Presentation and Status in Health Basket
30 X 200 mg
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.
Coronary insufficiency arrhythmias resistant to other treatments.
– Sinus bradycardia and sinoatrial heart block without pacemaker. – Sinus node disease (Sick sinus syndrome) without a pacemaker (risk of sinus arrest).
– Severe atrioventricular conduction disorders without a pacemaker.
– Thyroid dysfunction. Thyroid function tests should be performed in all patients prior to therapy.
– Known hypersensitivity to iodine, amiodarone or to one of the excipients.
– pregnancy, unless exceptional circumstance .
– Breast-feeding women.
– Combination with medicinal products liable to induce torsades de pointes.
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 established. Therefore, its use in paediatric is not recommended.
• Patients should be instructed to avoid exposure to sun and to use protective measures during therapy.
• Concomitant use of amiodarone is not recommended with the following drugs: beta-blockers, heart rate lowering calcium channel inhibitors (verapamil, diltiazem), stimulating laxative agents which may cause hypokalaemia.
• Amiodarone can cause serious adverse reactions affecting the eyes, heart, lung, liver, thyroid gland, skin and peripheral nervous system. Because these reactions may be delayed, patient on long-term treatment should be carfuly supervised. As undesirable effects are usually dose-related, the minimum effective maintenance dose should be given.
• 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, sometimes fatal, have been reported. It is important, but difficult, to differentiate a lack of efficacy of the drug from a proarrhythmic effect, whether or not this is associated with a worsening of the cardiac condition.
Proarrhythmic effects generally occur in the context of QT prolonging factors such as drug interactions and/or electrolytic disorders. Despite QT interval prolongation, amiodarone exhibits a low torsadogenic activity.
• 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, AmioCard 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.
• AmioCard 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, AmioCard 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.
See prescribing information for full details.
– Very common: Corneal microdeposits usually limited to then area under the pupil, which are usually only discernable by slit-lamp examinations. They may be associated with colored halos in dazzling light or blurred vision. Corneal microdeposits consist of complex lipid deposits and are reversible following discontinuation of treatment.
– Very rare: Optic neuropathy/neuritis that may progress to blindness
– Very common: photosensitivity.
– Common: Slate grey or bluish pigmentations of light-exposed skin, particularly the face in case of prolonged treatment with high daily dosages; such pigmentations slowly disappear following treatment discontinuation.
Very rare: – erythema during the course of radiotherapy,
– skin rashes, generally not very specific,
– exfoliative dermatitis,
– hair loss (alopecia).
Not known: Urticaria.
Common: Hypothyroidism, Hyperthyroidism (sometimes fatal).
Very rare: syndrome of inappropriate antidiuretic hormone secretion (SIADH)
Common: Pulmonary toxicity (hypersensitivity pneumonitis , alveolar/interstitial pneumonitis or fibrosis, pleuritis, bronchiolitis obliterans organizing pneumonia/BOOP), sometimes fatal
Very rare: – Bronchospasm in patients with severe respiratory failure and especially, in asthmatic patients.
– Adult acute respiratory distress syndrome, sometimes fatal, sometimes immediately following surgery (a possible interaction with high doses of oxygen).
Not known: Pulmonary haemorrhage
Common: – extra-pyramidal Tremor,
– sleep disorders
Uncommon: Peripheral sensorimotor neuropathy and/or myopathy, usually reversible on withdrawal of the drug.
Very rare: – Cerebellar ataxia,
– Benign intracranial hypertension (pseudo-tumor cerebri),
– Very common: Generally moderate and isolated elevation in transaminases (1.5 to 3 times normal) occurring at the beginning of therapy. It may return to normal with dose reduction or even spontaneously.
– Common: Acute liver damage with elevated blood transaminases and/or jaundice, including hepatic failure, occasionally with a fatal outcome
– Very rare: chronic liver disease (pseudo alcoholic hepatitis, cirrhosis) (sometimes fetal)
– Common: generally moderate, dose-dependent bradycardia.
– Uncommon: conduction disturbances (sino-atrial block, atrioventricular block of varying degrees). Onset or worsening of arrhythmia, sometimes followed by cardiac arrest.
– Very rare: marked bradycardia or sinus arrest in patients with sinus node dysfunction and/or in eldery patients.
Not known: Torsade de pointes
– Very common: benign gastrointestinal disturbances (nausea, vomiting, dysgeusia), usually occurring during initial treatment and disappearing when the dosage is reduced.
Effects on the reproductive system:
– Very rare: epididymitis, epididymo-orchitis, impotence
– Very rare: Vasculitis
Abnormal laboratory findings:
– Very rare: Increased serum creatinine
Effects on the blood and lymphatic system:
– Very rare: thrombocytopenia, haemolytic anemia, aplastic anaemia.
In patients taking amiodarone there have been incidental findings of bone marrow granulomas. The clinical significance of this is unknown.
Immune system disorder:
Not Known: Angioedema (there have been some reports of angioedema, although exact frequencies are not known)
Not Known: Granuloma, including bone marrow granuloma.
Combination with medicinal products liable to induce torsades de pointes:
– class Ia antiarrhythmics (e.g quinidine, hydroquinidine, disopyramide, bepridil)
– class III antiarrhythmics (e.g sotalol, dofetilide, ibutilide)
– Non-antiarrhythmic agents such as vincamine, some neuroleptic agents, cisapride
– Intravenous erythromycin, co-trimoxazole or pentamidine injection
– Some anti-psychotics (e.g Chlorpromazine, Thioridazine, Fluphenazine, Pimozide Haloperidol, Amisulpiride and Sertindole)
– Lithium and tricyclic anti-depressants (e.g Doxepin, Maprotiline and Amitriptyline)
– Certain antihistamines (e.g Terfenadine, Astemizole and Mizolastine)
– Anti-malarials (e.g Quinie, Mefloquine, Chloroquine and Halofantrine)
Drugs prolonging QT:
Co-administration of amiodarone with drugs known to prolong the QT interval must be based on a careful assessment of the potential risks and benefits for each patient since the risk of torsade de pointes may increase and patients should be monitored for QT prolongation.
Fluoroquinolones should be avoided in patients receiving amiodarone.
Drugs lowering heart rate or causing automaticity or conduction disorders:
Combined therapy with these drugs is not recommended.
Beta-blockers and heart rate lowering calcium channel inhibitors (Verapamil, diltiazem) as potentiation of negative chronotropic properties and conduction slowing effects may occur.
Agents which may induce hypokalaemia:
– Combined therapy with the following drugs is not recommended.
Stimulating laxative agents which may cause hypokalaemia thus increasing the risk of torsade de pointes; other types of laxatives should be used.
– Caution should be exercised when using the following drugs which may also cause hypokalaemia and/or hypomagnesaemia in combination with amiodarone:
Diuretics inducing hypokalaemia, either alone or combined
Systemic corticosteroids (gluco-, mineralo-), tetracosactide
Amphotericin B (IV)
It is necessary to prevent the onset of hypokalaemia (and to correct hypokalaemia); the QT interval should be monitored and, in case of torsade de pointes, anti-arrhythmic agents should not be given (ventricular pacing should be initiated; IV magnesium may be used).
Caution is advised in patients undergoing general anaesthesia, or receiving high dose oxygen therapy.
Potentially severe complications have been reported in patients undergoing anaesthesia: bradycardia (unresponsive to atropine), hypotension, conduction disorders, decreased cardiac output.
Very rare cases of severe respiratory complications (adult acute respiratory distress syndrome), sometimes fatal, have been observed usually in the period immediately following surgery. A possible interaction with a high oxygen concentration may be implicated.
Effect of amiodarone on other medicinal products
Amiodarone and /or its metabolite, desethylamiodarone, inhibit CYP1A1, CYP1A2, CYP3A4, CYP2C9, CYP2D6 and P-glycoprotein and may increase exposure of their substrates.
Due to the long half-life of amiodarone, interactions may be observed for several months after discontinuation of amiodarone.
PgP substrates: Amiodarone is a PgP inhibitors. Co administration with PgP substrates is expected to result in an increase of their exposure.
– Digitalis: Disturbances in automaticity (excessive bradycardia) and atrioventicular conduction (synergistic action) may occur; in addition, an increase in plasma digoxin concentrations is possible due to the decrease in digoxin clearance.
ECG, and digoxin plasma levels should be monitored, and patients should be observed for clinical signs of digitals toxicity. It may be necessary to adjust dosage of digitals treatment.
– Dabigatran: Caution should be exercised when amiodarone is co administered with dabigatran due to the risk of bleeding. It may be necessary to adjust the dosage of dabigatran as per its label.
CYP2C9 substrates: Amiodarone raises the concentrations of CYP2C9 substrates such as warfarin or phenytoin by inhibition of cytochromne P450 2C9.
– Warfarin: The combination of warfarin with amiodarone may exacerbate the effect of the oral anticoagulant thus increasing the risk of bleeding. It is necessary to monitor prothrombin (INR) levels more regulary and to adjust oral doses of anticoagulant agents both during treatment with amiodarone and after discontinuation of amiodarone treatment.
– Phynytoin: The combination of phynytoin with amiodarone may lead to phynytoin overdosage, resulting in neurological signs. Clinical monitoring should be undertaken and phynytoin dosage should be reduced as soon as overdosage signs appear; phynytoin plasma levels should be determined.
– Flecainide: Amiodarone raises plasma concentrations of flecainide by inhibition of cytochrome CYP2D6.
Therefore, flecainide dosage should be adjusted.
CYP P450 3A4 substrates: When such drugs are co-administered with amiodarone, an inhibitor of CYP 3A4, this may result in a higher level of their plasma concentrations, which may lead to a possible increase in their toxicity:
– Cyclosporin: its combination with amiodarone may increase cyclosporin plasma levels. Dosage should be adjusted.
– Fentanyl: its combination with amiodarone may enhance the pharmacologic effects of fentanyl and increase the risk of its toxicity.
– Statins: The risk of muscular toxicity is increased by concomitant administration of amiodarone with statins metabolized by CYP 3A 4 such as simvastatin, atorvastatin and lovastatin. It is recommended to use a statin not metabolized by CYP 3A4 when given with amiodarone.
– Other drugs metabolized by CYP 3A4: lidocaine, tacrolimus, sildenafil, midazolam, triazolam, dihydroergotamine, ergotamine, colchicine.
Metadone: Increased risk of ventricular arrhythmias,,particularly torsades de pointes. ECG and clinical monitoring.
Orlistat: Risk of a reduction in plasma concentrations of amiodarone and of its active metabolism.
Clinical monitoring and, if necessary, ECG monitoring.
CYP3A4 inhibitors and CYP2C8 inhibitors may have a potential to inhibit amiodarone metabolism and to increase its exposure.
It is recommended to avoid CYP 3A4 inhibitors (e.g. grapefruit juice and certain medicinal products) during treatment with amiodarone.
OTHER DRUG INTERACTIONS WITH AMIOCARD: Co-administration of amiodarone with sofosbuvir alone or in combination with another HCV direct acting antiviral (such as daclatasvir, simeprevir or ledipasvir) is not recommended as it may lead to serious symptomatic bradycardia.
If co-administration cannot be avoided, cardiac monitoring is recommended.
Pregnancy and Lactation
Pregnancy: In view of its effects on the fetal thyroid gland, amiodarone is contraindicated during pregnancy, except if the benefits outweigh the risks.
Lactation: Amiodarone is excreted in breast milk in significant quantities and is therefore contraindicated in breast-feeding mothers.
There is little documentation available on the acute administration of high doses of amiodarone. A few cases of sinus bradycardia, ventricular tachycardia, heart block, , torsades de pointes, circulatory failure 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. If bradycardia occurs beta-adrenostimulants or glucagon may be given. Spontaneously resolving attacks of ventricular tachycardia may also occur.
Amiodarone and its metabolites are not dialysable.