Carvedilol - Warnings and Precautions

5 WARNINGS AND PRECAUTIONS In clinical trials of extended-release carvedilol phosphate capsules in subjects with hypertension (338 subjects) and in subjects with left ventricular dysfunction following a myocardial infarction or heart failure (187 subjects), the profile of adverse events observed with carvedilol phosphate was generally similar to that observed with the administration of immediate-release carvedilol.

Therefore, the information included within this section is based on data from controlled clinical trials with extended-release carvedilol phosphate capsules as well as immediate-release carvedilol.

Acute exacerbation of coronary artery disease upon cessation of therapy: Do not abruptly discontinue.

Bradycardia, hypotension, worsening heart failure/fluid retention may occur.

Reduce the dose as needed. ( 5.2 , 5.3 , 5.4 ) Non-allergic bronchospasm (e.g., chronic bronchitis and emphysema): Avoid beta-blockers.

However, if deemed necessary, use with caution and at lowest effective dose.

Diabetes: Monitor glucose as beta-blockers may mask symptoms of hypoglycemia or worsen hyperglycemia.

5.1 Cessation of Therapy Patients with coronary artery disease, who are being treated with carvedilol phosphate extended-release capsules, should be advised against abrupt discontinuation of therapy.

Severe exacerbation of angina and the occurrence of myocardial infarction and ventricular arrhythmias have been reported in patients with angina following the abrupt discontinuation of therapy with beta-blockers.

The last 2 complications may occur with or without preceding exacerbation of the angina pectoris.

As with other beta-blockers, when discontinuation of carvedilol phosphate extended-release capsule is planned, the patients should be carefully observed and advised to limit physical activity to a minimum.

Carvedilol phosphate extended-release capsules should be discontinued over 1 to 2 weeks whenever possible.

If the angina worsens or acute coronary insufficiency develops, it is recommended that carvedilol phosphate extended-release capsules be promptly reinstituted, at least temporarily.

Because coronary artery disease is common and may be unrecognized, it may be prudent not to discontinue therapy with carvedilol phosphate extended-release capsules abruptly even in patients treated only for hypertension or heart failure.

5.2 Bradycardia In clinical trials with immediate-release carvedilol, bradycardia was reported in about 2% of hypertensive subjects, 9% of subjects with heart failure, and 6.5% of subjects with myocardial infarction and left ventricular dysfunction.

Bradycardia was reported in 0.5% of subjects receiving carvedilol phosphate extended-release capsules in a trial of subjects with heart failure and subjects with myocardial infarction and left ventricular dysfunction.

There were no reports of bradycardia in the clinical trial of carvedilol phosphate extended-release capsules in hypertension.

However, if pulse rate drops below 55 beats per minute, the dosage of extended-release carvedilol should be reduced.

5.3 Hypotension In clinical trials of primarily mild-to-moderate heart failure with immediate-release carvedilol, hypotension and postural hypotension occurred in 9.7% and syncope in 3.4% of subjects receiving carvedilol compared with 3.6% and 2.5% of placebo subjects, respectively.

The risk for these events was highest during the first 30 days of dosing, corresponding to the up-titration period and was a cause for discontinuation of therapy in 0.7% of carvedilol subjects, compared with 0.4% of placebo subjects.

In a long-term, placebo-controlled trial in severe heart failure (COPERNICUS), hypotension and postural hypotension occurred in 15.1% and syncope in 2.9% of subjects with heart failure receiving carvedilol compared with 8.7% and 2.3% of placebo subjects, respectively.

These events were a cause for discontinuation of therapy in 1.1% of carvedilol subjects, compared with 0.8% of placebo subjects.

In a trial comparing subjects with heart failure switched to carvedilol phosphate extended-release capsules or maintained on immediate-release carvedilol, there was a 2-fold increase in the combined incidence of hypotension, syncope, or dizziness in elderly subjects (older than 65 years) switched from the highest dose of carvedilol (25 mg twice daily) to carvedilol phosphate extended-release capsules 80 mg once daily [see Dosage and Administration , Use in Specific Populations ] .

In the clinical trial of carvedilol phosphate extended-release capsules in hypertensive subjects, syncope was reported in 0.3% of subjects receiving carvedilol phosphate extended-release capsules compared with 0% of subjects receiving placebo.

There were no reports of postural hypotension in this trial.