Each tablet contains: Carvedilol 6.25, 12.5 mg and 25 mg.
Pharmacology: Pharmacodynamics: Carvedilol is a potent antihypertensive agent with a dual mechanism of action. It possesses both B-adrenergic receptor blocking activity and alpha-adrenergic antagonistic activity. Carvedilol is non-selective beta adrenoreceptor antagonist at clinically relevant doses. Alpha-blocking activity of carvedilol is thought to be the predominant mechanism of validation. However, there is no reflex tachycardia because of associated-blockade. At higher concentration it also exerts calcium channel antagonist property. The calcium channel blocking activity of carvedilol is responsible for increasing the blood flow in some regional vascular beds.
Pharmacokinetics: Carvedilol is well absorbed from the gastrointestinal tract but is subject to considerable first-pass metabolism in the liver; the absolute bioavailability is about 25%. Peak plasma concentration occur 1 to 2hours after an oral dose. It has lipid solubility. Carvedilol is more than 98% bound to plasma proteins. It is extensively metabolized in the liver, primarily by the cytochrome P450 isoenzymes CYP2D6 and CYP2C9, and the metabolites are excreted mainly in the bile. The elimination half-life is about 6 to 10 hours. Carvedilol has been shown to accumulate in breast milk in animals.
Used in the management of essential hypertension and angina pectoris, and as an adjunct to standard therapy in symptomatic heart failure.
Hypertension: The recommended starting dose of Carvedilol is 6.25 mg twice. If this dose is tolerated, the dose should be maintained for 7 to 14 days, and then increased to 12.5 mg twice daily. The dose may be increased further, if necessary, at intervals of at least two weeks, to 50 mg once daily or in divided doses, or as prescribed by the physician. A dose of 12.5 mg once daily may be adequate for elderly patients.
Heart Failure: The initial dose is 3.125 mg twice daily by mouth. If tolerated, the dose should be doubled after two weeks to 6.25 mg twice daily and then increased gradually, at intervals not less than two weeks, to the maximum dose tolerated, this should not exceed 25 mg twice daily in patients with severe heart failure or in those weighing less than 85 kg (187 lbs) or 50 mg twice daily in patients with mild to moderate heart failure weighing more than 85 kg, or as prescribed by the physician. It should be taken with food to reduce the risk of hypotension.
Angina Pectoris: Initial dose of 12.5 mg twice daily by mouth, increased after two days to 25 mg twice daily or as prescribed by the physician.
Left Ventricular Dysfunction following Myocardial Infarction: The initial dose is 6.25 mg twice daily, increased after 3 to 10 days, if tolerated, to 12.5 mg twice daily and then to a target dose of 25 mg twice daily. A lower initial dose may be used in symptomatic patients. Or as prescribed by the physician.
It should not be given to patients with bronchospasm or asthma or those with a history of obstructive airways disease. Other contraindications include metabolic acidosis, cardiogenic shock, hypotension, severe peripheral arterial disease, sinus bradycardia and second or third degree atrioventricular block.
Carvedilol is widely metabolized in the liver and is not recommended in patients with hepatic impairment. Acute renal failure and renal abnormalities have been reported in patients with heart failure who also suffered from diffuse vascular disease and/or renal impairment. The risk of hypotension may be reduced by taking carvedilol with food to decrease the rate of absorption.
Carvedilol may mask the symptoms of hyperthyroidism and of hypoglycemia. They may unmask myasthenia gravis. Psoriasis may be aggravated. Chest pain has been reported in patients with Prinzmetal's angina. Patients with a history of anaphylaxis to an antigen may be more reactive to repeated challenge with an antigen while taking carvedilol.
Abrupt withdrawal of beta blockers has sometimes resulted in angina, myocardial infarction, ventricular arrhythmias, and death. Patients on long-term treatment with beta blocker should have their medication discontinued gradually over a period of 1 to 2 weeks.
Use of carvedilol in pregnancy before delivery has occasionally resulted in bradycardia and other adverse effects such as hypoglycemia and hypotension in neonates. Carvedilol are distributed into breast milk.
Carvedilol is generally well tolerated, partly because of the combined alpha and beta blocking properties of the molecule allow clinical efficacy to be attained with lower dosages than might be required if it were a single-action drug. The most frequently reported adverse events in patients being treated with carvedilol are related to its vasodilatory (postural hypotension, dizziness and headaches) and Beta-blocking (dyspnea, bronchospasm, bradycardia, malaise and asthenia) properties. Adverse events are generally more common early in therapy, are dosage-related and appear to have a lower incidence than is seen with pure Beta-blockade.
The adverse events reported frequently with carvedilol in clinical trials in patients with congestive heart failure were hyperuricemia, hypoglycemia, hyponatremia, increased alkaline phosphatase, glycosuria, somnolence, impotence, abnormal renal function, and albuminuria.
Anesthetics: Hypotensive effects of carvedilol may be potentiated by general anesthetics, and anesthetic that cause myocardial depression such as ether, cyclopropane, and trichloroethylene should preferably be avoided.
Antiarrhythmics: Use of carvedilol with antiarrhythmic drugs and other drugs affecting cardiac conduction can precipitate bradycardia and heart block. Quinidine and carvedilol have negative inotropic action on the heart; bradycardia and hypotension have occurred in patients given with carvedilol.
Antibacterials: Plasma concentration of Carvedilol may be reduced by rifampicin.
Antidepressants: Bradycardia and heart block, occurring shortly after starting fluoxetine therapy have been reported. Use of fluoxetine increased the plasma concentration of Carvedilol in patients with heart failure but no clinical effects were noted.
Antihypertensive: An enhanced antihypertensive effect is seen when other antihypertensives are given with betablockers. Carvedilol can potentiate the severe orthostatic hypotension that may follow the initial dose of alpha blockers prazosin and can exacerbate rebound hypertension following withdrawal of clonidine treatment.
Calcium Channel Blockers: Use of calcium channel blockers with beta blockers (Carvedilol) has resulted in hypotension, bradycardia, conduction defect, and heart failure.
Cardiac Glycosides: Carvedilol has been reported to increase plasma concentrations of digoxin.
Cyclosporin: Cyclosporin plasma concentrations increased when carvedilol was added to treatment regimen. It is recommended that cyclosporin concentrations should be monitored carefully if cyclosporin and carvedilol are used together.
Store at temperatures not exceeding 30°C.
C07AG02 - carvedilol ; Belongs to the class of alpha and beta blocking agents. Used in the treatment of cardiovascular diseases.
Karvil 6.25: Tab 6.25 mg (white to off-white, round, flat beveled edge uncoated tablets with breakline on one side and plain on other side) x 15's.
Karvil 12.5: Tab 12.5 mg (old rose mottled, round, flat beveled edge uncoated tablet with breakline on one side and plain on other side) x 15's.
Karvil 25: Tab 25 mg (white to off-white, round, flat, beveled-edge uncoated tablets with breakline on one side and plain on other side) x 30's.