XICARD Tablet

Essential Hypertension: It can be used alone or in combination with other antihypertensive agents (e.g. calcium channel blockers, diuretics).

Angina Pectoris: chronic stable angina and unstable angina.

Chronic Heart Failure: Stable, mild, moderate and severe chronic heart failure of ischaemic or cardiomyopathic origin as an adjunct to standard therapy (diuretics, ACE inhibitors and digitalis) to increase the survival and to reduce the risk of hospitalization. It may be used in patients who are not receiving digitalis, hydralazine or nitrate therapy.

Dosage and Administration

Treatment with Xicard is a long-term therapy. Treatment should not be stopped abruptly but rather gradually reduced at weekly intervals. This is particularly important i the case of patients with concomitant coronary heart disease.

Dosage must be individualized in the following diseases:

Essential Hypertension: 12.5mg once daily or 6.25mg twice daily increased after 2 days to 25mg once daily or 12.5mg twice daily.

Alternatively, an initial dose of 6.25mg is given twice daily, increased after 1-2 weeks to 25mg once daily or 12.5mg twice daily. The dose may be increased further, if necessary, at intervals of at least 2 weeks to 50mg once daily or 25mg twice daily.

XICARD should be taken with food to slow the rate of absorption and reduce the incidence of orthostatic effects. Addition of diuretic can be expected to produce additive effects and exaggerate the orthostatic component of XICARD.

Elderly patients: A dose of 12.5mg once daily or 6.25mg twice daily may be adequate.

Angina Pectoris

For initiation of therapy is 12.5mg twice daily for the first 2 days. Thereafter the recommended dose is 25mg twice daily. If necessary, the dose may subsequently be increased at intervals of at least 2 weeks up to the recommended maximum daily dose of 50mg twice daily.

Alternatively, an initial dose of 6.25m twice daily and increased after 3-10 days, based on tolerability to 12.5mg twice daily, then again to the target dose of 25mg twice daily.

Chronic Heart Failure

Dosage must be closely monitored by a physician during up titration. The recommended dose for initiation of therapy is 3.125mg twice daily for 2 weeks. If tolerated the dose should be increased, at intervals of not less than 2 weeks, to 6.25mg, 12.5mg and 25mg twice daily. The dose should not exceed 25mg twice daily in patient weighing less than 85kg or 50mg twice daily in patients weighing more than 85kg.

If XICARD treatment is discontinued for more than 1 week, therapy should be recommended at a lower dose level (twice daily) and up titrated in line with the above dosing recommendation.

If XICARD treatment is discontinued for more than 2 weeks, therapy should be recommended at 3.125mg in line with the above dosing recommendations.

XICARD should be taken with food to sow the rate of absorption.

In patients having:

- Hypersensitivity to carvedilol or any component of the product.

- Stable/decompensated heart failure, severe bradycardia, severe hypotension cardiogenic shock.

- 2nd & 3rd degree AV block.

- Sick sinus syndrome

- History of Chronic Obstructive Pulmonary Disease (COPD) that constrict the respiratory tract (such as bronchial asthma, chronic bronchitis, pulmonary emphysema), allergic rhinitis, swelling of laryngeal mucosa.

- Clinically manifest liver dysfunction.

Dizziness, headache, fatigue and the most frequently reported adverse effects. These symptoms are usually mild and occur particularly at the beginning of the treatment.

Adverse effects in chronic heart failure

Common: Postural hypotension, hypotension, bradycardia, oedema, nausea, diarrhea, vomiting, weight increase, hypercholesterolemia, hyperglycemia, hypoglycemia, worsening control of blood glucose in patients with pre-existing diabetes mellitus, vision abnormalities.

Uncommon: Syncope (including presyncope), AV block and cardiac failure during up-titration.

Rare: Thrombocytopenia, acute renal failure and renal function. Isolated cases of leucopenia have been reported.

The frequency of adverse reactions is not dose dependent, with the exception of dizziness, abnormal vision and bradycardia.

Adverse effects in Hypertension and Angina Pectoris

Common: Bradycardia, postural hypotension (especially at the beginning of treatment), asthma, dyspnea in predisposed patients, gastrointestinal upset (nausea, abdominal pain, diarrhea), pain in extremities, reduced lacrimation.

Uncommon: Depressed mood, sleep disturbances, paresthesia, asthenia, syncope, hypotension, disturbances of peripheral circulation, AV block, angina pectoris, symptoms of heart failure, peripheral oedema, constipation, vomiting, cases of sexual impotence, disturbed vision, skin reactions. Psoriatic skin lesions may occur or existing lesions exacerbated.

Rare: Stuffy nose, wheezing and flu-like symptoms, dryness of mouth and disturbances of micturition and eye irritation.

Isolated cases of increase in serum transaminases, thrombocytopenia, leucopoenia and allergic reaction have been reported.

Due to the beta-blocking properties it is also possible for latent diabetic mellitus to become manifest, manifest diabetes to the aggravated, and blood glucose counter-regulation to be inhibited.

See the package insert about the derails below:

- Catecholamine-depleting agents

- Clonidine

- Cyclosporine

- Digoxin

- Calcium channel blockers

- Insulin or oral hypoglycemics

- Inducers and inhibitors of hepatic metabolism (e.g. rifampicin, cimetidine)

- Anesthetic agents (e.g. ether, cyclopropane, and trichloroethylene)

- Inhibitors of CYP2D6 (e.g. quinidine, fluoxetine, paroxetine, propafenone)

- α1-receptor antagonists

Pregnancy

There are no adequate or well-controlled studies in pregnant women. Carvedilol should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

Lactation

It is not known whether carvedilol is excreted in human milk. Because many drugs are excreted in human milk and because of the potential for serious adverse reactions in nursing infants from carvedilol, a decision should be made whether, to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother.

- Patients with coronary artery disease, who are being treated with carvedilol. Should be advised against abrupt discontinuation of therapy. As with other beta-blockers, when discontinuation of carvedilol is planned, the patients should be carefully observed and advised to limit physical activity to a minimum. If the angina worsens or acute coronary insufficiency develops, it is recommended that carvedilol be promptly reinstituted, at least temporarily Because coronary artery disease is common and may be unrecognized, it may be prudent not to discontinue carvedilol therapy abruptly even in patients treated only for hypertension or heart failure.

- Beta-blockers can precipitate or aggravate symptoms of arterial insufficiency in patients with peripheral vascular disease. Caution should be exercised in such individuals.

- Rarely, use of carvedilol in patients with congestive heart failure has resulted in deterioration of renal function. In patients with low blood pressure (systolic blood pressure <100mmHg), ischemic heart disease and diffuse vascular disease, and/or underlying renal insufficiency, it is recommended that renal function be monitored during up-titration of carvedilol and the drug discontinued or dosage reduced if worsening of renal function occurs.

- Vasodilatory symptoms often do not require treatment, but it may be useful to separate the time of dosing of carvedilol from that of the ACE inhibitor or to reduce temporarily the dose of the ACE inhibitor. The dose of carvedilol should not be increased until symptoms of worsening heart failure or vasodilation have been stabilized. Fluid retention (with or without transient worsening heart failure symptoms) should be treated by an increase dose of diuretics. The dose of carvedilol should be reduced if patients experience bradycardia (heart rate <55 beats/minute).

- Worsening heart failure of fluid retention may occur during up-titration of carvedilol. If such symptoms occur, diuretics should be increased and the carvedilol dose should not be advanced until clinical stability resumes. Occasionally it is necessary to lower the carvedilol dose or temporarily discontinue it.

- Caution should be taken in the administration of carvedilol to patients suspected of having pheochromocytoma.

- Caution should be taken in the administration of carvedilol to patients suspected of having Prinzmetal’s variant angina.

- Patients with bronchospastic disease should, in general, not receive beta-blockers. Carvedilol may be used with caution, however, in patients who do not respond to, or cannot tolerate, other antihypertensive agents.

- During treatment with carvedilol the eyes must be examined regularly at 6-month intervals.

- Care should be taken in administering carvedilol to patients with a history of serious hypersensitivity reactions and in those undergoing desensitization therapy as beta-blockers may increase both the sensitivity towards allergens and the seriousness of anaphylactic reactions.

- Patients with a history of psoriasis associated with beta-blocker therapy should be given carvedilol only after consideration of the risk-benefit ratio.

Carvedilol is a vasodilating non-selective beta-blocking agent with antioxidant properties. Vasodilation is predominantly mediated through α1 receptor antagonism.

Carvedilol reduces the peripheral vascular resistance through vasodilation and suppresses the renin-angiotensin-aldosterone system through beta-blockade. Carvedilol is a racemate of two stereoisomers. Beta-blockade is attributed to the S(-)enantiomer; in contrast, both enantiomers exhibit the same α1-blocking activity.

Carvedilol is a potent antioxidant, a scavenger of reactive oxygen radicals ad an anti-proliferative agent.