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  • Amiodacore Tablets
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    Active Ingredient

    Status in Israel
    RX

    Presentation and Status in Health Basket

    Presentation Basket Yarpa Pharmasoft

    Tablets

    30 X 200 mg

    full basket chart 206 1235

    Related information


    Dosage

     Initial treatment: The usual dosage regimen is 3 tablets per day, for 8 to 10 days. In some cases, the initial treatment has involved higher doses (4 to 5 tablets per day), always for short periods and under electrocardiographic monitoring.
    Maintenance treatment: Seek the minimum effective dose, which varies depending on the patient, ranging from 1/2 tablet per day (1 tablet every 2 days) to 2 tablets every day.


    Indications

    Cardiac arrhythmia, chronic angina states, coronary insufficiency, cardiopathies of ischemic type, sequelae of cardiac infarction, short term (up to 48 hours) I.V. therapy in severe refractive CHF.


    Contra-Indications

    Known hypersensitivity to amiodarone or to iodine. Patients with sinus bradycardia, all degress of atrioventricular (AV) block and in episodes of bradycardia sufficient to cause syncope, unless used in conjunction with a pacemaker. Patients with evidence or a history of thyroid dysfunction. Both hyper- and-thyroidism have occurred during treatment. Combined therapy with drugs which may induce torsade de pointes. Pregnancy and breastfeeding.


    Special Precautions

    – 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.
    – Electrolyte disturbances, particularly hypokalaemia: it is important to take into account situations liable to be associated with hypokalaemia that may favour the onset of proarrhythmic effects.
    – Hypokalaemia should be corrected before amiodarone is administered.
    – The undesirable effects mentioned below are usually related to excessive drug levels; they can be avoided or their severity minimised by carefully seeking the minimum maintenance dosage. • In children, the safety and efficacy of amiodarone have not been evaluated by controlled clinical trials
    – Combination with : – Beta-blockers other than sotalol (contraindicated combination) and esmolol (combination requiring precautions for use). – Verapamil and diltiazem should only be considered in the prevention of life-threatening ventricular arrhythmias.
    Cardiac effects
    – An ECG must be performed before starting treatment and serum potassium measurement. Monitoring of ECG is recommended during treatment.
    – Slowing of heart rate may be accentuated in elderly patients.
    – The electrocardiogram is modified under amiodarone. This “amiodaronic” modification consists of a prolongation in QT reflecting a repolarisation prolongation, possibly with the appearance of a U wave and deformed T-waves; 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 onset of a new arrhythmia or the worsening of pre-existing and treated arrhythmia has been reported.
    – The arrythmogenic effect of amiodarone is weak, even less than that of most antiarrhythmic drugs, and generally occurs in some drug combinations or electrolyte balance disturbances. • Too high a dosage may lead to severe bradycardia and conduction disturbances with the appearance of an idioventricular rhythm, particularly in elderly patients or during digitalis therapy. In these circumstances, Amiodacore treatment should be withdrawn. If necessary beta-adrenostimulants or glucagon may be given. Because of the long half-life of amiodarone, if bradycardia is severe and symptomatic the insertion of pacemaker should be considered.
    – Amiodacore is not contra-indicated in patients with latent or manifest heart failure but caution should be exercised as, occasionally, existing heart failure may be worsened. In such cases, Amiodacore may be used with other appropriate therapies. • Amiodarone may increase the defibrillation threshold and/or pacing threshold in patients with an implantable cardioverter defibrillator or a pacemaker, which may adversely affect the efficacy of the device. Regular tests are recommended to ensure the proper function of the device after initiation of treatment or change in posology.
    Thyroid signs – The presence of iodine in the medicinal product distorts certain thyroid tests (binding of radioactive iodine, PBI); however, thyroid function assessment is still possible (T3, T4, TSHUS).
    – Amiodarone can cause thyroid anomalies, particularly in patients with a history of thyroid disorders. Assay of TSH is recommended in all patients before treatment and then regularly throughout treatment and several months after discontinuation, as well as in the event of clinical suspicion of dysthyroidism.
    – Hypothyroidism: hypothyroidism should be suspected if the following clinical signs occur: weight gain, cold intolerance, reduced activity, excessive bradycardia. The diagnosis is supported by an increase in serum usTSH and an exaggerated TSH response to TRH. T3 and T4 levels may be low. Euthyrodism is usually obtained within 3 monthes following the discontinuation of treatment. In life-threatening situations, amiodacore therapy can be continued, in combination with levothyroxine. The dose of levothyroxine is adjusted according to TSH levels.
    – Hyperthyroidism: hyperthyroidism may occur during amiodarone treatment, or, up to several months after discontinuation. Clinical features, such as weight loss, asthenia, restlessness, increase in heart rate, onset of arrhythmia, angina, and congestive heart failure should alert the physician. The diagnosis is supported by a decrease in serum usTSH level, an elevated T3 and a reduced TSH response to thyrotropin releasing hormone. Elevation of reverse T3 (rT3) may also be found.
    – In life-threatening situations where clinical evidence of thyroid disorders exist, amiodarone therapy can be continued in combination with levothyroxine. The dose of levothyroxine is adjusted according to TSH levels In the case of Hyperthyroidism, therapy should be withdrawn. Clinical recovery usually occurs within a few months, although severe cases, sometimes resulting in fatalities, have been reported. Clinical recovery precedes the normalization of thyroid function tests. Courses of anti-thyroid drugs have been used for the treatment of severe thyroid hyperactivity; large doses may be required initially. These may not always be effective and concomitant high dose corticosteroid therapy (e.g. 1mg/kg prednisolone) may be required for several weeks.
    Pulmonary signs The onset of dyspnoea or a dry cough, alone or associated with a deterioration in general condition, should suggest the possibility of pulmonary toxicity, such as interstitial pneumopathy, and requires radiological control. The onset of effort dyspnoea or dry cough – either isolated or associated with a deterioration in general condition (fatigue, weight loss, febricula) – requires radiological control and, if necessary, suspension of treatment. These types of pneumopathy can actually develop into pulmonary fibrosis Early withdrawal of amiodarone – associated or not with corticosteroid therapy – leads to a regression in the disturbances. Clinical signs usually disappear within 3 or 4 weeks. Radiological and function improvement is usually slower (several months). Patients should be carefully evaluated clinically and consideration given to chest X-rays before starting therapy. During treatment, if pulmonary toxicity is suspected, this should be repeated and associated with lung function testing including, where possible, measurement of transfer factor. Initial radiological changed may be difficult to distinguish from pulmonary venous congestion. Pulmonary toxicity has usually been reversible following early withdrawal of amiodarone therapy, with or without corticosteroid. Clinical symptoms often resolve within a few weeks followed by slower radiological and lung function improvement. Some patients can deteriorate despite discontinuing amiodacore.
    Hepatic signs Amiodarone may be associated with a variety of hepatic effects, including cirrhosis, hepatitis, jaundice and hepatic failure. Some fatalities have been reported, mainly following long-term therapy, although rarely they have occurred soon after starting treatment particularly after Amiodacore intravenous. It is advisable to monitor liver function particulary transaminases before treatment and six monthly thereafter . At the beginning of therapy, elevation of serum transaminases which can be in isolation may occur. These may return to normal with dose reduction, or sometimes spontaneously. Isolated cases of acute liver disorders with elevated serum transaminases and/or jaundice may occur; in such cases treatment should be discontinued. There have been reports of chronic liver disease. Alteration of laboratory tests which may be minimal (transamininases elevated 1.5 to 5 times normal) or clinical signs during treatment for longer than 6 months should suggest this diagnosis. Routine monitoring of liver function tests is therefore advised. Abnormal clinical and laboratory test results usually regress upon cessation of treatment, but fetal cases have been reported. Histological findings may resemble pseudo-alcoholic hepatitis, but they can be variable and include cirrhosis. Although there have been no literature on the potentiation of hepatic adverse effects of alcohol, patients should be advised to moderate their alcohol intake while taking amiodacore.
    Neuromuscular signs Amiodarone can cause sensory, motor or mixed peripheral neuropathies and myopathies. Both these conditions may be severe, although recovery usually occurs within several months after amiodarone withdrawal, but may sometimes be incomplete.
    Ocular signs In the event of blurred vision or a reduction in visual acuity, a complete ophthalmological assessment, including eye fundus, must be rapidly performed. It is necessary to discontinue amiodarone in the event of the onset of amiodarone-induced neuropathy or optic neuritis due to the potential risk of progression to blindness.
    Skin and subcutaneous tissue signs Patient should be instructed to avoid exposure to sun and to use protective measures during therapy as patients taking amiodacore can become unduly sensitive to sunlight, which may persist after several months of discontinuation of amiodacore. In most cases symptoms are limited to tingling, burning and erythema of sun-exposed skin but severe phototoxic reactions with blistering may be seen.
    Anaesthesia The anaesthesiologist should be informed that the patient is being treated with amiodarone before surgery. Chronic amiodarone treatment is liable to add to the haemodynamic risk associated with general or local anaesthesia, in terms of undesirable effects. Undesirable effects include in particular bradycardia, hypotension, reduced cardiac output and conduction disturbances. Furthermore, some cases of acute respiratory distress syndrome have been observed in patients treated with amiodarone in the period immediately after surgery. It is therefore recommended that these patients be closely monitored during artificial ventilation.
    See prescribing information for full details.


    Side Effects

    Amiodarone side effects are dose-related. The most serious reactions are pulmonary toxicity, exacerbation of arrhythmias and rarely, serious liver injury. Most adverse side effects appear to become mor frequent with continued treatment over 6 months. Malaise and fatigue, tremor and involuntary movements, poor coordination and gait and peripheral neuropathy. Gastrointestinal complaints, most commonly nausea, vomiting, constipation and anorexia. Asymptomatic corneal micro-deposits in virtually all adult patients. Flushing, abnormal taste and smell, edema, abnormal salivation, coagulation abnormalities, abnormal liver tests.
    See prescribing information for full details.


    Drug interactions

    Medicinal products liable to induce torsades de pointes: This serious arrhythmia can be induced by a number of medicinal products, antiarrhythmics or otherwise. Hypokalaemia is a predisposing factor, as is bradycardia or a congenital or acquired pre-existing prolongation in QT interval. The medicinal products liable to cause torsades de pointes are, in particular, class Ia antiarrhythmics, class III antiarrhythmics and certain neuroleptics. In cases of hypokalaemia, corrective action should be taken and QT interval monitored. In case of torsades de pointes antiarrhythmic agents should be given; pacing may be instituted and IV magnesium may be used.
    Bradycardic agents: Many medicines can cause bradycardia. This is the case particularly with class Ia antiarrhythmic drugs, beta blockers, some class III antiarrhythmic drugs, some calcium channel blockers, digitalis drugs, pilocarpine and anticholinesterase agents. Risk of excessive bradycardia (cumulative effect).
    Contraindicated combinations+ Medicinal products liable to induce torsades de pointes:
    class Ia antiarrhythmics (quinidine, hydroquinidine, disopyramide).
    class III antiarrhythmics (dofetilide, ibutilide, sotalol).
    Intravenous erythromycin, co-trimoxazole or pentamidine injection.
    Some anti-psychotics (Chlorpromazine, Thioridazine, Fluphenazine, Pimozide, Haloperidol, Amisulpiride and Sertindole).
    Lithium and anti-depressants (Doxepin, Maprotiline and Amitriptyline).
    Certain antihistamines (Terfenadine, Astemizole and Mizolastine).
    Anti-malarials (Quinie, Mefloquine, Chloroquine and Halofantrine).
    Moxifloxacin.
    Inadvisable combinations:
    Ciclosporin: Increase in circulating cyclosporin levels due to reduced metabolism by the liver, with the risk of nephrotoxic effects. Assay of blood ciclosporin concentrations, control of renal function and dosage adjustment during treatment with amiodarone and after treatment discontinuation.
    Injectable CCBs (diltiazem, verapamil): Risk of bradycardia and atrioventricular heart block. If this combination cannot be avoided, close clinical supervision and continuous ECG monitoring are essential.
    Antiparasitic drugs liable to induce torsades de pointes (Halofantrine, pentamidine, lumefantrine):
    Increased risk of ventricular arrhythmias, particularly torsades de pointes. If possible, discontinue.the azole anti-fungal agents. If this combination cannot be avoided, prior control of the QT interval and ECG monitoring are essential.
    Neuroleptics liable to induce torsades de pointes: some phenothiazine neuroleptics (chlorpromazine, cyamemazine, levomepromazine, thioridazine, trifluoperazine), benzamides (amisulpride, sulpiride, tiapride, veralipride), butyrophenones (droperidol, haloperidol), and other neuroleptics (pimozide). Increased risk of ventricular arrhythmias, particularly torsades de pointes.
    Metadone: Increased risk of ventricular arrhythmias,,particularly torsades de pointes. ECG and clinical monitoring. .
    Combinations requiring precautions for use:
    Oral anticoagulants: Increase in the anticoagulant effect and in the risk of haemorrhage due to increased plasma concentrations of the anticoagulant. More frequent control of prothrombin levels and monitoring of INR. Adjust the dosage of the oral anticoagulant during treatment with amiodarone and after treatment discontinuation.
    Beta-blockers other than sotalol (contraindicated combination) and esmolol (combination requiring precautions for use): Contractility, automaticity and conduction disorders (suppressed compensatory sympathetic mechanisms). ECG and clinical monitoring.
    See prescribing information for full details.


    Pregnancy and Lactation

    Pregnancy: Animal studies have not demonstrated any teratogenic effects. In the absence of a teratogenic effect in animals, no teratogenic effects are expected in humans. To date, substances causing malformations in humans have been shown to be teratogenic in animals during studies conducted properly in two species. In a clinical context, there are not yet enough relevant data in order to evaluate the possible teratogenic effect of amiodarone when administered during the first trimester of pregnancy. Since the foetal thyroid gland begins to bind iodine from week 14 of amenorrhoea, no effects on the foetal thyroid gland are expected in the event of previous administration. Iodine overload with the use of this product beyond this period may give rise to biological or clinical (goitre) foetal hypothyroidism. Consequently, use of this medicinal product is contraindicated from the 2nd trimester of pregnancy.
    Lactation: Amiodarone and its metabolite, together with iodine, are extracted in 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 medicinal product.


    Overdose

    There is little documentation available on the acute administration of high doses of amiodarone. A few cases of sinus bradycardia, ventricular arrhythmias, particularly torsades de pointes, and hepatic impairment have been reported. Treatment must be symptomatic, gastric lavage may be employed to reduce absorption in addition to general supportive measures. 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.

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