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 |
| Molecular Weight | 338.76 |
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 | Avoid; associated with increased risk of birth defects, including cardiac anomalies, and may cause fetal hypotension and hypoxia due to maternal hypovolemia. |
| 2nd trimester | Use only if clearly needed; risk of reduced placental perfusion, fetal growth restriction, and oligohydramnios. Monitor fetal growth and amniotic fluid volume. |
| 3rd trimester | Avoid; may cause fetal hypotension, hypoxia, and electrolyte abnormalities in the neonate, including neonatal jaundice and thrombocytopenia. |
Clinical note
Other antihypertensive drugs can have additive effects Lithium levels may be increased Can cause hypokalemia and hyponatremia.
| Placental transfer | Chlorthalidone crosses the placenta. It is extensively bound to plasma proteins and distributes to fetal tissues. Fetal concentrations are approximately 15% of maternal levels. |
| Breastfeeding | Chlorthalidone is excreted into breast milk in small amounts, but may suppress lactation and/or cause neonatal electrolyte disturbances. Monitor infant for signs of dehydration, weight loss, and electrolyte imbalances. Avoid if possible, especially in high doses. |
■ FDA Black Box Warning
None.
| Common Effects | edema |
| Serious Effects |
AnuriaHypersensitivity to chlorthalidone or other sulfonamide-derived drugsHepatic comaSevere hepatic impairmentRefractory hypokalemiaHypercalcemiaSymptomatic hyperuricemia
| Precautions | Electrolyte disturbances (hypokalemia, hyponatremia, hypomagnesemia), Hyperuricemia, Hyperglycemia in diabetics, Postural hypotension, Photosensitivity, Exacerbation of systemic lupus erythematosus, Acute angle-closure glaucoma (rare) |
| Food/Dietary | Avoid high-potassium foods (bananas, oranges, potatoes, spinach, avocados) unless potassium levels are monitored. Grapefruit juice may increase drug levels and risk of side effects. Limit alcohol as it can worsen hypotension and dehydration. Salt substitutes containing potassium should be used with caution. Avoid excessive vitamin D or calcium supplements due to risk of hypercalcemia. |
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| Lactation Rating | L4 (Possibly Hazardous) |
| 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. |
| 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. |
| Clinical Pearls | Chlorthalidone is a thiazide-like diuretic with a longer duration of action (up to 72 hours) than hydrochlorothiazide, making it preferred for once-daily dosing in hypertension. It is first-line for managing hypertension, especially in patients with edema due to heart failure. Monitor serum potassium and magnesium, as hypokalemia and hypomagnesemia are common. Avoid in severe renal impairment (CrCl <30 mL/min). May exacerbate gout; monitor uric acid levels. Drug interactions: NSAIDs reduce efficacy; lithium toxicity risk increased. |
| Patient Advice | Take chlorthalidone in the morning to avoid nighttime urination. · Avoid alcohol and grapefruit juice as they may increase blood pressure or side effects. · Report symptoms of low potassium (muscle cramps, weakness, irregular heartbeat) or dehydration (excessive thirst, dry mouth, decreased urination). · Do not take over-the-counter potassium supplements or salt substitutes unless directed by your doctor. · This medication may make you more sensitive to sunlight; use sunscreen and protective clothing. |