Guidelines for the Use of Carvedilol (Coreg) in Heart Failure

A. Contraindications:

1.  Carvedilol is contraindicated in the following situations:

            a. Bronchial asthma or related bronchospastic conditions.  The beta-2 adrenoceptor blocking affects of carvedilol can prevent the bronchodilatory action of sympathomimetic amines or catecholamines.  Two cases of death secondary to status asthmaticus have been reported with single doses of carvedilol.

            b.  NYHA Class IV decompensated cardiac failure requiring intravenous inotropic therapy or in cardiogenic shock.  Carvedilol can block the beta-1 adrenoceptors of the heart and antagonize the positive inotropic effects of catecholamines which can cause further clinical decompensation.

            c. Sick sinus syndrome without placement of a permanent pacemaker.  Carvedilol is a negative chronotropic agent and would be hazardous during the bradycardic phase of the disorder.

            d. Severe bradycardia or second or third degree heart block.  Carvedilol is a negative chronotropic agent and can cause worsening of bradycardia.  Carvedilol, like other beta-blockers, can also increase AV nodal refractoriness and worsen AV block.

2. Carvedilol should not be used or used with caution in the following clinical situations:

            a. Severe hepatic dysfunction.  Carvedilol is extensively metabolized by the liver and the metabolites are primarily excreted in the bile.  Hence, carvedilol could accumulate if used in this population.

            b. If the blood pressure is less than or equal to 90/60mmHg or the patient’s heart rate is at or below 60bpm. 

B.  Indications and Dosage:

1. Carvedilol is indicated for the treatment of mild to moderate (NYHA class II and III) heart failure of ischemic or cardiomyopathic origin, in combination with digitalis, diuretics, and ACE inhibitors, to reduce the progression of disease as evidenced by cardiovascular death, cardiovascular hospitalization, or the need to adjust other heart failure medications.  Carvedilol may be used in patients unable to tolerate an ACE inhibitor.  Carvedilol may be used in patients who are or are not receiving digitalis, hydralazine or nitrate therapy.

2. The dosage of carvedilol should be individualized and the response to drug initiation and titration should be closely monitored.  Some patients will not tolerate even the lowest dose of carvedilol and others will not be able to be titrated up to the target doses (see below).  Patients not achieving the target dose can still derive clinical benefit from carvedilol therapy.

3. Carvedilol should be given with food to decrease the rate of absorption.  This will reduce the extent of blood pressure reduction.

4. To initiate therapy, start all patients, regardless of previous beta blocker history or other drug usage, on 3.125 mg bid for 2 weeks. 

5.  All  patients should be observed for at least one hour after the initial dose and with each increase in dosage strength, by a physician or competent caregiver.

6. If the initial dose is tolerated it can be increased to 6.25 mg bid for 2 weeks.  Subsequent incremental dosage should be adjusted every two weeks.  If tolerated, the dose is doubled each time up to a maximum of 25 mg bid for patients under 85 kg and 50 mg for patients over 85 kg.

7. If any dosage increase is not tolerated the patient should be continued on the last tolerated dose and treated for another 2 weeks before trying the titration again.

C. Monitoring of Adverse Events:

1.  Some patients may experience adverse effects from vasodilation, worsening CHF, bradycardia, AV block, diarrhea, generalized edema and vision abnormalities. The most common adverse effect of carvedilol is dizziness secondary to vasodilation (32.4% of carvedilol patients versus 22.4% of patients receiving placebo). For each of the following adverse events these measures are recommended:

            a.  If the patient experiences symptoms of vasodilation (dizziness) or has a blood pressure of 90/60 or below, make sure the patient is taking the medication with food and that carvedilol is being given 2 hours before an ACE inhibitor or other vasodilating drug.  If these preventative measures were being followed, decrease the diuretic or ACE inhibitor dose.  If the symptoms persist, decrease the dose of carvedilol.  If carvedilol needs to be discontinued from maintenance therapy, decrease the dose gradually over 1-2 weeks.

            b.  If the patient experiences symptoms of mildly worsening CHF (edema, weight gain,  SOB), increase the oral diuretic dose, if the symptoms persist, decrease carvedilol.

            c.  If the patient experiences bradycardia (HR < 55bpm) or prolonged AV conduction block, decrease carvedilol.

D. Significant Potential Drug Interactions:

1. Propafenone, quinidine, fluoxetine, paroxetine, diphenhydramine - increase levels of carvedilol

2. Carvedilol can increase the levels of digoxin.  Monitoring digoxin levels is prudent when the dosage of carvedilol is altered substantially.

E. Converting from immediate release to controlled release carvedilol

       Immediate Release                       Controlled Release

• 3.125mg BID              =          10mg QD
• 6.25mg BID                =          20mg QD
• 12.5mg BID                =          40mg QD
• 25.0mg BID                =          80mg DQ

1. Controlled release carvedilol is once rather than twice daily
2. The AUC is the same but the Cmax is lower
   1. The risk of dizziness is attenuated
3. An excellent option for patient on immediate release for whom dizziness is a concern