HYDROCHLOROTHIAZIDE
Clinical safety rating: safe
Animal studies have demonstrated safety
Thiazide diuretic that inhibits the sodium-chloride symporter (NCC) in the distal convoluted tubule of the kidney, reducing reabsorption of sodium and chloride, leading to increased excretion of water and electrolytes.
| Metabolism | Not extensively metabolized; primarily excreted unchanged in urine. |
| Excretion | Primarily renal (≥95%) via glomerular filtration and tubular secretion, with approximately 60% of the dose excreted unchanged in urine. Minor biliary/fecal excretion accounts for <5%. |
| Half-life | Terminal elimination half-life is 5.6–14.8 hours (mean ~9 hours). In patients with renal impairment (CrCl <30 mL/min), half-life is prolonged up to 24–48 hours, necessitating dose adjustment. |
| Protein binding | Approximately 68% bound to plasma albumin (primarily) and alpha-1-acid glycoprotein. |
| Volume of Distribution | Volume of distribution is 3.6–9.0 L/kg (mean ~4.8 L/kg), indicating extensive distribution into extravascular tissues, including erythrocytes. |
| Bioavailability | Oral bioavailability is 60–70% (range 50–80%), with food slightly increasing absorption. |
| Onset of Action | Oral: diuresis begins within 2 hours; peak effect at 4–6 hours. |
| Duration of Action | Approximately 6–12 hours; antihypertensive effect may persist up to 24 hours, allowing once-daily dosing. |
Oral: 25-100 mg daily in 1-2 divided doses. Maximum dose 200 mg/day.
| Dosage form | CAPSULE |
| Renal impairment | GFR 30-50 mL/min: usual dose. GFR 15-29 mL/min: 12.5-25 mg once daily. GFR <15 mL/min: not recommended. |
| Liver impairment | Child-Pugh A: no adjustment. Child-Pugh B: caution, reduce dose by 50%. Child-Pugh C: contraindicated. |
| Pediatric use | Oral: 2-3 mg/kg/day in 2 divided doses. Maximum: 100 mg/day. |
| Geriatric use | Start at 12.5-25 mg once daily; titrate slowly to avoid electrolyte disturbances and 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 | Hydrochlorothiazide is excreted in human milk in low amounts; M/P ratio not well established. Caution in breastfeeding due to potential for infant electrolyte disturbances and suppression of lactation. Consider alternatives, especially in preterm or ill infants. |
| Teratogenic Risk | First trimester: Not associated with major malformations in human data; second/third trimester: Risk of fetal or neonatal adverse effects including electrolyte imbalance, jaundice, thrombocytopenia, and possible fetal/neonatal hypotension. Avoid for treatment of gestational hypertension as it reduces plasma volume and placental perfusion. |
■ FDA Black Box Warning
No FDA black box warning.
| Common Effects | Limited data available |
| Serious Effects |
["Anuria","Hypersensitivity to hydrochlorothiazide or sulfonamide derivatives","Cross-sensitivity with sulfonamides (potential)"]
| Precautions | ["Hypokalemia and hypomagnesemia may occur; monitor electrolytes.","Hyperuricemia may precipitate gout.","May cause hyperglycemia in diabetic patients.","Photosensitivity reactions.","May exacerbate systemic lupus erythematosus."] |
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| Fetal Monitoring | Monitor maternal electrolytes (especially potassium, sodium, magnesium, chloride), renal function, and blood pressure. Fetal monitoring for growth and amniotic fluid volume (oligohydramnios risk). Neonatal monitoring for jaundice, thrombocytopenia, and electrolyte imbalance. |
| Fertility Effects | No direct evidence of altered fertility in humans. Theoretical concerns due to electrolyte disturbances or volume depletion affecting reproductive function, but not well documented. |