CHLOROTHIAZIDE
Clinical safety rating: caution
Comprehensive clinical and safety monograph for CHLOROTHIAZIDE (CHLOROTHIAZIDE).
Chlorothiazide inhibits the Na+-Cl- symporter in the distal convoluted tubule, reducing sodium and chloride reabsorption and promoting diuresis. It also causes vasodilation by reducing peripheral vascular resistance.
| Metabolism | Chlorothiazide is not extensively metabolized; it is primarily excreted unchanged via the kidneys. |
| Excretion | Renal: ~95% (tubular secretion); Fecal: <5% |
| Half-life | Terminal half-life: 45–120 minutes (prolonged in renal impairment); clinical context: short duration requires frequent dosing |
| Protein binding | ~95% (primarily to albumin) |
| Volume of Distribution | 0.2–0.5 L/kg; large Vd indicates extensive tissue binding; clinical meaning: distribution primarily into extracellular fluid |
| Bioavailability | Oral: 30–50% (dose-dependent, saturable absorption); IV: 100% |
| Onset of Action | Oral: 2 hours; IV: 15–30 minutes |
| Duration of Action | Oral: 6–12 hours; IV: 2–6 hours; clinical note: acts at distal convoluted tubule; may need twice-daily dosing for sustained effect |
500 mg to 1000 mg orally or intravenously once or twice daily.
| Dosage form | TABLET |
| Renal impairment | GFR ≥50 mL/min: no adjustment; GFR 10-50 mL/min: use lowest effective dose; GFR <10 mL/min: avoid or use with extreme caution (ineffective). |
| Liver impairment | Mild to moderate impairment (Child-Pugh A/B): no adjustment; severe impairment (Child-Pugh C): avoid due to risk of electrolyte disturbances and hepatic encephalopathy. |
| Pediatric use | Neonates: 20-40 mg/kg/day orally divided every 12 hours; Infants/Children: 20-40 mg/kg/day orally divided every 12 hours; maximum 2000 mg/day. |
| Geriatric use | Start at lowest effective dose (e.g., 250-500 mg daily); monitor electrolytes, renal function, and orthostatic blood pressure closely; avoid in patients with significant renal impairment. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for CHLOROTHIAZIDE (CHLOROTHIAZIDE).
| Breastfeeding | Chlorothiazide is excreted into breast milk in low amounts. M/P ratio not well established. May suppress lactation. Use with caution in breastfeeding only if benefit outweighs risk; monitor infant for jaundice and electrolyte disturbances. |
| Teratogenic Risk | Chlorothiazide crosses the placenta. First trimester: Limited data, but risk of fetal anomalies not significantly increased based on population studies; however, thiazides may cause electrolyte disturbances. Second and third trimesters: Associated with fetal/neonatal jaundice, thrombocytopenia, and electrolyte imbalances. Use only if clearly needed. |
■ FDA Black Box Warning
None
| Serious Effects |
["Anuria","Hypersensitivity to chlorothiazide or other sulfonamide-derived drugs"]
| Precautions | ["Hypokalemia","Hypomagnesemia","Hypocalcemia","Hyperuricemia","Hyperglycemia","Hyperlipidemia","Photosensitivity","Systemic lupus erythematosus exacerbation","Acute angle-closure glaucoma","Cross-allergy with sulfonamides"] |
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| Fetal Monitoring | Monitor maternal blood pressure, serum electrolytes (especially potassium, sodium, chloride), renal function, and urine output. Fetal monitoring includes assessment of growth and amniotic fluid volume. In neonates, monitor for jaundice, thrombocytopenia, and electrolyte imbalances. |
| Fertility Effects | No well-documented adverse effects on fertility in humans. In animal studies, no significant reproductive toxicity reported. |