What to Know About Enbrel (Etanercept)

The first TNF blocker approved for rheumatoid arthritis

Enbrel (etanercept) is a biologic drug derived from living cells. It is used to treat rheumatoid arthritis, ankylosing spondylitis, and other types of rheumatic disease that cause pain, stiffness, and inflammation.

Enbrel is classified as a TNF blocker, meaning that it suppresses immune system activity by blocking the activity of a cytokine protein in the body called tumor necrosis factor alpha (TNF-alpha). Excess TNF is closely associated with rheumatic disease.

When TNF is activated, it binds to cell receptors in tissues all over the body and triggers systemic inflammation. Enbrel alleviates rheumatic symptoms by blocking TNF production so that it cannot perform this action.

Although Enbrel is a highly effective medication for many people, it does come with considerable risk. This article covers the uses and benefits of Enbrel along with the risks you should know about before you take it.


Enbrel is approved by the Food and Drug Administration (FDA) to treat:

Off-Label Uses

Enbrel may be prescribed off-label for numerous conditions, including:

  • Juvenile forms of arthritis such as of psoriatic arthritis and ankylosing spondylitis
  • Inflammatory conditions such as Behçet’s disease and pyoderma gangrenosum
  • Autoimmune conditions such as Crohn’s disease

Before Taking

Before you start taking any medication, you should discuss with your healthcare provider your medical and family history, any current conditions you may have, and any drugs or supplements you’re taking.

Precautions and Contraindications

Enbrel is not recommended for:

  • People with serious infections when starting the drug
  • People prone to infection due to illnesses that weaken the immune system, such as uncontrolled diabetes

Enbrel may trigger or worsen neurological problems in some people. Healthcare providers use caution when prescribing Enbrel to people with the following nervous system disorders:

Enbrel also isn’t recommended for people with moderate to severe alcoholic hepatitis due to an increased risk of death after six months of use.

Pregnancy and Lactation

According to the FDA, there’s no statistically significant increase in the risk of birth defects in babies born to women taking Enbrel and no pattern of birth defects associated with it.

A European study comparing outcomes in nine countries found a 5% increase in premature birth when a mother used TNF inhibitors as well as a significant increase in the risk of low birth weight.

A 2015 review of systemic drugs’ impact on fertility, pregnancy, and lactation found evidence that Enbrel has no negative impact on fertility in men or women; that it appears to cross the placenta in lower amounts than the TNF inhibitors Humira (adalimumab) and Remicade (infliximab); and that its levels in breast milk appear to be insignificant and not bio-available to healthy, full-term infants.

It’s unknown whether it’s safe to give live or live-attenuated vaccines to babies exposed to Enbrel in the uterus.

While the risk of birth defects and other problems due to Enbrel appears low, if you are pregnant and considering taking this drug, be sure to discuss your baby’s health and the drug’s potential impact with your health care team.

Other TNF Inhibitors

Enbrel was the second TNF-inhibiting drug approved by the FDA, shortly after Remicade in 1998. Then came Humira, Simponi (golimumab), and Cimzia (certolizumab pegol) in the following decade.

For Enbrel and Remicade, scientists combine human and rodent DNA to produce what are called monoclonal antibodies, which are human-made, cloned antibodies (cells that fight infection.) Humira, Simponi, and Cimzia are made from fully human proteins that produce monoclonal antibodies.


Enbrel is given by injection under the skin, which you (or a friend or family member) can do at home. It’s available in pre-filled syringes, an auto-injector pen, or vials that you use to fill syringes.

Indication Dosage
Ankylosing spondylitis (adults) 50 milligrams (mg) per week
Juvenile idiopathic arthritis (children) Based on weight; maximum of 50 mg per week
Juvenile plaque psoriasis (children) Based on weight; maximum of 50 mg per week
Plaque psoriasis (adults) 50 mg twice a week for 3 months, then stepped down to once weekly
Psoriatic arthritis (adults) 50 mg per week
Rheumatoid arthritis (adults)

50 mg per week

Enbrel can be used in combination with methotrexate in patients who do not respond to methotrexate alone. The Enbrel dosage is typically the same regardless of whether it's taken alongside another drug.

How to Take and Store

Enbrel should be stored at a temperature of between 36 and 46, but you should allow it to naturally warm up to room temperature before injecting it. (Don’t try to heat it fast. Just take it out of the refrigerator and let it sit out.)

Enbrel can be kept at room temperature for up to 14 days, if needed. It should never be stored in the freezer.

According to the manufacturer, if you’re traveling with your medication for more than a few hours, you should wrap Enbrel in bubble wrap and place it in a travel cooler packed with ice. Add a thermometer to the cooler and check it every few hours to make sure it’s staying in the correct temperature range.

You can obtain a free travel bag for Enbrel by calling the Enbrel Support line at 1-888-4ENBREL or visiting them online. If you’re traveling by airplane, check with the airline for their rules and guidelines about transporting temperature-sensitive medication.

Laura Porter / Verywell

Side Effects

All drugs come with a risk of side effects. Not everyone experiences them, but if you do, talk to your healthcare provider about them. Some side effects may go away with continued medication use, but others may be a signal that you need to stop taking the drug.


Common side effects associated with Enbrel include:

These generally don’t require medical attention. If any side effects become severe or persist for a long time, call your healthcare provider.


Enbrel is associated with some serious adverse reactions, including:

  • New-onset multiple sclerosis or other demyelinating diseases
  • New-onset seizure disorders
  • Myelitis (inflammation of spinal cord)
  • Optic neuritis (inflammation of optic nerve)
  • Pancytopenia (low numbers of red blood cells, white blood cells, and platelets)

Risk of Infections

This drug carries a black box warning, the FDA’s most serious type of warning, about the increased risk of serious infections, including tuberculosis. If you develop an infection while taking Enbrel, contact your healthcare provider before taking another dose. You may need to stop taking Enbrel, have special monitoring to ensure the infection doesn’t become serious, or both.

Warnings and Interactions

In studies, Enbrel has been associated with a higher incidence of certain serious diseases, including some forms of cancer. These include:

An allergic reaction is possible with Enbrel. If you have symptoms including throat closure and difficulty breathing (anaphylactic shock), get emergency medical help immediately.

If you have a latex allergy, be sure to alert your healthcare provider and pharmacist, as components of needles or auto-injectors may contain natural rubber, which is derived from latex.


You shouldn’t get live vaccines while taking Enbrel. If your child has been prescribed this drug, you should bring them up-to-date on vaccinations before they start it, if possible. Be sure you discuss this with your pediatrician.

Drug Interactions

Enbrel may interact negatively with certain medications. This drug should not be combined with other immunosuppressive biologic drugs aside from Azulfidine (sulfasalazine), which is one exception to this guideline.

Make sure your healthcare provider knows all of the drugs you’re taking, including over-the-counter medications and dietary supplements, so they can watch for any potential problems. Your pharmacist is also a valuable resource for ensuring your mix of treatments is safe.


A Word From Verywell

5 Sources
Verywell Health uses only high-quality sources, including peer-reviewed studies, to support the facts within our articles. Read our editorial process to learn more about how we fact-check and keep our content accurate, reliable, and trustworthy.
  1. National Library of Medicine: DailyMed. Enbrel—etanercept solution [drug label].

  2. Tirado-Sánchezab A, de la Fuente-Garcíaa V, Ponce-Oliveraa RM. Off-label uses of etanercept in dermatology. Rev Méd del Hospital Gen de Méx. 2016;79(1):26-32. doi:10.1016/j.hgmx.2015.10.005

  3. Immunex Corporation. Starting Enbrel: what to expect.

  4. Weber-Schoendorfer C, Oppermann M, Wacker E, et al. Pregnancy outcome after TNF-α inhibitor therapy during the first trimester: a prospective multicentre cohort studyBr J Clin Pharmacol. 2015;80(4):727-739. doi:10.1111/bcp.12642

  5. Grunewald S, Jank A. New systemic agents in dermatology with respect to fertility, pregnancy, and lactationJ Dtsch Dermatol Ges. 2015;13(4):277-290. doi:10.1111/ddg.12596

By Carol Eustice
Carol Eustice is a writer covering arthritis and chronic illness, who herself has been diagnosed with both rheumatoid arthritis and osteoarthritis.