Active ingredients: Amiodarone (Amiodarone hydrochloride)
Amiodar 200 mg tablets
Why is Amiodar used? What is it for?
Amiodar contains the active ingredient amiodarone. Amiodar is an antiarrhythmic medicine, that is, it is used to treat and prevent heart rhythm disorders such as:
- rapid heartbeat (paroxysmal and non-paroxysmal supraventricular tachycardias) or irregular heartbeats (atrial extrasystoles, atrial flutter and fibrillation, ventricular extrasystoles and tachycardias)
- rapid heartbeat, sometimes present as paroxysmal reciprocating tachycardia such as in a disease called Wolff-Parkinson-White syndrome.
Amiodar can be used to treat irregular heartbeat when other medicines have either not worked or cannot be used.
Amiodar is also used in the prevention of angina pectoris crises (chest pains caused by problems related to heart disease).
Contraindications When Amiodar should not be used
Do not take Amiodar
- if you are allergic to amiodarone, iodine or any of the other ingredients of this medicine
- if you have heart rhythm disturbances such as:
- slow heart rate (sinus bradycardia) or a disease called "sinoatrial block"
- if you have any other heart rhythm problems and have not implanted a pacemaker (e.g. severe atrioventricular block, bi- or trifascicular block)
- if you have a disease called 'sinus disease' and have not implanted a pacemaker
- if you are taking medicines that can cause a heart disorder called "torsade de pointes" (torsade de pointes, rapid heart beat-ventricular tachycardia) (see section "Other medicines and Amiodar").
- if you have or have had thyroid problems. In case of doubt or cases of thyroid problems in the family, it is advisable to have a thyroid function test before treatment
- if you are pregnant or suspect to be pregnant, except in exceptional cases (see section "Pregnancy and breastfeeding")
- if you are breast-feeding (see section "Pregnancy and breast-feeding").
Precautions for use What you need to know before taking Amiodar
Talk to your doctor or pharmacist before taking Amiodar.
Avoid sun exposure and use protective measures while taking Amiodar.
Your doctor may have an electrocardiogram (ECG) and / or blood tests done before you start and during treatment with Amiodar.
General anesthesia
If you need to undergo surgery under general anesthesia, please inform the anesthetist that you are taking Amiodar. In fact, cases of heart or lung problems, sometimes fatal, have been observed following the anesthesia.
Disorders of the thyroid gland
Amiodarone can cause thyroid problems to work. Take special care if you have had thyroid problems in the past or if you are an elderly person.
Talk to your doctor if you notice any symptoms, even mild ones, listed below, which may occur up to several months after stopping therapy:
- weight gain or loss
- cold intolerance
- reduced activity
- slow heartbeat
- heart rhythm disturbances
- chest pains
- swelling with fluid retention or other heart problems.
Your doctor will decide whether to discontinue treatment with Amiodar or possibly give you appropriate therapy.
Disorders of the liver
Do not use Amiodar if you have ongoing liver disease.
Acute (including severe, sometimes fatal) and chronic changes in the liver, enlarged liver, or bile or gallbladder disorders may occur during treatment with amiodarone.
In all these cases your doctor will tell you whether to stop or reduce the medicine.
Lung problems
Amiodarone can cause lung toxicity. If you have heart disease (cardiomyopathy and severe coronary heart disease) you are at particular risk.
Talk to your doctor if you notice the symptoms listed below, which may occur weeks after stopping therapy:
- inflammation of the alveoli (pulmonary alveolitis), inflammation of the lungs (pneumonia) and other lung problems (interstitial pneumonia, pulmonary fibrosis)
- difficulty in breathing due to narrowing of the bronchi (bronchial asthma)
- dry cough
- difficulty in breathing (dyspnoea)
- fever
- fatigue
- weight loss
Your doctor may prescribe a chest x-ray, appropriate therapy and / or discontinuation of Amiodar therapy.
Heart ailments
The action of amiodarone causes visible changes in the electrocardiogram (ECG) pattern, which are not to be regarded as signs of toxicity.
If you are an elderly patient, the slowing of the heart rate may be more pronounced.
If you develop severe heart problems, new arrhythmias or worsening of previously treated arrhythmias, your doctor will decide whether to stop taking Amiodar.
Pacemaker
If you have a pacemaker, your doctor will repeatedly check the function of the device before and during Amiodar therapy.
Nerve and muscle disorders
Amiodarone can induce nerve and muscle damage. Healing may take several months after stopping Amiodar and may sometimes not be complete.
Eye disorders
If you experience blurred vision or decreased vision, notify your doctor immediately, who will have a complete eye exam performed immediately.
If you experience damage to the optic nerve your doctor will tell you to stop taking Amiodar to avoid the possibility of losing your sight.
Children and adolescents
The safety and efficacy of amiodarone in children and adolescents has not been established. Amiodar is not recommended in these patients.
Interactions Which drugs or foods can modify the effect of Amiodar
Tell your doctor or pharmacist if you are using, have recently used or might use any other medicines.
Do not use Amiodar together with the following medicines as side effects, including potentially fatal ones, can occur:
- Antiarrhythmics (medicines used to treat heart rhythm disorders) eg. sotalol, bepridil
- Vincamine (medicine used for cerebral ischaemia)
- Some psychiatric drugs including sultopride
- Cisapride (medicine used for stomach ailments)
- Intravenous erythromycin or pentamidine (for non-oral administration) (antibiotics)
- Fluoroquinolones (antibiotics)
- Medicines for depression (monoamine oxidase inhibitors)
- Medicines for high blood pressure (beta blockers and calcium channel blockers)
- Verapamil, diltiazem (medicines that reduce heart rate) as they can cause slow heart beat (bradycardia)
- Stimulant laxatives, as they can reduce potassium levels in the blood
Tell your doctor if you are using one or more of the medicines listed below, as they will monitor you during treatment with Amiodar:
- medicines that stimulate urine production (diuretics, used to reduce swelling from fluid accumulation and reduce high blood pressure), alone or in combination
- glucocorticoid and mineralocorticoid medicines (cortisone) by mouth or by injection
- tetracosactide (hormone)
- amphotericin B (medicine against fungal infections) intravenously.
- Digitalis (heart medicine)
- Medicines that reduce blood clotting eg. dabigatran, warfarin
- Phenytoin (anti-epilepsy medicine)
- Flecainide (medicine for heart rhythm disturbances)
- Statins (medicines to lower cholesterol)
- Ciclosporin (immunosuppressant)
- Fentanyl (pain reliever)
- Lidocaine (local anesthetic)
- Tacrolimus (immunosuppressant)
- Sildenafil (erectile dysfunction medicine)
- Midazolam and triazolam (tranquilizers)
- Colchicine (gout medicine)
- Dihydroergotamine, ergotamine (medicines against circulatory disorders)
Interactions between Amiodar and other medicines can be observed for several months after stopping treatment.
If you are unsure, ask your doctor or pharmacist.
Amiodar with food and drink
The effect and toxicity of Amiodar may be increased if the fruit or grapefruit juice is ingested at the same time.
Warnings It is important to know that:
Pregnancy and breastfeeding
If you are pregnant or breast-feeding, think you may be pregnant or are planning to have a baby, ask your doctor or pharmacist for advice before taking this medicine.
Amiodar should not be used in pregnancy unless the benefit to the mother outweighs the risk to the fetus due to its effects on the fetal thyroid.
Amiodar should not be used in nursing mothers, as it passes into breast milk.
Driving and using machines
Based on the safety data of amiodarone, no influence on the ability to drive and use machines was evidenced.
Amiodar contains lactose (a milk sugar)
Amiodar tablets contain lactose: if you have been told by your doctor that you have an intolerance to some sugars, contact your doctor before taking this medicine.
Dosage and method of use How to use Amiodar: Dosage
Always take this medicine exactly as your doctor has told you. If in doubt, consult your doctor or pharmacist.
Amiodarone has very variable effects from individual to individual, for this reason the doctor will evaluate the route of administration, the starting dose and the maintenance dose based on the severity of the disease and its response.
Treatment of rhythm disturbances
The recommended dose is 600 mg (3 tablets of 200 mg) per day until a good response to treatment is achieved, on average within two weeks.
Thereafter, your doctor may reduce the dose gradually until the maintenance dose is established, which is usually between 100-400 mg (between half a tablet and 2 tablets) per day.
When it is difficult to establish a satisfactory daily maintenance dose, your doctor may prescribe discontinuous therapy (5 days a week or 2/3 weeks a month).
Preventive treatment of angina crises
Attack therapy: The recommended dose is 600 mg (3 tablets of 200 mg) per day for approximately 7 days.
Maintenance therapy: the recommended dose is 100-400 mg (between half a tablet and 2 tablets) per day or intermittently (5 days a week or 2/3 weeks a month).
Use in children and adolescents
The safety and efficacy of amiodarone in children and adolescents has not been established. Amiodar is not recommended in these patients.
If you forget to take Amiodar
Do not take a double dose to make up for a forgotten dose.
If you stop taking Amiodar
If you have any further questions on the use of this medicine, ask your doctor or pharmacist.
Overdose What to do if you have taken too much Amiodar
If you take too much Amiodar, tell your doctor immediately or go to the nearest hospital.
If you have any further questions on the use of Amiodar, ask your doctor or pharmacist.
Not much information is available regarding excessive amiodarone dosage.
There have been some reports of sinus bradycardia (slow heart rate), heart arrest, ventricular tachycardia (rapid heart beat), "torsade de pointes" (disturbances in the electrical activity of the heart), problems with blood circulation and liver damage.
Side Effects What are the side effects of Amiodar
Like all medicines, this medicine can cause side effects, although not everybody gets them and the severity may be different.
The most frequently observed undesirable effects do not justify discontinuation of treatment.
However, serious side effects have been reported, particularly affecting the lung or liver.
In any case, the doctor will decide whether to reduce the dose or discontinue treatment according to both the potential severity of the undesirable effect and the severity of the disease.
Very common side effects (may affect more than 1 in 10 people)
- Microdeposits in the cornea, usually limited to the area under the pupil. They can be accompanied by colored halos in dazzling light or blurred vision
- Appearance of spots or redness on the skin following exposure to sunlight or sunlamps
- Increased levels of transaminases in the blood (indicating liver damage)
- Nausea, vomiting
- Changes in taste
Common side effects (may affect up to 1 in 10 people)
- Slow heart rate (bradycardia)
- Itchy, reddish rash (eczema). Abnormal slate gray or bluish skin discolouration
- Poor thyroid function
- Over-functioning of the thyroid gland sometimes fatal
- Acute liver damage, with elevated blood levels of transaminases and / or yellowing of the skin, mucous membranes and eye (jaundice) accompanied by sometimes fatal liver failure
- Pulmonary toxicity (e.g. alveolar / interstitial pneumonia or fibrosis, pleurisy, obliterative bronchiolitis with organized pneumonia), sometimes fatal
- Tremor
- Nightmares
- Sleep disorders
- Constipation
Uncommon side effects (may affect up to 1 in 100 people)
- Disturbances in the electrical activity of the heart (conduction disturbances, sino-atrial block, A-V block of varying degrees)
- Onset or worsening of rhythm disturbances, sometimes followed by heart failure
- Damage to nerves and muscles reversible on stopping the medicine
- Dry mouth
Very rare side effects (may affect up to 1 in 10,000 people)
- Reduction in the number of red blood cells from destruction (haemolytic anemia)
- Reduction in the number of red blood cells from non-production (aplastic anemia)
- Low platelet count (thrombocytopenia)
- Slow heart beat (marked bradycardia) or sinus arrest
- Inflammation and / or damage of the optic nerve (neuropathy / optic neuritis) which can progress to cause blindness
- Redness of the skin during radiotherapy
- Rashes on the skin
- Inflammation with flaking of the skin (exfoliative dermatitis)
- Loss of hair and hair
- Syndrome of inappropriate antidiuretic hormone secretion (SIADH), a disease due to an excess of the hormone ADH (adiurethin) in the blood
- Chronic liver damage (pseudo-alcoholic hepatitis, cirrhosis) sometimes fatal
- Bronchospasm (asthmatic reaction)
- Severe pulmonary reactions (ADRS, adult acute respiratory distress syndrome), sometimes fatal
- Increased creatinine in the blood
- Loss of coordination of movements
- High blood pressure inside the benign skull (pseudo-tumor cerebri)
- Headache
- Inflammation of the epididymis (epididymitis), a structure over the testicle
- Impotence
- Inflammation of the vessels (veins and arteries)
Undesirable effects with frequency not known (frequency cannot be estimated from the available data)
- Inflammatory lesion (granuloma) of the bone marrow
- Alteration of the electrical activity of the heart (Torsade de pointes)
- Severe allergic reactions (anaphylactic reaction, anaphylactic shock)
- Sudden inflammation of the pancreas (acute pancreatitis)
- Severe, life-threatening skin reactions characterized by rash, skin blistering, skin peeling and pain (toxic epidermal necrolysis (TEN), Stevens-Johnson syndrome (SJS), bullous dermatitis, drug reaction with eosinophilia and systemic symptoms ( DRESS)).
- Decreased appetite
- Abnormal muscle movements, stiffness, tremor and restlessness (parkinsonism); abnormal perception of odors (parosmia)
- Confusion (delirium)
- Urticaria
- Inflammatory lesion (granuloma) of the liver
- Bleeding from the lungs
- Swelling due to fluid accumulation (edema), especially in the lower limbs and face (angioneurotic edema)
Reporting of side effects
If you get any side effects, talk to your doctor or pharmacist. This includes any possible side effects not listed in this leaflet. You can also report side effects directly via the national reporting system at www.agenziafarmaco.it/it/responsabili. By reporting side effects you can help provide more information on the safety of this medicine.
Expiry and Retention
Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date which is stated on the carton after EXP. The expiry date refers to the last day of that month.
Do not throw any medicines via wastewater or household waste. Ask your pharmacist how to throw away medicines you no longer use. This will help protect the environment.
Other information
What Amiodar contains
- The active ingredient is amiodarone hydrochloride. Each tablet contains 200 mg of amiodarone hydrochloride.
- The other ingredients are lactose monohydrate, maize starch, polyvidone, anhydrous colloidal silica, magnesium stearate.
Description of what Amiodar looks like and contents of the pack
Cardboard box containing 2 blisters of 10 tablets each.
Source Package Leaflet: AIFA (Italian Medicines Agency). Content published in January 2016. The information present may not be up-to-date.
To have access to the most up-to-date version, it is advisable to access the AIFA (Italian Medicines Agency) website. Disclaimer and useful information.
01.0 NAME OF THE MEDICINAL PRODUCT
AMIODAR TABLETS
02.0 QUALITATIVE AND QUANTITATIVE COMPOSITION
One tablet contains:
Active principle: 200 mg of amiodarone hydrochloride.
For the full list of excipients, see section 6.1
03.0 PHARMACEUTICAL FORM
Divisible tablets.
04.0 CLINICAL INFORMATION
04.1 Therapeutic indications
Treatment and prevention of severe rhythm disturbances resistant to other specific therapies: supraventricular tachycardias (paroxysmal and non-paroxysmal), atrial extrasystoles, atrial flutter and fibrillation.
Reciprocating supraventricular paroxysmal tachycardias as in the course of Wolff-Parkinson-White Syndrome. Ventricular extrasystoles and tachycardias.
Prophylactic treatment of angina pectoris crises.
04.2 Posology and method of administration
Amiodarone has peculiar pharmacological characteristics (50% oral absorption, extensive tissue distribution, slow elimination, delayed oral therapeutic response) widely variable from individual to individual; for this reason the route of administration, the initial and maintenance dosage must be evaluated case by case, adapting them to the severity of the disease and the clinical response.
The recommended dosages are:
Treatment of rhythm disturbances:
The recommended starting average dosage is 600 mg per day until a good therapeutic response is achieved, on average within two weeks. Thereafter, the dose can be gradually reduced until the maintenance dose is usually established between 100-400 mg per day.
When it is difficult to establish a satisfactory daily maintenance dose, discontinuous therapy can be used (eg 2/3 weeks per month or 5 days per week).
Prophylactic treatment of angor crises:
• attack: 600 mg per day for about 7 days
• maintenance: 100-400 mg per day or intermittently (5 days a week or 2/3 weeks a month).
Concomitant therapy
For patients taking amiodarone concomitantly with HMG-CoA reductase inhibitors (statins), see sections 4.4 and 4.5.
04.3 Contraindications
• Hypersensitivity to the active substance, to iodine or to any of the excipients.
• Sinus bradycardias; sinoatrial block; severe conduction disturbances, without electro-stimulator (severe atrioventricular blocks, bi- or trifascicular blocks).
• Sinus disease without electro stimulator (risk of sinus arrest).
• Combination with drugs capable of causing "torsade de pointes" (see section 4.5).
• Distyroidism or thyroid antecedents. In doubtful cases (uncertain background, family history of thyroid), perform a thyroid function test before treatment.
• Pregnancy, except in exceptional cases (see section 4.6).
• Breastfeeding (see section 4.6)
04.4 Special warnings and appropriate precautions for use
Special warnings
Amiodarone can cause collateral manifestations of varying frequency and severity.
The most frequently observed manifestations do not justify treatment discontinuation (see section 4.8). However, serious side effects have been reported, particularly in the lung or chronic hepatitis injuries.
Pulmonary toxicity
Pulmonary toxicity related to the intake of amiodarone is a frequent and serious adverse reaction that can occur in up to 10% of patients and that can be fatal in about 8% of affected patients, mainly due to a lack of diagnosis. The time of onset of the reaction during therapy varies from a few days to a few months or years of intake; in some cases the onset may also occur after a certain period of time from the suspension of treatment.
However, the risk of toxicity does not make the risk / benefit ratio of amiodarone unfavorable, which maintains its usefulness. However, the utmost attention must be paid to immediately identify the first signs of pulmonary toxicity, especially in patients suffering from cardiomyopathy and severe coronary heart disease. in which such identification can be more problematic.
The risk of amiodarone pulmonary toxicity increases with doses above 400 mg / day, but can also occur at low doses taken for less than 2 years.
Pulmonary toxicity is manifested by pulmonary alveolitis, pneumonia, interstitial pneumonia, pulmonary fibrosis, bronchial asthma.Patients who develop pulmonary toxicity often present with non-specific symptoms, such as non-productive cough, dyspnoea, fever, and weight loss.
All these symptoms can be masked by the pathology for which amiodarone is indicated, and can be considerably serious in patients over 70 years of age, who usually have reduced functional capacity or pre-existing cardiac diseases. ?respiratory. Early diagnosis by means of pulmonary radiographic control and possibly the necessary clinical and instrumental investigations, is of crucial importance as pulmonary toxicity is highly reversible, especially in the forms of obliterating bronchiolitis and pneumonia. Pulmonary symptoms and objectivity must therefore be checked periodically, and therapy must be suspended in the event of suspected pulmonary toxicity, taking into account cortisone therapy: symptoms usually regress within 2-4 weeks of discontinuing amiodarone. In some cases, pulmonary toxicity can manifest itself late, even weeks after the discontinuation of therapy: subjects with suboptimal organic functions, who could eliminate the drug more slowly, must therefore be carefully monitored.
In any case, the reduction of the dosage or the suspension of the treatment will have to be considered in function of both the potential severity of the side effect and the severity of the cardiac form in progress.
The drug should therefore be used only after having carefully evaluated the patient's condition in order to assess whether the expected benefits compensate for the hypothetical disadvantages; furthermore, the patient must be carefully monitored from a clinical and laboratory point of view in order to be able to detect adverse manifestations at their first signs and adopt suitable measures.
Cardiac disorders (see section 4.8)
The pharmacological action of amiodarone causes electrocardiographic changes: QT prolongation (related to a lengthening of repolarization), with the possible appearance of U waves. However, these are not signs of toxicity.
The slowing of the heart rate may be more pronounced in elderly patients.
Treatment should be discontinued if 2nd or 3rd degree A-V block, sinoatrial block, or bifascicular block occurs.
There have been reports of new arrhythmias or worsening of treated arrhythmias, sometimes fatal. It is important, but difficult, to differentiate a loss of drug efficacy from a proarrhythmic effect, in any case this is associated with a worsening of the heart condition. Proarrhythmic effects are reported more rarely with amiodarone than with other antiarrhythmics and generally occur in the context of drug interactions and / or electrolyte disturbances (see sections 4.5 and 4.8).
In case of concomitant prescription of other cardiological drugs, ensure that there are no known drug interactions (see section 4.5).
Due to the reduced negative inotropic effect, amiodarone can be used orally in case of heart failure.
Hyperthyroidism (see sections 4.4 "precautions for use" and 4.8)
It can occur during treatment with amiodarone or up to several months after its discontinuation. Clinical signs, usually mild, such as weight loss, onset of arrhythmia, angina, congestive heart failure should alert the physician. The diagnosis is supported by a clear decrease in the serum level of ultrasensitive TSH (usTSH). In this case, amiodarone treatment should be discontinued. Recovery is generally achieved within a few months of stopping treatment; clinical recovery precedes normalization of thyroid function tests. Severe cases, with clinical manifestation of thyrotoxicity, sometimes fatal, require emergency therapeutic intervention. Treatment must be adapted. in the individual case: antithyroid drugs (which may not always be effective) and possible corticosteroid therapy.
Hepatic disorders (see section 4.8)
Close monitoring of liver function (transaminases) is recommended at the initiation of amiodarone therapy, and regularly during treatment. Acute liver disorders (including severe hepatocellular insufficiency or hepatic insufficiency, sometimes fatal) and chronic liver disorders may occur with amiodarone orally and intravenously and within the first 24 hours of IV administration. Therefore, the amiodarone dose should be reduced or treatment discontinued if the transaminase elevation is greater than 3 times the upper limit of normal.
The clinical and biological signs of chronic liver disorders due to oral amiodarone may be minimal (hepatomegaly, transaminase elevations up to 5 times the value corresponding to the upper limit of normal) and reversible on discontinuation of treatment, however cases have been reported. with a fatal outcome.
In case of hepatomegaly or suspected cholestasis, the drug should be promptly discontinued and the patient undergo ultrasound control. For these reasons the drug cannot be used in patients with evident clinical and laboratory signs of active liver disease; in milder cases it can be used only when indispensable and must be suspended when a worsening of liver damage occurs.
Neuromuscular disorders (see section 4.8)
Amiodarone can induce peripheral sensorimotor neuropathy and / or myopathy. Healing is usually achieved within several months after stopping amiodarone, but it can sometimes be incomplete.
Eye disorders (see section 4.8)
In the event of visual blurring or decreased visual acuity, a complete ophthalmological examination including fundoscopy should be performed immediately.
The onset of optic neuropathy and / or optic neuritis requires discontinuation of amiodarone to avoid potential progression to blindness.
Drug interactions (see section 4.5)
The concomitant use of amiodarone with the following drugs is not recommended: beta blockers, calcium channel blockers that reduce heart rate (verapamil, diltiazem), stimulant laxatives that can cause hypokalaemia.
Lactose
Each tablet contains 71 mg of lactose, therefore according to the recommended dosage the maximum amount of lactose that can be taken with AMIODAR is 213 mg per day. Patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency, or glucose-galactose malabsorption should not take this medicine.
Precautions for use
Since undesirable effects (see section 4.8) are generally dose-dependent, the lowest effective maintenance dose should be administered.
Advise patients to avoid sun exposure and to use protective measures during treatment (see section 4.8).
Monitoring (see sections 4.4 "Special warnings" and 4.8)
Before initiating treatment with amiodarone it is recommended to perform an ECG and measure serum potassium. It is recommended to monitor transaminases (see section 4.4 "Special warnings") and ECG during treatment. In addition, as amiodarone can cause hypothyroidism or hyperthyroidism, it is recommended that clinical and biological monitoring (usTSH) be performed prior to initiation and during treatment, and for several months thereafter, particularly in those patients with a personal history of thyroid disorders or in the elderly. the suspension. In the event of suspected thyroid dysfunction, serum usTSH levels should be measured.
Particularly in the context of chronic administration of antiarrhythmic drugs, there have been reports of increased ventricular defibrillation and / or pacing threshold of the pacemaker or implantable cardioversor defibrillator device, which can potentially modify its efficacy. verification of device operation before and during amiodarone therapy.
Thyroid abnormalities (see section 4.8).
The presence of iodine in the amiodarone molecule can interfere with the fixation of radioactive iodine. However, the thyroid function tests (free T3, free T4, ultra-sensitive TSH) remain interpretable.
Amiodarone inhibits the peripheral conversion of thyroxine (T4) to triiodothyronine (T3) and can cause isolated biochemical changes (serum increase in free T4, while free T3 decreases slightly or even remains at normal levels) in clinically euthyroid patients. In such cases there is no reason to discontinue amiodarone treatment.
Suspicion of hypothyroidism should be considered if the following generally mild clinical signs occur: weight gain, cold intolerance, reduced activity, excessive bradycardia. Diagnosis is supported by a clear increase in serum usTSH. Euthyroidism usually returns within 1 to 3 months after stopping treatment. In life-threatening situations, amiodarone therapy can be continued in combination with L-thyroxine. The dose of L-thyroxine is adjusted according to the TSH levels.
Pediatric patients
The safety and efficacy of amiodarone have not been demonstrated in these patients. Therefore it is not recommended for use in these patients.
Anesthesia (see sections 4.5 and 4.8)
Before surgery, the anesthetist should be informed that the patient is being treated with amiodarone.
Association with statins
It is recommended that a statin not metabolised by CYP 3A4 be used when co-administered with amiodarone (see section 4.5).
04.5 Interactions with other medicinal products and other forms of interaction
Contraindicated associations
- Drugs capable of causing "torsade de pointes" (see section 4.3):
• antiarrhythmics such as those of Class IA, sotalol, bepridil.
• non-antiarrhythmics such as vincamine, some neuroleptic drugs including sultopride, cisapride, erythromycin E.V., pentamidine (for parenteral administration), as there may be an increased risk of life-threatening "torsade de pointes".
- MAOIs drugs
Associations not recommended
- Beta-blockers and calcium channel blockers that reduce heart rate (verapamil, diltiazem) due to the possibility of automatism (excessive bradycardia) and conduction disorders.
- Stimulant laxatives: due to the appearance of a possible hypokalaemia, consequently increasing the risk of "torsade de pointes"; other types of laxatives must therefore be used.
- Fluoroquinolones should be avoided in patients on amiodarone therapy.
Associations requiring caution
- Drugs capable of causing hypokalemia:
• diuretics capable of causing hypokalaemia, alone or in combination
• systemic glucocorticoids and mineralocorticoids, tetracosactide
• amphotericin B via the E.V.
Hypokalaemia should be prevented (and corrected), QT interval monitored, and antiarrhythmics should not be administered in the event of "torsade de pointes" (ventricular pacing should be initiated; IV magnesium may be used).
- Oral anticoagulants:
Amiodarone increases warfarin concentrations by inhibition of cytochrome P450 2C9. The combination of warfarin and amiodarone may potentiate the effect of the oral anticoagulant, thus increasing the risk of bleeding. It is necessary to monitor the prothrombin levels more regularly and to adjust the dosage of the anticoagulants both during treatment with amiodarone and after treatment. its interruption.
- Digital
Disturbances in automatism (excessive bradycardia) and in atrioventricular conduction (synergistic action) may occur; in addition, an increase in plasma digoxin concentrations due to a decrease in digoxin clearance is possible.
Electrocardiographic and plasma digoxin levels should therefore be monitored; and patients should be monitored for clinical signs of digitalis toxicity. Digitalis dosage may need to be adjusted.
- Phenytoin
Amiodarone increases plasma concentrations of phenytoin by inhibition of cytochrome P450 2C9. The combination of phenytoin with amiodarone may therefore lead to phenytoin overdose resulting in neurological symptoms. Clinical monitoring should be performed and the dosage of phenytoin should be reduced as soon as symptoms of overdose appear; plasma phenytoin levels should be determined. .
- Flecainide
Amiodarone increases plasma concentrations of flecainide by inhibition of cytochrome CYP 2D6. Then the flecainide dosage should be adjusted.
- Drugs metabolised by cytochrome P450 3A4:
When these drugs are co-administered with amiodarone, an inhibitor of CYP 3A4, an increase in their plasma concentrations may occur which may lead to an increase in their toxicity.
• Statins: The risk of muscle toxicity is increased by the concomitant administration of amiodarone with statins metabolised by CYP 3A4 such as simvastatin, atorvastatin and lovastatin. It is recommended that a statin not metabolised by CYP 3A4 be used when co-administered with amiodarone.
• Ciclosporin: Combination with amiodarone may increase plasma levels of cyclosporine. The dosage should be adjusted.
• Fentanyl: Combination with amiodarone may enhance the pharmacological effects of fentanyl and increase its risk of toxicity.
• Other drugs metabolised by CYP 3A4: lidocaine, tacrolimus, sildenafil, midazolam, triazolam, dihydroergotamine, ergotamine.
General anesthesia (see sections 4.4 "precautions for use" and 4.8)
Potentially serious complications have been reported in patients undergoing general anesthesia: bradycardia (insensitive to atropine), hypotension, conduction disturbances, decreased cardiac output.
Very rare cases of severe respiratory complications (adult acute respiratory distress syndrome), sometimes fatal, have been observed, generally in the period immediately following surgery. This may be related to a possible interaction with a high concentration of oxygen.
04.6 Pregnancy and breastfeeding
Pregnancy
Amiodarone is contraindicated in pregnancy, unless the benefit outweighs the risk, due to its effects on the fetal thyroid.
Feeding time
Amiodarone is contraindicated in nursing mothers as it is excreted in breast milk in significant quantities.
04.7 Effects on ability to drive and use machines
Based on the safety data of amiodarone, no influence on the ability to drive and use machines was evidenced.
04.8 Undesirable effects
The following adverse reactions are classified by system organ class and frequency using the following convention: very common (> = 10%), common (> = 1% and = 0.1% and = 0.01% and
Disorders of the blood and lymphatic system
Very rare:
• Hemolytic anemia
• Aplastic anemia
• Thrombocytopenia
Cardiac pathologies
Common:
bradycardia, usually moderate and dose-dependent.
Uncommon:
• conduction disturbances (sino-atrial block, varying degrees of A-V block) (see section 4.4 "precautions for use").
• onset or worsening of arrhythmia, sometimes followed by cardiac arrest (see section 4.4 "Special warnings" and 4.5).
- Very rare:
Marked bradycardia or sinus arrest in patients with sinus node dysfunction and / or in elderly patients.
Ocular pathologies
- Very common
Corneal microdeposits, generally limited to the area under the pupil. They can accompany the perception of colored halos in dazzling light or blurred vision. Corneal microdeposits are made up of complex lipid deposits and are reversible after discontinuation of treatment.
- Very rare
Neuropathy / optic neuritis which can progress to blindness (see section 4.4 "Special warnings").
Skin and subcutaneous tissue disorders
- Very common
Photosensitization (see section 4.4 "precautions for use")
- Common
Skin pigmentations of slate gray or bluish color in case of prolonged treatment with high daily dosages; these pigmentations disappear slowly after discontinuation of treatment.
- Very rare
• erythema during radiotherapy
• generally non-specific skin rashes
• exfoliative dermatitis
• alopecia
- Frequency not known
Urticaria
Endocrine disorders (see sections 4.4 "Special warnings" and 4.4 "Precautions for use")
- Common:
• Hypothyroidism
• Hyperthyroidism sometimes fatal
- Very rare:
Syndrome of Inappropriate Antidiuretic Hormone Secretion (SIADH)
Hepatobiliary disorders (see sections 4.4 "Special warnings" and 4.4 "Precautions for use")
- Very common:
isolated increase in serum transaminases, usually moderate (1.5 to 3 times normal). at the start of therapy, they can return to normal with dose reduction or even spontaneously.
- Common:
Acute liver disease with elevated serum transaminase levels and / or jaundice, including hepatic failure sometimes fatal.
- Very rare:
Chronic liver diseases (pseudo-alcoholic hepatitis, cirrhosis) sometimes fatal.
Respiratory, thoracic and mediastinal disorders (see section 4.4 "Special warnings")
- Severe pulmonary toxicity, sometimes fatal, can occur in about 10% of patients, especially if not diagnosed promptly. This toxicity includes pulmonary alveolitis, pneumonia, asthma symptoms, lipoid pneumonia and pulmonary fibrosis. Pulmonary toxicity, cough and dyspnoea may be accompanied by radiographic and functional signs of interstitial pneumonia (altered alveolar-capillary diffusion); the emergence of these clinical signs requires the suspension of therapy and the administration of corticosteroid drugs.This symptomatology can also manifest itself late after discontinuation of therapy: careful and prolonged monitoring of the patient is therefore required in order to identify possible alterations in pulmonary function.
• In patients who experience dyspnoea on exertion, alone or associated with a deterioration of the general state (fatigue, weight loss, fever) a chest X-ray should be performed.
• Lung disorders are usually reversible after early discontinuation of amiodarone therapy. Clinical signs generally resolve within 3-4 weeks, followed by slower improvement in lung function and radiological picture (several months). Therefore, amiodarone therapy should be discontinued and corticosteroid therapy should be considered.
- Common:
pulmonary toxicity (alveolar / interstitial pneumonia or fibrosis, pleurisy, bronchiolitis obliterans with organized pneumonia / BOOP), sometimes fatal (see section 4.4 "Special warnings").
- Very rare:
• bronchospasm in patients with severe respiratory insufficiency, and especially in asthmatic patients
• adult acute respiratory distress syndrome, sometimes fatal, usually immediately after surgery (possible interaction with a "high concentration of oxygen)" (see sections 4.4 "Special warnings", 4.4 "precautions for use" and 4.5) .
- Frequency not known: pulmonary haemorrhage
Disorders of the immune system
- Frequency not known: angioneurotic edema (Quincke's edema)
Gastrointestinal disorders
- Very common:
benign gastrointestinal disturbances (nausea, vomiting, dysgeusia) which generally occur with the loading dose and resolve with dose reduction.
Diagnostic tests
-Very rare:
increase in blood creatinine.
Nervous system disorders
- Common:
• extrapyramidal tremor.
• nightmares.
• sleep disorders.
- Uncommon:
• peripheral sensorimotor neuropathy and / or myopathy, usually reversible on discontinuation of the drug (see section 4.4 "Special warnings").
- Very rare:
• cerebellar ataxia.
• benign intracranial hypertension (pseudo-tumor cerebri).
• headache.
Diseases of the reproductive system and breast
- Very rare:
• epididymitis.
• impotence.
Vascular pathologies
- Very rare:
vasculitis.
04.9 Overdose
Not much information is available regarding acute overdose with amiodarone. A few cases of sinus bradycardia, cardiac arrest, ventricular tachycardia, "torsade de pointes", circulatory failure and liver damage have been reported.
Treatment must be symptomatic. Amiodarone and its metabolites are not dialyzable.
05.0 PHARMACOLOGICAL PROPERTIES
05.1 Pharmacodynamic properties
Pharmacotherapeutic group: Cardiovascular system, antiarrhythmics, class III. ATC code: C01BD01
Anti-arrhythmic properties:
- Phase 3 elongation of the action potential of the cardiac fiber mainly due to a decrease in potassium current (Class III according to the classification of Vaughan Williams); this elongation is not correlated with heart rate.
- Reduced sinus automaticity, leading to bradycardia, insensitive to the administration of atropine.
- Non-competitive alpha- and beta-adrenergic inhibition.
- Slowing in sinoatrial, atrial and nodal conduction, which is more pronounced when the heart rate is high.
- No changes in intraventricular conduction.
- At the atrial, nodal and ventricular level: increase in the refractory period and decrease in excitability of the myocardium.
- Slowing of conduction and prolongation of refractory periods in accessory atrioventricular tracts.
Anti-ischemic properties:
- Moderate drop in peripheral resistance and decrease in heart rate with consequent reduction in oxygen requirements.
- Non-competitive antagonism for alpha- and beta-adrenergic receptors.
- Increased coronary output due to a direct effect on the smooth muscle of the myocardial arteries.
- Maintenance of cardiac output due to decreased aortic pressure and peripheral resistance.
Other:
- No significant negative inotropic effects.
05.2 Pharmacokinetic properties
After oral administration, amiodarone is slowly and variably absorbed.
Amiodarone has a very large but variable volume of distribution due to extensive accumulation in various districts (adipose tissue, highly perfused organs such as the liver, lungs and spleen).
The oral bioavailability varies between 30 and 80%, depending on the individual patient (the mean value is about 50%). After single administration, peak plasma concentration is reached after 3-7 hours. Therapeutic effects are obtained. usually after a week (a few days to two weeks) depending on the loading dose.
Amiodarone has a long half-life and shows considerable individual variability (from 20 to 100 days). During the first days of therapy, the drug accumulates in almost all tissues, especially adipose tissue. Elimination occurs after a few days. and steady-state plasma concentration is achieved between one and several months, depending on the individual patient.
Considering the above characteristics, loading doses must be used to rapidly obtain the tissue levels necessary to have a therapeutic effect.
Each 200 mg dose of amiodarone contains 75 mg of iodine, of which 6 mg detaches from the molecule as free iodine. Amiodarone is mainly excreted via the biliary and faecal routes. Renal excretion is negligible: this allows the administration of standard doses in patients with renal insufficiency.
After discontinuation of treatment, elimination continues for several months; therefore, the persistence of the pharmacodynamic effect from 10 days to one month should be taken into account.
05.3 Preclinical safety data
Acute toxicity: LD50 in rat 170 mg / kg E.V.,> 3000 mg / kg os, in mice 450 mg / kg i.p.,> 3000 mg / kg os, in beagle dog 85-150 mg / kg E.V.
Chronic toxicity: no mortality, weight loss or changes in biological parameters were detected at oral doses up to 37.5 mg / kg / day (4 weeks) and 16 mg / kg / day (52 weeks) in rats and up to to 12.5 mg / kg / day in dogs.
Teratogenesis: investigations carried out in rats (100 mg / kg / day) and rabbits (75 mg / kg / day) did not reveal any signs of fetal toxicity.
06.0 PHARMACEUTICAL INFORMATION
06.1 Excipients
Lactose monohydrate, corn starch, polyvidone, anhydrous colloidal silica, magnesium stearate.
06.2 Incompatibility
There are no known incompatibilities.
06.3 Period of validity
3 years.
06.4 Special precautions for storage
This medicine does not require any special storage conditions.
06.5 Nature of the immediate packaging and contents of the package
Cardboard box containing 2 blisters of 10 tablets each.
06.6 Instructions for use and handling
No special instructions.
07.0 MARKETING AUTHORIZATION HOLDER
SIGMA-TAU Industrie Farmaceutiche Riunite S.p.A.
Viale Shakespeare, 47 -00144 Rome
08.0 MARKETING AUTHORIZATION NUMBER
A.I.C. n. 022033031
09.0 DATE OF FIRST AUTHORIZATION OR RENEWAL OF THE AUTHORIZATION
Authorization: 24/02/1971
Renewal: 01.06.2005
10.0 DATE OF REVISION OF THE TEXT
June 2010
