BREXIN TABLETS

Israel - English - Ministry of Health

Buy It Now

Active ingredient:
PIROXICAM AS BETA-CYCLODEXTRIN
Available from:
TARO INTERNATIONAL LTD, ISRAEL
ATC code:
M02AA07
Pharmaceutical form:
TABLETS
Composition:
PIROXICAM AS BETA-CYCLODEXTRIN 20 MG
Administration route:
PER OS
Prescription type:
Required
Manufactured by:
CHIESI FARMACEUTICI S.P.A., ITALY
Therapeutic group:
PIROXICAM
Therapeutic area:
PIROXICAM
Therapeutic indications:
Piroxicam is indicated for symptomatic relief of osteoarthritis rheumatoid arthritis or ankylosing spondylitis. When an NSAID is indicated piroxicam should be considered as a second line option. The desicion to prescribe piroxocam should be based on an assesment of the individual's patient overall risk.
Authorization number:
136 61 29695 00
Authorization date:
2012-04-30

Documents in other languages

Patient Information leaflet Patient Information leaflet - Arabic

20-01-2021

Patient Information leaflet Patient Information leaflet - Hebrew

06-07-2020

Patient leaflet in accordance with the Pharmacists' Regulations (Preparations)

- 1986

This medicine is dispensed with a doctor’s prescription only

BREXIN

Tablets

Active ingredient:

Each tablet contains: piroxicam (as beta-cyclodextrin) 20 mg

List of inactive ingredients and allergens in this medicine: See section 6 ‘Additional

information' and section 2 under ‘Important information about some of this medicine’s

ingredients’.

Read the entire leaflet carefully before you start using this medicine. This leaflet

contains concise information about this medicine. If you have any further questions, consult

your doctor or pharmacist.

This medicine has been prescribed to treat your illness. Do not pass it on to others. It may

harm them, even if it seems to you that their illness is similar to yours.

1.

What is this medicine intended for?

An anti-inflammatory medicine and pain reliever used to relieve symptoms such as pain,

swelling and stiffness in the joints that are due to rheumatic illnesses or to ankylosing

spondylitis.

Your doctor will prescribe you with this medicine only when other medicines in the same

group have not helped you.

Therapeutic group:

Non-Steroidal Anti-Inflammatory Drug (NSAID)

2.

Before using this medicine

Brexin –PIL ENG – Notification 03.20

! Special warnings about using this medicine

Before taking BREXIN tell your doctor if:

you are elderly (especially if you are over 70 years old) because you have a higher

chance of getting side effects from this medicine.

you are asthmatic or subject to asthma attacks.

you have eye problems.

you have diabetes.

you have kidney problems.

you have liver problems.

you have heart or blood vessel problems like heart attack, stroke or congestive heart

failure or you think you may be at risk of any of these conditions (if, for example, you

have high blood pressure or diabetes or you are a smoker), because medicines like

BREXIN may slightly increase the risk of heart attack or stroke.

If you have any of the conditions listed above, consult your doctor who will order additional

tests.

Using this medicine in patients older than 80 years is not advisable.

Like all NSAIDs, this medicine may cause:

Do not use this medicine if:

you are allergic to the active ingredient of to any of the other active ingredients in this

medicine (listed in section 6).

you previously had any allergic reaction and/or skin reactions, regardless of severity,

such as erythema multiforme, Stevens-Johnson syndrome and toxic epidermal

necrolysis, after taking other medicines, other NSAIDs, or medicines containing the

same active substance.

you have had symptoms of angioedema, asthma, rash, nasal polyposis or rhinitis due to

the use of NSAIDs or acetylsalicylic acid (aspirin).

you are taking other NSAIDs or acetylsalicylic acid (aspirin) to relieve pain.

you currently have a stomach and/or duodenal ulcer, or you have digestion problems

(dyspepsia) or stomach inflammation (gastritis).

you have had intestinal or stomach ulcer, bleeding, or perforation (including blood in

vomit or in stools or black, tarry stools).

you have an inflammation or bleeding in the stomach or intestines even if caused by

diseases such as gastrointestinal cancer, diverticulitis, ulcerative colitis, Crohn’s

disease.

you have a severe liver or kidney disease.

you have high blood pressure or serious heart problems (moderate to severe heart

failure).

you have a tendency to bleed frequently or severe coagulation problems, or if you are

taking blood thinners (anticoagulants).

you are pregnant or think you may be pregnant or if you are breastfeeding (see the

section ”Pregnancy, breastfeeding, and fertility”).

you are under 18 years old.

Brexin –PIL ENG – Notification 03.20

severe or even fatal bleeding, ulcers and perforation in the stomach and intestines at

any time, with or without warning signs, even if you have no history of serious

conditions of this type.

in rare cases, serious and in some cases, fatal skin reactions that include reddening,

blisters or skin peeling (for example Stevens-Johnson syndrome and toxic epidermal

necrolysis). The risk is higher in the earlier stages of treatment.

The risk of having side effects increases with high doses and prolonged use. Follow your

doctor's instructions carefully.

STOP your treatment and contact your doctor:

if you experience any symptom in your stomach and intestines, especially in the

case of bleeding;

if you notice any change in your skin (rash), sores in mucous membranes or any

other sign of allergic reaction (reddening, itching, swelling of face or throat with

breathing difficulties, sudden fall in blood pressure).

BREXIN may interfere with the results of certain blood tests, for example clotting time.

Always tell your doctor that you are taking BREXIN in these cases.

! Children and adolescents

Children and adolescents under 18 years old must NOT take BREXIN.

! Other medicines and BREXIN

If you are taking or have recently taken other medicines, including nonprescription

medications and dietary supplements, tell your doctor or pharmacist. Particularly if

you are taking:

medicines containing cortisone (corticosteroids)

blood thinners (anticoagulants or platelet antiaggregating medicines) such as

warfarin or aspirin (acetylsalicylic acid)

medicines for high blood pressure such as diuretics, ACE inhibitors, and angiotensin

II antagonists

medicines containing potassium

medicines known as 'selective serotonin reuptake inhibitors' (SSRIs), used to treat

depression

other NSAIDs or salicylates or acetylsalicylic acid (aspirin) to relieve pain

lithium as an anti-depressant

cimetidine, used to treat stomach ulcers

quinolone antibiotics used to treat bacterial infections

if you are using any intrauterine device

cyclosporin and tacrolimus, medicines that reduce immune system activity

! Using this medicine and food

This medicine can be taken with or without food.

! Using this medicine and alcohol consumption

It is advisable not to consume alcohol during treatment with this medicine.

! Pregnancy, breastfeeding, and fertility

Brexin –PIL ENG – Notification 03.20

Do not use BREXIN if you are pregnant or think you may be pregnant as it may damage the

heart, lungs or kidneys of your unborn baby or cause complications during delivery.

Do not use BREXIN when breastfeeding.

This medicine may impair fertility. If you have fertility problems and are taking BREXIN, stop

using it.

If you are pregnant, think you may be pregnant or plan to become pregnant, or if you are

breastfeeding, you may only use BREXIN if there is a real need for it and under your

doctor’s supervision. Ask your doctor for advice before taking this medicine

! Driving and using machines

This medicine may cause dizziness or unusual tiredness, pay particular attention when

driving or operating dangerous machinery.

! Important information about some of this medicine’s ingredients

This medicine contains lactose monohydrate. If you have been told by a doctor that you

have an intolerance to certain sugars, consult your doctor before you start taking this

medicine.

This medicine contains less than 1 mmol (23mg) of sodium per tablet, so it is considered

sodium-free.

3.

How to use this medicine?

Always use this medicine according to your doctor's instructions. Check with your doctor or

pharmacist if you are not sure about your dose or about how to take this medicine.

Only your doctor will determine your dose and how you should take this medicine. The

recommended dosage is usually: 1 tablet once a day.

Your doctor may prescribe a lower dose or another drug to protect your stomach, especially

if you are over 70 years old.

The maximum dose is 1 tablet once a day.

Do not exceed the recommended dose!

Taking this medicine: Take the tablet with a glass of water. The score on the tablet is

intended to ease splitting and swallowing it and not so that it can be divided into two equal

parts. To make it easier to swallow, you may, if necessary, split the tablet immediately

before taking it. Swallow both halves together immediately after you have split the tablet.

To split the tablet, put it on a flat surface with the score facing upward. Press gently with

your thumb to break the tablet into two parts.

There is no information about crushing/chewing the tablets.

If you have taken an overdose, or if a child has accidentally swallowed some

medicine, immediately see a doctor or go to a hospital emergency room and bring the

medicine package with you. You may experience vomiting, drowsiness, fainting, dizziness,

headache.

Brexin –PIL ENG – Notification 03.20

If you forget to take the medicine at the scheduled time, do not take a double dose to

compensate for the missed dose. Take the next dose at the usual time and consult your

doctor if you have further questions about using this medicine.

Adhere to the treatment as recommended by your doctor.

Do not take medicines in the dark! Check the label and dose every time you take

medicine. Wear glasses if you need them.

If you have any further questions about using this medicine, consult your doctor or

pharmacist.

4.

Side effects

Like with all medicines, using BREXIN may cause side effects in some users. Do not be

alarmed by this list of side effects; you may not experience any of them.

Stop treatment with BREXIN immediately and contact your doctor in the following

cases:

serious abdominal pain, bleeding or burning abdominal pain due to stomach or

duodenal ulcers;

sudden, intense pain in the center of the stomach (perforation of the ulcer);

vomit with blood (hematemesis) or black stools (melaena) together with stomach or

intestinal bleeding or excessive fatigue with reduced urination (due to undetected

bleeding);

allergic reactions, including severe ones, with swelling (angioedema) of the face, lips

and throat, that may cause difficulty in breathing or swelling of the hands, including

serum disease (a hypersensitivity reaction involving the immune system which

usually manifests with fever, rash, and inflamed and painful joints);

sudden drop in blood pressure (shock) that may cause confusion, increase of heart

rate, paleness, fatigue or weakness, or breathing difficulty (warning symptoms);

serious skin reactions such as blisters, reddening or skin peeling (for example

Stevens-Johnson syndrome and toxic epidermal necrolysis, exfoliative dermatitis,

erythema multiforme).

Common side effects (may affect up to 1 in 10 users)

decrease in red blood cells (anemia);

headache;

vertigo, tinnitus (ringing in the ears);

abdominal discomfort or pain, constipation, diarrhea, gas (flatulence), stomach pain

or discomfort, nausea, vomiting, indigestion;

skin rashes, itching.

Uncommon side effects (may affect up to 1 in 100 users)

dizziness;

drowsiness;

blurred vision;

inflammation of mouth with ulcers (

ulcerative stomatitis

Brexin –PIL ENG – Notification 03.20

Rare side effects (may affect up to 1 in 1,000 users)

reduced level of blood hemoglobin due to a fall in the production of red blood cells

by the bone marrow (aplastic anemia);

reduced level of blood hemoglobin due to production of antibodies that destroy red

blood cells (hemolytic anemia);

decrease in number of platelets (thrombocytopenia), decrease in number of white

blood cells (leukopenia), increase in eosinophil white blood cells (eosinophilia),

decrease in number of red and white blood cells and platelets (pancytopenia);

swelling (edema) of face and hands due to allergic reactions;

vision impairment;

yellowing of the skin or eyes (jaundice);

fatal inflammation of the liver (fatal hepatitis);

skin sensitivity to sunlight (photosensitization of the skin), urticaria;

reddening of the skin due to blood leaking from small blood vessels (non-

thrombocytopenic purpura);

Henoch-Schonlein purpura (inflammation that affects the blood vessels of the skin,

bowel and kidneys);

inflammation of the kidneys (interstitial nephritis), severe kidney impairment (renal

papillary necrosis, nephrotic syndrome);

swelling (edema);

increase in liver function indexes.

Very rare side effects (may affect up to 1 in 10,000 users)

bladder problems.

Side effects of unknown frequency (the frequency of these effects has not been

established yet)

fluid retention;

increase or decrease in blood sugar levels (hyperglycemia, hypoglycemia);

abnormal weight gain;

depression, strange dreams, hallucinations, sleeping problems (insomnia),

confusion, mood swings, nervousness, increased excitability;

impaired hearing;

inflammation of blood vessels (vasculitis);

narrowing of bronchi (bronchospasm);

nose bleeding (epistaxis);

stomach inflammation (gastritis); pancreas inflammation (pancreatitis);

mouth dryness;

liver inflammation (hepatitis);

hair loss (alopecia);

peeling skin;

bruises (ecchymosis);

excessive sweating;

abnormal nail growth;

blood in the urine (hematuria), difficulty urinating (dysuria);

Brexin –PIL ENG – Notification 03.20

malaise, fatigue;

lack of or reduced appetite (anorexia);

abnormal blood indices (decrease in hemoglobin or hematocrit, increased

transaminase levels, positive test for antinuclear antibody);

exacerbation of inflammation of the colon (colitis) and Crohn's disease;

changes in kidney function (acute renal failure);

increase in blood pressure, reduced function of the heart (cardiovascular diseases).

If you experience any side effect, if any side effect gets worse, or if you experience a

side effect not mentioned in this leaflet, consult your doctor.

You can report side effects to the Ministry of Health by following the link ‘Reporting Side

Effects of Drug Treatment' on the Ministry of Health home page (www.health.gov.il)

which

links to an online form for reporting side effects. You can also use this link:

https://sideeffects.health.gov.il/

5.

How to store the medicine?

Prevent poisoning! To prevent poisoning, keep this, and all other medicines, in a closed

place, out of the reach and sight of children and/or infants. Do not induce vomiting unless

explicitly instructed to do so by a doctor.

Do not use the medicine after the expiry date (exp. date) which is stated on the package.

The expiry date refers to the last day of that month.

Storage conditions

Store below 25°C.

6.

Additional information

In addition to the active ingredient, this medicine also contains:

lactose monohydrate, crospovidone, sodium starch glycollate, colloidal hydrated silica,

pregelatinized starch, magnesium stearate.

What the medicine looks like and contents of the pack:

Light yellow, hexagonal tablet with score line.

This medicine is available in blister packages of 4, 10, 20, and 30 tablets.

Not all pack sizes may be marketed.

Registration holder’s name and address: Taro International Ltd., 14

Hakitor Street, Haifa Bay, 2624761

Manufacturer’s name and address: Chiesi Farmaceutici S.P.A., via Palermo 26/A, Parma,

Italy

Revised in March 2020.

Registration number of the medicine in the Ministry of Health’s National Drug Registry:

136-61-29695-00

Brexin –PIL ENG – Notification 03.20

SUMMARY OF PRODUCT CHARACTERISTICS

1.

NAME OF THE MEDICINAL PRODUCT:

BREXIN TABLETS

2.

QUALITATIVE AND QUANTITATIVE COMPOSITION:

Tablets

Each tablet contains:

piroxicam β-cyclodextrin 191.2 mg, (equivalent to piroxicam 20 mg).

Excipient with known effect: lactose monohydrate, sodium

3.

PHARMACEUTICAL FORM

Tablets

4.

CLINICAL PARTICULARS

4.1

Therapeutic indications

Piroxicam

indicated

symptomatic

relief

osteoarthritis

rheumatoid

arthritis or ankylosing spondylitis. When an NSAID is indicated piroxicam

should

considered

second

line

option.

decision

prescribe

piroxicam should be based on an assessment of the individual's patient overall

risk.

4.2

Posology and method of administration

Posology

The prescription of piroxicam should be initiated by physicians with experience

in the diagnostic evaluation and treatment of patients with inflammatory or

degenerative rheumatic diseases.

The maximum recommended daily dose is 20 mg.

Undesirable effects may be minimised by using the minimum effective dose for

the shortest duration necessary to control symptoms. The benefit and tolerability

of treatment should be reviewed within 14 days. If continued treatment is

considered necessary, this should be accompanied by frequent review.

Given that piroxicam has been shown to be associated with an increased risk of

gastrointestinal complications, the possible need for combination therapy with

gastro-protective agents (e.g. misoprostol or proton pump inhibitors) should be

carefully considered, in particular for elderly patients.

Paediatric population

Dosage and indications in children have not been established yet.

Elderly

In elderly patients, posology must be carefully established by the physician who

will have to consider a possible reduction of the dosage indicated above.

Method of administration

BREXIN should be administered once daily.

Brexin - SmPC final-03.2020

Tablets

1 tablet per day. Tablets are for oral use. The score line is intended to ease the

splitting and swallowing of the tablet and not to divide it into equal parts. To

divide the tablet, put it on a flat surface with the score upwards. Press gently

with your thumb to break the tablet into equal parts.

4.3

Contraindications

Hypersensitivity to the active substance or to any of the excipients listed in

section 6.1.

History of gastrointestinal ulceration, bleeding or perforation.

Patient history of gastrointestinal disorders that predispose to bleeding disorders

such

ulcerative

colitis,

Crohn’s

disease,

gastrointestinal

cancer

diverticulitis.

Patients with active peptic ulcer, inflammatory gastrointestinal disorders or

gastrointestinal bleeding. Patients with gastritis, dyspepsia, severe hepatic or

renal disorders, moderate or

severe heart failure, severe hypertension, severe

blood changes or haemorrhagic diathesis. Concomitant use of other NSAIDs,

including COX-2 selective inhibitors and acetylsalicylic acid at analgesic doses.

Concomitant use of anticoagulants. History of previous severe allergic drug

reactions of any type, especially skin reactions such as erythema multiforme,

Stevens-Johnson syndrome, toxic epidermal necrolysis. Previous skin reactions

(regardless of severity) to piroxicam, other NSAIDs and other medications.

For known or suspected pregnancy, during lactation or the use in children (refer

to section 4.6).

There is a potential for cross-sensitivity with acetylsalicylic acid and other non-

steroidal anti-inflammatory drugs. This product should not be given to patients in

whom acetylsalicylic acid or other non-steroidal anti-inflammatory drugs have

induced symptoms of asthma, rhinitis, nasal polyposis, angioedema, urticaria.

4.4

Special warnings and precautions for use

Undesirable effects may be minimised by using the lowest effective dose for the

shortest duration necessary to control symptoms.

The clinical benefit and tolerability of the treatment should be re-evaluated

periodically and treatment should be immediately discontinued at the first

appearance of skin reactions or significant gastrointestinal events.

Gastrointestinal (GI) effects, risk of gastrointestinal ulceration, bleeding, and

perforation.

NSAIDs,

including

piroxicam,

cause

serious

gastrointestinal

events

including bleeding, ulceration, and perforation of the stomach, small intestine or

colon, which can be fatal. These serious adverse events can occur at any time,

with or without warning symptoms, in patients treated with NSAIDs.

NSAID exposure of both short and long duration carries an increased risk of

severe gastrointestinal events. Evidence from observational studies suggests

that, compared to other NSAIDs, piroxicam may be associated with a high risk

of severe gastrointestinal toxicity.

Patients with significant risk factors for severe GI events should be treated with

piroxicam only after careful consideration (See below and section 4.3).

Brexin - SmPC final-03.2020

The possible need for combination therapy with gastro-protective agents (e.g.

misoprostol or proton pump inhibitors) should be carefully considered (see

section 4.2).

Severe gastrointestinal complications

Identification of at-risk subjects

The risk for developing serious gastrointestinal complications increases with

age. Being aged over 70 years is associated with a high risk of complications.

Administration to patients older than 80 years should be avoided.

Patients taking concomitant oral corticosteroids, selective serotonin reuptake

inhibitors (SSRIs), anticoagulants such as warfarin or platelet anti-aggregate

agents such as low-dose acetylsalicylic acid are at increased risk of severe

gastrointestinal

complications

(see

below

section

4.5).

with

other

NSAIDs, the use of piroxicam in combination with gastro-protectants agents

(e.g. misoprostol or proton pump inhibitors) must be considered for these at-risk

patients.

Patients

physicians

should

alert

signs

symptoms

gastrointestinal ulceration and/or bleeding during piroxicam treatment. Patients

should be asked to report any new or unusual abdominal symptom during

treatment.

If a

gastrointestinal complication is suspected during treatment,

piroxicam

should

discontinued

immediately

additional

clinical

evaluation and alternative treatment should be considered.

Cardiovascular and cerebrovascular effects

Suitable monitoring and instructions are necessary in patients with positive

anamnesis for hypertension and/or congestive heart failure, as water retention

and oedema have been reported in association with NSAIDs treatment.

Clinical studies and epidemiological data indicate that the use of some NSAIDs

(especially at high doses and for long-term treatment) may be associated with a

moderate increased risk of arterial thrombotic events (e.g. myocardial infarction

or stroke). There are not enough data to exclude such a risk for piroxicam.

Patients with uncontrolled hypertension, congestive heart failure, established

ischaemic

heart

disease,

peripheral

arterial

disease

and/or

cerebrovascular

disease should be treated with piroxicam only after careful evaluation. Similar

considerations should be made before starting long-term treatment in patients

with risk factors for cardiovascular disease (e.g. hypertension, hyperlipidemia,

diabetes mellitus, smoking).

Piroxicam,

like

other

NSAIDs,

reduces

platelet

aggregation

prolongs

bleeding time; this characteristic must be taken into account when blood tests

are performed and when the patient is concomitantly treated with other platelet

aggregation inhibitors.

Patients with impaired renal function should be periodically monitored, as in

such patients the inhibition of prostaglandin synthesis caused by piroxicam may

result in a severe decrease in renal perfusion that may lead to acute renal failure.

In this regard, elderly patients and patients treated with diuretics should be

considered as at risk.

Dehydrated patients are at risk for impairment of renal function.

Brexin - SmPC final-03.2020

Caution should also be paid in patients with impaired hepatic function. It is

advisable

periodically

monitor

their

clinical

laboratory

parameters,

especially in case of prolonged treatment.

Due to its interaction with arachidonic acid metabolism, the drug may induce

bronchospasms and possibly shock and other allergic phenomena in asthmatic

and predisposed patients.

As some ocular changes have been observed during therapy with NSAIDs,

periodic

ophthalmological

examinations

advised

during

prolonged

treatment.

It is also advisable to frequently check blood glucose levels in diabetic patients

prothrombin

time

patients

concomitantly

receiving

anticoagulant

treatment with dicoumarol derivatives.

Skin reactions

Evidence from observational studies suggests that piroxicam may be associated

with a higher risk of serious skin reactions than other non-oxicam NSAIDs.

In association with the use of Brexin, serious skin reactions, potentially fatal,

have

been

reported

including:

Stevens-Johnson

syndrome

(SJS)

toxic

epidermal necrolysis (TEN).

Patients should be advised and closely monitored for any signs and symptoms

of skin reactions. Patients appear to be at highest risk of appearance of SJS and

TEN during initial weeks of treatment. Treatment with BREXIN should be

discontinued at the first appearance of symptoms and signs of SJS or TEN (i.e.

progressive skin rash, often with blisters and mucosal lesions).

The best results in management of SJS and TEN are achieved with early

diagnosis and the prompt discontinuation of therapy whatever the

suspect

medication. The early discontinuation is associated with a better prognosis.

Patients developing SJS or TEN due to a therapy with BREXIN, should never

be treated with BREXIN again.

The use of piroxicam, as of any other prostaglandin synthesis and cyclo-

oxygenase

inhibitors,

recommended

women

planning

start

pregnancy.

The administration of piroxicam should be discontinued in women with fertility

problems or undergoing fertility investigations.

The tablet contains lactose: patients with rare hereditary problems of galactose

intolerance, Lapp lactase deficiency or glucose-galactose malabsorption should

not take this drug. This medicinal product contains less than 1 mmol (23 mg) of

sodium per tablet, and is basically sodium-free.

4.5

Interactions with other medicaments and other forms of interaction

Acetylsalicylic acid or other NSAIDs

: As with other NSAIDs, the use of

piroxicam together with acetylsalicylic acid or concomitant use with other

NSAIDs, including other piroxicam formulations, must be avoided, since data

are inadequate to show that such combinations produce greater improvement

Brexin - SmPC final-03.2020

than that achieved with piroxicam alone; moreover, the potential for adverse

reactions is increased (see section 4.4).

Human

studies

have

shown

that

concomitant

piroxicam

acetylsalicylic acid reduces the plasma piroxicam concentration to about 80% of

the usual value (see section 4.3).

Piroxicam interacts with acetylsalicylic acid, with other non-steroidal anti-

inflammatory drugs and with platelet aggregate inhibitors (see sections 4.3 and

4.4).

Corticosteroids

: increased risk of gastrointestinal ulceration or bleeding (see

section 4.4).

Anticoagulants

: NSAIDs, including piroxicam, may enhance the effects of

anticoagulants,

such

warfarin.

Therefore,

piroxicam

with

anticoagulants such as warfarin should be avoided (see section 4.3).

Platelet

anti-aggregate

agents

and

selective

serotonin

reuptake

inhibitors

(SSRIs):

increased risk of gastrointestinal bleeding (see section 4.4).

Diuretics, ACE-inhibitors and angiotensin II antagonists

: NSAIDs may reduce

the efficacy of diuretics and other anti-hypertensive drugs. In some patients with

impaired

renal

function

(e.g.

dehydrated

patients

elderly

patients

with

impaired renal

function), the

co-administration of

an ACE-inhibitor

or an

angiotensin II antagonist and agents that inhibit the cyclo-oxygenase system,

may further deteriorate renal function, with possible acute renal failure, which is

generally reversible. These interactions should be taken into consideration in

patients

taking

piroxicam

together

with

ACE-inhibitors

angiotensin

antagonists.

The combination should therefore be administered with caution, especially in

elderly patients.

Patients should be adequately hydrated and renal function monitoring should be

considered after starting concomitant therapy.

In case of concomitant intake of potassium-containing drugs, or diuretics that

cause

potassium

retention,

there

additional

risk

rise

serum

potassium concentration (hyperkalemia).

Lithium

: concomitant administration of lithium and NSAIDs, causes an increase

in plasma lithium levels; therefor these levels should be monitored at the

beginning, during and after the end of treatment with Piroxicam. Piroxicam is

highly protein bound and therefore displacement of other protein bound drugs

can be. Patients receiving piroxicam with other highly protein bound drugs must

be closely monitored by the doctor, in order to adjust dosage if necessary.

Piroxicam absorption was slightly increased after cimetidine administration.

However, this increase did not prove to be clinically significant.

Alcohol intake should be avoided.

Piroxicam may reduce the efficacy of intrauterine devices.

Concomitant use of non-steroidal anti-inflammatory drugs and quinolone drugs

is not recommended.

Brexin - SmPC final-03.2020

Cyclosporin

Tacrolimus:

administration

NSAIDs

together

with

cyclosporin or tacrolimus increases the risk of nephrotoxicity.

4.6

Fertility, Pregnancy and lactation

Piroxicam is contraindicated during ascertained or suspected pregnancy, and

during breast-feeding (see section 4.3).

Fertility

The use of piroxicam may impair female fertility and is not recommended in

women trying to become pregnant. Discontinuation of therapy with piroxicam

should be envisaged for women with difficulties in conceiving or those being

investigated for fertility.

Pregnancy

Inhibition of prostaglandin synthesis can adversely affect pregnancy and/or

embryo/foetal development.

Results from epidemiological studies suggest an increased risk of miscarriage,

cardiac malformation and gastroschisis after use of a prostaglandin synthesis

inhibitor during early pregnancy. The absolute risk of cardiac malformations

increased from less than 1% up to approximately 1.5%. It was considered that

the risk is dose-related and also increases with duration of therapy.

Studies on animals have shown reproductive toxicity (see section 5.3). In

animals, the administration of prostaglandin synthesis inhibitors has been shown

to cause an increase in pre- and post-implantation losses and in embryo-foetal

mortality.

Moreover, an increased incidence of various malformations, including

cardiovascular malformation, was reported in animals given prostaglandin

synthesis inhibitors during organogenesis.

During the third trimester of pregnancy, all prostaglandin synthesis inhibitors

can expose foetuses to:

- cardiopulmonary toxicity (with premature closure of the ductus arteriosus and

pulmonary hypertension);

- renal dysfunction, which may progress to renal failure with oligo-

hydroamniosis;

both mother and newborn child, at the end of pregnancy to:

- possible prolongation of bleeding time and anti-aggregating effect that can

even occur with very low doses;

- inhibition of uterine contractions resulting in delayed or prolonged labour.

Lactation

Data show that piroxicam concentration in breast milk lies between 1% and 3%

of maternal plasma concentration. Piroxicam is contraindicated during

breastfeeding because safety in newborns has not yet been established (see

section 4.3).

4.7

Effects on ability to drive and use machines

Piroxicam can alter the state of alertness to the extent of compromising the

ability to drive vehicles or perform activities requiring quick reflexes.

Brexin - SmPC final-03.2020

4.8

Undesirable effects

Oedema, hypertension and heart failure have been reported in association with

NSAID treatment.

Clinical studies and epidemiological data suggest that the use of some NSAIDs

(especially at high doses and for long-term treatment) may be associated with a

moderate increased risk of arterial thrombotic events (e.g. myocardial infarction

or stroke) (see section 4.4).

As for other substances with similar action, some patients showed increases in

blood urea nitrogen that do not exceed a certain level with prolonged treatment;

once therapy is discontinued values return to baseline.

Undesirable side effects are listed in the table below according to System Organ

Class and to the following frequency: very common (≥ 1/10); common (≥1/100

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

very rare (<1/10,000); not known (cannot be estimated from the available data).

According to MedDRA

System Organ Class

Adverse Reaction

Frequency

Hematopoetic tissue

Anaemia

Common

Aplastic anaemia, hemolitic

anaemia, thrombocytopenia,

leucopenia, eosinophilia,

pancytopenia

Rare

Immune system disorders

Serum disease, anaphylaxis,

allergic oedema (of hands and

face)

Rare

Hypersensitivity

Not known

Metabolism and nutrition

disorders

Fluid retention,

hypoglycaemia,

hyperglycaemia, abnormal

weight gain, loss of appetite,

anorexia

Not known

Psychiatric disorders

Depression, abnormal dreams,

hallucinations, insomnia,

confusion, mood swings,

nervousness, erethism

Not known

Nervous system disorders

Headache

Common

Dizziness, sleepiness

Uncommon

Eye disorders

Blurry vision

Uncommon

Sight impairment

Rare

Ear and labyrinth disorders

Vertigo, tinnitus

Common

Ear impairment

Not known

Brexin - SmPC final-03.2020

Vascular disorders

Vasculitis, shock (warning

symptoms)

Not known

Respiratory, thoracic and

mediastinal disorders

Bronchospasm, epistaxis

Not known

Gastrointestinal disorders

Abdominal distress, abdominal

pain, constipation, diarrhoea,

epigastric pain or distress,

flatulence, nausea, vomiting,

dyspepsia

Common

Ulcerative stomatitis

Uncommon

Gastritis, gastrointestinal

bleeding, gastrointestinal

perforation, melaena,

haematemesis, peptic ulcer

pancreatitis, mouth dryness

Not known

Hepatobiliary disorders

Jaundice

Rare

Hepatitis (rare cases of fatal

hepatitis)

Not known

Skin and subcutaneous

tissue disorders

Rash, pruritus

Common

Photosensitivity reaction,

urticaria, angioneurotic

oedema, non-

thrombocytopenic purpura,

Henoch-Schonlein purpura

Rare

Severe skin adverse reactions

(SCARs): Stevens-Johnson

syndrome (SJS), toxic

epidermal necrolysis (TEN)

(see section 4.4)

Very rare

Alopecia, skin desquamation,

erythema multiforme,

ecchymosis, sweating,

abnormal nail growth

Not known

Renal and urinary disorders

Interstitial nephritis, renal

papillary necrosis, nephrotic

syndrome, renal failure

Rare

Vesicular disorder

Very rare

Haematuria, dysuria

Not known

General Disorders and

Administration Site

Conditions

Oedema

Rare

Malaise, asthenia

Not known

Investigations

Liver function test abnormal

Rare

Increased transaminase levels,

positive antinuclear antibody,

abnormal haematology test,

Not known

Brexin - SmPC final-03.2020

decreased haemoglobin,

decreased haematocrit

The most commonly observed adverse events are gastrointestinal. Peptic ulcers,

gastrointestinal perforation or bleeding, sometimes fatal, may occur, especially

in the elderly (see section 4.4).

After piroxicam administration, exacerbation of colitis and Crohn's disease have

been observed (see section 4.4).

BREXIN has the prerequisites for being better tolerated than plain piroxicam in

the gastrointestinal tract; in fact, the shorter persistence of the active ingredient

in the gastrointestinal tract reduces the risk of contact irritation.

Piroxicam

therapy

should

however

discontinued

clinical

signs

symptoms of hepatic disturbances occur.

Some cases of haematuria, dysuria, acute renal failure, water retention, which

can occur as oedema especially in the declivous regions of the lower limbs or as

cardiovascular

disturbances

(hypertension,

decompensation)

have

been

reported.

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

National

Regulation

using

online

form

https://sideeffects.health.gov.il/

4.9

Overdose

Symptoms: the most indicative overdose symptoms are headache, vomiting,

somnolence, dizziness and syncope.

In the event of overdose, supportive and symptomatic therapy is indicated.

Although no studies have been performed so far, haemodialysis is not likely to

be useful in helping to eliminate piroxicam, as the drug is highly bound to

plasma proteins.

5.

PHARMACOLOGICAL PROPERTIES

5.1

Pharmacodynamic properties

Pharmacotherapeutic

group:

non-steroidal

anti-inflammatory/anti-rheumatic

drug.

ATC code: M01AC01.

Mechanism of action

Piroxicam,

belonging

class

benzothiazine-based

N-heterocyclic

carboxyamides, is the first compound of a new class of NSAIDs, the oxicams.

Piroxicam

anti-inflammatory,

analgesic

antipyretic

activity,

pharmacological

actions

similar

those

other

non-steroidal

anti-

inflammatory drugs.

Pharmacodynamic effects

Brexin - SmPC final-03.2020

Animal

studies

showed

piroxicam

affects

cell

migration

sites

inflammation.

Like other NSAIDs, piroxicam interferes with prostaglandin

synthesis by inhibiting cyclo-oxygenase.

Unlike

indomethacin,

piroxicam

reversible

inhibitor

prostaglandin

synthesis. In a study performed on 9 patients with active rheumatoid arthritis,

piroxicam

mg/day

days)

markedly

lowered

function

polymorphonuclear

(PMN)

cells,

production

superoxide

anions

peripheral blood and in synovial fluid, and the concentration of PMN and PMN-

elastase in synovial fluid. Modulation of PMN response may contribute to the

anti-inflammatory action of piroxicam.

BREXIN is a new formulation of piroxicam where the active compound is

complexed with ß-cyclodextrin.

ß-cyclodextrin is a cyclic oligosaccharide derived from enzymatic hydrolysis of

common starch. Due to its particular chemical structure, ß-cyclodextrin can

form inclusion complexes ('molecular encapsulation') with various drugs and so

improve their solubility, stability and bioavailability.

Piroxicam-ß-cyclodextrin was found to be very soluble in water and more

rapidly absorbed than piroxicam after oral and rectal administration.

The improved solubility results in a rapid increase in plasma levels of piroxicam

and means the peak value is reached sooner, which is clinically manifested with

a quicker onset and greater intensity of the analgesic and anti-inflammatory

effect.

As regards piroxicam, the extended plasma half-life in BREXIN is unchanged,

so allowing a once-a-day administration of the product.

The pharmacodynamic and pharmacokinetic properties of BREXIN make it

suitable for the treatment of markedly painful rheumatic and/or inflammatory

diseases,

which

seriously

compromise

patient's

general

condition

normal

activity,

where

necessary

obtain

rapid

intense

therapeutic effect.

Effectiveness and clinical safety

In the carrageenan-induced footpad oedema test, BREXIN produced an anti-

inflammatory activity more quickly than piroxicam; in the first hours after

administration, in fact, BREXIN was 2-3 times more active than piroxicam by

either oral or rectal route.

The analgesic activity was assessed in mice with the phenylquinone-induced

writhing test by oral route; 5 minutes after treatment, 99% of the maximum

inhibitory effect was obtained with BREXIN and 78% was obtained with

piroxicam. The activity of both drugs remained constant for two hours after

administration.

Therapeutic

index

values

BREXIN

piroxicam

were

calculated

comparing the anti-inflammatory effects, evaluated in rats with the carrageenan-

induced footpad oedema test, with the gastro-irritant effects in the same animal

species.

BREXIN by oral route had a therapeutic index 2.65 times higher than oral

piroxicam; the therapeutic index of BREXIN by rectal route was 2.31 times

higher than BREXIN by oral route.

The improved gastrointestinal tolerability of BREXIN was confirmed in man by

means of three double-blind controlled studies, in which the presence of blood

in the faeces was assessed using the

Cr-labelled red-cell method. In all these

Brexin - SmPC final-03.2020

studies, the treatment duration was 28 days. Two studies showed a significantly

lower faecal blood loss with BREXIN towards the end of the 4-week study

period, while in the third study a similar trend was seen.

further

study,

comparison

made

gastric

tolerability

BREXIN, piroxicam, indomethacin and placebo after administration over a 14-

day period; the gastric potential difference was also assessed (max GPD).

BREXIN

produced

lesser

effects

this

parameter

than

piroxicam

indomethacin, with a positive correlation between max GPD and endoscopic

results.

Therefore, BREXIN shows a more favourable ratio between pharmacodynamic

activity and gastrotoxicity than piroxicam.

5.2

Pharmacokinetic properties

Absorption

After oral administration of BREXIN, only the active ingredient (piroxicam) is

absorbed into the circulation, and not the complex as such.

Studies

healthy

volunteers

demonstrated

that,

equivalent

doses

piroxicam (20 mg), the piroxicam plasma peak is reached much earlier with

BREXIN (within 30-60 minutes, compared to an average of 2 hours with plain

piroxicam by oral route).

Biotransformation

ß-cyclodextrin is metabolized in the colon by bacterial microflora into linear

dextrin, maltose and glucose.

Distribution and elimination

The elimination parameters, Kel and half-life, do not differ from those of

piroxicam, as complexation with ß-cyclodextrin affects only absorption kinetics

and not elimination kinetics.

Urinary excretion of the active ingredient over 72 hours, for BREXIN and for

plain piroxicam, is about 10% of the administered dose.

After oral administration of the complex, no unchanged ß-cyclodextrin was

detected in plasma or urine.

5.3

Preclinical safety data

Non-clinical data show that there are no particular risks to humans, on the

basis of conventional studies on pharmacological safety, repeated dose

toxicity, genotoxicity, carcinogenic potential and reproduction toxicity.

As for other prostaglandin synthesis inhibitors, piroxicam, too, increases the

incidence of dystocia and post-term deliveries in animals when the drug is

administered throughout pregnancy. Administration of NSAIDs to pregnant

rats may cause constriction of the foetal ductus arteriosus. Moreover, in the

last trimester of pregnancy, gastro-duodenal toxicity is increased.

Non-clinical studies showed some effects such as gastrointestinal lesions and

Brexin - SmPC final-03.2020

renal papillary necrosis, at the highest dose used, which was about 60 times

higher than the suitable dose for humans.

Such exposure to piroxicam is therefore considered sufficiently in excess of

the maximum human exposure, indicating little relevance of these effects for

the clinical use of the drug.

6.

PHARMACEUTICAL PARTICULARS

6.1

List of excipients

Lactose monohydrate, crospovidone, sodium carboxymethyl starch, colloidal

anhydrous silica, modified starch, magnesium stearate.

6.2

Incompatibilities

None known

6.3

Expiry date

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

shelf-life period mentioned above refers to the product correctly stored in its

unopened package.

6.4.

Special precautions for storage

Store below 25°C.

6.5

Nature and contents of container

PVC/PVDC laminate blisters, sealed with Al/PVDC.

Pale yellow, hexagonal tablets with deep median score

Box of 4, 10, 20 or 30 tablets 20mg

Not all pack sizes may be marketed.

6.6.

Special precautions for disposal and handling

Any unused product or waste material deriving from it should be disposed of in

accordance with local requirements.

MANUFACTURER

Chiesi Farmaceutici S.p.A., Parma, Italy

8.

MARKETING AUTHORIZATION HOLDER

Taro International Ltd – 14 Hakitor st., Haifa Bay 2624761

9.

MARKETING AUTHORIZATION NUMBER

136-61-29695-00

Updated in March 2020.

Brexin - SmPC final-03.2020

ורת לנוישנרטניא

מ"עב

רוטיקה

.ד.ת

10347

הפיח ץרפמ ,

2624761

:לט

04-8475700

:סקפ

04-8727165

יאמ

2020

ה/דבכנ ה/אפור

ת/דבכנ ת/חקור

יכ םכעידוהל תשקבמ ורת תרבח ןולעה ןכרצל אפורלו רישכתה לש

Brexin Tablets

כדוע ונ

.

תוירקיעה תופסותה

נמוסמ תו

ב הטמ .םודא

ב הטמ תונמוסמ תויתוהמ תוקיחמ .הקיחמ וק םע לוחכ

ולעה םינ

כדועמה וחלשנ םינ

מוסרפ ךרוצל תואירבה דרשמל

:תואירבה דרשמ רתאבש תופורתה רגאמב

www.health.gov.il

לבקל ןתינו

ספדומ םי

:םושירה לעבל היינפ ידי לע

ורת לנוישנרטניא

רוטיקה בוחר ,מ"עב

ד.ת ,

10347

הפיח ץרפמ

2624761

,הכרבב

ןמדלוג הנירמ

הנוממ תחקור

Brexin Tablets

ליעפ ביכרמ

:

Piroxicam (as Beta-Cyclodextrin) 20mg

היוותהה

:רישכתל תרשואמה

Piroxicam is indicated for symptomatic relief of osteoarthritis rheumatoid arthritis or ankylosing

spondylitis

When an NSAID is indicated piroxicam should be considered as a second line

option. The decision to prescribe piroxicam should be based on assessment of the individual’s

patient overall risk

.

םינוכדע

םיירקיע ל ןולעב אפור

:

4.3

Contraindications

Patients with active peptic ulcer, inflammatory gastrointestinal disorders or gastrointestinal

bleeding. Patients with gastritis, dyspepsia, severe hepatic or renal disorders, moderate or

severe heart failure, severe hypertension, severe blood changes or haemorrhagic diathesis.

Concomitant use of other NSAIDs, including COX-2 selective inhibitors and acetylsalicylic

acid at analgesic doses. Concomitant use of anticoagulants. History of previous severe

allergic drug reactions of any type, especially skin reactions such as erythema multiforme,

Stevens-Johnson syndrome, toxic epidermal necrolysis. Previous skin reactions (regardless

of severity) to piroxicam, other NSAIDs and other medications.

For known or suspected pregnancy, during lactation or the use in children (refer to section

4.6).

There is a potential for cross-sensitivity with acetylsalicylic acid and other non-steroidal

anti-inflammatory

drugs.

This

product

should

given

patients

whom

acetylsalicylic acid or other non-steroidal anti-inflammatory drugs have induced symptoms

of asthma, rhinitis, nasal polyposis, angioedema, urticaria.

Porphyria

Severe heart failure

ורת לנוישנרטניא

מ"עב

רוטיקה

.ד.ת

10347

הפיח ץרפמ ,

2624761

:לט

04-8475700

:סקפ

04-8727165

4.4

Special warnings and precautions for use

Severe gastrointestinal complications

Identification of at-risk subjects

Patients taking concomitant oral corticosteroids, selective serotonin reuptake inhibitors

(SSRIs), anticoagulants such as warfarin or platelet anti-aggregate agents such as low-dose

acetylsalicylic acid are at increased risk of severe gastrointestinal complications (see below

and section 4.5). As with other NSAIDs, the use of piroxicam in combination with gastro-

protectants agents (e.g. misoprostol or proton pump inhibitors) must be considered for these

at-risk patients.

Cardiovascular and cerebrovascular effects

Suitable monitoring and instructions are necessary in patients with positive anamnesis for

hypertension and/or mild to moderate congestive heart failure, as water retention and

oedema have been reported in association with NSAIDs treatment.

Clinical studies and epidemiological data indicate that the use of some NSAIDs (especially

at high doses and for long-term treatment) may be associated with a moderate small

increased risk of arterial thrombotic events (e.g. myocardial infarction or stroke). There are

not enough data to exclude such a risk for piroxicam.

Patients with uncontrolled hypertension, congestive heart failure, established ischaemic

heart disease, peripheral arterial disease and/or cerebrovascular disease should be treated

with piroxicam only after careful evaluation. Similar considerations should be made before

starting long-term treatment in patients with risk factors for cardiovascular disease (e.g.

hypertension, hyperlipidemia, diabetes mellitus, smoking).

To avoid the risk of increased side effects, piroxicam should not be given with other non-

steroidal anti-inflammatory agents.

Piroxicam, like other NSAIDs, reduces platelet aggregation and prolongs bleeding time;

this characteristic must be taken into account when blood tests are performed and when the

patient is concomitantly treated with other platelet aggregation inhibitors.

Patients with impaired renal, cardiac function should be periodically monitored, as in such

patients the inhibition of prostaglandin synthesis caused by piroxicam may result in a

severe decrease in renal perfusion that may lead to acute renal failure. In this regard,

elderly patients and patients treated with diuretics should be considered as at risk.

Dehydrated patients are at risk for impairment of renal function.

Caution should also be paid in patients with impaired hepatic function. It is advisable to

periodically monitor their clinical and laboratory parameters, especially in case of

prolonged treatment.

Due to its interaction with arachidonic acid metabolism, the drug may induce

bronchospasms and possibly shock and other allergic phenomena in asthmatic and

predisposed patients.

As some ocular changes have been observed during therapy with NSAIDs, periodic

ophthalmological examinations are advised during prolonged treatment.

It is also advisable to frequently check blood glucose levels in diabetic patients and

prothrombin

time

patients

concomitantly

receiving

anticoagulant

treatment

with

dicoumarol derivatives.

ורת לנוישנרטניא

מ"עב

רוטיקה

.ד.ת

10347

הפיח ץרפמ ,

2624761

:לט

04-8475700

:סקפ

04-8727165

In rare cases, NSAIDs may cause interstitial nephritis, glomerulitis papillary necrosis and

nephrotic syndrome. They inhibit synthesis of renal prostaglandin that plays a supportive

role in maintaining renal perfusion in patients with reduced blood volume and renal blood

flow. In such patients, administration of a NSAID may precipitate overt renal

decompensation, which is followed by recovery to the pre-treatment state upon

discontinuation of NSAID therapy. Patients at greatest risk of such a reaction are those

with congestive heart failure, liver cirrhosis, nephrotic syndrome or overt renal disease.

Such patients should be monitored carefully whilst receiving NSAID therapy.

Skin reactions

Evidence from observational studies suggests that piroxicam may be associated with a

higher risk of serious skin reactions than other non-oxicam NSAIDs.

In association with the use of Brexin, serious skin reactions, potentially fatal, have been

reported including: exfoliative dermatitis, Stevens-Johnson syndrome (SJS) and toxic

epidermal necrolysis (TEN).

Patients should be advised and closely monitored for any signs and symptoms of skin

reactions. Patients appear to be at highest risk of appearance of SJS and TEN during initial

weeks of treatment. The onset of the reaction occurring in the majority of cases within the

first month of treatment.

Treatment with BREXIN should be discontinued at the first appearance of symptoms and

signs of SJS or TEN (i.e. progressive skin rash, often with blisters and mucosal lesions).

The best results in management of SJS and TEN are achieved with early diagnosis and the

prompt discontinuation of therapy whatever the suspect medication. The early

discontinuation is associated with a better prognosis.

Patients developing SJS or TEN due to a therapy with BREXIN, should never be treated

with BREXIN again.

The use of piroxicam, as of any other prostaglandin synthesis and cyclo-oxygenase

inhibitors, is not recommended in women planning to start a pregnancy.

The administration of piroxicam should be discontinued in women with fertility problems

or undergoing fertility investigations.

4.5

Interactions with other medicaments and other forms of interaction

Diuretics, ACE-inhibitors and angiotensin II antagonists

: NSAIDs may reduce the efficacy

of diuretics and other anti-hypertensive drugs. In some patients with impaired renal

function (e.g. dehydrated patients or elderly patients with impaired renal function), the co-

administration of an ACE-inhibitor or an angiotensin II antagonist and agents that inhibit

the cyclo-oxygenase system, may further deteriorate renal function, with possible acute

renal failure, which is generally reversible. These interactions should be taken into

consideration in patients taking piroxicam together with ACE-inhibitors and angiotensin II

antagonists.

The combination should therefore be administered with caution, especially in elderly

patients.

Patients should be adequately hydrated and renal function monitoring should be considered

after starting concomitant therapy.

ורת לנוישנרטניא

מ"עב

רוטיקה

.ד.ת

10347

הפיח ץרפמ ,

2624761

:לט

04-8475700

:סקפ

04-8727165

In case of concomitant intake of potassium-containing drugs, or diuretics that cause

potassium retention, there is an additional risk of a rise in serum potassium concentration

(hyperkalemia).

Alcohol intake should be avoided.

Piroxicam may reduce the efficacy of intrauterine devices.

Cyclosporin and Tacrolimus: the administration of NSAIDs together with cyclosporin or

tacrolimus increases the risk of nephrotoxicity.

Cardiac Glycosides

NSAIDs may exacerbate cardiac failure, reduce GFR and increase plasma cardiac

glycosides levels.

Concomitant administration of antacids had no effect on piroxicam plasma levels, nor did

concurrent therapy of piroxicam with digoxin or digitoxin affect the plasma levels of either

drug.

Mifepristone

In common with other NSAIDs, piroxicam should be avoided for at least 8 to 12 days

following mifepristone administration as NSAIDs can reduce the effect of mifepristone.

Methotrexate

There is decreased elimination of methotrexate with NSAIDs

Aminoglycosides

Reduction in renal function in susceptible individuals, decreased elimination of

aminoglycosides and increased plasma concentrations have been reported.

Probenecid

Reduction in metabolism and elimination of NSAID and metabolites occurs with

probenecid.

Oral Hypoglycaemic Agents

Inhibition of metabolism of sulfonylurea drugs, prolonged half-life and increased risk of

hypoglycaemia is known to occur with oral hypoglycaemic agents.

Fertility, Pregnancy and lactation

Piroxicam is contraindicated during ascertained or suspected pregnancy, and during breast-

feeding (see section 4.3).

Fertility

The use of piroxicam may impair female fertility and is not recommended in women trying

to become pregnant. Discontinuation of therapy with piroxicam should be envisaged for

women with difficulties in conceiving or those being investigated for fertility.

Pregnancy

Inhibition of prostaglandin synthesis can adversely affect pregnancy and/or embryo/foetal

development.

Results from epidemiological studies suggest an increased risk of miscarriage, cardiac

malformation and gastroschisis after use of a prostaglandin synthesis inhibitor during early

ורת לנוישנרטניא

מ"עב

רוטיקה

.ד.ת

10347

הפיח ץרפמ ,

2624761

:לט

04-8475700

:סקפ

04-8727165

pregnancy. The absolute risk of cardiac malformations increased from less than 1% up to

approximately 1.5%. It was considered that the risk is dose-related and also increases with

duration of therapy.

Studies on animals have shown reproductive toxicity (see section 5.3). In animals, the

administration of prostaglandin synthesis inhibitors has been shown to cause an increase in

pre- and post-implantation losses and in embryo-foetal mortality.

Moreover, an increased incidence of various malformations, including cardiovascular

malformation, was reported in animals given prostaglandin synthesis inhibitors during

organogenesis.

During the third trimester of pregnancy, all prostaglandin synthesis inhibitors can expose

foetuses to:

- cardiopulmonary toxicity (with premature closure of the ductus arteriosus and pulmonary

hypertension);

- renal dysfunction, which may progress to renal failure with oligo-hydroamniosis;

both mother and newborn child, at the end of pregnancy to:

- possible prolongation of bleeding time and anti-aggregating effect that can even occur

with very low doses;

- inhibition of uterine contractions resulting in delayed or prolonged labour.

Lactation

Data show that piroxicam concentration in breast milk lies between 1% and 3% of

maternal plasma concentration. Piroxicam is contraindicated during breastfeeding because

safety in newborns has not yet been established (see section 4.3).

4.8

Undesirable effects

As for other substances with similar action, some patients showed increases in blood urea

nitrogen that do not exceed a certain level with prolonged treatment; once therapy is

discontinued values return to baseline.

According to MedDRA

System Organ Class

Adverse Reaction

Frequency

Hematopoetic tissue

Anaemia

Common

Aplastic anaemia, hemolitic anaemia,

thrombocytopenia, leucopenia,

eosinophilia, pancytopenia

Rare

Metabolism and nutrition

disorders

Fluid retention, hypoglycaemia,

hyperglycaemia, abnormal weight gain or

decrease, loss of appetite, anorexia

Not known

Psychiatric disorders

Depression, abnormal dreams,

hallucinations, insomnia, confusion, mood

swings, nervousness, erethism

Not known

Nervous system disorders

Headache

Common

Dizziness, sleepiness, drowsiness,

paraesthesias

Uncommon

ורת לנוישנרטניא

מ"עב

רוטיקה

.ד.ת

10347

הפיח ץרפמ ,

2624761

:לט

04-8475700

:סקפ

04-8727165

Eye disorders

Blurry vision

Uncommon

Sight impairment, optic neuritis (unknown)

Rare

Vascular disorders

Vasculitis, shock (warning symptoms)

Not known

Respiratory, thoracic and

mediastinal disorders

Bronchospasm, epistaxis, asthma,

aggravated asthma, dyspnoea

Not known

Gastrointestinal disorders

Abdominal distress, abdominal pain,

constipation, diarrhoea, epigastric pain or

distress, flatulence, nausea, vomiting,

dyspepsia, indigestion

Common

Ulcerative stomatitis

Uncommon

Gastritis, gastrointestinal bleeding,

gastrointestinal perforation, melaena,

haematemesis, peptic ulcer pancreatitis,

mouth dryness

Not known

Skin and subcutaneous tissue

disorders

Rash, pruritus

Common

Photosensitivity reaction, urticaria,

angioneurotic oedema, non

thrombocytopenic purpura, Henoch-

Schonlein purpura

Rare

Severe skin adverse reactions (SCARs):

Stevens-Johnson syndrome (SJS), toxic

epidermal necrolysis (TEN),

vesiculo-bullous reactions (see section 4.4)

Very rare

Alopecia, skin desquamation, erythema

multiforme, ecchymosis, sweating,

abnormal nail growth

Not known

Renal and urinary disorders

Interstitial nephritis, renal papillary

necrosis, nephrotic syndrome, renal failure

Rare

Vesicular disorder

Very rare

Haematuria, dysuria

Not known

General Disorders and

Administration Site

Conditions

Oedema

Rare

Malaise, asthenia , palpitations

Not known

The most commonly observed adverse events are gastrointestinal. Peptic ulcers,

gastrointestinal perforation or bleeding, sometimes fatal, may occur, especially in the

elderly (see section 4.4).

After piroxicam administration, exacerbation of colitis and Crohn's disease have been

observed (see section 4.4).

Some cases of haematuria, dysuria, acute renal failure, water retention, which can occur as

oedema especially in the declivous regions of the lower limbs or as cardiovascular

disturbances (hypertension, decompensation) have been reported.

ורת לנוישנרטניא

מ"עב

רוטיקה

.ד.ת

10347

הפיח ץרפמ ,

2624761

:לט

04-8475700

:סקפ

04-8727165

ל ןולעב םיירקיע םינוכדע ןכרצ

1

.

תדעוימ המל הפורתה

?

.וליעוה אל תיטיופרת הצובק התואמ תורחא תופורת רשאכ קר וז הפורת ךל םושרי אפורה

2

.

הפורתב שומישה ינפל

הפורתב שומישל תועגונה תודחוימ תורהזא

:םא אפורל רפס ,ןיסקרבב לופיטה ינפל

שי .םייניע תויעב ךל

.תרכוס ךל שי

תוילכב תויעב ךל שי ןתשה תכרעמב וא

.דבכב תויעב ךל שי

שדוג םע בל תקיפס יא וא ץבש ,בל ףקתה ןוגכ םד ילכב וא בלב תויעב ךל שי התאש בשוח התאש וא הלא םיבצמל ןוכיסב

וא הובג םד ץחל ךל שי לשמל םא) ןשעמ התאש וא תרכוס

תופורתש ןוויכמ .ץבשל וא בל ףקתהל ןוכיסה תא טעמב תולעהל תולולע ןיסקרב ומכ

.תופסונ תוקידב עבקיש ךלש אפורל הנפ ,הלעמ םיטרופמה םיבצמהמ דחאמ לבוס התא םא

:םא הפורתב שמתשהל ןיא

בר תנמדא ןוגכ תונוש הרמוח תוגרדב תוירוע תובוגת וא/ו יהשלכ תיגרלא הבוגת רבעב תיווח

סנביטס תנומסת ,תיתרוצ

ינלער ימרדיפא קמנ וא ןוסנו'ג

(Toxic epidermal necrolysis)

רחאל ,תורחא תופורתב שומיש

םידיאורטס םניאש תקלד ידגונ

(NSAIDs)

,םירחא

םע תופורת וא .ההז ליעפ רמוח

המדאויגנא לש םינימסת ךל ויה שומיש ללגב ףאב תקלד וא ףאב םיפילופ ,החירפ ,המתסא , .(ןיריפסא) תיליצילס ליטצא הצמוחב וא םידיאורטס םניאש תקלד ידגונב

תלקהל (ןיריפסא) תיליצילס ליטצא הצמוח וא םירחא םידיאורטס םניאש תקלד ידגונ לטונ התא .באכ

בוס התאש וא ,ןוירסירתב וא/ו הביקב ילוכיע ביכמ לבוס התא וא לוכיע יישקמ ל הביקב תקלדמ .(סיטירטסג)

וא םומידמ ,ביכמ רבעב תלבס בוקינמ וא םד םע םיכרצ תיישע וא האקה ללוכ) הביקב וא םייעמב .(תפז תייומד הרוחש האוצ

ןטרס ןוגכ תולחמ ידי לע םרגנ םא וליפא םייעמב וא הביקב םומידמ וא תקלדמ לבוס התא ,לוכיעה תכרעמב םיפיעס תקלד

תיביכ (סיטילוק) יעמ תקלד ,(סיטילוקיטרביד) סגה יעמב תלחמ , .ןהורק

.הרומח תוילכ וא דבכ תלחממ לבוס התא

בלב תורומח תויעב וא הובג םד ץחל ךל שי בל תקיפס יא) דע תינוניב

.(הרומח

תורומח השירק תויעב ךל שי םא וא תובורק םיתיעל םמדל הייטנ ךל שי לטונ התא םא וא מ תופורת .(השירק ידגונ) םד תוללד

,ןויריהב תא ןויריהב תאש תבשוח וא

.("הקנהו ןויריה ,תוירופ" ףיעס יאר) הקינימ תא םא וא

ליגל תחתמ התא

ליג לעמ ךנה

ורת לנוישנרטניא

מ"עב

רוטיקה

.ד.ת

10347

הפיח ץרפמ ,

2624761

:לט

04-8475700

:סקפ

04-8727165

:הלולע םידיאורטס םניאש תקלד ידגונ תחפשממ תופורתה לכ ומכ ,וז הפורת

לולעש םומידל ףאו רומח םומידל םורגל וא םע ,ןמז לכב םייעמבו הביקב בוקינו םיביכ ,תוומל םורגל .הז גוסמ םירומח םיבצמ לש הירוטסיה ךל ןיא םא וליפא ,הרהזא ינמיס אלל

,תוומל םורגל תולולעש תוירוע תובוגתל םיתיעלו תורומח תוירוע תובוגתל םירידנ םירקמב םורגל מגודל) רועה תופלקתה וא תויחופלש ,םדוא תוללוכ רשא סנביטס תנומסת ,ה

ימרדיפא קמנו ןוסנו'ג ינלער

(Toxic epidermal necrolysis)

.לופיטה לש םימדקומה םיבלשב רתוי הובג ןוכיסה .(

.תונדפקב אפורה תוארוה רחא אלמ .ךשוממ שומישבו םיהובג םינונימב הלוע יאוול תועפותל ןוכיסה

קספה

:ךלש אפורל הנפו לופיטה תא

ןימסת שיגרמ התא םא .םומיד לש הרקמב דחוימב ,םייעמבו הביקב והשלכ

תיגרלא הבוגתל רחא ןמיס לכ וא תוירירב םיעצפ ,(החירפ) רועב והשלכ יונישב ןיחבמ התא םא .(םד ץחלב תימואתפ הליפנ ,המישנ יישק םע ןורגה וא םינפה תוחפנתה ,דרג ,םדוא)

!

םירגבתמו םידלי

ןיא

ליגל תחתמ םירגבתמבו םידליב הפורתב שמתשהל

תויתפורת ןיב תובוגת/תויצקארטניא !

...

,םינתשמ ןוגכ םד ץחל רתיב לופיטל תופורת

יבכעמ

ןיסנטויגנאל ןטלוקה ימסוחו

ןגלשא תוליכמה תופורת

הביק יביכב לופיטל שמשמה ןידיטמיס

ךות ןקתהב תשמתשמ תא םא

והשלכ ימחר

ןירופסולקיצ

ןוסיחה תכרעמ תוליעפ תא תודירומה תופורת ,סומילורקטו

(תואג תלחמל) דיצנבורפ

(סיזאירוספו ןטרסב לופיטל) טסקרטותמ

הארוא לינופלוס תצובקמ תרכוסל תופורת

(היספליפאל) ןיאוטינפ

(בלב בצק תוערפהל) ןיסקוגיד

םידימאנופלוסו םידיזוקילגונימא

הקנה ,ןויריה ! תוירופו

,ןויריהב תא םא ןיסקרבב שמתשהל ןיא

תואירב ,בלב עוגפל הלולע וז הפורתש ןוויכמ ןויריהב תאש תבשוח וא הדילה ךלהמב םיכוביסל םורגל וא רבועה לש תוילכב וא

.הקנהב ןיסקרבב שמתשהל ןיא ,ןיסקרב תלטונ תאו תוירופב תויעבמ תלבוס תא םא .תוירופב עוגפל הלולע וז הפורת .שומישה תא יקיספה

שי םא קר ןיסקרבב ישמתשה הקינימ תא םא וא ןויריה תננכתמ וא ןויריהב תאש תבשוח ,ןויריהב תא םא .ןיסקרבב שומישה ינפל אפורה םע יצעייתה .ךלש אפורה לש בקעמ תחתו ישממ ךרוצ

תונוכמב שומישו הגיהנ ! תופייע וא תרוחרחסל םורגל הלולע וז הפורת

תונוכמ תלעפה וא הגיהנ ןמזב דחוימב רהזיהל שי ,ןפוד תאצוי .תונכוסמ

3

.

?הפורתב שמתשת דציכ

ורת לנוישנרטניא

מ"עב

רוטיקה

.ד.ת

10347

הפיח ץרפמ ,

2624761

:לט

04-8475700

:סקפ

04-8727165

או ןונימה :אוה ללכ ךרדב לבוקמה ןונימה .דבלב אפורה ידי לע ועבקי לופיטה ןפו

.םויב םעפ הילבט

רתוי ךומנ ןונימ םושרי ךלש אפורהש ןכתיי

דחוימב ,הביקה תנגהל תפסונ הפורת ךל םושרי וא לעמ התא םא ליג

הפורתה ןמ דלי עלב תועטב םא וא רתי תנמ תלטנ םא אבהו םילוח תיב לש ןוימ רדחל וא אפורל דימ הנפ , .ךתיא הפורתה תזירא שאר באכ ,תרוחרחס ,ןופליע ,םונמנ ,תואקהמ לובסל לולע התא

4

.

יאוול תועפות

שי :םיאבה םירקמב אפורל תונפלו דימ שומישה תא קיספהל

רומח ןטב באכ ברוצ ןטב באכ וא םומיד , הביקב םיביכ בקע ןוירסירתב וא

;(ביכה תובקנתה) הביקה זכרמב ימואתפו זע באכ

וא םייעמב וא הביקב םומיד םע דחיב (הנלמ) הרוחש האוצ וא (סיזמטמה) םד םע האקה תושישת הבר ןתמב טועימ םע

;(הלגתה אלש םומיד בקע) ןתש

,תויגרלא תובוגת תורומח תובוגת ללוכ םייתפשה ,םינפה (המדאויגנא) תוחפנתה םע , ןורגהו רשא , ,םיידיה תוחפנתה וא המישנב ישוקל םורגל הלולע רתי תושיגר לש תבוגת) רזה בויסנה תלחמ ללוכ יבאכו תקלד ,החירפ ,םוחב תנייפואמו ןוסיחה תכרעמ תא תברעמה

;(םיקרפמ

וא תושישת ,ןורוויח ,בלה בצקב היילע ,לובלבל םורגל הלולע רשא (םלה) םד ץחלב תימואתפ הליפנ ;(הרהזא ינימסת) המישנב ישוק וא השלוח

סנביטס תנומסת ,המגודל) רועה תופלקתה וא םדוא ,תויחופלש ןוגכ תורומח תוירוע תובוגת

ןוסנו'ג ד ביטאילופסקא ,ינלער ימרדיפא קמנו בר תנמדא ,סיטיטמר

.(תיתרוצ

םייניעה ביבסמ תוחיפנ ,הזחב םיצחל ,הפירח תברצ ,םוח

תוחיכש יאוול תועפות דעב תועיפומש תועפות)

ךותמ

(םישמתשמ

;(הימנא) תומודא םד תוירודכב הדירי

;שאר באכ

,וגיטרו

;(םיינזואב לוצלצ) ןוטנט

,תוריצע ,ןטב באכ וא תוחונ יא םיזג ,לושלש (תוחיפנ) יישק ,האקה ,הליחב ,הביק באכ וא תוחונ יא , ;לוכיע

.דרג ,רועב החירפ

תורידנ יאוול תועפות

דעב תועיפומש תועפות)

ךותמ

1,000

(םישמתשמ

הימנא) םצעה חמ ידי לע תומודא םד תוירודכ לש רוצייב הדירי בקע םדב ןיבולגומהה תמרב הדירי ;(תיטסלפא

ולגומהה תמרב הדירי ;(תיטילומה הימנא) תומודא םד תוירודכ םיסרוהש םינדגונ תריצי בקע םדב ןיב

היילע ,(הינפוקיול) תונבלה םדה תוירודכ רפסמב הדירי ,(הינפוטיצובמורט) תויסטה רפסמב הדירי תומודאה םדה תוירודכ רפסמב הדירי ,(היליפוניזואא) םיליפוניזואא גוסמ תונבל םד תוירודכ רפסמב בו תונבלהו ;(הינפוטיצנפ) תויסט

;תויגרלא תובוגת בקע םיידיבו םינפב (תקצב) תוחיפנ

;הייארב תוקל

;(תבהצ) םייניעה וא רועה לש הבהצה

;(ילאטפ סיטיטפה) תוומל תמרוגש דבכב תקלד

,(רועה לש היצזיטיסנסוטופ) שמשה רואל רועה תושיגר ;תדפרס

ורת לנוישנרטניא

מ"עב

רוטיקה

.ד.ת

10347

הפיח ץרפמ ,

2624761

:לט

04-8475700

:סקפ

04-8727165

;(תינפוטיצובמורט אל תנמגרא) המקרל םינטקה םדה ילכמ םד תפילד בקע רועה תמדאה

ןיילנוש םש לע תנמגרא

;(תוילכבו יעמב ,רועב םדה ילכב תעגופש תקלד) ךונה

תנומסת ,יתיילכ ירליפפ קמנ) רומח יתיילכ יוקיל ,(תילאיציטסרטניא סיטירפנ) תוילכ תקלד ;(תיטורפנ

;(תקצב) תוחיפנ

היילע .ידבכ דוקפת ידדמב

דואמ תורידנ יאוול תועפות

דעב תועיפומש תועפות)

ךותמ

10,000

(םישמתשמ

.ןתשה תיחופלשב תויעב

העודי אל תוחיכשב יאוול תועפות

תועפות

ןתוחיכשש

םרט

(העבקנ

;םילזונ תריצא

;(הימקילגופיה ,הימקילגרפיה) םדב רכוסה תומרב הדירי וא היילע

הניקת אל היילע ;ףוגה לקשמב

תוררוע ,תונבצע ,חור בצמב תודונת ,לובלב ,(הינמוסניא) הניש ידודנ ,תויזה ,םירזומ תומולח ,ןואכיד ;רתי

;העימשב תוקל

;(סיטילוקסו) םד ילכ תקלד

;(םזאפסוכנורב) תונופמסה תורציה

;(סיסקטסיפא) ףאהמ םומיד

;(סיטיטאירקנפ) בלבלב תקלד ;(סיטירטסג) הביקב תקלד

שבוי

;הפב

;(סיטיטפה) דבכב תקלד

;(היצפולא) רעיש תרישנ

;רועה לע תשקשק

;(סיזומיכא) ימתכ םמד

;רתי תעזה

;םיינרופיצ תלידגב םייוניש

;(הירואסיד) ןתש ןתמב ישוק ,(הירוטמה) ןתשב םד

;תושישת ,תיללכ תוחונ רסוח תשגרה

;(היסקרונא) דורי ןובאית וא ןובאית רסוח

הקידב ,תוזנימאסנרט תומרב היילע ,טירקוטמהב וא ןיבולגומהב הדירי) םדב םיניקת אל םידדמ ;(ןיערגה דגנ םינדגונל תיבויח

;ןהורק תלחמ לשו (סיטילוק) סגה יעמה תקלד לש הרמחה

; ,(הפירח תוילכ תקיפס יא) תוילכ ידוקפתב םייוניש

קסווידרק תולחמ) דורי יבבל דוקפת ,םדה ץחלב היילע (תוירלו

Similar products

Search alerts related to this product

View documents history

Share this information