Rytmonorm®

1- NAME OF THE MEDICIAL PRODUCTRytomonorm 150 mg film coated tablet.2- QUALITATIVE AND QUANTITATIVE COMPOSITIONEach tablet contains 150 mg propafenone HCI3- PHARMACEUTICAL FORMFilm coated Tablets4.CLINICAL PARTICULARS4.1Therapeutic indicationsRytmonorm is indicated for the prophylaxis and treament ofventricular arrhythmias. Rytmonorm is also indicated for theprophylaxis and treatment of paroxysmal supraventriculartachyarrhythmias which include paroxysmal atrial flutter/fibrillationand paroxysmal re-entrant tachycardias involvingthe AV node oraccessory bypass tracts, when standard therapy has failed or iscontra-indicated.4.2 Posology and method of administrationIt is recommended that Ryytmonorm therapy should be initiatedunder hospital conditions, by a physician experienced in thetreatment of arrhythmias. The individual maintenance dose shouldbe determined under cardiological surveillance icluding ECGmonitoring and blood pressure control. if the QRS interval is prolonged by more than 20% the dose should be reduced ordiscontinued until the ECG returns to normal limits. Adults: Initially,150 mg three times daily increasing at a minimum of three-dayintervals to300 mg twice daily and if necessary, to a maximum of300 mg three times daily. Dose increases should not be attempteduntil the patient has been receiving treatment for three to fourdays. The tablets should be swallowed whole and taken with adrink after food. A reduction in the total daily dose is recommendedfor patients below 70 kg boodyweight. Elderly: No overall differncesin safety or effectiveness were observed in this patient population,but greater sensitivity of some older individuals cannot be ruledout, therefore, these patients should be carefully monitored.Treatment should be initiated gradully and with particular cautionin small incremental doses. The same applies to maintenancetherapy. Any dose increases that may be required should not beundertaken until after five to eight days of therapy. Children: Asuitable dosage from of Rytmonorm for children is not available. Hepatic/Renal Impairment: In patients whose liver and/or kidneyfunction is impaired, there may be drug accumulation adter standardtherapeutic doses. Nonetheless, patients with these conditionscan still be titrated on propafenone hydrochloride under ECG andplasma level monitoring. 4.3 Contraindications.known hypersensitivity to propafenone or to any the otheringredients. Rytmonorm is contraindicated in patients with knownBrugada Syndrome. Rytmonorm is contraindicated in patients withsignificant structural heart disease such as patients with an incidentof my ocardinal infarction within the last 3 months, uncontrolledcongestive heart failure where left ventricular output is less than35% cardiogenic shock ( unless arrhythmia-induced), severesymptomatic bradycardia, manifest electrolyte imbalance (e.g.,potassium metabolism disorders), severe obstructive pulmonarydisease or severe hypotension.Rytmonorm may worsen myasthenia gravis.Unless patients are adequately paced (see section 4.4 Special Warningsand Precautions for Use), Rytmonorm should not be used in thepresence 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 and propafenone hydrochloride iscontraindicated 4.4 Special Warnings and Precautions for UseThe week negative inotropic effect of Rytmonorm may assumeimportance in patients predisposed to cardiac failure. In common with other anti-arrhythmic drugs, Rytmonorm has beenshown to after sensitivity and pacing threshold. In patients with pacemakers, appropriate adjustments may be required.There is potential for conversion of paroxysmal atrial fibrillation toatrial flutter with accompanying 2:1conduction block or 1:1conduction (see section4.8) Because of the beta-blocking effect,care should be exercised in the treatment of patients with obstructiveairways disease e.g.. asthma.As with some other class Ic anti-arrhythmic agents, patients with significant strucural heart diseasemay be predisposed to serious adverse events, Thereforepropafenone is contraindicated in these patients (see section4.3).A Brugada syndrome may be unmasked or Brugada likeelectrocardiogram (ECG) changes may be provoked after exposureIt is essential that each patient given Rytmonorm be evaluatedelectrocardiographically and clinically prior to and during therapy to determine whether the response to Rytmonorm supportscontinued treatment.4.5 Interaction with other medicinal products and other formsof interactionPotential increase in adverse reactions may occur whenpropafenone is taken in conjunction with local anaesthetics (e,g.,pacemaker implantation, surgery or dental work) and other medicinalproducts which have an inhibitory effect on the heart rate and/ormyocardial contractility (e.g., beta blockers, tricyclic antidepressants).No significant effects on the pharmacokinetics of propafenone orlidocaine have been seen following their concomitant use in patients. However, concomitant use of propafenone hydrochlorideand intravenous lidocaine have been reported to increasse the risksof central nervous system side effects of lidocaine.Increased plasma levels and/or blood levels of propranolol,metoprolol, desipramine, ciclosporin, theophylline and digoxinhave been reported during propafenone therapy. Doses of these medicinal products should be reduced, as appropriate, if signs ofoverdose are observed.

Elevated levels of plasma propafenone may occur whenpropafenone is used concomitantly with SSRls, such as fluoxetineand proxetine. Concomitant administration of propafenone andfloxetine in extensive metabolisers increases the S-propafenoneCmax and AUC by 39 and 50% and the R-propafenoneCmax andAUC by 71 and 50% Lower doses of propafenone may therforebe sufficient to achieve the desired therapeutic response.Close monitoring of the clotting status in patients receivingconcomitant oral antticoagulants (e.g., phenprocoumon, warfarin)is recommended as propafenonemay enhance the plasma levelsof these meidicinal products resauliting in an increased prothrombintime. Doses of these meidicinal products should be adjusted ifnecessary.Coadministration of propafenone hydrochloride with durgsmetabolised by CYP2D6(such as venlafaxine) might lead toincreased levels of these drugs. Meidicinal products that inhibitCYP2D6, CYP1A2 and CYP3A4e.g., ketoconazole, cimetidine,quinidine, erythromycin and grapefruit juice might lead to increasedlevels of propafenone. When propafenone is administred withinhibitors of these enzymes, the patients should be closely monitroedand the dose adjusted accordingly.Combination therapy of amiodarone and propafenone hydrochloridecan affect conduction and repolarisation and lead to abnormalitiesthat have the potential to be proarrhythmic. Dose adjustments ofboth compounds based on therapeutic response may be required.Concomitant use of propafenone and phenobarbital and/orrifampicin (CYP3A4 inducers) may reduce the antiarrythmic efficacylevels, Hence, response to propafenone hydrochloride therapyshould be monitored during concomitant chronic phenobarbitaland/or rifampicin treatment.4.6 Pregnancy and lactationPregnancy:There are on adequate and well-controlled studies in pregnantwomen. Propafenone should be used during Pregnancy only if thepotential benefit justifies the potential risk to the fetus.propafenone is known to pass the placental barrier in humans,The concentration of propafenone in the umbilical cord has beenreported to be about 30% of that in the maternal blood. lactation:Excretion of propafenone in human breast milk has not beenstudied. Limited data suggests that propafenone may be excretedin human breast milk. propafenone should be used with cautionin nursing mothers. 4.7 Effects on ability to drive and use machinesBlurred vision, dizziness, fatigue and postural hypotension mayaffact the patient

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ability to operate machinery or motor vehicles.4.8 Undesirable effects a. Summary of the safety profileThe most frequent and very common adverse reactions relatedto propafenone therapy are dizziness, cardiac conduction disordersand palpitations.b. Tabulated summary of adverse reactionsthe following table displays adverse reactiond reported in clinicaltrials and from post-marketing experience with propafenone.The reactions considered at least possibly related to propafenoneare displayed by system organ class and frequency using thefollowing 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 estimatedfrom the available data). within each frequency grouping, adversereactions are presented in order of decreasing seriousness whenthe seriousness could be assessed. The frequencies are basedon clinical trial data from propafenone SR

Propafenone HCI 150 mg film coated tablet

1 May be manifested by cholestasis, blood dyscrasias and rash2 Excluding vertigo3 Including sinoatrial block, atrioventricular block and intraventricularblock4 Propafenone may be associated with proarrhythmic effectswhich manifest as an increase in heart rate ( tachycardia) orventricular fibrillation. Some of these arrhythmias can be life-threatening and may require resuscitation to prevent a potentially fatal outcome5 An aggravation of preexisting cardiac insufficiency may occur 6 Thid term covers abnormal liver function tests, such as aspartateaminotransferase increased, alanine aminotransferase increased,gamma-glutamyltransferase increased and blood alkalinephosphatase increased7 Decreased sperm count is reversible upon discontinuation of propafenone4.9 Overdose Symptoms of overdosing:Myocardial symptoms: The effects of propafenone overdose inthe myocardium manifest as impulse generation and conductiondisorders such as PQ prolongation, QRS widening, suppressionof sinus node automaticity, AV block, ventricular tachycardia andventricular fibrilation. Reduction of contractillity ( negative inotropiceffect) can cause hypotension which, in severe cases, can leadto cardiovascular shock.Non-cardiac symptoms: Headache, dizziness, blurred vision,paraesthesia, tremor, nausea, constipation and dry mouth may occur frequently. In extremely rare cases, convulsions have beenreported on overdose. Death has also been reported.In severe cases of poisoning. clonic-tonic convulsions,paraesthesia,somnolence, coma and respiratry arrest may occur.Treatment:In addition to general emergency measures, the patient

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parameters should be monitored in an intensive care setting, andrectified, as appropriate.Defibrillation as well as infusion of dopamine and isoproterenol have been effective in conrolling rhythm and blood pressure.Convulsions have been alleviated with intravenous diazepam.General supportive measures such as mechanical respiratotyassistance and external cardiac massage may be necessary.Attempts to achieve elimination via haemoperfusion are of limitedefficacy.Owing to high protein binding (>95%) and the large volume of distribution heamodialysis is ineffctive.5.PHARMACOLOGICAL PROPERTIES5.1 Pharmacodynamic propertiespropafenone is a class IC anti-arrhythmic agent.It has a stabilising action on myocardial membranes, reduces thefast inward current carried by sodium ions with a reduction in depolarisation rate and prolongs the impulse conduction time inthe atrium, AV node and primarily, in the His-Purkinje system.Impluse conduction through accessory pathways, as in WPWsyndrome, is either inhibited, by prolongation of the refractoryperiod or blockade of the conduction pathway, both in anterogradebut mostly retrograde direction.At the same time, spontaneous excitabillity is reduced by an increase of the myocardial stimulus thershold while electricalexcitabillity of the myocardium is decreased by an increase of the ventricular fibrillation theshold.Anti-arrhythmic effects: Slowing of upstroke velocity of the actionpotential, devrease of excitabillity, homogenisation of conduction