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) |
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 | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Other antihypertensive drugs can have additive effects Lithium levels may be increased Can cause hypokalemia and hyponatremia.
| FDA category | Animal |
| Breastfeeding | Hydralazine: Excreted into breast milk in small amounts (M/P ratio ~0.6-1.2); considered compatible with breastfeeding but monitor infant for hypotension. Hydrochlorothiazide: Excreted into breast milk in low concentrations (M/P ratio ~0.06-0.17); may suppress lactation; use caution in nursing mothers. |
| Teratogenic Risk |
■ 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 |
["Hypersensitivity to hydralazine, hydrochlorothiazide, or sulfonamide-derived drugs (thiazides are sulfonamides).","Anuria (contraindication for hydrochlorothiazide).","Coronary artery disease or severe tachycardia (relative contraindication for hydralazine; may increase myocardial oxygen demand).","Systemic lupus erythematosus (relative contraindication for hydralazine; may exacerbate condition)."]
| 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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| 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. |