HYDRALAZINE HYDROCHLORIDE W/ HYDROCHLOROTHIAZIDE 50/50
Clinical safety rating: safe
Other antihypertensive drugs can have additive effects Lithium levels may be increased Can cause hypokalemia and hyponatremia.
Hydralazine is a direct-acting vasodilator that relaxes arteriolar smooth muscle via mechanisms involving interference with calcium ion movement and possibly nitric oxide release. Hydrochlorothiazide is a thiazide diuretic that inhibits the sodium-chloride symporter in the distal convoluted tubule, reducing sodium and water reabsorption and decreasing plasma volume.
| Metabolism | Hydralazine is metabolized primarily by hepatic N-acetyltransferase (NAT2) and undergoes first-pass metabolism. Hydrochlorothiazide is not extensively metabolized; it is eliminated largely unchanged in the urine. |
| Excretion | Hydralazine: 80% renal (mainly as metabolites, 1-2% unchanged), 10% fecal. Hydrochlorothiazide: >95% renal (unchanged) via organic anion transporters. |
| Half-life | Hydralazine: 2-8 hours (acetylator phenotype dependent; slow acetylators up to 8h, fast acetylators 1-2h). Hydrochlorothiazide: 6-15 hours (mean 10h). |
| Protein binding | Hydralazine: 85-90% (mainly albumin). Hydrochlorothiazide: 40-68% (albumin). |
| Volume of Distribution | Hydralazine: 1.6 L/kg (large, extensive tissue distribution). Hydrochlorothiazide: 3-4 L/kg (distributes into erythrocytes). |
| Bioavailability | Hydralazine: 26-55% (oral, first-pass effect; higher in slow acetylators). Hydrochlorothiazide: 65-75% (oral). |
| Onset of Action | Hydralazine: oral 30-60 min, IV 5-20 min. Hydrochlorothiazide: oral 2 hours (diuresis). |
| Duration of Action | Hydralazine: 2-6 hours (oral), 1-4 hours (IV). Hydrochlorothiazide: 12-16 hours (antihypertensive effect). |
| Molecular Weight | Hydralazine HCl: 196.64 Da; Hydrochlorothiazide: 297.74 Da |
1 tablet (hydralazine 50 mg/hydrochlorothiazide 50 mg) orally twice daily, maximum 2 tablets daily.
| Dosage form | CAPSULE |
| Renal impairment | GFR 30-60 mL/min: reduce dose by 50% or extend interval to 24 h; GFR <30 mL/min: avoid use (hydrochlorothiazide ineffective). |
| Liver impairment | Child-Pugh Class B or C: reduce hydralazine dose by 50% due to reduced metabolism; contraindicated in severe hepatic impairment. |
| Pediatric use | Hydralazine: 0.75-1 mg/kg/dose orally every 6-12 h (max 200 mg/day); Hydrochlorothiazide: 1-2 mg/kg/day orally in two doses (max 100 mg/day). |
| Geriatric use | Initiate at half the adult dose (0.5 tablet daily) due to increased sensitivity, risk of hypotension, and electrolyte disturbances; monitor renal function. |
| 1st trimester | Avoid unless clearly needed. Hydralazine has been associated with fetal harm; hydrochlorothiazide may cause fetal or neonatal jaundice, thrombocytopenia, and electrolyte disturbances. |
| 2nd trimester | Use only if potential benefit justifies risk to fetus. Consider alternatives. |
| 3rd trimester | Avoid because hydrochlorothiazide can cause fetal or neonatal jaundice, thrombocytopenia, and electrolyte disturbances. Hydralazine may cause maternal hypotension reducing placental perfusion. |
Clinical note
Other antihypertensive drugs can have additive effects Lithium levels may be increased Can cause hypokalemia and hyponatremia.
| FDA category | Animal |
| Placental transfer | Both drugs cross the placenta. Hydralazine crosses readily; hydrochlorothiazide crosses and can cause adverse fetal/neonatal effects. |
■ FDA Black Box Warning
None
| Common Effects | edema |
| Serious Effects |
AnuriaHypersensitivity to hydralazine, hydrochlorothiazide, or sulfonamide-derived drugsSevere renal impairment (CrCl <30 mL/min)Coronary artery disease (relative)Mitral valve rheumatic heart disease
| Precautions | May cause drug-induced lupus-like syndrome (especially in slow acetylators). Monitor for hypotension, tachycardia, and myocardial ischemia. Possible electrolyte disturbances (hypokalemia, hyponatremia) due to hydrochlorothiazide. Use caution in patients with coronary artery disease, renal impairment, or hepatic disease. Monitor blood counts and antinuclear antibody titers. |
| Food/Dietary | Avoid high-sodium foods; may reduce antihypertensive effect. Avoid excessive potassium intake (e.g., salt substitutes, potassium-rich foods) unless directed. Alcohol may enhance hypotensive effects; limit consumption. |
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| Breastfeeding | Both hydralazine and hydrochlorothiazide are excreted in breast milk. Hydrochlorothiazide may suppress lactation. Avoid or use with caution; monitor infant for jaundice, electrolyte disturbances, and hypotension. |
| Lactation Rating | L4 (Possibly hazardous) |
| Teratogenic Risk | First trimester: Hydralazine crosses placenta; no increased risk of major malformations in human studies; hydrochlorothiazide associated with low risk of neural tube defects, oral clefts. Second/third trimester: Hydralazine may cause maternal hypotension leading to fetal distress; hydrochlorothiazide may cause fetal/neonatal jaundice, electrolyte disturbances, thrombocytopenia. Both drugs are considered second-line for hypertension in pregnancy due to risk of maternal hypovolemia and placental hypoperfusion. |
| Fetal Monitoring | Maternal: blood pressure, heart rate, serum electrolytes (K+, Na+, Cl-), renal function, uric acid, complete blood count. Fetal: ultrasound for growth and amniotic fluid volume (hydrochlorothiazide may reduce amniotic fluid), fetal heart rate monitoring. |
| Fertility Effects | No known significant effects on fertility. Hydrochlorothiazide may cause transient impotence in males but no direct effect on spermatogenesis. Hydralazine may rarely cause gynecomastia, but fertility is not impaired. |
| Clinical Pearls | Combination product; hydralazine is a direct vasodilator, hydrochlorothiazide is a thiazide diuretic. Monitor for lupus-like syndrome (arthralgias, rash, fever) with hydralazine, especially in slow acetylators. Check electrolytes, BUN, creatinine. Avoid in severe renal impairment (CrCl <30 mL/min). Titrate doses; may cause reflex tachycardia. |
| Patient Advice | Take exactly as prescribed; do not stop suddenly. · Report symptoms like joint pain, rash, fever, or swelling. · May cause dizziness or lightheadedness; rise slowly from sitting/lying. · Avoid prolonged sun exposure; use sunscreen. · Take with food or milk to reduce stomach upset. · Monitor blood pressure regularly. · Inform all healthcare providers you are taking this medication. |