Source: Medicines & Healthcare Products Regulatory Agency (GB) Revision Year: 2021 Publisher: Mylan Products Ltd., 20 Station Close, Potters Bar, Herts, EN6 1TL, United Kingdom
Known hypersensitivity to the active ingredient, propafenone hydrochloride or to any of the excipients listed in the Full List of Excipients section.
Arythmol is contraindicated in patients with known Brugada Syndrome (see Special Warnings and Precautions for Use).
Arythmol is contraindicated in patients with significant structural heart disease such as patients with an incident of myocardial infarction within the last 3 months, uncontrolled congestive heart failure where left ventricular output is less than 35%, cardiogenic shock (unless arrhythmia-induced), severe symptomatic bradycardia, manifest electrolyte imbalance (e.g. potassium metabolism disorders), severe obstructive pulmonary disease or severe hypotension.
Arythmol may worsen myasthenia gravis.
Unless patients are adequately paced (see section 4.4, Special Warnings and Precautions for Use), Arythmol 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.
Due to the potential for increased plasma concentrations, co-administration of ritonavir is contraindicated.
The weak negative inotropic effect of Arythmol may assume importance in patients predisposed to cardiac failure.
In common with other anti-arrhythmic drugs, Arythmol has been shown to alter sensitivity and pacing threshold. In patients with pacemakers, appropriate adjustments may be required.
There is potential for conversion of paroxysmal atrial fibrillation to atrial flutter with accompanying 2:1 conduction block or 1:1 conduction (see section 4.8).
Because of the beta-blocking effect, care should be exercised in the treatment of patients with obstructive airways disease e.g., asthma.
As with some other class Ic anti-arrhythmic agents, patients with significant structural heart disease may be predisposed to serious adverse events. Therefore propafenone is contraindicated in these patients (see section 4.3).
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, as ECG should be performed to rule out changes suggestive of Brugada syndrome.
Propafenone like other antiarrhythmics may cause proarrhythmic effects, i.e., it may cause new or worsen preexisting arrhythmias (see section 4.8). It is essential that each patient given Arythmol be evaluated electrocardiographically and clinically prior to and during therapy to determine whether the response to Arythmol supports continued treatment.
This medicine contains sodium
This medicine contains less than 1 mmol sodium (23 mg) per tablet, that is to say essentially ‘sodium-free’.
Potential increase in adverse reactions may occur when propafenone is taken in conjunction with local anaesthetics (e.g. pacemaker implantation, surgery or dental work) and other medicinal products which have an inhibitory effect on the heart rate and/or myocardial contractility (e.g. beta blockers, tricyclic antidepressants).
No significant effects on the pharmacokinetics of propafenone or lidocaine have been seen following their concomitant use in patients. However, concomitant use of propafenone hydrochloride and lidocaine have been reported to increase the risks of central nervous system side effects of lidocaine.
Increased plasma levels and/or blood levels of propranolol, metoprolol, desipramine, ciclosporin, theophylline and digoxin have been reported during propafenone therapy. Doses of these medicinal products should be reduced, as appropriate, if signs of overdose are observed.
Elevated levels of plasma propafenone may occur when propafenone is used concomitantly with SSRIs, such as fluoxetine and paroxetine. Concomitant administration of propafenone and fluoxetine in extensive metabolisers increases the S-propafenone Cmax and AUC by 39 and 50% and the R-propafenone Cmax and AUC by 71 and 50%. Lower doses of propafenone may therefore be sufficient to achieve the desired therapeutic response.
Close monitoring of the clotting status in patients receiving concomitant oral anticoagulants (e.g. phenprocoumon, warfarin) is recommended as propafenone may enhance the plasma levels of these medicinal products resulting in an increased prothrombin time. Doses of these medicinal products should be adjusted if necessary.
Coadministration of propafenone hydrochloride with drugs metabolised by CYP2D6 (such as venlafaxine) might lead to increased levels of these drugs.
Medicinal products that inhibit CYP2D6, CYP1A2 and CYP 3A4 e.g. ketoconazole, cimetidine, quinidine, erythromycin and grapefruit juice might lead to increased levels of propafenone. When propafenone is administered with inhibitors of these enzymes, the patients should be closely monitored and the dose adjusted accordingly.
Combination therapy of amiodarone and propafenone hydrochloride can affect conduction and repolarisation and lead to abnormalities that have the potential to be proarrhythmic. Dose adjustments of both compounds based on therapeutic response may be required.
Concomitant use of propafenone and phenobarbital and/or rifampicin (CYP3A4 inducers) may reduce the antiarrythmic efficacy of propafenone as a result of a reduction in propafenone plasma levels. Hence, response to propafenone hydrochloride therapy should be monitored during concomitant chronic phenobarbital and/or rifampicin treatment.
Interaction studies have only been performed in adults. It is not known whether the extent of interactions is similar in the paediatric age group to that in adults.
There are no adequate and well-controlled studies in pregnant women. Propafenone should be used during pregnancy only if the potential benefit justifies the potential risk to the foetus.
Propafenone is known to pass the placental barrier in humans. The concentration of propafenone in the umbilical cord has been reported to be about 30% of that in the maternal blood.
Excretion of propafenone in human breast milk has not been studied. Limited data suggests that propafenone may be excreted in human breast milk. Propafenone should be used with caution in nursing mothers.
Blurred vision, dizziness, fatigue and postural hypotension may affect the patient’s speed of reaction and impair the individual’s ability to operate machinery or motor vehicles.
The most frequent and very common adverse reactions related to propafenone therapy are dizziness, cardiac conduction disorders and palpitations.
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.
Uncommon: Thrombocytopenia
Not Known: Agranulocytosis, Leukopenia, Granulocytopenia
Not Known: Hypersensitivity1
Uncommon: Decreased appetite
Common: Anxiety, Sleep disorders
Uncommon: Nightmare
Not Known: Confusional state
Very common: Dizziness2
Common: Headache, Dysgeusia
Uncommon: Syncope, Ataxia, Paraesthesia
Not Known: Convulsion, Extrapyramidal symptoms, Restlessness
Common: Vision blurred
Uncommon: Vertigo
Very common: Cardiac conduction disorders3, Palpitations
Common: Sinus bradycardia, Bradycardia, Tachycardia, Atrial flutter
Uncommon: Ventricular tachycardia, Arrythmia4
Not Known: Ventricular fibrillation, Cardiac failure5, Heart rate reduced
Uncommon: Hypotension
Not Known: Orthostatic hypotension
Common: Dyspnoea
Common: Abdominal pain, Vomiting, Nausea, Diarrhoea, Constipation, Dry mouth
Uncommon: Abdominal distension, Flatulence
Not Known: Retching, Gastrointestinal disturbance
Common: Hepatic function abnormal6
Not Known: Hepatocellular injury, Cholestasis, Hepatitis, Jaundice
Uncommon: Urticaria, Pruritus, Rash, Erythema
Not Known: Acute generalized exanthematous pustulosis
Not Known: Lupus-like syndrome
Uncommon: Erectile dysfunction
Not Known: Sperm count decreased7
Common: 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. Some of these arrhythmias can be life- threatening and may require resuscitation to prevent a potentially fatal outcome
5 An aggravation of preexisting cardiac insufficiency may occur
6 This term covers abnormal liver function tests, such as aspartate aminotransferase increased, alanine aminotransferase increased, gamma-glutamyltransferase increased and blood alkaline phosphatase increased
7 Decreased sperm count is reversible upon discontinuation of propafenone
Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions directly via the Yellow Card Scheme at: www.mhra.gov.uk/yellowcard.
None.
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