CARIVALAN Film-coated tablet Ref.[51657] Active ingredients: Carvedilol Carvedilol and Ivabradine Ivabradine

Posology

The recommended dose of Carivalan is one tablet twice daily, once in the morning and once in the evening.

Carivalan should only be used in patients controlled on stable doses of the individual components given concurrently when carvedilol and ivabradine are at the optimal dose.

The fixed dose combination is not suitable for initiation therapy.

If a change of posology is required, titration should be done with the individual components carvedilol and ivabradine, ensuring the patient is maintained at an optimal dose of carvedilol and ivabradine. It is recommended that the decision to titrate treatment takes place with the availability of serial heart rate measurements, ECG or ambulatory 24-hour monitoring.

If during treatment, heart rate decreases below 50 beats per minute at rest or the patient experiences symptoms related to bradycardia such as dizziness, fatigue or hypotension, down titration should be done with the individual components carvedilol and ivabradine, ensuring the patient is maintained at an optimal dose of carvedilol and ivabradine. After dose reduction, heart rate should be monitored (see section 4.4). Treatment must be discontinued if heart rate remains below 50 bpm or symptoms of bradycardia persist despite dose reduction.

Renal impairment

No dosage adjustment is required in patients with renal insufficiency and creatinine clearance above 15 mL/min (see section 5.2) and SBP >100 mmHg.

No data are available in patients with creatinine clearance below 15 mL/min. Carivalan should be used with precaution in patients with creatinine clearance below 15 mL/min.

Monitoring of renal function is recommended in chronic heart failure patients with SBP <100 mmHg.

Hepatic impairment

It may be necessary to adjust the dose in patients with mild to moderate hepatic impairment.

Caution should be exercised in patients with moderate hepatic impairment (see sections 4.4 and 5.2).

Carivalan is contraindicated in patients with severe hepatic impairment (see sections 4.3 and 5.2).

Elderly

Carivalan can be administered in elderly patients with caution (see section 5.2).

Paediatric population

The safety and efficacy of Carivalan in children and adolescents have not been established. No data are available with Carivalan.

Method of administration

Oral use.

Carivalan tablet should be taken twice daily during a meal (see section 5.2).

There is no information on overdose with Carivalan in humans.

Symptoms

Linked to carvedilol

In case of an overdose, severe hypotension, bradycardia, heart failure, cardiogenic shock and cardiac arrest may occur. Respiratory distress, bronchospasm, vomiting, altered consciousness and generalised seizures may also occur.

Linked to ivabradine

Overdose may lead to severe and prolonged bradycardia (see section 4.8).

Management

In addition to general procedures, vital signs must be monitored and corrected, if necessary under intensive care conditions. Within 4 hours after ingestion, the absorption of carvedilol in the gastrointestinal tract can be reduced through gastric lavage, activated charcoal and induced vomiting.

Patients should be placed in the supine position. Atropine, 0.5 mg to 2 mg intravenous (i.v.) and/or glucagon 1 to 10 mg i.v. (followed by a slow i.v. infusion of 2 to 5 mg/hour if necessary) may be given when severe bradycardia is present, which should be treated symptomatically in a specialised environment. To support ventricular function intravenous administration of glucagon, or sympathomimetics (e.g. dobutamine, isoprenaline, orciprenaline, adrenaline and in accordance to body weight and effect) are recommended. In the event of bradycardia with poor haemodynamic tolerance, symptomatic treatment including intravenous beta-stimulating medicinal products such as isoprenaline may be considered temporary cardiac electrical pacing may be instituted if required. Extensive hypotension may be treated with administration of intravenous fluids. If positive inotropic effect is required, phosphodieseterase inhibitors, e.g. milrinone, should be considered. In the case of drug-resistant bradycardia, the initiation of pacemaker therapy may be required. If peripheral vasodilation dominates in the intoxication profile then norfenefrine or noradrenaline should be administered, with continuous monitoring of the circulation, either 5 to 10 micrograms i.v., repeated according to arterial blood pressure response, or 5 micrograms per minute by infusion titrated to arterial blood pressure.

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.

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

Carvedilol is not eliminated by dialysis, since the active substance cannot be dialysed, presumably due to its high degree of plasma protein binding.

24 months.

Store below 30°C.

PVC/PVDC/aluminum blister packed in cardboard cartons: Calendar packs containing 14 or 56 film-coated tablets.

Not all pack sizes may be marketed.

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