CARVEDILOL Film-coated tablet Ref.[6555] Active ingredients: Carvedilol

Oral use.

Essential Hypertension

Carvedilol may be used for the treatment of hypertension alone or in combination with other antihypertensives, especially thiazide diuretics. Once daily dosing is recommended, however the recommended maximum single dose is 25 mg and the recommended maximum daily dose is 50 mg.

Adults

The recommended initial dose is 12.5 mg once a day for the first two days. Thereafter, the treatment is continued at the dose 25 mg/day. If necessary, the dose may be further increased gradually at intervals of two weeks or more rarely.

Elderly

The recommended initial dose in hypertension is 12.5 mg once a day which may also be sufficient for continued treatment.

However, if the therapeutic response is inadequate at this dose, the dose may be further increased gradually at intervals of two weeks or more rarely.

Chronic stable angina pectoris

A twice-daily regimen is recommended.

Adults

The recommended initial dosage is 12.5 mg twice a day for the first two days. Thereafter, the treatment is continued at the dose 25 mg twice a day. If necessary, the dose may be further increased gradually at intervals of two weeks or more rarely to the recommended maximum dose of 100 mg a day divided into two doses (twice daily).

Elderly

The recommended initial dose is 12.5 mg twice daily for two days. Thereafter, the treatment is continued at the dose 25 mg twice daily, which is the recommended maximum daily dose.

Heart Failure

Carvedilol is given in moderate to severe heart failure in addition to conventional basic therapy with diuretics, ACE inhibitors, digitalis, and/or vasodilators. The patient should be clinically stable (no change in NYHA-class, no hospitalisation due to heart failure) and the basic therapy must be stabilized for at least 4 weeks prior to treatment. Additionally the patient should have a reduced left ventricular ejection fraction and heart rate should be >50 bpm and systolic blood pressure >85 mm Hg (see section 4.3).

The initial dose is 3.125 mg twice a day for two weeks. If this dose is tolerated, the dose may be increased slowly with intervals of not less than two weeks up to 6.25 mg twice a day, then up to 12.5 mg twice a day and finally up to 25 mg twice a day. The dosage should be increased to the highest tolerable level.

The recommended maximum dosage is 25 mg twice a day for patients with a body weight of less than 85 kg, and 50 mg twice a day for patients with a body weight above 85 kg, provided that the heart failure is not severe. A dose increase to 50 mg twice daily should be performed carefully under close medical supervision of the patient.

Transient worsening of symptoms of heart failure may occur at the beginning of treatment or due to a dose increase, especially in patients with severe heart failure and/or under high dose diuretic treatment. This does usually not call for discontinuation of treatment, but dose should not be increased. The patient should be monitored by a physician/cardiologist for two hours after starting treatment or increasing the dose. Before each dose increase, an examination should be performed for potential symptoms of worsening heart failure or for symptoms of excessive vasodilatation (e.g. renal function, body weight, blood pressure, heart rate and rhythm). Worsening of heart failure or fluid retention is treated by increasing the dose of diuretic, and the dose of carvedilol should not be increased until the patient is stabilized. If bradycardia appears or in case of lengthening of AV conduction, the level of digoxin should first be monitored. Occasionally it may be necessary to reduce the carvedilol dose or temporarily discontinue treatment altogether. Even in these cases, carvedilol dose titration can often be successfully continued.

Renal function, thrombocytes and glucose (in case of NIDDM and/or IDDM) should be monitored regularly during dose titration. However, after dose titration the frequency of monitoring can be reduced.

If carvedilol has been withdrawn for more than two weeks, the therapy should be reinitiated with 3.125 mg twice a day and increased gradually according to the above recommendations.

Renal insufficiency

Dosage must be determined for each patient individually, but according to pharmacokinetic parameters there is no evidence that dose adjustment of carvedilol in patients with renal impairment is necessary.

Moderate hepatic dysfunction

Dose adjustment may be required.

Paediatric population (<18 years)

Carvedilol is not recommended for the use in children below 18 years of age due to insufficient data on the efficacy and safety of carvedilol.

Elderly

Elderly patients may be more susceptible to the effects of carvedilol and should be monitored more carefully.

As with other beta-blockers and especially in patients with coronary disease, the withdrawal of carvedilol should be done gradually (see section 4.4).

Methods of administration

The tablets should be taken with the adequate supply of fluid. It is recommended that heart failure patients take their carvedilol medication with food to allow the absorption to be slower and the risk of orthostatic hypotension to be reduced.

Symptoms and signs

In the event of overdose, there may be severe hypotension, bradycardia, heart failure, cardiogenic shock and cardiac arrest. There may also be respiratory problems, bronchospasm, vomiting, disturbed consciousness and generalized seizures.

Treatment

In addition to general supportive treatment, the vital parameters must be monitored and corrected, if necessary, under intensive care conditions.

Atropine can be used for excessive bradycardia, while to support ventricular function intravenous glucagon, or sympathomimetics (dobutamine, isoprenaline) are recommended. If positive inotropic effect is required, phosphodiesterase inhibitors (PDE) should be considered. If peripheral vasodilation dominates the intoxication profile then norfenephrine or noradrenaline should be administered with continuous monitoring of the circulation. In the case of drug-resistant bradycardia, pacemaker therapy should be initiated.

For bronchospasm, β-sympathomimetics (as aerosol or intravenous) should be given, or aminophylline may be administered intravenously by slow injection or infusion. In the event of seizures, slow intravenous injection of diazepam or clonazepam is recommended.

Carvedilol is highly protein-bound. Therefore, it cannot be eliminated by dialysis.

In cases of severe overdose with symptoms of shock, supportive treatment must be continued for a sufficiently long period, i.e. until the patient’s condition has stabilised, as a prolongation of elimination half-life and redistribution of carvedilol from deeper compartments are to be expected.

3 years.

Do not store above 30°C.

PVC / PE / PVDC – Aluminum:

Package sizes: 5, 7, 10, 14, 15, 20, 28, 30, 40, 50, 56, 60, 90, 98, 100, 120, 150, 200, 250, 300, 400, 500 and 1000 filmcoated tablets.

Bottle of high density polyethylene (HDPE) with a white cap, opaque polypropylene:

Package sizes: 30, 50, 60, 100, 250, 500 and 1000 film-coated tablets.

Not all pack sizes may be marketed.

Any unused medicinal product or waste material should be disposed of in accordance with local requirements.