What to Know About Enbrel (Etanercept)

Enbrel (etanercept) is classified as a biologic response modifier and often referred to as a TNF-inhibitor (TNF-blocker). This drug is genetically engineered from living cells to be similar to receptors in your body that bind to a protein called tumor necrosis factor alpha (TNF-alpha), a cytokine involved in systemic inflammation. Excess TNF-alpha has been associated with rheumatoid arthritis (RA) and other forms of inflammatory arthritis. Enbrel works by 'soaking up' excess TNF-alpha before it can attach to your receptors.

Enbrel is a drug that you inject yourself with at home. It's only on the market under this one brand name and no generic forms are available.

Uses

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

• Rheumatoid arthritis
• Juvenile idiopathic arthritis
• Psoriatic arthritis
• Ankylosing spondylitis
• Plaque psoriasis (adult and pediatric)

Off-Label Uses

Enbrel is used off-label (without FDA approval) 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
• Vascular conditions such as Churg-Strauss vasculitis and giant cell arteritis
• Autoimmune conditions such as Crohn's disease, dermatomyositis, and antiphospholipid antibody syndrome

Before Taking

Before you start taking any medication, you should discuss certain things with your doctor, such as your medical and family history, any current conditions you may have, and any drugs 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 illness, such as uncontrolled diabetes

Doctors should use caution when prescribing Enbrel to people with certain conditions of the central or peripheral nervous system, including:

• Multiple sclerosis
• Transverse myelitis
• Optic neuritis
• Guillain-Barre syndromes

Enbrel also isn't recommended for people with:

• Wegener's granuloatosis who are taking another immunosuppressive drug due to an increased risk of malignancies
• Alcoholic hepatitis (moderate-to-severe) 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 breastmilk 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.

Other TNF-Inhibitors

Enbrel was the first TNF-inhibiting drug, gaining FDA approval in 1998. Remicade became the second in 1999. Then came Humira in 2002, and Simponi (golimumab) and Cimzia (certolizumab pegol) in 2009.

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.

Dosage

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.

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 degrees F, 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 cooler and ice pack for Enbrel by calling the Enbrel Support line at 1-888-4ENBREL. If you're traveling by airplane, check with the airline for their rules and guidelines about transporting temperature-sensitive medication.

Side Effects

All drugs come with a risk of side effects. Not everyone experiences them, but if you do, talk to your doctor 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

Common side effects associated with Enbrel include:

• Injection site reactions
• Upper respiratory infections, including sinus infections
• Headaches
• Dizziness
• Runny nose
• Throat irritation

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

Severe

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).

Warnings and Interactions

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

• Lymphoma
• Leukemia
• Skin cancer (both melanoma and non-melanoma)
• Worsening of and increased risk of death from pre-existing heart disease
• Pancytopenia (rare)
• Aplastic anemia (very rare)
• Hepatitis B reactivation
• New-onset autoimmune disease

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

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

Immunizations

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:

• Kineret (anakinra)
• Cytoxan (cyclophosphamide)
• Azulfidine (sulfasalazine)

Make sure your doctor 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.