TAMBOCOR INJECTION

Israel - English - Ministry of Health

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Active ingredient:
FLECAINIDE ACETATE
Available from:
MEGAPHARM LTD
ATC code:
C01BC04
Pharmaceutical form:
SOLUTION FOR INJECTION
Composition:
FLECAINIDE ACETATE 10 MG/ML
Administration route:
I.V
Prescription type:
Required
Manufactured by:
CENEXI , FRANCE
Therapeutic group:
FLECAINIDE
Therapeutic area:
FLECAINIDE
Therapeutic indications:
Serious sustained life threatening ventricular arrhthymias that have not respoded to other drugs.
Authorization number:
106 41 23294 00
Authorization date:
2012-07-31

העדוה

לע

הרמחה

עדימ

ןולעב )תוחיטב

אפורל

ךיראת

11/05/2015

םש

רישכת

תילגנאב

רפסמו

םושירה

Tambocor Injection 106-41-23294-00

םש

לעב

םושירה

םראפאגמ

מ"עב

ספוט

הז

דעוימ

טורפל

תורמחהה

דבלב

תורמחהה

תושקובמה

ןולעב

אפורל קרפ

ןולעב טסקט

יחכונ טסקט

שדח

Posology and

method of

administration

Children: Tambocor is not recommended in

children under 12

Children: Tambocor is not

recommended in children under 12, as

there is insufficient evidence of its use

in this age group.

Contraindications

Tambocor is contra-indicated in cardiac

failure and in patients with a history of

myocardial infarction who have either

asymptomatic ventricular ectopics or

asymptomatic non-sustained ventricular

tachycardia.

It is also contra-indicated in patients with

long

standing

atrial

fibrillation

whom

there has been no attempt to convert to sinus

rhythm,

patients

with

haemodynamically significant valvular heart

disease.

Unless pacing rescue is available, Tambocor

should not be given to patients with sinus

node dysfunction, atrial conduction defects,

second degree or greater atrioventricular

block, bundle branch

block or distal block.

Hypersensitivity to flecainide or to any of

the excipients.

Tambocor is contra-indicated in cardiac

failure and in patients with a history of

myocardial infarction who have either

asymptomatic ventricular ectopics or

asymptomatic non-sustained ventricular

tachycardia.

Flecainide is contra-indicated in the

presence of cardiogenic shock.

It is also contra-indicated in patients

with long standing atrial fibrillation in

whom there has been no

attempt to

convert

to sinus

rhythm,

and in

patients

with

haemodynamically

significant valvular heart disease.

Known Brugada syndrome.

Unless pacing rescue is available,

Tambocor should not be given to

patients with sinus node dysfunction,

atrial conduction defects, second

degree or greater atrioventricular

block, bundle branch

block or distal

block.

Special warnings

Electrolyte disturbances (e.g. hypo- and

hyperkalaemia) should be corrected before

Electrolyte disturbances (e.g. hypo- and

hyperkalaemia) should be corrected

and precautions

for use

using Tambocor

(see section 4.5 for some

drugs causing electrolyte disturbances) .

Since flecainide elimination from the plasma

can be markedly slower in patients with

significant hepatic impairment, flecainide

should not be used in such patients unless the

potential benefits clearly outweigh the risks.

Plasma level monitoring is strongly

recommended in these circumstances.

Tambocor is known to increase endocardial

pacing thresholds - ie to decrease

endocardial pacing sensitivity. This effect is

reversible and is more marked on the acute

pacing threshold than on the chronic.

Tambocor should thus be used with caution

in all patients with permanent pacemakers

or temporary

pacing electrodes, and should

not be administered to patients with existing

poor thresholds or non- programmable

pacemakers unless suitable pacing rescue is

available.

The minor negative inotropic effect of

flecainide may assume importance in

patients predisposed to cardiac failure.

Difficulty has been experienced in

defibrillating some patients. Most of the

cases reported had pre-existing heart

disease with cardiac enlargement, a history

of myocardial infarction, arterio-sclerotic

heart disease and cardiac failure.

Tambocor should be used with caution in

patients with acute onset of atrial fibrillation

following cardiac surgery.

before using Tambocor

(see section 4.5

for some drugs causing electrolyte

disturbances) .

Since flecainide elimination from the

plasma can be markedly slower in

patients with significant hepatic

impairment, flecainide should not be

used in such patients unless the potential

benefits clearly outweigh the risks.

Plasma level monitoring is strongly

recommended in these circumstances.

Tambocor is known to increase

endocardial pacing thresholds - ie to

decrease endocardial pacing sensitivity.

This effect is reversible and is more

marked on the acute pacing threshold

than on the chronic.

Tambocor should thus be used with

caution in all patients with permanent

pacemakers or temporary

pacing

electrodes, and should not be

administered to patients with existing

poor thresholds or non-

programmable pacemakers unless

suitable pacing rescue is available.

Generally, a doubling of either pulse

width or voltage is sufficient to regain

capture, but it may be difficult to

obtain ventricular thresholds less than

1 Volt at initial implantation in the

presence of Tambocor.

The minor negative inotropic effect of

flecainide may assume importance in

patients predisposed to cardiac

failure. Difficulty has been

experienced in defibrillating some

patients. Most of the cases reported

had pre-existing heart disease with

cardiac enlargement, a history of

myocardial infarction, arterio-

sclerotic heart disease and cardiac

failure.

Tambocor has been shown to increase

mortality risk of post-myocardial

infarction patients with asymptomatic

ventricular arrhythmia.

Tambocor, like other antiarrhythmics,

may cause proarrhythmic effects, i.e.

it may cause the appearance of a

more severe type of arrhythmia,

increase the frequency of an existing

arrhythmia or the severity of the

symptoms (see 4.8).

Tambocor should be used with caution

in patients with impaired renal function

(creatinine clearance ≤ 35 ml/min/1.73

m2) and therapeutic drug monitoring is

recommended.

The rate of flecainide elimination from

plasma may be reduced in the elderly.

This should be taken into

consideration when making dose

adjustments.

Tambocor is not recommended in

children under 12 years of age, as there

is insufficient evidence of its use in

this age group.

Severe bradycardia or pronounced

hypotension should be corrected before

using flecainide.

Tambocor should be avoided in

patients with structural organic heart

disease or abnormal left ventricular

function.

Tambocor should be used with caution

in patients with acute onset of atrial

fibrillation following cardiac surgery.

Treatment for patients with other

indications should continue to be

initiated in hospital. Intravenous

treatment with flecainide should be

initiated in hospital.

Continuous ECG monitoring is

recommended in all patients receiving

bolus injection.

Tambocor prolongs the QT interval

and widens the QRS complex by 12-

20 %. The effect on the JT interval is

insignificant.

A Brugada syndrome may be unmasked

due to flecainide therapy. In the case of

development of ECG changes during

treatment with flecainide that may

indicate Brugada syndrome,

consideration to discontinue the

treatment should be made.

In a large scale, placebo-controlled

clinical trial in post-myocardial

infarction patients with asymptomatic

ventricular arrhythmia, oral flecainide

was associated with a 2.2 fold higher

incidence

of mortality or non-fatal

cardiac arrest as compared with its

matching placebo. In that same study,

even higher incidence of mortality

was observed in flecainide-treated

patients with more than one

myocardial infarction. Comparable

placebo-controlled clinical trials have

not been done to determine if

flecainide is associated with higher risk

of mortality in other patient groups.

Dairy products (milk, infant formula

and possibly yoghurt) may reduce the

absorption of flecainide in children and

infants. Flecainide is not approved for

use in children below the age of 12

years, however flecainide toxicity has

been reported during treatment with

flecainide in children who reduced their

intake of milk, and in infants who were

switched from milk formula to dextrose

feedings.

Flecainide as a narrow therapeutic index

drug requires caution and close

monitoring when switching a

patient to

a different formulation.

For further warnings and precautions

please refer to section 4.5 (Interaction).

Interaction with

other medicinal

products and

other forms of

interaction

Cardiac glycosides; Flecainide can cause the

plasma digoxin level to rise by about

15%,

is recommended

that

digoxin

plasma level in digitalised patients should be

measured not

less than six hours after any

digoxin dose, before or after administration

of flecainide.

Anti-depressants; and other antidepressants

increases plasma flecainide concentration;

increased risk of arrhythmias with tricyclics;

manufacturer of reboxetine advises caution.

H2 antihistamines (for the treatment of gastric

Cardiac glycosides; Flecainide can cause

the plasma digoxin level to rise by about

15%, which is unlikely to be of clinical

significance for patients with plasma

levels in the therapeutic

range. It is

recommended that the digoxin plasma

level in digitalised patients should be

measured not

less than six hours after

any digoxin

dose,

before

after

administration of flecainide.

Anti-depressants; fluoxetine,

paroxetine and other antidepressants

increases plasma flecainide

ulcers): cimetidine inhibits metabolism of

flecainide. In healthy subjects receiving

cimetidine (1g daily) for one week, plasma

flecainide levels increased by about 30%

Anti-smoking aids: Co-administration of

bupropion

with

drugs

that

metabolized

CYP2D6

isoenzyme

including

flecainide, If

bupropion

added

treatment

regimen

patient already receiving

concentration; increased risk of

arrhythmias with tricyclics;

manufacturer of reboxetine advises

caution.

Life-threatening or even lethal adverse

events due to interactions causing

increased plasma

concentrations may

occur (see 4.9). Flecainide is

metabolised by CYP2D6 to a large

extent, and concurrent use of drugs

inhibiting (e.g. antidepressants,

neuroleptics, propranolol, ritonavir,

some antihistamines) or inducing (e.g.

phenytoin, phenobarbital,

carbamazepine) this iso-enzyme can

increase or decrease plasma

concentrations of flecainide,

respectively (see below).

An increase of plasma levels may also

result from renal impairment due to a

reduced clearance of flecainide

Hypokalaemia but also hyperkalaemia

or other electrolyte disturbances should

be corrected before

administration of

flecainide. Hypokalaemia may result

from the concomitant use of diuretics,

corticosteroids or laxatives.

H2 antihistamines (for the treatment of

gastric ulcers): cimetidine inhibits

metabolism of flecainide. In healthy

subjects receiving cimetidine (1g daily)

for one week, plasma flecainide levels

increased by about 30% and the half-

life increased by about 10%.

Anti-smoking

aids:

administration of bupropion with

drugs

that

metabolized

CYP2D6

isoenzyme

including

flecainide,

should

approached

with

caution

should

initiated at the

lower end of the

dose

range

concomitant

medication.If bupropion is added

treatment

regimen

patient already receiving

flecainide, the need to decrease the dose

of the original medication should be

considered.

Fertility,

Pregnancy information

Pregnancy information

Pregnancy and

lactation

Data have shown

that flecainide crosses the

placenta

foetus

in patients

taking

flecainide during pregnancy.

Flecainide should only be used in pregnancy if

the benefit outweighs the risks.

Lactation information

Flecainide is excreted in human milk. (see

5.2). Although the risk of adverse effects to

the nursing infant is very small,

There is no evidence as to drug safety in

human

pregnancy.

Zealand

White rabbits, high doses

of flecainide

caused some foetal abnormalities, but

these effects were not seen in Dutch

Belted rabbits

or rats (see 5.3). The

relevance of these findings to humans

has not

been

established.

Data

have

shown

that

flecainide

crosses

placenta to the foetus in patients taking

flecainide during pregnancy.

Flecainide should only be used in

pregnancy if the benefit outweighs the

risks.

Lactation information

Flecainide is excreted in human milk.

Plasma concentrations obtained in a

nursing infant are 5-10

times lower

than therapeutic drug concentrations

(see 5.2). Although the risk of adverse

effects to the nursing infant is very

small, flecainide should only be used

during lactation if the benefit

outweighs the risks.

Effects on ability

to drive and use

machines

----

Tambocor 10mg/ml Injection or

infusion has no or negligible influence

on the ability to drive and use

machines. However, driving ability,

operation of machinery and work

without a secure fit may be

affected by

adverse reactions such as dizziness and

visual disturbances (if present)

Undesirable

effects

Nervous system disorders:

Very common: dizziness, which is usually

transient

Rare: paraesthesia, ataxia, hypoaesthesia,

syncope, tremor, flushing, somnolence,

headache, neuropathy peripheral, convulsion,

dyskinesia

Cardiac disorders:

Common: Proarrhythmia (most likely in

patients with structural heart disease and/or

significant left ventricular impairment).

Uncommon: Patients with atrial flutter can

develop a 1:1 AV conduction with increased

heart rate.

Frequency not known (cannot be estimated

from the available data): atrioventricular block-

Nervous system disorders:

Very common: dizziness, which is

usually transient

Rare: paraesthesia, ataxia, hypoaesthesia,

hyperhidrosis, syncope, tremor, flushing,

somnolence,

headache, neuropathy

peripheral, convulsion, dyskinesia

Cardiac disorders:

Common: Proarrhythmia (most likely in

patients with structural heart disease and/

or significant left ventricular

impairment).

Frequency not known (cannot be

estimated from the available data). Dose-

related increases in PR and QRS

intervals may occur (see 4.4). Altered

pacing threshold (see 4.4).

second- degree and atrioventricular block third

degree, cardiac arrest, bradycardia, cardiac

failure/ cardiac

failure congestive, chest pain,

hypotension, myocardial infarction,

palpitations, sinus pause or arrest, and

tachycardia (AT or VT)

Respiratory, thoracic and mediastinal

disorders:

Common: dyspnoea

Rare: pneumonitis

Skin and subcutaneous tissue disorders:

Uncommon: dermatitis allergic, including rash,

Rare: serious urticaria

Very rare: photosensitivity reaction

Uncommon: Patients with atrial flutter

can develop a 1:1 AV conduction with

increased heart rate.

Frequency not known (cannot be

estimated from the available data):

atrioventricular block-second- degree

and atrioventricular block third degree,

cardiac arrest, bradycardia, cardiac

failure/ cardiac

failure congestive, chest

pain, hypotension, myocardial infarction,

palpitations, sinus pause or arrest, and

tachycardia (AT or VT) or ventricular

fibrillation. Demasking of a pre-existing

Brugada syndrome.

Respiratory, thoracic and

mediastinal disorders:

Common: dyspnoea

Rare: pneumonitis

Frequency not known (cannot be

estimated from the available data):

pulmonary fibrosis, interstitial lung

disease

Skin and subcutaneous tissue

disorders:

Uncommon: dermatitis allergic, including

rash, alopecia

Rare: serious urticaria

Very rare: photosensitivity reaction

Overdose

No specific antidote is known. There is no

known way to rapidly remove flecainide from

the system. Neither dialysis nor

haemoperfusion is effective.

Further measures may include inotropic agents

as well as mechanical ventilation and

circulatory assistance (e.g. ballon pumping).

Temporarily inserting a transvenous

pacemaker in the event of conduction block

should be considered.

Overdosage with flecainide is a

potentially life-threatening medical

emergency. Increased drug

susceptibility and plasma levels

exceeding therapeutic levels may also

result from drug interaction (see 4.5).

No specific antidote is known. There is

no known way to rapidly remove

flecainide from the system. Neither

dialysis nor haemoperfusion is effective.

Treatment should be supportive and

may include removal of unabsorbed

drug from the GI tract. Further

measures may include inotropic agents

or cardiac stimulants such as dopamine,

dobutamine or

isoproterenol as well as

mechanical ventilation and circulatory

assistance (e.g. ballon pumping).

Temporarily inserting a transvenous

pacemaker in the event of conduction

block should be considered. Assuming

a plasma half-life of approximately 20

h, these supportive treatments may

need to be continued for an extended

period of time. Forced diuresis with

acidification of the urine theoretically

promotes drug excretion.

Preclinical safety

data

----

One rabbit tribe showed teratogenicity

and embryotoxicity under flecainide.

This effect was neither present in

other rabbit tribes nor in rats or mice.

Prolongation of gestation was seen in

rats under a dose of 50 mg/kg. No

effects on fertility were observed. No

human data concerning pregnancy and

lactation are available.

Special

precautions for

disposal and other

handling

Dilution: When necessary Tambocor

injection should be diluted with, or

injected into, sterile solutions of 5%

dextrose. If chloride containing

solutions, such as sodium chloride or

Ringer’s lactate are used,

the injection

should be added to a volume of not less

than 500 ml, otherwise a precipitate will

form.

For single use only.

ב"צמ

ובש ,ןולעה

נמוסמ תו

תורמחהה

שקובמה תו

לע

עקר

בוהצ

םייוניש

םניאש

רדגב

תורמחה

ונמוס

עבצב )ןולעב(

.הנוש רבעוה

ראודב

ינורטקלא

ךיראתב

11/05/2015

_________

SUMMARY OF PRODUCT CHARACTERISTICS

1.

NAME OF THE MEDICINAL PRODUCT

Tambocor 10mg/ml Solution for Injection

2.

QUALITATIVE AND QUANTITATIVE COMPOSITION

Each ampoule contains 15 ml of a solution of flecainide acetate 10 mg/ml.

3.

PHARMACEUTICAL FORM

Solution for injection or infusion.

4.

CLINICAL PARTICULARS

4.1

Therapeutic indications

Serious sustained life threatening ventricular arrhthymias that have not respoded to other drugs.

4.2

Posology and method of administration

In an emergency or for rapid effect, or as a slow intravenous infusion when prolonged

administration is required.

a) Bolus injection:

Administer 2 mg/kg over not less than ten minutes, or in divided doses.

Alternatively dilute with 5% dextrose and give as a mini-infusion.

Continuous ECG monitoring is recommended. Stop the injection when the arrhythmia is

controlled.

For sustained ventricular tachycardia, or people with a history of cardiac failure (who may

become decompensated during administration) give the initial dose over 30 minutes and

monitor the ECG carefully.

The maximum recommended bolus dose is 150 mg.

b) Intravenous infusion:

The recommended procedure is to start with a slow injection of 2

mg/kg over 30 minutes, then continue intravenous infusion at the following rates:

First hour:

1.5 mg/kg per hour.

Second and later hours:

0.1 - 0.25 mg/kg per hour.

The maximum recommended infusion duration is 24 hours; if exceeded, and in patients

receiving high doses, monitor plasma levels.

The maximum cumulative dose over the first 24 hours should not exceed 600 mg.

In severe renal impairment (creatinine clearance < 35 ml/min/1.73 sq.m.) reduce the above

dosage recommendations by half.

Oral maintenance dosing should be started as soon as possible after stopping the infusion.

Children:

Tambocor is not recommended in children under 12, as there is insufficient

evidence of its use in this age group.

Elderly Patients:

The rate of flecainide elimination from plasma may be reduced in elderly

people. This should be taken into consideration when making dose adjustments.

4.3

Contraindications

Hypersensitivity to flecainide or to any of the excipients.

Tambocor is contra-indicated in cardiac failure and in patients with a history of myocardial

infarction who have either asymptomatic ventricular ectopics or asymptomatic non-sustained

ventricular tachycardia.

Flecainide is contra-indicated in the presence of cardiogenic shock.

It is also contra-indicated in patients with long standing atrial fibrillation in whom there has

been no

attempt to convert to sinus rhythm, and in patients with haemodynamically

significant valvular heart disease.

Known Brugada syndrome.

Unless pacing rescue is available, Tambocor should not be given to patients with sinus node

dysfunction, atrial conduction defects, second degree or greater atrioventricular block, bundle

branch

block or distal block.

4.4

Special warnings and precautions for use

Electrolyte disturbances (e.g. hypo- and hyperkalaemia) should be corrected before using

Tambocor (see section 4.5 for some drugs causing electrolyte disturbances) .

Since flecainide elimination from the plasma can be markedly slower in patients with

significant hepatic impairment, flecainide should not be used in such patients unless the

potential benefits clearly outweigh the risks. Plasma level monitoring is strongly

recommended in these circumstances.

Tambocor is known to increase endocardial pacing thresholds - ie to decrease

endocardial pacing sensitivity. This effect is reversible and is more marked on the acute

pacing threshold than on the chronic.

Tambocor should thus be used with caution in all patients with permanent pacemakers or

temporary pacing electrodes, and should not be administered to patients with existing poor

thresholds or non- programmable pacemakers unless suitable pacing rescue is available.

Generally, a doubling of either pulse width or voltage is sufficient to regain capture, but it

may be difficult to obtain ventricular thresholds less than 1 Volt at initial implantation in the

presence of Tambocor.

The minor negative inotropic effect of flecainide may assume importance in patients

predisposed to cardiac failure. Difficulty has been experienced in defibrillating some

patients. Most of the cases reported had pre-existing heart disease with cardiac enlargement,

a history of myocardial infarction, arterio-sclerotic heart disease and cardiac failure.

Tambocor has been shown to increase mortality risk of post-myocardial infarction patients

with asymptomatic ventricular arrhythmia.

Tambocor, like other antiarrhythmics, may cause proarrhythmic effects, i.e. it may cause the

appearance of a more severe type of arrhythmia, increase the frequency of an existing

arrhythmia or the severity of the symptoms (see 4.8).

Tambocor should be used with caution in patients with impaired renal function (creatinine

clearance ≤ 35 ml/min/1.73 m2) and therapeutic drug monitoring is recommended.

The rate of flecainide elimination from plasma may be reduced in the elderly. This should be

taken into consideration when making dose adjustments.

Tambocor is not recommended in children under 12 years of age, as there is insufficient

evidence of its use in this age group.

Severe bradycardia or pronounced hypotension should be corrected before using flecainide.

Tambocor should be avoided in patients with structural organic heart disease or abnormal

left ventricular function.

Tambocor should be used with caution in patients with acute onset of atrial fibrillation

following cardiac surgery.

Treatment for patients with other indications should continue to be initiated in hospital.

Intravenous treatment with flecainide should be initiated in hospital.

Continuous ECG monitoring is recommended in all patients receiving bolus injection.

Tambocor prolongs the QT interval and widens the QRS complex by 12-20 %. The effect on

the JT interval is insignificant.

A Brugada syndrome may be unmasked due to flecainide therapy. In the case of development

of ECG changes during treatment with flecainide that may indicate Brugada syndrome,

consideration to discontinue the treatment should be made.

In a large scale, placebo-controlled clinical trial in post-myocardial infarction patients with

asymptomatic ventricular arrhythmia, oral flecainide was associated with a 2.2 fold higher

incidence of mortality or non-fatal cardiac arrest as compared with its matching placebo. In

that same study, an even higher incidence of mortality was observed in flecainide-treated

patients with more than one myocardial infarction. Comparable placebo-controlled clinical

trials have not been done to determine if flecainide is associated with higher risk of mortality

in other patient groups.

Dairy products (milk, infant formula and possibly yoghurt) may reduce the absorption of

flecainide in children and infants. Flecainide is not approved for use in children below the age

of 12 years, however flecainide toxicity has been reported during treatment with flecainide in

children who reduced their intake of milk, and in infants who were switched from milk

formula to dextrose feedings.

Flecainide as a narrow therapeutic index drug requires caution and close monitoring when

switching a

patient to a different formulation.

For further warnings and precautions please refer to section 4.5 (Interaction).

4.5

Interaction with other medicinal products and other forms of interaction

Flecainide is a class I anti-arrhythmic and interactions are possible with other antiarrhythmic

drugs where additive effects may occur or where drugs interfere with the metabolism of

flecainide.

Flecainide should not be administered concomitantly with other class I antiarrythmics. The

following known categories of drugs may intereact with flecainide:

Cardiac glycosides; Flecainide can cause the plasma

digoxin

level to rise by about

15%, which is unlikely to be of clinical significance for patients with plasma levels in the

therapeutic

range. It is recommended that the

digoxin

plasma level in digitalised patients

should

measured

less

than

hours after

digoxin

dose,

before

after

administration of flecainide.

Class II anti-arrhythmics; the possibility of additive negative inotropic effects of betablockers,

and other cardiac depressants such as verapamil, with flecainide should be recognised.

Class III anti-arrhythmics; when flecainide is given in the presence of

amiodarone

, the usual

flecainide dosage should be reduced by 50% and the patient monitored closely for adverse

effects. Plasma level monitoring is strongly recommended in these circumstances

Class IV anti-arrhythmics; use of flecainide with other sodium channel blockers is not

recommended.

Anti-depressants;

fluoxetine, paroxetine

and other antidepressants increases plasma flecainide

concentration; increased risk of arrhythmias with

tricyclics

; manufacturer of

reboxetine

advises caution.

Life-threatening or even lethal adverse events due to interactions causing increased plasma

concentrations may occur (see 4.9). Flecainide is metabolised by CYP2D6 to a large extent,

and concurrent use of drugs inhibiting (e.g. antidepressants, neuroleptics, propranolol,

ritonavir, some antihistamines) or inducing (e.g. phenytoin, phenobarbital, carbamazepine)

this iso-enzyme can increase or decrease plasma concentrations of flecainide, respectively

(see below).

An increase of plasma levels may also result from renal impairment due to a reduced clearance

of flecainide

Hypokalaemia but also hyperkalaemia or other electrolyte disturbances should be corrected

before

administration of flecainide. Hypokalaemia may result from the concomitant use of

diuretics, corticosteroids or laxatives.

Anti-epileptics; limited data in patients receiving known enzyme inducers (

phenytoin,

phenobarbital, carbamazepine

) indicate only a 30% increase in the rate of flecainide

elimination.

Anti-psychotics:

clozapine

– increased risk of arrhythmias

Anti-histamines; increased risk of ventricular arrhythmias with

mizolastine

terfenadine

(avoid concomitant use)

Anti-malarials:

quinine

increases plasma concentration of flecainide.

Antivirals: plasma concentration increased by

ritonavir

lopinavar

indinavir

(increased

risk of ventricular arrhythmias) avoid concomitant use

Diuretics: Class effect due to hypokalaemia giving rise to cardiac toxicity.

H2 antihistamines (for the treatment of gastric ulcers):

cimetidine

inhibits metabolism of

flecainide. In healthy subjects receiving

cimetidine

(1g daily) for one week, plasma flecainide

levels increased by about 30% and the half-life increased by about 10%.

Anti-smoking aids: Co-administration of

bupropion

with drugs that are metabolized by

CYP2D6 isoenzyme including flecainide, should be approached with caution and should

be initiated

at the

lower end

of the

dose

range

concomitant medication.If

bupropion

is added to the treatment regimen of a patient already receiving

flecainide, the need to decrease the dose of the original medication should be considered.

Anticoagulants: Treatment with Tambocor is compatible with use of oral anti-coagulants.

4.6

Fertility, pregnancy and lactation

Pregnancy information

There is no evidence as to drug safety in human pregnancy. In New Zealand White rabbits,

high doses

of flecainide caused some foetal abnormalities, but these effects were not seen in

Dutch Belted rabbits or rats (see 5.3). The relevance of these findings to humans has not been

established. Data have shown

that flecainide crosses the placenta to the foetus in patients

taking flecainide during pregnancy.

Flecainide should only be used in pregnancy if the benefit outweighs the risks.

Lactation information

Flecainide is excreted in human milk. Plasma concentrations obtained in a nursing infant are

5-10 times lower than therapeutic drug concentrations (see 5.2). Although the risk of adverse

effects to the nursing infant is very small, flecainide should only be used during lactation if

the benefit outweighs the risks.

4.7

Effects on ability to drive and use machines

Tambocor 10mg/ml Injection or infusion has no or negligible influence on the ability to drive

and use machines. However, driving ability, operation of machinery and work without a

secure fit may be

affected by adverse reactions such as dizziness and visual disturbances (if

present)

4.8

Undesirable effects

Adverse events are listed below by system organ class and frequency. Frequencies are

defined as: very common (≥1/l0), common (≥1/100 and <1/10), uncommon (≥1/1000 and

<1/100), rare (≥ 1/10,000 and <1/1000) and very rare (<1/10,000), not known (cannot be

estimated from the available data).

Blood and lymphatic system disorders:

Uncommon:

red blood cell count decreased, white blood cell count decreased and platelet

count decreased

Immune system disorders:

Very rare:

antinuclear antibody increased with and without systemic inflammation

Psychiatric disorders:

Rare:

hallucination, depression, confusional state, anxiety, amnesia, insomnia

Nervous system disorders:

Very common:

dizziness, which is usually transient

Rare:

paraesthesia, ataxia, hypoaesthesia, hyperhidrosis, syncope, tremor, flushing,

somnolence, headache, neuropathy peripheral, convulsion, dyskinesia

Eye disorders:

Very common:

visual impairment, such as diplopia and vision blurred

Very rare:

corneal deposits

Ear and labyrinth disorders:

Rare:

tinnitus, vertigo

Cardiac disorders:

Common:

Proarrhythmia (most likely in patients with structural heart disease and/or

significant left ventricular impairment).

Frequency not known

(cannot be estimated from the available data). Dose-related increases in

PR and QRS intervals may occur (see 4.4). Altered pacing threshold (see 4.4).

Uncommon:

Patients with atrial flutter can develop a 1:1 AV conduction with increased heart

rate.

Frequency not known

(cannot be estimated from the available data): atrioventricular block-

second- degree and atrioventricular block third degree, cardiac arrest, bradycardia, cardiac

failure/ cardiac failure congestive, chest pain, hypotension, myocardial infarction,

palpitations, sinus pause or arrest, and tachycardia (AT or VT) or ventricular fibrillation.

Demasking of a pre-existing Brugada syndrome.

Respiratory, thoracic and mediastinal disorders:

Common:

dyspnoea

Rare:

pneumonitis

Frequency not known

(cannot be estimated from the available data): pulmonary fibrosis,

interstitial lung disease

Gastrointestinal disorders:

Uncommon:

nausea, vomiting, constipation, abdominal pain, decreased appetite, diarrhoea,

dyspepsia,

flatulence

Hepatobiliary disorders:

Rare:

hepatic enzymes increased with and without jaundice

Frequency not known

(cannot be estimated from the available data): hepatic dysfunction

Skin and subcutaneous tissue disorders:

Uncommon:

dermatitis allergic, including rash, alopecia

Rare:

serious urticaria

Very rare:

photosensitivity reaction

General disorders and administration site conditions:

Common:

asthenia, fatigue, pyrexia, oedema

Any suspected adverse events should be reported to the Ministry of Health according to the

National Regulation by using an online form

(http://forms.gov.il/globaldata/getsequence/getsequence.aspx?formType=AdversEffectMedic@

moh.health.gov.il ) or by email (adr@MOH.HEALTH.GOV.IL ).

4.9

Overdose

Overdosage with flecainide is a potentially life-threatening medical emergency. Increased drug

susceptibility and plasma levels exceeding therapeutic levels may also result from drug

interaction (see 4.5). No specific antidote is known. There is no known way to rapidly remove

flecainide from the system. Neither dialysis nor haemoperfusion is effective.

Treatment should be supportive and may include removal of unabsorbed drug from the GI

tract. Further measures may include inotropic agents or cardiac stimulants such as dopamine,

dobutamine or isoproterenol as well as mechanical ventilation and circulatory assistance (e.g.

ballon pumping).

Temporarily inserting a transvenous pacemaker in the event of conduction block should be

considered. Assuming a plasma half-life of approximately 20 h, these supportive treatments

may need to be continued for an extended period of time. Forced diuresis with acidification

of the urine theoretically promotes drug excretion.

5.

PHARMACOLOGICAL PROPERTIES

5.1

Pharmacodynamic properties

Tambocor is a Class 1 anti-arrhythmic (local anaesthetic) agent. ATC code: C01BC04.

Tambocor slows conduction through the heart, having its greatest effect on His

Bundle conduction. It also acts selectively to increase anterograde and particularlyretrograde

accessory pathway refractoriness. Its actions may be reflected in the ECG by prolongation of

the PR interval and widening of the QRS complex. The effect on the JT interval is

insignificant.

5.2

Pharmacokinetic properties

Intravenous administration of 0.5 - 2.0 mg/kg to healthy subjects resulted in plasma

concentrations ranging from 70 - 340 mcg/l. Protein binding is low (about 40 %). The

volume of distribution is 8.7 l/kg.

The elimination half-life after IV administration to patients was 7 to 19 hours.

5.3

Preclinical safety data

One rabbit tribe showed teratogenicity and embryotoxicity under flecainide. This effect was

neither present in other rabbit tribes nor in rats or mice. Prolongation of gestation was seen

in rats under a dose of 50 mg/kg. No effects on fertility were observed. No human data

concerning pregnancy and lactation are available.

6.

PHARMACEUTICAL PARTICULARS

6.1

List of excipients

Sodium Acetate

Glacial Acetic Acid

Water for injections

6.2

Incompatibilities

None known

6.3

Shelf life

3 year

6.4

Special precautions for storage

Do not store above 30°C. Do not freeze. Protect from light.

6.5

Nature and contents of container

Boxes containing 5 x 15 ml glass ampoules.

6.6

Special precautions for disposal and other handling

Dilution: When necessary Tambocor injection should be diluted with, or injected into, sterile

solutions of 5% dextrose. If chloride containing solutions, such as sodium chloride or Ringer’s

lactate are used,

the injection should be added to a volume of not less than 500 ml, otherwise a

precipitate will form.

For single use only.

7.

MANUFACTURER

Cenexi, Fontenay-sous-Bois, France for Meda Pharma GmbH & CO.KG, Bad Homburg,

Germany

8.

MARKETING AUTHORISATION HOLDER

Megapharm Ltd,

P.O.B 519 Hod Hasharon 4510501

Israel

The format of this leaflet was determined by the ministry of health and its content was

checked and approved in June 2015.

TAMB INJ 062015 P.1

העדוה העדוה

לע לע

הרמחה הרמחה

עדימ( עדימ(

)תוחיטב )תוחיטב חולשל(

(

alonim.urgent@moh.health.gov.il

ךיראת

_

ץרמב __

2012

______________________________

םש

רישכת

תילגנאב

___

TAMBOCOR INJECTION

_

__________

רפסמ

םושיר

_

106-41-23294-00

_______________________

םש

לעב

םושירה

_

תודבעמ

אפר

מ"עב

_________________

םייונישה

ןולעב

םינמוסמ

:עבצב בוהצ ,הפסוה= קורי ,הקיחמ= לוחכ יוניש=

.םוקמ ןולעב ןולעב

אפורל אפורל קרפ

ןולעב טסקט

יחכונ טסקט

שדח

Directions for

Use

a) Bolus injection: Tambocor

injection can be given in an

emergency, or for rapid effect, by a

slow injection of Administer 2 mg/

kg over not less than ten minutes,

or in divided doses. If preferred,

the dose may be diluted with 5%

glucose and given as a mini-

infusion.

Continuous ECG monitoring is

recommended in all patients

receiving the bolus dose. The

injection should be stopped when

there is control of the arrhythmia.

It is recommended that Tambocor

injection should be administered

more slowly to patients in

sustained ventricular tachycardia,

with careful monitoring of the

electrocardiogram. Similar caution

should apply to patients with a

history of cardiac failure, who may

become decompensated during the

administration. For such patients it

is recommended that the initial

dose is given over 30 minutes.

The maximum recommended

bolus dose is 150 mg.

b) Intravenous infusion: When

prolonged parenteral administration

is required, it is recommended that

therapy is initiated by slow injection

of 2 mg/kg over 30 minutes, and

continued by intravenous infusion at

the following rates:

First hour:1.5 mg/kg per hour.

Tambocor injection may be given as a bolus

injection in an emergency or for rapid effect,

or as a slow intravenous infusion when

prolonged administration is required.

a) Bolus injection: Tambocor injection can

be given in an emergency, or for rapid

effect, by a slow injection of Administer 2

mg/kg over not less than ten minutes, or in

divided doses. If preferred, the dose may be

Alternatively diluted with 5% glucose and

given as a mini-infusion.

Continuous ECG monitoring is recommended

in all patients receiving the bolus dose. Stop

tThe injection should be stopped when there

is control of the arrhythmia is controlled.

It is recommended that Tambocor injection

should be administered more slowly to

patients in For sustained ventricular

tachycardia, or people with careful monitoring

of the electrocardiogram. Similar caution

should apply to patients with a history of

cardiac failure, (who may become

decompensated during the administration).

For such patients it is recommended that the

initial dose is given the initial dose over 30

minutes and monitor the ECG carefully.

The maximum recommended bolus dose is

150 mg.

b) Intravenous infusion: When prolonged

parenteral administration is required, it is The

recommended procedure is to start with a that

therapy is initiated by slow injection of 2 mg/

kg over 30 minutes, and then continued by

intravenous infusion at the following rates:

First hour:1.5 mg/kg per hour.

Second and later hours: 0.1 - 0.25

mg/kg per hour.

It is recommended that the infusion

duration should not exceed 24

hours.; However, where this is

considered necessary, or for patients

receiving the upper end of the dose

range, plasma level monitoring is

strongly recommended. The

maximum cumulative dose given in

the first 24 hours should not exceed

600 mg.

In patients with severe renal

impairment (creatinine clearance of

less than 35 ml/min/1.73 sq.m.),

each of the above dosage

recommendations should be reduced

by half.

Transition to oral dosing should be

accomplished as soon as possible by

stopping the infusion and

administering the first required oral

dose.

Oral maintenance is then continued

as indicated in the relevant oral

dosage instructions in the data sheet.

Children:

Tambocor injection is not

recommended in children under 12 ,

as there is insufficient evidence of its

use in this age group.

Elderly Patients:

The rate of flecainide elimination of

from plasma may be reduced in

elderly people. This should be taken

into consideration when making dose

adjustments.

Plasma levels

Based on PVC suppression, it

appears that plasma levels of 200-

1000 ng/ml may be needed to obtain

the maximum therapeutic effect.

Plasma levels above 700-

1000 ng/ml are associated with the

increased likelihood of adverse

experiences.

Second and later hours: 0.1 - 0.25 mg/kg per

hour.

It is The maximum recommended that the

infusion duration should not exceed is 24

hours.; However, where this is considered

necessary, or for patients receiving the upper

end of the dose range, if exceeded, and in

patients receiving high doses, monitor plasma

levels monitoring is strongly recommended.

The maximum cumulative dose given in over

the first 24 hours should not exceed 600 mg.

In patients with severe renal impairment

(creatinine clearance < of less than 35 ml/min/

1.73 sq.m.), reduce each of the above dosage

recommendations should be reduced by half.

Transition to oral Oral maintenance dosing

should be accomplished started as soon as

possible by after stopping the infusion and

administering the first required oral dose.

Oral maintenance is then continued as

indicated in the relevant oral dosage

instructions in the data sheet.

Children:

Tambocor injection is nNot recommended in

children under 12 years , as there is

insufficient evidence of its use in this age

group.

Elderly Patients:

The rate of flecainide elimination of

flecainide from plasma may be reduced, in

elderly people. This should be taken into

consideration when making so dose

adjustments may be necessary.

Plasma levels

Based on PVC suppression, it appears that

plasma levels of 200-1000 ng/ml may be

needed to obtain the maximum therapeutic

effect. Plasma levels above 700-

1000 ng/ml are associated with the increased

likelihood of adverse experiences.

Contra-

indications and

Warnings

Mortality Tambocor was included in

the national Heart Lung Blood

Institute’s Cardiac Arrhythmia

(Special

introductory

boxed warning)

Suppression Trial (CAST), a long

term, multicenter, randomized,

double-blind study in patients with

asymptomatic non-life-threatening

ventricular arrhythmias who had a

myocardial infarction more than six

days, but less than two years

previously. An excessive mortality or

non-fatal cardiac arrest rate was seen

in patients treated with Tambocor

compared with that seen in a

carefully matched placebo-treated

group. This rate was 16/315 (5.1%)

for Tambocor and 7/309 (2.3%) for

its matched placebo. The average

duration of treatment with

Tambocor in this study was 10

months.

Ventricular Pro-arrhythmic Effects in

Patients with Atrial Fibrillation

Flutter A review of the world

literature revealed reports of 568

patients treated with oral Tambocor

for paroxysmal atrial

fibrillation/flutter (PAF). Ventricular

tachycardia was experienced in 0.4%

(2/568) of these patients. Of 19

patients in the literature with chronic

atrial fibrillation (CAF), 10.5% (2)

experienced VT or VF.

FLECAINIDE IS NOT

RECOMMENDED FOR USE IN

PATIENTS WITH CHRONIC

ATRIAL FIBRILATION. Case

reports of ventricular proarrhythmic

effects in patients treated with

Tambocor for atrial fibrillation/

flutter have included increased

PVCs, VT, ventricular fibrillation

(VF), and death.

As with other Class I agents, patients

treated with Tambocor for atrial

flutter have been reported with 1:1

atrioventricular conduction due to

slowing of the atrial rate. A

paradoxical increase in the

ventricular rate also may occur in

patients with atrial fibrillation who

receive Tambocor. Concomitant

negative chronotropic therapy such

as digoxin or beta-blockers may

lower the risk of this complication.

(See Indications)

Warnings and

precautions

Warnings and Precautions:

Electrolyte disturbances

should be corrected before

using Tambocor injection.

Since flecainide elimination

of from the plasma can be

markedly slower in patients

with significant hepatic

impairment., flecainide

should not be used in such

patients unless the potential

benefits clearly outweigh the

risks. Plasma level

monitoring is strongly

recommended in these

circumstances.

Tambocor injection is known

to increase endocardial

pacing thresholds – i.e. to

decrease endocardial pacing

sensitivity;. This effect is

reversible and is more

marked on the acute pacing

threshold than on the chronic.

Tambocor injection should

thus be used with caution in

all patients with permanent

pacemakers or temporary

pacing electrodes, and should

not be administered to

patients with existing poor

thresholds or non-

programmable pacemakers

unless suitable pacing rescue

is available.

Generally, a doubling of either pulse

width current is sufficient to regain

capture, but it may be difficult to

obtain ventricular thresholds less

than 1 Volt at initial implantation in

the presence of Tambocor injection.

The minor negative inotropic

effect of flecainide may

assume importance in

patients predisposed to

cardiac failure. Difficulty has

been experienced in

defibrillating some patients .

Most of the cases reported

had pre-existing heart disease

with cardiac enlargement, a

Warnings and

Precautions

:

Correct any Eelectrolyte disturbances

should be corrected before using

Tambocor injection.

Plasma Since flecainide elimination of

flecainide from the plasma can may be

markedly slower in patients with

significant hepatic impairment.,

flecainide should Do not be use,d in

such patients unless the potential

benefits clearly outweigh the risks.

Careful Pplasma level monitoring is

strongly recommended in these

circumstances.

Tambocor injection is known to

increase endocardial pacing thresholds

– i.e. to dDecreased endocardial

pacing sensitivity may occur;. Tthis

effect is reversible and is more marked

on the acute pacing threshold than on

the chronic.

Tambocor injection should thus be

uUsed with caution in all patients with

permanent pacemakers or temporary

pacing electrodes., and should Do not

be administered to patients with

existing poor thresholds, or non-

programmable pacemakers, unless

suitable pacing rescue is available.

Generally, a doubling of either pulse width

current is sufficient to regain capture, but it

may be difficult to obtain ventricular

thresholds less than 1 Volt at initial

implantation in the presence of Tambocor

injection.

Flecainide's The minor negative

inotropic effect of flecainide may

become assume importantce in

patients predisposed to cardiac failure.

Difficulty has been experienced in

defibrillating some patients has been

reported. Most of tThe majority of

these cases reported had pre-existing

heart disease with cardiac

enlargement, a history of myocardial

infarction, arteriosclerotic heart

disease and cardiac failure.

Tambocor injection should be avoided in

patients with structural organic heart disease

or abnormal left ventricular function.

history of myocardial

infarction, arteriosclerotic

heart disease and cardiac

failure.

Tambocor injection should be

avoided in patients with structural

organic heart disease or abnormal

left ventricular function.

Tambocor injection should be

used with caution in patients

with acute onset of atrial

fibrillation following cardiac

surgery.

In a large scale, placebo-controlled

clinical trial in post-myocardial

infarction patients with

asymptomatic ventricular

arrhythmia, oral flecainide was

associated with a 2.2 fold higher

incidence of mortality or non-fatal

cardiac arrest as compared with its

matching placebo. In that same

study, an even higher incidence of

mortality was observed in flecainide-

treated patients with more than one

myocardial infarction. Comparable

placebo-controlled clinical trials

have not been done to determine if

flecainide is associated with higher

risk of mortality in other patient

groups.

Tambocor injection should be uUsed

with cautiouslyn in patients with acute

onset of atrial fibrillation following

cardiac surgery.

In a large scale, placebo-controlled clinical

trial in post-myocardial infarction patients

with asymptomatic ventricular arrhythmia,

oral flecainide was associated with a 2.2 fold

higher incidence of mortality or non-fatal

cardiac arrest as compared with its matching

placebo. In that same study, an even higher

incidence of mortality was observed in

flecainide-treated patients with more than one

myocardial infarction. Comparable placebo-

controlled clinical trials have not been done to

determine if flecainide is associated with

higher risk of mortality in other patient

groups.

Use in

Pregnancy

and Lactation

There is no evidence as to drug

safety in human pregnancy. In New

Zealand White rabbits high doses of

flecainide caused some foetal

abnormalities, but these effects were

not seen in Dutch Belted rabbits or

rats. The relevance of these findings

to humans has not been established.

Data have shown that flecainide

crosses the placenta. to the foetus in

patients taking flecainide during

pregnancy. Flecainide is excreted in

human milk and appears in

concentrations which reflect those in

maternal blood. The risk of adverse

effects to the nursing infant is very

small.

There is no evidence as to drug safety in

human pregnancy. In New Zealand White

rabbits high doses of flecainide caused some

foetal abnormalities, but these effects were

not seen in Dutch Belted rabbits or rats. The

relevance of these findings to humans has not

been established. Data have shown that

fFlecainide crosses the placenta; however, the

safety of Tambocor injection in pregnancy has

not been established. to the foetus in patients

taking flecainide during pregnancy. Flecainide

is excreted in human milk and appears in

concentrations which reflect those in maternal

blood. The risk of adverse effects to the

nursing infant is very small.

Drug

Interactions

Flecainide is a class I anti-arrhythmic

and interactions are possible

Flecainide is a class I anti-arrhythmic. and

Possible interactions include: are possible

with other anti- arrhythmic

drugs where additive effects

may occur or where drugs

interfere with the metabolism

of flecainide. The following

known categories of drugs

interact with flecainide:

Cardiac glycosides;

Flecainide can cause the

plasma digoxin level to rise

by about 15%, which is

unlikely to be of clinical

significance for patients with

plasma levels in the

therapeutic range. It is

recommended that the

digoxin plasma level in

digitalised patients should be

measured not less than six

hours after any digoxin dose,

before or after administration

of flecainide.

Class II antiarrhythmics; The

possibility of additive

negative inotropic effects of

beta-blockers and other

cardiac depressants with

flecainide should be

recognized.

Class III anti-arrhythmics;

the dose of When flecainide

is given in the presence of

amiodarone, the usual

flecainide dosage should be

reduced by 50% and the

patient mMonitored patient

closely for adverse effects.

Plasma level monitoring is

strongly recommended in

these circumstances.

Class IV anti-arrhythmics;

use of flecainide with other

sodium channel blockers is

not recommended.

Anti-depressants; fluoexetine

increases plasma flecainide

concentration; tricyclics

increased risk of arrhythmias

with tricyclics; manufacturer

of reboxetine manufacturer

advises caution.

Additive effects with other anti-

arrhythmic drugs or with drugs where

additive eaffectings may occur or

where drugs interfere with the

metabolism of flecainide. The

following known categories of drugs

interact with flecainide:

Cardiac glycosides;: Flecainide can

cause the plasma digoxin level to rise

by about 15%, which is unlikely to be

of clinical significance for patients

with plasma levels in the therapeutic

range. It is recommended that the

dDigoxin plasma level in digitalised

patients should be measured not less

than six hours after any digoxin dose,

before or after administration of

flecainide.

Class II antiarrhythmics;: The

possibility of additive negative

inotropic effects of beta-blockers and

other cardiac depressants with

flecainide should be recognizsed.

Class III anti-arrhythmics;: Reduce the

dose of When flecainide by 50% is

given in the presence of amiodarone,

to avoid additive effects. the usual

flecainide dosage should be reduced

by 50% and the patient mMonitored

patients closely for adverse events

effects. and Pplasma level monitoring

is strongly recommended in these

circumstances.

Class IV anti-arrhythmics;: use of

flecainide with other sodium channel

blockers is not recommended.

Anti-depressants;: fFluoexetine

increases plasma flecainide

concentration;. tTricyclics increased

the risk of arrhythmias. with tricyclics;

manufacturer of rReboxetine

manufacturer advises caution.

Anti-epileptics;: limited data in

patients receiving kKnown enzyme

inducers (phenytoin, phenobarbital,

carbamazepine) increase the rate of

flecainide elimination by

approximately indicate only a 30%

increase in the rate of flecainide

elimination.

Anti-psychotics: cClozapine-

Anti-epileptics;limited data in

patients receiving known

enzyme inducers (phenytoin,

phenobarbital,

carbamazepine) increase the

rate of flecainide elimination

indicate only a 30% increase

in the rate of flecainide

elimination.

Anti-psychotics: clozapine-

increased risk of arrhythmias.

Anti-histamines; increased

risk of ventricular

arrhythmias with mizolastine

and terfenadine (avoid

concomitant use).

Anti-malarials: quinine

increases plasma

concentration of flecainide.

Antivirals: plasma

concentration increased by

ritonavir, lopinavir and

indinavir ( increased risk of

ventricular arrhythmias)

aAvoid concomitant use.

Diuretics: Class effect due to

hypokalaemia giving rise to

cardiac toxicity.

Ulcer healing drugs:

cimetidine inhibits

metabolism of flecainide. In

healthy subjects receiving

cimetidine (1g daily) for one

week, plasma flecainide

levels iIncreased by about

approximately 30% and the

half-life increased by about

10%.

Anti-smoking aids: Co-

administration of bupropion

with drugs that are

metabolized by CYP2D6

isoenzyme including

flecainide should be

approached with caution and

should be initiated at the

lower end of the dose range

of the concomitant

medication. if bupropion is

added to the treatment

regimen of a patient already

receiving flecainide the need

increasesd the risk of arrhythmias.

Anti-histamines;: increased risk of

ventricular arrhythmias with

mMizolastine and terfenadine

increase the risk of ventricular

arrhythmias (avoid concomitant use).

Anti-malarials: qQuinine increases

plasma flecainide concentration of

flecainide.

Antivirals: plasma flecainide

concentrations are increased by

ritonavir, lopinavir and indinavir ( to

increased risk of ventricular

arrhythmias.) aAvoid concomitant use.

Diuretics: Class effect due to

hHypokalaemia giving rise to may

cause cardiac toxicity.

Ulcer healing drugs:

cCimetidine: inhibits metabolism of

flecainide. In healthy subjects

receiving cimetidine (1g daily) for one

week, plasma flecainide levels

iIncreasesd plasma flecainide by about

approximately 30%. and the half-life

increased by about 10%.

Anti-smoking aids: Co-administration

of bBupropion may increase with

drugs that are metabolized by

CYP2D6 isoenzyme including

flecainide plasma concentration by

inhibitory effects on CYP2D6, the

isoenzyme responsible for should be

approached with caution and should be

initiated at the lower end of the dose

range of the concomitant medication.

if bupropion is added to the treatment

regimen of a patient already receiving

flecainide metabolism, the need to

decrease the dose of the original

medication should be considered.

Treatment with Tambocor injection is

compatible with use of oral anti-

coagulants.

to decrease the dose of the

original medication should be

considered.

Treatment with Tambocor is

compatible with use of oral anti-

coagulants.

Adverse

Reactions Side

effects:

Body as a whole: Asthenia,

fatigue, fever, oedema

Cardiovascular: Pro-arrhythmic

effects occur but are most likely

in patients with structural heart

disease and/or significant left

ventricular impairment.

In patients with atrial flutter the

use of Tambocor injection has

been associated with 1:1 AV

conduction following initial atrial

slowing with resultant ventricular

acceleration . This has been seen

most commonly seen following

the use of the injection for acute

conversion.

This effect is usually short lived

and abates quickly following

cessation of therapy. The

following adverse effects have

also been reported effects. AV

block-second-degree and third

degree, bradycardia, cardiac

failure/congestive cardiac failure,

chest pain, hypotension,

myocardial infarction,

palpiltation, sinus pause or arrest

and tachycardia (AT or VT).

Dermatological A range of

allergic skin reactions have been

reported including rashes,and rare

but serious reports of urticaria.

There have also been isolated

cases of photosensitivity.

Immune system: A small number

of cases of increases in anti-

nuclear antibodies have been

reported, with and without

systemic inflammatory

involvement.

Haematological: Reductions in

red blood cells, white blood cells

and platelets have been

occasionally reported. These

changes are usually mild.

Psychiatric: Rarely,

Body as a whole: Asthenia, fatigue,

fever, oedema

Cardiovascular: Pro-arrhythmic effects

occur but are - most likely in patients

with structural heart disease and/or

significant left ventricular impairment.

In patients with atrial flutter the use of

Tambocor injection has been associated

with 1:1 AV conduction following initial

atrial slowing with resultant ventricular

acceleration may occur. This has been

(seen most commonly seen following the

use of the injection for acute conversion).

This effect is usually short lived and

abates quickly once following cessation

of therapy is stopped. The following

adverse effects have also been Other

reported effects.: AV block-second-

degree and third degree, bradycardia,

cardiac failure/congestive cardiac failure,

chest pain, hypotension, myocardial

infarction, palpiltation, sinus pause or

arrest and tachycardia (AT or VT).

Dermatological

Skin and appendages: A

range of aAllergic skin reactions, have

been reported including rashes, and rare

but serious reports of urticaria,. There

have also been isolated cases of

photosensitivity.

Immune system: A small number of

cases of iIncreaseds in anti-nuclear

antibodies have been reported, with and

without systemic inflammatory

involvement.

Haematological: Reductions in red and

white blood cells, white blood cells and

platelets have been reported occasionally

reported. These changes are usually mild.

Psychiatric: Rarely, hHallucinations,

depression, confusion, and amnesia,

anxiety, and insomnia have been

reported.

Gastrointestinal: Occasionally nNausea,

and vomiting,. The following have been

also reported: abdominal pain, anorexia,

constipation, diarrhoea, dyspepsia, and

hallucinations, depression,

confusion and amnesia anxiety

and insomnia have been reported.

Gastrointestinal: Occasionally

nausea and vomiting. The

following have been also

reported: abdominal pain,

anorexia, constipation, diarrhoea,

dyspepsia, and flatulence

(bloating).

Hepatic: a number of cases of

elevated liver enzymes and

jaundice have been reported in

association with Tambocor

treatment. So far this has always

been reversible on stopping

treatment,. Hepatic dysfunction

has also been reported.

CNS: Most commonly giddiness,

dizziness and light-headedness

which are usually transient. Rare

instances of dyskinesia have been

reported, which have improved

on withdrawal of flecainide

therapy. Rare instances of

convulsions, and during long term

therapy a few cases of peripheral

neuropathy, paraesthesi, and

ataxia have been reported. There

also have been reports of

flushing, headache,

hypoaesthesia, increased

sweating, somnolence, syncope,

tinnitus, tremor and vertigo.

Ophthalmological: Visual

disturbances, such as double

vision and blurring of vision may

occur but these are usually

transient and disappear upon

continuing or reducing the

dosage. Extremely rare cases of

corneal deposits have also been

reported.

Respiratory: Dyspnea and rare

cases of pneumonitis have been

reported.

flatulence (bloating).

HepaticLiver and biliary system: a

number of cases of eElevated liver

enzymes, and jaundice have been

reported in association with Tambocor

treatment. So far this has always been

which is reversible on stopping

treatment,. Hhepatic dysfunction has also

been reported.

CNSNeurological: Most commonly

gGiddiness, dizziness, and light-

headedness, which are usually transient.

Rare instances of dyskinesia, have been

reported, which have improved on

withdrawal of flecainide therapy. Rare

instances of convulsions., and dDuring

long term therapy a few cases of

peripheral neuropathy, paraesthesia, and

ataxia, have been reported. There also

have been reports of flushing, headache,

hypoaesthesia, increased sweating,

somnolence, syncope, tinnitus, tremor,

and vertigo.

Ophthalmological: Visual disturbances,

such as dDouble vision, and blurreding

of vision, may occur but these are usually

transient and disappear upon continuing

or reducing the dosage. Extremely rare

cases of corneal deposits have also been

reported.

Respiratory: Dyspnoea, and rare cases of

pneumonitis have been reported.

Overdose

Overdosage with flecainide is a

potentially life threatening medical

emergency. No specific antidote is

known. There is no known way of

rapidly removing flecainide from the

system, but forced acid diuresis may

Overdosage with flecainide is a potentially

life threatening medical emergency. No

specific antidote or rapid method of removing

flecainide from the system is known. There is

no known way of rapidly removing flecainide

from the system, but fForced acid diuresis

theoretically be helpful. Neither

dialysis nor haemoperfusion are .

helpful and injections of

anticholinergics are not

recommended.

Treatment may include therapy with

an inotropic agent, intravenous

calcium, giving circulatory

assistance (e.g. balloon pumping),

mechanically assisting respiration, or

temporarily inserting a transvenous

pacemaker if there are severe

conduction disturbances or the

patient's left ventricular function is

otherwise compromised.

may theoretically be helpful (theoretically),.

Neither but dialysis and nor haemoperfusion

are not. helpful and iInjections of

anticholinergics are not recommended.

Treatment of flecainide overdosage may

include therapy with use of an inotropic agent,

intravenous calcium, giving circulatory

assistance (e.g. balloon pumping),

mechanically assisting respiration, or

temporarily inserting a transvenous

pacemaker if there are severe conduction

disturbances or the patient's left ventricular

function is otherwise compromised.

Pharmacologic

Properties

Pharmacodynamic

Tambocor is a Class 1 anti-

arrhythmic (local anaesthetic) agent.

Tambocor slows conduction through

the heart, having its greatest effect on

His Bundle conduction. It also acts

selectively to increase anterograde

and particularly retrograde accessory

pathway refractoriness. Its actions

may be reflected in the

ECG by prolongation of the PR

interval and widening of the QRS

complex. The effect on the JT

interval is insignificant

Pharmacokinetic

Intravenous administration of 0.5 -

2.0 mg/kg to healthy subjects

resulted in plasma concentrations

ranging from 70 - 340 mcg/l. Protein

binding ranges from 32 to 58%. The

volume of distribution in healthy

subjects following intravenous

infusion of 2 mg/kg averaged 512

litres.

The elimination half life after IV

administration to patients was 7 to 19

hours.

How

supplied/Storage

and handling

Dilution: When necessary

Tambocor injection should be

diluted with, or injected

into, sterile solutions of 5% glucose.

If chloride containing solutions, such

as sodium chloride or Ringer's lactate

are used, the injection should be

Dilution: When necessary Tambocor

injection should be diluted with, or injected

into, sterile solutions of 5% glucose. If

chloride containing solutions, such as

sodium chloride or Ringer's lactate are used,

the injection should be added to a volume of

not less than 500 ml, otherwise a precipitate

added to a volume of not less than

500 ml, otherwise a precipitate will

form.

Store between 5-30°C. Do not

freeze. Protect from light.

will form.

Do not Sstore above between 5-30°C. Do not freeze.

Protect from light.

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