HYDRALAZINE HYDROCHLORIDE W/ HYDROCHLOROTHIAZIDE 100/50
Clinical safety rating: safe
Other antihypertensive drugs can have additive effects Lithium levels may be increased Can cause hypokalemia and hyponatremia.
Hydralazine: Direct vasodilation of arterioles via unknown mechanism, possibly involving nitric oxide. Hydrochlorothiazide: Thiazide diuretic that inhibits the Na+/Cl- cotransporter in the distal convoluted tubule, increasing excretion of sodium and water.
| Metabolism | Hydralazine: Extensively metabolized via N-acetylation (polymorphic; slow acetylators have higher plasma concentrations) and other pathways. Hydrochlorothiazide: Not extensively metabolized; primarily excreted unchanged in urine. |
| Excretion | Hydralazine: 90% renal metabolites, 10% feces; Hydrochlorothiazide: >95% renal (tubular secretion) as unchanged drug |
| Half-life | Hydralazine: 2-8 hours (prolonged in renal impairment); Hydrochlorothiazide: 6-15 hours (increased in renal impairment) |
| Protein binding | Hydralazine: 85-90% (plasma proteins, mainly albumin); Hydrochlorothiazide: 40-70% (albumin) |
| Volume of Distribution | Hydralazine: 1.5-3.0 L/kg (extensive tissue distribution); Hydrochlorothiazide: 0.5-1.5 L/kg (distributes in extracellular fluid) |
| Bioavailability | Hydralazine: 20-50% (oral, extensive first-pass metabolism); Hydrochlorothiazide: 65-75% (oral) |
| Onset of Action | Hydralazine: 20-30 min (oral); Hydrochlorothiazide: 2 hours (oral) |
| Duration of Action | Hydralazine: 6-8 hours (oral); Hydrochlorothiazide: 6-12 hours (oral) |
| Molecular Weight | Hydralazine HCl: 196.64 Da; Hydrochlorothiazide: 297.74 Da; Combined formulation: composite molecular weight not applicable. |
1 tablet (hydralazine 100 mg / hydrochlorothiazide 50 mg) orally once daily. Maximum: 1 tablet daily. Titrate from lower doses of individual components.
| Dosage form | CAPSULE |
| Renal impairment | Contraindicated if GFR <30 mL/min. For GFR 30-50 mL/min: reduce dose or use with caution. For GFR >50 mL/min: no adjustment necessary. |
| Liver impairment | Child-Pugh A: no adjustment. Child-Pugh B: reduce hydralazine dose (start with 25 mg daily). Child-Pugh C: avoid use due to risk of hepatic encephalopathy. |
| Pediatric use | Safety and efficacy not established. Use not recommended in pediatric patients. |
| Geriatric use | Start at lowest possible dose (e.g., hydralazine 25 mg / HCTZ 25 mg daily). Monitor for hypotension, electrolyte imbalance, and renal function. |
| 1st trimester | Use only if potential benefit justifies potential risk to the fetus. Hydralazine and hydrochlorothiazide cross the placenta. First-trimester exposure to thiazides may be associated with an increased risk of congenital anomalies, though data are limited. |
| 2nd trimester | Use with caution. May cause fetal/neonatal adverse effects including electrolyte disturbances, jaundice, and thrombocytopenia. Avoid if possible, especially for management of chronic hypertension. |
| 3rd trimester | Contraindicated in pregnancy-induced hypertension (pre-eclampsia/eclampsia) due to risk of maternal hypovolemia and decreased placental perfusion. May cause fetal/neonatal jaundice, thrombocytopenia, and electrolyte imbalances. |
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 hydralazine and hydrochlorothiazide cross the placenta. Hydralazine is transferred to a moderate degree; hydrochlorothiazide readily crosses the placenta and can achieve fetal plasma concentrations similar to maternal levels. |
■ FDA Black Box Warning
Hydralazine may cause a drug-induced lupus-like syndrome, especially in slow acetylators. Patients should be monitored for symptoms such as arthralgia, fever, chest pain, and rash. Discontinue hydralazine if lupus-like symptoms develop.
| Common Effects | edema |
| Serious Effects |
AnuriaHypersensitivity to hydralazine, hydrochlorothiazide, sulfonamide-derived drugs, or any component of the formulationSevere renal impairment (CrCl <30 mL/min)Systemic lupus erythematosus (SLE) or history of SLECoronary artery disease or mitral valve rheumatic heart disease (due to risk of reflex tachycardia and increased myocardial oxygen demand)
| Precautions | May cause drug-induced lupus-like syndrome (see black box warning)., May exacerbate angina or cause myocardial infarction in patients with coronary artery disease; use with caution., Monitor for hypotension, especially in patients with cerebrovascular disease., Can cause peripheral neuritis (may respond to pyridoxine)., Hydrochlorothiazide: May cause electrolyte imbalances (e.g., hypokalemia, hyponatremia), hyperuricemia, and hypercalcemia., May increase blood glucose levels; monitor in diabetic patients., Hydrochlorothiazide: Can cause photosensitivity reactions; advise sun protection., Use with caution in patients with severe renal impairment (CrCl <30 mL/min); thiazides are less effective., Hydralazine is hepatically metabolized; adjust dose in hepatic impairment. |
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| Breastfeeding | Hydralazine and hydrochlorothiazide are excreted into breast milk in low amounts. Thiazide diuretics may suppress lactation, especially at high doses. Use with caution in breastfeeding mothers; monitor infant for signs of diuresis, electrolyte disturbances, and jaundice. |
| Lactation Rating | L3 - Moderately Safe |
| Teratogenic Risk | Hydralazine: First trimester: No evidence of increased risk of major malformations based on limited human data. Second/third trimester: May cause fetal hypotension, tachycardia, or thrombocytopenia; no known teratogenic effect. Hydrochlorothiazide: First trimester: Crosses placenta; potential for electrolyte disturbances, but no major teratogenicity reported. Second/third trimester: Risk of fetal/neonatal jaundice, thrombocytopenia, electrolyte imbalance, and possible intrauterine growth restriction (IUGR). Use generally avoided in pregnancy for hypertension due to plasma volume contraction. |
| Fetal Monitoring | Maternal: Blood pressure, heart rate, serum electrolytes, renal function, uric acid, and signs of lupus-like syndrome (hydralazine). Fetal: Ultrasound for fetal growth and amniotic fluid volume (due to thiazide-associated oligohydramnios); nonstress test in third trimester. Neonatal: Monitor for thrombocytopenia, electrolyte disturbances, and jaundice. |
| Fertility Effects | Hydralazine: No known adverse effect on human fertility in animal studies. Hydrochlorothiazide: No direct effect on fertility; chronic use may cause electrolyte imbalances but not typically linked to infertility. |
| Food/Dietary | Avoid potassium-rich foods (bananas, oranges, spinach) and salt substitutes without consulting doctor due to risk of hyperkalemia from hydralazine; limit sodium intake to enhance antihypertensive effect; avoid alcohol as it may potentiate hypotension. |
| Clinical Pearls | Monitor for lupus-like syndrome with prolonged hydralazine use, especially in slow acetylators; start low and go slow to avoid reflex tachycardia; check electrolytes and renal function periodically due to thiazide component; avoid in severe renal impairment (CrCl <30 mL/min); combination useful in resistant hypertension when monotherapy inadequate. |
| Patient Advice | Take exactly as prescribed, usually twice daily; do not skip doses or double up. · Avoid sudden discontinuation to prevent rebound hypertension. · May cause dizziness or lightheadedness; rise slowly from sitting or lying positions. · Notify doctor if you experience joint pain, fever, rash, or unexplained bruising (possible lupus-like reaction). · Monitor for signs of electrolyte imbalance: muscle cramps, weakness, irregular heartbeat. · Avoid excessive sun exposure; use sunscreen as hydrochlorothiazide increases photosensitivity. |