AMIODARONE HYDROCHLORIDE

Posology Adults 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 wellbeing. The following dosage regimen is generally effective.

Initial Stabilisation Treatment should be started with 200mg, three times a day and may be continued for 1 week. The dosage should then be reduced to 200mg, twice daily for a further week. Maintenance After the initial period the dosage should be reduced to 200mg daily, or less if appropriate.

Rarely, the patient may require a higher maintenance dose. The dosage should be titrated to the minimum required to maintain control of the arrhythmia. The maintenance dose should be regularly reviewed, especially where this exceeds 200 mg daily.

General Considerations Initial dosing A high dose is needed in order to achieve adequate tissue levels rapidly. Maintenance Too high a dose during maintenance therapy can cause side effects which are believed to be related to high tissue levels of amiodarone and its metabolites.

Amiodarone is strongly protein bound and has an average plasma half-life of 50 days (reported range 20-100 days). Therefore, sufficient time must be allowed for a new distribution equilibrium to be achieved between adjustments of dosage.

In patients with potentially lethal arrhythmias the long half-life is a valuable safeguard, as omission of occasional doses does not significantly influence the overall therapeutic effect. It is particularly important that the minimum effective dosage is used and the patient is monitored regularly to detect the clinical features of excess amiodarone dosage.

Therapy may then be adjusted accordingly. 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.

Paediatric population The safety and efficacy of amiodarone in children has not been established. 2 but no recommendation on posology can be made. Elderly 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 employed.

The following adverse reactions are classified by system organ class and ranked under heading of frequency using the following convention: very common (≥1/10), common (≥1/100 to <1/10); uncommon (≥1/1,000 to <1/100); rare (≥1/10,000 to <1/1,000), very rare (<1/10,000), not known (cannot be estimated from the available data).

Blood and lymphatic system disorders Very rare: • haemolytic anaemia • aplastic anaemia • thrombocytopenia. Not Known: • neutropenia • agranulocytosis In patients taking amiodarone there have been incidental findings of bone marrow granulomas.

The clinical significance of this is unknown. Cardiac disorders Common: • bradycardia, generally moderate and dose-related. 4) Very rare: • marked bradycardia or sinus arrest in patients with sinus node dysfunction and/or in elderly patients.

4) Common: • hypothyroidism • hyperthyroidism, sometimes fatal Very rare: • syndrome of inappropriate antidiuretic hormone secretion (SIADH) Eye disorders Very common: • corneal microdeposits usually limited to the area under the pupil, which are usually only discernable by slit-lamp examinations.

They may be associated with coloured halos in dazzling light or blurred vision. Corneal micro-deposits consist of complex lipid deposits and are reversible following discontinuation of treatment. The deposits are considered essentially benign and do not require discontinuation of amiodarone.

4). Gastrointestinal disorders Very common: • benign gastrointestinal disorders (nausea, vomiting, dysgeusia) usually occurring with loading dosage and resolving with dose reduction. 5 to 3 times normal range), occurring at the beginning of therapy.

It may return to normal with dose reduction or even spontaneously. Common: • acute liver disorders with high serum transaminases and/or jaundice, including hepatic failure, which are sometimes fatal. Very rare: • chronic liver disease (pseudo alcoholic hepatitis, cirrhosis), sometimes fatal.

This medicine contains lactose monohydrate. Patients with rare hereditary problems of galactose intolerance, total lactase deficiency or glucose- galactose malabsorption should not take this medicine. 8). Because these reactions may be delayed, patients on long-term treatment should be carefully supervised.

As undesirable effects are usually dose related the minimum effective maintenance dose should be given. 8). 8): Too high a dosage 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, treatment with Amiodarone Hydrochloride 200mg Tablets should be withdrawn. If necessary, beta-adrenostimulants or glucagon may be given. Because of the long half-life of amiodarone, if bradycardia is severe and symptomatic the insertion of a pacemaker should be considered.

Oral Amiodarone Hydrochloride 200mg Tablets are not contraindicated in patients with latent or manifest heart failure but caution should be exercised as, occasionally, existing heart failure may be worsened. In such cases, Amiodarone Hydrochloride 200mg Tablets may be used with other appropriate therapies.

The pharmacological action of amiodarone induces ECG changes:

QT prolongation (related to prolonged repolarisation) with the possible development of U-waves and deformed T-waves; these changes do not reflect toxicity. In the elderly, heart rate may decrease markedly. Treatment should be discontinued in case of onset of 2nd or 3rd degree A-V block, sino-atrial block or bifascicular block.

Amiodarone has a low pro-arrhythmic effect. 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 pro-arrhythmic effect, whether or not this is associated with a worsening of the cardiac condition.

1 (one 200mg tablet contains approximately 75mg iodine). Sinus bradycardia and sino-atrial heart block. In patients with severe conduction disturbances (high grade AV block, bifascicular or trifascicular block) or sinus node disease, Amiodarone Hydrochloride 200mg Tablets should be used only in conjunction with a pacemaker.

Evidence or history of thyroid dysfunction. Thyroid function tests should be performed in all patients prior to therapy. 5). 6). 6).