CHLORTHALIDONE
Clinical safety rating: caution
Animal studies have proved adverse effects but may be safe for humans
Thiazide-like diuretic; inhibits sodium-chloride cotransporter in distal convoluted tubule, increasing excretion of sodium, chloride, and water. Also lowers peripheral vascular resistance.
| Metabolism | Primarily excreted unchanged in urine; minimal hepatic metabolism. Metabolites (if any) are not clinically significant. |
| Excretion | Renal: 50-65% unchanged; biliary/fecal: minimal (<5%) |
| Half-life | Terminal half-life 40-60 hours (range 35-70h); prolonged in renal impairment |
| Protein binding | 75% primarily to albumin |
| Volume of Distribution | 3-4 L/kg (extensive tissue distribution, partitions into erythrocytes) |
| Bioavailability | Oral: ~65% (absorption 70%, first-pass metabolism minimal) |
| Onset of Action | Oral: 2-3 hours for diuretic effect; full antihypertensive effect over 2-4 weeks |
| Duration of Action | Diuretic effect: 24-72 hours; antihypertensive effect: 24-48 hours after single dose |
Oral: 25-100 mg once daily; initial dose 25 mg once daily; may increase to 50-100 mg once daily based on response.
| Dosage form | TABLET |
| Renal impairment | eGFR 30-59 mL/min: no adjustment; eGFR 15-29 mL/min: reduce dose by 50% or use every other day; eGFR <15 mL/min: consider alternative diuretic, use with caution at reduced dose. |
| Liver impairment | Child-Pugh A: no adjustment; Child-Pugh B: reduce starting dose by 50% (e.g., 12.5 mg once daily) and titrate carefully; Child-Pugh C: avoid use due to risk of hepatic encephalopathy. |
| Pediatric use | Oral: 0.5-2 mg/kg/dose once daily; maximum 50 mg/day; not recommended for infants <2 years due to limited safety data. |
| Geriatric use | Initiate at 12.5-25 mg once daily; monitor electrolytes, renal function, and blood pressure closely due to increased risk of hypokalemia, hyponatremia, and orthostatic hypotension. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Other antihypertensive drugs can have additive effects Lithium levels may be increased Can cause hypokalemia and hyponatremia.
| Breastfeeding | Small amounts excreted in human milk; M/P ratio not well established. Use with caution, monitor infant for electrolyte disturbances and hypotension. |
| Teratogenic Risk | First trimester: Limited data, no major malformations reported in humans, but caution due to potential for decreased placental perfusion. Second and third trimesters: May cause fetal or neonatal jaundice, thrombocytopenia, electrolyte disturbances, and possible fetal hypotension. Avoid use in pregnancy-induced hypertension due to risk of maternal hypovolemia and placental hypoperfusion. |
■ FDA Black Box Warning
None.
| Common Effects | edema |
| Serious Effects |
["Anuria","Sulfonamide allergy (cross-reactivity with thiazides)","Hypokalemia","Hepatic coma or pre-coma","Concomitant use with lithium (risk of toxicity)"]
| Precautions | ["Electrolyte disturbances (hypokalemia, hyponatremia, hypomagnesemia)","Hyperuricemia","Hyperglycemia in diabetics","Postural hypotension","Photosensitivity","Exacerbation of systemic lupus erythematosus","Acute angle-closure glaucoma (rare)"] |
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| Fetal Monitoring | Monitor maternal blood pressure, serum electrolytes (K+, Na+), uric acid, and blood glucose. Assess fetal growth and amniotic fluid volume via ultrasound. Monitor neonatal for hypoglycemia, electrolyte imbalance, and hypotension if used near term. |
| Fertility Effects | No direct evidence of fertility impairment; may interfere with ovulation in women with polycystic ovary syndrome due to decreased insulin sensitivity. Reversible upon discontinuation. |