THERAPEUTIC INDICATIONS

Serious rhythm disorders when the oral route is not appropriate, namely: atrial rhythm disorders, with rapid ventricular rhythm; Wolf-Parkinson-White syndrome tachycardia; documented symptomatic and disabling ventricular rhythm disorders.

POSOLOGY AND METHOD OF ADMINISTRATION

Because of the formulation of the product, do not use concentrations of less than 2 ampoules in 500 ml. Use only isotonic glucose solution. Do not add any other products to the infusion solution. Amiodarone must be administered by the central venous route. Intravenous infusion. Initial treatment: generally 5 mg/kg in glucose solution, preferably using an electric syringe, administered over 20 minutes to 2 hours and repeated 2 or 3 times per 24 hours period. The short action of the drug requires continuation of the infusion. Maintenance treatment: 10 to 20 mg/kg/day (generally 600 to 800 mg/24 hours, up to 1.2 g/24 hours) in 250 ml of glucose solution over a few days. Replace by the oral route (3 tablets per day) from the first day of infusion. The dosage may be increased to 4 or even 5 tablets per day.

CONTRA-INDICATIONS

This drug is contra-indicated in the following situations: Sinus bradycardia and sinoatrial heart block without a prosthesis; Sinus disease without a prosthesis (possible sinus arrest); High- degree conduction disorders without a prosthesis; Hyperthyroidism because of possible exacerbation by amiodarone; Known hypersensitivity to iodine or amiodarone; 2nd to 3rd trimesters of pregnancy; circulatory collapse; severe hypotension; in children aged less than 3 years due to the presence of benzyl alcohol; breast-feeding women; combination with drugs liable to induce torsades de pointes; class Ia antiarrhythmics (quinidine, hydroquinidine, disopyramide, etc).; class III antiarrhythmics (sotalol, dofetilide, ibutilide, etc.); sultopride; other drugs such as bepridil, cisapride, diphemanil, erythromycin IV, mizolastine, sparfloxacin, vincamine IV, etc. (see interactions with other drug and other forms of interaction).

SPECIAL WARNINGS AND PRECAUTIONS FOR USE: Warnings

Injectable amiodarone must be administered by the central venous route. In fact, administration by the peripheral venous route can cause local effects such as superficial phlebitis. Injectable amiodarone must be used exclusively as an infusion. In fact, even a very slow injection may exacerbate hypotension, heart failure or severe respiratory failure (see undesirable effects). Cardiac Disorders: Onsets of new arrhythmias or worsening of treated arrhythmias, sometimes fatal, have been reported. It is important, but difficult, to differentiate a lack of efficacy of the drug from a proarrhythmic effect, whether or not this is associated with a worsening of the cardiac condition. Proarrhythmic effects are more rarely reported with amiodarone than with the other antiarrhythmic agents, and generally occur in the context of QT prolonging factors such as drug interactions and / or electrolytic disorders. Despite QT interval prolongation, amiodarone exhibits a low torsadogenic activity. Severe skin disorders: Life-threatening or even fatal cutaneous reactions such as Stevens-Johnson syndrome or toxic epidermal necrolysis may occur. If patients experience signs 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 with medicinal products containing sofosbuvir in combination with amiodarone. If concomitant use of amiodarone is deemed necessary, it is recommended that patients undergo inpatient cardiac monitoring for the first 48 hours of co-administration, and following that outpatient monitoring or heart rate self-monitoring should be performed daily for at least the first 2 weeks of treatment. Precautions for use: Electrolyte disturbances, particularly hypokalaemia: it is important to take account of situations that may be associated with hypokalaemia as these may predispose to the onset of pro-arrhythmic effects. The hypokalaemia should be corrected before amiodarone is administered. Regular monitoring of liver function (transaminases) is helpful in the detection of amiodarone-induced hepatic disorders (see undesirable effects). Cordarone injection should only be administered in a specialist hospital environment and under continuous monitoring (ECG, BP). Anaesthesia: Prior to any surgery, the anaesthetist should be informed that the patient is receiving amiodarone. Long-term treatment with amiodarone may add, in terms of undesirable effects, to the haemodynamic risk inherent to local or general anesthesia. This in particular concerns its bradycardiac and hypertensive effects, the reduction in cardiac output and conduction disorders. In addition, a few cases of acute respiratory distress have been observed immediately following surgery in patients receiving amiodarone. In consequence, close monitoring is recommended during artificial ventilation in such patients. 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: Drugs liable to induce torsades de pointes: class Ia antiarrhythmics (quinidine, hydroquinidine, disopyramide); class III antiarrhythmics (dofetilide, ibutilide, sotalol); other drugs such as bepridil, cisapride, diphemanil, erythromycin IV, mizolastine, vincamine IV; sultopride: Enhanced risk of ventricular rhythm disorders, particularly torsades de pointes. Sparfloxacin: Risk of torsades de pointes by lengthening of the QT interval (addition of the electrophysiological effects). Inadvisable combinations: Sofobusvir: Co-administration of amiodarone and sofosbuvir may result in severe symptomatic bradycardia. Use only if no alternative treatment is available. Close monitoring is recommended when these medicinal products are co-administered; Neuroleptics liable to induce torsades de pointes: certain phenothiazine neuroleptics (chlorpromazine, cyamemazine, levomepromazine, thioridazine, trifluoperazine), benzamides (amisulpride, sulpiride, tiapride), butyrophenones (droperidol, haloperidol), other neuroleptics (pimozide); Halofantrine, moxifloxacin, pentamidine; Diltiazem injection; Beta-blockers other than sotalol and esmolol. Combinations requiring precautions for use: Oral anticoagulants; Ciclosporin; Diltiazem per os; Digitalis drugs; Esmolol; Hypokalaemic agents: hypokalaemic diuretics (alone or in combination), stimulant laxatives, glucocorticoids (systemic route), tetracosactide, amphotericin B (IV route); 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); Statins.

PREGNANCY AND LACTATION

Pregnancy: Studies in animals have not shown any teratogenic effects. In clinical practice, the information currently available is insufficiently pertinent to evaluate whether amiodarone causes malformations when administered in the first trimester of pregnancy. This drug is contra-indicated from the 2nd trimester of pregnancy.

Lactation: Amiodarone, its metabolite and iodine pass into breast milk at concentrations greater than those in maternal plasma. If the mother is receiving treatment with this drug, breast-feeding is contra-indicated because of the risk of hypothyroidism in the infant.

EFFECT ON ABILITY TO DRIVE AND USE MACHINES : Not relevant

UNDESIRABLE EFFECTS

Locally: possible inflammatory reaction such as superficial phlebitis when administered by direct peripheral route; Hot flushes, sweating, nausea, hair loss; Generally moderate and transient fall in blood pressure; Bradycardia; Rare pro-arrhythmic effect. Cases of hepatic disorders have been reported; these cases were diagnosed by elevated serum transaminases. The following have been reported: Generally moderate and isolated elevation in transaminases (1.5 to 3 fold normal levels) regressing after dosage reduction, or even spontaneously. Various effects which appear to occur only exceptionally rarely (a few isolated cases) have been described following direct IV administration ; anaphylactic shock, benign intracranial hypertension (pseudotomor cerebri), bronchosparsm and/or apnoea in the event of severe respiratory failure, particulary in asthmatics.

OVERDOSAGE

No information regarding amiodarone overdose by the IV route is available. As regards the oral form, few cases concerning the acute administration of high doses amiodarone have been documented. A few cases of sinus bradycardia, ventricular rhythm disorders, particularly torsades de pointes and liver damage have been reported. Treatment must be symptomatic. Given the kinetic profile of the product, cardiac monitoring in particular, over a sufficiently long period of time, is recommended. Amiodarone and its metabolites are not dialysable.

PHARMACODYNAMIC PROPERTIES

Class III Antiarrhythmic (ATC: C01BD01).

Manufactured by

Sanofi Winthrop Industrie, Carbon Blanc, Cedex-France.

Imported by

PT Aventis Pharma, Jakarta, Indonesia.

PRESENTATION

Cordarone® 150 mg/3 ml Reg. No. : DKI1077402943A1.

HARUS DENGAN RESEP DOKTER

Based on approval 3 October 2021 (EU PSUSA Bradyarrythmia)

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

CORDARONE 150 mg/3 ml Injection