TRICHLORMETHIAZIDE
Clinical safety rating: caution
Comprehensive clinical and safety monograph for TRICHLORMETHIAZIDE (TRICHLORMETHIAZIDE).
Inhibits sodium-chloride symporter in distal convoluted tubule, increasing excretion of sodium, chloride, and water.
| Metabolism | Primarily renal excretion of unchanged drug; minimal hepatic metabolism. |
| Excretion | Primarily renal (tubular secretion); ~70% excreted unchanged in urine; minor biliary/fecal (<10% total). |
| Half-life | Terminal elimination half-life is approximately 2-6 hours (average 3.5 h); clinical context: short half-life necessitates once or twice daily dosing for sustained diuresis. |
| Protein binding | Highly protein bound: ~99% bound to albumin and other plasma proteins. |
| Volume of Distribution | Volume of distribution is approximately 1.5-2.5 L/kg; clinical meaning: indicates extensive tissue binding and limited central compartment distribution. |
| Bioavailability | Oral bioavailability is approximately 70-85% (well absorbed); no other relevant routes. |
| Onset of Action | Oral: diuresis begins within 2 hours; peak effect at 4-6 hours. IV: not typically administered; no data. |
| Duration of Action | Duration of diuretic effect is 12-24 hours after oral administration; clinical notes: antihypertensive effect may persist longer than diuresis. |
2-4 mg orally once daily; maximum 4 mg/day.
| Dosage form | TABLET |
| Renal impairment | eGFR 30-59 mL/min: reduce dose by 50%; eGFR <30 mL/min: use alternative agent or maximum 2 mg/day. |
| Liver impairment | Child-Pugh A: no adjustment; Child-Pugh B: reduce dose by 50%; Child-Pugh C: contraindicated. |
| Pediatric use | 0.02-0.04 mg/kg orally once daily; maximum 0.2 mg/kg/day. |
| Geriatric use | Start at 2 mg orally once daily; titrate cautiously due to increased risk of electrolyte imbalance and hypotension. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for TRICHLORMETHIAZIDE (TRICHLORMETHIAZIDE).
| Breastfeeding | Excreted into human milk in small amounts; M/P ratio unknown. May suppress lactation. Caution in breastfeeding due to risk of neonatal electrolyte disturbances and thiazide effects. |
| Teratogenic Risk | First trimester: Limited data; thiazides are generally avoided due to potential placental hypoperfusion and electrolyte disturbances. Second and third trimesters: Use may cause fetal or neonatal jaundice, thrombocytopenia, and electrolyte imbalances. Avoid for treatment of gestational hypertension as it reduces plasma volume and may impair uteroplacental perfusion. |
■ FDA Black Box Warning
No black box warning.
| Serious Effects |
["Anuria","Hypersensitivity to sulfonamides or thiazide diuretics"]
| Precautions | ["Hypokalemia","Hyponatremia","Hypomagnesemia","Hypercalcemia","Dehydration","Azotemia","Sulfonamide allergy cross-reactivity","Photosensitivity","Exacerbation of systemic lupus erythematosus"] |
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| Fetal Monitoring | Monitor maternal blood pressure, serum electrolytes (especially potassium and sodium), blood glucose, and uric acid levels. Assess fetal growth and amniotic fluid volume via ultrasound if used in pregnancy. |
| Fertility Effects | No direct evidence of impaired fertility in humans; thiazides may cause reversible impotence in males but effects on female fertility are unknown. |