BENZTHIAZIDE
Clinical safety rating: caution
Comprehensive clinical and safety monograph for BENZTHIAZIDE (BENZTHIAZIDE).
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.
| 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. |
| Molecular Weight | 352.82 |
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. |
| 1st trimester | Avoid; associated with increased risk of fetal abnormalities and maternal electrolyte disturbances. |
| 2nd trimester | Avoid; may cause fetal electrolyte imbalance and potential teratogenic effects. |
| 3rd trimester | Avoid; may cause fetal or neonatal jaundice, thrombocytopenia, and electrolyte disturbances. |
Clinical note
Comprehensive clinical and safety monograph for BENZTHIAZIDE (BENZTHIAZIDE).
| Placental transfer | Benzthiazide crosses the placenta and has been detected in cord blood and fetal tissues. |
| Breastfeeding | Benzthiazide is excreted in breast milk in low amounts; however, due to potential for adverse effects in the infant, such as electrolyte disturbances and hypersensitivity, caution is advised. Use only if clearly needed. |
■ FDA Black Box Warning
None
| Serious Effects |
AnuriaHypersensitivity to thiazide diureticsSevere renal impairment (CrCl <30 mL/min)
| 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 Pearls |
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| Lactation Rating |
| L3 (Moderately Safe) |
| 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 | Maternal: Serum electrolytes, renal function, blood pressure, blood glucose. Fetal: Ultrasound for growth, amniotic fluid index, fetal heart rate monitoring. |
| Fertility Effects | No specific adverse effects on fertility reported; however, electrolyte disturbances may indirectly impact reproductive function. |
| Monitor serum potassium and glucose due to risk of hypokalemia and hyperglycemia. Use cautiously in patients with renal impairment (CrCl <30 mL/min may be ineffective). May cause photosensitivity; advise sun protection. Avoid in anuria or sulfonamide allergy (cross-reactivity possible). |
| Patient Advice | Take with food or milk to reduce stomach upset. · Avoid excessive sunlight or use sunscreen; you may sunburn more easily. · Do not stop taking this medication abruptly without consulting your doctor. · Report symptoms of muscle weakness, cramps, or irregular heartbeat. · Limit alcohol intake as it may increase side effects. · Stand up slowly from sitting or lying to prevent dizziness. |