Published: February 2005

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Keep an Eye on Amiodarone Patients

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Prescriber Update 26(1): 5–6
February 2005

Medsafe Pharmacovigilance Team

Amiodarone has been associated with serious adverse reactions affecting the eyes, lungs, liver, heart and thyroid gland. Prescribers should be vigilant for these unwanted effects, and are reminded of the importance of intensive clinical monitoring of patients receiving amiodarone. Patients should also be informed of the warning symptoms of amiodarone toxicities and to seek immediate medical advice should these occur.

Amiodarone indicated for treatment of cardiac rhythm disorders
NZ reports include serious adverse reactions associated with amiodarone
Baseline assessment and ongoing monitoring is recommended
Expect the unexpected … as well as the expected
Specialist, GP and patient co-ordination facilitates monitoring
References

Amiodarone indicated for treatment of cardiac rhythm disorders

Amiodarone hydrochloride (Cordarone X^®, Aratac^®) is a Class III antiarrhythmic agent approved in New Zealand for the treatment of tachyarrhythmias associated with Wolff-Parkinson-White syndrome; and paroxysmal tachyarrhythmias, atrial flutter and atrial fibrillation when other agents cannot be used^1,2. Amiodarone acts by reducing membrane excitability in myocardial tissue, primarily by prolonging the duration of the action potential and subsequent refractory period of atrial, nodal and ventricular tissue³. The long half-life of amiodarone (approximately 50 days) may contribute to the slow resolution of adverse effects following cessation of the medicine⁴. The most serious potential unwanted effect of amiodarone is pulmonary toxicity (with a fatality rate of about 10%⁵); other harmful effects include visual disturbances as well as hepatic, cardiac and thyroid toxicities.^1,2,4-6

NZ reports include serious adverse reactions associated with amiodarone

The Centre for Adverse Reactions Monitoring has received 340 adverse reaction reports associated with amiodarone therapy, up to the end of December 2004. These reports include the following serious adverse reactions (number of reported cases is given in brackets):

Visual Disturbances
Eye problems including keratitis (13), corneal ulceration (1), eye pain (1), corneal oedema (1), optic neuritis (1), retinal disorder (1) and scotoma (1). There have also been 19 reports of corneal deposits and 10 reports of abnormal vision.

Pulmonary Toxicity
Serious pulmonary reactions include pulmonary fibrosis (10), pneumonitis (8), pneumonia (5), alveolitis (3), pleural effusion (2), interstitial lung disease (2), pulmonary oedema (1) and respiratory failure (1).

Hepatotoxicity
Cases of serious liver toxicity including cirrhosis (2), necrosis (2), hepatitis (3) and hepatocelluar damage (6). There have been 15 reports of liver enzyme disturbance.

Cardiac Toxicity
There have been a number of adverse reactions affecting the cardiovascular system including arrhythmias (10), hypotension (10), hypertension (4), torsades de pointes (2), cardiac arrest (1), cardiac failure (2), pulmonary embolism (1), sudden death (2), and several reports of aggravation of chest pain.

Thyroid Toxicity
Thyroid disturbances include reports of hypothyroidism (12), thyrotoxicosis (1) and thyroid disorder (4).

Baseline assessment and ongoing monitoring is recommended

Before a patient is commenced on amiodarone therapy, prescribers should ensure that the following baseline assessments are completed:^1,2,4-6

• pulmonary function assessment (including chest X-ray)
• ECG and serum potassium levels
• liver function tests
• thyroid function tests
• ophthalmological examination if there is pre-existing visual impairment.

Many of the adverse effects of amiodarone are related to dosage and duration of use^4,6. Therefore, in addition to using the lowest possible dose, it is recommended that patients on long-term amiodarone therapy should regularly undergo the following monitoring^1,2,4-6:

• lung function assessment (including six-monthly chest x-ray)
• ECG and serum potassium levels (ideally every 6-12 months)
• liver function tests (six-monthly)
• thyroid function tests (six-monthly)
• annual eye examinations (e.g. slit lamp biomicroscopy, visual acuity, fundoscopy) but more immediately or frequently if visual changes occur.

Expect the unexpected … as well as the expected

Amiodarone can cause hyperthyroidism and hypothyroidism.^1,2,4-6  The risk of amiodarone-induced hyperthyroidism may remain present for at least three months after the medicine has been stopped. Consequently, thyroid function should continue to be monitored for several months following discontinuation of amiodarone^1,2,4. It is worth noting that amiodarone can affect thyroid function test results, therefore, serum TSH level should be measured when thyroid disturbance is suspected.^1,2  Furthermore, if new signs of arrhythmia appear, consider hyperthyroidism as the potential cause.⁵

Corneal deposits develop in almost all patients taking amiodarone but are generally considered benign^1,2,4. However, all patients should promptly receive an ophthalmological examination (including fundoscopy) if visual symptoms such as blurred, or decreased, vision develop or worsen^1,2,5.

Photosensitivity is another common side effect associated with amiodarone, and may persist for some months after treatment discontinuation. The risk of photosensitivity can be minimised by advising patients to avoid sun exposure as much as practical and to use protective measures (e.g. sunscreen) during, and for at least three months after stopping, amiodarone therapy^1,2,4.

Specialist, GP and patient co-ordination facilitates monitoring

Amiodarone is fully subsidised when prescribed by, or on the recommendation of, a specialist⁷. While a specialist is likely to initiate amiodarone therapy, the patient's general practitioner (GP) may well prescribe maintenance therapy. Therefore, it is useful to ensure that the lead carer is clearly identified. Liaison between specialists and GPs is important in ensuring that patient monitoring is carried out, and that adverse effects are appropriately managed⁴. In addition, patients should be informed of potential symptoms of amiodarone toxicity and encouraged to promptly contact their doctor if symptoms develop.

Competing interests (authors): none declared.

References

1. Healthcare Logistics. Cordarone X tablets data sheet 18 Feb 2004. www.medsafe.govt.nz/profs/Datasheet/c/CordaroneXtabinj.htm
2. Pacific Pharmaceuticals Ltd. Aratac tablets data sheet 26 May 2004. www.medsafe.govt.nz/profs/Datasheet/a/Aratactab.htm
3. Khan MH. Oral class III antiarrhythmics: What is new? Current Opinion in Cardiology 2004;19(1):47-51.
4. Using oral amiodarone safely. Drug and Therapeutics Bulletin 2003;41(2):9-11.
5. Product Information. Physicians Desk Reference 55th edn. 2001: Medical Economics Company, New Jersey, USA. p3354-3357.
6. Siddoway LA. Amiodarone: Guidelines for use and monitoring. American Family Physician 2003;68(11):2189-2196.
7. Pharmaceutical Management Agency (Pharmac). New Zealand Pharmaceutical Schedule December 2004.