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Enbrel: 7 things you should know

Medically reviewed by Carmen Fookes, BPharm. Last updated on March 18, 2022.

1. How it works

  • Enbrel is a brand (trade) name for etanercept which may be used to treat inflammatory conditions such as psoriasis or rheumatoid arthritis.
  • Enbrel works by acting as a decoy p75 TNF receptor. TNF (tumor necrosis factor) is a naturally occurring cytokine (cytokines are small proteins that are involved in interactions and communications between cells). Cytokines and other proteins play an important role in the development of many inflammatory conditions such as psoriasis and rheumatoid arthritis and the resulting joint destruction. Elevated levels of TNF are found in the tissues and body fluids of people with these conditions. TNF binds to one of two receptors on cells – these are called p55 TNF receptors or p75 TNF receptors. By acting as a decoy p75 TNF receptor, TNF-alpha and TNF-beta bind to Enbrel instead of the cell surface TNF receptors. This renders TNF inactive.
  • Enbrel belongs to the class of medicines known as TNF inhibitors.

2. Upsides

  • Approved to treat moderate to severe Rheumatoid arthritis in adults either in combination with methotrexate or alone and in children aged 2 or older with moderately to severely active polyarticular juvenile idiopathic arthritis (JIA).
  • May be used to treat moderate to severe plaque psoriasis in adults and children who are at least 4 years old who are candidates for systemic therapy or phototherapy. It may be used with or without methotrexate to reduce the signs and symptoms, inhibit structural progression, and improve the physical function of adults with psoriatic arthritis.
  • Approved for reducing the signs and symptoms of active ankylosing spondylitis.
  • A fragment of human immunoglobulin G1 is attached to the structure of Enbrel which gives it a more profound and long-lasting effect than naturally occurring soluble TNF receptors.
  • May be given by a doctor or nurse or people can be taught to self-administer it.
  • Available as a single dose vial, a single-dose prefilled syringe, a single-dose prefilled SureClick autoinjector, and Enbrel mini single-dose prefilled cartridges for use with the AutoTouch reusable autoinjector. Administration is easy to learn.
  • Injected subcutaneously (under the skin) once or twice a week depending on the condition being treated, for example: adult rheumatoid arthritis, ankylosing spondylitis, and psoriatic arthritis: 50mg once weekly; psoriasis: 50mg twice weekly for three months then once weekly thereafter.
  • Effects include less pain, stiffness, and swelling, and improvements in movement and laboratory markers of inflammation.

3. Downsides

If you are between the ages of 18 and 60, take no other medication or have no other medical conditions, side effects you are more likely to experience include:

  • Injection site reactions (such as redness, pain, swelling at the injection site) and upper respiratory tract infections are the most common side effects reported.
  • Post-marketing reports indicate that Enbrel increases a person’s risk of developing an infection by about 20%. Infections reported include invasive fungal infections, including histoplasmosis, coccidioidomycosis, candidiasis, aspergillosis, blastomycosis, and pneumocystosis; bacterial infections; viral infections, and other infections, such as legionella or listeria. May not be suitable for people with a history of chronic or recurrent infection.
  • All patients should be tested for latent TB and, if found to be positive, treatment should be initiated before starting Enbrel.
  • Before starting treatment with Enbrel, ensure all patients have received all their appropriate immunizations for their age as recommended by National guidelines. It is important people administered Enbrel DO NOT receive live vaccines.
  • Unable to be given orally (like most other biologics) because it is such an unstable molecule it barely gets absorbed. This is why it needs to be given by injection.
  • May not be suitable for some people including those with a previous hepatitis B infection, heart failure, or nervous system problems.
  • Enbrel is associated with a slightly increased risk of lymphoma and other cancers.
  • Must be kept refrigerated at between 2°C to 8°C [36°F to 46°F]). Store in the original carton to protect from light. May be kept at room temperature of up to 77ºF (25ºC) for up to 14 days. Do not shake, heat, freeze, or put in direct sunlight. Once stored at room temperature, do not place it back in the refrigerator and discard Enbrel if not used within 14 days.
  • It is not known how Enbrel affects a developing baby but your doctor may consider using it during pregnancy if the benefits outweigh the risks. Tell your doctor immediately if you become pregnant while being administered Enbrel. It is not known if live vaccinations administered to neonates soon after delivery are affected by previous Enbrel administration. Enbrel is present in low levels in human milk and minimally absorbed by a breastfed infant. No data are available on its effects.
  • No generic version of Enbrel is available.

Note: In general, seniors or children, people with certain medical conditions (such as liver or kidney problems, heart disease, diabetes, seizures) or people who take other medications are more at risk of developing a wider range of side effects. View complete list of side effects

4. Bottom Line

Enbrel is a subcutaneous injection that is usually self-administered once or twice a week for inflammatory conditions such as rheumatoid arthritis, psoriasis, psoriatic arthritis, or ankylosing spondylitis. Injection site reactions and upper respiratory tract infections are the most common side effects reported.

5. Tips

  • Make sure you have read the Enbrel Medication guide prior to starting treatment with Enbrel. Ask questions if you have any before treatment.
  • If your healthcare provider has shown you how to administer Enbrel and you are comfortable doing it, then you can administer it yourself. Before administering Enbrel, take it out of the refrigerator and allow it to warm up to room temperature for 30 minutes. This will make the injection feel more comfortable. Do not attempt to warm it up with a microwave or hot water as this will destroy the medicine. Do not shake the Enbrel injection.
  • You should only inject Enbrel into your thigh, stomach area (except for a 2 inch [5cm]) area around your belly button, or the outer area of your upper arm (if somebody else is administering it to you). Wash your hands with soap and water.
  • Check the injection status through the viewing window of your Enbrel autoinjector. The fluid inside should look clear and colorless. There may be some small white particles in the medicine. Do not use if the medicine is cloudy or discolored or contains large particles. Also, check the expiry date located on the side of the autoinjector and do not use it if expired.
  • Choose an injection site and wipe it with an alcohol wipe. Let it dry. Do not use a site where the skin is discolored, bruised, broken, covered with a psoriatic lesion, or has a rash. Pull the Enbrel autoinjector cap straight off. Do not leave the cap off for more than five minutes as this can dry out the medicine. Create a firm surface on your injection site by either using your fingers to stretch out the skin or pinch it up. Place the autoinjector on your chosen injection site at a 90° angle (straight up and down). Firmly press and hold down the Enbrel autoinjector. Once you are ready to inject, push down on the purple start button. This will insert the needle and start the injection. You will hear a clicking sound. Hold the autoinjector down firmly until the clicking sound stops and the viewing window turns from clear to yellow when the injection is done. You may hear a second click. If the window doesn’t change color contact your health care provider. Dispose of your autoinjector and cap in an approved sharps bin. Do not put the cap back on the autoinjector. Each SureClick autoinjector is administered just one time only. The status button on AutoTouch reusable injector flashes green after starting the injection and then turns off at the end of the injection.
  • People do report stinging for up to 20 seconds after Enbrel administration. When cleaning the injection site with an alcohol swab, always allow the alcohol to evaporate off so that your skin is dry before administering Enbrel. Numbing the area with ice before and after administration may also help reduce stinging. Injecting into the stomach area is generally less painful than injecting into the thigh. Make sure you rotate injection sites to reduce scar tissue build-up. Allowing a family member or friend to give you the shots instead can help reduce the anticipation, which generally makes it less painful.
  • Tell your doctor if you experience any of the following, which may indicate that you have an infection: burning when you urinate or urinating more often than normal; coughing; diarrhea; fever, sweats or chills; muscle aches; shortness of breath; stomach pain; tiredness; warm, painful or red skin or sores on your body; or weight loss.
  • Seek immediate medical help if you develop an allergic reaction after taking Enbrel (symptoms include anaphylaxis or urticaria). The needle cover of the prefilled syringe, the cover within the white cap of the SureClick, and the purple cap within the Enbrel mini cartridge all contain latex.
  • You can take Enbrel (etanercept) if you have a cold, but make sure you let your doctor know that you have a cold because he/she may wish to monitor your health while your cold symptoms are present, as you are at a higher risk of developing a more serious infection because you are taking Enbrel.
  • Enbrel should be kept refrigerated at between 36°F to 46°F (2°C to 8°C) until it needs to be administered. Enbrel may be left unrefrigerated for up to 14 days, as long as it is protected from light and not exposed to heat. Once Enbrel has been taken out of the refrigerator for more than 15 minutes, do not put it back in the refrigerator. If Enbrel has not been used within 14 days of being taken out of the refrigerator, discard it. Always check the expiry date and do not administer Enbrel that has expired. Do not freeze Enbrel.
  • Tell your doctor immediately if you experience any new medical conditions, such as heart failure or autoimmune disorders) or if your condition worsens.
  • It is not known how Enbrel affects a developing baby but your doctor may consider using it during pregnancy if the benefits outweigh the risks. Tell your doctor immediately if you become pregnant while being administered Enbrel.
  • Do not store Enbrel in extreme heat and cold such as the car glove box or trunk.

6. Response and effectiveness

  • Starts to have some effect within one to two weeks, although it may take 3 to 6 months for the full effects to develop.
  • Trials investigating the efficacy of Enbrel use a measure called the American College of Rheumatology (ACR) response. This is defined as follows: ACR 50: A 50% improvement in the number of tender and number of swollen joints, and a 50% improvement in three of the following five criteria: patient global assessment, physician global assessment, functional ability measure [most often Health Assessment Questionnaire (HAQ)], visual analog pain scale, and erythrocyte sedimentation rate or C-reactive protein (CRP). In some studies, over 42% of people achieved a definite clinical response (ACR 50) by month 3 and 15% achieved a significant clinical response (ACR 70) by month 3.
  • Trials have also shown using Enbrel in combination with methotrexate increases response.

7. Interactions

Medicines that interact with Enbrel may either decrease its effect, affect how long it works for, increase side effects, or have less of an effect when taken with Enbrel. An interaction between two medications does not always mean that you must stop taking one of the medications; however, sometimes it does. Speak to your doctor about how drug interactions should be managed.

Enbrel interacts with over 387 medications; most of these interactions are considered major or moderate. Common medications that may interact with Enbrel include:

  • benzodiazepines such as clonazepam or diazepam
  • bleomycin
  • capecitabine, carboplatin, cyclophosphamide
  • cholesterol-lowering agents such as atorvastatin or fluvastatin
  • cladribine
  • heart medications such as amiodarone or nifedipine
  • hormones such as ethinylestradiol or levonorgestrel
  • hydroxyurea
  • immunosuppressants such as azathioprine or cyclosporine
  • interferon or peginterferon
  • live vaccines such as measles, mumps, rubella, yellow fever, varicella, or zoster vaccines
  • methotrexate
  • opioids such as methadone
  • other biologics, such as adalimumab, anakinra, abatacept, golimumab, or infliximab
  • sulfasalazine
  • steroids such as betamethasone and dexamethasone
  • thalidomide
  • theophylline
  • warfarin.

People with significant exposure to the varicella virus should temporarily discontinue Enbrel and be considered for prophylactic treatment with varicella zoster immune globulin.

May be taken with antibiotics if a doctor has prescribed them for people with a current bacterial infection. However, if a person develops a serious infection or sepsis, a doctor may choose to stop Enbrel, either temporarily or permanently, while the person is receiving treatment for the infection.

Note that this list is not all-inclusive and includes only common medications that may interact with Enbrel. You should refer to the prescribing information for Enbrel for a complete list of interactions.


Further information

Remember, keep this and all other medicines out of the reach of children, never share your medicines with others, and use Enbrel only for the indication prescribed.

Always consult your healthcare provider to ensure the information displayed on this page applies to your personal circumstances.

Copyright 1996-2022 Revision date: March 18, 2022.