THERAPEUTIC INDICATIONS

Cordarone® is indicated only for the treatment of severe rhythm disorders, not responding to other therapy or when other treatment cannot be used : Atrial rhythm disorders (conversion of fibrillation or flutter, and maintenance of sinus rhythm following conversion); Modal rhythm disorders; Ventricular rhythm disorders (life-threatening ventricular tachycardia solves, prevention of ventricular tachycardia attacks or ventricular fibrillation episodes; Rhythm disorders associated with Wolf- Parkinson-While syndrome. In view of its pharmaceutical properties, amiodarone is indicated in the above rhythm disorders especially when they are associated with an underlying heart disease (coronary insufficiency, heart failure).

POSOLOGY AND METHOD OF ADMINISTRATION

Initial stabilization : usual dosage is 600mg daily and may be continued for 8 to 10 days. Maintenance: The minimum effective dosage should be used; according to individual response, it may range between 100mg daily to 400mg daily. Cordarone® may be given on alternate (200 mg may be given every other day where 100mg are recommended daily).

CONTRA-INDICATIONS

This medicine is contraindicated in the following situations: Sinus bradycardia and sino-atrial block not corrected by a pacemaker; Sinus disease not corrected by a pacemaker (risk of sinus arrest) ; High-degree conduction disorders not corrected by a pacemaker; Hyperthyroidism due to its possible exacerbation by amiodarone ; Known hypersensitivity to iodine or amiodarone ; The last 6 months of pregnancy; Breast-feeding; Combination with medicines that can induce torsades de pointes: class la antiarrhythmics (quinidine, hydroquinidine, disopyramide, etc), class III antiarrhythmics (sotalol, dofetillide, ibutilide, etc), sultopride, other medicines, such as bepridil, cisapride, diphemanil, erythromycin IV, mizolastine, sparfloxacin, etc. (cf. Interactions with other medicinal products and other forms of interaction).

SPECIAL WARNINGS AND PRECAUTIONS FOR USE:

Warnings: An ECG must be performed before starting treatment. Slowing of heart rate may be accentuated in elderly patients; The electrocardiogram is modified under amiodarone. This "cordaronic" modification consists of a prolongation in QT reflecting a repolarization prolongation, possibly with the appearance of a U wave; this is a sign of therapeutic impregnation and not of toxicity; The onset of 2nd or 3rd-degree atrioventricular block, sino-atrial block or bifascicular block should lead to suspension of treatment. 1st-degree atrioventricular block should lead to increased monitoring; The presence of iodine in the medicinal product falsifies certain thyroid tests (binding of radioactive iodine, PBI); however, thyroid function assessment is still possible (T3, T4, TSHus);

Such a proarrhythmic effect may occur especially if there are factors that promote QT interval prolongation, such as certain drug combinations and hypokalemia (see Sections 4.5 and 4.8), The risk of drug-induced torsades de pointes seems lower with amiodarone compared with other anti-arrhythmic agents in patients with the same degree of QT interval prolongation; Combination (cf. Interactions with other medicinal products and other forms of interaction) with: beta-blockers other than sotalol (contraindicated combination) and esmolol (combination requiring precautions for use). Verapamil and ditiazem, should only be considered in the prevention of life-threatening ventricular arrhythmias. Due to the presence of lactose, this medicinal product is contraindicated in the event of congenital galactosaemia, glucose and galactose malabsorption syndrome or lactase deficiency. The onset of dyspnoea or a dry cough, alone or associated with a deterioration in general condition, should suggest the possibility of pulmonary toxicity and requires X-ray (Cf. Undesirable effects). Severe skin disorders: Life-threatening or even fatal cutaneous reactions such as Stevens-Johnson syndrome or toxic epidermal necrolysis may occur. Ifsigns or symptoms indicative of these conditions (e.g. progressive skin rash with blisters or mucosal lesions), amiodarone treatment should be discontinued immediately. Severe bradycardia and conduction disorders: Cases of severe, potentially life-threatening bradycardia and conduction disorders have been observed when amiodarone is used in combination with sofosbuvir in combination with another antiviral (DAA) acting directly on the hepatitis C virus (HCV), such as daclatasvir, simeprevir, or ledipasvir. If concomitant use of amiodarone is deemed necessary, it is recomomended that patients undergo inpatient cardiac monitoring for the first 48 hours of co-administration, following out patient monitoring or heart rate sel-monitoring performed daily at least the first 2 weeks of treatment.

Precautions for use: Electrolyte balance disturbance and, in particular, hypokalaemia: it is important to take into account situations that may be associated with hypokalaemia since the latter can promote the onset of proarrhythmic effects. Hypokalaemia should be corrected prior to administration of amiodarone.

Anaesthesia: Before surgery, the anaesthetist must be informed that the patient is treated with amiodarone. Chronic treatment with amiodarone may lead to exacerbation, in terms of undesirable effects, of the haemodynamic risks of general or local anaesthetics. These concern, in particular, bradycardiac and hypotensive effects, reduced cardiac output and conduction disturbances. In addition, a few cases of acute respiratory distress have been observed immediately after surgery in patients treated with amiodarone. Consequently, close monitoring is recommended during artificial ventilation of such patients (Cf. Undesirable effects).

Transplantation: in retrospective studies, amiodarone use in the transplant recipient prior to heart transplant has been associated with an increased risk of primary graft dysfunction (PDG). PDG is a life-threatening complication of heart transplantation that presents as left, right or biventricular dysfunction occurring within the first 24 hours of transplant surgery for which there is no identifiable secondary cause (see Undesirable Effects). Severe PGD may be irreversible. For patients who are on the heart transplant waiting list, consideration should be given to use an alternative antiarrhythmic drug as early as possible before transplant.

DRUG INTERACTIONS

Amiodarone and/or its metabolite, desethylamiodarone, inhibit CYP1A1, CYP1A2, CYP3A4, CYP2C9, CYP2D6 and P-glycoprotein and may increase exposure of their substrates. Given the long-acting effect of amiodarone, these interactions may be observed for several months after treatment discontinuation. Contraindicated combinations: Medicinal products that can induce torsades de pointes: Class Ia antiarrhythmics (quinidine, hydroquinidine, disopyramide); Class III antiarrhythmics (dofetilide, ibutilide, sotalol); Other medicinal products, such as: bepridil, cisapride, diphemanil, erythromycin IV,mizolastine, vincamine IV; Sultopride: Increased risk of ventricular arrhythmia and in particular, torsades de pointes; Sparfloxacin: Risk of torsades de pointes due to a prolongation in QT interval (addition of electrophysiological effects). Inadvisable combinations: Sofobusvir (Co-administration of amiodarone with sofosbuvir may result in severe symptomatic bradycardia. Use only if no alternative treatment is available. Close monitoring is recommended when these products are co-administered.); Neuroleptics inducing torsade de pointes: Some phenothiazine neuroleptics, benzamide neuroleptics, butyrophenone neuroleptics, other neuroleptics (pimozide); Halofantrine, moxifloxacine, pentamidine; Injectable diltiazem; Beta-blockers (other than sotalol and esmolol). Combinations requiring precautions for use: Oral anticoagulants; Ciclosporin; Oral diltiazem; Digitalis drugs; Esmolol; Potassium-lowering drugs; Phenytoin; Bradycardiac durgs: bradycardiac calcium antagonists (diltiazem, verapamil), beta-blockers (except sotalol), clonidine; guanfacine, digitalis drugs, mefloquine; anticholinesterase drugs (donezepil, galantamine, rivastigmine, tacrine, ambemonium, pyridostigmine, neostigmine); Simvastatin; Statins.

PREGNANCY AND LACTATION

Pregnancy: Animal studies have not revealed any teratogenic effect. Clinically, no sufficiently relevant data are currently available to be able to assess a potential malformative effect of amiodarone when it is administered during the first three months of pregnancy. Iodine overload related to the use of this medicine after this time can lead to foetal hypothyroidism, which may be biological or even clinical (goitre). Consequently, the use of this medicine is contraindicated after the first 3 months of pregnancy.

Lactation: Amiodarone and its metabolite, along with iodine, cross into breast milk at concentrations greater than those in maternal plasma. Due to the risk of hypothyroidism in the newborn infant, breast-feeding is contraindicated in the event of treatment with this medicine.

EFFECT ON ABILITY TO DRIVE AND USE MACHINES

Not relevant

UNDESIRABLE EFFECTS

Ocular signs: Corneal micro-deposits, skin and subcutaneous tissue disorders: Photosensitisation, Thyroid signs: Hypothyroidism, Pulmonary signs, Neurological effects, Hepatic signs, Cardiac effects, Miscellaneous effects: Benign gastrointestinal disturbances (nausea, vomiting, dysgeusia). For uncommon, rare and very rare side effects see full prescribing information.

OVERDOSAGE

There is little documentation available on the acute administration of high doses of amiodarone. A few cases of sinus bradycardia, ventricular arrhythmia - in particular, torsades de pointes - and liver damage have been reported. Treatment should be symptomatic. Given the kinetics of the product, monitoring for a sufficiently long period of time - particularly cardiac monitoring - is recommended. Amiodarone and its metabolites cannot be dialysed.

PHARMACODYNAMIC PROPERTIES

Class III Antiarrhythmic (ATC: C01BD01).

Manufactured by

PT Aventis Pharma, Jakarta, Indonesia

PRESENTATION

Cordarone® 200 mg tablet Reg. No. DKL1421205810A1. HARUS DENGAN RESEP DOKTER

Based on approval 24 October 2021 (EU PSUSA Bradyarrythmia)

This information is intended for Health Care Professional only. See local product information for full details information

CORDARONE TABLETS 200 mg