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. |
| Molecular Weight | 441.53 |
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 | Avoid unless essential; crosses placenta; potential for teratogenicity (theoretical risk based on other thiazides). |
| 2nd trimester | Use only if clearly needed; may cause electrolyte disturbances, reduced placental perfusion. |
| 3rd trimester | Avoid; risk of neonatal thrombocytopenia, electrolyte imbalance, jaundice. |
Clinical note
Comprehensive clinical and safety monograph for CHLOROTHIAZIDE SODIUM (CHLOROTHIAZIDE SODIUM).
| Placental transfer | Chlorothiazide crosses the placenta; detected in cord blood and fetal tissues. |
| Breastfeeding | Chlorothiazide is excreted into breast milk in small amounts; may suppress lactation and cause adverse effects in the infant including electrolyte disturbances and hyperbilirubinemia. Use with caution. |
■ FDA Black Box Warning
No FDA black box warning.
| Serious Effects |
AnuriaHypersensitivity to chlorothiazide or sulfonamide-derived drugsRenal failure with oliguria or anuriaHepatic coma or precoma
| Precautions | Hypokalemia, Hypomagnesemia, Hypercalcemia, Hypersensitivity reactions (including anaphylaxis), Exacerbation of systemic lupus erythematosus, Photosensitivity |
| Food/Dietary | Avoid excessive intake of high-potassium foods (bananas, oranges, spinach) unless hypokalemic. Alcohol may potentiate orthostatic hypotension. Grapefruit juice may alter absorption; limited data but caution advised. High-sodium diet may reduce antihypertensive efficacy. |
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| Lactation Rating |
| L3 (Moderately Safe; use caution) |
| 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. |
| 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. |
| Clinical Pearls |
| Chlorothiazide sodium is a thiazide diuretic used for hypertension and edema. Monitor serum potassium and magnesium; hypokalemia increases digoxin toxicity risk. Onset of diuresis is within 2 hours, peak at 4 hours, duration 6–12 hours. Use with caution in renal impairment (CrCl <30 mL/min often ineffective). May cause hypercalcemia and hyperuricemia. IV form is highly alkaline (pH 9.2–10.0); avoid extravasation. Can cause photosensitivity. |
| Patient Advice | Take exactly as prescribed, preferably in the morning to avoid nighttime urination. · May cause dizziness or lightheadedness; avoid driving until you know how it affects you. · Limit alcohol and avoid excessive sun exposure; use sunscreen. · Do not take potassium supplements or salt substitutes without consulting your doctor. · Report symptoms of electrolyte imbalance: muscle cramps, weakness, irregular heartbeat, excessive thirst. · Monitor blood pressure and weight regularly as directed. · If you have diabetes, monitor blood sugar more frequently; this drug can increase blood sugar. |