1. Drugbank ID : DB00005 Half life : 102 +/- 30 hrs
Etanercept
Drugbank ID : DB00005
Half life : 102 +/- 30 hrs

2. Description : Indication : Pharmacodynamics :
Enbrel (etanercept) is a dimeric fusion protein consisting of the extracellular ligand-binding portion of the human 75 kilodalton (p75) tumor necrosis factor receptor (TNFR) linked to the Fc portion of human IgG1. The Fc component of etanercept contains the CH2 domain, the CH3 domain and hinge region, but not the CH1 domain of IgG1. Etanercept is produced by recombinant DNA technology in a Chinese hamster ovary (CHO) mammalian cell expression system. It consists of 934 amino acids and has an apparent molecular weight of approximately 150 kilodaltons
Indication :
For treatment of severe active rheumatoid arthritis in adults, severe juvenile idiopathic arthritis, ankylosing spondylitis, and severe plaque psoriasis.
Pharmacodynamics :
Tumor necrosis factor TNF is a naturally occurring cytokine that is involved in normal inflammatory and immune responses. Elevated levels of TNF are found in tissues and fluids of patients with rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis (AS), and plaque psoriasis. Etanercept binds specifically to tumor necrosis factor (TNF) and blocks its interaction with cell surface TNF receptors.

3. Mechanism of action : Clearance :
There are two distinct receptors for TNF (TNFRs), a 55 kilodalton protein (p55) and a 75 kilodalton protein (p75). The biological activity of TNF is dependent upon binding to either cell surface receptor (p75 or p55). Etanercept is a dimeric soluble form of the p75 TNF receptor that can bind to two TNF molecules, thereby effectively removing them from circulation.
Clearance :
* 160 +/- 80 mL/hr [RA patients]

4. Drug Interaction: Abatacept : avoid combination because of increased adverse effects of abatacept. Anakinra : avoid combination due to increased adverse effects of anakinra and increased risk of infections. Belimumab : avoid combination because of enhanced adverse effects of belimumab. Belimumab : avoid combination due to enhanced toxic effects of belimumab. Canakinumab : combination should be avoided because etanercept increase the toxic effects of canakinumab including neutropenia. Certolizumab pegol : avoid combination as certolizumab pegol toxic effects would be enhanced. Yclophosphamide : avoid combination due to enhanced adverse effects of cyclophosphasmide and increased risk of solid cancer development. Denosumab : monitor therapy as there may be an enhanced immunosuppressive effect. Infliximab : avoid combination because etanercept may increase immunosuppressive effects of infliximab. Leflunomide : consider modifying therapy due to enhanced adverse effects of leflunomide including hematologic toxicity. Natalizumab : avoid combination due to enhanced adverse effects of natalizumab and increased risk of infections. Pimecrolimus : avoid combination due to enhanced immunosuppressive effects. Rilonacept : results in increased immunosuppressive effects; increases the risk of infection. Roflumilast : due to enhanced immunosuppressive effects, therapy modification should be considered. Sipuleucel-t : monitor therapy because of reduced therapeutic effect of sipuleucel-t. Tacrolimus : avoid combination due to enhanced immunosuppressive effects tocilizumab : avoid combination due to enhanced immunosuppressive effects. Tofacitinib : etanercept increases the risk of added immunosuppression. It is recommended to avoid concurrent therapy. Trastuzumab : trastuzumab may increase the risk of neutropenia and anemia. Monitor closely for signs and symptoms of adverse events.

5. Targets : Affected organisms :
Tumor necrosis factor,Tumor necrosis factor receptor superfamily member 1B,High affinity immunoglobulin gamma Fc receptor I,Low affinity immunoglobulin gamma Fc region receptor III-A,Low affinity immunoglobulin gamma Fc region receptor II-a,Low affinity immunoglobulin gamma Fc region receptor II-b,Low affinity immunoglobulin gamma Fc region receptor II-c,Lymphotoxin-alpha,Low affinity immunoglobulin gamma Fc region receptor III-B,Complement C1s subcomponent,Complement C1r subcomponent,Complement C1q subcomponent subunit A,Complement C1q subcomponent subunit B,Complement C1q subcomponent subunit C
Affected organisms :
Humans and other mammals

6. Categories :
Immunosuppressive Agents
Patents :
Country Patent Number Approved Expires (estimated)
Canada
Canada
United States
United States
Sequence : LPAQVAFTPYAPEPGSTCRLREYYDQTAQMCCSKCSPGQHAKVFCTKTSDTVCDSCEDSTYTQLWNWVPECLSCGSRCSSDQVETQACTREQNRICTCRPGWYCALSKQEGCRLCAPLRKCRPGFGVARPGTETSDVVCKPCAPGTFSNTTSSTDICRPHQICNVVAIPGNASMDAVCTSTSPTRSMAPGAVHLPQPVSTRSQHTQPTPEPSTAPSTSFLLPMGPSPPAEGSTGDEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK

7. Brands : Enbrel
Company : Immunex Corp
Description : Enbrel (etanercept) is a dimeric fusion protein consisting of the extracellular ligand-binding portion of the human 75 kilodalton (p75) tumor necrosis factor receptor (TNFR) linked to the Fc portion of human IgG1. The Fc component of etanercept contains the CH2 domain, the CH3 domain and hinge region, but not the CH1 domain of IgG1. Etanercept is produced by recombinant DNA technology in a Chinese hamster ovary (CHO) mammalian cell expression system. It consists of 934 amino acids and has an apparent molecular weight of approximately 150 kilodaltons
Used for/Prescribed for : used to treat the symptoms of rheumatoid arthritis, psoriatic arthritis, or ankylosing spondylitis, and to prevent joint damage caused by these conditions. Enbrel is also used to treat plaque psoriasis in adults and polyarticular juvenile idiopathic arthritis in children who are at least 2 years old.
Formulation : supplied in a multiple-use vial as a sterile, white, preservative-free, lyophilized powder. Reconstitution with 1 mL of the supplied Sterile Bacteriostatic Water for Injection, USP (containing 0.9% benzyl alcohol) yields a multiple-use, clear, and colorless solution with a pH of 7.4 ± 0.3.
Form : lyophilized powder.
Route of administration : injected under the skin

8. Side effects : signs of infection (fever, chills, sore throat, body aches, confusion, neck stiffness, flu symptoms); shortness of breath with swelling, rapid weight gain; chest pain, ongoing cough, coughing up mucus or blood; signs of skin infection such as itching, swelling, warmth, redness, or oozing; black, bloody, or tarry stools; changes in mood or personality (in children); numbness, burning, pain, or tingly feeling; joint pain or swelling with fever, swollen glands, muscle aches, chest pain, unusual thoughts or behavior, and/or seizure (convulsions); or patchy skin color, red spots, or a butterfly-shaped skin rash over your cheeks and nose (worsens in sunlight). Less serious Enbrel side effects may include: mild nausea, vomiting, mild diarrhea, mild stomach pain; runny or stuffy nose, cold symptoms; or headache.

9. General references : #

10. References :