PROPAFENONE HYDROCHLORIDE

It is recommended that propafenone therapy should be initiated under hospital conditions, by a physician experienced in the treatment of arrhythmias. The individual maintenance dose should be determined under cardiological surveillance including ECG monitoring and blood pressure control.

If the QRS interval is prolonged by more than 160msec or the PQ interval is prolonged by more than 20%, the dose should be reduced or discontinued until the ECG returns to normal limits. Adults Initially, 150 mg three times daily increasing at a minimum of three-day intervals to 300 mg twice daily and if necessary, to a maximum of 300 mg three times daily.

The tablets should be swallowed whole and taken with a drink after food. A reduction in the total daily dose is recommended for patients below 70 kg bodyweight. Elderly No overall differences in safety or effectiveness were observed in this patient population, but greater sensitivity of some older individuals cannot be ruled out, therefore, these patients should be carefully monitored.

Treatment should be initiated gradually and with particular caution in small incremental doses. The same applies to maintenance therapy. Any dose increases that may be required should not be undertaken until after five to eight days of therapy.

Children A suitable dosage form of propafenone hydrochloride tablets for children is not available. Hepatic/Renal Impairment In patients whose liver and/or kidney function is impaired, there may be drug accumulation after standard therapeutic doses.

Nonetheless, patients with these conditions can still be titrated on propafenone hydrochloride under ECG and plasma level monitoring.

a. Summary of the safety profile The most frequent and very common adverse reactions related to propafenone therapy are dizziness, cardiac conduction disorders and palpitations. b. Tabulated summary of adverse reactions The following table displays adverse reactions reported in clinical trials and from post-marketing experience with propafenone.

The reactions considered at least possibly related to propafenone are displayed by system organ class and frequency using the following convention: very common (≥1/10), common (≥ 1/100 to < 1/10), uncommon (≥1/1,000 to < 1/100) and not known (adverse reactions from post-marketing experience; cannot be estimated from the available data).

Within each frequency grouping, adverse reactions are presented in order of decreasing seriousness when the seriousness could be assessed. The frequencies are based on clinical trial data from propafenone SR. It is expected that the adverse reactions and frequencies for IR formulations would be similar.

System Organ Class Very common 1/10 Common 1/100 to < 1/10 Uncommon 1/1,000 to < 1/100 Not Known (cannot be estimated from the available data) Blood and lymphatic system disorders Thrombocytopen ia Agranulocytosis Leukopenia Granulocytopenia Immune system disorders Hypersensitivity1 Metabolism and nutrition disorders Decreased appetite Psychiatric disorders Anxiety Sleep disorders Nightmare Confusional state Nervous system disorders Dizziness2 Headache Dysgeusia Syncope Ataxia Paraesthesia Convulsion Extrapyramidal symptoms Restlessness Eye disorders Vision blurred Ear and labyrinth disorders Vertigo Cardiac disorders Cardiac conduction disorders3 Palpitations Sinus bradycardia Bradycardia Tachycardia Atrial flutter Ventricular tachycardia Arrythmia4 Ventricular fibrillation Cardiac failure5 Heart rate reduced Vascular disorders Hypotension Orthostatic hypotension Respiratory, thoracic and mediastinal disorders Dyspnoea Gastrointesti nal disorders Abdominal pain Vomiting Nausea Diarrhoea Constipation Abdominal distension Flatulence Retching Gastrointestinal disturbance Dry mouth Hepatobiliar y disorders Hepatic function abnormal6 Hepatocellular injury Cholestasis Hepatitis Jaundice Skin and subcutaneou s tissue disorders Urticaria Pruritus Rash Erythema Acute generalized exanthematous pustulosis Musculoskel etal and connective tissue disorders Lupus-like syndrome Reproductiv e system and breast disorders Erectile dysfunction Sperm count decreased7 General disorders and administrati on site conditions Chest pain Asthenia Fatigue Pyrexia 1 May be manifested by cholestasis, blood dyscrasias and rash 2 Excluding vertigo 3 Including sinoatrial block, atrioventricular block and intraventricular block 4 Propafenone may be associated with proarrhythmic effects which manifest as an increase in heart rate (tachycardia) or ventricular fibrillation.

Electrolyte disturbances should first be treated before treatment with propafenone. The weak negative inotropic effect of propafenone may assume importance in patients predisposed to cardiac failure. In common with other anti-arrhythmic drugs, propafenone has been shown to alter sensitivity and pacing threshold.

In patients with pacemakers, appropriate adjustments may be required. 8). Because of the beta-blocking effect, care should be exercised in the treatment of patients with obstructive airways disease or asthma. As with some other class IC anti-arrhythmic agents, patients with significant structural heart disease may be predisposed to serious adverse effects.

3). There is a risk of pro-arrhythmic effects, as with other anti-arrhythmics. Worsening of the ventricular arrhythmias is possible. A Brugada syndrome may be unmasked or Brugada like electrocardiogram (ECG) changes may be provoked after exposure to propafenone in previously asymptomatic carriers of the syndrome.

After initiating therapy with propafenone, an ECG should be performed to rule out changes suggestive of Brugada syndrome. For the treatment of ventricular arrhythmias, the patient should be under cardiological surveillance including ECG monitoring and blood pressure control and defribillator facilities should be available.

8). It is essential that each patient given propafenone hydrochloride be evaluated electrocardiographically and clinically prior to and during therapy to determine whether the response to propafenone hydrochloride supports continued treatment.

Excipients This medicine contains less than 1 mmol sodium (23 mg) per tablet, that is to say essentially 'sodium-free'.

g. hyperkalemia or other potassium metabolism disorders), severe obstructive pulmonary disease or severe hypotension. • Propafenone may worsen myasthenia gravis. • Patients with known Brugada Syndrome. 4, Special Warnings and Precautions for Use), propafenone should not be used in the presence of sinus node dysfunction, atrial conduction defects, second degree or greater AV block, bundle branch block or distal block in the absence of an artificial pacemaker.

Minor prolongation of the PR interval and intra-ventricular conduction defects (QRS duration of less than 20%) are to be expected during treatment with propafenone and do not warrant dose reduction or drug withdrawal. Due to the potential for increased plasma concentrations, co-administration of ritonavir and propafenone hydrochloride is contraindicated.