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 |
| Molecular Weight | 295.72 |
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 | Avoid. Chlorothiazide crosses the placenta and may cause electrolyte disturbances, jaundice, and thrombocytopenia in the newborn. Insufficient data on first-trimester safety; use only if benefit outweighs risk. |
| 2nd trimester | Use with caution. May reduce placental perfusion and cause fetal/neonatal adverse effects including electrolyte imbalance and hyperbilirubinemia. |
| 3rd trimester | Avoid. May cause neonatal thrombocytopenia, electrolyte abnormalities, and jaundice. Considered contraindicated in pregnancy-induced hypertension due to decreased plasma volume. |
Clinical note
Comprehensive clinical and safety monograph for CHLOROTHIAZIDE (CHLOROTHIAZIDE).
| Placental transfer | Crosses the placenta; detectable in fetal serum and amniotic fluid. |
| Breastfeeding | Chlorothiazide is excreted into breast milk in low concentrations. It may suppress lactation and cause neonatal electrolyte disturbances or jaundice. Weigh benefits against risks; alternative diuretics preferred. |
■ FDA Black Box Warning
None
| Serious Effects |
AnuriaHypersensitivity to chlorothiazide or sulfonamide-derived drugsHepatic coma or pre-coma
| Precautions | Hypokalemia, Hypomagnesemia, Hypocalcemia, Hyperuricemia, Hyperglycemia, Hyperlipidemia, Photosensitivity, Systemic lupus erythematosus exacerbation, Acute angle-closure glaucoma, Cross-allergy with sulfonamides |
| Food/Dietary | Avoid high-potassium foods (e.g., bananas, oranges, spinach, potatoes) unless directed by a healthcare provider, as chlorothiazide can cause hyperkalemia in some patients. Limit alcohol and caffeine intake, as they can increase electrolyte depletion. Avoid salt substitutes containing potassium chloride. Take with food or milk to reduce gastrointestinal upset. |
Loading safety data…
| Lactation Rating | L3 (Moderately Safe) |
| 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. |
| 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. |
| Clinical Pearls | Chlorothiazide is a thiazide diuretic used for hypertension and edema. Monitor serum electrolytes, especially potassium and sodium, as hypokalemia and hyponatremia are common. Use cautiously in patients with renal impairment (CrCl <30 mL/min). It may exacerbate gout by increasing serum uric acid. Onset of diuresis is within 2 hours, peaking at 4 hours, with duration of 6-12 hours. Avoid use in patients with anuria or hypersensitivity to sulfonamide-derived drugs. |
| Patient Advice | Take chlorothiazide exactly as prescribed, usually once or twice daily. Take the last dose early in the day to prevent nighttime urination. · Monitor for signs of electrolyte imbalance: muscle cramps, weakness, dizziness, or irregular heartbeat. Report these to your healthcare provider. · Avoid alcohol and excessive sweating, which can increase dehydration and electrolyte loss. · Do not use potassium supplements or salt substitutes without consulting your doctor. · This medication may make you dizzy or have blurred vision; avoid driving until you know how it affects you. · Limit intake of foods high in potassium, such as bananas, oranges, and spinach, unless advised otherwise. |