Coreg
Coreg - General Information
Coreg is a non-selective beta blocker indicated in the treatment of mild to moderate congestive heart failure (CHF). It blocks beta-1 and beta-2 adrenergic receptors as well as the alpha-1 adrenergic receptors.
Pharmacology of Coreg
Coreg is a nonselective beta-adrenergic blocking agent with alpha1-blocking activity and is indicated for the treatment of hypertension and mild or moderate (NYHA class II or III) heart failure of ischemic or cardiomyopathic origin. Coreg is a racemic mixture in which nonselective b-adrenoreceptor blocking activity is present in the S(-) enantiomer and a-adrenergic blocking activity is present in both R(+) and S(-) enantiomers at equal potency. Coreg has no intrinsic sympathomimetic activity. The effect of carvedilol's b-adrenoreceptor blocking activity has been demonstrated in animal and human studies showing that carvedilol (1) reduces cardiac output in normal subjects; (2) reduces exercise-and/or isoproterenol-induced tachycardia and (3) reduces reflex orthostatic tachycardia.
Coreg for patients
Patients taking COREG (Carvedilol) should be advised of the following:
- they should not interrupt or discontinue using COREG without a physician's advice.
- congestive heart failure patients should consult their physician if they experience signs or symptoms of worsening heart failure such as weight gain or increasing shortness of breath.
- they may experience a drop in blood pressure when standing, resulting in dizziness and, rarely, fainting. Patients should sit or lie down when these symptoms of lowered blood pressure occur.
- if patients experience dizziness or fatigue, they should avoid driving or hazardous tasks.
- they should consult a physician if they experience dizziness or faintness, in case the dosage should be adjusted.
- they should take COREG with food.
- diabetic patients should report any changes in blood sugar levels to their physician.
- contact lens wearers may experience decreased lacrimation.
Coreg Interactions
Inhibitors of CYP2D6; poor metabolizers of debrisoquin: Interactions of carvedilol with strong inhibitors of CYP2D6 (such as quinidine, fluoxetine, paroxetine, and propafenone) have not been studied, but these drugs would be expected to increase blood levels of the R(+) enantiomer of carvedilol . Retrospective analysis of side effects in clinical trials showed that poor 2D6 metabolizers had a higher rate of dizziness during up-titration, presumably resulting from vasodilating effects of the higher concentrations of the a-blocking R(+) enantiomer.
Catecholamine-depleting Agents: Patients taking both agents with b-blocking properties and a drug that can deplete catecholamines (e.g., reserpine and monoamine oxidase inhibitors) should be observed closely for signs of hypotension and/or severe bradycardia.
Clonidine: Concomitant administration of clonidine with agents with b-blocking properties may potentiate blood-pressure- and heart-rate-lowering effects. When concomitant treatment with agents with b-blocking properties and clonidine is to be terminated, the b-blocking agent should be discontinued first. Clonidine therapy can then be discontinued several days later by gradually decreasing the dosage.
Cyclosporine: Modest increases in mean trough cyclosporine concentrations were observed following initiation of carvedilol treatment in 21 renal transplant patients suffering from chronic vascular rejection. In about 30% of patients, the dose of cyclosporine had to be reduced in order to maintain cyclosporine concentrations within the therapeutic range, while in the remainder no adjustment was needed. On the average for the group, the dose of cyclosporine was reduced about 20% in these patients. Due to wide interindividual variability in the dose adjustment required, it is recommended that cyclosporine concentrations be monitored closely after initiation of carvedilol therapy and that the dose of cyclosporine be adjusted as appropriate.
Digoxin: Digoxin concentrations are increased by about 15% when digoxin and carvedilol are administered concomitantly. Both digoxin and COREG slow AV conduction. Therefore, increased monitoring of digoxin is recommended when initiating, adjusting, or discontinuing COREG.
Inducers and Inhibitors of Hepatic Metabolism: Rifampin reduced plasma concentrations of carvedilol by about 70%. Cimetidine increased AUC by about 30% but caused no change in Cmax.
Calcium Channel Blockers: Isolated cases of conduction disturbance (rarely with hemodynamic compromise) have been observed when COREG is co-administered with diltiazem. As with other agents with b-blocking properties, if COREG is to be administered orally with calcium channel blockers of the verapamil or diltiazem type, it is recommended that ECG and blood pressure be monitored.
Insulin or Oral Hypoglycemics: Agents with b-blocking properties may enhance the blood-sugar-reducing effect of insulin and oral hypoglycemics. Therefore, in patients taking insulin or oral hypoglycemics, regular monitoring of blood glucose is recommended.
Coreg Contraindications
COREG is contraindicated in patients with bronchial asthma (2 cases of death from status asthmaticus have been reported in patients receiving single doses of COREG) or related bronchospastic conditions, second- or third-degree AV block, sick sinus syndrome or severe bradycardia (unless a permanent pacemaker is in place), or in patients with cardiogenic shock or who have decompensated heart failure requiring the use of intravenous inotropic therapy. Such patients should first be weaned from intravenous therapy before initiating COREG.
Use of COREG in patients with clinically manifest hepatic impairment is not recommended.
COREG is contraindicated in patients with hypersensitivity to any component of the product.
Additional information about Coreg
Coreg Indication: For the treatment of mild or moderate (NYHA class II or III) heart failure of ischemic or cardiomyopathic origin.
Mechanism Of Action: Coreg is a racemic mixture in which nonselective beta-adrenoreceptor blocking activity is present in the S(-) enantiomer and alpha-adrenergic blocking activity is present in both R(+) and S(-) enantiomers at equal potency. Coreg's beta-adrenergic receptor blocking ability decreases the heart rate, myocardial contractility, and myocardial oxygen demand. Coreg also decreases systemic vascular resistance via its alpha adrenergic receptor blocking properties. Coreg and its metabolite BM-910228 (a less potent beta blocker, but more potent antioxidant) have been shown to restore the inotropic responsiveness to Ca2+ in OH- free radical-treated myocardium. Coreg and its metabolites also prevent OH- radical-induced decrease in sarcoplasmic reticulum Ca2+-ATPase activity. Therefore, carvedilol and its metabolites may be beneficial in chronic heart failure by preventing free radical damage.
Drug Interactions: Acetohexamide The beta-blocker decreases the symptoms of hypoglycemia
Chlorpropamide The beta-blocker decreases the symptoms of hypoglycemia
Citalopram The SSRI increases the effect of the beta-blocker
Clonidine Increased hypertension when clonidine stopped
Cyclosporine Increases the effect and toxicity of cyclosporine
Digoxin Increases levels/effect of digoxin
Dihydroergotamine Ischemia with risk of gangrene
Dihydroergotoxine Ischemia with risk of gangrene
Disopyramide The beta-blocker increases toxicity of disopyramide
Epinephrine Hypertension, then bradycardia
Ergonovine Ischemia with risk of gangrene
Ergotamine Ischemia with risk of gangrene
Escitalopram The SSRI increases the effect of the beta-blocker
Fenoterol Antagonism
Fluoxetine The SSRI increases the effect of the beta-blocker
Formoterol Antagonism
Gliclazide The beta-blocker decreases the symptoms of hypoglycemia
Glipizide The beta-blocker decreases the symptoms of hypoglycemia
Glisoxepide The beta-blocker decreases the symptoms of hypoglycemia
Glibenclamide The beta-blocker decreases the symptoms of hypoglycemia
Glycodiazine The beta-blocker decreases the symptoms of hypoglycemia
Ibuprofen Risk of inhibition of renal prostaglandins
Indomethacin Risk of inhibition of renal prostaglandins
Insulin The beta-blocker decreases the symptoms of hypoglycemia
Insulin-aspart The beta-blocker decreases the symptoms of hypoglycemia
Insulin-detemir The beta-blocker decreases the symptoms of hypoglycemia
Insulin-glargine The beta-blocker decreases the symptoms of hypoglycemia
Insulin-glulisine The beta-blocker decreases the symptoms of hypoglycemia
Insulin-lispro The beta-blocker decreases the symptoms of hypoglycemia
Isoproterenol Antagonism
Lidocaine The beta-blocker increases the effect and toxicity of lidocaine
Methysergide Ischemia with risk of gangrene
Orciprenaline Antagonism
Paroxetine The SSRI increases the effect of the beta-blocker
Pirbuterol Antagonism
Piroxicam Risk of inhibition of renal prostaglandins
Prazosin Risk of hypotension at the beginning of therapy
Procaterol Antagonism
Repaglinide The beta-blocker decreases the symptoms of hypoglycemia
Salbutamol Antagonism
Salmeterol Antagonism
Sertraline The SSRI increases the effect of the beta-blocker
Terbutaline Antagonism
Tolazamide The beta-blocker decreases the symptoms of hypoglycemia
Tolbutamide The beta-blocker decreases the symptoms of hypoglycemia
Verapamil Increased effect of both drugs
Food Interactions: Take with food, food slows the absorption rate and reduces the incidence of adverse effects (extent of absorption is not affected).
Generic Name: Carvedilol
Synonyms: Carvedilolum [Latin]
Drug Category: Vasodilator Agents; Antihypertensive Agents; Adrenergic Agents
Drug Type: Small Molecule; Approved
Other Brand Names containing Carvedilol: Coreg;
Absorption: Carvedilol is rapidly and extensively absorbed following oral administration, with an absolute bioavailability of approximately 25% to 35% due to a significant degree of first-pass metabolism.
Toxicity (Overdose): Not expected to be toxic following ingestion.
Protein Binding: 98%
Biotransformation: Hepatic. Carvedilol is metabolized primarily by aromatic ring oxidation and glucuronidation. The oxidative metabolites are further metabolized by conjugation via glucuronidation and sulfation. Demethylation and hydroxylation at the phenol ring produce three active metabolites with b-receptor blocking activity. The 4'-hydroxyphenyl metabolite is approximately 13 times more potent than carvedilol for b-blockade.
Half Life: 7-10 hours
Dosage Forms of Coreg: Tablet Oral
Chemical IUPAC Name: 1-(9H-carbazol-4-yloxy)-3-[2-(2-methoxyphenoxy)ethylamino]propan-2-ol
Chemical Formula: C24H26N2O4
Carvedilol on Wikipedia: https://en.wikipedia.org/wiki/Carvedilol
Organisms Affected: Humans and other mammals