Carvedilol

Exepress

Carvedilol

Description

Carvedilol (Exepress?) is a cardiovascular drug whose main pharmacological action is non-selective antagonism of ?-adrenergic receptors but it also possesses appreciable a1-adrenergic activity. It also has antiproliferative properties and is a scavenger of reactive free oxidant radicals.

Mode of action

Carvedilol (Exepress?) is a vasodilating non-selective beta-blocking agent with antioxidant properties. Vasodilation is predominantly mediated through a1 receptor antagonism. Carvedilol reduces the peripheral vascular resistance through vasodilation and suppresses the renin angiotensin-aldosterone system through ?-blockade. The activity of plasma renin is reduced and fluid retention is rare. Carvedilol has no intrinsic sympathomimetic activity and like propranolol, it has membrane stabilizing properties. Carvedilol is a potent antioxidant, a scavenger of reactive oxygen radicals and an anti-proliferative agent. The properties of carvedilol and its metabolites have been demonstrated in-vitro and in-vivo animal studies and in-vitro in a number of human cell types.

Pharmacokinetics

The absolute bioavailability of carvedilol is approximately 25% in humans. Bioavailability is stereoselective, 30% for the R-form and 15% for the S-form. Serum levels peak at approximately 1 hour after an oral dose. There is a linear relationship between the dose and serum concentrations. Food does not affect bioavailability or the maximum serum concentration although the time to reach maximum serum concentration is delayed. Carvedilol is highly lipophilic; approximately 98% to 99% is bound to plasma proteins.

Composition

Exepress? 6.25 mg tablet: Each tablet contains Carvedilol BP 6.25 mg.

Exepress? 12.5 mg tablet: Each tablet contains Carvedilol BP 12.5 mg.

Indications

Hypertension, angina, adjunct to diuretics, digoxin or ACE inhibitors in symptomatic chronic heart failure.

Dosage and administration

Hypertension, initially 12.5 mg once daily, increased after 2 days to usual dose of 25 mg once daily; if necessary may be further increased at intervals of at least 2 weeks to maximum 50 mg daily in single dose or divided doses; Elderly, initial dose of 12.5 mg daily may provide satisfactory control. Angina, initially 12.5 mg twice daily, increased after 2 days to 25 mg twice daily. Adjunct to heart failure, initially 3.125 mg twice daily (with food), dose increased at interval of at least 2 weeks to 12.5 mg twice daily, then to 25 mg twice daily; increase to highest dose tolerated, max. 25 mg twice daily in patients with severe heart failure or body weight less than 85 kg and 50 mg twice daily in patients over 85 kg.

Contraindications

Carvedilol is contraindicated in patients with marked fluid retention or overload requiring intravenous ionotropic support. Patients with obstructive airways disease, liver dysfunction, history of bronchospasm or asthma, 2nd and 3rd degree A-V heart block, (unless a permanent pacemaker is in place), severe bradycardia (< 50 bpm), cardiogenic shock, sick sinus syndrome (including sino-atrial block), severe hypotension (systolic blood pressure < 85 mm Hg), metabolic acidosis and phaeochromocytoma (unless adequately controlled by a-blockade).

Side effects

Postural hypotension, dizziness, headache, fatigue, gastro-intestinal disturbances, bradycardia, occasionally diminished peripheral circulation, peripheral oedema and painful extremities, dry mouth, dry eyes, eye irritation or disturbed vision, impotence, disturbances of micturition, influenza like symptoms, rarely angina, AV block, exacerbation of intermittent claudication or Raynaud?s phenomenon, allergic skin reactions, exacerbation of psoriasis , nasal stuffiness, wheezing, depressed mood, sleep disturbances, paraesthesia, heart failure, changes in liver enzymes, thrombocytopenia, leucopenia also reported.

Use in pregnancy and lactation

Carvedilol should not be used during pregnancy as no studies have been performed in this group. Carvedilol should not be used in breast feeding.

Precautions

In chronic heart failure patients, worsening cardiac failure or fluid retention may occur during uptitration of carvedilol. In hypertensive patients who have chronic heart failure controlled with digoxin, diuretics and/or an ACE inhibitor, Carvedilol should be used with caution since both digoxin and carvedilol may slow A-V conduction. As with other drugs with beta-blocking activity, carvedilol may mask the early signs of acute hypoglycemia in patients with diabetes mellitus. Reversible deterioration of renal function has been observed with carvedilol therapy in chronic heart failure patients with low blood pressure (systolic BP < 100 mm Hg), ischaemic heart disease and diffuse vascular disease, and/or underlying renal insufficiency. In patients with a tendency to bronchospastic reactions, respiratory distress can occur as a result of a possible increase in airway resistance.

Drug Interactions

As with other agents with ?-blocking activity, carvedilol may potentiate the effect of other concomitantly administered drugs that are antihypertensive in action (eg. a1-receptor antagonists) or have hypotension as part of their adverse effect profile. Patients taking an agent with a-blocking properties and a drug that can deplete catecholamines (eg. reserpine and monoamine oxidase inhibitors) should be observed closely for signs of hypotension and/or severe bradycardia. Isolated cases of conduction disturbance (rarely with haemodynamic disruption) have been observed when carvedilol and diltiazem were given concomitantly. Therefore, as with other drugs with ?-blocking activity, careful monitoring of ECG and blood pressure should be undertaken when co-administering calcium channel blockers of the verapamil or diltiazem type, or class I antiarrhythmic drugs. These types of drugs should not be co-administered intravenously in patients receiving carvedilol.

Overdosage

Profound cardiovascular effects such as hypotension and bradycardia would be expected after massive overdose. Heart failure, cardiogenic shock and cardiac arrest may follow. There may also be respiratory problems, bronchospasm, vomiting, disturbed consciousness and generalized seizures.

Storage

Keep out of reach of children. Store in a cool and dry place, protected from light.

Packaging

Exepress? 6.25 mg tablet: Each  carton contains 10X5 tablets in blister pack.

Exepress? 12.5 mg tablet: Each carton contains 10X3 tablets in blister pack.