COREG
Clinical safety rating: caution
Comprehensive clinical and safety monograph for COREG (COREG).
Carvedilol is a nonselective beta-blocker with alpha1-blocking activity. It competitively blocks beta1, beta2, and alpha1 adrenergic receptors, leading to decreased cardiac output, reduced sympathetic tone, and vasodilation. It also has antioxidant and anti-proliferative properties.
| Metabolism | Extensively metabolized by CYP2D6 and CYP2C9, with minor contributions from CYP3A4 and CYP1A2. Undergoes glucuronidation and sulfation. |
| Excretion | Renal excretion of unchanged drug and metabolites accounts for approximately 16% of the dose; fecal excretion accounts for about 84% (mainly as metabolites). Less than 2% is excreted unchanged in urine. |
| Half-life | Terminal elimination half-life is 7-10 hours in most patients, but may be prolonged in severe hepatic impairment (up to 14-18 hours). The half-life is not significantly altered in renal impairment. |
| Protein binding | Approximately 98-99% bound to plasma proteins, primarily albumin. The drug is extensively bound to alpha1-acid glycoprotein. |
| Volume of Distribution | Volume of distribution is approximately 4 L/kg, indicating extensive tissue distribution. This large Vd reflects high lipophilicity and penetration into tissues including the central nervous system. |
| Bioavailability | Oral bioavailability is approximately 25-35% due to extensive first-pass metabolism. Administration with food delays absorption but does not significantly alter overall bioavailability. |
| Onset of Action | Oral: Onset of beta-blockade occurs within 30-60 minutes; peak antihypertensive effect is seen within 2-4 hours. For heart failure, clinical benefit may be observed after several weeks of therapy. |
| Duration of Action | Beta-blockade persists for 12-24 hours after a single dose; however, sustained clinical effects in hypertension and heart failure require continuous once-daily or twice-daily dosing (twice daily is standard for heart failure due to trough effects). |
Heart failure: Start 3.125 mg orally twice daily; titrate up to target 25 mg twice daily as tolerated. Hypertension: Start 6.25 mg orally twice daily; increase to max 50 mg twice daily. Post-MI LV dysfunction: Start 3.125-6.25 mg orally twice daily; titrate to target 25 mg twice daily.
| Dosage form | TABLET |
| Renal impairment | No specific dose adjustment based on GFR; use with caution in severe renal impairment. Carvedilol is highly protein bound and not significantly removed by dialysis. |
| Liver impairment | Contraindicated in decompensated cirrhosis (Child-Pugh class C). In Child-Pugh class A or B, reduce starting dose: 3.125 mg twice daily; titrate slowly with close monitoring. |
| Pediatric use | Not FDA approved for pediatric patients. Limited data: For heart failure, start 0.1 mg/kg/dose twice daily (max 3.125 mg/dose); titrate to max 0.3-0.5 mg/kg/dose twice daily (not to exceed 25 mg/dose). Use only under expert guidance. |
| Geriatric use | Start at low end of dosing range (3.125 mg twice daily); titrate slowly due to increased risk of bradycardia, hypotension, and dizziness. Monitor renal function and volume status. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for COREG (COREG).
| Breastfeeding | Excreted in breast milk; M/P ratio not well defined. Limited data; consider withholding breastfeeding due to potential for bradycardia and hypotension in the infant. Alternatively, use with caution if benefits outweigh risks. |
| Teratogenic Risk | Pregnancy Category C. First trimester: No adequate studies; animal studies show embryotoxicity. Second and third trimesters: Risk of fetal bradycardia, hypotension, and growth restriction. Avoid in preeclampsia; may cause fetal bradycardia if used near term. |
| Fetal Monitoring |
■ FDA Black Box Warning
None.
| Serious Effects |
["Bronchial asthma or severe COPD","Sinus bradycardia, sick sinus syndrome, or heart block >1st degree (unless pacemaker)","Cardiogenic shock","Decompensated heart failure requiring IV inotropes","Hypersensitivity to carvedilol","Severe hepatic impairment"]
| Precautions | ["Worsening heart failure or fluid retention (initiation or dose escalation)","Bradycardia, heart block, hypotension","Abrupt withdrawal may exacerbate angina or precipitate MI","Bronchospasm in patients with asthma/COPD","Mask symptoms of hypoglycemia","May mask hyperthyroidism symptoms","Peripheral vascular disease exacerbation","Use with caution in hepatic impairment","Risk of anaphylaxis in patients with history of severe reactions"] |
| Food/Dietary | Avoid grapefruit juice; take with food to reduce dizziness; limit alcohol intake; maintain consistent dietary sodium intake if applicable. |
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| Monitor maternal blood pressure and heart rate regularly. Assess fetal growth and heart rate during third trimester. Watch for signs of fetal bradycardia or growth restriction. Monitor neonatal heart rate and glucose levels after delivery. |
| Fertility Effects | Not known to impair fertility based on limited animal studies; no human data available. |
| Clinical Pearls | Titrate slowly to minimize hypotension risk; use in stable heart failure (NYHA II-IV) with low starting doses; do not discontinue abruptly to avoid exacerbation; monitor for bradycardia, fluid retention, and worsening heart failure; use caution in asthma or COPD due to beta-blockade; can be used in combination with ACE inhibitors and diuretics. |
| Patient Advice | Take exactly as prescribed, usually twice daily. · Do not stop suddenly; abrupt withdrawal can worsen heart condition. · May cause dizziness or lightheadedness, especially early in treatment or after a dose increase. · Avoid grapefruit juice as it may increase drug levels. · Weigh yourself daily and report rapid weight gain or swelling. · Report shortness of breath, slow heartbeat, or fainting. · Avoid alcohol as it may lower blood pressure and increase side effects. |