DB00005 Half life 102 30 hrs Description Enbrel etanercept is a dimeric fusion protein consisting of the extracellular ligand binding portion of the human 75 kilodalton ID: 630317
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Slide1
Etanercept
Drugbank
ID :
DB00005
Half life :
102 +/- 30 hrs Slide2
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 C
H
2 domain, the CH3 domain and hinge region, but not the C
H
1 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. Slide3
Mechanism of action :
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] Slide4
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
:
r
esults 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. Slide5
Targets :
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 Slide6
Categories :
Immunosuppressive Agents
Patents
:
Country Patent Number Approved Expires
(estimated
)
Canada 2476934 2009
-06-
16 2023
-02-
27
Canada 2123593 2000
-03-
14 2013
-09-
14
United States 7276477 2007
-10-
02 2024
-07-
29
United States 36755 2000
-06-
27 2012
-10-23
Sequence
:
LPAQVAFTPYAPEPGSTCRLREYYDQTAQMCCSKCSPGQHAKVFCTKTSDTVCDSCEDSTYTQLWNWVPECLSCGSRCSSDQVETQACTREQNRICTCRPGWYCALSKQEGCRLCAPLRKCRPGFGVARPGTETSDVVCKPCAPGTFSNTTSSTDICRPHQICNVVAIPGNASMDAVCTSTSPTRSMAPGAVHLPQPVSTRSQHTQPTPEPSTAPSTSFLLPMGPSPPAEGSTGDEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK Slide7
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 C
H
2 domain, the CH3 domain and hinge region, but not the C
H
1 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 Slide8
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.
Slide9
General references :
# http://www.genome.jp/dbget-bin/www_bget?D00742. Slide10
References :
http://www.rxlist.com/enbrel-drug.htm
http
://www.drugs.com/enbrel.html
http
://www.drugs.com/drug-interactions/etanercept,enbrel.html