Etanercept - Uses, Dosage, Side Effects, and Drug Warnings

Overview:

Etanercept is an approved drug for the treatment of rheumatoid arthritis. It is the first anti-tumor necrosis factor agent that reduces the symptoms of rheumatoid arthritis and slows down the progression of radiographic damage. Etanercept helps boost the patient's functioning, thereby improving the quality of life.

Various clinical trials have been performed over the past decade to establish the efficacy and safety of this drug for early rheumatoid arthritis. Etanercept can be used alone or in combination with Methotrexate. Apart from rheumatoid arthritis, Etanercept can be used to treat psoriatic arthritis.

Indications:

• Rheumatoid arthritis, a disorder where the body attacks its own joints and leads to loss of function, pain, and swelling.

Other indications include:

• Psoriatic arthritis (joint pain with swelling and scales on the skin) in adults.

• Juvenile idiopathic arthritis affects children where the body attacks its own joints and delays growth and development in children two years or older.

• Ankylosing spondylitis (the body attacks its own joints leading to pain and damage to the spine).

• Chronic plaque psoriasis (a disease affecting the skin that leads to red, scaly patches on certain body parts in adults and children above four years).

Warnings:

Etanercept may affect the patient's immunity by decreasing the ability to fight infections leading to severe viral, bacterial, or fungal disease. The doctor must be informed about these infections ranging from minor to major chronic infections that do not resolve independently. These infections may require hospitalization and can be fatal. The patient must inform the doctor if they have diabetes, an acquired immunodeficiency syndrome (AIDS), any other disorder that alters their immunity, or any medication they are taking.

If the patient has tuberculosis (TB) and hepatitis B without any symptoms, Etanercept administration may increase the risk of developing severe symptoms. In this condition, the doctor might treat the infection first and then begin the administration of Etanercept. The doctor must be informed immediately about the symptoms of hepatitis B or other symptoms like:

• Excessive tiredness.

• Yellowing of the skin or eyes.

• Loss of appetite.

• Nausea or vomiting.

• Muscle aches.

• Dark urine.

• Clay-colored bowel movements.

• Fever.

• Chills.

• Stomach pain.

• Rash.

Other symptoms that require immediate medical attention include:

• Weakness.

• Sweating.

• Difficulty breathing.

• Stomach pain.

• Flu-like symptoms.

• Sore throat.

• Cough.

• Extreme tiredness.

• Diarrhea.

• Coughing up bloody mucus.

• Fever.

• Weight loss.

• Red, Warm, or painful skin.

Some children and teenagers taking Etanercept injections and similar drugs developed life-threatening cancers like lymphoma. The doctor must be intimated if any of the following symptoms develop in children:

• Unexplained weight loss.

• Swollen glands in the neck.

• Underarms or groin.

• Easy bruising or bleeding.

For Patients:

Why Is Etanercept Prescribed?

Etanercept is prescribed alone or with other drugs to manage the symptoms of certain autoimmune disorders (disorders where the immune system attacks healthy parts of the body, causing pain, swelling, and damage). It is used majorly for treating rheumatoid arthritis, a disorder where the body attacks its own joints and leads to loss of function, pain, and swelling.

Other indications include:

• Psoriatic arthritis (joint pain with swelling and scales on the skin) in adults.

• Juvenile idiopathic arthritis affects children where the body attacks its own joints and delays growth and development in children two years or older.

• Ankylosing spondylitis (the body attacks its own joints leading to pain and damage to the spine).

• Chronic plaque psoriasis (a disease affecting the skin that leads to red, scaly patches on certain body parts in adults and children above four years).

Etanercept belongs to tumor necrosis factor (TNF) inhibitors drugs, and it acts by blocking the action of TNF, a substance that produces inflammation in the body.

How to Use Etanercept?

Etanercept is available in the form of

• Injection solution or liquid in single-dose.

• Prefilled syringes.

• Dosing pens.

• Cartridges.

• Automatic injection devices.

Etanercept injection products are also available in powder form in a multi-dose vial that has to be mixed with the liquid provided.

• Etanercept has to be injected subcutaneously, usually once a week.

• For the treatment of chronic plaque psoriasis, Etanercept might be injected twice a week during the first three months and then once a week.

• The directions given by the doctor must be followed carefully, and the Etanercept injection must be administered exactly as directed by the doctor.

• The dose must not be increased or decreased without the doctor's consultation.

• The first dose of this medication is usually administered at the doctor’s clinic. Then further doses can be taken at home.

• The vials of Etanercept injection can be stored or refrigerated for 14 days after mixing if enough medication is available.

• Multi-dose vials of Etanercept injection products must be refrigerated as soon as possible and not after four hours of mixing.

• However, the contents of two Etanercept vials must not be mixed or combined to make a complete dose.

• If the drug is available in a single-dose dosing pen, cartridge, automatic injection device, prefilled syringe, or vial, they must be used only once, even if some solution is left.

• Before injecting the Etanercept injection that has been refrigerated, it must be kept for 15 to 30 minutes at room temperature. To warm the medication, it must never be heated in the microwave or hot water.

• Etanercept solution must be checked for expiry before injecting it, and cracked or broken injecting devices must not be used.

• The best area for injecting Etanercept is the front of the middle thighs. It can also be injected in the lower stomach below the navel, except the region two inches around the navel. If the drug is being injected by someone else, it can be administered in the upper arms. In the case of psoriasis, it must not be injected where the skin is scaly, raised, or thick.

• Etanercept injection helps to treat the condition but does not cure the condition completely.

• The medication must be continued even if the patient feels well and never be discontinued without consulting the doctor.

What Special Precautions Must Be Followed?

Allergies: The patient should inform the doctor about allergies to Etanercept, other medications, or any ingredient in Etanercept injections or concentration. The patient should ask about the ingredients present in the medication.

Drug History: The doctor should be provided with a list of prescribed or non-prescribed drugs that the patient is taking, including vitamins and natural or herbal supplements.

Medical History: The patient should tell the doctor about any past illness or any comorbidities like:

• Diabetes.

• Seizures.

• Transverse myelitis (spinal cord inflammation that may lead to inability to move the lower body, abnormal sensations, or loss of sensation).

• Any disorder involving the nervous system, like multiple sclerosis (numbness due to nerve damage, loss of coordination, and weakness).

• Liver disease.

• Heart failure.

• Guillain-Barré syndrome (weakness, tingling, and paralysis due to sudden nerve damage).

• Optic neuritis (nerve inflammation that sends messages from the eye to the brain).

• Bleeding problems.

• The patient must inform the doctor immediately if chickenpox is contracted while taking the Etanercept injection.

Pregnancy: The patient should tell the doctor about their pregnancy or if they are planning to conceive or are breastfeeding, as taking Etanercept injections during pregnancy may require a delay of vaccination in the newborn.

Surgery: The doctor must be informed about the medication before any surgery, including dental surgery.

What Special Dietary Instructions Should Be Followed?

A normal diet can be continued unless advised by the doctor otherwise.

What Should Be Done in Case of a Missed Dose?

The missed dose must be taken by the patient as soon as they remember. However, if it is almost time to take the next dose, the missed dose must not be taken, and the regular schedule should be continued. A double dose must not be administered to compensate for the missed dose.

Side Effects:

Etanercept injection products may lead to certain side effects. The doctor must be informed if the following symptoms appear at the site of injection:

• Redness.

• Itching.

• Pain.

• Swelling.

• Bleeding.

• Bruising.

Some serious side effects include:

• Seizures.

• Problems with vision.

• Swelling of the eyes, lips, face, tongue, or throat.

• Bruising.

• Bleeding.

• Rash.

• Hives.

• Pale skin.

• Red, scaly patches or pus-filled bumps on the skin.

• Itching.

• Difficulty breathing or swallowing.

• Shortness of breath.

• Numbness or tingling.

• Swelling of the feet, ankles, or lower legs.

• Rash on the face and arms that worsens in the sun.

• Weakness in the arms or legs.

• Vision problems.

• Dizziness.

Adults taking Etanercept injections are at greater risk of developing the following conditions:

• Leukemia (cancer affecting the white blood cells).

• Skin cancer.

• Lymphoma.

Etanercept injection may lead to other side effects as well.

Storage and Disposal of Etanercept:

• The container of Etanercept should be tightly closed and kept out of reach of children.

• Etanercept injections must be stored away from light.

• Etanercept injection must be stored in the refrigerator but not frozen.

• Etanercept should be refrigerated and not exposed to excessive moisture and heat.

• If Etanercept is no longer required, it should be disposed of properly so that pets and children do not consume the medications by mistake.

• If a vial of Etanercept powder is mixed with the provided liquid, it may be stored as a solution in the refrigerator for up to 14 days.

• The drug should not be frozen. If the patient is traveling, Etanercept can be stored at room temperature up to 77 degrees Fahrenheit for up to 14 days. Once Etanercept reaches room temperature, it cannot be refrigerated and used again.

Other Important Information:

• The patient must continue to visit the rheumatologist regularly to evaluate the improvement in the condition and signs of infection.

• Malignancies like lymphomas can be fatal and have been documented in children and teenagers where tumor necrosis factor (TNF) blockers have been administered.

• The patient should not advise others to take this medication without consulting a doctor.

• The heart rate or pulse should be recorded routinely, and any variation must be reported to the doctor immediately.

• Maintaining a written list of all the prescribed and non-prescribed (over-the-counter) drugs that are being taken by the patient, including other supplements like vitamins or minerals. The patient should carry this list for every visit to a doctor or a hospital. It is extremely important in case of emergencies.

For Doctors:

Etanercept is a biologic TNF inhibiting agent frequently used to manage rheumatoid arthritis, ankylosing spondylitis, plaque psoriasis, psoriatic arthritis, and juvenile idiopathic arthritis. Etanercept is a receptor that inhibits the inflammatory response in joints and skin characteristic of these autoimmune disorders by binding to TNF-alpha and TNF-beta. The drug can be administered with other immunosuppressants like Methotrexate and as a monotherapy (administered alone). Doctors can use Etanercept for approved and off-label indications.

Indications

FDA-Approved Indications

• Rheumatoid arthritis.

• Ankylosing spondylitis.

• Juvenile idiopathic arthritis in children two years or older.

• Plaque psoriasis in patients four years or older.

• Psoriatic arthritis.

Non-FDA Approved Indications

• Behcet disease.

• Acute graft-versus-host disease (combined with Methylprednisolone).

• Hidradenitis suppurativa.

• Pemphigus vulgaris.

• Pustular psoriasis.

• Kawasaki disease.

• Pyoderma gangrenosum.

• Scleroderma or systemic sclerosis.

Mechanism of Action:

Etanercept is a biological tumor necrosis factor (TNF) inhibiting agent. The drug is a Tumor necrosis factor (TNF) soluble receptor. Moreover, it also binds to TNF-alpha and TNF-beta. Etanercept acts by blocking the effects of TNF-alpha, a pro-inflammatory cytokine that increases in rheumatoid arthritis, psoriatic arthritis, psoriasis, juvenile idiopathic arthritis and ankylosing spondylitis.

TNF is a cytokine involved in inflammation and the immune response that binds to TNF receptor 1 (TNFR1) or TNF receptor 2 (TNFR2). Tumor necrosis factor activates essential inflammatory pathways and binds to TNFR1 or TNFR2.

Administration

For Rheumatoid Arthritis, Psoriatic Arthritis, and Ankylosing Spondylitis:

• 50 milligram is injected once a week.

• 25 milligram, an alternative dose, is administered subcutaneously twice weekly, with 72 to 96 hours intervals between the injections.

For Psoriasis:

• 50 milligram dose twice weekly for three months, followed by 50 milligram once a week.

For Children with Juvenile Idiopathic Arthritis:

• The dosage of 0.8 milligram per kg once a week, up to 50 milligram.

• Etanercept is administered through subcutaneous injection, usually on the thigh, upper arm, and lower abdomen.

• The injection must not be administered within the two-inch region around the navel. Injections must be administered around one inch away from previous injection sites. The medication comes in an automatic injection device, pre-filled syringe, or multiple-dose vial.

• After the initial Etanercept injection at the doctor’s clinic, the patients can inject it themselves, at home after proper training.

Contraindications

Etanercept is contraindicated in patients with:

• Sepsis.

• Hypersensitive reaction to the medication ingredients.

• Herpes zoster infection.

• Active bacterial infections, including active or latent tuberculosis.

• Untreated Hepatitis B or C infection.

• Active invasive fungal infections.

Adverse Effects:

Common Adverse Effects Include:

• Injection site reactions include erythema, itching, swelling, pain, bleeding, and bruising.

• Infection of upper respiratory tract infections, including viral, bacterial, and fungal infections.

Rare Adverse Effects Include:

• Blood and Lymph Disorders: Aplastic anemia, leukopenia, neutropenia, pancytopenia, thrombocytopenia.

• Infections: Reactivation of hepatitis B or tuberculosis, aspergillosis, coccidioidomycosis, Cryptococcus, herpes zoster, candidiasis, histoplasmosis, Legionella pneumonia, listeriosis, Pneumocystis pneumonia, nocardiosis, Salmonella infection, and septic arthritis.

• Stomach and Liver Problems: Autoimmune hepatitis, elevated transaminases, diarrhea, nausea, and inflammatory bowel disease.

• Cancers: Skin cancers and lymphoma.

• Cardiopulmonary Problems: Interstitial lung disease and congestive heart failure.

• Immune and Inflammatory Conditions: Angioedema, lupus-like syndrome, hypersensitivity reaction, pyrexia, sarcoidosis, uveitis, and vasculitis.

• Nervous System Disorders: Multiple sclerosis, headache, paresthesias, optic neuritis, seizures, and transverse myelitis.

Warnings and Precautions:

1. Malignancies: Malignancies have been reported in patients taking Etanercept, particularly adolescents and children. The most frequently occurring cancers include lymphomas and melanoma, followed by other skin cancers. The exact relation between malignancies and Etanercept has not been understood yet. The clinical trials and other data indicate an increased incidence of malignancies in patients taking Etanercept as compared to the normal population. However, it must be noted that rheumatoid arthritis alone correlates with increased lymphoma and leukemia rates.

2. Infections: Patients taking Etanercept are at an increased risk of developing severe and deadly infections, like reactivation of latent tuberculosis or developing active tuberculosis. Infections were more frequent in patients receiving adjunct immunosuppressive drugs, like Methotrexate or corticosteroids. There are cases of viral, bacterial, and fungal infections, including opportunistic infections. Doctors must advise antifungal therapy for patients living or traveling to areas endemic to invasive fungal infections. Doctors must be cautious while prescribing Etanercept, including immunocompromised patients, elderly patients, those exposed to endemic mycoses or tuberculosis, and patients with a history of opportunistic infections.

Monitoring:

• Before initiating Etanercept, patients must be screened for any infections, especially latent tuberculosis or hepatitis B. Patients on Etanercept have to be monitored for symptoms of infection and reactivation of tuberculosis and hepatitis B.

• Patients with a history of heart failure must also be monitored during Etanercept treatment.

• The treatment must be discontinued if a severe infection or sepsis occurs during Etanercept treatment.

• Patients should also be monitored for symptoms of hypersensitivity reactions, lupus-like syndrome, or malignancy.

Toxicity:

No dose-limiting toxicities have been observed during clinical trials, in vivo, and in vitro studies. The long-term toxicity of Etanercept treatment is still unknown.

Involvement of Healthcare Professionals:

The doctors must weigh the risks and benefits of prescribing Etanercept as a treatment, including drug cost, method of administration, effectiveness, and adverse effects. Etanercept is one of the options for treating rheumatoid arthritis, plaque psoriasis, ankylosing spondylitis, juvenile idiopathic arthritis, and psoriatic arthritis. Etanercept usage has serious side effects such as malignancies, infections, and autoimmune conditions as it acts biologically.

To provide the best healthcare facilities, an interprofessional team approach must properly diagnose, manage and treat patients with mental disorders. The interprofessional team approach includes clinicians, nurses, mid-level practitioners, therapists, pharmacists, and patients. This team helps the patients understand their illness and encourages them to take the treatment.

Before initiating the treatment, the doctors must know the guidelines regarding Etanercept, like monitoring the patient for signs of heart failure, hepatitis B, tuberculosis, and other infections. Clinicians must give the patients proper instructions to the patients regarding injecting the medicine at home. Clinicians and pharmacists must inform the patient about drug interactions and possible adverse effects.