7 Enbrel Side Effects You Should Know About

Autoimmune disorders happen when your immune system is overactive and attacks your body. Over 20 million people in the U.S. live with these disorders. They can cause intense inflammation and pain that may come and go over time.

If you’re living with an autoimmune disorder, your healthcare provider may have recommended the medication Enbrel (etanercept). It blocks tumor necrosis factor — a type of protein in your body that causes inflammation. This helps reduce the pain and swelling from autoimmune conditions like rheumatoid arthritis, psoriatic arthritis, or ankylosing spondylitis.

Enbrel is usually well tolerated, but it still has a few side effects you should be aware of. Here, we’ll discuss seven side effects of Enbrel and how to manage them.

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1. Injection site reactions

Enbrel is injected under your skin once or twice a week, depending on what you’re using it for. Because of this, injection site reactions are common, especially in the first months of taking it. These reactions appear in the area where the injection is given. As you continue to use Enbrel, you should notice a decrease in these reactions.

Symptoms of an injection site reaction may include:

• Redness

• Pain

• Bleeding

• Bruising

• Itchiness

• Swelling

These reactions are usually mild and will go away on their own in 3 to 5 days. There are also some steps you can take to help ease the discomfort:

• Rotate injection sites. Changing where you inject Enbrel each time can help reduce the chance of injection site reactions.

• Take pain relievers. Over-the-counter (OTC) medications like acetaminophen (Tylenol) or ibuprofen (Motrin, Advil) may help with pain, swelling, and redness. Check with your healthcare provider or pharmacist to make sure they’re safe for you to take.

• Use a cold compress. Applying a cold compress like an ice pack can help relieve swelling and redness, too. You can also apply it for a few minutes before your injection to numb the skin. Make sure to wrap your cold compress in a towel before putting it on your skin. And don’t leave it on for more than 10 minutes at a time. This can help prevent damage to your skin.

If injection site reactions continue or are bothersome, talk to your healthcare provider. They can help make sure you’re injecting Enbrel correctly. But if the pain, swelling, or redness around the injection site doesn’t go away or worsens, seek medical care right away. This could be the sign of an infection.

2. Infections

Enbrel lowers your body’s ability to fight off infections. Because of this, infections are a common side effect of taking it. Rarely, this may include serious or life-threatening infections like sepsis.

Upper respiratory infections are the most common with Enbrel. These include sinus infections or the common cold. If you get an upper respiratory infection, your best bet is to stay hydrated and get plenty of rest. You can also try OTC medications to help with your symptoms if your healthcare provider says it’s OK.

Serious infections aren’t as common while taking Enbrel. But there is still a risk of developing them. You may be more at risk of developing a serious infection if you take additional immunosuppressant medications, like corticosteroids or methotrexate. Your risk also goes up if you’re over the age of 65 or have other chronic health conditions.

Signs of a serious infection include:

• Fever

• Flu-like symptoms

• Muscle aches and pains

• Diarrhea with or without stomach pain

• Night sweats

• Trouble breathing

• Urinating (peeing) more often or burning while urinating

Call your healthcare provider if you have any of these symptoms. Depending on your symptoms, your healthcare provider may ask you to temporarily stop taking your Enbrel doses. This will allow your body to fight the infection.

Enbrel can sometimes reactivate previous infections of tuberculosis or hepatitis B. Because of this, your healthcare provider will likely screen for these before starting Enbrel therapy.

3. Diarrhea

You may have diarrhea while taking Enbrel. But it should improve as your body adjusts to the medication. In the meantime, be sure to drink plenty of fluids, stick to bland foods, or try OTC anti-diarrhea medications like loperamide (Imodium A-D).

While diarrhea is usually not dangerous, it can be a sign of a more serious health condition. Call your healthcare provider if your diarrhea worsens or doesn’t go away. And seek medical care right away if you have severe stomach pain, a high fever, or stools that appear black or tarry. These could be signs of a more severe issue.

4. Heart failure

Heart failure is when your heart doesn’t work well enough to keep up with your body’s demand for oxygen-rich blood. Enbrel can cause or worsen heart failure in people who take it. Symptoms to watch out for include:

• Shortness of breath

• Fatigue or weakness, even after resting

• Coughing

• Swelling in your legs and ankles

• Rapid weight gain

• Difficulty breathing when lying flat

If you develop any of these symptoms, get medical care right away. Heart failure can be fatal if left untreated.

5. Low blood cell counts

Enbrel can lower the number of certain types of blood cells in your body. This reduces your body’s ability to fight infections and also puts you at risk for bleeding. While this is a rare side effect, it’s a serious one.

Your healthcare provider will likely monitor for this while you’re taking Enbrel. But if you notice increased bruising, signs of bleeding, or have a fever that won’t go away, contact them right away.

6. Cancer

You have a higher risk of developing certain types of cancers while taking Enbrel. Lymphoma and skin cancers seem to be the most common. This is a rare side effect. Children, people with rheumatoid arthritis, or those taking other immunosuppressant medications along with Enbrel have the greatest risk.

While on Enbrel, get periodic skin exams to help detect skin cancer. Report any symptoms, such as unexplained weight loss, night sweats, or weakness that won’t go away, to your healthcare provider.

7. Nerve damage

Although extremely rare (< 0.1% in clinical trials), Enbrel can cause the protective layer (myelin) around your nerves to disappear. When this occurs, nerve signals can slow down or stop. If this happens, symptoms like vision changes, muscle weakness, and changes in behavior or thinking can occur. If you notice any of these symptoms, seek medical care right away.

Enbrel can also worsen nervous system disorders you may already have, like multiple sclerosis or Guillain-Barre syndrome. If you already have a nervous system disorder and have concerns about taking Enbrel, be sure to talk to your healthcare provider.

When should I contact my healthcare provider about Enbrel side effects?

As your body adjusts to Enbrel, many common side effects generally get better over time. But if they worsen or continue to be bothersome, reach out to your healthcare provider.

If you notice symptoms of your autoimmune disorder return or worsen while taking Enbrel, let your healthcare provider know. You may need a different dose, or Enbrel may not be the right medication for you.

You should seek medical care right away if you have a fever, difficulty breathing, or notice blood in your urine or stool. These could be signs of more serious side effects.

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Written by:

Emilie White, PharmD

Emilie White is a clinical pharmacist with over a decade of hospital pharmacy experience. Her professional areas of interest include critical care as well as infectious and autoimmune diseases.

Edited by:

Stacia Woodcock, PharmD

Stacia Woodcock, PharmD, is a pharmacy editor for GoodRx. She earned her Doctor of Pharmacy degree from the University of Kentucky and is licensed in New York and Massachusetts.

Reviewed by:

Christina Aungst, PharmD

Christina Aungst, PharmD, is a pharmacy editor for GoodRx. She began writing for GoodRx Health in 2019, transitioning from freelance writer to editor in 2021.

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