Enbrel ® 25 mg Solution

ENBREL is a biological medicine and is a type of protein called tumour necrosis factor (TNF) blocker that blocks the action of TNF in your body’s immune system. People with an auto immune disease have too much TNF in their bodies. ENBREL blocks the action of TNF, helping to treat your disease. But, in doing so, ENBREL lowers the ability of your immune system to fight infections.

ENBREL is an anti - rheumatic medicine used to treat:

• The signs and symptoms of active rheumatoid arthritis (RA) in adults and children. It is reserved for patients who have not responded to or have responded poorly to other disease - modifying medicines (DMARDS) used for rheumatoid arthritis. ENBREL can be used alone or in combination with methotrexate.
• Severe, active and progressive rheumatoid arthritis in adults not previously treated with methotrexate.
• Polyarticular - course juvenile idiopathic arthritis in children and adolescents from the age of 2 years, when the response to one or DMARDS has proved inadequate.
• Polyarticular - course juvenile idiopathic arthritis and extended oligoarthritis in children and adolescents from the age of 2 years when treatment with methotrexate has not worked well enough or is not suitable for them.
• Psoriatic arthritis in adolescents from the age of 12 years when treatment with methotrexate has not worked well enough or is not suitable for them.
• Enthesitis - related arthritis in adolescents from the age of 12 years when other widely used treatments have not worked well enough or are not suitable for them.
• The signs and symptoms of psoriatic arthritis (PS), and for inhibiting the progression of structural damage of active arthritis in patients. ENBREL can be used in combination with methotrexate in patients who do not respond adequately to methotrexate alone.
• Adults with a type of arthritis called ankylosing spondylitis (AS), and where your doctor may or may not be able to see swelling in the sacroiliac (pelvic) joints and/or your spine using X - rays and in patients where other widely used treatments have not worked well enough or are not suitable for them.
• Adults (aged 18 and over), for treatment of chronic moderate to severe plaque psoriasis, who are candidates for systemic therapy or phototherapy.
• Chronic severe plaque psoriasis in children and adolescents, (from the age of 6 years), who have had an inadequate response to, or are unable to take phototherapies or other systemic therapies.

RA, PS and AS are inflammatory diseases that can affect the joints in your body. Psoriasis is an inflammatory disease that affects the skin and can cause raised, thick, red and scaly patches (psoriatic skin lesions) that can occur anywhere in the body. Psoriatic arthritis is usually seen in patients with psoriasis and affects both the joints and the skin.

Do not use ENBREL:

• if you are hypersensitive (allergic) to etanercept or to any of the other ingredients of ENBREL (listed in section 6)
• if you have or are at risk of sepsis (blood poisoning)
• if you have an infection of any type including tuberculosis or chronic infections and local infections (such as a leg ulcer)

Warnings and precautions

Take special care with ENBREL:

• if you are prone to infection (i.e. if you think you have an infection, are being treated for an infection, have signs of an infection such as fever, cough, flu - like symptoms and have open sores on your body). ENBREL may lessen the body’s ability to fight infections. You should be evaluated for infections, specifically for tuberculosis before, during and after treatment with ENBREL.
• if you are about to have any surgery or if you develop a new infection.
• if you have any immune system disorders, cancer, advanced or poorly controlled diabetes mellitus (sugar diabetes). ENBREL may lessen the body’s ability to fight infection.
• if you have tuberculosis (TB), or if you have been in close contact with someone who has had tuberculosis
• if you have or have had hepatitis B or hepatitis C
• if you have liver disease caused by the excessive intake of alcohol
• if you have or have ever had lymphoma (a type of blood cancer) or any other cancer. Patients with severe rheumatoid arthritis, who have had the disease for a long time, may be at higher than average risk of developing lymphoma. There have been reports of children and adolescents developing cancers, including lymphoma and skin cancers who have received ENBREL or other medicines that work in the same way as ENBREL. Tell your doctor if you or your child develops any change in the appearance of the skin or growths on the skin
• if you have any blood disorders (signs include persistent fever, bruising, bleeding, or paleness). ENBREL may increase the risk of blood disorders such as anaemia. There have been rare reports of serious blood disorders, some resulting in death
• do not have any vaccinations (immunisations) without your doctor’s approval
• if you have any diseases of the central nervous system such as multiple sclerosis, seizures, or optic neuritis (inflammation of the nerves of the eyes). ENBREL may make these conditions worse
• if you have any heart problems. ENBREL may worsen congestive heart failure
• if you are being treated for diabetes, as ENBREL may lower your blood sugar levels. ENBREL has been tested in elderly patients (65 – 87 years of age) with similar response rates and safety profiles as seen in adult patients under 65 years of age

Other medicines and ENBREL

Always tell your health care provider if you are taking any other medicine. (This includes all complementary or traditional medicines.) ENBREL should NOT be used together with:

• live attenuated vaccines, such as the oral polio vaccine
• anakinra as it may increase the risk of serious infection and blood disorders
• abatacept as it may increase the incidence of serious adverse events
• sulfasalazine as it may decrease your white blood cell count
• any other medicine in the same syringe

Pregnancy and breastfeeding

If you are pregnant or breastfeeding, think you may be pregnant or are planning to have a baby, please consult your doctor, pharmacist or other health care provider for advice before using this medicine. You should only be treated with ENBREL during pregnancy if clearly needed. It is important that you tell your health care provider about the use of ENBREL during pregnancy before the baby receives any vaccine. You should only be treated with ENBREL during breastfeeding if clearly needed. Talk to your doctor if you want to breastfeed while on ENBREL treatment. It is important that you tell your baby’s doctors and other health care providers about the use of ENBREL during breastfeeding before your baby receives any vaccine. Safety in pregnancy and lactation has not been established.

Do not share medicines prescribed for you with any other person. Always use ENBREL exactly as your doctor or pharmacist has told you. Check with your doctor or pharmacist if you are not sure. To help you remember, write in a diary which days of the week you should have an injection. Your doctor will prescribe the appropriate dose for you or your child according to the condition. Your doctor will tell you how long your treatment with ENBREL will last. Do not stop treatment early. If you have the impression that the effect of ENBREL is too strong or too weak, tell your doctor or pharmacist.

Adults

The usual adult dose of ENBREL for rheumatoid arthritis is 25 mg given twice a week (3 – 4 days apart) or 50 mg given once weekly, and can be administered as follows:

• once weekly two ENBREL 25 mg pre - filled syringes administered subcutaneously at approximately the same time, or
• one ENBREL 25 mg pre - filled syringe administered twice weekly, 3 – 4 days apart (i.e. two 25 mg pre - filled syringes per week), or
• ENBREL 50 mg pre - filled syringe or pre - filled pen administered once weekly as a subcutaneous injection.

If you have psoriatic arthritis, ankylosing spondylitis or non - radiographic axial spondylarthritis, the recommended dose is 50 mg per week (given as one ENBREL 25 mg pre - filled syringe given twice weekly, 3 – 4 days apart). Doses other than 25 mg administered twice weekly have not been studied. If you have plaque psoriasis, the recommended starting dose of ENBREL for adult patients is 50 mg per week as one ENBREL 25 mg pre - filled syringe administered twice weekly, 3 – 4 days apart or ENBREL 50 mg pre - filled syringe or pre - filled pen administered once weekly. After three months your doctor will tell you whether to reduce your dose.

Children

The recommended dose of ENBREL for children with juvenile rheumatoid arthritis, idiopathic arthritis and psoriasis is based upon the child’s body weight. Your child’s doctor will tell you the amount of ENBREL your child should use. See your doctor at regular visits. It is important that your doctor checks your progress to make sure that this medicine is working properly.

Route of administration

ENBREL is injected under the skin. Your doctor will show you how and where to give the injection. Follow the detailed instructions on ENBREL injection preparation and injection procedure as provided below. ENBREL 25 mg PS and ENBREL 50 mg PS pre - filled syringes or pre - filled pen are ready for use.

ENBREL can have side effects. Not all side effects reported for ENBREL are included in this leaflet. Should your general health worsen or if you experience any untoward effects while using ENBREL, please consult your health care provider for advice.

If any of the following happens, stop using ENBREL and tell your doctor immediately or go to the casualty department at your nearest hospital:

• Serious allergic reactions such as a tight chest, wheezing, dizziness, fast heartbeat, difficulty swallowing, swelling of the face, eyelids or around the eyes, lips or tongue and skin rash
• Signs of blood disorders such as unusual bleeding, bruising or paleness especially if fever and sore throat are also present
• Signs of serious infections, such as high fever that may be accompanied by a cough, shortness of breath, chills, weakness, or a hot, red, tender, sore area on the skin or joints

These are all very serious side effects. If you have them, you may have had a serious reaction to ENBREL. You may need urgent medical attention or hospitalisation.

Tell your doctor immediately or go to the casualty department at your nearest hospital if you notice any of the following:

Frequent side effects

• infections such as respiratory infections (cough, fever, chills, sneezing, congestion, sore throat), kidney infections (frequent or painful urination) or skin infections (skin rash, redness, swelling or itching of skin). You should be evaluated for infections before, during and after treatment
• autoimmune reactions where antibodies are made that may harm the normal tissues in the body
• general itching of the skin, rash
• reactions at the injection site including redness, bleeding, bruising, itching, swelling or pain at the place of injection or previously used site
• fever or chills

Less frequent side effects

• serious infections (including pneumonia, deep skin infections, joint infections, blood infection, infections at various sites and infections caused by parasites)
• tuberculosis, opportunistic infections, (including fungal, bacterial and viral infections)
• melanoma and non - melanoma skin cancers
• low blood platelet count, low red blood cell count, low white blood cell count, low neutrophil (a type of white blood cell) count, failure of the bone marrow to produce crucial blood cells
• inflammation of the blood vessels affecting multiple organs
• serious allergic reactions (including severe localised swelling of the skin, wheezing)
• an immune disorder that can affect the lungs, skin and lymph nodes (sarcoidosis)
• nervous system disorders (with severe muscle weakness and signs and symptoms similar to those of multiple sclerosis or inflammation of the nerves of the eyes or spinal cord)
• seizure (fit)
• inflammation of the eye
• new onset or worsening of existing congestive heart failure including shortness of breath or troubled breathing, chest pain, numbness on one side of the face or body
• inflammation or scarring of the lungs
• elevated liver blood tests, inflammation of the liver caused by the body's own immune system (autoimmune hepatitis)
• localised swelling of the skin (angioedema)
• psoriasis (new or worsening)
• hives (elevated patches of red or pale skin that often itch)
• extreme sensitivity reaction resulting in inflammation and damage to the blood vessels mainly in the skin.
• lupus - like syndrome (symptoms may include persistent rash, fever, pain or back pain, joint or muscle pain or stiffness, loss of energy and tiredness)

Side effects where the frequency is unknown

• recurrence of hepatitis B (a liver infection)
• Listeria (infections caused by certain types of bacteria)
• lymphoma (a type of blood cancer)
• leukaemia (cancer affecting the blood and bone marrow)
• Merkel cell carcinoma (a type of skin cancer)
• a condition where your body stops producing new blood cells (aplastic anaemia)
• histiocytosis haematophagic (excessive activation of white blood cells associated with inflammation)
• headache
• a condition where the immune system attacks the nerves (Guillain - Barré syndrome)
• inflammation of the nerves which can result in loss in sensation, tingling and pain, difficulty walking and weakness
• pain from nerve damage which can cause muscle weakening and wasting to be experienced
• abdominal cramps and pain, diarrhoea, weight loss or blood in the stool (signs of bowel problems)
• painful red or purplish rash that can cause blistering or peeling of the skin. These may be signs of lupus erythematosus or Stevens - Johnson Syndrome, or toxic epidermal necrolysis (TEN)
• damage to the tiny filters inside your kidneys leading to poor kidney function (glomerulonephritis)

If you notice any side effects not mentioned in this leaflet, please inform your doctor or pharmacist.

Reporting of side effects

If you get side effects, talk to your doctor or pharmacist. You can also report side effects to SAHPRA via the Med Safety APP (Medsafety X SAHPRA) and eReporting platform (who - umc.org) found on SAHPRA website. By reporting side effects, you can help provide more information on the safety of ENBREL. You can report any suspected adverse drug reactions associated with the use of the medicine directly to Pfizer via [email protected].

ENBREL 25 mg and 50 mg PS solution for injection in pre - filled syringe or pre - filled pen:

• Store all medicines out of the reach of children
• Store ENBREL PS pre - filled syringes and ENBREL PS pre - filled pens in the refrigerator (2 – 8 °C). DO NOT FREEZE
• Before injection, ENBREL PS pre - filled syringes and pre - filled pens should be taken out the refrigerator and allowed to reach room temperature (approximately 15 to 30 minutes). The needle cover or cap should not be removed while allowing the pre - filled syringe or pre - filled pen to reach room temperature
• Return all unused medicine to your pharmacist
• Do not dispose of unused medicine in drains or sewerage systems (e.g. toilets)