Coreg: Uses, Taking, Side Effects, Warnings

If pulse rate drops below 55 beats per minute, the dosage should be reduced. Reversible elevations in serum transaminases (ALT or dexamethasone synthroid AST) have been observed during treatment with COREG. Rates of transaminase elevations (2 to 3 times the upper limit of normal) observed during controlled clinical trials have generally been similar between subjects treated with COREG and those treated with placebo. However, transaminase elevations, confirmed by rechallenge, have been observed with COREG. Severe exacerbation of angina, heart attack and ventricular arrhythmias has been reported in angina patients following the abrupt discontinuation of therapy with beta-blockers like Coreg. Effectiveness of COREG (carvedilol) in patients younger than 18 years of age has not been established.

Report Problems to the Food and Drug Administration

Compared with carvedilol, the 3 active metabolites exhibit weak vasodilating activity. Plasma concentrations of the active metabolites are about one-tenth of those observed for carvedilol and have pharmacokinetics similar to the parent. For therapyresistant bradycardia, pacemaker therapy should be performed. Overdosage may cause severe hypotension, bradycardia, cardiac insufficiency, cardiogenic shock, and cardiac arrest.

Before taking this medicine

Exercise tolerance was the primary end point in 3 trials; in none was a statistically significant effect found. Since carvedilol undergoes substantial oxidative metabolism, the metabolism and pharmacokinetics of carvedilol may be affected by induction or inhibition of cytochrome P450 enzymes. Plasma levels of carvedilol average about 50% higher in the elderly compared with young subjects. The primary P450 enzymes responsible for the metabolism of both R(+) and S(-)- carvedilol in human liver microsomes were CYP2D6 and CYP2C9 and to a lesser extent YP3A4, 2C19, 1A2, and 2E1.

• Of the 1,156 subjects randomized to COREG in a long‑term, placebo‑controlled trial in severe heart failure, 47% (547) were aged 65 years or older, and 15% (174) were aged 75 years or older.
• In addition, absorption of levothyroxine may be decreased and/or delayed by foods such as soybean flour, cotton seed meal, walnuts, dietary fiber, calcium, calcium fortified juices and grapefruit or grapefruit juice.
• High blood pressure makes the heart work harder to pump blood through the body and causes damage to blood vessels.
• Respiratory problems, bronchospasms, vomiting, lapses of consciousness, and generalized seizures may also occur.

Carvedilol was titrated from a starting dose of 3.125 mg twice daily to the maximum tolerated dose or up to 25 mg twice daily over a minimum of 6 weeks. The trial was conducted in Eastern and Western Europe, the United States, Israel, and Canada. Similar numbers of subjects per group (about 100) withdrew during the titration period. Although carvedilol is metabolized primarily by the liver, plasma concentrations of carvedilol have been reported to be increased in patients with renal impairment.

What Drugs, Substances, or Supplements Interact with Coreg?

COREG has been evaluated for safety in survivors of an acute myocardial infarction with left ventricular dysfunction in the CAPRICORN trial which involved 969 subjects who received COREG and 980 who received placebo. Approximately 75% of the subjects received COREG for at least 6 months and 53% received COREG for at least 12 months. Subjects were treated for an average of 12.9 months and 12.8 months with COREG and placebo, respectively. Α1-adrenoreceptor blocking activity has been demonstrated in human and animal studies, showing that carvedilol (1) attenuates the pressor effects of phenylephrine, (2) causes vasodilation, and (3) reduces peripheral vascular resistance.

In about 30% of subjects, 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 subjects. 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. This dose should also be maintained for 7 to 14 days and can then be adjusted upward to 25 mg twice daily if tolerated and needed. The full antihypertensive effect of COREG is seen within 7 to 14 days. COREG®, also known as carvedilol, is a prescription medicine known as a beta-blocker.

Medicines that lower blood pressure may lower your chance of having a stroke or heart attack. Treatment of the index infarction included aspirin (85%), IV or oral β‑blockers (37%), nitrates (73%), heparin (64%), thrombolytics (40%), and acute angioplasty (12%). In the Australia‑New Zealand trial, death and total hospitalizations were reduced by about 25% over 18 to 24 months. In the 3 largest U.S. trials, death and total hospitalizations were reduced by 19%, 39%, and 49%, nominally statistically significant in the last 2 trials.

Patients with coronary artery disease, who are being treated with COREG, 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 β-blockers. Coreg is available in strengths of 3.125, 6.25, 12.5, or 25 mg tablets. Coreg is usually taken with food; the recommended starting dose of Coreg (carvedilol) is 3.125 mg twice daily for 2 weeks for heart failure while for other problems, the starting dose is 6.25 mg twice a day.

Steady‑state plasma concentrations of carvedilol and its enantiomers increased proportionally over the 6.25- to 50- mg dose range in subjects with heart failure. Compared with healthy subjects, subjects with heart failure had increased mean AUC and Cmax values for carvedilol and its enantiomers, with up to 50% to 100% higher values observed in 6 subjects with NYHA class IV heart failure. The mean apparent terminal elimination half‑life for carvedilol was similar to that observed in healthy subjects.

CYP2D6 Inhibitors And Poor Metabolizers

The pharmacokinetics of carvedilol do not appear to be different in poor metabolizers of S-mephenytoin (patients deficient in cytochrome P450 2C19). Β-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. Significant β-adrenoreceptor blocking effect is usually seen within 1 hour of drug administration. Agents with non-selective β-blocking activity may provoke chest pain in patients with Prinzmetal’s variant angina. There has been no clinical experience with carvedilol in these patients although the α-blocking activity may prevent such symptoms. However, caution should be taken in the administration of carvedilol to patients suspected of having Prinzmetal’s variant angina.