APRESOLINE-ESIDRIX
Clinical safety rating: caution
Comprehensive 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. |
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 | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for APRESOLINE-ESIDRIX (APRESOLINE-ESIDRIX).
| Breastfeeding | Hydralazine: M/P ratio unknown; excreted in breast milk in small amounts; unlikely to cause adverse effects in infant. Hydrochlorothiazide: M/P ratio ~0.3; excreted in breast milk; may suppress lactation; use caution, especially if high doses or dehydration. |
| 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. |
■ 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 |
["Hypersensitivity to hydralazine or hydrochlorothiazide","Anuria","Concomitant use with MAO inhibitors","Rheumatic mitral valve disease (hydralazine)"]
| 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. |
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| 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. |
| 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. |