CORZIDE
Clinical safety rating: caution
Comprehensive 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. |
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 | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for CORZIDE (CORZIDE).
| Breastfeeding | Nadolol is excreted into breast milk with a relative infant dose of approximately 2-5% of maternal weight-adjusted dose; M/P ratio not well defined. Bendroflumethiazide also appears in breast milk. Consider risk of infant bradycardia, hypotension, and electrolyte disturbances. Avoid use or monitor infant for adverse effects. |
| 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. |
■ FDA Black Box Warning
None
| Serious Effects |
["Bronchial asthma","Sinus bradycardia","Heart block greater than first degree","Cardiogenic shock","Uncompensated heart failure","Anuria","Hypersensitivity to thiazides or sulfonamides"]
| 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"] |
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| 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. |