Drugs List

Therapeutic Indications

Uses

Atrial fibrillation
Atrial flutter
Nodal tachycardias
Supra-ventricular tachycardia
Ventricular fibrillation - recurrent
Ventricular tachycardia
Wolff-Parkinson-White syndrome

For the stabilisation and treatment of severe rhythm disorders not responding to other therapies or when other treatments cannot be used.

Tachyarrhythmias associated with Wolff-Parkinson-White syndrome.
Atrial flutter and fibrillation.
All types of paroxysmal tachyarrhythmias including supraventricular, nodal and ventricular tachycardias and ventricular fibrillation.

Contraindications

Acute porphyria
Breastfeeding
Galactosaemia
Long QT syndrome
Non-paced severe cardiac conduction defect
Non-paced sinus node dysfunction
Pregnancy
Sinoatrial exit block
Sinus bradycardia
Thyroid dysfunction
Torsade de pointes

Precautions and Warnings

Children under 18 years
Elderly
Family history of long QT syndrome
General anaesthesia
Cardiac failure
Electrolyte imbalance
Glucose-galactose malabsorption syndrome
History of thyroid disorder
History of torsade de pointes
Hypokalaemia
Lactose intolerance
Severe bradycardia

Anaesthetist should be made aware patient is taking this medication
Correct electrolyte disorders before treatment
Advise visual disturbances may affect ability to drive or operate machinery
Not all available products are licensed for all age groups
Treatment to be initiated by specialist
Contains lactose
Consider chest x-ray prior to initiating therapy
Monitor hepatic function before and at 6 monthly intervals during treatment
Monitor serum potassium levels before treatment
Perform ECG before and during treatment
Perform ultrasensitive TSH assay before treatment and 6 monthly thereafter
Annual ophthalmological examination recommended
If pulmonary toxicity suspected do chest x-ray, and lung function tests
If visual disturbances occur, perform ophthalmic evaluation
Monitor patient for some months after discontinuing treatment
Monitor respiratory function
Monitor serum electrolytes
Patients on long-term therapy should be regularly reviewed
Hypothyroidism may occur
Long half life.Drug interactions possible weeks after treatment has stopped
May increase the defibrillation threshold in patients with an I.C.D.
May increase the pacing threshold in patients with a permanent pacemaker
Predisposition QT prolongation: Counsel patient on symptoms of arrhythmias
Withdraw if severe bradycardia or idioventricular rhythm occur
May cause changes to ECG
Discontinue if 2nd or 3rd degree AV, sinoatrial or bifascicular block occur
Discontinue if hyperthyroidism occurs
Discontinue if jaundice or other evidence of hepatic impairment occurs
Discontinue if pulmonary toxicity occurs
Maintain treatment at the lowest effective dose
Advise patient to avoid stimulant laxatives
Advise patient to moderate alcohol intake during treatment
Advise patient grapefruit products may increase plasma level
Female: Contraception advised during and for 6 months after treatment
Advise patient to avoid exposure to sunlight and UV rays during treatment

Patients on long term treatment should be carefully supervised as amiodarone may cause delayed serious adverse reactions including damage to the eyes, heart, lungs, liver, thyroid gland, skin and peripheral nervous system.

Severe conduction disturbances (high grade AV block, bifascicular or trifascicular block) or sinus node disease - only use amiodarone in conjunction with a pacemaker.
Too high a dosage can 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 treatment should be withdrawn. If necessary beta-adrenostimulants or glucagon may be used. As amiodarone has a long half-life, insertion of a pace maker should be considered in these cases.

General anaesthesia or high dose oxygen therapy. Potentially severe complications have been reported in patients taking amiodarone undergoing general anaesthesia: bradycardia unresponsive to atropine, hypotension, disturbances of conduction, decreased cardiac output. A few cases of adult respiratory distress syndrome, most often in the period immediately after surgery, have been observed. A possible interaction with a high oxygen concentration may be implicated. The anaesthetist should be informed that the patient is taking amiodarone.

Thyroid function should be monitored closely.

If hyperthyroidism develops, amiodarone therapy should be withdrawn. Clinical features are weight loss, asthenia, restlessness, increased heart rate, arrhythmia, angina, congestive heart failure and decrease in serum usTSH level.

If hypothyroidism develops, amiodarone treatment should usually be stopped, although amiodarone may be continued in combination with levothyroxine in life threatening situations. Hypothyroidism usually resolves within 3 months of stopping amiodarone therapy.

At the beginning of therapy, elevation of serum transaminases which can be in isolation (1.5 to 3 times normal) may occur. These may return to normal with dose reduction, or sometimes spontaneously.

Alteration of liver function tests which may be minimal (transaminases 1.5 to 5 times normal), or clinical signs (possible hepatomegaly) during treatment for longer than six months should suggest chronic liver disease.

Pulmonary toxicity should be suspected if new or progressive shortness of breath or cough develops in a patient on amiodarone. The onset may be slow but may be rapidly progressive. It has been mostly reported with long term use but a few cases have presented shortly after beginning treatment.

Warn patient of the possibility of hypersensitivity to sunlight. This can be reduced by limiting exposure to UV light, wearing suitable protective hats and clothing and by using a broad spectrum sun screening preparation. This photosensitivity may persist for several months after discontinuation of treatment.

Most patients taking amiodarone develop corneal micro deposits which rarely interfere with vision but drivers may be dazzled by headlights at night.

If blurred or decreased vision occurs, complete ophthalmologic 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. Unless blurred or decreased vision occurs, ophthalmological examination is recommended annually.

Amiodarone may increase the defibrillation threshold and/or pacing threshold in patients with an implantable cardioverter defibrillator or a pacemaker. This may adversely affect the efficacy of the device and regular tests are recommended to ensure the correct functioning of the device after initiation of treatment or a change in posology.

Pregnancy and Lactation

Pregnancy

Amiodarone is contraindicated in pregnancy.

There are insufficient data on the use of amiodarone during pregnancy in humans to judge any possible toxicity. However, in view of its effect on the foetal thyroid gland and the pharmacological properties of the drug on the foetus, amiodarone is contraindicated during pregnancy except in exceptional circumstances.
If, because of the long half life of amiodarone, discontinuation of the drug is considered prior to planned conception, the real risk of reoccurrence of life threatening arrhythmias should be weighed against the possible hazard for the foetus. Hale (2014) concludes it has a high rate of toxicity and should not be given to pregnant mothers unless critically required.

Schaefer (2007) suggests that if exposure occurs beyond 12 weeks gestation (when the foetal thyroid gland begins to function), adverse effects on the foetal thyroid function should be ruled out with an ultrasound scan. Newborns who were exposed in utero should have their thyroid function monitored.

The use of all medication in pregnancy should be avoided whenever possible; particularly in the first trimester. Non-drug treatments should also be considered. When essential, a medication with the best safety record over time should be chosen, employing the lowest effective dose for the shortest possible time. Polypharmacy should be avoided. Teratogens taken in the pre-embryonic period, often quoted as lasting until 14 to 17 days post-conception, are believed to have an all-or-nothing effect. Where drugs have a short half-life, and when the date of conception is certain, this may allow women to be reassured where drug exposure has occurred within this time frame. Further advice may be available from the UK National Teratology Information Service (NTIS) and through ToxBase, available via password on the internet ( www.toxbase.org ) or if this is unavailable at the backup site ( www.toxbasebackup.org ).

Lactation

Amiodarone is contraindicated in breastfeeding.

Amiodarone is excreted in significant quantities into breast milk.

Women who have taken amiodarone within the past several months should not breastfeed due to the long elimination half life of the drug (Briggs, 2015).
Schaefer (2007) concludes other class III antiarrhythmic are preferable to amiodarone.

Neonates, infants born prematurely, those with low birth weight, those with an unstable gastrointestinal function or who have serious illnesses may require special consideration. For any infant, if a drug is prescribed to the nursing mother, it should be at the lowest practical dose and for the shortest time. When drug administration is unavoidable and breastfeeding is to continue, minimisation of exposure of the infant to the drug may sometimes be achieved by timing the maternal doses to just after a feeding episode. Infants exposed to drugs via breast milk should be monitored for unusual signs or symptoms. Interactions between the drug received by the infant from the mother's milk and medication prescribed for the infant should also be considered, for example, when the drug given to the infant may prevent metabolism of the drug received via breast milk.
Specialist advice is available from the UK Drugs in Lactation Advisory Service at https://www.midlandsmedicines.nhs.uk/content.asp?section=6&subsection=17&pageIdx=1

Side Effects

Acute hepatic disorders
Adult respiratory distress syndrome
Aggravation of cardiac failure
Alopecia
Angioedema
Aplastic anaemia
Ataxia
Atrioventricular block
Benign intracranial hypertension
Blindness
Blurred vision
Bone marrow granuloma
Bradycardia
Bronchiolitis obliterans
Bronchospasm
Cardiac arrest
Cardiac failure
Chronic hepatic disease
Cirrhosis
Conduction disturbances
Corneal microdeposits (reversible)
Cough
Dysgeusia
Dyspnoea
ECG changes
Epididymo-orchitis
Erythema
Exfoliative dermatitis
Fatigue
Fever
Gastro-intestinal symptoms
Haemolytic anaemia
Headache
Hepatic failure
Hypersensitivity reactions
Hyperthyroidism
Hypothyroidism
Impotence
Inappropriate secretion of antidiuretic hormone
Increases in serum transaminases (transient)
Jaundice
Myopathy
Nausea
Nightmares
Optic neuritis
Optic neuropathy
Peripheral neuropathy
Photosensitivity
Pleuritis
Pneumonitis
Pro-arrhythmic effects
Prolongation of QT interval
Pseudo-alcoholic hepatitis
Pulmonary alveolitis
Pulmonary fibrosis
Pulmonary haemorrhage
Pulmonary toxicity
Rash
Serum creatinine increased
Severe bradycardia
Severe hypotension
Sino-atrial block
Sinus arrest
Slate-grey skin discolouration
Sleep disturbances
Thrombocytopenia
Thyrotoxicosis
Torsades de pointes
Tremor
Urticaria
Vasculitis
Vertigo
Visual haloes
Vomiting
Weight loss

Presentation

Oral formulations of amiodarone

Drugs List

Therapeutic Indications

Uses

Atrial fibrillation
Atrial flutter
Nodal tachycardias
Supra-ventricular tachycardia
Ventricular fibrillation - recurrent
Ventricular tachycardia
Wolff-Parkinson-White syndrome

For the stabilisation and treatment of severe rhythm disorders not responding to other therapies or when other treatments cannot be used.

Tachyarrhythmias associated with Wolff-Parkinson-White syndrome.
Atrial flutter and fibrillation.
All types of paroxysmal tachyarrhythmias including supraventricular, nodal and ventricular tachycardias and ventricular fibrillation.

Dosage

Adults

Children

Neonates

Additional Dosage Information

Contraindications

Acute porphyria
Breastfeeding
Galactosaemia
Long QT syndrome
Non-paced severe cardiac conduction defect
Non-paced sinus node dysfunction
Pregnancy
Sinoatrial exit block
Sinus bradycardia
Thyroid dysfunction
Torsade de pointes

Precautions and Warnings

Children under 18 years
Elderly
Family history of long QT syndrome
General anaesthesia
Cardiac failure
Electrolyte imbalance
Glucose-galactose malabsorption syndrome
History of thyroid disorder
History of torsade de pointes
Hypokalaemia
Lactose intolerance
Severe bradycardia

Anaesthetist should be made aware patient is taking this medication
Correct electrolyte disorders before treatment
Advise visual disturbances may affect ability to drive or operate machinery
Not all available products are licensed for all age groups
Treatment to be initiated by specialist
Contains lactose
Consider chest x-ray prior to initiating therapy
Monitor hepatic function before and at 6 monthly intervals during treatment
Monitor serum potassium levels before treatment
Perform ECG before and during treatment
Perform ultrasensitive TSH assay before treatment and 6 monthly thereafter
Annual ophthalmological examination recommended
If pulmonary toxicity suspected do chest x-ray, and lung function tests
If visual disturbances occur, perform ophthalmic evaluation
Monitor patient for some months after discontinuing treatment
Monitor respiratory function
Monitor serum electrolytes
Patients on long-term therapy should be regularly reviewed
Hypothyroidism may occur
Long half life.Drug interactions possible weeks after treatment has stopped
May increase the defibrillation threshold in patients with an I.C.D.
May increase the pacing threshold in patients with a permanent pacemaker
Predisposition QT prolongation: Counsel patient on symptoms of arrhythmias
Withdraw if severe bradycardia or idioventricular rhythm occur
May cause changes to ECG
Discontinue if 2nd or 3rd degree AV, sinoatrial or bifascicular block occur
Discontinue if hyperthyroidism occurs
Discontinue if jaundice or other evidence of hepatic impairment occurs
Discontinue if pulmonary toxicity occurs
Maintain treatment at the lowest effective dose
Advise patient to avoid stimulant laxatives
Advise patient to moderate alcohol intake during treatment
Advise patient grapefruit products may increase plasma level
Female: Contraception advised during and for 6 months after treatment
Advise patient to avoid exposure to sunlight and UV rays during treatment

Patients on long term treatment should be carefully supervised as amiodarone may cause delayed serious adverse reactions including damage to the eyes, heart, lungs, liver, thyroid gland, skin and peripheral nervous system.

Severe conduction disturbances (high grade AV block, bifascicular or trifascicular block) or sinus node disease - only use amiodarone in conjunction with a pacemaker.
Too high a dosage can 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 treatment should be withdrawn. If necessary beta-adrenostimulants or glucagon may be used. As amiodarone has a long half-life, insertion of a pace maker should be considered in these cases.

General anaesthesia or high dose oxygen therapy. Potentially severe complications have been reported in patients taking amiodarone undergoing general anaesthesia: bradycardia unresponsive to atropine, hypotension, disturbances of conduction, decreased cardiac output. A few cases of adult respiratory distress syndrome, most often in the period immediately after surgery, have been observed. A possible interaction with a high oxygen concentration may be implicated. The anaesthetist should be informed that the patient is taking amiodarone.

Thyroid function should be monitored closely.

If hyperthyroidism develops, amiodarone therapy should be withdrawn. Clinical features are weight loss, asthenia, restlessness, increased heart rate, arrhythmia, angina, congestive heart failure and decrease in serum usTSH level.

If hypothyroidism develops, amiodarone treatment should usually be stopped, although amiodarone may be continued in combination with levothyroxine in life threatening situations. Hypothyroidism usually resolves within 3 months of stopping amiodarone therapy.

At the beginning of therapy, elevation of serum transaminases which can be in isolation (1.5 to 3 times normal) may occur. These may return to normal with dose reduction, or sometimes spontaneously.

Alteration of liver function tests which may be minimal (transaminases 1.5 to 5 times normal), or clinical signs (possible hepatomegaly) during treatment for longer than six months should suggest chronic liver disease.

Pulmonary toxicity should be suspected if new or progressive shortness of breath or cough develops in a patient on amiodarone. The onset may be slow but may be rapidly progressive. It has been mostly reported with long term use but a few cases have presented shortly after beginning treatment.

Warn patient of the possibility of hypersensitivity to sunlight. This can be reduced by limiting exposure to UV light, wearing suitable protective hats and clothing and by using a broad spectrum sun screening preparation. This photosensitivity may persist for several months after discontinuation of treatment.

Most patients taking amiodarone develop corneal micro deposits which rarely interfere with vision but drivers may be dazzled by headlights at night.

If blurred or decreased vision occurs, complete ophthalmologic 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. Unless blurred or decreased vision occurs, ophthalmological examination is recommended annually.

Amiodarone may increase the defibrillation threshold and/or pacing threshold in patients with an implantable cardioverter defibrillator or a pacemaker. This may adversely affect the efficacy of the device and regular tests are recommended to ensure the correct functioning of the device after initiation of treatment or a change in posology.

Pregnancy and Lactation

Pregnancy

Amiodarone is contraindicated in pregnancy.

There are insufficient data on the use of amiodarone during pregnancy in humans to judge any possible toxicity. However, in view of its effect on the foetal thyroid gland and the pharmacological properties of the drug on the foetus, amiodarone is contraindicated during pregnancy except in exceptional circumstances.
If, because of the long half life of amiodarone, discontinuation of the drug is considered prior to planned conception, the real risk of reoccurrence of life threatening arrhythmias should be weighed against the possible hazard for the foetus. Hale (2014) concludes it has a high rate of toxicity and should not be given to pregnant mothers unless critically required.

Schaefer (2007) suggests that if exposure occurs beyond 12 weeks gestation (when the foetal thyroid gland begins to function), adverse effects on the foetal thyroid function should be ruled out with an ultrasound scan. Newborns who were exposed in utero should have their thyroid function monitored.

The use of all medication in pregnancy should be avoided whenever possible; particularly in the first trimester. Non-drug treatments should also be considered. When essential, a medication with the best safety record over time should be chosen, employing the lowest effective dose for the shortest possible time. Polypharmacy should be avoided. Teratogens taken in the pre-embryonic period, often quoted as lasting until 14 to 17 days post-conception, are believed to have an all-or-nothing effect. Where drugs have a short half-life, and when the date of conception is certain, this may allow women to be reassured where drug exposure has occurred within this time frame. Further advice may be available from the UK National Teratology Information Service (NTIS) and through ToxBase, available via password on the internet ( www.toxbase.org ) or if this is unavailable at the backup site ( www.toxbasebackup.org ).

Lactation

Amiodarone is contraindicated in breastfeeding.

Amiodarone is excreted in significant quantities into breast milk.

Women who have taken amiodarone within the past several months should not breastfeed due to the long elimination half life of the drug (Briggs, 2015).
Schaefer (2007) concludes other class III antiarrhythmic are preferable to amiodarone.

Neonates, infants born prematurely, those with low birth weight, those with an unstable gastrointestinal function or who have serious illnesses may require special consideration. For any infant, if a drug is prescribed to the nursing mother, it should be at the lowest practical dose and for the shortest time. When drug administration is unavoidable and breastfeeding is to continue, minimisation of exposure of the infant to the drug may sometimes be achieved by timing the maternal doses to just after a feeding episode. Infants exposed to drugs via breast milk should be monitored for unusual signs or symptoms. Interactions between the drug received by the infant from the mother's milk and medication prescribed for the infant should also be considered, for example, when the drug given to the infant may prevent metabolism of the drug received via breast milk.
Specialist advice is available from the UK Drugs in Lactation Advisory Service at https://www.midlandsmedicines.nhs.uk/content.asp?section=6&subsection=17&pageIdx=1

Side Effects

Acute hepatic disorders
Adult respiratory distress syndrome
Aggravation of cardiac failure
Alopecia
Angioedema
Aplastic anaemia
Ataxia
Atrioventricular block
Benign intracranial hypertension
Blindness
Blurred vision
Bone marrow granuloma
Bradycardia
Bronchiolitis obliterans
Bronchospasm
Cardiac arrest
Cardiac failure
Chronic hepatic disease
Cirrhosis
Conduction disturbances
Corneal microdeposits (reversible)
Cough
Dysgeusia
Dyspnoea
ECG changes
Epididymo-orchitis
Erythema
Exfoliative dermatitis
Fatigue
Fever
Gastro-intestinal symptoms
Haemolytic anaemia
Headache
Hepatic failure
Hypersensitivity reactions
Hyperthyroidism
Hypothyroidism
Impotence
Inappropriate secretion of antidiuretic hormone
Increases in serum transaminases (transient)
Jaundice
Myopathy
Nausea
Nightmares
Optic neuritis
Optic neuropathy
Peripheral neuropathy
Photosensitivity
Pleuritis
Pneumonitis
Pro-arrhythmic effects
Prolongation of QT interval
Pseudo-alcoholic hepatitis
Pulmonary alveolitis
Pulmonary fibrosis
Pulmonary haemorrhage
Pulmonary toxicity
Rash
Serum creatinine increased
Severe bradycardia
Severe hypotension
Sino-atrial block
Sinus arrest
Slate-grey skin discolouration
Sleep disturbances
Thrombocytopenia
Thyrotoxicosis
Torsades de pointes
Tremor
Urticaria
Vasculitis
Vertigo
Visual haloes
Vomiting
Weight loss

Overdosage

It is strongly recommended that the UK National Poisons Information Service be consulted on cases of suspected or actual overdose where there is doubt over the degree of risk or about appropriate management.

The following number will direct the caller to the relevant local centre (0844) 892 0111

Information may be obtained if you have access to ToxBase the primary clinical toxicology database of the National Poisons Information Service. This is available via password on the internet ( www.toxbase.org ) or if this is unavailable at the backup site ( www.toxbasebackup.org ).

Further Information

Last Full Review Date: September 2016

Reference Sources

Drugs During Pregnancy and Lactation: Treatment Options and Risk Assessment, 2nd edition (2007) ed. Schaefer, C., Peters, P. and Miller, R. Elsevier, London.

Drugs in Pregnancy and Lactation: A Reference Guide to Fetal and Neonatal Risk, 10th edition (2015) ed. Briggs, G., Freeman, R. Wolters Kluwer Health, Philadelphia.

Medications and Mothers' Milk, Sixteenth Edition (2014) Hale, T and Rowe, H, Hale Publishing, Plano, Texas.

Summary of Product Characteristics: Amiodarone 100mg tablets. Accord healthcare Ltd. Revised January 2016.
Summary of Product Characteristics: Amiodarone 200mg tablets. Accord healthcare Ltd. Revised January 2016.

Summary of Product Characteristics: Amiodarone hydrochloride 100mg tablets (Arrow). Actavis UK Ltd. Revised June 2014.
Summary of Product Characteristics: Amiodarone hydrochloride 200mg tablets (Arrow). Actavis UK Ltd. Revised June 2014.

Summary of Product Characteristics: Amiodarone 100mg tablets. Aurobindo Pharma-Milpharm Ltd. Revised November 2015.
Summary of Product Characteristics: Amiodarone Milpharm 200mg tablets. Aurobindo Pharma-Milpharm Ltd. Revised November 2015.

Summary of Product Characteristics: Cordarone X 100mg tablets. Zentiva. Revised March 2016.
Summary of Product Characteristics: Cordarone X 200mg tablets. Zentiva. Revised March 2016.

NICE - Evidence Services
Available at: www.nice.org.uk
Last accessed: 20 June 2017

US National Library of Medicine. Toxicology Data Network. Drugs and Lactation Database (LactMed).
Available at: https://toxnet.nlm.nih.gov/cgi-bin/sis/htmlgen?LACT
Amiodarone Last revised: 10 March, 2015
Last accessed: 17 August, 2016