CHLOROTHIAZIDE SODIUM
Clinical safety rating: caution
Comprehensive clinical and safety monograph for CHLOROTHIAZIDE SODIUM (CHLOROTHIAZIDE SODIUM).
Inhibits sodium-chloride symporter in distal convoluted tubule of nephron, reducing sodium reabsorption and promoting diuresis.
| Metabolism | Minimal hepatic metabolism; primarily excreted unchanged by kidneys. |
| Excretion | Primarily renal excretion via tubular secretion; approximately 95% of absorbed dose excreted unchanged in urine within 24 hours, with less than 5% eliminated via bile/feces. |
| Half-life | Terminal elimination half-life is 45–120 minutes in patients with normal renal function; prolonged in renal impairment (up to 24 hours in anuria). |
| Protein binding | Approximately 95% bound, primarily to albumin. |
| Volume of Distribution | 0.2–0.3 L/kg; reflects distribution primarily in extracellular fluid. |
| Bioavailability | Oral: approximately 30–50% due to incomplete absorption and first-pass metabolism. |
| Onset of Action | Oral: 2 hours; Intravenous: within 15 minutes. |
| Duration of Action | Oral: diuretic effect lasts 6–12 hours; antihypertensive effect lasts up to 24 hours. Intravenous: diuresis ends within 2 hours. |
500 mg to 1 g orally or intravenously once or twice daily.
| Dosage form | INJECTABLE |
| Renal impairment | GFR 20-50 mL/min: administer every 12 hours; GFR 10-19 mL/min: administer every 24 hours; GFR <10 mL/min: avoid use or administer every 48 hours with close monitoring. |
| Liver impairment | No specific dose adjustment recommended; use with caution in severe hepatic impairment due to risk of electrolyte disturbances. |
| Pediatric use | 2 to 4 mg/kg/day orally in two divided doses; maximum 12 mg/kg/day or 1 g/day. |
| Geriatric use | Start at lowest effective dose; monitor electrolytes, renal function, and blood pressure closely due to increased sensitivity and risk of hypokalemia and hyponatremia. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for CHLOROTHIAZIDE SODIUM (CHLOROTHIAZIDE SODIUM).
| Breastfeeding | Chlorothiazide is excreted in breast milk in small amounts (M/P ratio unknown). It may suppress lactation and cause adverse effects in the infant such as electrolyte imbalance or dehydration. Use with caution, monitor infant for adequate weight gain and hydration, and consider alternative agents if possible. |
| Teratogenic Risk | First trimester: Limited data; thiazides are generally avoided due to potential for maternal hypovolemia and reduced placental perfusion. Second/third trimester: May cause fetal or neonatal jaundice, thrombocytopenia, and electrolyte disturbances. Not associated with major malformations but should be used only if clearly needed for maternal hypertension. |
■ FDA Black Box Warning
No FDA black box warning.
| Serious Effects |
["Anuria","Hypersensitivity to chlorothiazide or sulfonamide-derived drugs"]
| Precautions | ["Hypokalemia","Hypomagnesemia","Hypercalcemia","Hypersensitivity reactions (including anaphylaxis)","Exacerbation of systemic lupus erythematosus","Photosensitivity"] |
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| Fetal Monitoring | Monitor maternal blood pressure, serum electrolytes (especially potassium and sodium), renal function, and complete blood count. Fetal monitoring includes ultrasound for growth restriction and amniotic fluid index due to potential for placental insufficiency. In late pregnancy, monitor for signs of neonatal jaundice and thrombocytopenia after delivery. |
| Fertility Effects | No known direct effects on human fertility. However, thiazides can cause metabolic disturbances (e.g., hypokalemia) that may indirectly affect reproductive hormone balance. Reversible upon discontinuation. |