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 |
| Molecular Weight | 332.75 |
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 | Avoid unless benefit outweighs risk; associated with low birth weight and neonatal jaundice. |
| 2nd trimester | Use only if clearly needed; may cause electrolyte disturbances, reduced placental perfusion. |
| 3rd trimester | Use only if clearly needed; risk of neonatal thrombocytopenia, electrolyte imbalance, and hypoglycemia. |
Clinical note
Comprehensive clinical and safety monograph for HYDROFLUMETHIAZIDE (HYDROFLUMETHIAZIDE).
| Placental transfer | Crosses placenta; detectable in fetal plasma and amniotic fluid. |
| Breastfeeding | Hydroflumethiazide is excreted into breast milk in low amounts; monitor infant for electrolyte disturbances, dehydration, and weight loss. Use with caution. |
| Lactation Rating |
■ FDA Black Box Warning
None.
| Serious Effects |
AnuriaSulfonamide allergySevere renal impairment (CrCl <30 mL/min)Severe hepatic impairment
| 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) |
| Food/Dietary | Avoid excessive intake of potassium-rich foods (e.g., bananas, oranges, spinach) unless advised by clinician due to risk of hyperkalemia? Actually thiazides cause hypokalemia, so potassium-rich foods are encouraged. However, avoid salt substitutes containing potassium chloride without medical advice. Limit alcohol and caffeine as they can enhance diuresis and electrolyte loss. |
Loading safety data…
| L3 (Moderately Safe) |
| 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. |
| 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. |
| Clinical Pearls | Hydroflumethiazide is a thiazide diuretic used primarily for hypertension and edema. Monitor serum potassium and magnesium; hypokalemia increases digoxin toxicity risk. Onset of diuresis is ~2 hours, peak at 4-6 hours, duration 12-24 hours. Avoid in anuria, sulfonamide allergy, and severe renal impairment (CrCl <30 mL/min). May elevate uric acid, calcium, and glucose. Use with caution in patients with history of gout, diabetes, or hypercalcemia. Dose adjustment needed in hepatic impairment due to risk of electrolyte imbalance. |
| Patient Advice | Take this medication exactly as prescribed; do not skip doses or double up. · Monitor for signs of electrolyte imbalance: muscle cramps, weakness, irregular heartbeat, excessive thirst, or unusual tiredness. · This drug may increase blood sugar; monitor glucose if diabetic. · Avoid prolonged sun exposure; use sunscreen as this medication can cause photosensitivity. · Report any rash, itching, or swelling to your healthcare provider immediately as it may indicate an allergic reaction. · This medication can make you dizzy; avoid driving or operating machinery until you know how it affects you. |