HYDRA-ZIDE
Clinical safety rating
cautionComprehensive 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. |
| Molecular Weight | 297.74 |
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 | Hydrochlorothiazide crosses the placenta. Use in first trimester is not recommended due to potential for teratogenic effects, including neural tube defects and other malformations. Alternative antihypertensives preferred. |
| 2nd trimester | Use only if clearly needed. May cause fetal or neonatal jaundice, electrolyte disturbances, and thrombocytopenia. Avoid for pregnancy-induced hypertension. |
| 3rd trimester | Contraindicated in third trimester due to risk of fetal or neonatal electrolyte abnormalities, hypoglycemia, and thrombocytopenia. May cause volume depletion and placental hypoperfusion. |
Clinical note
Comprehensive clinical and safety monograph for HYDRA-ZIDE (HYDRA-ZIDE).
| Placental transfer | Hydrochlorothiazide crosses the placenta. It accumulates in fetal plasma and amniotic fluid. Reported to be a weak inhibitor of placental aromatase. |
| Breastfeeding | Hydrochlorothiazide passes into breast milk in small amounts. Use with caution in breastfeeding; monitor infant for signs of electrolyte imbalance, dehydration, or thrombocytopenia. Avoid high doses or combination with other diuretics. |
| Lactation Rating | L3 (Moderately Safe) |
| 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. |
| 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. |
■ FDA Black Box Warning
There is no FDA black box warning for Hydra-Zide.
| Serious Effects |
AnuriaHypersensitivity to hydrochlorothiazide or any sulfonamide-derived drugsSevere renal impairment (CrCl <30 mL/min)Severe hepatic impairmentHypercalcemiaSymptomatic hyperuricemiaAddison's disease
| 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. |
| Food/Dietary | Avoid high-potassium foods (bananas, oranges, tomatoes, spinach, salt substitutes) unless directed. Take with food to reduce gastrointestinal upset. Grapefruit juice may increase drug levels; avoid consumption. |
| Clinical Pearls | Monitor serum potassium and creatinine before initiation and periodically; hypokalemia common early, but may cause hyperkalemia in renal impairment. Avoid use in pregnancy (category D). Titrate dose slowly to minimize orthostatic hypotension. Add-on therapy often requires lower doses of each component. |
| Patient Advice | Take exactly as prescribed; do not skip doses or stop without consulting your doctor. · This drug contains two medicines; your doctor may adjust other medications accordingly. · Stand up slowly to prevent dizziness or fainting. · Report symptoms of electrolyte imbalance: muscle cramps, weakness, irregular heartbeat, or excessive thirst. · Avoid alcohol and NSAIDs (ibuprofen, naproxen) unless approved by your doctor. |
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