HYDROFLUMETHIAZIDE
Clinical safety rating: caution
Comprehensive clinical and safety monograph for HYDROFLUMETHIAZIDE (HYDROFLUMETHIAZIDE).
Hydroflumethiazide is a thiazide diuretic that inhibits the sodium-chloride symporter (NCC) in the distal convoluted tubule of the nephron, reducing sodium and chloride reabsorption and promoting diuresis. It also causes vasodilation by reducing peripheral vascular resistance.
| Metabolism | Hydroflumethiazide is minimally metabolized in the liver; primarily excreted unchanged by the kidneys. |
| Excretion | Primarily renal (approximately 85% as unchanged drug via glomerular filtration and tubular secretion); minor biliary/fecal elimination (<10%) |
| Half-life | Terminal elimination half-life of 6-9 hours in patients with normal renal function; clinically, this supports once-daily dosing in hypertension but may require twice-daily dosing in some patients with impaired renal function |
| Protein binding | Approximately 50-60%; primarily bound to albumin |
| Volume of Distribution | 2-3 L/kg; indicates extensive distribution to extravascular tissues |
| Bioavailability | Oral: approximately 50-60%; interindividual variability due to incomplete absorption and first-pass metabolism |
| Onset of Action | Oral: diuresis begins within 2 hours; peak effect at 4-6 hours |
| Duration of Action | Approximately 18-24 hours for diuretic effect; antihypertensive effect may persist longer with chronic dosing |
Oral: 25-50 mg once daily; may increase to 100 mg/day in divided doses if needed.
| Dosage form | TABLET |
| Renal impairment | GFR 30-90: usual dose; GFR <30: avoid or use only if other thiazides fail; GFR <15: not recommended. |
| Liver impairment | Child-Pugh A-B: no adjustment; Child-Pugh C: use with caution, consider lower initial dose due to risk of electrolyte imbalances. |
| Pediatric use | Oral: 0.5-1 mg/kg/dose once daily; maximum 50 mg/day. Not recommended for children <2 years. |
| Geriatric use | Start at 12.5-25 mg once daily; monitor renal function and electrolytes closely. Avoid if GFR <30. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for HYDROFLUMETHIAZIDE (HYDROFLUMETHIAZIDE).
| Breastfeeding | Excreted into breast milk in low amounts; M/P ratio not established. Use caution in nursing mothers, as thiazides may suppress lactation and cause neonatal electrolyte imbalance. |
| Teratogenic Risk | First trimester: Limited human data; animal studies show no evidence of teratogenicity at therapeutic doses. Second and third trimesters: May cause fetal or neonatal jaundice, thrombocytopenia, and electrolyte disturbances. Avoid use in pregnancy-induced hypertension due to decreased placental perfusion. |
■ FDA Black Box Warning
None.
| Serious Effects |
["Anuria","Hypersensitivity to hydroflumethiazide or sulfonamide-derived drugs","Severe renal impairment (creatinine clearance <30 mL/min)"]
| Precautions | ["May cause electrolyte imbalances (hypokalemia, hyponatremia, hypomagnesemia)","May increase serum uric acid and precipitate gout","May increase serum glucose and worsen diabetes","May cause photosensitivity","May exacerbate systemic lupus erythematosus","Risk of acute angle-closure glaucoma (rare)"] |
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| Fetal Monitoring |
| Monitor maternal blood pressure, serum electrolytes (sodium, potassium, chloride), renal function, and fetal growth via ultrasound during prolonged use. |
| Fertility Effects | No direct evidence of impaired fertility in humans; theoretical risk of electrolyte disturbances affecting reproductive function. |