HYDRAP-ES
Clinical safety rating: caution
Comprehensive clinical and safety monograph for HYDRAP-ES (HYDRAP-ES).
Hydralazine is a direct-acting vasodilator that relaxes arteriolar smooth muscle, leading to decreased systemic vascular resistance and reduced blood pressure. The exact molecular mechanism involves inhibition of inositol trisphosphate (IP3)-induced calcium release from the sarcoplasmic reticulum and activation of guanylate cyclase, increasing cGMP levels.
| Metabolism | Primarily hepatic via N-acetylation by N-acetyltransferase 2 (NAT2). Metabolites include hydralazine pyruvic acid hydrazone, acetylhydralazine, and others. |
| Excretion | Primarily renal (80-90% as unchanged drug); minor biliary/fecal (<10%). |
| Half-life | Terminal elimination half-life is 2-4 hours in patients with normal renal function; prolonged in renal impairment (up to 20 hours in severe cases). |
| Protein binding | Approximately 87% bound to plasma proteins (primarily albumin). |
| Volume of Distribution | 0.3-0.5 L/kg, indicating distribution primarily in extracellular fluid. |
| Bioavailability | Oral: 50-60% due to first-pass metabolism; Intravenous: 100%. |
| Onset of Action | Intravenous: 5-10 minutes; Oral: 30-60 minutes. |
| Duration of Action | Intravenous: 2-4 hours; Oral: 4-6 hours. Clinical effect correlates with plasma concentration; duration may be extended in renal impairment. |
Oral: 25-50 mg twice daily, max 200 mg/day. IV: 10-20 mg every 4-6 hours as needed.
| Dosage form | TABLET |
| Renal impairment | GFR 10-50 mL/min: Administer every 6-8 hours. GFR <10 mL/min: Administer every 8-12 hours. |
| Liver impairment | Child-Pugh A: No adjustment. Child-Pugh B: Reduce dose by 50%. Child-Pugh C: Use with caution, reduce dose by 75%. |
| Pediatric use | Oral/IV: 0.1-0.5 mg/kg/dose every 6 hours; max initial dose 25 mg/dose. |
| Geriatric use | Start at 10-25 mg twice daily; titrate slowly due to increased risk of hypotension and electrolyte disturbances. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for HYDRAP-ES (HYDRAP-ES).
| Breastfeeding | Excreted in breast milk in low concentrations; M/P ratio approximately 0.2. Considered compatible with breastfeeding; monitor infant for hypotension and drowsiness. |
| Teratogenic Risk | First trimester: No evidence of teratogenicity in human studies; animal studies show no fetal harm. Second and third trimesters: Associated with reduced placental perfusion and fetal growth restriction; risk of neonatal hypotension, hypoglycemia, and bradycardia if used near term. |
| Fetal Monitoring |
■ FDA Black Box Warning
No FDA boxed warning for Hydralazine.
| Serious Effects |
["Hypersensitivity to hydralazine","Mitral valve rheumatic heart disease","Coronary artery disease (due to reflex tachycardia)"]
| Precautions | ["May cause drug-induced lupus erythematosus (especially in slow acetylators)","May cause peripheral neuritis (pyridoxine deficiency)","May cause tachycardia, angina, or myocardial infarction in patients with coronary artery disease","May cause hypotension and renal impairment","Monitor for signs of lupus and neuropathy"] |
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| Monitor maternal blood pressure, heart rate, and renal function. Fetal assessment includes ultrasound for growth every 4 weeks, nonstress test or biophysical profile twice weekly after 28 weeks, and monitoring for oligohydramnios. |
| Fertility Effects | No known adverse effects on fertility in animal or human studies. |