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AMIODARONE 50 MG/ML SOLUTION FOR I.V. INJECTION

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Amiodarone 50mg/ml solution for IV injection

Each 3ml ampoule contains 150mg of Amiodarone hydrochloride

Infohealth Laboratories Ltd

PATIENT INFORMATION LEAFLET
Read all of this leaflet carefully before you start
having this medicine.
Keep this leaflet. You may need to read it again.
If you have further questions, please ask your doctor, nurse
or pharmacist.
This medicine has been prescribed for you. Do not pass it on to
others. It may harm them, even if their symptoms are the same
as yours.
If any of the side effects get serious, or if you notice any side effects
not listed in this leaflet, please tell your doctor or pharmacist.

In this leaflet
1. What Amiodarone Injection is and what it is given for.
2. Before you are given Amiodarone Injection.
3. How Amiodarone Injection is given.
4. Possible side effects.
5. How to store Amiodarone Injection.

If you are taking certain other medicines such as:




some other heart drugs (e.g. beta-blockers such as sotalol);



medicines to treat mental illness (antipsychotics, e.g.
chlorpromazine, thioridazine, fluphenazine, pimozide,
haloperidol, amisulpride and sertindole; or antidepressants,
including lithium and tricyclic antidepressants e.g. doxepin,
maprotiline amitriptyline);



medicines to treat allergic reactions (antihistamines, e.g.
terfenadine, mizolastine);




medicines to treat or prevent malaria (antimalarials);



stimulant laxatives.

antibiotics (e.g. erythromycin injection, co-trimoxazole or
moxifloxacin);

pentamidine injections (used to treat e.g. AIDS or
pneumonia);

You must inform your doctor if you are taking any of these
medications.

6. Further Information.

Grapefruit juice can increase the blood level of Amiodarone Injection
and should be avoided during treatment with Amiodarone 50mg/ml
solution for IV injection.

1. WHAT AMIODARONE INJECTION IS AND WHAT
IT IS GIVEN FOR

Amiodarone Injection should be given to you with
SPECIAL CARE:

Amiodarone is used to control an irregular or rapid heart rate when
other treatments have been ineffective or cannot be used. This type
of medicine is known as an anti-arrhythmic.

If it is being given as an infusion and you have low blood pressure,
severe heart failure or severe cardiomyopathy (weakness of the
heart muscle);

Amiodarone Injection should only be given in a hospital by a
doctor. It can be used where a rapid response is required. Your
blood pressure and heart rate should be monitored whilst receiving
Amiodarone Injection.

If you are going to have an anaesthetic or high dose
oxygen therapy;
If you suffer from asthma or any other breathing disorder;
If you suffer from liver disease;

2. BEFORE YOU ARE GIVEN AMIODARONE
INJECTION
Amiodarone Injection should NOT be given to you:

If you suffer from porphyria (a rare genetic blood disorder).

Pregnancy

If you suffer from problems with your heart, such as heart block,
which can cause a slow heart rate, a slow pulse or dizziness.

Your doctor will prescribe Amiodarone Injection only if he/she
considers the benefit of treatment outweighs the risks during your
pregnancy.

If you have or have had thyroid problems. (Your doctor will test
your thyroid before prescribing this medicine).

Breast-feeding

If you have serious breathing difficulties.

You should not be given Amiodarone Injection if you are breastfeeding.

If you have very low blood pressure (dizziness or feeling faint
at times).

Premature and newborn babies

If it is given as a single injection and you have serious breathing
difficulties, low blood pressure, heart failure or cardiomyopathy
(weakness of the heart muscle).

Amiodarone Injection should only be given to premature babies
and newborns up to 1 month old if they have a heart rate disorder
that is life-threatening and other treatment does not work, or is not
possible. Amiodarone Injection should only be used in a special
care unit under continuous monitoring (ECG and blood pressure).

If you have an allergy to:





amiodarone,

Children up to 3 years old

iodine or

The benzyl alcohol in this product may cause toxic and allergic
reactions in infants and children up to 3 years old.

any of the other ingredients.

If you are pregnant or likely to become pregnant, except in
exceptional circumstances.
If you are breast-feeding.

Driving and using machines
This medicine should not affect your ability to drive. However, if
you experience any dizziness, make sure that you are fit to drive or
operate machinery before attempting to do so.

Taking other medicines
Before Amiodarone Injection is given to you, please inform
your doctor or pharmacist if you are taking, or have recently
taken, any other medicine – even those which your doctor has
not prescribed for you, but which you have bought yourself from
your chemist/pharmacy.
In particular, please check with your doctor if you are taking
any of the following, (in addition to the drugs listed in section 2,
‘Before you are given Amiodarone Injection’):

If you experience any of the following side effects you should
tell your doctor immediately, who will decide whether to
stop the medication.

The most common potentially serious side effects include:




a slow pulse
a decrease in blood pressure, leading to collapse

Other very rare but potentially serious side effects reported
with Amiodarone Injection include:






Digoxin (used to treat certain heart conditions);



Chest pain or palpitations (awareness of heart beat), or
abnormal heart rhythm or cardiac arrest

Anticoagulants (used to thin the blood e.g. warfarin);



Liver disorders, including jaundice (yellowing of the skin or
eyes), and may lead to liver failure



Generalised allergic reactions such as swelling of the face lips
and/or tongue, shortness of breath which may be fatal










Breathing difficulties (with or without fever), inability to breath

Ciclosporin (used after transplant operations);




Phenytoin (used to treat epilepsy);
Some calcium channel inhibitors (used to treat high blood
pressure and angina e.g. verapamil, diltiasem);

Simvastatin or other statins (used to lower cholesterol levels);
other drugs like lidocaine, tacrolimus, sildenafil, fentanyl,
midazolam and ergotamine;
Flecainide (used to treat irregular heart rhythms);
Fluoroquinolones e.g. ciprofloxacin (antibiotics used to treat a
wide range of infections);

drugs which may change the levels of potassium or magnesium
in your blood: e.g. diuretics (water tablets), steroid tablets or the
antifungal amphotericin (when given directly into a vein).

3. HOW AMIODARONE INJECTION IS GIVEN
Amiodarone Injection should only be given in a hospital by a doctor.
Your blood pressure and heart rate should be monitored whilst
receiving Amiodarone Injection.
Amiodarone Injection is given directly into the blood stream using a
drip (or central line). It should not be given too rapidly.
This medicine is given diluted in a sugar (5% dextrose) solution.
The usual dose of Amiodarone Injection is 5 mg for every kg body
weight, given by intravenous infusion over 20 minutes to 2 hours.
This may then be followed by further infusions up to 1200 mg in 24 hours.
The correct dose and dilution for you will have been decided by the
doctor and will depend upon your condition.
Children and the elderly may be prescribed lower doses.
IV injection may be given at an initial dose at 5mg for every kg body
weight. This dose should be given over a minimum of 3 minutes and
should not be repeated less than 15 minutes after initial dose. This
dose regimen may be considered only in exceptional circumstances
and emergencies.

wheezing and breathing difficulties in patients with asthma
Bone marrow disorders
Raised pressure around the brain causing headaches and
visual disturbance

Other common less serious side effects are:



local injection site reactions including swelling, pain, redness,
infection and pigmentation (skin colouring) changes

Very rare and less serious side effects reported include:





Hot flushes, sweating
Nausea (feeling sick)
Headaches

5. HOW TO STORE AMIODARONE INJECTION
Keep all medicines out of
the reach and sight of children.
Do not use Amiodarone Injection after the expiry date, which is
marked on both the outer carton and on each ampoule.
Do not store above 25°C. Store in the original container, protected
from light. Keep the ampoules in the outer carton.

6. FURTHER INFORMATION
What Amiodarone Injection contains
Each ampoule contains 150mg of the active substance,
amiodarone hydrochloride. The other ingredients are benzyl
alcohol, polysorbate 80 and water for injections.

What Amiodarone Injection looks like and contents of
the pack
Each carton contains 10 ampoules. Each ampoule contains 3ml of
clear, pale yellow solution for injection.

Marketing Authorisation Holder
Like all medicines, Amiodarone Injection can have side effects. The
side effects mentioned here have been divided into how often they
occur according to the following frequencies:

Infohealth Laboratories Ltd
28 Chipstead Valley Road
Coulsdon
Surrey
CR5 2RA
UK

Very common:

affects more than 1 in 10 people

Manufacturer

Common:

affects more than 1 in 100 people

Uncommon:

affects more than 1 in 1,000 people

Rare:

affects more than 1 in 10,000 people

Very rare:

affects less than 1 in 10,000 people

L A B O R A T O R I E S

Haupt Pharma Livron
1, rue Comte de Sinard
BP 1 - 26250 Livron Sur Drome
France
This leaflet does not contain all the information about your
medicine. If you have any questions or are not sure about
anything, ask your doctor or pharmacist.

Product licence number
PL 19664/0001

Date of preparation of leaflet: April 2009.

51716796

4. POSSIBLE SIDE EFFECTS

Amiodarone 50mg/ml solution for IV injection

Each 3ml ampoule contains 150mg of Amiodarone hydrochloride

Infohealth Laboratories Ltd

TECHNICAL INFORMATION LEAFLET
1. NAME OF THE MEDICINAL PRODUCT
Amiodarone 50mg/ml solution for I.V. injection.
2. QUALITATIVE AND QUANTITATIVE COMPOSITION
Each 3ml ampoule contains 150mg amiodarone hydrochloride.
Each ml contains 50mg amiodarone hydrochloride. For excipients, see 6.1.
3. PHARMACEUTICAL FORM
Solution for injection. The solution is clear and has a pale yellow colour.
4. CLINICAL PARTICULARS
4.1 Therapeutic indications
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.
Tachyarrhythmias associated with Wolff-Parkinson-White syndrome.
All types of tachyarrhythmias including supraventricular, nodal and ventricular
tachycardias; atrial flutter and fibrillation; ventricular fibrillation; when other
drugs cannot be used.
Amiodarone 50mg/ml solution for I.V. injection can be used where a rapid
response is required or where oral administration is not possible.
4.2 Posology and method of administration
Amiodarone 50mg/ml solution for I.V. injection should only be used when
facilities exist for cardiac monitoring, defibrillation, and cardiac pacing.
Amiodarone 50mg/ml solution for I.V. injection may be used prior to
DC cardioversion.
The standard recommended dose is 5mg/kg bodyweight given by
intravenous infusion over a period of 20 minutes to 2 hours. This should be
administered as a dilute solution in 250ml 5% dextrose. This may be followed
by repeat infusion up to 1200mg (approximately 15mg/kg bodyweight) in up
to 500ml 5% dextrose per 24 hours, the rate of infusion being adjusted on the
basis of clinical response (see section 4.4).
In extreme clinical emergency the drug may, at the discretion of the clinician,
be given as a slow injection of 150-300mg in 10-20ml 5% dextrose over a
minimum of 3 minutes. This should not be repeated for at least 15 minutes.
Patients treated in this way with Amiodarone 50mg/ml solution for I.V. injection
must be closely monitored, e.g. in an intensive care unit. (see section 4.4).
Changeover from intravenous to oral therapy
As soon as an adequate response has been obtained, oral therapy should be
initiated concomitantly at the usual loading dose (200mg three times a day).
Amiodarone 50mg/ml solution for I.V. injection should then be phased
out gradually.
Paediatric population
Due to the presence of benzyl alcohol, intravenous amiodarone is usually
contraindicated in neonates and premature babies (see section 4.3).
No controlled paediatric studies have been undertaken. In published
uncontrolled studies effective doses for children were (see section 4.4):
Loading dose: 5mg/kg body weight over 20 minutes to 2 hours.
Maintenance dose: 10 to 15mg/kg/day from a few hours to several days.
If needed, oral therapy may be initiated concomitantly.
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. Particular attention should
be paid to monitoring thyroid function (see section 4.3, 4.4 and 4.8).
Cardio Pulmonary resuscitation
The recommended dose for ventricular fibrillations/pulseless ventricular
tachycardia resistant to defibrillation is 300 mg (or 5 mg/kg body-weight)
diluted in 20 ml 5% dextrose and rapidly injected. An additional 150 mg (or
2.5 mg/kg body-weight) IV dose may be considered if ventricular
fibrillation persists.
See section 6.2 for information on incompatibilities.
4.3 Contraindications
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 should be used only in conjunction
with a pacemaker.
Evidence or history of thyroid dysfunction. Thyroid function tests should be
performed where appropriate prior to therapy in all patients.
Severe respiratory failure, circulatory collapse, or severe arterial hypotension;
hypotension, heart failure and cardiomyopathy are also contra-indications
when using Amiodarone 50mg/ml solution for I.V. injection as a bolus injection.
Known hypersensitivity to iodine or to Amiodarone 50mg/ml solution for I.V.
injection, or to any of the excipients. (One ampoule contains approximately
56mg iodine).
The combination of Amiodarone 50mg/ml solution for I.V. injection with drugs
which may induce torsades de pointes is contra indicated (see section 4.5).
Amiodarone 50mg/ml solution for I.V. injection ampoules contain benzyl
alcohol. There have been reports of fatal ‘gasping syndrome’ in neonates
(hypotension, bradycardia and cardiovascular collapse) following the
administration of intravenous solution containing this preservative.
Amiodarone 50 mg/ml solution for I.V. injection should not be given
to neonates or premature babies unless the rhythm disturbance is life
threatening and either resistant to other medication or alternative therapy is
deemed inappropriate.
Pregnancy - except in exceptional circumstances (see section 4.6).
Lactation (see section 4.6).
All these above contra-indications do not apply to the use of amiodarone for
cardiopulmonary resuscitation of shock resistant ventricular fibrillation.




4.4 Special warnings and precautions for use
Benzyl alcohol may cause toxic reactions and allergic reactions in infants and
children up to 3 years old.
Amiodarone 50mg/ml solution for I.V. injection should only be used in a
special care unit under continuous monitoring (ECG and blood pressure).
I.V. infusion is preferred to bolus due to the haemodynamic effects sometimes
associated with rapid injection (see section 4.8). Circulatory collapse may be
precipitated by too rapid administration or overdosage (atropine has been
used successfully in such patients presenting with bradycardia).
Repeated or continuous infusion via peripheral veins may lead to injection
site reactions (see section 4.8). When repeated or continuous infusion is
anticipated, administration by a central venous catheter is recommended.
When given by infusion Amiodarone 50mg/ml solution for I.V. injection may
reduce drop size and, if appropriate, adjustments should be made to the rate
of infusion.
Anaesthesia (see section 4.5): before surgery, the anaesthetist should be
informed that the patient is taking amiodarone.
Amiodarone should not be used in patients with porphyria. It should be
prescribed only when the benefit outweighs the risk and in such cases
treatment should be discussed with an expert centre.
Cardiac disorders
Caution should be exercised in patients with hypotension, decompensated
cardiomyopathy and severe heart failure (also see section 4.3).
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. Pro-arrhythmic effects generally occur in the context of
drug interactions and/or electrolytic disorders (see sections 4.5 and 4.8).
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,
Amiodarone 50mg/ml solution for I.V. injection treatment 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.
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.
Respiratory, thoracic and mediastinal disorders (see section 4.8)
Very rare cases of interstitial pneumonitis have been reported with
intravenous amiodarone. When the diagnosis is suspected, a chest X-ray
should be performed. Amiodarone therapy should be re-evaluated since
interstitial pneumonitis is generally reversible following early withdrawal of
amiodarone, and corticosteroid therapy should be considered (see section
4.8). Clinical symptoms often resolve within a few weeks followed by slower
radiological and lung function improvement. Some patients can deteriorate
despite discontinuing Amiodarone 50mg/ml solution for I.V. injection. Fatal
cases of pulmonary toxicity have been reported.
Very rare cases of severe respiratory complications, sometimes fatal, have
been observed usually in the period immediately following surgery (adult
acute respiratory distress syndrome); a possible interaction with a high
oxygen concentration may be implicated (see sections 4.5 and 4.8).
Hepato-biliary disorders (see section 4.8)
Severe hepatocellular insufficiency may occur within the first 24 hours of I.V.
amiodarone, and may sometimes be fatal. Close monitoring of transaminases
is therefore recommended as soon as amiodarone is started.
Drug interactions (see section 4.5)
Concomitant use of amiodarone with the following drugs is not
recommended: beta-blockers, heart rate lowering calcium channel
inhibitors (verapamil, diltiazem), stimulant laxative agents which may cause
hypokalaemia.
Increased plasma levels of flecainide have been reported with coadministration of amiodarone. The flecainide dose should be reduced
accordingly and the patient closely monitored.
4.5 Interaction with other medicinal products and other forms of interaction
Some of the more important drugs that interact with amiodarone include
warfarin, digoxin, phenytoin and any drug which prolongs the QT interval.
Amiodarone raises the plasma concentrations of oral anticoagulants
(warfarin) and phenytoin by inhibition of CYP 2C9. The dose of warfarin
should be reduced accordingly. More frequent monitoring of prothrombin
time both during and after amiodarone treatment is recommended. Phenytoin
dosage should be reduced if signs of overdosage appear, and plasma levels
may be measured.
Administration of amiodarone to a patient already receiving digoxin will bring
about an increase in the plasma digoxin concentration and thus precipitate
symptoms and signs associated with high digoxin levels. Clinical, ECG
and biological monitoring is recommended and digoxin dosage should be
halved. A synergistic effect on heart rate and atrioventricular conduction is
also possible.
Combined therapy with the following drugs which prolong the QT interval is
contra indicated (see section 4.3) due to the increased risk of torsades de
pointes; for example:
Class Ia anti-arrhythmic drugs e.g. quinidine, procainamide, disopyramide.
Class III anti-arrhythmic drugs e.g. sotalol, bretylium.
Intravenous erythromycin, co-trimoxazole or pentamidine injection.
Some anti-psychotics e.g. chlorpromazine, thioridazine, fluphenazine,
pimozide, haloperidol, amisulpride and sertindole.
Lithium and tricyclic anti-depressants e.g. doxepin, maprotiline,
amitriptyline.
Certain antihistamines e.g. terfenadine, astemizole, mizolastine.
Anti-malarials e.g. quinine, mefloquine, chloroquine, halofantrine.
Moxifloxacin.










51716796

INFORMATION FOR THE DOCTOR

Fluoroquinolones
There have been rare reports of QTc interval prolongation, with or without
torsades de pointes, in patients taking amiodarone with fluoroquinolones.
Concomitant use of amiodarone with fluoroquinolones should be avoided
(concomitant use with moxifloxacin is contra-indicated, see above).
Combined therapy with the following drugs is not recommended:
Beta blockers and certain calcium channel inhibitors (diltiazem, verapamil);
potentiation of negative chronotropic properties and conduction slowing
effects may occur.
Stimulant laxatives, which may cause hypokalaemia thus increasing the risk
of torsades de pointes; other types of laxatives should be used.
Caution should be exercised over combined therapy with the following drugs
which may also cause hypokalaemia and/or hypomagnesaemia: e.g.
diuretics, systemic corticosteroids, tetracosactide, intravenous amphotericin.
In cases of hypokalaemia, corrective action should be taken and QT interval
monitored. In case of torsades de pointes antiarrhythmic agents should not be
given; pacing may be instituted and I.V. magnesium may be used.
Caution is advised in patients undergoing general anaesthesia, or receiving
high dose oxygen therapy.
Potentially severe complications have been reported in patients taking
amiodarone undergoing general anaesthesia: bradycardia unresponsive to
atropine, hypotension, disturbances of conduction, decreased cardiac output.
A few cases of adult respiratory distress syndrome, most often in the period
immediately after surgery, have been observed. A possible interaction with a
high oxygen concentration may be implicated.
Grapefruit juice inhibits cytochrome P450 3A4 and may increase the plasma
concentration of amiodarone. Grapefruit juice should be avoided during
treatment with oral amiodarone.
Drugs metabolised by cytochrome P450 3A4
When drugs are co-administered with amiodarone, an inhibitor of CYP 3A4,
this may result in a higher level of their plasma concentrations, which may lead
to a possible increase in their toxicity:
Ciclosporin: Plasma levels of ciclosporin may increase as much as 2-fold
when used in combination. A reduction in the dose of ciclosporin may be
necessary to maintain the plasma concentration within the therapeutic range.
Other drugs metabolised by cytochrome P450 3A4: examples of such
drugs are the statins lidocaine, tacrolimus, sildenafil, fentanyl, midazolam
and ergotamine.
Simvastatin in combination with amiodarone has been associated with
reports of myopathy/rhabdomyolysis (refer to manufacturer’s prescribing
information for simvastatin).
Flecainide
Given that flecainide is mainly metabolised by CYP 2D6, by inhibiting
this isoenzyme, amiodarone may increase flecainide plasma levels; it is
advised to reduce the flecainide dose by 50% and to monitor the patient
closely for adverse effects. Monitoring of flecainide plasma levels is strongly
recommended in such circumstances.
Interaction with substrates of other CYP 450 isoenzymes
In vitro studies show that amiodarone also has the potential to inhibit CYP 1A2,
CYP 2C19 and CYP 2D6 through its main metabolite. When coadministered,
amiodarone would be expected to increase the plasma concentration of drugs
whose metabolism is dependent upon CYP 1A2, CYP 2C19 and CYP 2D6.
4.6 Pregnancy and lactation
Pregnancy
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.
Lactation
Amiodarone is excreted into the breast milk in significant quantities and
breast-feeding is contra-indicated.
4.7 Effects on ability to drive and use machines
Not relevant.
4.8 Undesirable effects
The following adverse reactions are classified by system organ class and
ranked under heading of frequency using the following convention: very
common (> = 10%), common (> = 1% and < 10%), uncommon (> = 0.1%
and < 1%), rare (> = 0.01% and < 0.1%), very rare (< 0.01%).
Cardiac disorders
Common: Bradycardia, generally moderate.
Very rare: Marked bradycardia, sinus arrest requiring discontinuation of
amiodarone, especially in patients with sinus node dysfunction and/or in
elderly patients.
Onset of worsening of arrythmia, sometimes followed by cardiac arrest (see
sections 4.4 and 4.5).
Blood and lymphatic system disorders
In patients taking amiodarone there have been incidental findings of bone
marrow granulomas. The clinical significance of this is unknown.
Gastrointestinal disorders
Very rare: Nausea.
General disorders and administration site conditions
Common: Injection site reactions such as pain, erythema, oedema, necrosis,
extravasation, infiltration, inflammation, induration, thrombophlebitis, phlebitis,
cellulitis, infection, pigmentation changes.
Hepato-biliary disorders
Very rare: Isolated increase in serum transaminases, which is usually moderate
(1.5 to 3 times normal range) at the beginning of therapy. They may return to
normal with dose reduction or even spontaneously.
Acute liver disorders with high serum transaminases and/or jaundice, including
hepatic failure, sometimes fatal (see section 4.4).
Immune system disorders
Very rare: Anaphylactic shock.








Nervous system disorders
Very rare: Benign intra-cranial hypertension (pseudo tumor cerebri), headache.
Respiratory, thoracic and mediastinal disorders
Very rare: Interstitial pneumonitis (see section 4.4).
Severe respiratory complications (adult acute respiratory distress syndrome),
sometimes fatal (see sections 4.4 and 4.5).
Bronchospasm and/or apnoea in case of severe respiratory failure, and
especially in asthmatic patients.
Skin and subcutaneous tissue disorders
Very rare: Sweating.
Vascular disorders
Common: Decrease in blood pressure, usually moderate and transient.
Cases of hypotension or collapse have been reported following overdosage or
a too rapid injection. Very rare: Hot flushes.
4.9 Overdose
There is no information regarding overdosage with intravenous amiodarone.
Little information is available regarding acute overdosage with amiodarone.
Few cases of sinus bradycardia, heart block, attacks of ventricular tachycardia,
torsades de pointes, circulatory failure and hepatic injury have been reported.
In the event of overdose, treatment should be symptomatic, in addition
to general supportive measures. The patient should be monitored and if
bradycardia occurs beta-adrenostimulants or glucagon may be given.
Spontaneously resolving attacks of ventricular tachycardia may also occur.
Due to the pharmacokinetics of amiodarone, adequate and prolonged
surveillance of the patient, particularly cardiac status, is recommended.
Neither amiodarone nor its metabolites are dialysable.
5. PHARMACOLOGICAL PROPERTIES
Pharmacotherapeutic class : Antiarrhythmics, class III
ATC code : C01BD01
5.1 Pharmacodynamic properties
Amiodarone 50mg/ml solution for I.V. injection is a product for the treatment
of tachyarrhythmias and has complex pharmacological actions. Its effects are
anti-adrenergic (partial alpha and beta blockers). It has haemodynamic effects
(increased blood flow and systematic/coronary vasodilation). The drug reduces
myocardial oxygen consumption and has been shown to have a sparing
effect of rat 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 ATP-ase.
5.2 Pharmacokinetic properties
Pharmacokinetics of amiodarone are unusual and complex, and have not been
completely elucidated. Absorption following oral administration is variable
and may be prolonged with enterohepatic cycling. The major metabolite is
desethylamiodarone. Amiodarone is highly protein bound (> 95%). Renal
excretion is minimal and faecal excretion is the major route.
A study in both healthy volunteers and patients after intravenous administration
of amiodarone reported that the calculated volumes of distribution and total
blood clearance using a two-compartment open model were similar for both
groups. Elimination of amiodarone after intravenous injection appeared to be
biexponential with a distribution phase lasting about 4 hours. The very high
volume of distribution combined with a relatively low apparent volume for
the central compartment suggests extensive tissue distribution. A bolus I.V.
injection of 400mg gave a terminal T1/2 of approximately 11 hours.
5.3 Preclinical safety data
There are no pre-clinical data of relevance to the prescriber which are
additional to that already included in other sections of the SPC.
6. PHARMACEUTICAL PARTICULARS
6.1 List of excipients
Benzyl alcohol.
Polysorbate 80.
Water for Injections.
6.2 Incompatibilities
Amiodarone 50mg/ml solution for I.V. injection is incompatible with saline and
should be administered solely in 5% dextrose solution. Amiodarone 50mg/ml
solution for I.V. injection, diluted with 5% dextrose solution to a concentration
of less than 0.6 mg/ml, is unstable. Solutions containing less than 2 ampoules
Amiodarone 50mg/ml solution for I.V. injection in 500ml dextrose 5% are
unstable and should not be used.
The use of administration equipment or devices containing plasticizers such as
DEHP (di-2-ethylhexyphthalate) in the presence of amiodarone may result in
leaching out of DEHP. In order to minimise patient exposure to DEHP, the final
amiodarone dilution for infusion should preferably be administered through
non DEHP-containing sets.
6.3 Shelf life
36 months.
6.4 Special precautions for storage
Do not store above 25°C. Store in the original container. Keep ampoules in the
outer carton.
6.5 Nature and contents of container
Each carton contains 10 x 5ml amber glass (type I) ampoules, containing 3ml
of solution.
6.6 Instructions for use and handling
Refer to 4.2 above.
After dilution in 5 % isotonic dextrose solution, the solution should be kept for
maximal 8 hours at room temperature.
7. MARKETING AUTHORISATION HOLDER
Infohealth Laboratories Ltd, 28 Chipstead Valley Road,
Coulsdon, Surrey, CR5 2RA, UK
8. MARKETING AUTHORISATION NUMBER
PL 19664/0001
9. DATE OF FIRST AUTHORISATION/RENEWAL
OF THE AUTHORISATION
26/02/2008
10. DATE OF REVISION OF THE TEXT
January 2009
Legal Category
POM.

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Source: Medicines and Healthcare Products Regulatory Agency

Disclaimer: Every effort has been made to ensure that the information provided here is accurate, up-to-date and complete, but no guarantee is made to that effect. Drug information contained herein may be time sensitive. This information has been compiled for use by healthcare practitioners and consumers in the United States. The absence of a warning for a given drug or combination thereof in no way should be construed to indicate that the drug or combination is safe, effective or appropriate for any given patient. If you have questions about the substances you are taking, check with your doctor, nurse or pharmacist.

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