COUMADIN 6 MG

Israel - English - Ministry of Health

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Active ingredient:
WARFARIN SODIUM
Available from:
TARO PHARMACEUTICAL INDUSTRIES LTD
ATC code:
B01AA03
Pharmaceutical form:
TABLETS
Composition:
WARFARIN SODIUM 6 MG
Administration route:
PER OS
Prescription type:
Required
Manufactured by:
TARO PHARMACEUTICAL INDUSTRIES LTD
Therapeutic group:
WARFARIN
Therapeutic area:
WARFARIN
Therapeutic indications:
Coumadin is indicated for the prophylaxis and/or treatment of venous thrombosis and its extension, and pulmonar embolis. Coumadin is indicated for the prophylaxis and/or treatment of the thromboembolic complications associated with atrial fibrillation and/or cardiac valve replacement. Coumadin is indicated to reduce the risk of death, recurrent myocardial infarction, and thromboembolic events such as stroke or systemic embolization after myocardial infarction.
Authorization number:
111 49 29379 00
Authorization date:
2013-06-30

Documents in other languages

Patient Information leaflet Patient Information leaflet - Hebrew

16-08-2020

Final Physician Leaflet 08.2020

Prescribing Information

COUMADIN TABLETS

1. Name of the medicinal product

COUMADIN 1 mg

COUMADIN 2 mg

COUMADIN 2.5 mg

COUMADIN 5 mg

2. Qualitative and quantitative composition

Each tablet of Coumadin 1 mg contains 1 mg warfarin sodium.

Each tablet of Coumadin 2 mg contains 2 mg warfarin sodium.

Each tablet of Coumadin 2.5 mg contains 2.5 mg warfarin sodium.

Each tablet of Coumadin 5 mg contains 5 mg warfarin sodium.

For excipients, see 6.1.

3. Pharmaceutical form

Tablets.

Presentation:

COUMADIN 1 mg tablets are pink, flat capsule shaped, beveled tablets, one side engraved

with “WARFARIN” and "TARO", and other side scored and engraved with “1”.

COUMADIN 2 mg tablets are lavender, flat capsule shaped, beveled tablets, one side

engraved with “WARFARIN” and "TARO", and other side scored and engraved with “2”.

COUMADIN 2.5 mg tablets are green, flat capsule shaped, beveled tablets, one side

engraved with “WARFARIN” and "TARO", and other side scored and engraved with “2½”.

COUMADIN 5 mg tablets are peach, flat capsule shaped, beveled tablets, one side engraved

with “WARFARIN” and "TARO", and other side scored and engraved with “5”.

The tablet can be divided into equal halves.

4. Clinical particulars

4.1 Therapeutic indications

COUMADIN is indicated for the prophylaxis and/or treatment of venous thrombosis and its

extension, and pulmonary embolism.

COUMADIN is indicated for the prophylaxis and/or treatment of the thromboembolic

complications associated with atrial fibrillation and/or cardiac valve replacement.

COUMADIN is indicated to reduce the risk of death, recurrent myocardial infarction, and

thromboembolic events such as stroke or systemic embolization after myocardial infarction.

Final Physician Leaflet 08.2020

4.2 Posology and method of administration

The dosage and administration of COUMADIN must be individualized for each patient

according to the particular patient's PT/INR response to the drug. The dosage should be

adjusted based upon the patient's PT/INR.

Venous Thromboembolism (including deep venous thrombosis [DVT] and pulmonary

embolism [PE])

For patients with a first episode of DVT or PE secondary to a transient (reversible) risk factor,

treatment with warfarin for 3 months is recommended. For patients with a first episode of

idiopathic DVT or PE, warfarin is recommended for at least 6 to 12 months. For patients with

two or more episodes of documented DVT or PE, indefinite treatment with warfarin is

suggested. For patients with a first episode of DVT or PE who have documented

antiphospholipid antibodies or who have two or more thrombophilic conditions, treatment for

12 months is recommended and indefinite therapy is suggested. For patients with a first

episode of DVT or PE who have documented deficiency of antithrombin, deficiency of Protein

C or Protein S, or the Factor V Leiden or prothrombin 20210 gene mutation, homocystinemia,

or high Factor VIII levels (>90th percentile of normal), treatment for 6 to 12 months is

recommended and indefinite therapy is suggested for idiopathic thrombosis. The risk-benefit

should be reassessed periodically in patients who receive indefinite anticoagulant treatment.

The dose of warfarin should be adjusted to maintain a target INR of 2.5 (INR range, 2.0 to 3.0)

for all treatment durations. These recommendations are supported by the 7th ACCP

guidelines.

Atrial Fibrillation

Five recent clinical trials evaluated the effects of warfarin in patients with non-valvular atrial

fibrillation (AF). Meta-analysis findings of these studies revealed that the effects of warfarin in

reducing thromboembolic events including stroke were similar at either moderately high INR

(2.0-4.5) or low INR (1.4-3.0). There was a significant reduction in minor bleeds at the low

INR. Similar data from clinical studies in valvular atrial fibrillation patients are not available.

The trials in non-valvular atrial fibrillation support the American College of Chest Physicians'

(ACCP) recommendation that an INR of 2.0-3.0 be used for long term warfarin therapy in

appropriate AF patients.

Oral anticoagulation therapy with warfarin is recommended in patients with persistent or

paroxysmal AF (PAF) (intermittent AF) at high risk of stroke (i.e., having any of the following

features: prior ischemic stroke, transient ischemic attack, or systemic embolism, age >75

years, moderately or severely impaired left ventricular systolic function and/or congestive

heart failure, history of hypertension, or diabetes mellitus). In patients with persistent AF or

PAF, age 65 to 75 years, in the absence of other risk factors, but who are at intermediate risk

of stroke, antithrombotic therapy with either oral warfarin or aspirin, 325 mg/day, is

recommended. For patients with AF and mitral stenosis, anticoagulation with oral warfarin is

recommended (7th ACCP). For patients with AF and prosthetic heart valves, anticoagulation

with oral warfarin should be used; the target INR may be increased and aspirin added

Final Physician Leaflet 08.2020

depending on valve type and position, and on patient factors.

Post-Myocardial Infarction

The results of the WARIS II study and 7th ACCP guidelines suggest that in most healthcare

settings, moderate- and low-risk patients with a myocardial infarction should be treated with

aspirin alone over oral vitamin-K antagonist (VKA) therapy plus aspirin. In healthcare settings

in which meticulous INR monitoring is standard and routinely accessible, for both high- and

low-risk patients after myocardial infarction (MI), long-term (up to 4 years) high-intensity oral

warfarin (target INR, 3.5; range, 3.0 to 4.0) without concomitant aspirin or moderate-intensity

oral warfarin (target INR, 2.5; range, 2.0 to 3.0) with aspirin is recommended. For high-risk

patients with MI, including those with a large anterior Ml, those with significant heart failure,

those with intracardiac thrombus visible on echocardiography, and those with a history of a

thromboembolic event, therapy with combined moderate-intensity (INR, 2.0 to 3.0) oral

warfarin plus low- dose aspirin (≤l00 mg/day) for 3 months after the MI is suggested.

Mechanical and Bioprosthetic Heart Valves

For all patients with mechanical prosthetic heart valves, warfarin is recommended. For

patients with a St. Jude Medical (St. Paul, MN) bileaflet valve in the aortic position, a target

INR of 2.5 (range, 2.0 to 3.0) is recommended. For patients with tilting disk valves and

bileaflet mechanical valves in the mitral position, the 7th ACCP recommends a target INR of

3.0 (range, 2.5 to 3.5). For patients with caged ball or caged disk valves, a target INR of 3.0

(range, 2.5 to 3.5) in combination with aspirin, 75 to 100 mg/day is recommended. For

patients with bioprosthetic valves, warfarin therapy with a target INR of 2.5 (range, 2.0 to 3.0)

is recommended for valves in the mitral position and is suggested for valves in the aortic

position for the first 3 months after valve insertion.

Recurrent Systemic Embolism and Other Indications

Oral anticoagulation therapy has not been evaluated by properly designed clinical trials in

patients with valvular disease associated with atrial fibrillation, patients with mitral stenosis,

and patients with recurrent systemic embolism of unknown etiology. A moderate dose regimen

(INR 2.0 to 3.0) is recommended for these patients.

An INR of greater than 4.0 appears to provide no additional therapeutic benefit in most

patients and is associated with a higher risk of bleeding.

Initial Dosage

The dosing of COUMADIN must be individualized according to patient's sensitivity to the drug

as indicated by the PT/INR. Use of a large loading dose may increase the incidence of

hemorrhagic and other complications, does not offer more rapid protection against thrombi

formation, and is not recommended. Lower initiation and maintenance doses are

recommended for elderly and/or debilitated patients and patients with potential to exhibit

greater than expected PT/INR response to COUMADIN. Based on limited data, Asian patients

Final Physician Leaflet 08.2020

may also require lower initiation and maintenance doses of COUMADIN. It is recommended

that COUMADIN therapy be initiated with a dose of 2 to 5 mg per day with dosage

adjustments based on the results of PT/INR determinations.

Maintenance

Most patients are satisfactorily maintained at a dose of 2 to 10 mg daily. Flexibility of dosage

is provided by breaking scored tablets in half. The individual dose and interval should be

gauged by the patient's prothrombin response.

If the prescribed dosing regimen requires splitting tablets, it can be done using a dedicated

device (tablet splitter).

Duration of Therapy

The duration of therapy in each patient should be individualized. In general, anticoagulant

therapy should be continued until the danger of thrombosis and embolism has passed.

Missed Dose

The anticoagulant effect of COUMADIN persists beyond 24 hours. If the patient forgets to take

the prescribed dose of COUMADIN at the scheduled time, the dose should be taken as soon

as possible on the same day. The patient should not take the missed dose by doubling the

daily dose to make up for missed doses, but should refer back to his or her physician.

4.3 Contraindications

Hypersensitivity to the active substance or to any of the excipients listed in section 6.1.

Haemorrhagic stroke (see section 4.4 for further details)

Clinically significant bleeding

Within 72 hours of major surgery with risk of severe bleeding (for information on other

surgery, see section 4.4)

Within 48 hours postpartum

Pregnancy (first and third trimesters, see section 4.6)

Drugs where interactions may lead to a significantly increased risk of bleeding (see section

4.5)

4.4 Special warnings and precautions for use

Most adverse events reported with warfarin are a result of over anticoagulation therefore it is

important that the need for therapy is reviewed on a regular basis and therapy discontinued

when no longer required.

Commencement of therapy

Monitoring

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When warfarin is started using a standard dosing regimen the INR should be determined daily

or on alternate days in the early days of treatment. Once the INR has stabilised in the target

range the INR can be determined at longer intervals.

INR should be monitored more frequently in patients at an increased risk of over coagulation

e.g. patients with severe hypertension, liver or renal disease.

Patients for whom adherence may be difficult should be monitored more frequently.

Thrombophilia

Patients with protein C deficiency are at risk of developing skin necrosis when starting

warfarin treatment. In patients with protein C deficiency, therapy should be introduced without

a loading dose of warfarin even if heparin is given. Patients with protein S deficiency may also

be at risk and it is advisable to introduce warfarin therapy slowly in these circumstances.

Risk of haemorrhage

The most frequently reported adverse effect of all oral anticoagulants is haemorrhage.

Warfarin should be given with caution to patients where there is a risk of serious haemorrhage

(e.g. concomitant NSAID use, recent ischaemic stroke, bacterial endocarditis, previous

gastrointestinal bleeding).

Risk factors for bleeding include high intensity of anticoagulation (INR >4.0), age ≥65, highly

variable INRs, history of gastrointestinal bleeding, uncontrolled hypertension, cerebrovascular

disease, serious heart disease, risk of falling, anaemia, malignancy, trauma, renal

insufficiency, concomitant drugs (see section 4.5). All patients treated with warfarin should

have INR monitored regularly. Those at high risk of bleeding may benefit from more frequent

INR monitoring, careful dose adjustment to desired INR, and a shorter duration of therapy.

Patients should be instructed on measures to minimise risk of bleeding and to report

immediately to physicians signs and symptoms of bleeding.

Checking the INR and reducing or omitting doses depending on INR level is essential,

following consultation with anticoagulation services if necessary. If the INR is found to be too

high, reduce dose or stop warfarin treatment; sometimes it will be necessary to reverse

anticoagulation. INR should be checked within 2–3 days to ensure that it is falling.

Any concomitant anti-platelet drugs should be used with caution due to an increased risk of

bleeding.

Haemorrhage

Haemorrhage can indicate an overdose of warfarin has been taken. For advice on treatment

of haemorrhage see section 4.9.

Unexpected bleeding at therapeutic levels should always be investigated and INR monitored.

Ischaemic stroke

Anticoagulation following an ischaemic stroke increases the risk of secondary haemorrhage

into the infarcted brain. In patients with atrial fibrillation long term treatment with warfarin is

beneficial, but the risk of early recurrent embolism is low and therefore a break in treatment

after ischaemic stroke is justified. Warfarin treatment should be re-started 2–14 days following

ischaemic stroke, depending on the size of the infarct and blood pressure. In patients with

Final Physician Leaflet 08.2020

large embolic strokes, or uncontrolled hypertension, warfarin treatment should be stopped for

14 days.

Calciphylaxis

Calciphylaxis is a rare syndrome of vascular calcification with cutaneous necrosis, associated

with high mortality. The condition is mainly observed in patients with end-stage renal disease

on dialysis or in patients with known risk factors such as protein C or S deficiency,

hyperphosphataemia, hypercalcaemia or hypoalbuminaemia. Rare cases of calciphylaxis

have been reported in patients taking warfarin, also in the absence of renal disease. In case

calciphylaxis is diagnosed, appropriate treatment should be started and consideration should

be given to stopping treatment with warfarin.

Surgery

For surgery where there is no risk of severe bleeding, surgery can be performed with an INR

of <2.5.

For surgery where there is a risk of severe bleeding, warfarin should be stopped 3 days prior

to surgery.

Where it is necessary to continue anticoagulation e.g. risk of life-threatening

thromboembolism, the INR should be reduced to <2.5 and heparin therapy should be started.

If surgery is required and warfarin cannot be stopped 3 days beforehand, anticoagulation

should be reversed with low-dose vitamin K.

The timing for re-instating warfarin therapy depends on the risk of post-operative

haemorrhage. In most instances warfarin treatment can be re-started as soon as the patient

has an oral intake.

Dental Surgery

Warfarin need not be stopped before routine dental surgery, eg, tooth extraction.

Active peptic ulceration

Due to a high risk of bleeding, patients with active peptic ulcers should be treated with caution.

Such patients should be reviewed regularly and informed of how to recognize bleeding and

what to do in the event of bleeding occurring.

Interactions

Many drugs and foods interact with warfarin and affect the prothrombin time (see section 4.5).

Any change to medication, including self-medication with OTC products, warrants increased

monitoring of the INR. Patients should be instructed to inform their doctor before they start to

take any additional medications including over the counter medicines, herbal remedies or

vitamin preparations.

Thyroid disorders

The rate of warfarin metabolism depends on thyroid status. Therefore patients with hyper- or

hypo-thyroidism should be closely monitored on starting warfarin therapy.

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Additional circumstances where changes in dose may be required

The following also may exaggerate the effect of warfarin tablets, and necessitate a reduction

of dosage:

Loss of weight

Acute illness

Cessation of smoking

The following may reduce the effect of warfarin tablets, and require the dosage to be

increased:

Weight gain

Diarrhoea

Vomiting

Other warnings

Acquired or inherited warfarin resistance should be suspected if larger than usual daily doses

of warfarin are required to achieve the desired anticoagulant effect.

Genetic information

Genetic variability particularly in relation to CYP2C9 and VKORC1 can significantly affect

dose requirements for warfarin. If a family association with these polymorphisms is known

extra care is warranted.

Patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or

glucose-galactose malabsorption should not take this medicine.

4.5 Interaction with other medicinal products and other forms of interaction

Warfarin has a narrow therapeutic range and care is required with all concomitant therapy.

The individual product information for any new concomitant therapy should be consulted for

specific guidance on warfarin dose adjustment and therapeutic monitoring.

If no information is provided the possibility of an interaction should be considered. Increased

monitoring should be considered when commencing any new therapy if there is any doubt as

to the extent of interaction.

Pharmacodynamic interactions

Drugs which are contraindicated

Concomitant use of drugs used in the treatment or prophylaxis of thrombosis, or other drugs

with adverse effects on haemostasis may increase the pharmacological effect of warfarin,

increasing the risk of bleeding.

Fibrinolytic drugs such as streptokinase and alteplase are contraindicated in patients receiving

warfarin.

Drugs which should be avoided if possible

The following examples should be avoided, or administered with caution with increased

clinical and laboratory monitoring:

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Clopidogrel

NSAIDs (including aspirin and cox-2 specific NSAIDS)

Sulfinpyrazone

Thrombin inhibitors such as bivalirudin, dabigatran

Dipyridamole

Unfractionated heparins and heparin derivatives, low molecular weight heparins

Fondaparinux, rivaroxaban

Glycoprotein IIb/IIIa receptor antagonists such as eptifibatide, tirofiban and abciximab

Prostacyclin

SSRI and SNRI antidepressants

Other drugs which inhibit haemostasis, clotting or platelet action

Low-dose aspirin with warfarin may have a role in some patients but the risk of gastrointestinal

bleeding is increased. Warfarin may initially be given with a heparin in the initial treatment of

thrombosis, until the INR is in the correct range.

Metabolic interactions

Warfarin is a mixture of enantiomers which are metabolised by different CYPP450

cytochromes. R-warfarin is metabolized primarily by CYP1A2 and CYP3A4. S-warfarin is

metabolised primarily by CYP2C9. The efficacy of warfarin is affected primarily when the

metabolism of S-warfarin is altered.

Drugs that compete as substrates for these cytochromes or inhibit their activity may increase

warfarin plasma concentrations and INR, potentially increasing the risk of bleeding. When

these drugs are co-administered, warfarin dosage may need to be reduced and the level of

monitoring increased.

Conversely, drugs which induce these metabolic pathways may decrease warfarin plasma

concentrations and INR, potentially leading to reduced efficacy. When these drugs are co-

administered, warfarin dosage may need to be increased and the level of monitoring

increased.

There is a small subset of drugs for which interactions are known; however their clinical effect

on the INR is variable. In these cases increased monitoring on starting and stopping therapy is

advised.

Care should also be taken when stopping or reducing the dose of a metabolic inhibitor or

inducer, once patients are stable on this combination (offset effect).

Listed below are drugs which are known to interact with warfarin in a clinically significant way.

Examples of drugs which potentiate the effect of warfarin

allopurinol, capecitabine, erlotinib, disulfiram, azole antifungals (ketoconazole, fluconazole

etc), omeprazole, paracetamol (prolonged regular use), propafenone, amiodarone, tamoxifen,

methylphenidate, zafirlukast, fibrates, statins (not pravastatin; predominantly associated with

fluvastatin), erythromycin, sulfamethoxazole, metronidazole

Examples of drugs which antagonise the effect of warfarin

Barbiturates, primidone, carbamazepine, griseofulvin, oral contraceptives, rifampicin,

azathioprine, phenytoin

Examples of drugs with variable effect

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Corticosteroids, nevirapine, ritonavir

Other drug interactions

Broad spectrum antibiotics may potentiate the effect of warfarin by reducing the gut flora

which produce vitamin K. Similarly, orlistat may reduce absorption of vitamin K.

Cholestyramine and sucralfate potentially decrease absorption of warfarin.

Increased INR has been reported in patients taking glucosamine and warfarin. This

combination is not recommended.

Interactions with herbal products

Herbal preparations containing St John's Wort (Hypericum perforatum) must not be used

whilst taking warfarin due to a proven risk of decreased plasma concentrations and reduced

clinical effects of warfarin.

Many other herbal products have a theoretical effect on warfarin; however most of these

interactions are not proven. Patients should generally avoid taking any herbal medicines or

food supplements whilst taking warfarin, and should be told to advise their doctor if they are

taking any, as more frequent monitoring is advisable.

Alcohol

Acute ingestion of a large amount of alcohol may inhibit the metabolism of warfarin and

increase INR. Conversely, chronic heavy alcohol intake may induce the metabolism of

warfarin. Moderate alcohol intake can be permitted.

Interactions with food and food supplements

Individual case reports suggest a possible interaction between warfarin and cranberry juice, in

most cases leading to an increase in INR or bleeding event. Patients should be advised to

avoid cranberry products. Increased supervision and INR monitoring should be considered for

any patient taking warfarin and regular cranberry juice.

Limited evidence suggests that grapefruit juice may cause a modest rise in INR in some

patients taking warfarin.

Certain foods such as liver, broccoli, Brussels sprouts and green leafy vegetables contain

large amounts of vitamin K. Sudden changes in diet can potentially affect control of

anticoagulation. Patients should be informed of the need to seek medical advice before

undertaking any major changes in diet.

There are limited data on possible drug interactions with glucosamine, but increments in the

INR parameter have been reported with oral vitamin K antagonists. Patients treated with oral

vitamin K antagonists should therefore be closely monitored at the time of initiation or

termination of glucosamine therapy.

Many other food supplements have a theoretical effect on warfarin; however most of these

interactions are not proven. Patients should generally avoid taking any food supplements

whilst taking warfarin, and should be told to advise their doctor if they are taking any, as more

frequent monitoring is advisable.

Laboratory tests

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Heparins and danaparoid may prolong the prothrombin time, therefore a sufficient time

interval should be allowed after administration before performing the test.

4.6. Fertility, pregnancy and lactation

Pregnancy

Based on human experience warfarin causes congenital malformations and foetal death when

administered during pregnancy.

Warfarin is contraindicated in pregnancy in the first and third trimester.

Women of child-bearing age who are taking warfarin tablets should use effective

contraception during treatment.

Breast-feeding:

Warfarin is excreted in breast milk in small amounts. However, at therapeutic dose of warfarin

no effects on the breast-feeding child are anticipated. Warfarin can be used during breast-

feeding.

4.7 Effects on ability to drive and use machines

Warfarin has no influence on the ability to drive and use machines.

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 (≥1/10); common (≥1/100

to <1/10); uncommon (≥1/1,000 to <1/100); rare (≥1/10,000 to <1/1,000); very rare

(<1/10,000) and not known – cannot be estimated from the available data.

System organ class

Frequency

Adverse Reaction

Infections and infestations

Not known

Fever

Immune system disorders

Not known

Hypersensitivity

Nervous system disorders

Not known

Cerebral haemorrhage;

Cerebral subdural haematoma

Vascular disorders

Not known

Haemorrhage

Respiratory, thoracic and

mediastinal disorders

Not known

Haemothorax, epistaxis

Gastrointestinal disorders

Not known

Gastroinestinal haemorrhage,

rectal haemorrhage,

haematemesis; pancreatitis;

diarrhoea; nausea; vomiting;

melaena

Hepatobiliary disorders

Not known

Jaundice; hepatic dysfunction

Skin and subcutaneous

disorders

Not known

Rash; alopecia; purpura; 'purple

toes' syndrome; erythematous

swollen skin patches leading to

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ecchymosis, infarction and skin

necrosis; calciphylaxis

Renal and Urinary disorders

Not known

Haematuria

Investigations

Not known

Unexplained drop in

haematocrit; haemoglobin

decreased

Reporting of suspected adverse reactions

Reporting suspected adverse reactions after authorization of the medicinal product is

important. It allows continued monitoring of the benefit/risk balance of the medicinal product.

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

National Regulation by using an online form:

https://sideeffects.health.gov.il

4.9 Overdose

The benefit of gastric decontamination is uncertain. If the patient presents within 1 hour of

ingestion of more than 0.25 mg/kg or more than the patient's therapeutic dose, consider

activated charcoal (50 g for adults; 1 g/kg for children)

In cases of life-threatening haemorrhage

Stop warfarin treatment, give prothrombin complex concentrate (factors II, VII, IX, and X) 30–

50 units/kg or (if no concentrate available) fresh frozen plasma 15 mL/kg. Discuss with local

haematologist or National Poisons Information Service, or both.

Non-life threatening haemorrhage

Where anticoagulation can be suspended, give slow intravenous injection of phytomenadione

(vitamin K1) 10–20 mg for adults (250 micrograms/kg for a child)

Where rapid re-anticoagulation is desirable (e.g., valve replacements) give prothrombin

complex concentrate (factors II, VII, IX, and X) 30–50 units/kg or (if no concentrate available)

fresh frozen plasma 15 mL/kg.

Monitor INR to determine when to restart normal therapy. Monitor INR for at least 48 hours

post overdose.

For patients on long-term warfarin therapy without major haemorrhage

INR >8.0, no bleeding or minor bleeding—stop warfarin, and give phytomenadione (vitamin

K1) 0.5–1 mg for adults, 0.015– 0.030 mg/kg (15–30 micrograms/kg) for children by slow

intravenous injection or 5 mg by mouth (for partial reversal of anticoagulation give smaller oral

doses of phytomenadione e.g., 0.5–2.5 mg using the intravenous preparation orally); repeat

dose of phytomenadione if INR still too high after 24 hours. Large doses of phytomenadione

may completely reverse the effects of warfarin and make re-establishment of anticoagulation

difficult.

INR 6.0–8.0, no bleeding or minor bleeding—stop warfarin, restart when INR <5.0

INR <6.0 but more than 0.5 units above target value—reduce dose or stop warfarin, restart

when INR <5.0

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For patients NOT on long-term anticoagulants without major haemorrhage

Measure the INR (prothrombin time) at presentation and sequentially every 24–48 hours after

ingestion depending on the initial dose and initial INR.

If the INR remains normal for 24–48 hours and there is no evidence of bleeding, there should

be no further monitoring necessary.

Give vitamin K1 (phytomenadione) if:

a) There is no active bleeding and the patient has ingested more than 0.25 mg/kg;

b )The prothrombin time is already significantly prolonged (INR >4.0).

The adult dose of vitamin K1 is 10–20 mg orally (250 micrograms/kg body weight for a child).

Delay oral vitamin K1 at least 4 hours after any activated charcoal has been given. Repeat

INR at 24 hours and consider further vitamin K1.

5. Pharmacological properties

5.1 Pharmacodynamic properties

Pharmatherapeutic group: Antithrombotic agents, Vitamin K antagonists

ATC code: B01AA03

Mechanism of action

Coumadin is a synthetic anticoagulant of the coumarin series. It acts by inhibiting the

formation of active clotting factors II, VII, IX and X.

5.2 Pharmacokinetic properties

Absorption

Coumadin is readily absorbed from the gastro-intestinal tract.

Distribution

Its plasma half-life is about 40 hours.

Biotransformation

It is metabolised in the liver.

Elimination

It is excreted in the urine mainly as metabolites.

5.3 Preclinical safety data

No further data of relevance

6. Pharmaceutical particulars

6.1 List of excipients

COUMADIN Tablets for oral use also contain:

All strengths:

Lactose anhydrous, pregelatinized starch and magnesium stearate

1 mg:

D&C Red No. 6 Barium Lake

2 mg:

FD&C Blue No. 2 Lake and

FD&C Red No. 40 Lake

2.5 mg:

FD&C Blue No. 2 Lake and

D&C Yellow No. 10 Lake

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5 mg:

D&C Red No. 6 Barium Lake and

D&C Yellow No. 10 Lake

6.2 Incompatibilities

None

6.3 Expiry date

The expiry date of the product is indicated on the packaging materials

6.4 Special precautions for storage

Store below 25°C

6.5 Nature and contents of container

HDPE bottles with child-resistant PP cap containing either 30, 100 or 1000 tablets of

Coumadin.

Not all packs may be marketed.

6.6 Special precautions for disposal and other handling

No special requirements for disposal.

7. Manufacturer and registration holder

Taro Pharmaceutical Industries Ltd., 14 Hakitor St., Haifa Bay 2624761

8. Marketing authorization numbers

COUMADIN 1 mg tablets:

43.29373

COUMSDIN 2 mg tablets:

44.29374

COUMADIN 2.5 mg tablets:

45.29375

COUMADIN 5 mg tablets:

48.29378

Revised in August 2020.

ורת תיחקור הישעת

מ"עב

רוטיקה

.ד.ת

10347

הפיח ץרפמ ,

2624761

:לט

04-8475700

:סקפ

04-8727165

טסוגוא

2020

ה/דבכנ ה/אפור

ת/דבכנ ת/חקור

יכ םכעידוהל תשקבמ ורת תרבח ןולעה

ןכרצל

אפורלו

לש רישכתה

Coumadin 1, 2, 2.5, 5 mg, tablets

כדוע ונ

.

םייוניש ושענ םהב םיפיעסה קר םיניוצמ וז העדוהב םייתוהמ

ןכרצל ןולעב

אפורל ןולעבו עבצב ונמוס תופסות . םודא לוחכ עבצב ונמוס תוקיחמה ,

הקיחמ וק

ולעה םינ

כדועמה םינ

חלשנ

מוסרפ ךרוצל תואירבה דרשמל

:תואירבה דרשמ רתאבש תופורתה רגאמב

www.health.gov.il

לבקל ןתינו

ספדומ םי

:םושירה לעבל היינפ ידי לע

ורת תיחקור הישעת

רוטיקה בוחר ,מ"עב

ד.ת ,

10347

הפיח ץרפמ

2624761

,הכרבב

ןמדלוג הנירמ

הנוממ תחקור

Coumadin 1, 2, 2.5, 5 mg, tablets

ליעפ ביכרמ

:

Warfarin sodium 1, 2, 2.5, 5 mg

היוותהה

:רישכתל תרשואמה

Coumadin is indicated for the prophylaxis and/or treatment of venous thrombosis and its extension, and

pulmonary embolis.

Coumadin is indicated for the prophylaxis and/or treatment of the thromboembolic complications

associated with atrial fibrillation and/or cardiac valve replacement.

Coumadin is indicated to reduce the risk of death, recurrent myocardial infarction, and thromboembolic

events such as stroke or systemic embolization after myocardial infarction.

םינוכדע

:ןכרצל ןולעב

ןיב תובוגת

-

תויצקארטניא/תויתפורת

אפורה תא עדייל שי ש ינפל חקול התא

רתה תא תואבה תופו

:

רפסמ םד תשירק תעינמל תושמשמה תופורת לש םיגוס

ןוגכ ,ןירפרוו לורמוקיד ןומוקורפנפ , לורמוקונצא ,

יאולפו

ןויד וקולג םע דחיב תוחקלנשכ רתוי הקזח תויהל הלולע ולא תופורת לש העפשהה .( .ןימז רשא םילפוטמ םילטונ

תוריהזב םירטונמ תויהל םיכירצ הלאכ םיבוליש רשאכ הרתי .ןימזוקולג םע לופיט םימייסמ וא םיליחתמ

הפורתה תעפשה תא תוריבגמ רשא תופורת

:

חקול התא םא אפורה תא עדייל שי

:

ןימטיו

ב דבכ ןמשב וא הנוזת יפסותב) ןימטיו לש הכירצב תימואתפ הדירי :(הלק

העפשהה תא ריבגהל הלולע ןירפרוו לש

רשא תופורת תותיחפמ הפורתה תעפשה תא

:

חקול התא םא אפורה תא עדייל שי

:

ןימטיו

ןימטיו לש הכירצב הילע

ןירפרוו לש העפשהה תא ןיטקהל הלולע

(הלקב דבכ ןמשב וא הנוזת יפסותב

הפורתב שומיש

ןוזמו

תויצומח ץימ תייתשמ ענמיה

וא תוילוכשא

וא

תויצומח ירצומ תליטנ

וא תוילוכשא

תא ריבגהל םילולע ולא הפורתה לש התעפשה

ורת תיחקור הישעת

מ"עב

רוטיקה

.ד.ת

10347

הפיח ץרפמ ,

2624761

:לט

04-8475700

:סקפ

04-8727165

ל ןולעב םינוכדע אפור

:

Interactions with food and food supplements

There are limited data on possible drug interactions with glucosamine, but increments in the INR

parameter have been reported with oral vitamin K antagonists. Patients treated with oral vitamin

K antagonists should therefore be closely monitored at the time of initiation or termination of

glucosamine therapy.

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