Usage
Etanercept is prescribed for the treatment of:
- Rheumatoid Arthritis (RA): A chronic inflammatory disorder affecting joints.
- Juvenile Idiopathic Arthritis (JIA): A chronic inflammatory joint disease affecting children.
- Psoriatic Arthritis (PsA): A type of arthritis associated with psoriasis.
- Ankylosing Spondylitis (AS): A type of arthritis that primarily affects the spine.
- Non-Radiographic Axial Spondyloarthritis (nr-axSpA): Inflammatory back pain with no radiographic evidence of AS.
- Plaque Psoriasis: A chronic skin condition characterized by red, raised, scaly patches.
- Paediatric Plaque Psoriasis: Plaque psoriasis in children.
Pharmacological Classification: Tumor Necrosis Factor (TNF) inhibitor, Disease-modifying antirheumatic drug (DMARD), Biologic.
Mechanism of Action: Etanercept works by binding to TNF-alpha, a cytokine involved in inflammatory processes. By neutralizing TNF-alpha, etanercept reduces inflammation and thus alleviates symptoms of the aforementioned conditions.
Alternate Names
International Nonproprietary Name (INN): Etanercept
Brand Names: Enbrel
How It Works
Pharmacodynamics: Etanercept binds specifically to TNF-alpha, preventing it from interacting with its cell surface receptors. This inhibits TNF-alpha mediated cellular responses, leading to a decrease in inflammation.
Pharmacokinetics:
- Absorption: Administered subcutaneously; bioavailability is approximately 76%.
- Metabolism: Not extensively metabolized.
- Elimination: Primarily eliminated through slow clearance with a terminal half-life of approximately 70 hours. It appears that the drug is eliminated through a combination of processes, including intracellular catabolism and extracellular degradation.
Mode of Action: Binds to TNF-alpha, inhibiting its interaction with p55 and p75 cell surface TNF receptors. This prevents TNF-alpha-mediated cellular responses, leading to decreased inflammation and immune modulation.
Receptor Binding: Binds to soluble and transmembrane forms of TNF-alpha.
Elimination Pathways: Primarily involves proteolytic degradation in serum and intracellular catabolism. Renal and hepatic elimination is minimal.
Dosage
Standard Dosage
Adults:
- RA, PsA, AS, nr-axSpA: 50 mg subcutaneously once weekly or 25 mg subcutaneously twice weekly (3-4 days apart).
- Plaque Psoriasis: 50 mg subcutaneously twice weekly for 12 weeks, then 50 mg once weekly or 25 mg twice weekly. An alternative dosing is 50mg or 25mg once weekly, depending on efficacy of initial treatment.
Children:
- JIA (≥2 years): 0.4 mg/kg (up to a maximum of 25 mg per dose) subcutaneously twice weekly (3-4 days apart) or 0.8 mg/kg (up to a maximum of 50 mg per dose) subcutaneously once weekly.
- Paediatric Plaque Psoriasis (≥4 years): 0.8 mg/kg (up to a maximum of 50 mg per dose) subcutaneously once weekly.
Special Cases:
- Elderly Patients: No dose adjustment required.
- Patients with Renal Impairment: No dose adjustment required.
- Patients with Hepatic Dysfunction: No dose adjustment required.
- Patients with Comorbid Conditions: Dose adjustments may be needed depending on the specific comorbidity.
Clinical Use Cases
Etanercept is not typically used in acute clinical settings like intubation, surgical procedures, mechanical ventilation, ICU use, or emergency situations. It is a long-term treatment for chronic inflammatory conditions.
Dosage Adjustments
No specific dosage adjustments are required based on renal or hepatic function. Dosage modifications may be necessary in patients with certain comorbidities or in case of adverse events.
Side Effects
Common Side Effects
- Injection site reactions (pain, redness, swelling)
- Upper respiratory infections
- Headaches
- Nausea
Rare but Serious Side Effects
- Serious infections (e.g., tuberculosis, sepsis)
- Malignancies (e.g., lymphoma)
- Demiselization
- Heart failure
- Liver dysfunction
- Blood disorders (e.g., pancytopenia)
- Allergic reactions
Long-Term Effects
- Increased risk of infections
- Possible increased risk of certain cancers with long-term use
Adverse Drug Reactions (ADR)
- Hypersensitivity reactions (including anaphylaxis)
- Drug-induced lupus-like syndrome
- Stevens-Johnson syndrome
Contraindications
- Active serious infections (e.g., sepsis, tuberculosis).
- Known hypersensitivity to etanercept or any of its components.
- Patients with demyelinating disorders, such as Multiple Sclerosis.
- Caution in patients with congestive heart failure.
Drug Interactions
- Live vaccines (avoid concomitant use).
- Other immunosuppressants (increased risk of infection).
- Anakinra or Abatacept (increased risk of serious infections without increased efficacy).
- Theophylline (monitor levels).
- Sulfonylureas (monitor blood glucose levels).
- Warfarin (monitor INR levels).
- Methotrexate can be used concurrently with etanercept. Other DMARDs like sulfasalazine, hydroxychloroquine, and leflunomide can also be used.
Pregnancy and Breastfeeding
- Pregnancy Safety Category: B (Animal reproduction studies have failed to demonstrate a risk to the fetus, and there are no adequate and well-controlled studies in pregnant women.)
- Caution advised during pregnancy; use only if clearly needed.
- Etanercept is present in human milk. Women using etanercept should discuss risks and benefits with their physicians.
Drug Profile Summary
- Mechanism of Action: TNF-alpha inhibitor.
- Side Effects: Injection site reactions, infections, headache, nausea. Serious side effects include serious infections, malignancies, and allergic reactions.
- Contraindications: Active serious infections, hypersensitivity, demyelinating disorders.
- Drug Interactions: Live vaccines, other immunosuppressants, Anakinra, Abatacept.
- Pregnancy & Breastfeeding: Use with caution if clearly needed. Present in human milk.
- Dosage: Adults: 50 mg once weekly or 25 mg twice weekly. Children: Dose based on weight, see pediatric guidelines.
- Monitoring Parameters: Monitor for infections, signs of malignancy, liver function tests, complete blood count. Assess clinical response to treatment.
Popular Combinations
- Methotrexate: Commonly used in combination with etanercept for RA, PsA, and JIA.
Precautions
- Screen for latent tuberculosis before initiating therapy.
- Monitor for infections during treatment.
- Caution in patients with heart failure.
- Evaluate for malignancies.
FAQs (Frequently Asked Questions)
Q1: What is the recommended dosage for Etanercept?
A: Adults: 50 mg subcutaneously once weekly or 25 mg twice weekly. Children: 0.4 mg/kg (up to 25mg) twice weekly, or 0.8 mg/kg (up to 50 mg) once weekly, depending on the indication.
Q2: How is Etanercept administered?
A: Subcutaneously.
Q3: What are the most common side effects?
A: Injection site reactions, infections, headaches.
Q4: Can Etanercept be used during pregnancy?
A: Use with caution; only if the benefit clearly outweighs the risk. Discuss risks and benefits with the physician.
Q5: What should be monitored before initiating Etanercept?
A: Latent tuberculosis infection.
Q6: Can Etanercept be used with other DMARDs?
A: Yes, it is frequently combined with Methotrexate. Other DMARDS are also occasionally used in combination with etanercept. Concurrent use with Anakinra or Abatacept is not recommended.
Q7: What are the serious side effects of Etanercept?
A: Serious infections (e.g., tuberculosis, sepsis), malignancies, heart failure, and allergic reactions.
Q8: How long does it take for Etanercept to work?
A: Clinical response is usually seen within 12 weeks of treatment.
Q9: What should a patient do if they miss a dose of Etanercept?
A: Administer the missed dose as soon as remembered, unless it is close to the time for the next dose. Do not double the dose.
Q10: Can Etanercept cure rheumatoid arthritis?
A: Etanercept does not cure RA, but it can significantly reduce inflammation, relieve symptoms, and slow the progression of joint damage.
