Consumer medicine information

Amiodarone Sandoz

Amiodarone hydrochloride


Brand name

Amiodarone Sandoz

Active ingredient

Amiodarone hydrochloride




Consumer medicine information (CMI) leaflet

Please read this leaflet carefully before you start using Amiodarone Sandoz.

What is in this leaflet

This leaflet answers some common questions about Amiodarone Sandoz.

It does not contain all the available information. It does not take the place of talking to your doctor or pharmacist.

All medicines have risks and benefits. Your doctor has weighed the risk of you taking Amiodarone Sandoz against the benefits it is expected to have for you.

If you have any concerns about taking this medicine, ask your doctor or pharmacist.

Keep this leaflet with the medicine. You may need to read it again.

What Amiodarone Sandoz is used for

Amiodarone Sandoz is used to control a fast or irregular heart beat.

It contains the active ingredient amiodarone hydrochloride. Amiodarone hydrochloride belongs to a group of medicines called antiarrhythmics.

It works by lengthening the gap between one heart beat and the next, thus helping to bring the heart rate to a slower and more regular pace.

Ask your doctor if you have any questions about why this medicine has been prescribed for you.

This medicine is available only with a doctor's prescription.

Amiodarone Sandoz is not recommended for children.

There is no evidence that this medicine is addictive.

Before you take Amiodarone Sandoz

When you must not take it

Do not take Amiodarone Sandoz if you have an allergy to:

  • amiodarone hydrochloride, the active ingredient, or iodine, or any of the inactive ingredients mentioned at the end of this leaflet under Product Description
  • any other similar medicines.

Symptoms of an allergic reaction include:

  • shortness of breath
  • wheezing or difficulty breathing
  • swelling of the face, lips, tongue or other parts of the body
  • rash, itching or hives on the skin.

Do not take this medicine if you have or have had any of the following medical conditions:

  • thyroid problems
  • heart problems that may cause you to faint. If you have a pacemaker, your doctor may allow the use of it.
  • severe breathing problems
  • low blood pressure
  • heart disease or failure
  • shock
  • other heart conditions.

Do not take this medicine if you are taking MAO inhibitors (a type of medicine used to treat depression).

Do not take this medicine if you are pregnant or are thinking of getting pregnant. Amiodarone Sandoz is best avoided in the 3 months before getting pregnant and during pregnancy.

This is because it can stay in the body for several months even after you stop taking it.

Do not breastfeed if you are taking this medicine as it can be found in breast milk. If you are breastfeeding, alternative feeding arrangements such as bottle feeding should be made for your baby.

Talk to your doctor about the risks and benefits of taking Amiodarone Sandoz during pregnancy and breastfeeding.

Do not take this medicine after the expiry date printed on the pack or if the packaging is torn or shows signs of tampering. If it has expired or is damaged, return it to your pharmacist for disposal.

If you are not sure whether you should start taking this medicine, talk to your doctor.

Before you start to take Amiodarone Sandoz

Tell your doctor if you have allergies to any other medicines, foods, preservatives or dyes.

Tell your doctor if you have had any of the following medical conditions:

  • thyroid problems
  • other heart conditions
  • blood pressure problems
  • liver problems
  • breathing problems.

If you have not told your doctor about any of the above, tell him/her before you start taking Amiodarone Sandoz.

Taking other medicines

Tell your doctor or pharmacist if you are taking any other medicines, including any that you get without a prescription from your pharmacy, supermarket or health food shop.

Some medicines and Amiodarone Sandoz may interfere with each other. These include:

  • any medicines for your heart
  • any medicines for your blood pressure
  • medicines which reduce the activity of your immune system such as ciclosporin, cortisone or tacrolimus
  • diuretics (water tablets)
  • antibiotics, including intravenous erythromycin and pentamidine
  • stimulant laxatives e.g. Bisacodyl, castor oil, senna
  • MAO inhibitors (a type of medicine used to treat depression)
  • antipsychotics (medicines used to treat certain mental and emotional conditions)
  • phenytoin (a medicine used to treat epilepsy)
  • warfarin and other medicines which thin the blood
  • simvastatin and other statins (medicines used to lower cholesterol)
  • colchicine (a medicine used to treat heart conditions)
  • digoxin (a medicine used to treat heart conditions)
  • medicines used to treat a fast or irregular heart beat (such as flecainide and sotalol)
  • fentanyl (a medicine used to treat pain)
  • sildenafil (Viagra)
  • triazolam (a medicine used to treat insomnia)
  • ergotamine (a medicine used to treat migraine).
  • general anaesthesia
  • lignocaine (a topical anaesthetic)
  • amphotericin B (a medicine used to treat fungal infections)
  • antiviral medication eg sofosbuvir, daclatasvir, simeprevir, ledipasvir.

These medicines may be affected by Amiodarone Sandoz or may affect how well it works. You may need to use different amounts of your medicines, or you may need to take different medicines.

Your doctor and pharmacist have more information on medicines to be careful with or avoid while taking this medicine.

How to take Amiodarone Sandoz

Follow all directions given to you by your doctor or pharmacist carefully. They may differ from the information contained in this leaflet.

If you do not understand the instructions, ask your doctor or pharmacist for help.

How much to take

The usual dose is 200 mg three times a day for one week.

Therapy is then continued with 200 mg, two times a day for a further week.

The dose may then be reduced to 200 mg a day (or less if your doctor says so).

Ask your doctor or pharmacist if you are unsure of the correct dose for you.

They will tell you exactly how much to take.

Follow the instructions they give you.

If you take the wrong dose, Amiodarone Sandoz may not work as well and your problem may not improve.

How to take it

Swallow tablets whole with a little water or other liquid.

If you need to break Amiodarone Sandoz, hold tablet with both hands and snap along break line.

When to take Amiodarone Sandoz

The tablets should be taken consistently, at the same time with regards to food.

How long to take Amiodarone Sandoz

Continue taking your medicine for as long as the doctor tells you.

Do not stop taking it unless your doctor tells you to, even if you feel better.

If you forget to take it

Take your dose as soon as you remember, and continue to take it as you would normally.

If it is almost time for your next dose, skip the dose you missed and take your next dose when you are meant to.

Do not take a double dose to make up for the dose you missed. This may increase the chance of you getting an unwanted side effect.

If you are not sure what to do, ask your doctor or pharmacist.

If you have trouble remembering when to take your medicine, ask your pharmacist for some hints.

If you take too much (overdose)

Immediately telephone your doctor or the Poisons Information Centre (telephone Australia 13 11 26 or New Zealand 0800 POISON or 0800 764766) for advice, or go to Accident and Emergency at your nearest hospital, if you think you or anyone else may have taken too much Amiodarone Sandoz. Do this even if there are no signs of discomfort or poisoning. You may need urgent medical attention.

While you are taking Amiodarone Sandoz

Things you must do

If you are about to be started on any new medicine, remind your doctor and pharmacist that you are taking Amiodarone Sandoz.

Tell any other doctors, dentists and pharmacists who treat you that you are taking this medicine.

If you become pregnant while taking this medicine, tell your doctor immediately.

Keep all of your doctor's appointments so that your progress can be checked.

Your doctor may do following tests from time to time to make sure the medicine is working and to prevent unwanted side effects:

  • ECG
  • Eye tests
  • Chest X-rays
  • Liver function tests
  • Thyroid tests

Things you must not do

Do not take Amiodarone Sandoz to treat any other complaint unless your doctor tells you to.

Do not give your medicine to anyone else, even if they have the same condition as you.

Do not stop taking your medicine without checking with your doctor.

Things to be careful of

Always use a 30+ sunscreen and wear a hat and protective clothing when you are outdoors. Do not use a sunlamp. Using Amiodarone Sandoz may make your skin more sensitive to the sun or sunlamps. This can range from an increased tendency to tan to intense redness and swelling of the skin.

If you are going to have surgery, tell the surgeon or anaesthetist that you are taking this medicine. It may affect other medicines used during surgery.

Avoid drinking large quantities of grapefruit juice as it may affect the absorption of amiodarone.

Side effects

Tell your doctor or pharmacist as soon as possible if you do not feel well while you are taking Amiodarone Sandoz.

All medicines can have side effects. Sometimes they are serious, most of the time they are not. You may need medical attention if you get some of the side effects.

Do not be alarmed by the following lists of side effects. You may not experience any of them.

Ask your doctor or pharmacist to answer any questions you may have.

Tell your doctor or pharmacist if you notice any of the following and they worry you:

  • symptoms of an overactive thyroid such as increase in appetite, weight loss, restlessness, heat intolerance, increased sweating, tremors, swelling of the neck (goitre) and a rapid heart rate
  • symptoms of an underactive thyroid such as tiredness, lethargy, muscle weakness, cramps, feeling the cold, a slow heart rate, dry and flaky skin, hair loss, a deep and husky voice and weight gain
  • allergic condition which causes joint pain, skin rashes, fever and kidney problems
  • slow heart beat
  • intense sunburn or increased skin sensitivity to sunlight - always wear a sunscreen while taking Amiodarone Sandoz
  • bluish skin discolouration
  • rash or hives
  • nausea
  • metallic taste
  • constipation
  • loss of appetite
  • tremor, insomnia or other sleep disorders, vivid dreams or nightmares
  • a feeling of "pins and needles" or numbness in the hands, legs or feet
  • muscle weakness, uncontrolled movements or poor coordination
  • small cloudy sports forming on the eyeball . These usually go away after you stop the drug and rarely affect your sight.

Tell your doctor immediately if you notice any of the following:

  • yellowing of the skin or eyes (called jaundice, a symptom of liver changes)
  • shortness of breath, difficulty in breathing
  • clumsiness and lack of coordination affecting balance, limb or eye movements and/or speech, difficulty walking
  • blurred or decreased vision
  • chest pain, cough or spitting up of blood
  • nausea or vomiting, stomach pain, yellow skin, unusual tiredness or passing dark-coloured urine
  • faintness or light headedness
  • blurring or deterioration of vision, sensitisation of eyes to light
  • severe blisters and bleeding in the lips, eyes, mouth, nose and genitals.

The above list includes serious side effects that may require medical attention.

If any of the following happen, tell your doctor immediately, or go to Accident and Emergency at your nearest hospital:

  • swelling of the face, lips, mouth or throat which may cause difficulty in swallowing or breathing
  • breathlessness or any difficulty breathing
  • any disturbance in heart beat, such as pounding heart, very rapid or very slow heart beat.

The above list includes very serious side effects. You may need urgent medical attention or hospitalisation.

Tell your doctor or pharmacist if you notice anything else that is making you feel unwell. Other side effects not listed above may also occur in some people.

Some of these side effects can only be found when your doctor does tests from time to time to check your progress. This will involve blood tests to check how well your liver and thyroid are functioning. It will also involve regular chest x-rays, ECGs and eye tests. Your doctor will tell you how often you need to have these tests. This will depend on how long you are on Amiodarone Sandoz for and what dose you are on.

After taking Amiodarone Sandoz


Keep your medicine in the original container.

If you take it out of its original container it may not keep well.

Keep your medicine in a cool dry place where the temperature stays below 25°C.

Do not store Amiodarone Sandoz or any other medicine in the bathroom or near a sink. Do not leave it on a window sill or in the car.

Heat and dampness can destroy some medicines.

Keep it where children cannot reach it. A locked cupboard at least one-and-a-half metres above the ground is a good place to store medicines.


If your doctor tells you to stop taking this medicine or the expiry date has passed, ask your pharmacist what to do with any medicine that is left over.

Product description

What it looks like

Amiodarone Sandoz comes in two types of tablets:

Amiodarone Sandoz 100 mg tablets - white, round tablets, scored on one side and convex on the other.

Amiodarone Sandoz 200 mg tablets - white, round tablets, biconvex with score on one side.

Available in blister packs of 30 tablets.

Note: 100 mg tablet is not marketed


Active ingredient:

Amiodarone Sandoz 100 mg tablet - 100 mg amiodarone hydrochloride

Amiodarone Sandoz 200 mg tablet - 200 mg amiodarone hydrochloride

Inactive ingredients:

  • maize starch
  • lactose monohydrate
  • povidone
  • magnesium stearate
  • anhydrous colloidal silica.

This medicine does not contain sucrose, gluten, tartrazine or any other azo dyes.


Sandoz Pty Ltd
ABN 60 075 449 553
54 Waterloo Road
Macquarie Park, NSW 2113
Tel: 1800 726 369

Novartis New Zealand Ltd
Private Bag 65904 Mairangi Bay
Auckland 0754
New Zealand
Tel: 0800 354 335

This leaflet was revised in August 2019.

Australian Register Numbers

Amiodarone Sandoz 100 mg tablets: AUST R 77738

Amiodarone Sandoz 200 mg tablets: AUST R 77739

Published by MIMS October 2019


Brand name

Amiodarone Sandoz

Active ingredient

Amiodarone hydrochloride




1 Name of Medicine

Amiodarone hydrochloride.

2 Qualitative and Quantitative Composition

Each Amiodarone Sandoz 100 mg tablets contains 100 mg amiodarone hydrochloride.
Each Amiodarone Sandoz 200 mg tablets contains 200 mg amiodarone hydrochloride.

Excipients with known effect.

Lactose monohydrate.
For the full list of excipients, see Section 6.1 List of Excipients.

3 Pharmaceutical Form

Amiodarone Sandoz 100 mg tablets: white, round tablets, one side convex, the other side scored.
Amiodarone Sandoz 200 mg tablets: white, round tablets, biconvex with one-sided score notch.

4 Clinical Particulars

4.1 Therapeutic Indications

Severe cases of tachyarrhythmias (e.g. Wolff-Parkinson-White syndrome; supraventricular, nodal and ventricular tachycardias; atrial flutter and fibrillation; ventricular fibrillation) not responding to other therapy. Treatment should be initiated in hospital. It is recommended that the patient should be regularly monitored for possible toxicity (e.g. thyroid function, chest X-ray, ophthalmological examination, hepatic function) during the entire course of therapy and for several months after discontinuation.

4.2 Dose and Method of Administration


Due to poor absorption and wide interpatient variability of absorption, the initial loading and subsequent maintenance, dosage schedules in clinical use of the drug have to be individually titrated. It is particularly important that the minimum effective dose be used. In all cases, the patient's management must be judged on the individual response and well-being.
The following dosage regimen is usually effective.

Initial stabilisation.

Treatment should be started with 200 mg three times daily and may be continued for one week. The dosage should then be reduced to 200 mg twice daily for a further week.


After the initial period the dosage should be reduced to 200 mg daily, or less if appropriate. Rarely, the patient may require a higher maintenance dose. The scored 100 mg tablet should be used to titrate the minimum dosage required to maintain control of the arrhythmia. The maintenance dose should be regularly reviewed especially where this exceeds 200 mg daily.

General considerations.

The high initial dose is necessary because of the slow onset of action whilst the necessary tissue levels of amiodarone are achieved. However, excessive dosing during maintenance therapy can cause side effects, some of which are believed to be related to excessive tissue retention of amiodarone. Side effects slowly disappear as the tissue levels fall after the dosage is reduced or the drug withdrawn. If the drug is withdrawn, residual tissue bound amiodarone may persist for three to twelve months, but the likelihood of recurrence of cardiac arrhythmias during this period should be a consideration. The important factor is that the patient requires monitoring regularly to ensure that adverse effects are detected early and the dosage adjusted accordingly. It is particularly important that the minimum effective dose be used.

Method of administration.

Because of the effect of food on absorption, amiodarone should be administered consistently with regards to meals.

Dosage adjustment.


As with all patients, it is important that the minimum effective dose is used. Whilst there is no evidence that dosage requirements are different for this group of patients, they may be more susceptible to bradycardia and conduction defects if too high a dose is used. Particular attention should be paid to monitoring of thyroid function. (See Section 4.4 Special Warnings and Precautions for Use).


The safety and effectiveness of amiodarone has not been established. (See Section 4.4 Special Warnings and Precautions for Use).

4.3 Contraindications

Pregnancy and lactation (see Section 4.6 Fertility, Pregnancy and Lactation, Use in pregnancy, Use in lactation).
In patients in whom bradycardia or atrioventricular block is sufficient to cause syncope, patients with sick sinus syndrome (risk of sinus arrest) or with severe atrioventricular conduction disorders, amiodarone should only be used in conjunction with a pacemaker.
Evidence or a history of thyroid dysfunction.
Known hypersensitivity to amiodarone or iodine or to any of the excipients.
Combined therapy with drugs that may induce torsades de pointes (see Section 4.5 Interactions with Other Medicines and Other Forms of Interactions).
Intravenous amiodarone is contraindicated in the case of hypotension, severe respiratory failure, myocardiopathy, heart failure, circulatory collapse, and severe arterial hypotension, bi- or tri-fascicular conduction disorders, unless a permanent functioning pacemaker is fitted or, unless the patient is in a special care unit and amiodarone is used under the cover of electrosystolic pacing.
Sinus bradycardia and sinoatrial heart block.
Pre-existing QT prolongation.
Concomitant treatment with MAO inhibitors.

4.4 Special Warnings and Precautions for Use

It is recommended to perform an ECG and serum potassium measurement before treatment initiation.
Caution should be exercised in case of hypotension, severe respiratory failure, uncompensated or severe heart failure.

Thyroid hormone abnormalities.

As amiodarone may induce thyroid disorders (see Section 4.8 Adverse Effects (Undesirable Effects)), particularly in patients with personal or family history of thyroid disorders, clinical and biological monitoring (ultrasensitive TSH (usTSH) assay) is recommended before starting treatment, during treatment and for several months following treatment discontinuation. Serum usTSH levels should be measured when thyroid dysfunction is suspected. Severe cases, with clinical presentation of thyrotoxicosis, sometimes fatal, require emergency therapeutical management.
Amiodarone contains iodine and thus may interfere with radioiodine uptake. However, thyroid function tests (free T3, free T4, usTSH) remain interpretable. Amiodarone inhibits peripheral conversion of thyroxine (T4) to triiodothyronine (T3) and may cause isolated biochemical changes (increase in serum free T4, free T3 being slightly decreased or even normal) in clinically euthyroid patients. There is no reason in such cases to discontinue amiodarone treatment.
Hypothyroidism should be suspected if the following clinical signs, usually slight, occur: weight gain, cold intolerance, reduced activity, excessive bradycardia. The diagnosis is supported by a clear increase in serum usTSH. Euthyroidism is usually obtained within 1 to 3 months following the discontinuation of treatment. In life threatening situations, amiodarone therapy can be continued, in combination with L-thyroxine. The dose of L-thyroxine is adjusted according to TSH levels.


Hyperthyroidism may occur during amiodarone treatment, or, up to several months after discontinuation. Clinical features, usually slight, such as weight loss, onset of arrhythmia, angina, and congestive heart failure should alert the physician. The diagnosis is supported by a clear decrease in serum ultrasensitive TSH (usTSH) level, in which case amiodarone should be withdrawn. Recovery usually occurs within a few months following withdrawal of treatment; clinical recovery precedes the normalisation of thyroid function tests. Severe and sometimes fatal cases, with clinical presentation of thyrotoxicosis, require emergency therapeutical management. The treatment should be adjusted to each individual case: for example antithyroid drugs, corticosteroid therapy, beta-blockers.

Neuromuscular disorders.

Amiodarone may induce peripheral sensorimotor neuropathy and/or myopathy. Recovery usually occurs within several months after amiodarone withdrawal, but may sometimes be incomplete.

Pacemakers/implantable defibrillators.

In the context of chronic administration of antiarrhythmic drugs, cases of increase in ventricular defibrillation and/or pacing threshold of pacemakers or implantable cardioverter defibrillator devices have been reported, potentially affecting their efficacy. Therefore, a repeated verification of the functioning of such devices before and during amiodarone treatment is recommended.


Before surgery the anaesthetist should be informed that the patient is taking amiodarone. Potentially severe complications have been reported in patients undergoing general anaesthesia, such as bradycardia unresponsive to atropine, hypotension, disturbances of conduction, decreased cardiac output (see Section 4.5 Interactions with Other Medicines and Other Forms of Interactions).

Cardiac disorders.

The pharmacological action of amiodarone induces ECG changes such as QT prolongation (related to prolonged repolarisation) with the possible development of U waves. However these changes do not reflect toxicity.
Amiodarone Sandoz is not contraindicated in patients with latent or manifest heart failure, but caution should be exercised as existing heart failure may occasionally be worsened. In such cases, amiodarone should be associated with the usual cardiotonic and diuretic treatment.
Excessive doses may lead to atropine resistant bradycardia and to conduction disturbances, particularly in elderly patients or during digitalis therapy. Amiodarone, like quinidine and disopyramide, has caused atypical ventricular tachycardia (see Section 4.8 Adverse Effects (Undesirable Effects), Cardiovascular). In patients with previous history of the above condition, amiodarone should be avoided. Use of higher doses of amiodarone is not advisable in persons with a history of atypical ventricular tachycardia previously induced by another antiarrhythmic agent.
Treatment should be discontinued in case of onset of second or third degree A-V block, sinoatrial block, bifascicular or trifascicular block.
Onsets of new arrhythmias or worsening of treated arrhythmias, 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 are more rarely reported with amiodarone than with the other antiarrhythmic agents, and generally occur in the context of drug interactions and/or electrolytic disorders (see Section 4.5 Interactions with Other Medicines and Other Forms of Interactions).
Cases of severe, potentially life threatening bradycardia and heart block have been observed when amiodarone is used in combination with sofosbuvir alone or in combination with another hepatitis C virus (HCV) direct acting antiviral (DAA), such as daclatasvir, simeprevir or ledipasvir. Therefore, coadministration of these agents with amiodarone is not recommended. If concomitant use with amiodarone cannot be avoided, it is recommended that patients are closely monitored when initiating sofosbuvir alone or in combination with other DAAs. Patients who are identified as being at high risk of bradyarrhythmia should be continuously monitored for at least 48 hours in an appropriate clinical setting after initiation of the concomitant treatment with sofosbuvir. Due to the long half-life of amiodarone, appropriate monitoring should also be carried out for patients who have discontinued amiodarone within the past few months and are to be initiated on sofosbuvir alone or in combination with other direct DAAs. Patients receiving these hepatitis C medicines with amiodarone, with or without other medicines that lower heart rate, should be warned of the symptoms of bradycardia and heart block (such as shortness of breath, light-headedness, palpitations and fainting), and should be advised to seek urgent medical advice if they experience them.

Primary graft dysfunction (PGD) post cardiac transplant.

In retrospective studies, amiodarone use in the transplant recipient prior to heart transplant has been associated with an increased risk of PGD.
For patient who are on the heart transplant waiting list, consideration should be given to the use of an alternative antiarrhythmic drug as early as possible before transplant.

Electrocardiographic monitoring.

Regular ECG monitoring is recommended in patients on long-term therapy with amiodarone. U waves, deformed T waves and QT prolongation (related to prolonged repolarisation) may occur in the ECG because of the fixing of amiodarone in the myocardial tissues, and is not an indication for withdrawing amiodarone.
The prolongation of QT interval occurs in almost all patients, as this is related to the electrophysiological and antiarrhythmic properties of the drug. Prolongation of the actual QT above 0.6 seconds rather than QTC or QRS widening, may be an important warning sign that requires modification of therapy. Too high a dosage may lead to severe bradycardia and to conduction disturbances with the appearance of an idioventricular rhythm (atypical ventricular tachycardia; torsades de pointes), particularly in elderly patients or during digitalis or other antiarrhythmic therapy. In such circumstances amiodarone should be temporarily withdrawn.

Ocular changes.

Corneal deposits develop in almost all patients (see Section 4.8 Adverse Effects (Undesirable Effects), Ocular) and regular ophthalmological monitoring (e.g. slit lamp biomicroscopy, visual acuity, ophthalmoscopy) is recommended. If blurred or decreased vision occurs, complete ophthalmological examination including fundoscopy should be promptly performed. Appearance of optic neuropathy and/or optic neuritis requires amiodarone withdrawal due to the potential progression to blindness.

Pulmonary lesions.

Clinical and radiological evidence of pulmonary fibrosis and/or pneumonitis has been reported, sometimes presenting as unexplained or disproportionate dyspnoea (see Section 4.8 Adverse Effects (Undesirable Effects), Respiratory). Regular chest X-ray should be performed routinely in patients undergoing long-term therapy or when diagnosis is suspected. The effect has usually been reversible with corticosteroid therapy and/or reduction or withdrawal of amiodarone therapy.
Onset of dyspnoea or nonproductive cough may be related to pulmonary toxicity (see Section 4.8 Adverse Effects (Undesirable Effects)) such as interstitial pneumonitis. Very rare cases of interstitial pneumonitis have been reported with intravenous amiodarone. A chest X-Ray should be performed when the diagnosis is suspected, in patients developing effort dyspnoea whether isolated, or, associated with deterioration of general health status (fatigue, weight loss, fever). Amiodarone therapy should be re-evaluated since interstitial pneumonitis is generally reversible following early withdrawal of amiodarone (clinical signs usually resolving within 3 to 4 weeks, followed by slower radiological and lung pulmonary function improvement within several months), and corticosteroid therapy should be considered.
Very rare cases of severe respiratory complications, sometimes fatal, have been observed usually in the period immediately following surgery (adult acute respiratory distress syndrome); a possible interaction with a high oxygen concentration may be implicated.

Hepatic dysfunction.

Regular monitoring of liver function tests (transaminases) is recommended as soon as amiodarone is started and during treatment.
Elevation of hepatic enzyme levels (e.g. serum aspartate aminotransferase, serum alanine aminotransferase, glutamyl transpeptidase) occurs quite commonly in patients undergoing treatment with amiodarone and in some cases are asymptomatic. The changes appear to be dose dependent rather than an idiosyncratic type. Hepatotoxicity has occasionally been reported (see Section 4.8 Adverse Effects (Undesirable Effects), Hepatic) and close monitoring of hepatic function is recommended as soon as amiodarone is started and regularly during treatment.
Acute liver disorders (including severe hepatocellular insufficiency or hepatic failure, sometimes fatal) and chronic liver disorders may occur. Therefore, amiodarone dose should be reduced or the treatment discontinued if the transaminases increase exceeds three times the normal range.
Clinical and biological signs of chronic liver disorders due to oral amiodarone may be minimal (hepatomegaly, transaminases increased up to five times the normal range) and reversible after treatment withdrawal, however fatal cases have been reported.

Skin reactions.

Photosensitivity is quite common (see Section 4.8 Adverse Effects (Undesirable Effects), Dermatological) and there is a wide spectrum of skin reactions, ranging from an increased propensity to suntan to intense burning and erythema and swelling of the exposed area. The intensity of these reactions could be alleviated by a reduction in dosage or by application of a protective sunscreen. Patients should be instructed to avoid exposure to the sun or use protective measures during therapy. This also applies to UV light applications and solaria.
Some patients have developed skin pigmentation (slate grey/ purple colour) of the exposed areas. This pigmentation can be avoided if doses are kept as low as possible. If the pigmentation is cosmetically unsightly, amiodarone should be discontinued if alternative therapy is possible. Even after amiodarone discontinuation, sun protection is necessary for some more time.
If symptoms or signs of Stevens-Johnson syndrome (SJS) or Toxic Epidermal Necrolysis (TEN) (e.g. progressive skin rash often with blisters or mucosal lesions) are present, amiodarone treatment should be discontinued immediately.

Neurological toxicity.

Peripheral neuropathy could occur in patients on long-term high dosage (generally over 400 mg/day) regimen (see Section 4.8 Adverse Effects (Undesirable Effects), Nervous system). Intracellular inclusion bodies, similar to those seen in skin, have been demonstrated in peripheral nerve fibres. Sensorimotor neuropathy, with a glove and stocking distribution, and myopathy have been reported in patients. Histologically, segmental demyelination of the nerve fibres has also been demonstrated. After discontinuation of the drug, the neurological complication is slowly and incompletely resolved.

Drug interactions.

Concomitant use of amiodarone is not recommended with the following drugs: beta-blockers, heart rate lowering calcium channel inhibitors (verapamil, diltiazem) or stimulating laxative agents, which may cause hypokalaemia (see Section 4.5 Interactions with Other Medicines and Other Forms of Interactions).

Use in hepatic impairment.

Because of the potential risk of hepatotoxicity and/or accumulation, amiodarone should be used with extreme caution in patients with hepatic disease.

Use in renal impairment.

Renal excretion of the drug is minimal. This suggests that modification of the dose of amiodarone in patients with renal failure is unnecessary.

Use in the elderly.

In the elderly, heart rate may decrease markedly.

Paediatric use.

The safety and efficacy of amiodarone in paediatric patients have not been established. Therefore its use in paediatric patients is not recommended.

Effects on laboratory tests.

Thyroid function tests.

Amiodarone contains two atoms of iodine and bears a structural resemblance to the molecule of thyroxine. A 300 mg maintenance dose of amiodarone has been reported to yield 9 mg/day of iodine at steady state, well in excess of the highest normal dietary intake.
As a consequence of taking the drug and in the absence of any clinical thyroid dysfunction, changes in tests of thyroid function may occur, variable in number and degree. Typically, the protein bound iodine (PBI), iodine uptake, serum thyroxine (T4), reverse triiodothyronine (rT3) and free thyroxine index (FTI) rise and serum triiodothyronine (T3) falls.
Abnormalities, either multiple or single, may occur in approximately 12% of patients. In particular, a low T3 syndrome has been described, as with other drugs such as dexamethasone.

4.5 Interactions with Other Medicines and Other Forms of Interactions

Drugs inducing torsades de pointes.

Combined therapy with drugs that may induce torsades de pointes is contraindicated (see Section 4.3 Contraindications).

Antiarrhythmic agents.

Such as:
Class 1A antiarrhythmic agents. Including:
Disopyramide: Combined treatment of amiodarone and disopyramide causes an increase in the QT interval.
Procainamide: Serum levels of procainamide increased significantly with coadministration of amiodarone and secondary to this increase cardiac, gastrointestinal and neural toxicity developed.
Quinidine: Atypical ventricular tachycardia with QT prolongation developed after amiodarone was added to a stable quinidine regimen. This is thought to be due to either a change in the protein or receptor binding of quinidine. Serum levels of quinidine increased significantly with concomitant amiodarone therapy. Careful monitoring of the electrocardiogram for QT interval prolongation and of serum levels of quinidine is indicated when amiodarone is added to quinidine treatment.
Mexiletine. Coadministration with amiodarone increases QT interval.
Flecainide. Possible increases of flecainide plasma levels, dosage of flecainide should be adjusted.

Nonantiarrhythmic agents.

Such as vincamine, some neuroleptic agents, cisapride, erythromycin IV or pentamidine IV, moxifloxacin, lithium and tricyclic anti-depressants e.g. doxepin, amitriptyline, anti-malarials e.g. quinine, mefloquine, chloroquine, some antihistamines e.g. terfenadine, astemizole as there is an increased risk of potentially lethal torsades de pointes.

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 torsades de pointes may increase (see Section 4.4 Special Warnings and Precautions for Use) 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 the following drugs is not recommended.

Beta-adrenergic blocking drugs.

Amiodarone itself exhibits noncompetitive alpha and beta-adrenergic inhibition. It should be used with caution in patients on beta-blockers as it may potentiate bradycardia and conduction disorders may occur.

Calcium antagonists.

Coadministration of amiodarone with drugs of the calcium antagonist type may lead to undue bradycardia and conduction disorders may occur.

Monoamine oxidase (MAO) inhibitors.

Coadministration with MAOIs is contraindicated on theoretical grounds.

Agents that may induce hypokalaemia.

Combined therapy with the following drugs is not recommended.

Stimulant laxative agents.

Their use may cause hypokalaemia and therefore increase the risk of torsades de pointes; other types of laxative agents should be used.
Caution to be exercised when using the following drugs in combination with amiodarone. Diuretics inducing hypokalaemia, either alone or combined.
Systemic corticosteroids (gluco-, mineralo-); tetracosactin.
It is necessary to prevent the onset of hypokalaemia (and to correct hypokalaemia); the QT interval should be monitored and, in case of torsades de pointes, antiarrhythmic agents should not be given (ventricular pacing should be initiated; IV magnesium may be used).

General anaesthesia, oxygen therapy (see Section 4.4 Special Warnings and Precautions for Use; Section 4.8 Adverse Effects (Undesirable Effects)).

Potentially severe complications have been reported in patients undergoing general anaesthesia, such as bradycardia unresponsive to atropine, hypotension, disturbances of conduction, decreased cardiac output.
A few cases of severe respiratory complications, such as adult acute respiratory distress syndrome, resulting sometimes in fatalities, have been observed most often in the period immediately after 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.
P-gp substrates. Amiodarone is a P-gp inhibitor. Co administration with P-gp substrates is expected to result in an increase of their exposure.


Digoxin coadministration to patients already receiving digitalis increases plasma digoxin concentrations by about 70%. This is possibly due to the decrease in digoxin clearance and therefore precipitates toxicity and could lead to disturbances in automaticity (severe bradycardia) and conduction disturbances with the appearance of idioventricular rhythm. The mechanism of action is unknown, but amiodarone may displace tissue glycoside or interfere with digoxin excretion. ECG and digoxin plasma levels should be monitored and patients should be observed for clinical signs of digoxin toxicity. It may be necessary to adjust dosage of digoxin treatment.


Caution should be exercised when amiodarone is coadministered with dabigatran due to the risk of bleeding. It may be necessary to adjust the dosage of dabigatran as per its label.
CYP3A4 substrates. When such drugs are coadministered with amiodarone, an inhibitor of CYP3A4, this may result in a higher level of their plasma concentrations, which may lead to a possible increase in their toxicity.

Statins metabolized by CYP3A4.

The risk of muscular toxicity is increased by concomitant administration of amiodarone with statins metabolized by CYP3A4 such as simvastatin, atorvastatin and lovastatin. It is recommended to use a statin not metabolized by CYP3A4 when given with amiodarone.


Because of the possible increase of cyclosporin plasma levels related to a decrease of the clearance of this drug, dosages should be adjusted.


Combination with amiodarone may enhance the pharmacological effects of fentanyl and increase the risk of its toxicity.

Other drugs metabolised by CYP3A4.

Lignocaine, tacrolimus, sildenafil, midazolam, triazolam, dihydroergotamine, ergotamine, colchicine.
CYP2D6 substrates.


Amiodarone increases the concentration of flecainide plasma levels (through inhibition of the cytochrome CYP2D6). The dosage of flecainide should be adjusted.
CYP2C9 substrates. Amiodarone raises the concentrations of CYP2C9 substrates such as phenytoin or warfarin by inhibition of the cytochrome P450 2C9.


Amiodarone raises plasma concentrations of phenytoin. The combination of phenytoin and amiodarone may lead to increases in plasma phenytoin levels with signs of overdosage (particularly neurological signs); clinical monitoring should be undertaken and phenytoin dosage should be reduced as soon as overdosage signs appear; phenytoin plasma levels should be determined.

Warfarin and other anticoagulant agents.

Amiodarone raises the concentration of warfarin. The combination of warfarin with amiodarone potentiates anticoagulant therapy and increases the risk of bleeding. More frequent monitoring of prothrombin level and dosage adjustment of oral anticoagulant during treatment with, and after discontinuation of, amiodarone therapy is necessary.

Effect of other medicinal products on amiodarone.

CYP3A4 inhibitors and CYP2C8 inhibitors may have a potential to inhibit amiodarone metabolism and to increase its exposure.
It is recommended to avoid CYP3A4 inhibitors (e.g. grapefruit juice and certain medicinal products) during treatment with amiodarone.
Coadministration 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. The mechanism for this bradycardia effect is unknown. If coadministration cannot be avoided, cardiac monitoring is recommended (see Section 4.4 Special Warnings and Precautions for Use).
Other consideration should be given to the possibility that amiodarone may alter the plasma concentration of other drugs particularly those which are highly protein bound.

4.6 Fertility, Pregnancy and Lactation

Effects on fertility.

No data available.
(Category C)
Because of the long half-life of amiodarone and its major metabolite, and the potential to cause abnormal thyroid function effects on the foetal thyroid gland and bradycardia in the foetus, its use is probably best avoided in the three months before and throughout the duration of pregnancy. Amiodarone is contraindicated in pregnancy. Where exposure of the foetus is unavoidable, thyroid function (including thyroid stimulating hormone levels) should be assessed promptly in the newborn infant. Growth disturbances, preterm birth and thyroid dysfunctions in the neonate are the most frequent complications. Hypothyroidism, bradycardia and prolonged QT intervals have been ascertained in some neonates. In isolated cases, thyroid enlargement or cardiac murmur have been found. The possibility of cardiac defects should be taken into consideration.
No teratogenic effects have been observed in animals. The drug does cross the placenta. In one study, in a 35 year old woman administered amiodarone in the last weeks of pregnancy, the transplacental passage of amiodarone and desethylamiodarone was found to be 10% and 25% respectively. Changes in maternal thyroid function were similar to those seen in other patients receiving amiodarone therapy (see Section 4.8 Adverse Effects (Undesirable Effects), Endocrine) but there was no evidence of clinical hyperthyroidism. The baby's TSH level on day 4 was normal and it had no goitre and was clinically euthyroid. However, the authors caution the use of amiodarone in pregnancy or in those likely to conceive whilst on amiodarone therapy. The long half-life of the drug requires that the drug be stopped several months before conception. The possible adverse effects of amiodarone on the fetal thyroid are of concern since administration of iodine (of which there is 75 mg in a 200 mg dose of amiodarone) during pregnancy may cause fetal goitre, hypothyroidism and mental retardation.
Another patient received amiodarone 800 mg for one week (maintenance dose thereafter was 400 mg daily) in her thirty-fourth week of pregnancy. Neonatal levels of amiodarone were 25% of the maternal level. Although the infant's liver and thyroid function tests were normal, it was bradycardic during labour and for the first 48 hours after birth.
Amiodarone is contraindicated in pregnancy.
As amiodarone and its desethyl metabolite are secreted in breast milk and its safety in the newborn infant has not been established, it should not be given to breast-feeding mothers. Amiodarone is contraindicated in breast-feeding mothers. If a situation demands that amiodarone be given to a breast-feeding mother, alternative infant feeding should be instituted.

4.7 Effects on Ability to Drive and Use Machines

According to the safety data for amiodarone, there is no evidence that amiodarone impairs the ability to drive a vehicle or operate machinery.

4.8 Adverse Effects (Undesirable Effects)

Amiodarone has been reported to cause frequent and potentially serious toxicity. The incidence, variety and severity of the effects varies from study to study. Most of the adverse effects are also related to dosage and duration of amiodarone, concurrent use of other antiarrhythmic agents, severity of the underlying disease state, and individual variation in the pharmacokinetic profile of the drug.

More common reactions.

Biochemical abnormalities. Abnormal liver function tests (increased AST, ALT and alkaline phosphatase) have been reported.
Abnormal thyroid function tests (see Section 4.4 Special Warnings and Precautions for Use, Effects on laboratory tests).
Cardiovascular. Atypical ventricular tachycardia (torsades de pointes).
Amiodarone induced atypical ventricular tachycardia has been described. Earlier reports describe combination therapy in which other drugs, or clinical situations, could have been implicated. However, in two patients given disopyramide and amiodarone, on withdrawal of the amiodarone, the disopyramide did not induce atypical ventricular tachycardia.


Marked bradycardia or sinus arrest has occasionally been reported in patients with sinus node dysfunction or elderly patients. Reports of moderate and dose related bradycardia are common.

Cardiac failure.

Exacerbation of cardiac failure has been reported rarely.


Sinus arrest and intrahisian block have been reported.
Dermatological. Photosensitivity with increased tendency to sunburn which can lead to erythema and rash commonly occurs in patients on amiodarone therapy. This can usually be alleviated by the use of topical sunscreens and other protective measures. Less frequently, bluish skin discolouration and slate grey facial pigmentation have been reported. These adverse effects are partially dependent on dose and duration of treatment. Erythema, during the course of radiotherapy; erythema nodosum, little specific exanthema, facial flushing and hair loss have been reported.
Skin rashes, usually nonspecific, including exceptional cases of exfoliative dermatitis have been reported; the relationship with the drug has not been formally established.
Gastrointestinal. Nausea, vomiting, anorexia, constipation and dysgeusia have been reported.

Effects on the thyroid.

Both hyperthyroidism and hypothyroidism have occurred during or soon after treatment with amiodarone. Simple monitoring of the usual biochemical tests is confusing because some (protein bound iodine (PBI) and 131I uptake) are invalidated and others (T4, T3 and free thyroxine index (FTI)) may be altered where the patient is clearly euthyroid. Clinical monitoring is therefore recommended before starting treatment, during treatment and should be continued for some months after discontinuation of amiodarone treatment. Serum usTSH level should be measured when thyroid dysfunction is suspected.
The signs of thyroid hyperactivity to be sought are weight loss, asthenia, restlessness, a recurrence of cardiac dysrhythmia, onset of angina or congestive heart failure. The diagnosis may be confirmed by the finding of an elevated serum triiodothyronine (T3), a low level of thyroid stimulating hormone (TSH) and a reduced TSH response to thyrotropin releasing hormone (TRH). (Elevation of reverse triiodothyronine (rT3) may also be found). Hyperthyroidism occurring during amiodarone therapy could be serious and sometimes fatal due to coexistence of ischaemic heart disease and/or life threatening arrhythmias in most of the patients. The risk of developing hyperthyroidism persists for at least three months after discontinuation of treatment. Patients who receive amiodarone should be instructed to consult their doctor in the event of exacerbation of angina or recurrence of tachycardia after successful therapeutic response, even when such untoward episodes occur up to six months after the drug is discontinued.
The clinical features of hypothyroidism, e.g. weight gain and reduced activity, and/or, excessive bradycardia with regard to the expected effect of amiodarone should alert the clinician. The onset may be abrupt. The diagnosis may be supported by the presence of an elevated serum TSH level and an exaggerated TSH response to TRH. The thyroxine (T4), T3 and FTI may be low.
Courses of antithyroid drugs have been used for the treatment of thyroid hyperactivity; large doses may be required initially.
Thyroid hypofunction may be treated cautiously with L-thyroxine.


Weight gain has occasionally been reported.
Hepatic. Elevations of hepatic enzymes may occur from time to time during therapy and are usually transient or respond to a reduction in dosage. Isolated elevation of serum transaminases, which are usually moderate have been reported at the beginning of therapy. They may regress with dose reduction or even spontaneously.
A few cases of acute liver disorders with high serum transaminases and/or jaundice, including hepatic failure, have also been reported; in such cases treatment should be discontinued, which results in most cases in normalisation of liver function tests. However, some cases of death related to acute liver disorders have infrequently been reported.
There have also been reports of chronic liver disease (pseudoalcoholic hepatitis, cirrhosis) sometimes fatal. Clinical signs and biological changes may be minimal (possible hepatomegaly, transaminases elevated 1.5 to 5 times normal). Regular monitoring of liver function is therefore recommended during therapy. Clinical and biological abnormalities usually regress when treatment is stopped but fatal cases have been reported.
Central nervous system. CNS effects include tremor, insomnia, headaches, dizziness, vertigo, fatigue, sleep disorders, vivid dreams, nightmares, paraesthesiae, gait abnormalities and abnormal nerve conduction.
Extrapyramidal symptoms appeared in 2 of 51 (4%) patients taking amiodarone 800 mg/day for 4 to 18 months, and in one patient given 100 mg/day for five to six days respectively.
Uncommon reports of peripheral sensorimotor neuropathy and/or myopathy, usually reversible on withdrawal of the drug, have been received. Several cases of neuropathy indicating amiodarone induced neurolipidosis have been reported. In two studies electron microscope findings are detailed. Neuromyopathy has been reported in one patient given alternating doses of 200 to 400 mg/day and peripheral neuropathy in five patients taking between 600 and 800 mg/day for periods ranging from 4 to 18 months. Proximal muscle weakness has been described in 4 to 6% of patients, with thigh muscle being involved in patients taking high doses (800 mg/day or more).


Exceptional benign intracranial hypertension (pseudotumour cerebri).
Ocular. Corneal microdeposits occur in over 90% of patients. In one study, microdeposits were present in 30% of patients at five to eight weeks, in 55% at three months and in 95% at nine months. In another study corneal deposits took eight weeks to develop but were evident in all patients. Amiodarone keratopathy is related to dosage and duration of treatment. Patients on low doses (100 to 200 mg/day) retain clear corneas or show stage 1 changes (characterised by the coalescence of fine punctate, greyish golden brown opacities into a horizontal linear pattern in the inferior cornea). Those on high doses (400 to 1,400 mg/day) develop stage 2 (characterised by additional arborising and horizontal lines) and stage 3 (characterised by a verticillate, whorl-like pattern) changes which are dependent on duration of treatment. The keratopathy progresses even with reduced dosage, however complete regression occurs when the drug is withdrawn. Complete clearing is reported to occur from between three and seven months after withdrawal of the drug.
Corneal microdeposits are essentially benign in nature causing no visual disturbances and have only rarely given rise to symptoms such as visual coloured haloes in dazzling light or blurred vision. Corneal microdeposits consist of complex lipid deposits and are reversible following discontinuation of treatment.
A few cases of neuropathy/ optic neuritis have been reported. At present, the relationship to amiodarone has not been formally established. If blurred or decreased vision occurs, ophthalmological examination including fundoscopy should be promptly performed. Appearance of optic neuropathy and/or optic neuritis requires amiodarone withdrawal due to the potential progression to blindness.
Psychiatric. Chronic anxiety has been reported.
Respiratory. Cases of pulmonary toxicity (atypical pneumonia as symptom of a hypersensitivity reaction [hypersensitivity pneumonitis], alveolar/ interstitial pneumonitis or fibrosis, pleuritis, bronchiolitis obliterans organizing pneumonia/ BOOP), sometimes resulting in fatalities have been reported.
Chest X-ray should be performed in patients developing dyspnoea (at effort), or any new respiratory symptom, while taking amiodarone, whether in isolation or associated with deterioration of general health status (fatigue, weight loss, fever).
Pulmonary disorders are generally reversible following early withdrawal of amiodarone therapy. Corticosteroid therapy may also be considered. Clinical signs usually resolve within 3 to 4 weeks, followed by slower radiological and lung function improvement (several months).
A few cases of bronchospasm have been reported in patients with severe respiratory failure and especially in asthmatic patients.
A few cases of adult acute respiratory distress syndrome, sometimes resulting in death, have been observed, usually immediately after surgery (a possible interaction with high oxygen concentration may be implicated).

Less common reactions.


Onset or worsening of arrhythmia, sometimes followed by cardiac arrest.
Conduction disturbances (sinoatrial block, A-V block of various degrees); in individual cases asystole was observed.
Marked bradycardia or sinus arrest in patients with sinus node dysfunction and/or in elderly patients.
Cases of torsade de pointes have been reported.


Enhanced pustular psoriasis has been observed, alopecia, urticaria, eczema have been reported.


Worsening of chronic renal failure, impaired renal function (temporarily) and one case of symptomatic hypercalcaemia have been reported.


There has been a single case of bone marrow depression, but cause and effect were not established. There have been rare cases of various clinical features which may suggest a hypersensitivity reaction. These include vasculitis, renal involvement with elevation of creatinine levels, thrombocytopenia.
A few exceptional cases of haemolytic anaemia or aplastic anaemia have also been reported.
Neutropenia, agranulocytosis and granuloma, including bone marrow granuloma has been reported.


Positive antinuclear antibodies and elevated immunoglobulin levels were noted in one patient with amiodarone induced pulmonary fibrosis.

Musculoskeletal and connective tissue disorders.

Lupus like syndrome has been reported.

Nervous system.

Delay in nerve conduction.
Parkinsonism and parosmia have also been reported.


Interference with visual acuity has been rarely observed in association with corneal microdeposits; gritty eyes; blurred vision; itching or burning.


Syndrome of inappropriate antidiuretic hormone secretion (SIADH).


Pancreatitis/acute pancreatitis, dry mouth, constipation and decreased appetite have been reported.

Psychiatric disorders.

Confusional state/ delirium and hallucination have very occasionally been reported.


There have been reports of epididymitis, epididymo-orchitis, as well as some other cases of impotence and decreased libido.
Isolated cases of angioneurotic oedema (Quincke's oedema) and pulmonary haemorrhage have been reported. Cerebellar ataxia, benign intracranial hypertension (pseudotumour cerebri) are very rarely reported.

Severe or life threatening reactions.


Bradycardia, conduction disturbances; atypical ventricular tachycardia.

Injury, poisoning and procedural complications.

Primary graft dysfunction post cardiac transplant.


Pulmonary fibrosis and/or alveolitis.

Immune system disorders.

Anaphylactic/anaphylactoid reaction including shock.


Severe skin reactions, sometimes fatal, including toxic epidermal necrolysis/ Stevens-Johnson syndrome, bullous dermatitis and drug reaction with eosinophilia and systematic symptoms.

Reporting suspected adverse effects.

Reporting suspected adverse reactions after registration of the medicinal product is important. It allows continued monitoring of the benefit-risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions at

4.9 Overdose


A case of attempted suicide with amiodarone 2600 mg is reported in the literature. No clinical symptoms, change in heart rate or blood pressure were reported. The ECG revealed considerable lengthening of the QT interval and T wave inversion in the precordial leads with transient disappearance of R wave in leads V1 to V4, simulating an anteroseptal infarction.
In another case of attempted suicide with amiodarone 8 g, the only symptom reported was profuse perspiration. No signs of cyanosis, dyspnoea or decreased sensitivity were found. No clinical side effects were documented over the monitored period of three months.
Overdosage may lead to severe bradycardia and to conduction disturbances with the appearance of an idioventricular rhythm, particularly in elderly patients or during digitalis therapy. In these circumstances amiodarone should be temporarily withdrawn and if necessary beta-adrenostimulants or glucagon given.


In the event of ingestion of a toxic dose, gastric lavage should be employed to reduce absorption and in addition supportive measures should be applied.
For information on the management of overdose, contact the Poison Information Centre on 131126 (Australia).

5 Pharmacological Properties

5.1 Pharmacodynamic Properties

Mechanism of action.

Site and mode of action. Amiodarone is a Class III antiarrhythmic agent prolonging the action potential duration and hence refractory period of atrial, nodal and ventricular tissues, thereby giving a very broad spectrum of activity. An increase in the refractory period of the atrial cells is a major contributing action to the control of atrial tachyarrhythmias.
A reduction in the permeability of the atrioventricular node, both anterograde and retrograde, explains the efficacy of the drug in nodal tachycardias caused by re-entry through the atrioventricular node.
Its action on ventricular arrhythmias is explained by a number of mechanisms. The effect on the atrium and atrioventricular node results in a reduction in the frequency of stimuli reaching the entricle, thus giving the ventricular cell mass time to repolarise in cases where there has been desynchronisation of the refractory periods. Furthermore, lengthening of the refractory period of the His-Purkinje system and ventricular contractile fibres reduces or prevents micro re-entry.
Amiodarone increases coronary blood flow, decreases cardiac oxygen requirements without producing negative inotropic effects and also suppresses ectopic pacemakers, and this is particularly valuable in arrhythmias associated with ischaemic damage or angina pectoris.
The site and mode of action of amiodarone can be summarised in terms of its effect on myocardial electrophysiology.
Myocardial electrophysiology.

Sinus node.

It decreases sinus automaticity by reducing the slow diastolic depolarisation gradient in the nodal cell. This is a direct effect and is not mediated through the sympathetic or parasympathetic system.

Atrioventricular node.

It reduces the speed of conduction and increases the refractory period of the atrioventricular node.

His-Purkinje system.

It increases the refractory period but does not modify the speed of conduction of the His-Purkinje system.

Contractile fibres.

It increases the action potential but does not alter the rate of depolarisation of the atrial or ventricular myocardial cells; an effect that is more marked in the atria than the ventricles.

Clinical trials.

No data available.

5.2 Pharmacokinetic Properties


In general, pharmacokinetic data relating to amiodarone are incomplete. Amiodarone is incompletely and erratically absorbed following oral administration. Absolute bioavailability ranges from 22 to 86% but there is extensive intersubject variation.
Food increases the rate and extent of absorption of amiodarone, amiodarone should be administered consistently with regard to meals.
A high pressure liquid chromatography (HPLC) method is available for estimation of amiodarone plasma levels. However, the value of this is limited because the correlation of therapeutic effect and plasma level has not been established. Steady-state plasma levels are generally around 1 to 2 microgram/mL, although intersubject variations are common.
Considerably higher values have been reported, especially subsequent to large single doses. Peak plasma concentrations of 6.9 ± 4.2 microgram/mL have been recorded following a single dose of 1600 mg and 1.7 ± 0.3 microgram/mL after a single dose of 800 mg. Steady-state levels of 1.57 ± 0.1 microgram/mL and 3.9 microgram/mL have been recorded after daily oral dosing in the range 800 to 1800 mg.
The half-life of amiodarone is long and with chronic oral dosing can be from 14 to 110 days, but is usually in the range of 14 to 59 days.


Amiodarone is highly protein bound and is thought to bind strongly to protein at concentrations of 10 microgram/mL.
The apparent volume of distribution after oral amiodarone 200 to 400 mg is 6.31 ± 4.93 L/kg. Amiodarone appears to accumulate in adipose tissue and in highly perfused organs (lung, bone marrow, adrenals, liver, pancreas, heart, spleen and kidney). Concentration of amiodarone in packed red blood cells is approximately 60% of that in plasma.


First-pass metabolism in the gut wall and/or in the liver may be a factor in determining the availability of the drug.
The principal metabolite of amiodarone, which has been detected in the plasma and other tissues, is desethylamiodarone. This metabolite is reported to have a longer half-life than amiodarone, i.e. ten hours after a single dose of amiodarone and 60 to 90 days after chronic dosing with amiodarone. The activity of this metabolite is not known.


It is believed that most of the drug is excreted via the liver and gastrointestinal tract by biliary excretion. There may be some hepatic recirculation.

5.3 Preclinical Safety Data


Although mutagenicity findings were negative, an epigenic rather than genotoxic mechanism is proposed for this type of tumour induction.


In a carcinogenicity study in rats, amiodarone caused a dose related increase in thyroid follicular tumours (adenomas and/or carcinomas) in both sexes. In the mouse, carcinomas were not observed but dose dependent thyroid follicular hyperplasia was seen. The relevance of these findings to humans is unknown. Clinical experience has indicated that amiodarone can effect thyroid function.

6 Pharmaceutical Particulars

6.1 List of Excipients

Amiodarone Sandoz tablets also contain as inactive ingredients maize starch, lactose monohydrate, povidone, magnesium stearate and anhydrous colloidal silica.

6.2 Incompatibilities

Incompatibilities were either not assessed or not identified as part of the registration of this medicine.
For information on interactions with other medicines and other forms of interactions, see Section 4.5 Interactions with Other Medicines and Other Forms of Interactions.

6.3 Shelf Life

In Australia, information on the shelf life can be found on the public summary of the Australian Register of Therapeutic Goods (ARTG). The expiry date can be found on the packaging.

6.4 Special Precautions for Storage

Store below 25°C. Protect from light.

6.5 Nature and Contents of Container

Amiodarone Sandoz 100 mg tablets: PVC/PVDC/Al or PP/Al blister packs of 30's*.
Amiodarone Sandoz 200 mg tablets: PVC/PVDC/Al or PP/Al blister packs of 30's.
*Not marketed in Australia.

6.6 Special Precautions for Disposal

In Australia, any unused medicine or waste material should be disposed of in accordance with local requirements.

6.7 Physicochemical Properties

Amiodarone hydrochloride is a white or almost white, fine crystalline powder, very slightly soluble in water, freely soluble in methylene chloride, soluble in methanol, sparingly soluble in alcohol and very slightly soluble in hexane.
Chemical formula: 2-butylbenzofuran-3-yl[4-[2-(diethylamino) ethoxy]-3,5-diiodophenyl] methanone hydrochloride. Molecular formula: C25H29NI2O3.HCl. Molecular weight: 681.8.

Chemical structure.

CAS number.


7 Medicine Schedule (Poisons Standard)


Summary Table of Changes