferred for acute management, but hydralazine remains a reasonable alternative and is widely available in low-resource settings. Risk of maternal hypotension and reflex tachycardia with IV use.
| Placental transfer | Crosses placenta readily, with cord blood concentrations similar to maternal plasma levels. |
| Breastfeeding | Hydralazine is excreted into breast milk in small amounts (<0.5% of maternal dose). No reports of adverse effects in breastfed infants. Monitor infant for hypotension, tachycardia, or gastrointestinal disturbances. |
| Lactation Rating | L2 (Safer) |
| Teratogenic Risk | FDA Pregnancy Category C. First trimester: No well-controlled studies; animal studies show no evidence of teratogenicity but embryotoxicity at high doses. Second/Third trimesters: Associated with maternal hypotension potentially reducing placental perfusion; no fetal malformations reported, but neonatal thrombocytopenia, lupus-like syndrome, and arrhythmias reported with chronic use near term. |
| Fetal Monitoring | Maternal: Blood pressure (baseline and during therapy), heart rate, signs of drug-induced lupus (arthralgia, myalgia, rash, fever), peripheral neuropathy, and complete blood counts. Fetal: Serial ultrasound for growth, fetal heart rate monitoring; biophysical profile/Doppler if IUGR suspected. |
| Fertility Effects | No documented effects on human fertility. Animal studies suggest no impairment at therapeutic doses. Priapism (rare) may affect male fertility, but case reports are sparse. |
■ FDA Black Box Warning
Systemic lupus erythematosus-like syndrome (drug-induced lupus) with long-term use at high doses.
| Serious Effects |
Hypersensitivity to hydralazine or hydrazine derivativesCoronary artery diseaseMitral valve rheumatic heart diseaseHigh-output heart failureDissecting aortic aneurysmSystemic lupus erythematosus (active or history)
| Precautions | May cause drug-induced lupus erythematosus; discontinue if symptoms develop., Peripheral neuritis (pyridoxine deficiency) with long-term use., May precipitate angina or myocardial infarction in patients with coronary artery disease., Tachycardia and palpitations may occur; use with beta-blockers if needed., Blood dyscrasias (rare). |
| Food/Dietary | Take with food or milk to reduce stomach upset and slow absorption. Avoid high-tyramine foods (e.g., aged cheese, cured meats, fermented products) if taking a combination product containing hydralazine and hydrochlorothiazide–though hydralazine alone has no known significant food interactions. Limiting salt intake enhances antihypertensive effect. |
| Clinical Pearls | Hydralazine is a direct-acting vasodilator; first dose may cause profound hypotension—administer with food to减缓 absorption. Monitor for drug-induced lupus (especially in slow acetylators); baseline ANA recommended. Tachyphylaxis occurs; combine with beta-blocker and diuretic to counteract reflex tachycardia and fluid retention. Adjust dose in renal impairment (creatinine clearance < 10 mL/min). |
| Patient Advice | Take this medication exactly as prescribed, usually 3-4 times daily. Swallow tablets whole with a glass of water. · Do not stop taking this drug suddenly, as this may cause a rapid increase in blood pressure. · This medication may cause dizziness or lightheadedness, especially when getting up from a sitting or lying position. Rise slowly. · Report any unexplained fever, joint pain, rash, or sore throat to your healthcare provider immediately—these could be signs of a lupus-like reaction. · Avoid alcohol, as it can increase side effects like dizziness or drowsiness. · If you miss a dose, take it as soon as you remember unless it is almost time for the next dose. Do not double the dose. |
Loading safety data…