carvedilol

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/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

Contraind./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.

Adv. 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)

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 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.
NSAIDs may ↓ antihypertensive effects.
Rifampin may ↓ levels and effectiveness.
May ↑ levels and risk of toxicity of digoxin and cyclosporine; closely monitor levels.

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 pulse frequently during dose adjustment period and periodically during therapy. Assess for orthostatic hypotension when assisting patient up from supine position. If heart rate decreases below 55 beats/min, decrease dose.
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, triglycerides, and uric acid levels.
- May cause ↑ in ANA titers.
- May cause ↑ in blood glucose levels.

Toxicity and 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.

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 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, 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. Discontinue carvedilol slowly over 1–2 wk. Advise patient to read Patient Information before starting therapy and with each Rx refill in case of changes.
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.
Advise patients with diabetes to 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.
Rep: Advise females of reproductive potential to notify health care professional if pregnancy is planned or suspected, or if breastfeeding. If carvedilol is taken during third 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, and smoking cessation). Medication controls but does not cure hypertension.

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Pronunciation ⬇

Classifications ⬆ ⬇

Indications ⬆ ⬇

Action ⬆ ⬇

Pharmacokinetics ⬆ ⬇