carvedilol

General

Genetic Implications:

Pronunciation:
kar-vay-di-lol

Trade Name(s)

Coreg
Coreg CR

Ther. Class.

antihypertensives

Pharm. Class.

beta blockers

Indications

Hypertension.
HF (ischemic or cardiomyopathic) with digoxin, diuretics, and ACE inhibitors.
Left ventricular dysfunction after MI.

Action

Blocks stimulation of beta₁ (myocardial) and beta₂ (pulmonary, vascular, and uterine)-adrenergic receptor sites.
Also has alpha₁ blocking activity, which may result in orthostatic hypotension.

Therapeutic Effect(s):

Decreased HR and BP.
Improved cardiac output, slowing of the progression of HF and decreasing risk of death.

Pharmacokinetics

Absorption: Well absorbed but rapidly undergoes extensive first-pass hepatic metabolism, resulting in 25–35% bioavailability. Food slows absorption.

Distribution: Widely distributed to tissues.

Protein Binding: 98%.

Metabolism and Excretion: Extensively metabolized by the liver via the CYP2D6 and CYP2C9 isoenzymes; the CYP2D6 enzyme system exhibits genetic polymorphism; ~7% of population may be poor metabolizers and may have significantly ↑ carvedilol concentrations and an ↑ risk of adverse effects. Excreted in feces via bile; <2% excreted unchanged in urine.

Half-life: 7–10 hr.

TIME/ACTION PROFILE (cardiovascular effects)

ROUTE	ONSET	PEAK	DURATION
PO	within 1 hr	1–2 hr	12 hr
PO-CR	unknown	5 hr	24 hr

Contraindication/Precautions

Contraindicated in:

Hypersensitivity;
Pulmonary edema;
Cardiogenic shock;
Bradycardia, heart block, or sick sinus syndrome (unless a pacemaker is in place);
Decompensated HF requiring IV inotropic agents (wean before starting carvedilol);
Severe hepatic impairment;
Asthma or other bronchospastic disorders.

Use Cautiously in:

Diabetes mellitus (may mask signs of hypoglycemia);
Thyrotoxicosis (may mask symptoms);
Peripheral vascular disease;
History of severe allergic reactions (intensity of reactions may be ↑);
Patients undergoing cataract surgery (↑ risk of intraoperative floppy iris syndrome);
OB: Crosses placenta and may cause fetal/neonatal bradycardia, hypotension, hypoglycemia, or respiratory depression;
Lactation: Use while breastfeeding only if potential maternal benefit justifies potential risk to infant;
Pedi: Safety and effectiveness not established in children;
Geri: Older adults may have ↑ sensitivity to beta blockers; initial dose ↓ recommended.

Adverse Reactions/Side Effects

CV: BRADYCARDIA, HF

Derm: itching, rash, STEVENS-JOHNSON SYNDROME, TOXIC EPIDERMAL NECROLYSIS, urticaria

EENT: blurred vision, dry eyes, intraoperative floppy iris syndrome, nasal stuffiness

Endo: hyperglycemia, hypoglycemia

GI: diarrhea, constipation, nausea

GU: erectile dysfunction, ↓ libido

MS: arthralgia, back pain, muscle cramps

Neuro: dizziness, fatigue, weakness, anxiety, depression, drowsiness, insomnia, memory loss, mental status changes, nervousness, nightmares, paresthesia

Resp: bronchospasm, PULMONARY EDEMA, wheezing

Misc: drug-induced lupus syndrome, HYPERSENSITIVITY REACTIONS (including anaphylaxis and angioedema)

* CAPITALS indicate life-threatening.
Underline indicate most frequent.

Interactions

Drug-Drug

General anesthetics, phenytoin, diltiazem, and verapamil may cause ↑ myocardial depression.
↑ risk of bradycardia with clonidine, digoxin, diltiazem, ivabradine, and verapamil.
Amiodarone, cimetidine, and fluconazole may ↑ levels and risk of toxicity.
↑ hypotension may occur with other antihypertensives, acute ingestion of alcohol, or nitrates.
May ↑ withdrawal phenomenon from clonidine ; discontinue carvedilol first.
Concurrent administration of thyroid preparations may ↓ effectiveness.
May alter the effectiveness of insulin or oral hypoglycemic agents ; dose adjustments may be necessary.
May ↓ effectiveness of theophylline.
May ↓ beneficial beta₁ -cardiovascular effects of dopamine or dobutamine.
Use cautiously within 14 days of MAO inhibitor therapy; may result in hypotension/bradycardia.
NSAIDs may ↓ antihypertensive effects.
Rifampin may ↓ levels and effectiveness.
May ↑ levels and risk of toxicity of digoxin and cyclosporine ; monitor levels closely.

Route/Dosage

Hypertension

PO (Adults): Immediate release: 6.25 mg twice daily; may be ↑ every 7–14 days up to 25 mg twice daily. Extended release: 20 mg once daily; dose may be doubled every 7–14 days up to 80 mg once daily.

Heart Failure

PO (Adults): Immediate release: 3.125 mg twice daily; dose may be doubled every 2 wk as tolerated (not to exceed 25 mg twice daily in patients <85 kg or 50 mg twice daily in patients >85 kg). Extended release: 10 mg once daily; dose may be doubled every 2 wk as tolerated up to 80 mg once daily.

Left Ventricular Dysfunction After Myocardial Infarction

PO (Adults): Immediate release: 6.25 mg twice daily; ↑ after 3–10 days to 12.5 twice daily; then to target dose of 25 mg twice daily; some patients may require lower initial doses and slower titration. Extended release: 20 mg once daily; dose may be doubled every 3–10 days up to 80 mg once daily.

Availability (generic available)

Extended-release capsules: 10 mg, 20 mg, 40 mg, 80 mg

Tablets: 3.125 mg, 6.25 mg, 12.5 mg, 25 mg

Assessment

Monitor BP and HR frequently during dose adjustment and periodically during therapy. Assess for bradycardia and orthostatic hypotension. If HR ↓ to <55 bpm, ↓ dose.
Monitor intake and output and daily weight. Assess patient routinely for evidence of fluid overload (peripheral edema, dyspnea, rales/crackles, fatigue, weight gain, jugular venous distention). Patients with HF may have worsening of symptoms during therapy initiation.

Lab Test Considerations:

May ↑ BUN, triglycerides, and uric acid levels.

May ↑ blood glucose.

Implementation

Do not confuse carvedilol with captopril.
- Discontinuation of concurrent clonidine should be gradual, with carvedilol discontinued first over 1–2 wk with limitation of physical activity; then, after several days, discontinue clonidine.
PO Take HR before administering. If <50 bpm or if arrhythmia occurs, hold therapy.
- Administer with food to minimize orthostatic hypotension.
- Administer extended-release capsules in the morning. DNC: Swallow whole; do not crush or chew. Extended-release capsules may be opened and sprinkled on cold applesauce and taken immediately; do not store mixture.
- To convert from immediate-release to extended-release product, convert 3.125 mg twice daily dose to 10 mg once daily; convert 6.25 mg twice daily dose to 20 mg once daily; convert 12.5 mg twice daily dose to 40 mg once daily; convert 25 mg twice daily dose to 80 mg once daily.

Patient/Family Teaching

Explain purpose and side effects of medication. Advise patient to read Patient Information before starting therapy. Instruct patient to take at the same time each day, even if feeling well. Do not skip or double up on missed doses. Take missed doses as soon as possible up to 4 hr before next dose.
Advise patient that abrupt withdrawal may precipitate life-threatening arrhythmias, hypertension, or myocardial ischemia. Discontinue carvedilol slowly over 1–2 wk as directed by a health care professional.
Instruct patient on how to check HR daily and BP biweekly. Advise patient to hold dose and contact health care professional for HR <50 bpm or if there are significant BP changes.
May cause drowsiness or dizziness. Caution patients to avoid driving or other activities that require alertness until response to therapy is known.
Advise patient to change positions slowly to minimize orthostatic hypotension, especially during initiation of therapy or with dose ↑.
Caution patient that carvedilol may ↑ sensitivity to cold.
Advise patient to notify health care professional of all Rx or OTC medications, vitamins, or herbal products being taken and to consult health care professional before taking other medications.
Advise patients with diabetes to closely monitor blood glucose, especially if weakness, malaise, irritability, or fatigue occurs. Carvedilol may mask some signs of hypoglycemia, but dizziness and sweating may still occur.
Advise patient to notify health care professional if difficulty breathing, wheezing, cold hands and feet, dizziness, confusion, depression, rash, fever, sore throat, or unusual bleeding or bruising occurs.
Instruct patient to inform health care professional of medication regimen before treatment or surgery.
Advise patient to carry identification describing disease and medication regimen at all times.
Rep: Advise women of reproductive potential to notify health care professional if pregnancy is planned or suspected or if breastfeeding. If carvedilol is taken during 3rd trimester, monitor newborn for symptoms of hypotension, bradycardia, hypoglycemia, and respiratory depression and manage accordingly.
Hypertension: Reinforce the need to continue additional therapies for hypertension (weight loss, sodium restriction, stress reduction, regular exercise, moderation of alcohol consumption, smoking cessation). Medication controls but does not cure hypertension.

Evaluation/Desired Outcomes

Decrease in heart rate and BP.
Improved cardiac output, slowing of the progression of HF and decreased risk of death.