BENZTHIAZIDE

Clinical safety rating: caution

Comprehensive clinical and safety monograph for BENZTHIAZIDE (BENZTHIAZIDE).

How it works

Inhibits sodium-chloride symporter in the distal convoluted tubule of the nephron, reducing sodium reabsorption and increasing excretion of water, sodium, chloride, potassium, and hydrogen ions. Also causes vasodilation via direct arteriolar relaxation.

What the body does with it

Metabolism	Primarily hepatic via CYP450 enzymes; minimal metabolism, mostly excreted unchanged in urine.
Excretion	Renal: ~90% (60% unchanged, 30% as glucuronide conjugate); biliary/fecal: minimal (<5%).
Half-life	Terminal elimination half-life: 8-12 hours; clinical context: supports once-daily dosing for hypertension, but duration of action may extend beyond half-life due to tissue distribution.
Protein binding	~94% bound, primarily to albumin.
Volume of Distribution	0.5-1.5 L/kg; clinical meaning: extensive tissue distribution, including binding to erythrocytes and vascular smooth muscle.
Bioavailability	Oral: ~80% (well absorbed, but first-pass metabolism reduces absolute bioavailability).
Onset of Action	Oral: diuresis begins within 2 hours; peak effect at 4-6 hours.
Duration of Action	Oral: antihypertensive effect lasts 12-24 hours; diuretic effect lasts 12-18 hours. Clinical note: longer duration than half-life due to binding to erythrocytes and renal tubular cells.

Classification & Brands

Dosing & administration

Adults: 25-50 mg orally once daily initially, may increase to 100 mg daily in a single dose or two divided doses. Maximum dose: 100 mg/day.

Dosage form	TABLET
Renal impairment	eGFR 30-60 mL/min: Use with caution; consider dose reduction to 12.5-25 mg once daily. eGFR <30 mL/min: Avoid use; thiazides are ineffective.
Liver impairment	Child-Pugh Class A: No adjustment necessary. Child-Pugh Class B/C: Use with caution; consider starting at 12.5 mg once daily due to risk of electrolyte disturbances and worsening hepatic encephalopathy.
Pediatric use	Children >6 months: Initially 0.5-1 mg/kg orally once daily; maximum 2 mg/kg/day divided every 12-24 hours. Not recommended for neonates.
Geriatric use	Start at 12.5 mg orally once daily; monitor electrolytes, renal function, and blood pressure closely. Titrate slowly to avoid hypotension and electrolyte imbalance.

Use during pregnancy

1st trimester	Consult provider
2nd trimester	Consult provider
3rd trimester	Consult provider

Clinical note

Comprehensive clinical and safety monograph for BENZTHIAZIDE (BENZTHIAZIDE).

Breastfeeding	Excreted in breast milk in low amounts; M/P ratio not established. Use with caution, monitor infant for electrolyte disturbances and diuretic effects.
Teratogenic Risk	First trimester: Limited data; potential for adverse effects due to electrolyte disturbances. Second/third trimester: Increased risk of fetal hypoglycemia, thrombocytopenia, electrolyte imbalances; possible association with intrauterine growth restriction (IUGR).
Fetal Monitoring

Warnings & precautions

■ FDA Black Box Warning

None

Side Effect Profile

Serious Effects

Absolute Contraindications

["Anuria","Hypersensitivity to thiazides or sulfonamides","Severe renal impairment (CrCl <30 mL/min)","Hepatic coma or precoma"]

Clinical Precautions

Precautions	["Hypokalemia","Hyponatremia","Hypomagnesemia","Hypercalcemia","Azotemia","Sulfonamide allergy cross-sensitivity","Exacerbation of systemic lupus erythematosus","Orthostatic hypotension"]
Food/Dietary	Avoid potassium-rich foods (e.g., bananas, oranges, spinach) unless directed, due to risk of hyperkalemia when used with potassium-sparing diuretics. Limit salt substitutes containing potassium. Alcohol may enhance orthostatic hypotension.

Clinical Tips & Counseling

Drug interactions

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BENZTHIAZIDE

Clinical safety rating: caution

Comprehensive clinical and safety monograph for BENZTHIAZIDE (BENZTHIAZIDE).

How it works

What the body does with it

Metabolism	Primarily hepatic via CYP450 enzymes; minimal metabolism, mostly excreted unchanged in urine.
Excretion	Renal: ~90% (60% unchanged, 30% as glucuronide conjugate); biliary/fecal: minimal (<5%).
Half-life	Terminal elimination half-life: 8-12 hours; clinical context: supports once-daily dosing for hypertension, but duration of action may extend beyond half-life due to tissue distribution.
Protein binding	~94% bound, primarily to albumin.
Volume of Distribution	0.5-1.5 L/kg; clinical meaning: extensive tissue distribution, including binding to erythrocytes and vascular smooth muscle.
Bioavailability	Oral: ~80% (well absorbed, but first-pass metabolism reduces absolute bioavailability).
Onset of Action	Oral: diuresis begins within 2 hours; peak effect at 4-6 hours.
Duration of Action	Oral: antihypertensive effect lasts 12-24 hours; diuretic effect lasts 12-18 hours. Clinical note: longer duration than half-life due to binding to erythrocytes and renal tubular cells.

Classification & Brands

Dosing & administration

Adults: 25-50 mg orally once daily initially, may increase to 100 mg daily in a single dose or two divided doses. Maximum dose: 100 mg/day.

Dosage form	TABLET
Renal impairment	eGFR 30-60 mL/min: Use with caution; consider dose reduction to 12.5-25 mg once daily. eGFR <30 mL/min: Avoid use; thiazides are ineffective.
Liver impairment	Child-Pugh Class A: No adjustment necessary. Child-Pugh Class B/C: Use with caution; consider starting at 12.5 mg once daily due to risk of electrolyte disturbances and worsening hepatic encephalopathy.
Pediatric use	Children >6 months: Initially 0.5-1 mg/kg orally once daily; maximum 2 mg/kg/day divided every 12-24 hours. Not recommended for neonates.
Geriatric use	Start at 12.5 mg orally once daily; monitor electrolytes, renal function, and blood pressure closely. Titrate slowly to avoid hypotension and electrolyte imbalance.

Use during pregnancy

1st trimester	Consult provider
2nd trimester	Consult provider
3rd trimester	Consult provider

Clinical note

Comprehensive clinical and safety monograph for BENZTHIAZIDE (BENZTHIAZIDE).

Breastfeeding	Excreted in breast milk in low amounts; M/P ratio not established. Use with caution, monitor infant for electrolyte disturbances and diuretic effects.
Teratogenic Risk	First trimester: Limited data; potential for adverse effects due to electrolyte disturbances. Second/third trimester: Increased risk of fetal hypoglycemia, thrombocytopenia, electrolyte imbalances; possible association with intrauterine growth restriction (IUGR).
Fetal Monitoring

Warnings & precautions

■ FDA Black Box Warning

None

Side Effect Profile

Serious Effects

Absolute Contraindications

["Anuria","Hypersensitivity to thiazides or sulfonamides","Severe renal impairment (CrCl <30 mL/min)","Hepatic coma or precoma"]

Clinical Precautions

Precautions	["Hypokalemia","Hyponatremia","Hypomagnesemia","Hypercalcemia","Azotemia","Sulfonamide allergy cross-sensitivity","Exacerbation of systemic lupus erythematosus","Orthostatic hypotension"]
Food/Dietary	Avoid potassium-rich foods (e.g., bananas, oranges, spinach) unless directed, due to risk of hyperkalemia when used with potassium-sparing diuretics. Limit salt substitutes containing potassium. Alcohol may enhance orthostatic hypotension.

Clinical Tips & Counseling

Drug interactions

Loading safety data…