HYDRALAZINE HYDROCHLORIDE
Clinical safety rating
safeMAOIs may cause excessive hypotension Can cause drug-induced lupus erythematosus and peripheral neuropathy.
Vasodilation of arterioles by direct relaxation of vascular smooth muscle, likely involving interference with calcium movement.
| Metabolism | Extensively metabolized in the liver via N-acetylation (N-acetyltransferase 2, NAT2) and subsequent conjugation; also metabolized by cytochrome P450 (CYP) enzymes. |
| Excretion | Hydralazine is primarily metabolized in the liver via N-acetylation (polymorphic) and hydroxylation. Less than 10% of the dose is excreted unchanged in urine. The major metabolites are hydralazine pyruvic acid hydrazone and other conjugates, which are excreted renally. Fecal elimination is negligible. |
| Half-life | The terminal elimination half-life of hydralazine is approximately 2–4 hours in patients with normal renal function, but it is prolonged in renal impairment (up to 7–16 hours). The antihypertensive effect often lasts longer than the half-life due to persistent binding to arteriolar receptors. |
| Protein binding | Approximately 85–90% bound to plasma proteins, primarily albumin and alpha-1-acid glycoprotein. |
| Volume of Distribution | 1.5–1.8 L/kg. This large Vd indicates extensive distribution into tissues, including arteriolar smooth muscle. |
| Bioavailability | Oral bioavailability is about 26–50% due to significant first-pass metabolism. Bioavailability is higher in slow acetylators compared to rapid acetylators. |
| Onset of Action | Oral: 20–30 minutes; Intravenous: 5–20 minutes; Intramuscular: 10–30 minutes. |
| Duration of Action | Oral: 3–8 hours (dose-dependent, with higher doses producing longer duration); Intravenous: 2–6 hours. Duration may be shorter in rapid acetylators. |
| Molecular Weight | 196.64 |
| Action Class | Potassium channel opener |
| Brand Substitutes | Dralgeen 20mg Injection |
Oral: Initiate with 10 mg 4 times daily for 2-4 days, then increase to 25 mg 4 times daily for the remainder of the week, then titrate to 50 mg 4 times daily. Maximum daily dose: 300 mg. Intravenous: 5-20 mg IV bolus, may repeat every 20-30 minutes as needed, or continuous IV infusion 0.5-10 mg/hour.
| Dosage form | TABLET |
| Renal impairment | CrCl 10-50 mL/min: Administer every 8 hours. CrCl <10 mL/min: Administer every 8-16 hours. Dose reduction may be necessary to avoid accumulation. |
| Liver impairment | Child-Pugh Class A and B: No specific recommendations; use with caution. Child-Pugh Class C: Contraindicated due to risk of hepatotoxicity and reduced drug clearance. |
| Pediatric use | Oral: 0.75-1 mg/kg/day divided every 6-12 hours, maximum 5 mg/kg/day. Intravenous: 0.1-0.2 mg/kg/dose IV every 4-6 hours as needed, maximum 0.5 mg/kg/dose (20 mg). |
| Geriatric use | Initiate at lower doses (e.g., 10 mg 2-3 times daily) and titrate slowly due to increased risk of hypotension and drug accumulation; monitor renal function closely. |
| 1st trimester | Use only if potential benefit justifies risk. Limited human data; no evidence of major teratogenicity. |
| 2nd trimester | May cause maternal hypotension and decreased uteroplacental perfusion; monitor closely. |
| 3rd trimester | May cause neonatal thrombocytopenia and hypotension; avoid near term unless necessary. |
Clinical note
MAOIs may cause excessive hypotension Can cause drug-induced lupus erythematosus and peripheral neuropathy.
| FDA category | Animal |
| Placental transfer | Crosses placenta readily; fetal serum concentrations similar to maternal. |
| Breastfeeding | Excreted into breast milk in small amounts; unlikely to affect nursing infant. Use with caution. |
| Lactation Rating | L3 (Moderately Safe) |
| Teratogenic Risk | First trimester: Limited human data; animal studies show no teratogenicity. Second/third trimester: Associated with maternal hypotension and potential fetal distress; no known structural anomalies. |
| Fetal Monitoring | Monitor maternal blood pressure and heart rate. Assess fetal heart rate during maternal hypotension. Consider ultrasound for fetal growth if prolonged use. |
| Fertility Effects | No known adverse effects on human fertility based on limited data. |
■ FDA Black Box Warning
May cause a syndrome resembling systemic lupus erythematosus (SLE), especially with prolonged use or high doses.
| Serious Effects |
Hypersensitivity to hydralazineMitral valve rheumatic heart diseaseSystemic lupus erythematosus
| Precautions | May cause drug-induced lupus, peripheral neuritis (pyridoxine deficiency), myocardial infarction (precipitate angina), hypotension, tachycardia, and blood dyscrasias. Use with caution in patients with coronary artery disease, cerebrovascular disease, or renal impairment. |
| Food/Dietary | Hydralazine absorption is significantly increased when taken with food; it is recommended to take with meals for consistent effect. Avoid high-tyramine foods (aged cheeses, cured meats, fermented products) if combined with MAOIs, though hydralazine itself is not an MAOI. No specific dietary restrictions otherwise. |
| Clinical Pearls | Hydralazine is a direct-acting arterial vasodilator; its antihypertensive effect is limited by reflex tachycardia and fluid retention, so it is typically used in combination with a beta-blocker and a diuretic. Slow acetylators are at increased risk of drug-induced lupus, especially with doses >200 mg/day. Administer with food to enhance bioavailability; onset of action occurs within 20-30 minutes IV. For hypertensive urgency, IV hydralazine 5-20 mg every 20-30 min is used, but avoid in suspected myocardial ischemia due to reflex tachycardia. |
| Patient Advice | Take exactly as prescribed, with food or milk to increase absorption. · Do not stop abruptly; sudden cessation can cause severe rebound hypertension. · Report symptoms like chest pain, rapid heartbeat, joint pain, rash, or fever to your doctor. · Avoid alcohol and other antihypertensives unless approved by your doctor. · Inform your doctor if you become pregnant or plan to become pregnant. · May cause dizziness; rise slowly from sitting or lying down. |
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