Preventing recurrences of

· Vital-threatening ventricular tachycardia: Treatment must be instituted in hospital under surveillance

· Documented, symptomatic and disabling ventricular tachycardias

Documented supraventricular tachycardia, where the need for treatment is established in case of resistance or contraindication, other therapeutics

· Ventricular fibrillation.

Treatment of supraventricular tachycardia: slowing down or reducing atrial fibrillation or atrial flutter

Amiodarone may be used in the presence of coronary artery disease and / or impaired left ventricular function (see section 5.1). >
Attack processing

The usual dosage regimen is from 3 tablets per day for 8 to 10 days.
In some cases, the attack treatment was able to use higher dosages (4, 5 tablets per day), always on short periods and under surveillance, electrocardiographic. >

Maintenance treatment

Search for the minimum effective dose, variable according to the patient, from ½ tablet per day (1 tablet every other day) to 2 tablets every day. >
No information in the marketing authorization.

ANTIARYTHMIC

(C01BD01: system, cardiovascular)

Anti-arrhythmic properties

· Prolongation of phase 3 of the cardiac action potential resulting essentially from a decrease in the potassium current (class III of Vaughan, Williams)

· Bradycardia effect by decreasing sinus automatism. This effect is not antagonized by atropine

· Non-competitive antagonist properties alpha and beta, adrenergic

· Slower sino-atrial conduction, atrial and nodal all the more marked as the rhythm is faster

· No change in conduction at intra-ventricular level

· Increased periods, refractory and decreased excitability, myocardial atrial, nodal and ventricular stage

· Slowing conduction and prolonging refractory periods in the accessory pathways, atrio-ventricular.

Other properties

· Decreased oxygen consumption by moderately falling resistance, peripheral and decreased heart rate

Increased coronary flow by direct effect on the smooth musculature of the myocardial arteries and maintenance of cardiac output by decreasing pressure and peripheral resistances and absence of negative inotropic effect

A meta-analysis of thirteen randomized, controlled prospective studies, including 6553 patients with infarction, recent myocardium (78%) or heart failure, chronic (22%).

The average follow-up of patients varied between 0.4 and 2.5 years. The daily maintenance dose averaged between 200 and 400 mg.

This meta-analysis showed a significant reduction in amiodarone, 13% of total mortality (95% CI 0.78 - 0.99, P '= 0.030) and 29% mortality Rhythm (IC 95;% 0.59 - 0.85, P '= 0.0003). However, these results should be interpreted with caution, taking into account the heterogeneity of the studies included (heterogeneity related mainly to the selected population, duration of follow-up, methodology and outcomes; Studies).

The percentage of discontinuation of treatment was higher in the amiodarone group (41%) than in the placebo group (27%).
Seven percent of patients undergoing amiodarone had hypothyroidism, compared with 1% in the placebo group. Hyperthyroidism was detected in 1.4% of patients treated with amiodarone, compared with 0.5% in the placebo group.
Interstitial pneumonia occurred in 1.6% of patients treated with amiodarone versus 0.5% in the placebo group.
Not applicable.

This medication is contraindicated in the following situations:

· Sinus bradycardia and non-paired sino-auricular blocks

· Non-paired sinus disease (risk of sinus arrest)

· Conductive disorders of high degree not paired

· Hyperthyroidism due to its possible, aggravation by amiodarone

· Known hypersensitivity to iodine or amiodarone

· The 2nd and 3rd trimesters of pregnancy

· Breastfeeding

· Combinations with medicines giving torsades de pointes

O, class Ia antiarrhythmic drugs (quinidine, hydroquinidine, disopyramide ...)

O Class III antiarrhythmic drugs (sotalol, dofetilide, ibutilide ...)

O, certain neuroleptics (thioridazine, chlorpromazine, levomepromazine, trifluoperazine, cyamemazine, sulpiride, sultopride, amisulpride, tiapride, pimozide, haloperidol, droperidol ...)
O, other drugs such as bepridil, cisapride, diphenemil, erythromycin IV, mizolastine, sparfloxacin, vincamine IV ...
(See Interaction with other medicinal products and other forms of interaction).

This medicinal product is GENERALLY DISCLAIMED in combination with diltiazem injectable as well as with halofantrine and pentamidine (see section 4.3), with other medicinal products and other forms of interaction. >

Warnings

An ECG should be performed prior to the initiation of treatment.

· The slowing heart rate may be more pronounced in the elderly

Under amiodarone, the electrocardiogram is modified. This "cordaronic" modification consists of a QT elongation indicating the extension of the repolarization, possibly with the appearance of a U wave, it is a sign of therapeutic impregnation and not of toxicity.

· Treatment of an atrioventricular block of the 2 nd or 3 rd degree of a sino-atrial block or of a bifascicular block should stop the treatment. A 1st degree atrioventricular block must do, strengthen the monitoring.

The presence of iodine in the molecule distorts certain thyroid tests (iodine fixation, radioactive, PBI), but a thyroid assessment is always possible (T 3, T 4, TSH us). Code>
Combination with other beta-blockers, such as sotalol (contraindicated combination) and esmolol (see Interactions with other medicinal products and other forms of interactions), verapamil and diltiazem (See Interactions with other medicinal products and other forms of interactions) will be considered only in the prevention of life-threatening ventricular rhythm disorders

Due to the presence of lactose, this drug is contraindicated in cases of congenital galactosemia, glucose and galactose malabsorption syndrome or lactase deficiency.

Precautions for use

Electrolytic disturbances, especially hypokalaemia: it is important to take into account situations that may be associated with hypokalaemia, the latter may favor the occurrence of proarrhythmic effects.Hypokalemia will be corrected prior to administration Amiodarone.

· The adverse reactions mentioned below are most often related to drug overload, and will be avoided or minimized by careful consideration of the minimum dosage, maintenance, etc. During treatment, Not to expose themselves to or protect themselves from the sun.

• Amiodarone may cause abnormalities in the thyroid gland (see section 4.4) .A TSH dose is recommended in all patients before treatment and then regularly during treatment, for example every 6 months, and several TSH should be assayed in case of clinical suspicion of dysthyroidism (see section 4.4).

>
Chronic treatment with amiodarone is likely to be additive in terms of adverse effects to the hemodynamics of general or local anesthetics. These include bradycardia and hypotensive effects, decreased heart rate and conduction disturbances, and some cases of acute respiratory distress have been observed in the immediate aftermath of surgery in patients Treated with amiodarone. Accordingly, close monitoring is recommended during the artificial ventilation of these patients.


+ Drugs that can induce torsades de pointes: class Ia antiarrhythmics (quinidine, hydroquinidine, disopyramide ...) and class III (sotalol, dofetilide, ibutilide ...), certain neuroleptics (thioridazine, chlorpromazine, levomepromazine, trifluoperazine , Cyclamemazine, sulpiride, sultopride, amisulpride, tiapride, pimozide, haloperidol, droperidol ...), bepridil, cisapride, diphenemil, erythromycin IV, mizolastine, sparfloxacin, vincamine IV ... >

Increased risk of rhythm disorders, including ventricular torsades de pointes

Associations, deprecated

+ Diltiazem injectable

Risk of bradycardia and block, atrioventricular. If this association proves to be essential, do it only under clinical control and continuous ECG.
+ Halofantrine, pentamidine

Increased risk of rhythm disorders, including ventricular torsades de pointes

If possible, discontinue the non-anti-infectious torsadogenic drug. If the association can not be avoided QT checking and ECG monitoring monitored

Associations subject to precautions for use

+ Oral anticoagulants

Described for acenocoumarol, and warfarin. Increased effect of oral anticoagulants and hemorrhagic risk requires more frequent monitoring of prothrombin levels and monitoring of INR. Adjustment of dosage of oral anticoagulant during treatment with amiodarone and after discontinuation

+ Ciclosporin

Increased ciclosporin levels by decreased hepatic metabolism with risk, nephrotoxic effects

Reduction in the dosage of ciclosporin and control of renal function

Dosage of plasma concentrations of ciclosporin and dose adjustment during treatment with amiodarone and after discontinuation

+ Digital

Depression of automatism (excessive bradycardia) and conduction disorders: atrioventricular.
For Digoxin: Possible Increase in Digoxinemia by Decrease in Digoxin Clearance

Clinical monitoring and ECG, and if there is a need to control digoxinemia and adapt the dosage of digoxin

+ Bradycardiac drugs (bradycardia calcium antagonists: diltiazem per os, verapamil, beta-blockers, clonidine, guanfacine)
Increased risk of rhythm disorders, including ventricular torsades de pointes

Clinical and electrocardiographic monitoring.

+ Medications, hypokalaemicants (hypokalemic diuretics, stimulatory laxatives, amphotericin B (lane IV), glucocorticoids, tetracosactide)
Increased risk of rhythm disorders, including ventricular torsades de pointes

Correct any hypokalaemia before, administer the product and perform clinical, electrolytic, and electrocardiographic surveillance.

+ Phenytoin

Increase in phenytoin plasma levels with signs of overdose (in particular neurological) (decreased metabolism, hepatic phenytoin)

Clinical monitoring and reduction of phenytoin doses at the onset of signs of overdose

Possibly check the plasma phenytoin level.

+ Anticholinesterasics (tacrine, rivastigmine, donézepil)

Risk of excessive bradycardia (addition, bradycardiac effects).

Clinical monitoring, regular.

Not applicable.

Acute intake of high doses of amiodarone is poorly documented. Some cases of bradycardia, sinus, disorder of the ventricular rhythm, particularly of torsades, spikes and hepatic involvement have been reported. Due to the kinetics of the product, a sufficiently prolonged, especially cardiac, monitoring is recommended.


Pregnancy

Studies in animals have not shown any teratogenic effect. In the absence of teratogenic effect in animals, a malformative effect in the human species is not expected. Indeed, to date, the substances responsible for malformations in the human species have been found to be teratogenic in animals in well-conducted studies of two species

In clinical terms, there is currently no adequate data to assess a possible malformative effect of amiodarone when administered in the first trimester of pregnancy.

The fetal thyroid begins to fix iodine from 14 weeks of amenorrhea, and no effects on the fetal thyroid are expected in the case of prior administration. >

Iodine overload with the use of this product after this term may lead to fetal, biological, or even clinical (goiter) hypothyroidism.
Accordingly, the use of this medicament is contraindicated from the 2 nd quarter.


Amiodarone and its metabolite, as well as iodine, pass into milk at concentrations greater than the maternal plasma. Because of the risk of hypothyroidism in infants, breast-feeding is contraindicated when treated with this medication.

Manifestations, eyepieces

Micro-deposits of the cornea, which are almost constant in adults, usually remain localized to the subpupillary area and do not contraindicate the continuation of the treatment.Exceptionally, they may be accompanied by perception of halos Colored in dazzling light, or feeling of fog.
Constituted of complex lipid deposits, the micro-corneal deposits are always completely reversible at the end of treatment.
Some cases of optic neuropathy (optic neuritis) with visual blur and decreased vision and papillary edema in the fundus have been reported. The evolution may be towards a more or less severe diminution of visual acuity. The relationship with amiodarone is not presently established. In the absence of any other etiology, however, it is advisable to discontinue treatment.

Manifestations, cutaneous

Photosensitization. During treatment, it is advisable not to expose yourself to the sun (and, in general, to ultraviolet rays).

Cases of erythema have also been reported during treatment with radiotherapy.

Observations of skin rashes, which are generally not very specific, some exceptional cases of exfoliative dermatitis, have been reported without clearly establishing the relation to the product

Exceptional cases of pigmentation, cutaneous, liliaceous or slate gray occur at daily, high, prescribed dosages over a long period. After discontinuation of the treatment, the disappearance of these pigments is slow (10 to 24 months).
Thyroid symptoms

Apart from any clinical sign of dysthyroidism, dissociated thyroid hormoneemia (increase in T 4, T 3, normal or slightly lowered) does not justify the discontinuation of treatment. >

Hypothyroidism takes a classical form: weight gain, apathy, somnolence, frank elevation of TSH signs the diagnosis The discontinuation of the administration results in a gradual return to euthyroidism within a period of 1, at 3 months, this decision is not mandatory: if the indication warrants, amiodarone may be continued, by combining thyroxine-based L-thyroxine-based opotherapy, Code>
Hyperthyroidism is more misleading, pauci-symptomatic (slight weight loss, unexplained, decreased efficacy, antianginal and / or antiarrhythmic), psychiatric forms of the subject, elderly or even thyrotoxicosis The collapse of ultra-sensitive TSH Makes it possible to affirm the diagnosis.

The cessation of amiodarone is imperative: it is usually sufficient to initiate, within 3 to 4 weeks, the clinical cure. Severe cases that may result in the patient's death necessitate an emergency start-up of appropriate treatment. When thyrotoxicosis is of concern, either in itself or because of its repercussion on a precarious myocardial equilibrium, the inconsistent efficacy of the antithyroid synthesis leads to the recommendation of a clear (1 mg / kg) and sufficiently prolonged corticosteroid (3 months).

Cases of hyperthyroidism have been reported for up to several months after the discontinuation of amiodarone.
Manifestations, pulmonary

Cases of interstitial or diffuse alveolar pneumonia and ocular bronchiolitis obliterans (BOOP) have been reported.


The early cessation of amiodarone, with or without corticosteroid therapy, leads to regression of the disorders. The clinical signs usually disappear in 3 or 4 weeks, the radiological and functional improvement is slower (several months).



Neurological effects

They are rare

Prolonged administration of amiodarone may cause neuropathies, peripheral sensory, motor or mixed and myopathies. They may occur only after a few months of treatment but sometimes after several years of treatment. They are generally reversible upon cessation of treatment. However, this recovery may be incomplete, very slow and only manifested for several months, after discontinuation of treatment.
· Other disorders reported: tremors or other extrapyramidal symptoms, ataxia, cerebellar, intracranial hypertension, exceptional benign, sleep disorders including: nightmares.
Manifestations, hepatic

Hepatopathies have been reported, these cases have been diagnosed by the elevation of serum transaminases. Indeed, have been reported

· Elevation of transaminases, isolated and generally moderate (1.5-fold to 3-fold) regressing after dosage reduction, or even spontaneously.
Acute exceptional hepatopathy (isolated cases) with hypertransaminaseemia and / or jaundice, sometimes fatal, requiring discontinuation of treatment

Rare cases of chronic liver disease during prolonged treatment. The histology is that of a pseudo-alcoholic hepatitis. Clinical and biological discretion (hepatomegaly inconstant, hypertransaminasemia between 1.5 and 5 times normal), justifies the regular monitoring of the function, hepatic. Hypertransaminasea, even moderate, occurring after a treatment of more than 6 months must evoke the diagnosis of chronic liver disease. Clinical and biological disorders usually regress after treatment discontinuation. Some cases of irreversible evolution have been reported.

Cardiac effects

· Bradycardia is generally moderate, dose-dependent. In some cases (sinus dysfunction, elderly subjects), a marked bradycardia, more exceptionally a stopping, sinus, have been reported Rarely: conduction disorders (sino-atrial block, blocks, auriculo-ventricular of different degrees) The arrhythmogenic effect of amiodarone is low, lower than that of most antiarrhythmics, and usually occurs in some drug combinations (see section 4.3 Interactions with other medicinal products and other forms of interactions ) Or electrolyte disorders.

Miscellaneous effects

Benign digestive disorders (nausea, vomiting, dysgeusia) usually contemporaneous with attack treatment and disappearing with reduction in dosage. Some observations of epididymitis have been reported. The relationship with the product does not appear to be established. Some cases of alopecia have been observed.

A few isolated cases of varied expression were observed in a context suggestive of a hypersensitivity reaction, vasculitis, renal involvement with elevation, moderate creatinine, thrombocytopenia. >

Prevention of recurrence of life-threatening ventricular tachycardia: Treatment must be instituted in a hospital setting under surveillance • Documented ventricular tachycardia symptomatic and disabling • Documented supraventricular tachycardia When the need for treatment Is established in case of resistance or contraindication to other therapeutics Ventricular fibrillation Treatment of supraventricular tachycardia: slowing down or reducing atrial fibrillation or atrial flutter Amiodarone can be used In the presence of coronary artery disease and / or impairment of left ventricular function (see section 5.1)