APRESOLINE
Clinical safety rating
cautionComprehensive clinical and safety monograph for APRESOLINE (APRESOLINE).
Direct-acting arteriolar vasodilator that relaxes vascular smooth muscle, leading to decreased peripheral resistance and blood pressure. The exact molecular mechanism is unclear but may involve interference with calcium movement or inhibition of inositol trisphosphate-induced calcium release.
| Metabolism | Extensively metabolized in the liver via acetylation (N-acetyltransferase, NAT2) and oxidation (CYP450, primarily CYP3A4 and CYP2C19). |
| Excretion | Primarily renal; 86-90% of an oral dose is excreted in urine as metabolites (N-acetylhydralazine, hydralazine pyruvic acid hydrazone) and unchanged drug (<10% unchanged); biliary/fecal excretion is minimal (<10%). |
| Half-life | Terminal elimination half-life is 3-7 hours in patients with normal renal function; prolonged to 7-16 hours in renal impairment. Acetylator phenotype affects half-life: in slow acetylators, half-life may be 4-5 hours; in fast acetylators, 1-2 hours, but clinical effect (antihypertensive) lasts longer due to persistent binding to vascular tissue. |
| Protein binding | 87-90% bound to plasma proteins, primarily albumin; binding is reduced in uremia. |
| Volume of Distribution | 1.5-1.8 L/kg; distributes widely into total body water, with high affinity for vascular smooth muscle, where it accumulates; Vd is larger in slow acetylators due to higher free drug levels. |
| Bioavailability | Oral immediate-release: 30-50% in fast acetylators; 50-75% in slow acetylators. Bioavailability is increased when taken with food (peak concentration enhanced 50-70%). |
| Onset of Action | Intravenous: 5-20 minutes; Intramuscular: 10-30 minutes; Oral: 20-30 minutes for immediate-release; occurs later for sustained-release formulations (1-2 hours). |
| Duration of Action | Intravenous: 2-4 hours; Intramuscular: 2-4 hours; Oral immediate-release: 2-4 hours (antihypertensive effect); Oral sustained-release: 8-12 hours. Duration is longer in slow acetylators and shorter in fast acetylators due to metabolic clearance. |
| Molecular Weight | 236.27 |
Initial: 10 mg oral 4 times daily for 2-4 days; increase to 25 mg 4 times daily for the first week. Maintenance: 50 mg 4 times daily; maximum 300 mg/day. IV: 20-40 mg IM or slow IV push, repeat as needed.
| Dosage form | TABLET |
| Renal impairment | CrCl 10-50 mL/min: administer every 8 hours. CrCl <10 mL/min: administer every 8 hours or reduce dose by 50%. |
| Liver impairment | Child-Pugh Class B: reduce dose by 50%. Child-Pugh Class C: avoid use or reduce dose by 75%. |
| Pediatric use | Oral: 0.75-3 mg/kg/day in 2-4 divided doses, maximum 7.5 mg/kg/day or 200 mg/day. IV: 0.1-0.2 mg/kg/dose every 4-6 hours as needed. |
| Geriatric use | Start at 10 mg 2-3 times daily; increase gradually to avoid hypotension. Maximum 200 mg/day. Monitor for orthostatic hypotension and reflex tachycardia. |
| 1st trimester | Limited human data; animal studies show no evidence of teratogenicity. Use only if clearly needed. |
| 2nd trimester | May cause maternal hypotension and reduced uteroplacental perfusion. Monitor blood pressure closely. |
| 3rd trimester | Risk of neonatal hypotension, thrombocytopenia, and meconium-stained amniotic fluid. Avoid near term. |
Clinical note
Comprehensive clinical and safety monograph for APRESOLINE (APRESOLINE).
| Placental transfer | Crosses placenta; fetal concentrations approximately 50-70% of maternal levels. |
| Breastfeeding | Small amounts excreted into breast milk; likely compatible with breastfeeding. Monitor infant for hypotension. |
| Lactation Rating | L2 |
| Teratogenic Risk | First trimester: Limited human data; animal studies show no teratogenicity at clinically relevant doses, but risk cannot be excluded. Second and third trimesters: May cause fetal tachycardia, neonatal hypotension, and ileus; associated with maternal hypotension and potential uteroplacental insufficiency. FDA Pregnancy Category C. |
| Fetal Monitoring | Monitor maternal blood pressure frequently; assess for maternal hypotension, tachycardia, and lupus-like syndrome. Fetal monitoring: heart rate and growth; neonatal monitoring for hypotension and ileus if used near delivery. |
| Fertility Effects | No known adverse effects on human fertility. Animal studies have not shown impairment of fertility. |
■ FDA Black Box Warning
None.
| Serious Effects |
Hypersensitivity to hydralazineMitral valve rheumatic heart diseaseSystemic lupus erythematosus (SLE)
| Precautions | May cause drug-induced lupus erythematosus, especially in slow acetylators; monitor for symptoms. Use cautiously in patients with coronary artery disease (may cause reflex tachycardia and exacerbate angina). Can cause peripheral neuritis (pyridoxine deficiency), alone with high doses. May cause sodium and water retention, requiring concomitant diuretic therapy. |
| Food/Dietary | Food may increase bioavailability of hydralazine; take with food to reduce peak concentrations and potential side effects. Avoid tyramine-rich foods (e.g., aged cheeses, cured meats) if taking MAOIs concurrently. No specific dietary restrictions otherwise. |
| Clinical Pearls | Hydralazine (Apresoline) is a direct-acting vasodilator primarily used for hypertension management, especially in preeclampsia and hypertensive emergencies. It can cause a lupus-like syndrome, especially in slow acetylators; testing for N-acetyltransferase 2 (NAT2) phenotype may be considered. Tachyphylaxis can occur; concomitant beta-blocker and diuretic therapy are often required. Onset of action is 10-20 minutes IV, 20-30 minutes IM. Avoid in patients with coronary artery disease due to reflex tachycardia. |
| Patient Advice | Take exactly as prescribed; do not stop suddenly as this can cause a rapid rise in blood pressure. · May cause dizziness or lightheadedness; avoid driving or operating machinery until you know how this medicine affects you. · Report any unexplained joint pain, fever, chest pain, or rash to your doctor immediately as these may be signs of a serious reaction (drug-induced lupus). · Avoid alcohol consumption as it can increase the blood pressure lowering effects and dizziness. · Do not take over-the-counter cold, sinus, or weight loss products without checking with your doctor, as many contain ingredients that can raise blood pressure. |
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