ported with a frequency of greater than 1% but less than or equal to 3% and more frequently with carvedilol: flu syndrome, cerebrovascular accident, peripheral vascular disorder, hypotonia, depression, gastrointestinal pain, arthritis, and gout. The overall rates of discontinuations due to adverse events were similar in both groups of subjects. In this database, the only cause of discontinuation greater than 1% and occurring more often on carvedilol was hypotension (1.5% on carvedilol, 0.2% on placebo).
Hypertension
COREG CR was eva luated for safety in an 8-week double-blind trial in 337 subjects with essential hypertension. The profile of adverse events observed with COREG CR was generally similar to that observed with immediate-release carvedilol. The overall rates of discontinuations due to adverse events were similar between COREG CR and placebo.
Table 3. Adverse Events (%) Occurring More Frequently with COREG CR than with Placebo in Subjects with Hypertension (Incidence ≥1% in Subjects Treated with Carvedilol, Regardless of Causality)
Adverse Event
COREG CR
(n = 253)
Placebo
(n = 84)
Nasopharyngitis
4
0
Dizziness
2
1
Nausea
2
0
Edema peripheral
2
1
Nasal congestion
1
0
Paresthesia
1
0
Sinus congestion
1
0
Diarrhea
1
0
Insomnia
1
0
The following information describes the safety experience in hypertension with immediate-release carvedilol.
Carvedilol has been eva luated for safety in hypertension in more than 2,193 subjects in U.S. clinical trials and in 2,976 subjects in international clinical trials. Approximately 36% of the total treated population received carvedilol for at least 6 months. In general, carvedilol was well tolerated at doses up to 50 mg daily. Most adverse events reported during carvedilol therapy were of mild to moderate severity. In U.S. controlled clinical trials directly comparing carvedilol monotherapy in doses up to 50 mg (n = 1,142) with placebo (n = 462), 4.9% of carvedilol subjects discontinued for adverse events versus 5.2% of placebo subjects. Although there was no overall difference in discontinuation rates, discontinuations were more common in the carvedilol group for postural hypotension (1% versus 0). The overall incidence of adverse events in U.S. placebo‑controlled trials was found to increase with increasing dose of carvedilol. For individual adverse events this could only be distinguished for dizziness, which increased in frequency from 2% to 5% as total daily dose increased from 6.25 mg to 50 mg as single or divided doses.
TABLE 4 shows adverse events in U.S. placebo‑controlled clinical trials for hypertension that occurred with an incidence of greater than or equal to 1% regardless of causality and that were more frequent in drug‑treated subjects than placebo‑treated subjects.
Table 4. Adverse Events (% Occurrence) in U.S. Placebo-Controlled Hypertension Trials with Immediate-Release Carvedilol (Incidence ≥1% in Subjects Treated with Carvedilol, Regardless of Causality)a
Adverse Event
Carvedilol
(n = 1,142)
Placebo
(n = 462)
Cardiovascular
Bradycardia
2
Postural hypotension
2
—
Peripheral edema
1
—
Central Nervous System
Dizziness
6
5
Insomnia
2
1
Gastrointestinal
Diarrhea
2
