carvedilol, Coreg, Coreg CR

 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 Effects:

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 significantlyqcarvedilol concentrations and anq

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

Contraindications/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:

qsensitivity 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,plibido.

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.

Interactions

Drug-Drug: General anesthetics, IV phenytoin,

diltiazem, and verapamil may causeqmyocardial

depression.qrisk of bradycardia with digoxin. Amiodarone

or fluconazole mayqlevels.qhypotension

may occur with other antihypertensives, acute ingestion

of alcohol, or nitrates. Concurrent use with

clonidineqhypotension and bradycardia. Mayqwithdrawal

phenomenon from clonidine (discontinue carvedilol

first). Concurrent administration of thyroid

preparations maypeffectiveness. May alter the effectiveness

of insulins or oral hypoglycemic agents

(dose adjustments may be necessary). Maypeffectiveness

of theophylline. Maypbeneficial beta1-cardiovascular

effects of dopamine or dobutamine. Use

cautiously within 14 days of MAO inhibitor therapy

(may result in hypotension/bradycardia). Cimetidine

mayqtoxicity from carvedilol. Concurrent NSAIDs

maypantihypertensive action. Effectiveness may bep

by rifampin. Mayqserum digoxin levels. Mayq

blood levels of cyclosporine (monitor blood levels).

Route/Dosage

PO (Adults): Hypertension—6.25 mg twice daily,

may beqq 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 beqto 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,qafter

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.