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. |
| Molecular Weight | 380.66 |
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 | Use only if potential benefit outweighs risk; may cause fetal harm based on thiazide diuretic effects. |
| 2nd trimester | Use only if clearly needed; may reduce placental perfusion and cause electrolyte disturbances. |
| 3rd trimester | Use with caution; may cause neonatal thrombocytopenia, jaundice, electrolyte imbalance. |
Clinical note
Comprehensive clinical and safety monograph for TRICHLORMETHIAZIDE (TRICHLORMETHIAZIDE).
| Placental transfer | Crosses placenta; low to moderate transfer documented. |
| Breastfeeding | Excreted into breast milk in small amounts; may suppress lactation and cause electrolyte disturbances in infant. |
| Lactation Rating |
■ FDA Black Box Warning
No black box warning.
| Serious Effects |
AnuriaHypersensitivity to thiazides or sulfonamidesHepatic coma
| Precautions | Hypokalemia, Hyponatremia, Hypomagnesemia, Hypercalcemia, Dehydration, Azotemia, Sulfonamide allergy cross-reactivity, Photosensitivity, Exacerbation of systemic lupus erythematosus |
| Food/Dietary | Avoid excessive intake of high-potassium foods (e.g., bananas, oranges, potatoes) unless directed otherwise. Limit sodium intake to enhance antihypertensive effect. Grapefruit juice may increase drug absorption; avoid large amounts. |
| Clinical Pearls |
Loading safety data…
| L3 (Moderately Safe) |
| 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. |
| 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. |
| Monitor serum potassium closely due to hypokalemia risk; use cautiously in patients with hepatic impairment or cirrhosis (can precipitate hepatic encephalopathy). May exacerbate gout; check uric acid levels. Onset of action is within 2 hours, peak at 4-6 hours, duration 12-24 hours. Use with caution in patients with sulfonamide allergy (cross-sensitivity). |
| Patient Advice | Take exactly as prescribed, usually once daily in the morning to avoid nighttime urination. · Avoid potassium supplements or salt substitutes without consulting your doctor. · Report symptoms of low potassium (muscle cramps, weakness, irregular heartbeat) or high blood sugar (increased thirst, frequent urination). · May cause dizziness or lightheadedness; rise slowly from sitting or lying down. · Limit alcohol intake as it may enhance blood pressure lowering effects. |