INDICATIONS     CONTRA-INDICATIONS     DOSAGE     SIDE-EFFECTS     PREGNANCY     OVERDOSE     IDENTIFICATION     PATIENT INFORMATION

Logo BIO-AMIODARONE (Tablets)

SCHEDULING STATUS:
S4

PROPRIETARY NAME
(and dosage form):

BIO-AMIODARONE (Tablets)

COMPOSITION
Active ingredient:       
Amiodarone Hydrochloride 200 mg
Other ingredients:        Maize starch, Lactose monohydrate, Povidone, Magnesium stearate, Colloidal anhydrous silica and Pre-gelatinised starch.

PHARMACOLOGICAL CLASSIFICATION
A 6.2 Cardiac depressants

PHARMACOLOGICAL ACTION
Amiodarone is an anti-arrhythmic compound belonging to class III anti-arrhythmic agents.
Amiodarone prolongs the duration of the action potential, particularly in the nodal and Purkinje tissue. Amiodarone does not appear to alter the resting membrane potential, but depresses membrane responsiveness and prolongs the refractory period in the atria, AV node, His-Purkinje system, ventricles and accessory atrio-ventricular conduction pathways. The conduction rate is reduced in the atria, AV node and accessory pathways. Amiodarone also demonstrates non-competitive alpha and beta adrenoreceptor antagonism. Amiodarone is strongly protein bound (96%) and the plasma half-life is usually approximately 50 days. However, there may be considerable inter-patient variation.

INDICATIONS
Prevention of tachyarrhythmia's associated with Wolff-Parkinson-White syndrome and other types of tachyarrhythmias of paroxysmal nature including supraventricular, nodal and ventricular tachycardia, atria] flutter and atrial fibrillation, and ventricular fibrillation when other medicines cannot be used.

CONTRA-INDICATIONS
- Sinus bradycardia and sino-atrial blocks without pacemaker.
- Sinus disease without pacemaker.
- Acute conduction disturbances without pacemaker.
- Hyperthyroidism; evidence or history of thyroid dysfunction.
- Known hypersensitivity to iodine.
- Medicines producing torsades de pointe.
- Severe hypotension.
- Class la antiarrhythmic drugs, sotalol, stimulant laxatives, and injectable diltiazem.
- Pregnant or breast-feeding women.
- Avoid in patients with acute porphyria.

WARNINGS
- An ECG should be performed before treatment initiation.
- The slowing down in heart rate may be more pronounced in elderly patients.
- While on amiodarone, the electrocardiogram is modified.
- The occurrence - on treatment - of a 2nd or 3rd degree atrioventricular block, or of a sino-atrial or bifascicular block should prompt treatment discontinuation.
- Thyroid function should be monitored regularly in order to detect amiodarone-induced hyper- or hypothyroidism. Thyroxine, tri-iodothyronine and thyrotropin (thyroid stimulating hormone, TSH) concentration should be measured; clinical assessment alone is unreliable.

DOSAGE AND DIRECTIONS FOR USE
It is particularly important that the minimum effective dose be used. In all cases the patient management must be judged on the individual response and well being.
Initial treatment
The usual dosage is 200 mg, 3 times a day and may be continued for 1 week. The dosage should then be reduced to 200 mg twice daily for a further week.
Maintenance treatment
After the initial period the dosage should be reduced to 200 mg daily, or less if appropriate. The second 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.

SIDE-EFFECTS AND SPECIAL PRECAUTIONS
Eye manifestations:
- Cortical micro deposits develop in the majority of patients. These are reversible on stopping therapy.
- Some cases of optic neuropathy with blurred vision and decrease in visual acuity have been reported.
- During long term therapy regular ophthalmologic examination is recommended.
Skin reactions:
- Photosensitization. Sun exposure (and more generally exposure to UV) should be avoided during treatment.
  Cases of erythema were also reported during radiotherapy.
- Skin pigmentation, whether liliaceous or blue-grey occurs less frequently
Thyroid manifestations
- Amiodarone is reported to reduce the peripheral transformation of thyroxine (T4) to tri-iodothyronine (T3) and to increase the formation of reverse T3.
  It can affect thyroid function and may induce hypo- or hyperthyroidism
- Hypothyroidism has a usual presentation: weight gain, apathy, and somnolence.
- Hyperthyroidism can be more deceptive: pauci-symptomatic; psychiatric forms in elderly.
- In case of hyperthyroidism, BIO-AMIODARONE should be withdrawn.
Pulmonary manifestations:
- There have been reports of severe pulmonary toxicity including pulmonary fibrosis and interstitial pneumonitis. Test of pulmonary function should be carried out regularly in patients on long-term therapy. These pulmonary effects may be potentially fatal although reversible on withdrawal.
Neurological effects:
- Sensory-motor peripheral neuropathy and/or myopathy, usually reversible with treatment discontinuation.
- Other reported symptoms: extra-pyramidal tremor, cerebellar-like taxia, less frequently benign intracranial hypertension, nightmares, vertigo, headaches and sleeplessness.
Hepatic manifestations:
- Regular monitoring of hepatic function (transaminases) is recommended during treatment:
- Increases in transaminases which can be in isolation (1,5 to 3 times the normal level) regressing after reduction in doses, or even spontaneously regressing. Cirrhosis or hepatitis has been reported. Cardiac effects:
- Generally moderate anti dose-related bradycardia.
- Less frequently conduction disturbances (sino-atrial block, atrioventricular blocks of various degrees).
- In some cases marked bradycardia or sinus arrest has occurred.
Other effects:
- Benign gastro-intestinal disorders (nausea, vomiting, dysgeusia)
- Some isolated cases varying in aspect have been observed in a context evoking hypersensitivity reactions vasculitis, renal impairment with moderate increase in creatinine, thrombocytopenia.

SPECIAL PRECAUTIONS
- Electrolytic disturbances, especially hypokalaemia.
- During treatment, it should be advised to avoid sun exposure or to be protected.
- In patients with thyroid disease history - whether personal or family - and in hypothyroid patients treated with thyroid hormones, the treatment - where necessary- should be administered with caution, i.e. at minimally active posology and under strict clinical and biological monitoring.
- Caution in patients with moderate or severe renal impairment because of the possibility of iodine accumulation

INTERACTIONS
Contra-indicated combinations:
Non antiarrhythmic agents producing torsades de pointes (like astemizole, bepridil, IV erythromycin, halofantrin, pentamidin, sparfloxacin, sultopride, terfenadine, vincamin): increased risk of potentially lethal torsades de pointes.
Inadvisable combinations:
- Class 1a antiarrhythmics (quinidine-like medicines, disopyramide), sotalol; increased risk of potentially lethal torsades de pointes.
- Stimulant laxatives; risk of torsades de pointes. Use another type of laxative.
- Injectable diltiazem; risk of bradycardia and atrioventricular block. If this combination is deemed absolutely necessary, it should be used only under clinical supervision and continuous ECG monitoring.
Combinations requiring precautions of use:
- Beta-blockers and some calcium antagonists (verapamil, diltiazem): potentiation of bradycardia, sinus arrest and atrioventricular (AV) block results.
- Hypokalaemic agents (risk of torsades de pointes):
Hypokalaemic diuretics used alone or in combination;
Steroids (gluco, mineralocorticosteroids, used systemically), tetracosactide; amphotericin B via IV route.
- Hypokalaemia should be prevented (and where necessary corrected) QT interval should be monitored, and in case of torsades de pointes, antiarrhythmics should not be administered (electrosystolic stimulation, magnesium sulphate via intravenous route).
- Oral anticoagulants: the increase in oral anticoagulants' effects thus of the haemorrhagic risk requires a more frequent verification of prothrombin level by the INR.
- Digoxin and digoxin-like: excessive bradycardia and atrioventricular conduction disturbances. For digoxin: possible increase of digoxin plasma levels due to a reduction in digoxin clearance. Clinical supervision and ECG monitoring, and when necessary, adjust digoxin dosage.
- Phenytoin: increase in phenytoin plasma concentrations with signs of overdosage (particularly neurological signs). Clinical supervision and reduction of phenytoin doses as soon as overdosage signs occur. If necessary, control phenytoin plasma levels.
General anaesthetics:
Potentially serious complications have been reported when amiodarone is combined to general anaesthetics: atropine resistant bradycardia, hypotension, conduction disturbances, decrease in cardiac output.
Some cases of acute respiratory distress have been observed just after cardiovascular surgery: possible potentialisation of oxygen toxic effect has been suggested.

KNOWN SYMPTOMS OF OVERDOSAGE AND PARTICULARS OF ITS TREATMENT
Overdosage may lead to severe bradycardia or spontaneously reversible episodes of ventricular tachycardia. Most often, it remains asymptomatic. However, because of the products kinetics, a sufficiently prolonged monitoring, especially cardiac monitoring is recommended. Treatment is symptomatic and supportive.

IDENTIFICATION
Scored, flat, white tablets.

PRESENTATION
Boxes containing 30 tablets in PVC/ALU blister

STORAGE INSTRUCTIONS
Keep at room temperature (15-25ºC), protected from light
Do not remove the blisters from the cartons until required for use.
KEEP OUT OF REACH OF CHILDREN

REGISTRATION NUMBER
34/6.2/0119

NAME AND BUSINESS ADDRESS OF THE APPLICANT
Biotech Laboratories (Pty) Ltd
106 16th Road
Midrand,
1685

DATE OF PUBLICATION OF THIS PACKAGE INSERT
24 January 2003

P 340119/1

Product launch: January 2007
Source: Pharmaceutical Industry

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