HYGROTON
Clinical safety rating: caution
Comprehensive clinical and safety monograph for HYGROTON (HYGROTON).
Inhibits sodium reabsorption in the distal convoluted tubule by binding to the thiazide-sensitive sodium-chloride cotransporter (NCC), leading to increased excretion of sodium, chloride, and water.
| Metabolism | Primarily metabolized in the liver via CYP450 enzymes; metabolites are excreted renally. |
| Excretion | Renal (approximately 50-60% as unchanged drug and metabolites); biliary/fecal elimination accounts for a minor fraction, less than 10%. |
| Half-life | Terminal elimination half-life is approximately 40-50 hours, extending up to 70 hours in patients with renal impairment, allowing for once-daily dosing. |
| Protein binding | 75-95% bound to plasma proteins, primarily albumin and erythrocyte carbonic anhydrase. |
| Volume of Distribution | Approximately 3-4 L/kg (3.0-4.0 L/kg), indicating extensive tissue distribution and binding to erythrocytes. |
| Bioavailability | Oral: Approximately 65-70% due to incomplete absorption; no parenteral formulation available. |
| Onset of Action | Oral: 2 hours for initial diuresis; peak antihypertensive effect may require 2-4 weeks. |
| Duration of Action | Diuretic effect persists for 24-48 hours; antihypertensive effect lasts for up to 24 hours with once-daily dosing. |
25-50 mg orally once daily; may increase to 100 mg once daily for resistant hypertension or edema. Maximum dose 100 mg/day.
| Dosage form | TABLET |
| Renal impairment | GFR 15-29 mL/min: 25 mg every 48 hours; GFR <15 mL/min: avoid use (ineffective); GFR 30-59 mL/min: 25 mg once daily; GFR ≥60 mL/min: no adjustment. |
| Liver impairment | Child-Pugh A: no adjustment; Child-Pugh B: reduce dose by 50%; Child-Pugh C: avoid use due to risk of electrolyte imbalance and encephalopathy. |
| Pediatric use | Infants and children: 0.5-1 mg/kg/dose orally once daily; maximum 50 mg/day. |
| Geriatric use | Start at 12.5-25 mg orally once daily; monitor renal function and electrolytes closely; avoid doses >50 mg/day due to increased risk of hyponatremia and hypokalemia. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for HYGROTON (HYGROTON).
| Breastfeeding | Chlorthalidone is excreted in human breast milk with a milk-to-plasma ratio of approximately 0.05–0.15. Adverse effects have not been reported in nursing infants, but caution is advised as thiazides may suppress lactation. Monitor infant for signs of electrolyte imbalance or jaundice. Avoid if breastfeeding preterm or jaundiced infants. M/P ratio: ~0.15. |
| Teratogenic Risk | Chlorthalidone (Hygroton) is a thiazide-like diuretic classified as FDA Pregnancy Category B. Data from controlled studies in pregnant women are insufficient; however, thiazides cross the placenta and may cause fetal or neonatal effects such as jaundice, electrolyte disturbances, and thrombocytopenia. Use in the first trimester is not associated with major malformations, but second and third trimester exposure may lead to adverse fetal/neonatal effects. Avoid for treatment of gestational hypertension due to decreased maternal plasma volume and potential for placental hypoperfusion. Risk summary: Minimal teratogenic risk in first trimester, but caution in second and third trimester. |
■ FDA Black Box Warning
No boxed warning.
| Serious Effects |
["Anuria","Hypersensitivity to chlorthalidone or other sulfonamide-derived drugs"]
| Precautions | ["Electrolyte disturbances: hypokalemia, hyponatremia, hypomagnesemia","Hyperuricemia and gout","Hyperglycemia","Orthostatic hypotension","Sulfonamide hypersensitivity cross-reactivity","Impaired renal function"] |
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| Fetal Monitoring | Monitor maternal blood pressure, serum electrolytes (especially potassium, sodium, chloride), renal function, and uric acid. In pregnancy, monitor fetal growth and amniotic fluid volume via ultrasound due to potential for placental hypoperfusion. Assess for signs of neonatal jaundice, thrombocytopenia, and electrolyte disturbances after delivery. |
| Fertility Effects | No known significant impact on fertility. Thiazide diuretics may cause minor changes in menstrual cycle but no established effect on conception or reproductive function. |