Amiodarone

Registered South African indications:

• Tachyarrhythmias
• Cardiopulmonary resuscitation

Contraindications

• Hypersensitivity to the active ingredient or any of its excipients
• Hypersensitivity to iodine
• Pregnancy (except in exceptional circumstances)
• Breastfeeding
• Sinus bradycardia and sino-atrial heart block
• Severe conduction disturbances (high-grade AV block, bifascicular or trifascicular block) or sinus node disease when not used in conjunction with a pacemaker 
• Evidence or history of thyroid dysfunction
• Severe respiratory failure (inj)
• Circulatory collapse (inj)
• Severe arterial hypotension (inj)
• Hypotension (when given as a bolus inj)
• Cardiac failure (when given as a bolus inj)
• Cardiomyopathy (when given as a bolus inj)
• Newborns, premature neonates, infants and children <3 years (inj)
• Coadministration with agents that may induce torsades de pointes

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These contraindications do not apply when used for cardiopulmonary resuscitation of shock-resistant ventricular fibrillation (inj)

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Cautions

• Severe hepatic impairment
• Elderly
• Porphyria
• Decompensated cardiomyopathy
• Hypotension
• Severe cardiac failure
• QT prolongation factors
• Transplant recipients prior to heart transplantation
• History of thyroid disorders
• Patients with an implantable cardioverter defibrillator or a pacemaker
• Ophthalmological disorders  
• Peripheral neuropathy and/or myopathy
• Respiratory disorders (dyspnoea)
• Photosensitivity and skin reactions
• Long-term treatment
• Too rapid administration or overdosage(inj)
• Mixing with other medicinal preparations in syringe or injection into the same line (inj)
• Repeated or continuous infusion via peripheral veins (inj)
• Galactose intolerance
• Lapp lactase deficiency
• Glucose-galactose malabsorption

Forms avail. in SA and covered in this monograph: inj, tab

Tachyarrhythmias associated with Wolff-Parkinson-White syndrome 
Tachyarrhythmias (when other agents cannot be used) 
- Supraventricular
- Nodal and ventricular
- Atrial flutter and fibrillation
- Ventricular fibrillation

• IV: Initial: 5mg/kg as an infusion over 20min-2hrs as a dilute solution in 250ml 5% dextrose; Repeat infusion up to 1200mg (approximately 15mg/kg) in up to 500ml 5% dextrose/24hrs with the rate of infusion being adjusted on clinical response

In an extreme clinical emergency

• IV:150–300mg as a slow injection in 10–20ml 5% dextrose over at least 3min. Do not repeat for at least 15 minutes

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Patients treated in an extreme clinical emergency must be closely monitored, e.g. in an intensive care unit at the discretion of the clinician

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Only to be used when facilities exist for cardiac monitoring, defibrillation, and cardiac pacing

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Amiodarone IV may be used prior to DC cardioversion

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As soon as an adequate response has been obtained, oral therapy should be initiated concomitantly at the usual loading dose (i.e. 200 mg three times a day). Amiodarone IV should then be phased out gradually

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• Oral (tab): Initial: 200mg, 8hrly for 1 week then reduce to 200mg, 12hrly for 1 week; Maintenance: 200mg, dly

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After the initial dosage period, the dosage should be reduced  to 200mg daily, or less

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The scored 100mg tablet should be used to titrate the minimum dosage required to maintain control of the arrhythmia

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Rarely, the patient may require a higher maintenance dose

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The maintenance dose should be regularly reviewed, especially where this exceeds 200mg daily

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Cardiopulmonary resuscitation
- Shock resistant ventricular fibrillation

• IV: Initial: 300mg OR 5mg/kg diluted in 20ml 5% dextrose solution rapidly injected; repeat with 150mg OR 2.5mg/kg if ventricular fibrillation persists 

Not established for use in children

Pregnancy

• Contraindicated
• 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, amiodarone is contraindicated during pregnancy, except in exceptional circumstances
• If, because of the long half-life of amiodarone, discontinuation of the medicine 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

Breastfeeding 

• Contraindicated
• Amiodarone is excreted into breast milk in significant quantities and breastfeeding is contraindicated

Renal Impairment

• No dose adjustment recommended

Hepatic Impairment

• Mild to moderate (Child-Pugh Class A & B): No dose adjustment recommended
• Severe (Child-Pugh Class C): Caution; no dose adjustment recommended
  Initial: 400-600mg, dly in divided doses; Limit loading dose to 6g; Maintenance; 100-200mg, dly
  The dose should be adjusted according to the clinical response, emergency need and the changes in liver function

Elderly

• Caution; dose adjustment recommended
  Loading dose: No adjustment necessary; Maintenance: Max: 100mg/24hrs 

Porphyria Information

• Probably porphyrinogenic (PRP)

Drugs in Sport

• Permitted - No warnings

Central Nervous System Disorders

• Benign intracranial hypertension (pseudotumour cerebri)
• Headache
• Confusional state
• Extrapyramidal tremor
• Nightmares
• Sleep disorders
• Peripheral sensorimotor neuropathy and/or myopathy
• Cerebellar ataxia
• Parkinsonism
• Parosmia

Cardiovascular Disorders

• Bradycardia
• Sinus arrest
• Worsening of arrhythmia
• Cardiac arrest
• Conduction disturbances
  - Sinoatrial block
  - AV block of various degrees
• Torsade de Pointes
• Hypotension
• Hot flushes
• Primary graft dysfunction post-cardiac transplant
• Vasculitis

Respiratory Disorders

• Interstitial pneumonitis
• Fibrosis
• Severe respiratory complications (adult acute respiratory distress syndrome)
• Bronchospasm
• Apnoea
• Pulmonary toxicity
  - Hypersensitivity
  - Pneumonitis
  - Alveolar/ interstitial pneumonitis or fibrosis
  - Pleuritis
  - Bronchiolitis obliterans organising pneumonia (BOOP)
• Pulmonary haemorrhage

Gastrointestinal Disorders

• Benign gastrointestinal disorders
• Nausea and vomiting
• Pancreatitis
• Constipation
• Dry mouth

Genitourinary Disorders

• Decreased libido
• Impotence
• Epididymo-orchitis
• Increased blood creatinine

Hepatobiliary Disorders

• Increase in serum transaminases
• Acute hepatic disorders
• Chronic hepatic disease
  - Pseudo alcoholic hepatitis
  - Cirrhosis
• Jaundice
• Hepatic failure

Endocrine and Metabolic Disorders

• Hyperthyroidism
• Hypothyroidism
• Syndrome of inappropriate antidiuretic hormone secretion (SIADH)
• Decreased appetite

Musculoskeletal Disorders

• Back pain
• Bona marrow granuloma
• Lupus-like syndrome

Skin and Subcutaneous Tissue Disorders

• Sweating
• Eczema
• Erythema
• Non-specific rashes
• Exfoliative dermatitis
• Alopecia
• Urticaria
• Severe skin reactions
  - Toxic epidermal necrolysis
  - Stevens-Johnson syndrome
  - Bullous dermatitis
  - Drug reaction with eosinophilia and systematic symptoms
• Injection site reactions
  - Pain
  - Erythema
  - Oedema
  - Necrosis
  - Extravasation
  - Infiltration
  - Inflammation
  - Induration
  - Thrombophlebitis
  - Phlebitis
  - Cellulitis
  - Infection
  - Pigmentation changes
• Photosensitivity
• Slate grey or bluish pigmentations of light-exposed skin, particularly the face

Immune, Blood and Lymphatic System Disorders

• Bone marrow granulomas
• Neutropenia
• Agranulocytosis
• Haemolytic anaemia
• Aplastic anaemia
• Thrombocytopaenia
• Anaphylactic shock
• Anaphylactoid reaction, including shock
• Angioneurotic oedema (Quincke's Oedema)

Sensory Disorders

• Optic neuropathy
• Neuritis
• Blindness
• Corneal micro-deposits
• Vertigo
• Dysgeusia

Others

• Granuloma

• Warfarin
• Digoxin
• Phenytoin
• Agents that prolong the QT interval or induce Torsade de Pointes
• Class Ia antiarrhythmic agents  
• Quinidine
• Procainamide
• Disopyramide
• Class III antiarrhythmic agents
• Sotalol
• Bretylium
• IV Erythromycin
• IV Cotrimoxazole
• IV Pentamidine
• IV Clarithromycin
• Antipsychotics
• Chlorpromazine
• Thioridazine
• Fluphenazine
• Pimozide
• Haloperidol
• Amisulpride
• Sertindole
• Lithium
• Tricyclic antidepressants
• Doxepin
• Maprotiline
• Amitriptyline
• Antihistamines
• Terfenadine
• Astemizole
• Mizolastine
• Antimalarials  
• Quinine
• Mefloquine
• Chloroquine
• Halofantrine
• Moxifloxacin
• Fluoroquinolones  
• Beta-blockers
• Calcium channel inhibitors  
• Diltiazem
• Verapamil
• Agents that cause hypokalaemia
• Stimulant laxatives
• Agents that cause hypomagnesaemia
• Diuretics
• Systemic corticosteroids
• Tetracosactide
• Intravenous amphotericin B
• General anaesthesia
• High dose oxygen therapy
• P-glycoprotein substrates
• Dabigatran
• CYP2C9 substrates
• Oral anticoagulants
• Warfarin
• CYP2C9 substrates
• Flecainide
• CYP3A4 substrates
• Ciclosporin
• Statins
• Lidocaine
• Tacrolimus
• Sildenafil
• Fentanyl
• Midazolam
• Triazolam
• Ergotamine
• Dihydroergotamine
• Colchicine
• Sofosbuvir

Other interactions

• Grapefruit juice
• Alcohol

• ECG
• Blood pressure
• Hepatic function
• Thyroid function
• Serum electrolytes (especially potassium and magnesium)

None routine. Specific cases may require

• Prothrombin time
• Pulmonary toxicity
  - Baseline pulmonary function tests
  - Chest X-ray
• Pacing and defibrillation thresholds of implantable cardiac devices

Additional observations

• Signs and symptoms of
  - Lethargy
  - Oedema of the hands or feet
  - Weight loss
• Ophthalmic examination

Considerations for use

• Treatment should be initiated and normally monitored only under hospital or specialist supervision. Amiodarone is indicated only for the treatment of severe rhythm disorders not responding to other therapies or when other treatments cannot be used
• 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
• As soon as an adequate response has been obtained, oral therapy should be initiated concomitantly at the usual loading dose (i.e. 200 mg three times a day). Amiodarone IV should then be phased out gradually

Dosage reduction/ withdrawal

• Side effects slowly disappear as tissue levels fall. Following drug withdrawal, residual tissue bound amiodarone may protect the patient for up to a month. However, the likelihood of recurrence of arrhythmia during this period should be considered

Amiodarone inhibits adrenergic stimulation (partial alpha- and beta-blocker) and has haemodynamic effects, such as increased blood flow and systemic and coronary vasodilation. It reduces myocardial oxygen consumption and has been shown to have a sparing effect of myocardial ATP utilisation, with decreased oxidative processes. Amiodarone inhibits the metabolic and biochemical effects of catecholamines on the heart and inhibits Na⁺ and K⁺ activated ATPase.

Tablet 100mg

• Arycor (Sanofi Aventis)
• Cordarone X (Sanofi Aventis) originator
• Hexarone (Sandoz)

Tablet 200mg

• Arycor (Sanofi Aventis)
• Bio-Amiodarone (Biotech)
• Cordarone X (Sanofi Aventis) originator
• Hexarone (Sandoz)

Injection (per 3ml) 150mg

• Adcorone (Adcock Ingram)
• Amiotach (Pharmacare)
• Cordarone X (Sanofi Aventis) originator