DILATREND Tablet Ref.[51031] Active ingredients: Carvedilol

Method of Administration

The tablets are to be swallowed with sufficient fluid.

Duration of Treatment

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

Essential hypertension

Adults

The recommended dose for initiation of therapy is 12,5 mg once a day for the first two days. Thereafter the recommended dosage is 25 mg once a day. Combination with a diuretic may also give the desired response.

Elderly

The recommended dose for initiation of therapy is 12,5 mg once daily, which has provided satisfactory control in some patients. If the response is inadequate, the dose may be titrated at intervals of at least two weeks up to the recommended daily dose of 25 mg once a day or in divided doses.

In hypertensive patients it is not necessary to time the dose in relation to meals.

At doses higher than 25 mg the incidence of side effects increases significantly with only a marginal increase in efficacy.

Treatment of symptomatic congestive heart failure

DILATREND should be taken with food to slow the rate of absorption and reduce the incidence of orthostatic effects. Dosage must be individualised and closely monitored by a medical practitioner experienced in the management of heart failure, during up-titration. For those patients receiving digoxin, diuretics and ACE-inhibitors, dosing of these medicines should be stabilised prior to initiation of DILATREND treatment.

The recommended dose for initiation of therapy is 3,125 mg twice daily for at least 2 weeks. If this dose is tolerated, the dosage may subsequently be increased, at intervals of not less than two weeks, to 6,25 mg twice daily, followed by 12,5 mg twice daily and thereafter 25 mg twice daily. Dosing should be increased to the highest level tolerated by the patient. The maximum recommended dose is 25 mg twice daily in patients weighing less than 85 kg and 50 mg twice daily in patients weighing more than 85 kg.

Before each dose increase, the patient should be evaluated by the medical practitioner for symptoms of worsening heart failure or vasodilation. Transient worsening of heart failure or fluid retention should be treated with increased doses of diuretics, although occasionally it may be necessary to lower the dose of DILATREND or temporarily discontinue DILATREND treatment.

If DILATREND treatment is discontinued for more than two weeks, therapy should be recommenced at 3,125 mg twice daily and up-titrated in line with the above dosing recommendation. Symptoms of vasodilation such as postural hypotension, headache and dizziness may be managed initially by a reduction in the dose of diuretics. If symptoms persist, the dose of ACE inhibitor (if used) may be reduced, followed by a reduction in the dose of DILATREND if necessary. Under these circumstances, the dose of DILATREND should not be increased until symptoms of worsening heart failure or vasodilation have been stabilised.

Left ventricular dysfunction following otherwise uncomplicated acute myocardial infarction

Dosage must be individualised and closely monitored by a medical practitioner during up-titration. Treatment may be started as an inpatient or outpatient when the patient is haemodynamically stable and fluid retention has been minimised.

Prior to initiating DILATREND: Haemodynamically stable patients should have received an ACE inhibitor for at least 48 hours, given at a stable dose during at least the preceding 24 hours. DILATREND can then be started between day 3 and day 21 after the myocardial infarction.

First dose of DILATREND: The initial recommended dose is 6,25 mg. Patients should remain under close medical supervision for at least 3 hours following the initial dose. See WARNINGS AND SPECIAL PRECAUTIONS.

Subsequent doses of DILATREND: If the patient has tolerated the first dose (i.e. heart rate >50 beats/minute, systolic blood pressure >80 mmHg, measured with the patient seated, and absence of clinical signs of intolerance), the dose should be increased to 6,25 mg twice daily and maintained for 3 to 10 days.

The dose should be reduced to 3,125 mg twice daily if the patient develops signs of intolerance during this period, in particular bradycardia <50 beats/minute, systolic blood pressure <80 mmHg, measured with the patient seated, or fluid retention. If this dose is not tolerated, treatment should be stopped.

If it is well tolerated, it should be increased again to 6,25 mg twice daily after 3 to 10 days.

Subsequent up-titration: if the dose of 6,25 mg twice daily is well tolerated, the dose should be increased at intervals of 3 to 10 days to 12,5 mg twice daily and then to 25 mg twice daily. The maintenance dose is the maximum dose tolerated by the patient. The maximum recommended dose is 25 mg twice daily, irrespective of the patient’s weight.

Special Dosage Instructions

Renal impairment

Available pharmacokinetic data in patients with varying degrees of renal impairment (including renal failure) suggest no changes in DILATREND dosing recommendations are warranted in patients with moderate to severe renal insufficiency.

Hepatic impairment

DILATREND is contraindicated in patients with clinical manifestations of liver dysfunction. See CONTRAINDICATIONS. A pharmacokinetic study in cirrhotic patients has shown that exposure (AUC) to DILATREND was increased by 6,8-fold in patients with liver impairment as compared to healthy subjects.

Diabetic Patients

DILATREND may increase insulin resistance and mask hypoglycaemic symptoms and decrease the body’s response to hypoglycaemia.

Elderly

There is no evidence to support dose adjustment.

Children

The safety and efficacy of DILATREND in children and adolescents (<18 years) has not been established. See PHARMACOKINETICS, Special populations.

Symptoms

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

Treatment

Patients should be monitored for the above mentioned signs and symptoms and managed according to the best judgment of the treating medical practitioners and according to standard practice for patients with βblocker overdose (e.g. atropine, transvenous pacing, glucagon, phosphodiesterase inhibitor such as amiodarone or milrinone, β-sympathomimetics).

Important Note: In the event of severe intoxication where there are symptoms of shock, treatment with antidotes must be continued for a sufficiently long period of time since a prolonged elimination half-life of DILATREND from deeper compartments can be expected. The duration of the supportive therapy depends on the severity of the overdose. The supportive treatment should therefore be continued until the patient’s condition has stabilised.

Store at or below 30°C in the original package to protect from light. Store out of reach of children.

DILATREND 6,25 mg tablets: available in blisters containing 10, 30 or 100 tablets.

DILATREND 12,5 mg tablets: available in blisters containing 30 or 100 tablets.

DILATREND (25 mg) Tablet: available in blisters containing 30 or 100 tablets.