, treatment with antidotes must be continued for a sufficiently long period of time consistent with the 7- to 10-hour half-life of carvedilol.
There is no experience of overdosage with COREG CR. Cases of overdosage with carvedilol alone or in combination with other drugs have been reported. Quantities ingested in some cases exceeded 1,000 milligrams. Symptoms experienced included low blood pressure and heart rate. Standard supportive treatment was provided and individuals recovered.
11 DESCRIPTION
Carvedilol phosphate is a nonselective β‑adrenergic blocking agent with α1-blocking activity. It is (2RS)-1-(9H-Carbazol-4-yloxy)-3-[[2-(2-methoxyphenoxy)ethyl]amino]propan-2-ol phosphate salt (1:1) hemihydrate. It is a racemic mixture with the following structure:
carvedilol phosphate chemical structure
Carvedilol phosphate is a white-to-almost white solid with a molecular weight of 513.5 (406.5 carvedilol free base) and a molecular formula of C24H26N2O4•H3PO4•1/2 H2O.
COREG CR is available for once-a-day administration as controlled-release oral capsules containing 10, 20, 40, or 80 mg carvedilol phosphate. COREG CR hard gelatin capsules are filled with carvedilol phosphate immediate-release and controlled-release microparticles that are drug-layered and then coated with methacrylic acid copolymers. Inactive ingredients include crospovidone, hydrogenated castor oil, hydrogenated vegetable oil, magnesium stearate, methacrylic acid copolymers, microcrystalline cellulose, and povidone.
12 CLINICAL PHARMACOLOGY
12.1 Mechanism of Action
Carvedilol is a racemic mixture in which nonselective β‑adrenoreceptor blocking activity is present in the S(-) enantiomer and α1‑adrenergic blocking activity is present in both R(+) and S(-) enantiomers at equal potency. Carvedilol has no intrinsic sympathomimetic activity.
12.2 Pharmacodynamics
Heart Failure and Left Ventricular Dysfunction following Myocardial Infarction
The basis for the beneficial effects of carvedilol in patients with heart failure and in patients with left ventricular dysfunction following an acute myocardial infarction is not known. The concentration-response relationship for β1‑blockade following administration of COREG CR is equivalent (±20%) to immediate-release carvedilol tablets.
Hypertension
The mechanism by which β‑blockade produces an antihypertensive effect has not been established.
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.
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. These effects contribute to the reduction of blood pressure and usually are seen within 30 minutes of drug administration.
Due to the α1‑receptor blocking activity of carvedilol, blood pressure is lowered more in the standing than in the supine position, and symp |
