APRESAZIDE
Clinical safety rating
cautionComprehensive clinical and safety monograph for APRESAZIDE (APRESAZIDE).
Apresazide is a combination of hydralazine, a direct-acting vasodilator that relaxes arteriolar smooth muscle, and hydrochlorothiazide, a thiazide diuretic that inhibits sodium and chloride reabsorption in the distal convoluted tubule.
| Metabolism | Hydralazine: primarily hepatic acetylation by N-acetyltransferase; Hydrochlorothiazide: not extensively metabolized, eliminated renally. |
| Excretion | Hydralazine: ~75% renal (metabolites), <10% unchanged; Hydrochlorothiazide: >95% renal (unchanged). |
| Half-life | Hydralazine: 2-4 hours (fast acetylators), 4-8 hours (slow acetylators); Hydrochlorothiazide: 6-15 hours. Clinical context: Dosing interval typically 12 hours for hydralazine component. |
| Protein binding | Hydralazine: 85-90% (plasma proteins); Hydrochlorothiazide: 40-68% (albumin). |
| Volume of Distribution | Hydralazine: 1.5 L/kg; Hydrochlorothiazide: 3-4 L/kg. Clinical meaning: Hydralazine distributes widely; Hydrochlorothiazide distributes into extracellular fluid. |
| Bioavailability | Hydralazine: 26-50% (oral, first-pass metabolism); Hydrochlorothiazide: 65-70% (oral). |
| Onset of Action | Hydralazine: 20-30 minutes (oral); Hydrochlorothiazide: 2 hours (oral). |
| Duration of Action | Hydralazine: 2-4 hours (fast acetylators), 4-8 hours (slow acetylators); Hydrochlorothiazide: 12-16 hours. Clinical note: Effect of hydralazine is shorter, requiring twice-daily dosing. |
| Molecular Weight | 280.3 |
1 capsule (hydralazine 25 mg / hydrochlorothiazide 25 mg) orally twice daily; may increase to 2 capsules twice daily if needed. Maximum: 4 capsules daily.
| Dosage form | CAPSULE |
| Renal impairment | Contraindicated in anuria. For GFR 30-50 mL/min: reduce dose to 1 capsule daily. For GFR <30 mL/min: avoid use due to thiazide inefficacy. |
| Liver impairment | Child-Pugh A: no adjustment. Child-Pugh B: reduce dose by 50% (start with 1 capsule daily). Child-Pugh C: contraindicated. |
| Pediatric use | Weight-based: hydralazine 0.75-1 mg/kg/dose every 6-12 hours (max 50 mg/dose); hydrochlorothiazide 1-2 mg/kg/day divided every 12 hours. Combination not recommended; adjust individual components. |
| Geriatric use | Start with 1 capsule daily; titrate slowly due to increased risk of hypotension and electrolyte imbalance. Monitor renal function and serum potassium. |
| 1st trimester | Avoid in first trimester; associated with congenital malformations (e.g., neural tube defects, cardiovascular defects) due to hydralazine component. |
| 2nd trimester | Use only if clearly needed; hydralazine may cause fetal hypotension and growth restriction; hydrochlorothiazide may cause fetal electrolyte disturbances. |
| 3rd trimester | Avoid due to risk of fetal/neonatal hypotension, thrombocytopenia, and electrolyte imbalances; may decrease placental perfusion. |
Clinical note
Comprehensive clinical and safety monograph for APRESAZIDE (APRESAZIDE).
| Placental transfer | Both components cross the placenta; hydralazine has moderate transfer, hydrochlorothiazide readily crosses. |
| Breastfeeding | Hydrochlorothiazide may suppress lactation or cause neonatal electrolyte disturbances; hydralazine is excreted in breast milk in small amounts. Use with caution, especially in premature or ill infants. |
| Lactation Rating | L4 (Possibly Hazardous) |
| Teratogenic Risk | Apresazide is a fixed-dose combination of hydralazine and hydrochlorothiazide. Hydralazine: First trimester: limited data, no clear evidence of major malformations; second and third trimesters: risk of neonatal thrombocytopenia, lupus-like syndrome, and hypotension. Hydrochlorothiazide: First trimester: possible association with neural tube defects and oral clefts (weak); second and third trimesters: fetal or neonatal jaundice, thrombocytopenia, electrolyte imbalance, and possible growth restriction. Overall, use only if benefit outweighs risk. |
| Fetal Monitoring | Monitor maternal blood pressure, renal function, electrolytes (especially potassium, sodium), and uric acid levels. Monitor fetal growth and amniotic fluid volume via ultrasound due to possible oligohydramnios from hydrochlorothiazide. Assess for signs of neonatal thrombocytopenia or jaundice at birth. |
| Fertility Effects | Hydralazine: no known significant effects on fertility. Hydrochlorothiazide: no known direct effects on fertility. No conclusive evidence of impairment. |
■ FDA Black Box Warning
None
| Serious Effects |
AnuriaHypersensitivity to hydralazine or hydrochlorothiazideSystemic lupus erythematosus (hydralazine may exacerbate)Severe renal impairment (creatinine clearance <30 mL/min)
| Precautions | May cause drug-induced lupus erythematosus (hydralazine), Peripheral neuritis (hydralazine), Electrolyte imbalances (hypokalemia, hyponatremia) due to hydrochlorothiazide, Sulfonamide hypersensitivity cross-reaction, Exacerbation or activation of systemic lupus erythematosus, Possible myocardial infarction or angina pectoris in patients with coronary artery disease |
| Food/Dietary | Avoid high-potassium foods if potassium-sparing effect is not desired (but hydrochlorothiazide causes potassium loss; monitor accordingly). Take with food to reduce GI upset. Avoid natural licorice as it may enhance potassium loss and worsen hypertension. |
| Clinical Pearls | Combination product of hydralazine and hydrochlorothiazide. Monitor for lupus-like syndrome (especially with high hydralazine doses). Check electrolytes and renal function regularly. Use with caution in patients with coronary artery disease or high-output heart failure. |
| Patient Advice | Take exactly as prescribed, do not skip doses. · May cause dizziness or faintness, especially when rising from sitting or lying position. · Avoid sudden discontinuation; taper under medical supervision. · Report symptoms like joint pain, fever, chest pain, or rash immediately. · Limit alcohol intake as it can exacerbate hypotension. |
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