COREG CR
Clinical safety rating: caution
Comprehensive clinical and safety monograph for COREG CR (COREG CR).
Nonselective beta-1, beta-2, and alpha-1 adrenergic receptor antagonist; no intrinsic sympathomimetic activity; reduces myocardial oxygen demand, decreases peripheral vascular resistance, and suppresses renin-angiotensin-aldosterone system.
| Metabolism | Extensively metabolized via aromatic ring oxidation and glucuronidation by CYP2D6 and CYP2C9, with significant first-pass effect; active metabolites include 4'-hydroxyphenylcarvedilol. |
| Excretion | Renal (16% unchanged, 60% as glucuronide conjugates), biliary/fecal (20%) |
| Half-life | Terminal elimination half-life is 7-10 hours; due to controlled-release formulation, effective half-life is prolonged to support once-daily dosing |
| Protein binding | 98% bound primarily to albumin |
| Volume of Distribution | 4.0 L/kg (extensive tissue distribution, consistent with high lipophilicity) |
| Bioavailability | Oral: 25-35% (extensive first-pass metabolism; relative to immediate-release carvedilol, controlled-release formulation shows 85% relative bioavailability) |
| Onset of Action | Oral: 30-60 minutes (first detectable beta-blockade); peak effect at 2-4 hours |
| Duration of Action | 24 hours (sustained beta-blockade and antihypertensive effect due to controlled-release matrix); trough levels maintain efficacy |
Initial dose 20 mg orally once daily for patients with heart failure; may increase at 2-week intervals to a target dose of 80 mg once daily.
| Dosage form | CAPSULE, EXTENDED RELEASE |
| Renal impairment | No dose adjustment required for GFR ≥30 mL/min. For GFR <30 mL/min, initiate at 20 mg once daily and titrate cautiously, monitoring renal function. |
| Liver impairment | Child-Pugh Class A: no dose adjustment. Class B: initial dose 20 mg once daily; increase cautiously. Class C: not recommended, or use with extreme caution; start at 20 mg once daily and titrate slowly. |
| Pediatric use | Approved for heart failure in children ≥1 year: initial 0.2 mg/kg/dose (max 6.25 mg) twice daily; target 0.4 mg/kg/dose (max 12.5 mg) twice daily. For hypertension: not established for age <1 year; for ≥1 year, use oral extended-release capsules. |
| Geriatric use | Start at lower end of dosing range (20 mg once daily) due to increased sensitivity and potential for bradycardia; titrate slowly with careful monitoring of heart rate and blood pressure. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for COREG CR (COREG CR).
| Breastfeeding | Excreted in breast milk; M/P ratio not established. Unknown effect on infant. Use with caution; monitor infant for bradycardia and hypotension. |
| Teratogenic Risk | Category C: First trimester - no adequate human studies; animal studies show risk. Second and third trimesters - may cause fetal bradycardia, intrauterine growth restriction, and placental hypoperfusion. Avoid use unless benefit outweighs risk. |
| Fetal Monitoring |
■ FDA Black Box Warning
None.
| Serious Effects |
["Bronchial asthma or bronchospastic conditions","Decompensated heart failure requiring intravenous inotropic therapy","Sick sinus syndrome or severe bradycardia (unless pacemaker present)","Cardiogenic shock","Severe hepatic impairment","Hypersensitivity to carvedilol or any component"]
| Precautions | ["Exacerbation of coronary artery disease upon abrupt withdrawal","Bradycardia, heart block, or hypotension","Worsening of heart failure or fluid retention during dose titration","Masking of hypoglycemia in diabetic patients","Peripheral vascular disease exacerbation","Bronchospasm in patients with COPD/asthma","May cause hepatic injury; monitor liver function","Anaphylactic reactions may be unresponsive to epinephrine"] |
| Food/Dietary | Take with food to reduce risk of orthostatic hypotension; avoid alcohol, which may enhance hypotensive effects. No other significant food interactions. |
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| Monitor maternal heart rate, blood pressure, and signs of heart failure. Fetal monitoring: heart rate, growth via ultrasound, and amniotic fluid index. |
| Fertility Effects | No known direct effect on fertility in humans; data limited. Animal studies show no impairment. |
| Clinical Pearls | COREG CR (carvedilol phosphate extended-release) is a nonselective beta-blocker with alpha-1 blocking activity, providing additional vasodilation. Use cautiously in patients with bronchospastic disease, diabetes (may mask hypoglycemia), or peripheral vascular disease. Do not crush or chew capsules; may be sprinkled on applesauce if swallowing difficulty. Monitor for heart failure exacerbation, bradycardia, and hypotension during titration. |
| Patient Advice | Take COREG CR once daily in the morning with food. Swallow capsule whole, or open and sprinkle contents over a spoonful of applesauce; consume immediately. · Do not skip doses or stop suddenly; sudden discontinuation may worsen chest pain or cause heart attack. · May cause dizziness or lightheadedness, especially when rising from sitting/lying position; change positions slowly. · Monitor for unusual weight gain, shortness of breath, or swelling in feet/ankles (signs of heart failure worsening). · Warn patients with diabetes that carvedilol may mask signs of hypoglycemia (tachycardia) but not other symptoms like sweating. |