HEXAKAPRON TABLETS

This leaflet format has been determined by the Ministry of Health and

the content thereof has been checked and approved.

PATIENT

PA

C

KAGE

INSERT

IN

ACCORDANCE

WIT

H

T

H

E

PHARMACISTS'

REGULATIONS

(PREPARATI

ONS

-

1986

)

The dispensing of this medicine requires a doctor's prescription.

Read this package insert carefully in its entirety before using

this medicine.

HEXAKAPRON

Tablets

COMPOSITION

Each tablet contains:

Tranexamic acid

500 mg

Inactive Ingredients

THERAPEUTIC GROUP

Antifibrinolytic.

THERAPEUTIC ACTIVITY

Treatment of hemorrhages.

WHEN SHOULD THE PREPARATION NOT BE USED?

Do not use this medicine if you are sensitive to any of its ingredients.

Do not use this medicine if you suffer or have suffered in the past

from thromboembolic disease.

Do not use this medicine if you have renal failure.

Do not use this medicine if you have acquired color blindness.

Do not take this medicine without consulting a doctor before

starting treatment if you are pregnant or breastfeeding, if you are

suffering, or have suffered in the past, from impaired function of the

heart and/or vascular system, the kidney/urinary tract, if you have

undergone prostatectomy, if you have blood in urine, in cases of family

history

blood

clots

blood

vessels

(thrombosis, stroke),

have

ever had uncontrollable bleeding.

WARNINGS

If you are sensitive to any type of food or medicine, inform your doctor

before commencing treatment with this medicine.

In cases of treatment that will last more than a few days, patients

DRUG INTERACTIONS

If you are taking another drug concomitantly or if you have just finished

treatment with another medicine, including non prescription medications

or nutritional supplements, inform the attending doctor, in order to

prevent hazards or lack of efficacy arising from drug interactions. This

SIDE EFFECTS

In addition to the desired effect of the medicine, adverse reactions

may occur during the course of taking this medicine, for example:

diarrhea, nausea/vomiting.

Effects that require special attention:

Changes or vision disturbances, bleeding in the eye (rare): stop

treatment and refer to a doctor immediately!

Allergic skin reactions causing itching, swelling and redness of skin

(rare): refer to a doctor immediately!

Feeling of discomfort or swelling in a leg or arm, pain or feeling of

heaviness in your chest might be symptoms of a blood clot in your

blood vessel (rare): refer to a doctor immediately!

In the event that you experience side effects not mentioned in

this leaflet, or if there is a change in your general health, consult

your doctor immediately.

DOSAGE

According to doctor’s instructions only.

Do not exceed the recommended dosage.

DIRECTIONS FOR USE

Do not chew! The tablet may be divided on the score line.

Swallow the tablet with a small amount of water.

This medicine may be taken with food.

AVOID

POISONING!

This medicine, and all other medicines, must be stored in a safe place

out of the reach of children and/or infants, to avoid poisoning. If you

have taken an overdose, or if a child has accidentally swallowed the

medicine, proceed immediately to a hospital emergency room and

bring the package of the medicine with you.

induce

iting unless explicitly instructed to do so by a doctor!

This medicine has been prescribed for the treatment of your ailment;

in another patient it may cause harm. Do not give this medicine to

your relatives, neighbours or acquaintances.

take

medicine

dark! Check the label and the dose e

time you take your medicine. Wear glasses if you need them.

Storage

Store this medicine in a dry place, below 25

Even if kept in their original container and stored as recommended,

medicines may be kept for a limited period only. Please note the expiry

date of the medicine! In case of doubt, consult the pharmacist who

dispensed the medicine to you.

Do not store different medications in the same package.

Drug Registration No.: 016 35 24864 00

Teva Pharmaceutical Industries Ltd.,

P.O.Box 3190, Petah-Tikva

322K038020913

Hexakapron

217x135 mm side B

Microcrystalline

cellulose,

sodium starch glycolate,

magnesium

stearate, methylcellulose, colloidal silicon dioxide, talc, purified

water.

should have their eyes examined prior to, and frequently after

starting treatment.

especially

important

treated

with

anticoagulant

medicines.

!

/

1

9

8

6

-

"

(

)

Tranexamic Acid 500 mg

322K038020913

Hexakapron

217x135 mm side A

Microcrystalline

cellulose,

sodium starch glycolate,

magnesium

stearate, methylcellulose, colloidal silicon dioxide, talc, purified

water.

Hexakapron tablets , 6. 6. 2011, RH

"

ע עבקנ הז ןולע טמרופ

"

רשואו קדבנ ונכותו תואירבה דרשמ י

."

רשואמ ןולע

יאמ

2011

“This leaflet format has been determined by the Ministry of Health and the content thereof has been

checked and approved.” Date of approval: May 2011.

HEXAKAPRON

®

TABLETS

Composition

Each tablet contains:

Active Ingredient

Tranexamic acid

500 mg

Other Ingredients

Mycrocrystalline

cellulose,

sodium

starch

glycolate,

magnesium

stearate,

methylcellulose, talc, colloidal silicon dioxide.

Mechanism of Action

Hexakapron is an antifibrinolytic agent which inhibits conversion of plasminogen to

plasmin.

Hexakapron is well absorbed orally.

Indications

Treatment

hemorrhage

occurring

some

forms

surgery,

including

prostatectomy.

Hematuria.

Menorrhagia.

Hereditary angioneurotic edema.

Contraindications

Known

hypersensitivity

tranexamic

acid

other

ingredient

preparation.

Patients

with

active

thromboembolic

disease

such

deep

vein

thrombosis,

pulmonary embolism, and cerebral thrombosis .

History of venous or arterial thrombosis

Fibrinolytic conditions following consumption coagulopathy.

Patients

with

subarachnoid

hemorrhage.

Anecdotal

experience

indicates

that

cerebral edema and cerebral infarction may be caused by tranexamic acid in such

patients.

Patients with acquired defective color vision, since this prohibits measuring one

endpoint that should be followed as a measure of toxicity (see Warnings)

History of convulsions.

Severe renal impairment because of risk of accumulation.

Warnings

The dose of tranexamic acid should be reduced in patients with renal impairment

because of the risk of accumulation (see Dosage and Administration). Isolated cases

of obstruction of the urinary tract due to blood clots have been observed when

tranexamic acid has been used to treat severe bleeding from the upper urinary tract.

Tranexamic acid therapy is not indicated in haematuria caused by diseases of the

renal parenchyma. Intravascular precipitation of fibrin frequently occurs in these

conditions and may aggravate the disease. In addition, in cases of massive renal

haemorrhage of any cause, antifibrinolytic therapy carries the risk of clot retention in

the renal pelvis.

Hexakapron tablets , 6. 6. 2011, RH

Although clinical evidence shows no significant increase in thrombosis, possible risk

of thrombotic complications cannot be ruled out. Venous and arterial thrombosis or

thromboembolism has been reported in patients treated with tranexamic acid. In

addition, cases of central retinal artery and central retinal vein obstruction have been

reported. A few patients have developed intracranial thrombosis with tranexamic acid

but further observation is needed to assess the significance of this potential hazard.

There are no data on the use of tranexamic acid in women taking oral contraceptive

agents.

Patients with a high risk for thrombosis (a previous thromboembolic event and a

family history of thromboembolic disease) should use tranexamic acid only if there is a

strong medical indication and under strict medical supervision.

Tranexamic acid should not be administered concomitantly with Factor IX Complex

concentrates or Anti-inhibitor Coagulant concentrates, as the risk of thrombosis may

be increased.

Blood in body cavities such as pleural space, joint spaces and urinary tract (e.g.

renal

pelvis,

bladder)

develop

'indissoluble

clots'

these

cavities

extravascular blood clots which may be resistant to physiological fibrinolysis.

Patients with irregular menstrual bleeding should not use tranexamic acid until the

cause of the irregularity has been established. If menstrual bleeding is not adequately

reduced by tranexamic acid an alternative treatment should be considered.

Patients with disseminated intravascular coagulation (DIC) who require treatment

with tranexamic acid must be under the strict supervision of a physician experienced

in treating this disorder.

Focal areas of retinal degeneration have developed in cats, dogs and rats following

oral or intravenous tranexamic acid at doses between 250 to 1600 mg/kg/day (6 to

40 times the recommended usual human dose) from 6 days to 1 year. The incidence

of such lesions has varied from 25% to 100% of animals treated and was dose

related. At lower doses some lesions have appeared to be reversible.

Limited data in cats and rabbits showed retinal changes in some animals with doses

as low as 126 mg/kg/day (only about 3 times the recommended human dose)

administered for several days to two weeks.

No retinal changes have been reported or noted in eye examinations in patients

treated with tranexamic acid for weeks to months in clinical trials. However, visual

abnormalities, often poorly characterized, represent the most frequently reported

postmarketing adverse reaction in Sweden. For patients who are to be treated

continually for longer than several days, an ophthalmological examination, including

visual acuity, color vision, eye-ground and visual fields is advised, before commencing

and at regular intervals during the course of treatment. Tranexamic acid should be

discontinued if changes in examination results are found.

Patients who experience visual disturbance should be withdrawn from treatment

Use in Pregnancy

Safety of use of tranexamic acid in pregnancy has not been established.

Drugs which have been taken by only a limited number or pregnant women and

women of childbearing age, without an increase in the frequency of malformation or

other direct or indirect harmful effects on the human foetus having been observed.

Reproduction studies performed in mice, rats and rabbits have not revealed any

evidence of impaired fertility or adverse effects on the foetus due to tranexamic acid.

Hexakapron tablets , 6. 6. 2011, RH

The long-term clinical experience is limited to 21 pregnant women, treated for 1 to 18

weeks, in most cases to prevent further haemorrhage in connection with ablatio

placentae. All women delivered alive and normal children except for prematurity. The

short-term experience comprises 67 women with abruptio placentae treated with a

single dose just before delivery by caesarean section. All deliveries went well and

were not further complicated by haemorrhage.

There are no adequate and well-controlled studies in pregnant women. However,

tranexamic acid is known to cross the placenta and appears in cord blood at

concentrations

approximately

equal

maternal

concentration.

Because

animal

reproduction studies are not always predictive of human response, tranexamic acid

should be used during pregnancy only if clearly needed.

Use in Breastfeeding

Tranexamic acid is secreted into the mother's milk at a concentration of about one

hundredth of the corresponding serum level. Therefore, caution should be exercised

when administered to nursing mothers.

Adverse Reactions

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)

including isolated reports, not known (cannot be estimated from the available data).

Immune system disorders

Very rare: Hypersensitivity reactions including anaphylaxis

Eye disorders

Rare: Colour vision disturbances, retinal/artery occlusion

Vascular disorders

Rare: Thromboembolic events

Very rare: Arterial or venous thrombosis at any sites

Gastro-intestinal disorders

Very rare: Digestive effects such as nausea, vomiting and diarrhoea, may occur but

disappear when the dosage is reduced.

Skin and subcutaneous tissue disorders

Rare: Allergic skin reactions

Precautions

Caution should be exercised in patients with hepatic, cardiac or renal insufficiency,

and in massive hematuria from the upper urinary tract.

Caution should also be exercised in patients exhibiting a thrombotic tendency, even

if an anticoagulant is administered simultaneously.

Treatment should be discontinued if disturbances in color vision arise.

Tranexamic

acid

should

withdrawn

patient

develops

muscle

pain

weakness.

Caution

should

exercised

patients

have

undergone

transurethral

prostatectomy

since

intravascular

clotting

occur,

following

pre-

post-

operative tranexamic acid therapy to reduce blood loss.

Hexakapron tablets , 6. 6. 2011, RH

Drug Interactions

Clinically

important

interactions

have

been

observed

with

tranexamic

acid

tablets. Because of the absence of interaction studies, simultaneous treatment with

anticoagulants must take place under the strict supervision of a physician experienced

in this field.

Dosage and Administration

Doses should be reduced in renal impairment.

Adults

The recommended standard dosage is 2-3 tablets, 2-3 times daily.

For the indications listed below, specific recommendations are made as follows:

(please refer also to the Physicians’ Prescribing Information for Hexakapron injection)

Prostatectomy

Following I.V. administration (

refer to the Physicians’ Prescribing Information for the

injection

), 2-3 Hexakapron tablets, 2-3 times daily, until macroscopic hematuria is no

longer present.

Dental Surgery

Factor VIII or IX concentrates and Hexakapron 10 mg/kg body weight should be

administered intravenously immediately before surgery. Following surgery, 25 mg/kg

body weight should be administered orally, 3-4 times daily, for 6-8 days. As a rule, it is

not necessary to administer factor VIII or IX concentrates following surgery.

Epistaxis

Hexakapron injection may be applied topically to the nasal mucosa, either using a

spray or by soaking a gauze strip in the solution and then packing the nasal cavity.

Hematuria

2-3 tablets, 2-3 times daily, until macroscopic hematuria is no longer present.

Menorrhagia

2-3 tablets, 3-4 times daily, for 3-4 days. Hexakapron therapy should be initiated

only after heavy bleeding has started. Use of the drug should be restricted to not more

than 3 menstrual cycles.

Hereditary Angioneurotic Edema

Some patients are aware of the onset of the illness. A suitable treatment for these

patients is 2-3 tablets, intermittently, 2-3 times daily for several days. Other patients

are treated continuously at this dosage.

Children

Dosage should be calculated according to body weight, as 25 mg/kg orally.

Overdosage

Overdose

data

limited.

There

report

overdosage

which

seventeenyear-old ingested 37 g of tranexamic acid and after receiving treatment with

gastric lavage, mild intoxication was reported.

Symptoms

overdose

include

dizziness,

headache,

nausea,

vomiting,

diarrhoea, orthostatic symptoms and hypotension.

There is no known antidote for tranexamic acid overdose. In the event of overdose,

the patient should be treated symptomatically and supportive measures should be

instituted as required.

Hexakapron tablets , 6. 6. 2011, RH

Activated charcoal may reduce absorption of tranexamic acid if given within one or

two hours after ingestion. In patients who are not fully conscious or have impaired gag

reflex,

consideration

should

given

administering

activated

charcoal

nasogastric tube once the airway is protected.

In addition to this, monitor vital signs to detect a possible hypotensive episode.

Monitor fluid and electrolyte status in patients with severe vomiting or diarrhoea and

administer IV fluids and replace electrolytes as necessary. Monitor urine output and

maintain

adequate

diuresis.

Monitor

clinical

evidence

thromboembolic

complications (e.g. chest pain,

shortness

breath,

flank

pain, extremity

pain).

Because there is a risk of thrombosis in predisposed individuals; anticoagulant

therapy should be considered in these patients.

In symptomatic patients, support respiratory and cardiac function. Monitor blood

count, renal function, pulse oximetry and/or blood gases and obtain a chest x-ray.

Obtain an ECG and institute continuous cardiac monitoring.

Registration Number:

016.35.24864.00.

Storage:

Store in a dry place below 25

Manufacturer

Teva Pharmaceuticals Industries

P.O.Box 3190, Petach-Tikva