ENBREL POWDER AND SOLVENT

Israel - English - Ministry of Health

Buy It Now

Active ingredient:
ETANERCEPT
Available from:
PFIZER PHARMACEUTICALS ISRAEL LTD
ATC code:
L04AB01
Pharmaceutical form:
POWDER AND SOLVENT FOR SOLUTION FOR INJECTION
Composition:
ETANERCEPT 25 MG/VIAL
Administration route:
S.C
Prescription type:
Required
Manufactured by:
WYETH PHARMACEUTICALS LIMITED, U.K.
Therapeutic group:
ETANERCEPT
Therapeutic area:
ETANERCEPT
Therapeutic indications:
* Rheumatoid arthritis:Enbrel is indicated for the treatment of active rhematoid arthritis in adults when the response to disease-modifying antirheumatic drugs (DMARDs) including methotrexate (unless contraindicated) has been inadequate.. Enbrel can be used in combination with methotrexate in patients who do not respond adequately to methotrexate alone. Reducing signs and symptoms and inhibiting the progression of structural damage in patients with moderately to severely active rheumatoid arthritis.Enbrel, alone or in combination with methotrexate, has been shown to reduce the rate of progression of joint damage as measured by X-ray and to improve physical function.* Psoriatic arthritisTreatment of active and progressive psoriatic arthritis in adults when the response to previous disease-modifying antirheumatic drug therapy has been inadequate. Enbrel has been shown to improve physical function in patients with psoriatic arthritis, and to reduce the rate of progression of peripheral joint damage as measu
Authorization number:
119 12 30000 06
Authorization date:
2013-08-31

Documents in other languages

Patient Information leaflet Patient Information leaflet - Arabic

15-01-2021

Patient Information leaflet Patient Information leaflet - Hebrew

31-08-2020

Version V1.0

Congestive Heart

Failure

develop

symptoms

suggestive

congestive

heart failure or worsening

of existing congestive heart

failure, such as shortness of

breath, swelling of ankles,

persistent cough or fatigue,

seek

medical

attention

immediately.

Other Information

(please complete)

Patient’s Name:

Doctor’s Name:

Doctor’s Phone:

REPORTING OF

SUSPECTED ADVERSE

REACTIONS

Adverse

events

reported

directly

Ministry of Health using the

adverse

events

reporting

portal which is available on

the home page of the Ministry

of Health website:

www.health.gov.il

or by this link:

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

Side

effects

also

reported to Pfizer by email:

isr.aereporting@pfizer.com.

This card and its content has

been approved by the Ministry

of Health on July 2020.

ENBREL

®

Patient Safety

Information Card

Pfizer Pharmaceuticals Israel Ltd.

9 Shenkar St., Herzliya Pituach, Israel.

Tel: 09-9700500, Fax: 09-9700501

Patient Safety

Information Card

ENBREL

®

This card contains important

safety

information

that

need to be aware of before you

are given Enbrel

and during

treatment

with

Enbrel

you do not understand this

information, please ask your

doctor to explain it to you.

Show this card to any doctor

involved in your treatment.

Enbrel

package

leaflet for more information.

Keep

this

card

with

for 2 months after the last

Enbrel

dose,

since

side

effects may occur after your

last dose of Enbrel

It

is

important

that

you

and

your

doctor

record

the brand name and batch

number of your medication.

Infections

Enbrel

increase

your

risk

getting

infections,

which could be serious.

You should not use Enbrel

you have an infection. If you

are not sure, ask your doctor.

develop

symptoms

suggestive

infections,

such

fever,

persistent

cough,

weight

loss,

listlessness,

seek

medical

attention immediately.

You should be evaluated for

tuberculosis (TB). Ask your

doctor to record the dates

and the results of your last

screening for TB below:

Test:

Date:

Results:

Test:

Date:

Results:

Please ask your physician to

list

your

other

medications

that may increase your risk of

infection.

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1.

NAME OF THE MEDICINAL PRODUCT

Enbrel

LYOPHILIZED POWDER FOR INJECTION

2.

QUALITATIVE AND QUANTITATIVE COMPOSITION

Each vial contains 25 mg of etanercept.

Etanercept is a human tumour necrosis factor receptor p75 Fc fusion protein produced by

recombinant DNA technology in a Chinese hamster ovary (CHO) mammalian expression

system. Etanercept is a dimer of a chimeric protein genetically engineered by fusing the

extracellular ligand binding domain of human tumour necrosis factor receptor-2 (TNFR2/p75)

to the Fc domain of human IgG1. This Fc component contains the hinge, CH

and CH

regions, but not the CH

region of IgG1. Etanercept contains 934 amino acids and has an

apparent molecular weight of approximately 150 kilodaltons. The specific activity of

etanercept is 1.7 x 10

units/mg.

For the full list of excipients, see section 6.1.

3.

PHARMACEUTICAL FORM

Powder and solvent for solution for injection (powder for injection).

The powder is white. The solvent is a clear, colourless liquid.

4.

CLINICAL PARTICULARS

4.1

Therapeutic indications

Rheumatoid arthritis

Enbrel is indicated for the treatment of active rhematoid arthritis in adults when the response

to disease-modifying antirheumatic drugs (DMARDs) including methotrexate (unless

contraindicated) has been inadequate.

Enbrel can be used in combination with methotrexate in patients who do not respond

adequately to methotrexate alone.

Reducing signs and symptoms and inhibiting the progression of structural damage in patients

with moderately to severely active rheumatoid arthritis.

Enbrel, alone or in combination with methotrexate, has been shown to reduce the rate of

progression of joint damage as measured by X-ray and to improve physical function.

Juvenile idiopathic arthritis

Treatment of polyarthritis (rheumatoid factor positive or negative) and extended oligoarthritis

in children and adolescents from the age of 2 years who have had an inadequate response to,

or who have proved intolerant of, methotrexate.

Treatment of psoriatic arthritis in adolescents from the age of 12 years who have had an

inadequate response to, or who have proved intolerant of, methotrexate.

Treatment of enthesitis-related arthritis in adolescents from the age of 12 years who have had

an inadequate response to, or who have proved intolerant of, conventional therapy.

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Enbrel has not been studied in children aged less than 2 years.

Psoriatic arthritis

Treatment of active and progressive psoriatic arthritis in adults when the response to previous

disease-modifying antirheumatic drug therapy has been inadequate. Enbrel has been shown to

improve physical function in patients with psoriatic arthritis, and to reduce the rate of

progression of peripheral

joint damage as measured by X-ray in patients with polyarticular

symmetrical subtypes of the disease.

Axial spondyloarthritis

Ankylosing spondylitis (AS)

Treatment of adults with severe active ankylosing spondylitis who have had an inadequate

response to conventional therapy.

Non-radiographic axial spondyloarthritis

Treatment of adults with severe non-radiographic axial spondyloarthritis with objective signs

of inflammation as indicated by elevated C-reactive protein (CRP) and/or magnetic resonance

imaging (MRI) evidence, who have had an inadequate response to nonsteroidal anti-

inflammatory drugs (NSAIDs).

Plaque psoriasis

Treatment of adults patients (18 years or older) with moderate to severe plaque psoriasis who

are candidates for systemic therapy or phototherapy.

Paediatric plaque psoriasis

Treatment of chronic severe plaque psoriasis in children and adolescents from the age of

6 years who are inadequately controlled by, or are intolerant to, other systemic therapies or

phototherapies.

4.2

Posology and method of administration

Enbrel treatment should be initiated and supervised by specialist physicians experienced in

the diagnosis and treatment of rheumatoid arthritis, juvenile idiopathic arthritis, psoriatic

arthritis, ankylosing spondylitis, non-radiographic axial spondyloarthritis, plaque psoriasis or

paediatric plaque psoriasis.

Enbrel is available in strengths of 25.

Posology

Rheumatoid arthritis

25 mg Enbrel administered twice weekly is the recommended dose. Alternatively, 50 mg

administered once weekly has been shown to be safe and effective (see section 5.1).

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Psoriatic arthritis, ankylosing spondylitis and non-radiographic axial spondyloarthritis

The recommended dose is 25 mg Enbrel administered twice weekly, or 50 mg administered

once weekly.

For all of the above indications, available data suggest that a clinical response is usually

achieved within 12 weeks of treatment. Continued therapy should be carefully reconsidered in

a patient not responding within this time period.

Plaque psoriasis

The recommended dose of Enbrel is 25 mg administered twice weekly or 50 mg administered

once weekly. Alternatively, 50 mg given twice weekly may be used for up to 12 weeks

followed, if necessary, by a dose of 25 mg twice weekly or 50 mg once weekly. Treatment

with Enbrel should continue until remission is achieved, for up to 24 weeks. Continuous

therapy beyond 24 weeks may be appropriate for some adult patients (see section 5.1).

Treatment should be discontinued in patients who show no response after 12 weeks. If re-

treatment with Enbrel is indicated, the same guidance on treatment duration should be

followed. The dose should be 25 mg twice weekly or 50 mg once weekly.

Special populations

Renal and hepatic impairment

No dose adjustment is required.

Elderly

No dose adjustment is required. Posology and administration are the same as for adults 18-64

years of age.

Paediatric population

Juvenile idiopathic arthritis

The recommended dose is 0.4 mg/kg (up to a maximum of 25 mg per dose), given twice

weekly as a subcutaneous injection with an interval of 3-4 days between doses or 0.8 mg/kg

(up to a maximum of 50 mg per dose) given once weekly.

Discontinuation of treatment should be considered in patients who show no response after 4

months.

No formal clinical trials have been conducted in children aged 2 to 3 years. However, limited

safety data from a patient registry suggest that the safety profile in children from 2 to 3 years

of age is similar to that seen in adults and children aged 4 years and older, when dosed every

week with 0.8 mg/kg subcutaneously (see section 5.1).

There is generally no applicable use of Enbrel in children aged below 2 years in the indication

juvenile idiopathic arthritis.

Paediatric plaque psoriasis (age 6 years and above)

The recommended dose is 0.8 mg/kg (up to a maximum of 50 mg per dose) once weekly for

up to 24 weeks. Treatment should be discontinued in patients who show no response after 12

weeks.

If re-treatment with Enbrel is indicated, the above guidance on treatment duration should be

followed. The dose should be 0.8 mg/kg (up to a maximum of 50 mg per dose) once weekly.

There is generally no applicable use of Enbrel in children aged below 6 years in the indication

plaque psoriasis.

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Method of administration

Enbrel is administered by subcutaneous injection. Enbrel powder for solution must be

reconstituted in 1 ml of solvent before use (see section 6.6).

Comprehensive instructions for the preparation and administration of the reconstituted Enbrel

vial are given in the package leaflet, section 7, "Instructions for preparation and giving an

injection of Enbrel."

4.3

Contraindications

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

Sepsis or risk of sepsis.

Treatment with Enbrel should not be initiated in patients with active infections, including

chronic or localised infections.

4.4

Special warnings and precautions for use

In order to improve the traceability of biological medicinal products, the trademark and the

batch number of the administered product should be clearly recorded (or stated) in the patient

file.

Infections

Patients should be evaluated for infections before, during, and after treatment with Enbrel,

taking into consideration that the mean elimination half-life of etanercept is approximately

70 hours (range 7 to 300 hours).

Serious infections, sepsis, tuberculosis, and opportunistic infections, including invasive fungal

infections, listeriosis and legionellosis, have been reported with the use of Enbrel (see section

4.8). These infections were due to bacteria, mycobacteria, fungi, viruses and parasites

(including protozoa). In some cases, particular fungal and other opportunistic infections have

not been recognised, resulting in delay of appropriate treatment and sometimes death. In

evaluating patients for infections, the patient’s risk for relevant opportunistic infections (e.g.,

exposure to endemic mycoses) should be considered.

Patients who develop a new infection while undergoing treatment with Enbrel should be

monitored closely. Administration of Enbrel should be discontinued if a patient develops a

serious infection. The safety and efficacy of Enbrel in patients with chronic infections have

not been evaluated. Physicians should exercise caution when considering the use of Enbrel in

patients with a history of recurring or chronic infections or with underlying conditions that

may predispose patients to infections, such as advanced or poorly controlled diabetes.

Tuberculosis

Cases of active tuberculosis, including miliary tuberculosis and tuberculosis with extra-

pulmonary location, have been reported in patients treated with Enbrel.

Before starting treatment with Enbrel, all patients must be evaluated for both active and

inactive (‘latent’) tuberculosis. This evaluation should include a detailed medical history with

personal history of tuberculosis or possible previous contact with tuberculosis and previous

and/or current immunosuppressive therapy. Appropriate screening tests, i.e., tuberculin skin

test and chest X-ray, should be performed in all patients (local recommendations may apply).

It is recommended that the conduct of these tests should be recorded. Prescribers are

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reminded of the risk of false negative tuberculin skin test results, especially in patients who

are severely ill or immunocompromised.

If active tuberculosis is diagnosed, Enbrel therapy must not be initiated. If inactive (‘latent’)

tuberculosis is diagnosed, treatment for latent tuberculosis must be started with anti-

tuberculosis therapy before the initiation of Enbrel, and in accordance with local

recommendations. In this situation, the benefit/risk balance of Enbrel therapy should be very

carefully considered.

All patients should be informed to seek medical advice if signs/symptoms suggestive of

tuberculosis (e.g., persistent cough, wasting/weight loss, low-grade fever) appear during or

after Enbrel treatment.

Hepatitis B reactivation

Reactivation of hepatitis B in patients who were previously infected with the hepatitis B virus

(HBV) and had received concomitant TNF-antagonists, including Enbrel, has been reported.

This

includes reports of reactivation of hepatitis B in patients who were anti-HBc positive but

HBsAg negative. Patients should be tested for HBV infection before initiating treatment with

Enbrel. For patients who test positive for HBV infection, consultation with a physician with

expertise in the treatment of hepatitis B is recommended. Caution should be exercised when

administering Enbrel in patients previously infected with HBV. These patients should be

monitored for signs and symptoms of active HBV infection throughout therapy and for

several weeks following termination of therapy. Adequate data from treating patients infected

with

HBV with anti-viral therapy in conjunction with TNF-antagonist therapy are not

available. In patients who develop HBV infection, Enbrel should be stopped and effective

anti-viral therapy with appropriate supportive treatment should be initiated.

Worsening of hepatitis C

There have been reports of worsening of hepatitis C in patients receiving Enbrel. Enbrel

should be used with caution in patients with a history of hepatitis C.

Concurrent treatment with anakinra

Concurrent administration of Enbrel and anakinra has been associated with an increased risk

of serious infections and neutropenia compared to Enbrel alone. This combination has not

demonstrated increased clinical benefit. Thus, the combined use of Enbrel and anakinra is not

recommended (see sections 4.5 and 4.8).

Concurrent treatment with abatacept

In clinical studies, concurrent administration of abatacept and Enbrel resulted in increased

incidences of serious adverse events. This combination has not demonstrated increased

clinical benefit; such use is not recommended (see section 4.5).

Allergic reactions

Allergic reactions associated with Enbrel administration have been reported commonly.

Allergic reactions have included angioedema and urticaria; serious reactions have occurred. If

any serious allergic or anaphylactic reaction occurs, Enbrel therapy should be discontinued

immediately and appropriate therapy initiated.

Immunosuppression

The possibility exists for TNF-antagonists, including Enbrel, to affect host defences against

infections and malignancies since TNF mediates inflammation and modulates cellular

immune responses. In a study of 49 adult patients with rheumatoid arthritis treated with

Enbrel, there was no evidence of depression of delayed-type hypersensitivity, depression of

immunoglobulin levels, or change in enumeration of effector cell populations.

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Two juvenile idiopathic arthritis patients developed varicella infection and signs and

symptoms of aseptic meningitis, which resolved without sequelae. Patients with a significant

exposure to varicella virus should temporarily discontinue Enbrel therapy and be considered

for prophylactic treatment with Varicella Zoster Immune Globulin.

The safety and efficacy of Enbrel in patients with immunosuppression have not been

evaluated.

Malignancies and lymphoproliferative disorders

Solid and haematopoietic malignancies (excluding skin cancers)

Reports of various malignancies (including breast and lung carcinoma and lymphoma) have

been received in the postmarketing period (see section 4.8).

In the controlled portions of clinical trials of TNF-antagonists, more cases of lymphoma have

been observed among patients receiving a TNF-antagonist compared with control patients.

However, the occurrence was rare, and the follow-up period of placebo patients was shorter

than for patients receiving TNF-antagonist therapy. In the postmarketing setting, cases of

leukaemia have been reported in patients treated with TNF-antagonists. There is an increased

background risk for lymphoma and leukaemia in rheumatoid arthritis patients with long-

standing, highly active, inflammatory disease, which complicates risk estimation.

Based on current knowledge, a possible risk for the development of lymphomas, leukaemia or

other haematopoietic or solid malignancies in patients treated with a TNF-antagonist cannot

be excluded. Caution should be exercised when considering TNF-antagonist therapy for

patients with a history of malignancy or when considering continuing treatment in patients

who develop a malignancy.

Malignancies, some fatal, have been reported among children, adolescents and young adults

(up to 22 years of age) treated with TNF-antagonists (initiation of therapy ≤ 18 years of age),

including Enbrel, in the postmarketing setting. Approximately half the cases were

lymphomas. The other cases represented a variety of different malignancies and included rare

malignancies typically associated with immunosuppression. A risk for the development of

malignancies in children and adolescents treated with TNF-antagonists cannot be excluded.

Skin cancers

Melanoma and non-melanoma skin cancer (NMSC) have been reported in patients treated

with TNF-antagonists, including Enbrel. Postmarketing cases of Merkel cell carcinoma have

been reported very infrequently in patients treated with Enbrel. Periodic skin examination is

recommended for all patients, particularly those with risk factors for skin cancer.

Combining the results of controlled clinical trials, more cases of NMSC were observed in

patients receiving Enbrel compared with control patients, particularly in patients with

psoriasis.

Vaccinations

Live vaccines should not be given concurrently with Enbrel. No data are available on the

secondary transmission of infection by live vaccines in patients receiving Enbrel. In a

double-blind, placebo-controlled, randomised clinical study in adult patients with psoriatic

arthritis, 184 patients also received a multivalent pneumococcal polysaccharide vaccine at

week 4. In this study, most psoriatic arthritis patients receiving Enbrel were able to mount

effective B-cell immune response to pneumococcal polysaccharide vaccine, but titres in

aggregate were moderately lower, and few patients had two-fold rises in titres compared to

patients not receiving Enbrel. The clinical significance of this is unknown.

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Autoantibody formation

Treatment with Enbrel may result in the formation of autoimmune antibodies (see section

4.8).

Haematologic reactions

Rare cases of pancytopenia and very rare cases of aplastic anaemia, some with fatal outcome,

have been reported in patients treated with Enbrel. Caution should be exercised in patients

being treated with Enbrel who have a previous history of blood dyscrasias. All patients and

parents/caregivers should be advised that if the patient develops signs and symptoms

suggestive of blood dyscrasias or infections (e.g., persistent fever, sore throat, bruising,

bleeding, paleness) whilst on Enbrel, they should seek immediate medical advice. Such

patients should be investigated urgently, including full blood count; if blood dyscrasias are

confirmed, Enbrel should be discontinued.

Neurological disorders

There have been rare reports of CNS demyelinating disorders in patients treated with Enbrel

(see section 4.8). Additionally, there have been rare reports of peripheral demyelinating

polyneuropathies (including Guillain-Barré syndrome, chronic inflammatory demyelinating

polyneuropathy, demyelinating polyneuropathy, and multifocal motor neuropathy). Although

no clinical trials have been performed evaluating Enbrel therapy in patients with multiple

sclerosis, clinical trials of other TNF antagonists in patients with multiple sclerosis have

shown increases in disease activity. A careful risk/benefit evaluation, including a neurologic

assessment, is recommended when prescribing Enbrel to patients with pre-existing or recent

onset of demyelinating disease, or to those who are considered to have an increased risk of

developing demyelinating disease.

Combination therapy

In a controlled clinical trial of two years duration in rheumatoid arthritis patients, the

combination of Enbrel and methotrexate did not result in unexpected safety findings, and the

safety profile of Enbrel when given in combination with methotrexate was similar to the

profiles reported in studies of Enbrel and methotrexate alone. Long-term studies to assess the

safety of the combination are ongoing. The long-term safety of Enbrel in combination with

other disease-modifying antirheumatic drugs (DMARD) has not been established.

The use of Enbrel in combination with other systemic therapies or phototherapy for the

treatment of psoriasis has not been studied.

Renal and hepatic impairment

Based on pharmacokinetic data (see section 5.2), no dose adjustment is needed in patients

with renal or hepatic impairment; clinical experience in such patients is limited.

Congestive heart failure (Cardiac failure congestive)

Physicians should use caution when using Enbrel in patients who have congestive heart

failure (CHF). There have been postmarketing reports of worsening of CHF, with and without

identifiable precipitating factors, in patients taking Enbrel. There have also been rare (< 0.1%)

reports of new onset CHF, including CHF in patients without known pre-existing

cardiovascular disease. Some of these patients have been under 50 years of age. Two large

clinical trials evaluating the use of Enbrel in the treatment of CHF were terminated early due

to lack of efficacy. Although not conclusive, data from one of these trials suggest a possible

tendency toward worsening CHF in those patients assigned to Enbrel treatment.

Alcoholic hepatitis

In a phase II randomised placebo-controlled study of 48 hospitalised patients treated with

Enbrel or placebo for moderate to severe alcoholic hepatitis, Enbrel was not efficacious, and

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the mortality rate in patients treated with Enbrel was significantly higher after 6 months.

Consequently, Enbrel should not be used in patients for the treatment of alcoholic hepatitis.

Physicians should use caution when using Enbrel in patients who also have moderate to

severe alcoholic hepatitis.

Wegener's granulomatosis

A placebo-controlled trial, in which 89 adult patients were treated with Enbrel in addition to

standard therapy (including cyclophosphamide or methotrexate, and glucocorticoids) for a

median duration of 25 months, has not shown Enbrel to be an effective treatment for

Wegener’s granulomatosis. The incidence of non-cutaneous malignancies of various types

was significantly higher in patients treated with Enbrel than in the control group. Enbrel is not

recommended for the treatment of Wegener’s granulomatosis.

Hypoglycaemia in patients treated for diabetes

There have been reports of hypoglycaemia following initiation of Enbrel in patients receiving

medication for diabetes, necessitating a reduction in anti-diabetic medication in some of these

patients.

Special populations

Elderly

In the Phase 3 studies in rheumatoid arthritis, psoriatic arthritis, and ankylosing spondylitis,

no overall differences in adverse events, serious adverse events, and serious infections in

patients age 65 or older who received Enbrel were observed compared with younger patients.

However, caution should be exercised when treating the elderly and particular attention paid

with respect to occurrence of infections.

Paediatric population

Vaccinations

It is recommended that paediatric patients, if possible, be brought up to date with all

immunisations in agreement with current immunisation guidelines prior to initiating Enbrel

therapy (see Vaccinations, above).

Inflammatory bowel disease (IBD) and uveitis in patients with juvenile idiopathic arthritis

(JIA)

There have been reports of IBD and uveitis in JIA patients being treated with Enbrel (see

section 4.8).

4.5

Interaction with other medicinal products and other forms of interaction

Concurrent treatment with anakinra

Adult patients treated with Enbrel and anakinra were observed to have a higher rate of serious

infection when compared with patients treated with either Enbrel or anakinra alone (historical

data).

In addition, in a double-blind, placebo-controlled trial in adult patients receiving background

methotrexate, patients treated with Enbrel and anakinra were observed to have a higher rate of

serious infections (7%) and neutropenia than patients treated with Enbrel (see sections 4.4 and

4.8). The combination Enbrel and anakinra has not demonstrated increased clinical benefit,

and is therefore not recommended.

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Concurrent treatment with abatacept

In clinical studies, concurrent administration of abatacept and Enbrel resulted in increased

incidences of serious adverse events. This combination has not demonstrated increased

clinical benefit; such use is not recommended (see section 4.4).

Concurrent treatment with sulfasalazine

In a clinical study of adult patients who were receiving established doses of sulfasalazine, to

which Enbrel was added, patients in the combination group experienced a statistically

significant decrease in mean white blood cell counts in comparison to groups treated with

Enbrel or sulfasalazine alone. The clinical significance of this interaction is unknown.

Physicians should use caution when considering combination therapy with sulfasalazine.

Non-interactions

In clinical trials, no interactions have been observed when Enbrel was administered with

glucocorticoids, salicylates (except sulfasalazine), nonsteroidal anti-inflammatory drugs

(NSAIDs), analgesics, or methotrexate. See section 4.4 for vaccination advice.

No clinically significant pharmacokinetic drug-drug interactions were observed in studies

with methotrexate, digoxin or warfarin.

4.6

Fertility, pregnancy and lactation

Women of childbearing potential

Women of childbearing potential should consider the use of appropriate contraception to

avoid becoming pregnant during Enbrel therapy and for three weeks after discontinuation of

therapy.

Pregnancy

Developmental toxicity studies performed in rats and rabbits have revealed no evidence of

harm to the foetus or neonatal rat due to etanercept. The effects of etanercept on pregnancy

outcomes have been investigated in two observational cohort studies. A higher rate of major

birth defects was observed in one observational study comparing pregnancies exposed to

etanercept (n=370) during the first trimester with pregnancies not exposed to etanercept or

other TNF-antagonists (n=164) (adjusted odds ratio 2.4, 95% CI: 1.0-5.5). The types of major

birth defects were consistent with those most commonly reported in the general population

and no particular pattern of abnormalities was identified. No change in the rate of

spontaneous abortion, stillbirth, or minor malformations was observed. In another

observational multi-country registry study comparing the risk of adverse pregnancy outcomes

in women exposed to etanercept during the first 90 days of pregnancy (n=425) to those

exposed to non-biologic drugs (n=3497), there was no observed increased risk of major birth

defects (crude odds ratio [OR]= 1.22, 95% CI: 0.79-1.90; adjusted OR = 0.96, 95% CI: 0.58-

1.60 after adjusting for country, maternal disease, parity, maternal age and smoking in early

pregnancy). This study also showed no increased risks of minor birth defects, preterm birth,

stillbirth, or infections in the first year of life for infants born to women exposed to etanercept

during pregnancy. Enbrel should only be used during pregnancy if clearly needed.

Etanercept crosses the placenta and has been detected in the serum of infants born to female

patients treated with Enbrel during pregnancy. The clinical impact of this is unknown,

however, infants may be at increased risk of infection. Administration of live vaccines to

infants for 16 weeks after the mother’s last dose of Enbrel is generally not recommended.

Breast-feeding

Etanercept has been reported to be excreted in human milk following subcutaneous

administration. In lactating rats following subcutaneous administration, etanercept was

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excreted in the milk and detected in the serum of pups. Because immunoglobulins, in

common with many medicinal products, can be excreted in human milk, a decision must be

made whether to discontinue breast-feeding or to discontinue Enbrel therapy, taking into

account the benefit of breast-feeding for the child and the benefit of therapy for the woman.

Fertility

Preclinical data about peri- and postnatal toxicity of etanercept and of effects of etanercept on

fertility and general reproductive performance are not available.

4.7

Effects on ability to drive and use machines

No studies on the effects on the ability to drive and use machines have been performed.

4.8

Undesirable effects

Summary of the safety profile

The most commonly reported adverse reactions are injection site reactions (such as pain,

swelling, itching, reddening and bleeding at the puncture site), infections (such as upper

respiratory infections, bronchitis, bladder infections and skin infections), allergic reactions,

development of autoantibodies, itching, and fever.

Serious adverse reactions have also been reported for Enbrel. TNF-antagonists, such as

Enbrel, affect the immune system and their use may affect the body’s defenses against

infection and cancer. Serious infections affect fewer than 1 in 100 patients treated with

Enbrel. Reports have included fatal and life-threatening infections and sepsis. Various

malignancies have also been reported with use of Enbrel, including cancers of the breast,

lung, skin and lymph glands (lymphoma).

Serious haematological, neurological and autoimmune reactions have also been reported.

These include rare reports of pancytopenia and very rare reports of aplastic anaemia. Central

and peripheral demyelinating events have been seen rarely and very rarely, respectively, with

Enbrel use. There have been rare reports of lupus, lupus-related conditions, and vasculitis.

Tabulated list of adverse reactions

The following list of adverse reactions is based on experience from clinical trials in adults and

on postmarketing experience.

Within the organ system classes, adverse reactions are listed under headings of frequency

(number of patients expected to experience the reaction), using the following categories: 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); not known (cannot be estimated from the

available data).

System

Organ

Class

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

< 1/10,00

0

Frequency

Not Known

(Cannot be

Estimated

from

Available

Data)

Infections

infestations

Infection

(including

upper

respiratory

tract

infection,

bronchitis,

Serious

infections

(including

pneumonia,

cellulitis,

arthritis

bacterial, sepsis

Tuberculosis,

opportunistic

infection

(including invasive

fungal, protozoal,

bacterial, atypical

mycobacterial,

Hepatitis B

reactivation,

listeria

מ"עב לארשי הקיטבצמרפ רזייפ

רקנש 'חר

.ד.ת ,

12133

לארשי ,חותיפ הילצרה

46725

:לט

972-9-9700500

:סקפ

972-9-9700501

ינוי

2019

,ה/דבכנ ת/חקור ,ה/אפור

ןוכדע לע ךעידוהל וננוצרב ןולעב

אפורל

ןולעב לש ןכרצל

Enbrel

:

:ליעפה ביכרמה

ETANERCEPT 25 MG/VIAL

Indicated for:

Rheumatoid arthritis

Enbrel is indicated for the treatment of active rhematoid arthritis in adults when the response to disease-

modifying

antirheumatic

drugs

(DMARDs)

including

methotrexate

(unless

contraindicated)

been

inadequate.

Enbrel can be used in combination with methotrexate in patients who do not respond adequately to

methotrexate alone.

Reducing

signs

symptoms

inhibiting

progression

structural

damage

patients

with

moderately to severely active rheumatoid arthritis.

Enbrel, alone or in combination with methotrexate, has been shown to reduce the rate of progression of joint

damage as measured by X-ray and to improve physical function.

Juvenile idiopathic arthritis

Treatment of polyarthritis (rheumatoid factor positive or negative) and extended oligoarthritis in children and

adolescents from the age of 2 years who have had an inadequate response to, or who have proved intolerant

of, methotrexate.

Treatment of psoriatic arthritis in adolescents from the age of 12 years who have had an inadequate response

to, or who have proved intolerant of, methotrexate.

Treatment of enthesitis-related arthritis in adolescents from the age of 12 years who have had an inadequate

response to, or who have proved intolerant of, conventional therapy.

Enbrel has not been studied in children aged less than 2 years.

Psoriatic arthritis

Treatment of active and progressive psoriatic arthritis in adults when the response to previous disease-

modifying antirheumatic drug therapy has been inadequate. Enbrel has been shown to improve physical

function in patients with psoriatic arthritis, and to reduce the rate of progression of peripheral

joint damage

as measured by X-ray in patients with polyarticular symmetrical subtypes of the disease.

Axial spondyloarthritis

Ankylosing spondylitis (AS)

Treatment of adults with severe active ankylosing spondylitis who have had an inadequate response to

conventional therapy.

Non-radiographic axial spondyloarthritis

Treatment

adults

with

severe

non-radiographic

axial

spondyloarthritis

with

objective

signs

inflammation as indicated by elevated C-reactive protein (CRP) and/or magnetic resonance imaging (MRI)

evidence, who have had an inadequate response to nonsteroidal anti-inflammatory drugs (NSAIDs).

Plaque psoriasis

Treatment of adults patients (18 years or older) with moderate to severe plaque psoriasis who are candidates

for systemic therapy or phototherapy.

Paediatric plaque psoriasis

Treatment of chronic severe plaque psoriasis in children and adolescents from the age of 6 years who are

inadequately controlled by, or are intolerant to, other systemic therapies or phototherapies.

:אפורל ןולעב םיירקיעה םינוכדעה ןלהל

4.8

U

NDESIRABLE EFFECTS

Tabulated list of adverse reactions

The following list of adverse reactions is based on experience from clinical trials in adults and on

postmarketing experience.

Within the organ system classes, adverse reactions are listed under headings of frequency (number of

patients expected to experience the reaction), using the following categories: 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); not

known (cannot be estimated from the available data).

System Organ

Class

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

Frequency Not

Known (Cannot

be Estimated

from Available

Data)

Skin and

subcutaneous

tissue disorders

Pruritus, rash

Angioedema,

psoriasis (including

new onset or

worsening and

pustular, primarily

palms and soles),

urticaria,

psoriasiform rash

Stevens-Johnson

syndrome, cutaneous

vasculitis (including

hypersensitivity

vasculitis), erythema

multiforme, lichenoid

reactions

Toxic

epidermal

necrolysis

:ןכרצל ןולעב םיירקיעה םינוכדעה ןלהל

4

.

יאוול תועפות

לרבנאב שומישה ,הפורת לכב ומכ

.יאוולה תועפות תמישר ארקמל להבית לא .םישמתשמהמ קלחב יאוול תועפותל םורגל לולע .ןהמ תחא ףאמ לובסי/לובסת אל דליה /התאו ןכתי

...

תויושע( תורידנ יאוול תועפות ב עיפוהל

-

דע

1

לכמ

1,000

:)םישנא

המדמדא החירפ ( )תידיאונכיל הבוגת( תפלי

ו תדרגמ הלוגס

ןבל עבצב םיטוח ייומד םיווק וא

.)יריר םורק לע רופא

ץעייתהל ךילע ,ןולעב הניוצ אלש יאוול תעפותמ לבוס התא רשאכ וא ,הרימחמ יאוולה תועפותמ תחא םא ,יאוול תעפות העיפוה םא ורה םע .אפ

םייונישה בוהצ עקרב םישגדומה

חסונ ינוכדעו עדימ תטמשה ,עדימ תפסות םיללוכה םיפסונ םייוניש ועצוב ,ןכ ומכ .הרמחה םיווהמ .תואירבה דרשמ רתאב םינימז םינכדועמה םינולעה .הרמחה םיווהמ םניאש

https://www.old.health.gov.il/units/pharmacy/trufot/index.asp?safa=h

מ"עב לארשי הקיטבצמרפ רזייפ תרבחל תונפל ןתינ ספדומ אלמ ןולע תלבקל ,ןיפוליחל

רקנש

.ד.ת ,

12133

הילצרה

,חותיפ

46725

,הכרבב

קו'צשילופ הטירגרמ

הנוממ תחקור

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