Preventing recurrences of

· Life-threatening ventricular tachycardia: treatment should be initiated in hospitals, under monitoring

· Documented symptomatic and disabling ventricular tachycardias

· Supraventricular tachycardia documented 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 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, which varies according to the patient, from 1/2 tablet per day (1 tablet every two days) to 2 tablets every day.
ANTIARYTHMIC

(C01BD01: system, cardiovascular).

Anti-arrhythmic properties

· Prolongation of phase 3 of the action potential of the cardiac fiber resulting mainly from a decrease in potassium (Vaughan Williams class III)
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· Bradycardia effect by reduction of sinus automatism. This effect is not antagonized by atropine

· Non-competitive alpha and beta adrenergic antagonist properties

· Slowing down of Sino-auricular, atrial and nodal conduction all the more marked as the rhythm is more

· No change in conduction at intra-ventricular level

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

· Slowing of conduction and prolongation of periods, refractory in the accessory pathways, atrioventricular.
Other properties

· Decreased oxygen consumption per fall, moderate resistance, peripheral and reduced heart rate

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

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% in total mortality (95% CI 0.78 - 0.99, P = 0.030) and 29% in mortality (95% CI 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 to 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 stopping, sinus)

· Conductive disorders of high degree not paired

· Hyperthyroidism due to its possible worsening by amiodarone

· Known hypersensitivity to iodine or amiodarone

· The 2nd and 3rd trimesters of pregnancy

· Breastfeeding

· Combinations with medicaments giving torsades of spikes

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 Interactions 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.

· Slower heart rate may be more pronounced in elderly patients

Under amiodarone, the electrocardiogram is modified This "cordaronic" modification consists of an elongation of QT, reflecting the prolongation of the repolarization, with possibly the appearance of a U wave, it is a sign; Therapeutic impregnation and not toxicity.

Patients undergoing treatment with a second or third degree atrioventricular block, sino-atrial block, or bifascicular block should discontinue treatment A first degree atrioventricular block How and strengthening surveillance

The presence of iodine in the molecule distorts some thyroid tests (fixation of radioactive iodine, PBI), but a thyroid assessment is still possible (T 3, T 4, TSH us). >

· Combination with beta-blockers other than sotalol (contraindicated association) and esmolol (see Interactions with other medicines 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 arrhythmia
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Due to the presence of lactose, this drug is contraindicated in cases of galactosemia, congenital, glucose and galactose malabsorption syndrome or lactase deficiency. Br>

Precautions for use

Hypokalemia: 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 before administration Amiodarone.

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

Amiodarone may cause thyroid abnormalities (see section 4. Effects, undesirable) .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).




+ 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 levels of ciclosporin 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 as soon as signs of overdosage appear. Possibly check the rate of phenytoin plasma

+ 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 2nd trimester.

Breastfeeding

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.

Eye: Corneal micro-deposits, which are almost constant in adults, usually remain localized in the subpupillary area and do not contraindicate the continuation of the treatment, but may be accompanied by perception Of colored halos in dazzling light, or of fog sensation.

Constituted of complex lipid deposits, the micro-corneal deposits are always completely reversible at the end of treatment.
Some observations of 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 reduction of visual acuity. The relationship with amiodarone is not currently established. It is, however, recommended, in the absence of other manifest etiology, to discontinue treatment.

Manifestations: cutaneous: photosensitization. It is advised not to expose yourself to the sun (and, in general, to ultraviolet rays) during processing.
Cases of erythema have also been reported during radiotherapy.
Observations of cutaneous rashes, which are generally not very specific, some exceptional cases of exfoliative dermatitis, have been reported without any clear relationship to the product.

Exceptional skin pigments, liliaceous or slate gray, occurring at high daily dosages, prescribed for a long time, after discontinuation of treatment, the disappearance of these pigments is slow (10-24 months). >

Thyroid symptoms

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

· Hypothyroidism takes a classic form: weight gain, apathy, somnolence, frank elevation of TSH signs the diagnosis. The discontinuation of the administration leads to a gradual return to euthyroidism, and within 1 to 3 months this judgment is not imperative: if the indication warrants it, amiodarone may be prosecuted for Combining an L-thyroxine-based substitutive opotherapy, the TSH constituting a dosage guide.

Hyperthyroidism is more deceptive: pauci-symptomatic (slight unexplained weight loss, attenuation, anti-anginal and / or anti-arrhythmic efficacy), forms, psychiatric of the elderly, or even thyreotoxicosis. The collapse of the ultra-sensitive TSH confirms the diagnosis.

The discontinuation of amiodarone is imperative: it is usually sufficient to initiate, within 3-4 weeks, 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 broncholitis obliterans, organized (BOOP) have been reported.

The occurrence of dyspnoea, of effort, isolated or associated with an alteration of the general state (fatigue, emaciation, febrile) requires a radiological control and, if necessary, cessation of treatment. These pneumopathies can indeed evolve into pulmonary fibrosis.

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

· Peripheral sensory-motor neuropathies and / or myopathies, generally reversible at discontinuation of treatment

Other disorders reported: extrapyramidal tremor, cerebellar ataxia, hypertension, benign exceptional intracranial, 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 to 3 times normal) regressing after reduction, dosage, or even spontaneously
Acute exceptional hepatopathy (isolated cases) with hypertransaminase and / or jaundice, sometimes fatal, requiring discontinuation of treatment

· Rare cases of chronic liver disease during prolonged treatment histology is that of pseudoalcoholic hepatitis. The discretion of the clinical and biological picture (inconstant hepatomegaly, hypertransaminasemia between 1.5 and 5 times normal), justifies regular monitoring of liver function. 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

· Generally moderate bradycardia, dose-dependent. In some cases (dysfunction, sinus, elderly), marked bradycardia, more exceptionally sinus arrest, 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 antiarrhythmic drugs, and usually occurs in some combination medications (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 therapy and disappearing with dosage reduction. Some observations of epididymitis have been reported. The relationship with the product does not appear; Some cases of alopecia have been observed.

A few isolated cases of varied expression have been observed in a context suggestive of a hypersensitivity reaction: vasculitis, renal involvement with elevation, moderate creatinine, thrombocytopenia
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Prevention of recurrence of life-threatening ventricular tachycardia: treatment must be instituted in a hospital setting, under monitoring, · documented symptomatic and disabling ventricular tachycardias, · documented supraventricular tachycardia when the need for treatment Is established in case of resistance or contraindication to other therapeutic ventricular fibrillations Treatment of supraventricular tachycardia: slowing down or reducing atrial fibrillation or atrial flutter Amiodarone can be used in Presence of coronary artery disease and / or impairment of left ventricular function (see section 5.1)