APRESOLINE-ESIDRIX
Clinical safety rating
cautionComprehensive clinical and safety monograph for APRESOLINE-ESIDRIX (APRESOLINE-ESIDRIX).
Apresoline (hydralazine) is a direct-acting vasodilator that relaxes arteriolar smooth muscle via unknown mechanism; Esidrix (hydrochlorothiazide) is a thiazide diuretic that inhibits sodium and chloride reabsorption in the distal convoluted tubule.
| Metabolism | Hydralazine undergoes N-acetylation (polymorphic, NAT2) and CYP450; hydrochlorothiazide is not extensively metabolized (excreted unchanged in urine). |
| Excretion | Renal: Hydralazine 85-90% as metabolites, 5-10% unchanged; Hydrochlorothiazide 95% as unchanged drug. Biliary/fecal: Hydralazine <10%. |
| Half-life | Hydralazine: 2-8 h (prolonged in renal impairment); Hydrochlorothiazide: 6-15 h (mean 10 h, increased in renal failure). |
| Protein binding | Hydralazine: 85-90% (primarily albumin); Hydrochlorothiazide: 40-68% (albumin). |
| Volume of Distribution | Hydralazine: 1.5-1.8 L/kg (extensive tissue distribution); Hydrochlorothiazide: 0.83-1.2 L/kg. |
| Bioavailability | Hydralazine: 30-50% (oral, extensive first-pass metabolism; slower in slow acetylators); Hydrochlorothiazide: 65-75% (oral). |
| Onset of Action | Hydralazine: oral 20-30 min, IV 5-20 min; Hydrochlorothiazide: oral 2 h. |
| Duration of Action | Hydralazine: oral 2-4 h, IV 2-6 h; Hydrochlorothiazide: oral 6-12 h. |
| Molecular Weight | Hydralazine: 160.18 Da; Hydrochlorothiazide: 297.73 Da |
Hydralazine (Apresoline): Oral, initial 10 mg 4 times daily for first 2-4 days, then increase to 25 mg 4 times daily for first week, then 50 mg 4 times daily thereafter. Maximum daily dose: 300 mg. Hydrochlorothiazide (Esidrix): Oral, initial 12.5-25 mg once daily, may increase to 50 mg once daily if needed.
| Dosage form | TABLET |
| Renal impairment | Hydralazine: No adjustment for GFR >10 mL/min; for GFR <10 mL/min, reduce dose to 30-50% of normal. Hydrochlorothiazide: Not effective if GFR <30 mL/min; use alternative diuretic. For CrCl 30-50 mL/min, reduce dose or interval. |
| Liver impairment | Hydralazine: Child-Pugh A: no adjustment; Child-Pugh B: reduce dose by 50%; Child-Pugh C: contraindicated. Hydrochlorothiazide: Caution in severe liver disease due to electrolyte imbalances; no specific dose adjustment defined; use with monitoring. |
| Pediatric use | Hydralazine: Oral, initial 0.75-1 mg/kg/day in 2-4 divided doses, increase over 3-4 weeks to maximum 7.5 mg/kg/day or 200 mg/day. Hydrochlorothiazide: Oral, 1-2 mg/kg/day in 2 divided doses; maximum 6 mg/kg/day or 50 mg/day. |
| Geriatric use | Hydralazine: Start at lower end of dosing range (10 mg 4 times daily) and titrate slowly due to increased sensitivity and risk of hypotension. Hydrochlorothiazide: Start at 12.5 mg once daily, monitor renal function and electrolytes more frequently. |
| 1st trimester | Hydralazine and hydrochlorothiazide cross the placenta. First-trimester exposure to hydrochlorothiazide is associated with a possible increased risk of congenital anomalies, including neural tube defects. Use only if clearly needed with caution. |
| 2nd trimester | Second-trimester use may be considered for hypertension if benefits outweigh risks. Both drugs cross the placenta. Monitor fetal growth and amniotic fluid volume due to potential for decreased placental perfusion and electrolyte imbalance. |
| 3rd trimester | Third-trimester use may cause fetal/neonatal adverse effects including electrolyte disturbances, hypoglycemia, and thrombocytopenia. Hydrochlorothiazide may decrease amniotic fluid volume. Avoid use in pregnancy-induced hypertension or preeclampsia. |
Clinical note
Comprehensive clinical and safety monograph for APRESOLINE-ESIDRIX (APRESOLINE-ESIDRIX).
| Placental transfer | Both hydralazine and hydrochlorothiazide cross the placenta based on human data. Detectable in cord blood at levels 0.5-0.9 of maternal serum for hydralazine. |
| Breastfeeding | Hydralazine and hydrochlorothiazide are excreted into breast milk in low amounts. Hydrochlorothiazide may suppress lactation and reduce milk volume. The American Academy of Pediatrics considers hydralazine compatible with breastfeeding. Monitor infant for signs of electrolyte imbalance and hypotension. |
| Lactation Rating | L3: Limited Data - Probably Compatible |
| Teratogenic Risk | APRESOLINE-ESIDRIX (hydralazine/hydrochlorothiazide). First trimester: Hydrochlorothiazide (HCTZ) may cause fetal or neonatal jaundice, thrombocytopenia, and possibly other adverse reactions. Hydralazine has been associated with minor anomalies in animal studies but no well-controlled human studies; risk cannot be ruled out. Second/third trimester: Maternal hypotension may reduce uterine blood flow; HCTZ may cause fetal electrolyte disturbances, thrombocytopenia, and jaundice. Avoid use for edema in pregnancy; use only if clearly needed. |
| Fetal Monitoring | Monitor maternal blood pressure, serum electrolytes, renal function, and hydration status. Fetal monitoring: assess fetal heart rate and growth (ultrasound) if prolonged use; be alert for signs of fetal distress or oligohydramnios (HCTZ). Monitor neonatal jaundice and thrombocytopenia if used near term. |
| Fertility Effects | Hydralazine: No known adverse effects on fertility in animal studies. Hydrochlorothiazide: No known effect on fertility. No human data indicating impaired fertility from combination. |
■ FDA Black Box Warning
No black box warning specifically for the combination; hydralazine carries a warning for drug-induced lupus erythematosus.
| Common Effects | Headache Dizziness |
| Serious Effects |
AnuriaHypersensitivity to hydralazine, hydrochlorothiazide, or sulfonamide-derived drugsAcute myocardial infarctionDissecting aortic aneurysmSevere renal impairment (creatinine clearance <30 mL/min)Severe hepatic impairmentHyponatremia or hypokalemia refractory to treatmentSystemic lupus erythematosus (hydralazine may induce lupus-like syndrome)
| Precautions | Lupus erythematosus-like syndrome (hydralazine), Hypotension, Myocardial infarction (exacerbation due to reflex tachycardia), Electrolyte imbalances (hypokalemia, hyponatremia) from thiazide, Hyperuricemia, Sulfonamide allergy cross-reactivity (thiazide) |
| Food/Dietary | Avoid natural licorice (glycyrrhizin) as it can worsen hypokalemia and reduce antihypertensive effect. High-sodium foods should be limited as they can counteract the blood pressure-lowering effect. Grapefruit juice may enhance hydralazine absorption; consistent consumption is advised if intake is routine. Alcohol may potentiate orthostatic hypotension and dizziness. |
| Clinical Pearls | APRESOLINE-ESIDRIX is a fixed-dose combination of hydralazine (vasodilator) and hydrochlorothiazide (thiazide diuretic). Monitor for reflex tachycardia and fluid retention with hydralazine; hypokalemia, hyponatremia, and hyperuricemia with hydrochlorothiazide. Use with caution in severe renal impairment (CrCl <30 mL/min) and coronary artery disease. May cause lupus-like syndrome with prolonged high-dose hydralazine (usually >200 mg/day). Administer with food to reduce GI upset. |
| Patient Advice | Take this medication exactly as prescribed, usually once daily in the morning to avoid nighttime urination. · You may experience dizziness or lightheadedness, especially when standing up quickly; rise slowly from sitting or lying down. · Report any unexplained joint pain, rash, fever, or fatigue, as these may be signs of a lupus-like reaction. · Avoid alcohol, which can increase blood pressure-lowering effects and dizziness. · Drink adequate fluids unless otherwise advised by your doctor, but do not increase salt intake without consulting your healthcare provider. · Do not stop taking this medication abruptly, as sudden withdrawal may cause a rapid increase in blood pressure. |
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