HYDRA-ZIDE
Clinical safety rating: caution
Comprehensive clinical and safety monograph for HYDRA-ZIDE (HYDRA-ZIDE).
Hydra-Zide is a combination of hydrochlorothiazide (thiazide diuretic) and hydralazine (direct vasodilator). Hydrochlorothiazide inhibits the sodium-chloride symporter in the distal convoluted tubule, reducing electrolyte reabsorption and increasing urine output. Hydralazine relaxes arteriolar smooth muscle, decreasing systemic vascular resistance and afterload.
| Metabolism | Hydrochlorothiazide is not extensively metabolized; eliminated unchanged primarily by renal tubular secretion. Hydralazine undergoes extensive hepatic metabolism via acetylation (N-acetyltransferase) and hydroxylation, with glucuronidation and sulfation. |
| Excretion | Renal: 50-70% of hydralazine as metabolites, 30-40% as parent drug; thiazide: 95% renal as unchanged drug. |
| Half-life | Hydralazine: 2-4 hours (fast acetylators), 4-8 hours (slow acetylators); thiazide: 6-15 hours. |
| Protein binding | Hydralazine: 85-90% bound to albumin; thiazide: 40-70% bound to albumin. |
| Volume of Distribution | Hydralazine: 1.5-2.5 L/kg (distributes extensively into tissues); thiazide: 0.2-0.5 L/kg (primarily extracellular fluid). |
| Bioavailability | Hydralazine: 30-50% (oral, variable due to first-pass metabolism); thiazide: 60-80% (oral). |
| Onset of Action | Hydralazine: 20-30 minutes (oral), 5-20 minutes (IV); thiazide: 2 hours (oral). |
| Duration of Action | Hydralazine: 2-4 hours (oral), dose-dependent; thiazide: 6-12 hours. |
Oral, 1 tablet (25 mg hydrochlorothiazide / 50 mg hydralazine) twice daily, titrated up to maximum of 2 tablets twice daily based on blood pressure response.
| Dosage form | CAPSULE |
| Renal impairment | GFR >30 mL/min: No adjustment. GFR 10-30 mL/min: Use with caution, consider reducing dose (e.g., 1 tablet once daily) or extending interval; avoid if possible. GFR <10 mL/min: Not recommended due to thiazide ineffectiveness. |
| Liver impairment | Child-Pugh A: No adjustment. Child-Pugh B: Consider 50% dose reduction (e.g., 1 tablet once daily) and monitor liver function. Child-Pugh C: Contraindicated due to risk of hepatic encephalopathy and hydralazine accumulation. |
| Pediatric use | Not approved for pediatric use; safety and efficacy not established. Alternative antihypertensives preferred. |
| Geriatric use | Start at 0.5 tablet (12.5 mg hydrochlorothiazide / 25 mg hydralazine) once or twice daily; titrate slowly. Monitor for hypotension, electrolyte disturbances, and renal function. Maximum dose 2 tablets daily. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for HYDRA-ZIDE (HYDRA-ZIDE).
| Breastfeeding | Hydralazine and hydrochlorothiazide are excreted into breast milk in low amounts. M/P ratio not established. Hydrochlorothiazide may suppress lactation and cause neonatal electrolyte disturbances. Caution advised; monitor infant for jaundice, electrolyte imbalance, and dehydration. |
| Teratogenic Risk | First trimester: Hydralazine (component of HYDRA-ZIDE) not associated with major malformations; thiazide diuretics (hydrochlorothiazide) have equivocal risk, some studies suggest increased risk of congenital anomalies, but confounded by underlying disease. Second and third trimesters: Thiazides may cause fetal/neonatal electrolyte disturbances, thrombocytopenia, and jaundice; hydralazine may cause neonatal lupus-like syndrome, thrombocytopenia, and hypotension. Use only if clearly needed. |
■ FDA Black Box Warning
There is no FDA black box warning for Hydra-Zide.
| Serious Effects |
["Anuria","Hypersensitivity to hydrochlorothiazide, hydralazine, or sulfonamide-derived drugs","Severe renal impairment (CrCl <30 mL/min)","Use with MAO inhibitors (monoamine oxidase inhibitors)","Pregnancy (especially second and third trimester) due to hydralazine"]
| Precautions | ["May cause a lupus-like syndrome, especially in slow acetylators; discontinue if symptoms appear.","Risk of hypotension, especially with high doses or volume depletion.","Can cause electrolyte imbalances (hypokalemia, hyponatremia, hypercalcemia), monitor serum electrolytes.","May exacerbate renal impairment; use with caution in renal disease.","Possible hypersensitivity reactions including rash, urticaria, and angioedema."] |
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| Fetal Monitoring | Monitor maternal blood pressure, serum electrolytes (particularly potassium, sodium), renal function, and uric acid. Fetal monitoring: fetal growth (serial ultrasound), amniotic fluid volume (oligohydramnios with thiazides), and fetal heart rate monitoring during labor. Neonatal: observe for thrombocytopenia, hypoglycemia, and electrolyte disturbances. |
| Fertility Effects | No known effect on fertility from hydralazine or hydrochlorothiazide. However, uncontrolled hypertension may impair fertility due to vascular effects. |