CORZIDE
Clinical safety rating
cautionComprehensive clinical and safety monograph for CORZIDE (CORZIDE).
Combination of a beta-adrenergic receptor antagonist (nadolol) and a thiazide diuretic (bendroflumethiazide). Nadolol non-selectively blocks beta-1 and beta-2 receptors, reducing heart rate, myocardial contractility, and blood pressure. Bendroflumethiazide inhibits sodium-chloride symporter in the distal convoluted tubule, increasing excretion of sodium, chloride, and water.
| Metabolism | Nadolol: not extensively metabolized, excreted unchanged in urine. Bendroflumethiazide: minimally metabolized, excreted unchanged in urine. |
| Excretion | Nadolol: ~73% excreted unchanged in urine via glomerular filtration; bendroflumethiazide: ~30% excreted unchanged in urine, remainder as metabolites via renal and biliary routes. |
| Half-life | Nadolol: 14-24 hours (prolonged in renal impairment up to 45 hours); bendroflumethiazide: 8-9 hours (may be prolonged in renal dysfunction). |
| Protein binding | Nadolol: <30% bound to albumin; bendroflumethiazide: ~94% bound to albumin. |
| Volume of Distribution | Nadolol: 1.9-2.5 L/kg (low, consistent with hydrophilic nature); bendroflumethiazide: not well characterized but estimated ~0.5-1 L/kg (small Vd due to high protein binding). |
| Bioavailability | Nadolol: ~30-40% (variable, first-pass metabolism minimal); bendroflumethiazide: bioavailability ~65% (oral). |
| Onset of Action | Oral: peak effect for nadolol occurs in 3-4 hours, bendroflumethiazide diuresis begins in 2 hours. |
| Duration of Action | Nadolol: ~24 hours (allows once-daily dosing); bendroflumethiazide: diuretic effect lasts 12-24 hours. |
| Molecular Weight | Nadolol: 309.4 Da; Bendroflumethiazide: 421.4 Da |
Oral: 1 tablet daily containing nadolol 40 mg and bendroflumethiazide 5 mg. May increase to 2 tablets daily if needed.
| Dosage form | TABLET |
| Renal impairment | GFR 30-50 mL/min: administer every 24 hours; GFR 10-29 mL/min: administer every 24-36 hours; GFR <10 mL/min: administer every 48 hours. |
| Liver impairment | Child-Pugh Class B or C: use with caution; consider dose reduction or increased monitoring due to reduced clearance. |
| Pediatric use | Not recommended for use in pediatric patients due to lack of safety and efficacy data. |
| Geriatric use | Start at lower dose (e.g., 1 tablet containing nadolol 20 mg and bendroflumethiazide 2.5 mg) and titrate slowly; monitor renal function and electrolytes. |
| 1st trimester | Avoid; risk of fetal bradycardia, hypoglycemia, and growth retardation with beta-blockers. Thiazides may reduce placental perfusion. |
| 2nd trimester | Avoid; similar risks as t1. Monitor fetal growth if used. |
| 3rd trimester | Avoid; may cause neonatal bradycardia, hypoglycemia, and respiratory depression. Thiazides can cause electrolyte imbalance. |
Clinical note
Comprehensive clinical and safety monograph for CORZIDE (CORZIDE).
| Placental transfer | Nadolol crosses the placenta (relative infant dose 6-25%). Bendroflumethiazide crosses placenta and may cause fetal electrolyte disturbances. |
| Breastfeeding | Both nadolol and bendroflumethiazide are excreted in breast milk. Nadolol has a long half-life and may accumulate in infants. Monitor infant for bradycardia, hypotension, and diuretic effects. Use only if clearly needed. |
| Lactation Rating | L4 (Possibly Hazardous) |
| Teratogenic Risk | CORZIDE (nadolol/bendroflumethiazide) is associated with fetal risk. First trimester: Potential teratogenic effects including hypospadias and neural tube defects with bendroflumethiazide; β-blocker use may increase risk of intrauterine growth restriction. Second trimester: Continued risk of placental insufficiency. Third trimester: Neonatal bradycardia, hypoglycemia, hypotension, and respiratory depression due to nadolol; electrolyte disturbances and volume depletion from bendroflumethiazide. |
| Fetal Monitoring | Monitor maternal blood pressure, heart rate, serum electrolytes (especially potassium), and renal function. Fetal monitoring includes ultrasound for growth restriction, amniotic fluid volume, and fetal heart rate monitoring. Neonatal monitoring for bradycardia, hypoglycemia, and electrolyte disturbances after delivery. |
| Fertility Effects | Nadolol may reduce fertility in males by decreasing sperm motility and concentration. Bendroflumethiazide may have minimal impact on fertility. In females, no direct effects reported, but untreated hypertension may affect fertility. |
■ FDA Black Box Warning
None
| Serious Effects |
Bronchial asthma or related bronchospastic conditionsSinus bradycardiaHeart block (greater than first degree)Cardiogenic shockOvert cardiac failureAnuria (for bendroflumethiazide)Hypersensitivity to sulfonamide-derived drugs (bendroflumethiazide)
| Precautions | Bronchospasm in patients with asthma/COPD, Heart failure exacerbation, Peripheral vascular disease worsening, Abrupt withdrawal may cause angina or MI, Masking of hypoglycemia in diabetics, Electrolyte disturbances (hypokalemia, hyponatremia), Increased BUN and serum creatinine, Orthostatic hypotension, Systemic lupus erythematosus exacerbation |
| Food/Dietary | Avoid potassium-rich foods (bananas, oranges, spinach, potatoes) in excess unless directed by a physician, as thiazides may cause hypokalemia, but monitoring is needed. Alcohol may potentiate hypotensive effects. Grapefruit juice may increase nadolol levels; avoid concurrent intake. |
| Clinical Pearls | Corzide (bendroflumethiazide/nadolol) combines a thiazide diuretic and a non-selective beta-blocker. Monitor for bradycardia, hypotension, hypokalemia, and hyperglycemia. Avoid abrupt withdrawal due to beta-blocker rebound. Use cautiously in asthma, COPD, diabetes, and peripheral vascular disease. Dosage adjustments needed in renal impairment. |
| Patient Advice | Take exactly as prescribed, usually once daily in the morning to avoid nighttime urination. · Do not stop taking this medication suddenly; abrupt cessation can cause chest pain or heart attack. · Avoid alcohol, which can increase dizziness and drowsiness. · Report symptoms of low potassium (muscle cramps, weakness) or slow heart rate (dizziness, fainting). · May cause dizziness or lightheadedness; rise slowly from sitting or lying positions. · Use sunscreen and protective clothing as this medication may increase sensitivity to sunlight. |
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