General

Genetic Implications:

Pronunciation:
kar-ve-di-lole


Trade Name(s)

  • Coreg
  • Coreg CR

Pregnancy Category
Category C

Ther. Class.
antihypertensives

Pharm. Class.
beta blockers

Indications

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

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

Pharmacokinetics

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

Distribution: Unknown.

Protein Binding: 98%.

Metabolism and Excretion: Extensively metabolized (primarily by CYP2D6 and CYP2C9; 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)

ROUTEONSETPEAKDURATION
POwithin 1 hr1–2 hr12 hr
PO-CRunknown5 hr24 hr

Contraindication/Precautions

Contraindicated in:

  • History of serious hypersensitivity reaction (Stevens-Johnson syndrome, angioedema, anaphylaxis);
  • Pulmonary edema;
  • Cardiogenic shock;
  • Bradycardia, heart block or sick sinus syndrome (unless a pacemaker is in place);
  • Uncompensated HF requiring IV inotropic agents (wean before starting carvedilol);
  • Severe hepatic impairment;
  • Asthma or other bronchospastic disorders.

Use Cautiously in:

  • HF (condition may deteriorate during initial therapy);
  • Renal impairment;
  • Hepatic impairment;
  • Diabetes mellitus (may mask signs of hypoglycemia);
  • Thyrotoxicosis (may mask symptoms);
  • Peripheral vascular disease;
  • History of severe allergic reactions (intensity of reactions may be increased);
  • OB: Crosses placenta and may cause fetal/neonatal bradycardia, hypotension, hypoglycemia, or respiratory depression);
  • Lactation: Pedi: Safety not established;
  • Geri: ↑ sensitivity to beta blockers; initial dose reduction recommended.

Adverse Reactions/Side Effects

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

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

Resp: bronchospasm, wheezing

CV: BRADYCARDIA, HF, PULMONARY EDEMA

GI: diarrhea, constipation, nausea

GU: erectile dysfunction, ↓ libido

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

Endo: hyperglycemia, hypoglycemia

MS: arthralgia, back pain, muscle cramps

Neuro: paresthesia

Misc: ANAPHYLAXIS, ANGIOEDEMA, drug-induced lupus syndrome

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

Interactions

Drug-Drug

  • General anesthetics, IV phenytoin, diltiazem, and verapamil may cause ↑ myocardial depression.
  • ↑ risk of bradycardia with digoxin .
  • Amiodarone or fluconazole may ↑ levels.
  • ↑ hypotension may occur with other antihypertensives, acute ingestion of alcohol, or nitrates .
  • Concurrent use with clonidine ↑ hypotension and bradycardia.
  • May ↑ withdrawal phenomenon from clonidine (discontinue carvedilol first).
  • Concurrent administration of thyroid preparations may ↓ effectiveness.
  • May alter the effectiveness of insulins 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).
  • Cimetidine may ↑ toxicity from carvedilol.
  • Concurrent NSAIDs may ↓ antihypertensive action.
  • Effectiveness may be ↓ by rifampin .
  • May ↑ serum digoxin levels.
  • May ↑ blood levels of cyclosporine (monitor blood levels).

Route/Dosage

PO: (Adults) Hypertension– 6.25 mg twice daily, may be ↑ q 7–14 days up to 25 mg twice daily or extended-release– 20 mg once daily, dose may be doubled every 7–14 days up to 80 mg once daily; HF– 3.125 mg twice daily for 2 wk; may be ↑ to 6.25 mg twice daily. Dose may be doubled q 2 wk as tolerated (not to exceed 25 mg twice daily in patients <85 kg or 50 mg twice daily in patients >85 kg) or 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 MI– 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 or extended-release– 20 mg once daily, dose may be doubled every 3–10 days up to 80 mg once daily.

Availability (generic available)

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

Cost:

Generic: All strengths $7.18/100

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

Cost: all strengths $175.36/30

Assessment

  • Monitor BP and pulse frequently during dose adjustment period and periodically during therapy. Assess for orthostatic hypotension when assisting patient up from supine position.
  • Monitor intake and output ratios and daily weight. Assess patient routinely for evidence of fluid overload (peripheral edema, dyspnea, rales/crackles, fatigue, weight gain, jugular venous distention). Patients may experience worsening of symptoms during initiation of therapy for HF.
  • Hypertension: Check frequency of refills to determine adherence.

Lab Test Considerations: May cause ↑ BUN, serum lipoprotein, potassium, triglyceride, and uric acid levels.

  • May cause ↑ ANA titers.
  • May cause ↑ in blood glucose levels.

Toxicity Overdose:

Monitor patients receiving beta blockers for signs of overdose (bradycardia, severe dizziness or fainting, severe drowsiness, dyspnea, bluish fingernails or palms, seizures). Notify health care professional immediately if these signs occur.

Potential Diagnoses

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 apical pulse before administering. If <50 bpm or if arrhythmia occurs, withhold medication and notify health care professional.
    • Administer with food to minimize orthostatic hypotension.
    • Administer extended-release capsulesin the morning. Swallow whole; do not crush, break, 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, doses of 3.125 mg twice daily can be converted to 10 mg daily; doses of 6.25 mg twice daily can be converted to 20 mg daily; doses of 12.5 mg twice daily can be converted to 40 mg daily; and doses of 25 mg twice daily can be converted to 80 mg daily.

Patient/Family Teaching

  • Instruct patient to take medication as directed, 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. Abrupt withdrawal may precipitate life-threatening arrhythmias, hypertension, or myocardial ischemia.
  • Advise patient to make sure enough medication is available for weekends, holidays, and vacations. A written prescription may be kept in wallet in case of emergency.
  • Teach patient and family how to check pulse and BP. Instruct them to check pulse daily and BP biweekly. Advise patient to hold dose and contact health care professional if pulse is <50 bpm or BP changes significantly.
  • May cause drowsiness or dizziness. Caution patients to avoid driving or other activities that require alertness until response to the drug is known.
  • Advise patient to change positions slowly to minimize orthostatic hypotension, especially during initiation of therapy or when dose is increased.
  • Caution patient that this medication may increase sensitivity to cold.
  • Instruct 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 Rx, OTC, or herbal products, especially cold preparations, concurrently with this medication.
  • Patients with diabetes should closely monitor blood glucose, especially if weakness, malaise, irritability, or fatigue occurs. Medication may mask some signs of hypoglycemia, but dizziness and sweating may still occur.
  • Advise patient to notify health care professional if slow pulse, difficulty breathing, wheezing, cold hands and feet, dizziness, confusion, depression, rash, fever, sore throat, 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 process and medication regimen at all times.
  • Hypertension: Reinforce the need to continue additional therapies for hypertension (weight loss, sodium restriction, stress reduction, regular exercise, moderation of alcohol consumption, and smoking cessation). Medication controls but does not cure hypertension.

Evaluation/Desired Outcomes

  • Decrease in BP without appearance of detrimental side effects.
  • Decrease in severity of HF.