INDICATIONS     CONTRA-INDICATIONS     DOSAGE     SIDE-EFFECTS     PREGNANCY     OVERDOSE     IDENTIFICATION     PATIENT INFORMATION
AMIOTACH (sterile iv injection)

SCHEDULING STATUS:
S4

PROPRIETARY NAME
(and dosage form):

AMIOTACH (sterile iv injection)

COMPOSITION:
Each ampule contains Amiodarone Hydrochloride 150 mg/3 mL (50 mg/mL) and benzyl alcohol as preservative (2.02% m/v)

PHARMACOLOGICAL CLASSIFICATION:
A 6.2 Cardiac depressants

PHARMACOLOGICAL ACTION:
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 artria, AV-node, His-Purkinge system, ventricles and accessory antrioventricular conduction pathways. Amiodarone also demonstrates non-competitive-alpha and beta-adrenoceptor antagonism.

INDICATIONS:
Where rapid response is required in the control of tachyarrhythmias associated with Wolff-Parkinson-White syndrome and other types of tachyarrhythmias of paroxysmal nature including supraventricular, nodal and ventricular tachycardias, atrial flutter and atrial fibrillations and ventricular fibrillations which have proved to be resistant to other anti-arrhythmic therapy.

CONTRA-INDICATIONS:
AMIOTACH should not be used when the following medical problems exist:

•	Hypersensitivity to amiodarone.
•	Atrioventricular (AV) block, pre-existing 2nd or 3rd degree, without pacemaker (risk of complete heart block).
•	Bradycardic episodes resulting in syncope, unless controlled by pacemaker.
•	Severe sinus node function impairment, causing marked sinus bradycardia, less controlled by pacemaker (AMIOTACH reduces sinus node automatically and may cause atropine-resistant sinus bradycardia).
•	Acute hepatitis.
•	Severe respiratory failure, circulatory collapse and severe arterial hypotension.
•	Pregnancy and Lactation (see PREGNANCY AND LACTATION).

WARNINGS:
AMIOTACH is considered to be unsafe in patients with porphyria because it has been shown to be porphyrinogenic in in-vitro systems.
When the following medical problems exist, the risk-benefit should be considered:

•	Congestive heart failure
•	Hepatic function impairment (lower doses may be required)
•	Hypokalaemia (should be corrected prior to initiation of AMIOTACH therapy; AMIOTACH may be ineffective or arrhythmogenic).
•	Thyroid function impairment, including goitre or nodules (increased risk of hypothyroidism or hyperthyroidism)
•	Caution is recommended also during open-heart surgery inpatients receiving AMIOTACH because of the risk of hypotension upon discontinuation of cardiopulmonary bypass. AMIOTACH should be administered solely in 5% dextrose since it is incompatible with saline. Solutions containing less than 2 ampoules AMIOTACH in 500 mL 5% dextrose are unstable and should not be used.

INTERACTIONS:
Note: AMIOTACH may interact with other medications for weeks to months after it is discontinued because of its slow elimination.
Concomitant administration with arrhythmogenic drugs, for example phenothiazine anti psychotics, tricyclic antidepressants, halofantrine and terfenadine, should be avoided. AMIOTACH may produce additive cardiac effects with other antiarrhythmics and increase the risk of tachyarrhythmias; amiodarone increases plasma concentrations of quinidine, procainamide, flecainide and phenytoin; concurrent use of amiodarone with quinidine, disopyramide, procainamide, or mexiletine has been reported to result in a more prolonged OT interval and, rarely, torsades de pointes, and therefore, concurrent use with all class I antiarrhythmics requires great caution.
Since AMIOTACH inhibits metabolism and potentiates the anticoagulant effect, the effects of warfarin and other oral anticoagulants (coumarin-derivative) may be enhanced, beginning as early as 4 to 6 days after initiation of AMIOTACH therapy and persisting as long as weeks or months after it is withdrawn; prothrombin times may double or triple, but effect is very erratic; it is recommended that the dose of anticoagulant be reduced by one third to one half and that the prothrombin times be monitored closely.
In patients with underlying sinus function impairment, the concomitant administration of AMIOTACH with beta-adrenergic blocking agents and calcium channel blocking agents may cause potentiation of bradycardia, sinus arrest, and atrioventricular (AV) block. AMIOTACH increases serum concentrations of digoxin and probably other digitalis glycosides, possibly to toxic levels. This may produce additive effects on sinoatrial (SA) and AV nodes. Therefore, digitalis glycosides should be withdrawn or the dosage reduced by 50%. If continued, digitalis serum concentrations should be carefully monitored. Concurrent use of AMIOTACH with potassium-depleting diuretics (loop/thiazide diuretics/ indapamide) may lead to an increased risk of arrhythmias associated with hypokalaemia. AMIOTACH may increase plasma concentrations of phenytoin, resulting in increased adverse effects and/or toxicity.
Bradycardia unresponsive to AMIOTACH and hypotension are the potentially severe complications that have been reported in patients taking amiodarone and undergoing general anaesthesia. Patients receiving AMIOTACH should inform the anaesthetist.

PREGNANCY AND LACTATION:
Administration during pregnancy should be avoided since AMIOTACH crosses the placenta and has the potential to cause the following adverse effects:
bradycardia and effects on thyroid status (iodine is known to cause foetal goitre, hypothyroidism, and mental retardation) in the neonate.
AMIOTACH is distributed into human breast milk. Use by breastfeeding mothers is not recommended and mothers should be advised to contact a doctor before nursing.
One ampoule of AMIOTACH contains approximately 56 mg of iodine. Iodine freely crosses the placenta and may cause thyroid disorders in the foetus; the uncertainty as to the effect of this iodine load on the foetus has largely limited the use of amiodarone in pregnancy.

DOSAGE AND DIRECTIONS FOR USE:
AMIOTACH should only be used when facilities for close monitoring of cardiac function and resuscitation are available.
It is given by intravenous infusion usually in a dose of 5 mg/kg body-weight in 250 mL dextrose 5%, infused over 20 minutes to 2 hours; further doses may be given up to a maximum of 1200 mg in up to 500 mL of dextrose 5%, in 24 hours. Repeated infusions are preferably made through a central venous catheter. In emergencies it may be given in doses of 150 mg to 300 mg in 10 to 20 mL of dextrose by slow intravenous injection over a period of not less than 3 minutes; a second injection should not be given until at least 15 minutes after the first.
Maintenance treatment:
The intravenous route is not intended for long-term (longer than 3 weeks) maintenance treatment. Patients may be switched to oral amiodarone, once their arrhythmias have been suppressed by intravenous AMIOTACH. The optimal dose to use when changing from intravenous to oral amiodarone will depend on the dose of intravenous AMIOTACH already administered, as well as the bioavailability of oral amiodarone.
Clinical monitoring is recommended, particularly in elderly patients who are changed to oral amiodarone therapy.

SIDE-EFFECTS AND SPECIAL PRECAUTIONS:
Side Effects:
Adverse effects are common with AMIOTACH; many are dose-related and reversible with reduction in dose.
Vascular disorders
Frequent: hypotension.
Severe hypotension may follow intravenous administration particularly, though not exclusively, at rapid infusion rates.
Hypotension can also be precipitated by overdosage.
Frequency unknown: thrombophlebitis can occur if amiodarone is injected regularly or infused for prolonged periods into a peripheral vein. Rapid intravenous administration has been associated with anaphylactic shock and hot flushes.
Cardiac disorders
Less frequent: arrhythmias; congestive heart failure, sinus bradycardia, heart failure may be precipitated or aggravated.
Frequency unknown: severe bradycardia, sinus arrest, and conduction disturbances. Ventricular tachyarrhythmias; torsade de pointes appears to be less of a problem with AMIOTACH than other antiarrhythmics.
Endocrine disorders
Less frequent: hypothyroidism, hyperthyroidism.
AMIOTACH is reported to reduce the peripheral transformation of thyroxine [levothyroxine] (T4) to tri-iodothyronine (T3) and to increase the formation of reverse- T3. It can affect thyroid function and may induce hypo- or hyperthyroidism.
AMIOTACH's iodine content contributes to its thyrotoxicity.
Respiratory, thoracic and mediastinal disorders
Frequent: pulmonary fibrosis or interstitial pneumonitis/alveolitis.
Frequency unknown:severe pulmonary toxicity including pulmonary fibrosis and interstitial pneumonitis. These effects are usually reversible on withdrawal of amiodarone but are potentially fatal.
Hepatobiliary disorders
Frequency unknown: cirrhosis or hepatitis; fatalities have been reported.
In hepatitis, hepatic enzymes are commonly elevated to several times normal within 2 months after initiation of therapy; deaths as a result of hepatic failure resembling alcoholic cirrhosis have occurred rarely.
Eye disorders
Less frequent: ocular toxicity; including optic neuropathy and/or optic neuritis.
Frequency unknown: prolonged treatment with AMIOTACH causes the development of benign yellowish-brown corneal micro-deposits, but these are reversible on stopping therapy.
Skin and subcutaneous tissue disorders
Frequent: photosensitivity reactions are also common, particularly to long-wave ultraviolet-A [UVA] light.
Less frequent: blue-grey discolouration of the skin.
Reproductive system and breast disorders
Less frequent: non-infectious epididymitis.
Psychiatric disorders
Frequency unknown: nightmares.
Nervous system disorders
Frequent: neurotoxicity (trouble in walking; numbness or tingling in fingers or toes; trembling or shaking of hands; unusual and uncontrolled movements of the body; weakness of arms or legs), headaches.
Frequency unknown: tremor, sleeplessness, peripheral neuropathy, paraesthesias and ataxia.
Gastro-intestinal disorders
Frequent: nausea and vomiting.
General disorders and administration site conditions:
Less frequent: metallic taste.
Frequency unknown: sweating and fatigue.
Investigations
There may be abnormal liver function tests.

Special Precautions:
Cardiac disorders
AMIOTACH should not be given to patients with bradycardia, sino-atrial block, atrioventricular block or other severe conduction disorders (unless the patient has a pacemaker), severe hypotension, or severe respiratory failure. It may be used with caution in patients with heart failure. Electrolyte disorders should be corrected before starting treatment.
Endrocine disorders
The use of AMIOTACH should be avoided in patients with disorders of the thyroid gland, or with a history of thyroid disorders.
Investigations:
Thyroid function should be monitored regularly in order to detect AMIOTACH-induced hyper- or hypothyroidism. Tests of liver and pulmonary function also should be carried out regularly in patients on long-term therapy.
General disorders and administration site conditions:
The use of AMIOTACH should be avoided in patients with iodine sensitivity. Patients taking AMIOTACH should avoid exposure to sunlight.

KNOWN SYMPTOMS OF OVERDOSAGE AND PARTICULARS OF ITS TREATMENT:
Rapid administration or over dosage may precipitate circulatory collapse. Treatment is primarily supportive and symptomatic.
It is important to monitor cardiac rhythm and blood pressure.
A beta-adrenergic agonist or pacemaker may be indicated for bradycardia. In such patients presenting with bradycardia, the use of atropine has been successful.
Hypotension may respond to positive inotropic and/or vasopressor agents.

IDENTIFICATION:
A clear, pale yellow solution free from visible particles filled in 5 mL USP type 1 flint ampoule OPC-CUT and glazed with 2 yellow bands on stem.

PRESENTATION:
3 mL (50 mg/mL) AMIOTACH solution is filled in a 5 mL USP Type 1 flint ampoule OPC-CUT and glazed with 2 yellow bands on stem. 10 such ampoules are packed in an outer cardboard carton.

STORAGE INSTRUCTIONS:
Store below 25ºC in a cool place. Protect from light. Discard the diluted solution after 24 hours.
KEEP OUT OF THE REACH OF CHILDREN.

REGISTRATION NUMBER:
42/6.2/0035

NAME AND BUSINESS ADDRESS OF THE HOLDER OF THE CERTIFICATE OF REGISTRATION:
PHARMACARE LIMITED
Building 12
Healthcare Park
Woodlands Drive
Woodmead
Sandton

DATE OF PUBLICATION OF THIS PACKAGE INSERT:
14 September 2007        1009574

Updated on this site: November 2008
Source: Pharmaceutical Industry
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