Dosing and uses of Coreg, Coreg CR (carvedilol)
Adult dosage forms and strengths
capsule, extended release
- 10mg
- 20mg
- 40mg
- 80mg
tablet
- 3.125mg
- 6.25mg
- 12.5mg
- 25mg
Congestive Heart Failure
Immediate release
- 3.125 mg PO q12hr for 2 weeks, then increased every 2 weeks as tolerated to 6.25 mg, 12.5 mg, or 25 mg PO twice daily
- Maximum recommended dosage (mild-to-moderate heart failure): <85 kg, 25 mg PO q12hr; >85 kg: 50 mg PO twice daily
- Maximum recommended dosage (severe heart failure): 25 mg PO twice daily
Extended release
- 10 mg/day PO; maintained for 1-2 weeks if tolerated; may be increased to 20 mg/day, 40 mg/day, or 80 mg/day PO if necessary
Hypertension
Immediate release: 6.25 mg PO twice daily initially; after 7-14 days, increased as tolerated, first to 12.5 mg PO twice daily and then to 25 mg PO twice daily
Extended release: 20 mg/day PO; maintained for 1-2 weeks if tolerated; may be increased to 40 mg/day PO if necessary; not to exceed 80 mg/day PO
Left Ventricular Dysfunction Following Myocardial Infarction
Immediate release: 3.125-6.25 mg PO q12hr initially; after 3-10 days, increased as tolerated, first to 12.5 mg PO q12hr and then to 25 mg PO q12hr (target dosage)
Extended release: 10-20 mg/day PO; increased every 3-10 days as tolerated up to 80 mg/day PO (target dosage)
Angina pectoris
25-50 mg PO twice daily
Dosing Modifications
Renal impairment: No dosage adjustments necessary
Hepatic impairment: Contraindicated in severe liver impairment
Conversion to Extended Release Form
3.125 mg twice daily: Administer 10 mg PO qDay
6.25 mg twice daily: Administer 20 mg PO qDay
12.5 mg twice daily: Administer 40 mg PO qDay
25 mg twice daily: Administer 80 mg PO qDay
Administration
To be taken with food
May break capsule and sprinkle on spoonful of applesauce; to be eaten immediately
Pediatric dosage forms and strengths
Safety and efficacy not established
Coreg, Coreg CR (carvedilol) adverse (side) effects
>10%
Dizziness (2-32%)
Fatigue (4-24%)
Hypotension (9-20%)
Weight gain (10-12%)
Hyperglycemia (5-12%)
Diarrhea (1-12%)
1-10% (selected)
Bradycardia (2-10%)
Nausea (2-9%)
Cough (5-8%)
Headache (5-8%)
Atrioventricular block, edema (1-7%)
Angina (1-6%)
Hpercholesterolemia (1-4%)
Hypertriglyceredemia (1%)
Vomiting (1-6%)
Dyspnea (>3%)
Syncope (3%)
Rhinitis (2%)
Frequency not defined (selected)
Hypertension
Palpitations
Insomnia
Somnolence
Skin rash
Hepatotoxicity
Impotence
Bronchospasm
Rales
Depression
Decreased exercise tolerance
Raynaud phenomenon
Increased triglyceride levels and insulin resistance with decreased high-density lipoprotein (HDL) levels
Postmarketing Reports
Blood and lymphatic system: Aplastic anemia
Immune system: Hypersensitivity (eg, anaphylactic reactions, angioedema, urticaria) with Coreg and Coreg CR, including cases occurring after initiation of Coreg CR in patients previously treated with Coreg
Kidneys and urinary tract: Urinary incontinence
Respiratory system, thorax, and mediastinum: Interstitial pneumonitis
Skin and subcutaneous tissue: Stevens-Johnson syndrome, toxic epidermal necrolysis, erythema multiforme
Warnings
Contraindications
History of serious hypersensitivity reaction (eg, Stevens-Johnson syndrome, anaphylactic reaction, angioedema) to any component of this medication or other medications containing carvediloL
Bronchial asthma, bronchospasm
Chronic obstructive pulmonary disease (COPD)
2°/3° AV block, sick sinus syndrome without permanent pacemaker, cardiogenic shock, severe bradycardia, decompensated heart failure requiring IV inotropic medication
Severe hepatic impairment
Cautions
Use cautioin in anesthesia or surgery (myocardial depression), cerebrovascular insufficiency, diabetes mellitus, hyperthyroidism or thyrotoxicosis, liver disease, peripheral vascular disease (monitor for progression of arterial obstruction), compromised left ventricular function, heart failure, pheochromocytoma, and myasthenia gravis
Avoid beta-blocker use in non-allergic bronchospasm (e.g., chronic bronchitis and emphysema); if deemed necessary, use with caution and at lowest effective dose
Combined incidence of hypotension, syncope, or dizziness reported in elderly patients (>65 years) switched from highest dose of immediate-release carvedilol (25 mg q12hr) to extended-release carvedilol 80 mg/day
When elderly patients are switched from higher doses of immediate-release carvedilol to extended-release carvedilol, a lower starting dose is recommended
Sudden discontinuance can exacerbate angina and lead to myocardial infarction
Increased risk of stroke after surgery
Dosage should be reduced if bradycardia (HR <55 beats/min) develops
May mask hypoglycemia or hyperthyroidism
May worsen arterial insufficiency in patients with peripheral vascular disease
Use caution in patients with mild to moderate hepatic impairment
Heart failure patients may experience a worsening of renal function, especially during upward titration; dose reduction or temporary discontinuation may be necessary; may also need to adjust other medications
Extended release: Separate any form of alcohol intake by at least 2 hours
Elderly (liver function)
Intraoperative floppy iris syndrome observed during cataract surgery in some patients treated with alpha1-blocking agents
Beta-blockers may cause induction or exacerbation of psoriasis
Pregnancy and lactation
Pregnancy category: C; D in 2nd and 3rd trimesters (expert analysis)
Lactation: Unknown whether drug is excreted in milk; not recommended
Pregnancy categories
A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.
B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.
C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.
D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.
X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.
NA: Information not available.
Pharmacology of Coreg, Coreg CR (carvedilol)
Mechanism of action
Nonselective beta-adrenergic and alpha1-adrenergic blocking agent with no intrinsic activity for use in congestive heart failure and hypertension
Absorption
Bioavailability: 25-35% (immediate release)
Onset (antihypertensive): Initial response, 1 hr; peak response, 1-2 hr
Duration: 24 hr
Peak plasma time: 5 hr
Distribution
Protein bound: >98%
Vd: 115-132 L
Metabolism
Metabolized by CYP2D6 and CYP2C9 and, to a lesser extent, by CYP3A4, 2C19, 1A2, and 2E1
Metabolites: 4'-Hydroxyphenyl metabolite is approximately 13 times more potent than carvedilol for beta blockade
Elimination
Half-life: 7-10 hr
Dialyzable: HD, no
Excretion: Feces (60%), urine (16%)
