DIURIL
Clinical safety rating: caution
Comprehensive clinical and safety monograph for DIURIL (DIURIL).
Inhibits sodium reabsorption in the distal convoluted tubule by blocking the sodium-chloride symporter, leading to increased excretion of sodium, chloride, and water.
| Metabolism | Primarily excreted unchanged in urine; minimal hepatic metabolism. |
| Excretion | Primarily renal (90-95% excreted unchanged via glomerular filtration and tubular secretion); minimal biliary/fecal (<5%). |
| Half-life | Terminal elimination half-life is 6-15 hours (mean 10 hours). In renal impairment, half-life can exceed 24 hours. |
| Protein binding | Highly protein-bound (90-95%), primarily to albumin. |
| Volume of Distribution | Vd is 3-11 L/kg (mean 7 L/kg), indicating extensive tissue distribution. |
| Bioavailability | Oral bioavailability is 65-75% due to first-pass metabolism. |
| Onset of Action | Oral: 2 hours; IV: 15-30 minutes. |
| Duration of Action | Oral: 6-12 hours; IV: 2-6 hours. Effect duration is dose-dependent. |
Adults: 500 mg to 1000 mg orally once or twice daily; maximum 2000 mg per day.
| Dosage form | SUSPENSION |
| Renal impairment | GFR 30-50 mL/min: reduce dose by 50%; GFR <30 mL/min: avoid or use with extreme caution. |
| Liver impairment | Child-Pugh Class A: no adjustment; Class B: reduce dose by 50%; Class C: avoid. |
| Pediatric use | Children 2-12 years: 10-20 mg/kg orally once daily; maximum 375 mg per day. |
| Geriatric use | Start at lowest effective dose; monitor electrolytes and renal function; typical initial dose 250 mg once daily. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for DIURIL (DIURIL).
| Breastfeeding | Chlorothiazide is excreted into breast milk in low amounts (M/P ratio approximately 0.05-0.1). Not expected to cause adverse effects in infants at typical maternal doses; however, may suppress lactation. Use with caution, especially in preterm or jaundiced infants. |
| Teratogenic Risk | First trimester: Crosses placenta; limited human data but no clear teratogenic signal; potential for electrolyte disturbances in fetus. Second/third trimester: Associated with maternal hypovolemia and decreased placental perfusion; risk of fetal jaundice, thrombocytopenia, and electrolyte imbalances. Avoid for gestational hypertension due to plasma volume reduction. |
■ FDA Black Box Warning
None.
| Serious Effects |
["Anuria","Hypersensitivity to thiazides or sulfonamides","Hepatic coma or precoma (relative)","Severe renal impairment (creatinine clearance <30 mL/min; relative)"]
| Precautions | ["Electrolyte imbalances (hypokalemia, hyponatremia, hypochloremic alkalosis)","Increase in blood glucose and uric acid levels","Photosensitivity","Systemic lupus erythematosus exacerbation"] |
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| Fetal Monitoring | Monitor maternal blood pressure, serum electrolytes (especially potassium), uric acid, glucose, and renal function. Serial fetal growth ultrasound and amniotic fluid assessment due to potential placental hypoperfusion. Monitor for neonatal electrolyte disturbances and thrombocytopenia at delivery. |
| Fertility Effects | No significant adverse effects on human fertility reported. Theoretical impact from electrolyte disturbances or alterations in reproductive hormone levels, but clinical data lacking. |