HYDRAP-ES
Clinical safety rating
cautionComprehensive 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. |
| Molecular Weight | 196.25 |
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 | Limited data; hydralazine is associated with teratogenic effects in animal studies. Use only if potential benefit justifies risk. |
| 2nd trimester | Use with caution; monitor for maternal hypotension and fetal distress. May reduce placental perfusion. |
| 3rd trimester | Use with caution; may cause neonatal thrombocytopenia, hypotension, or withdrawal symptoms. Avoid near term if possible. |
Clinical note
Comprehensive clinical and safety monograph for HYDRAP-ES (HYDRAP-ES).
| Placental transfer | Crosses the placenta; achieves fetal concentrations similar to maternal levels. |
| Breastfeeding | Hydralazine is excreted into breast milk in small amounts; however, concentrations are low and unlikely to cause adverse effects in nursing infants. Monitor infant for signs of hypotension. |
| Lactation Rating | L2 (Safer) |
| 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 | 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. |
■ FDA Black Box Warning
No FDA boxed warning for Hydralazine.
| Serious Effects |
Hypersensitivity to hydralazineMitral valve rheumatic heart diseaseCoronary artery disease
| 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 |
| Food/Dietary | Take with food to reduce gastrointestinal upset. Avoid high-tyramine foods if taking concomitant MAOIs, though hydralazine itself has no direct tyramine interaction. No specific food restrictions, but limit alcohol as it may exacerbate hypotension. |
| Clinical Pearls | Hydralazine, the active component, is a direct-acting vasodilator used for hypertension. It can cause a lupus-like syndrome, especially in slow acetylators. Monitor for tachycardia and fluid retention; consider concomitant beta-blocker and diuretic. Do not use as monotherapy for long-term management. Onset of action is rapid (15-20 min) IV, but oral bioavailability is variable (30-50%). Dose adjustments needed in renal impairment. |
| Patient Advice | Take exactly as prescribed; do not skip doses or double up. · May cause dizziness or lightheadedness; rise slowly from sitting or lying down. · Report any joint pain, rash, fever, or unexplained bruising/bleeding. · May cause headaches or palpitations, especially early in therapy. · Avoid sudden discontinuation to prevent rebound hypertension. |
Loading safety data…