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Identification
NameAnakinra
Accession NumberDB00026  (BTD00060, BIOD00060)
TypeBiotech
GroupsApproved
DescriptionAnakinra is a recombinant, nonglycosylated human interleukin-1 receptor antagonist (IL-1Ra). The difference between anakinra and the native human IL-1Ra is that anakinra has an extra methionine residue at the amino terminus. It is manufactured by using the E. coli expression system. Anakinra is composed of 153 amino acid residues. FDA approved on November 14, 2001.
Protein structureDb00026
Related Articles
Protein chemical formulaC759H1186N208O232S10
Protein average weight17257.6 Da
Sequences
>DB00026 sequence
MRPSGRKSSKMQAFRIWDVNQKTFYLRNNQLVAGYLQGPNVNLEEKIDVVPIEPHALFLG
IHGGKMCLSCVKSGDETRLQLEAVNITDLSENRKQDKRFAFIRSDSGPTTSFESAACPGW
FLCTAMEADQPVSLTNMPDEGVMVTKFYFQEDE
Download FASTA Format
Synonyms
ICIL-1RA
IL-1ra
IL-1RN
IL1 inhibitor
Interleukin-1 receptor antagonist protein precursor
IRAP
External Identifiers Not Available
Approved Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Kineretinjection, solution100 mg/.67mLsubcutaneousSWEDISH ORPHAN BIOVITRUM AB (PUBL)2009-12-15Not applicableUs
KineretSolution for injection100 mgSubcutaneous useSWEDISH ORPHAN BIOVITRUM AB (PUBL)2002-03-08Not applicableEu
Kineretsolution150 mgsubcutaneousSWEDISH ORPHAN BIOVITRUM AB (PUBL)2002-05-29Not applicableCanada
KineretSolution for injection100 mgSubcutaneous useSWEDISH ORPHAN BIOVITRUM AB (PUBL)2002-03-08Not applicableEu
KineretSolution for injection100 mgSubcutaneous useSWEDISH ORPHAN BIOVITRUM AB (PUBL)2002-03-08Not applicableEu
Approved Generic Prescription ProductsNot Available
Approved Over the Counter ProductsNot Available
Unapproved/Other Products Not Available
International BrandsNot Available
Brand mixturesNot Available
SaltsNot Available
Categories
UNII9013DUQ28K
CAS number143090-92-0
Taxonomy
DescriptionNot Available
KingdomOrganic Compounds
Super ClassOrganic Acids
ClassCarboxylic Acids and Derivatives
Sub ClassAmino Acids, Peptides, and Analogues
Direct ParentPeptides
Alternative ParentsNot Available
SubstituentsNot Available
Molecular FrameworkNot Available
External DescriptorsNot Available
Pharmacology
IndicationFor the treatment of adult rheumatoid arthritis and treatment of Neonatal-Onset Multisystem Inflammatory Disease (NOMID).
PharmacodynamicsUsed to treat rheumatoid arthritis, Anakinra blocks the biologic activity of IL-1 by competitively inhibiting IL-1 binding to the interleukin-1 type I receptor (IL-1RI), which is expressed in a wide variety of tissues and organs. IL-1 production is induced in response to inflammatory stimuli and mediates various physiologic responses including inflammatory and immunological responses. Patients with rheumatoid arthritis have elevated levels of IL-1. The levels of the naturally occurring IL-1Ra in synovium and synovial fluid from rheumatoid arthritis (RA) patients are not sufficient to compete with the elevated amount of locally produced IL-1. Increasing the levels of IL-1Ra by artificial means reduces the negative effects (cartilage degradation, bone resorption) of IL-1.
Mechanism of actionAnakinra binds competitively to the Interleukin-1 type I receptor (IL-1RI), thereby inhibiting the action of elevated levels IL-1 which normally can lead to cartilage degradation and bone resorption.
Related Articles
AbsorptionWhen a 70 mg subcutaneous bolus injection is given to healthy subjects, the absolute bioavailability is 95%. Accumulation does not occur following daily subcutaneous doses. Tmax, SubQ, 1-2 mg/kg, healthy subjects = 3-7 hours; Cmax, SubQ, 3 mg/kg once daily, NOMID patients = 3628 ng/mL.
Volume of distributionNot Available
Protein bindingNot Available
MetabolismNot Available
Route of eliminationNot Available
Half lifeHealthy subjects = 4 - 6 hours; NOMID patients = 5.7 hours (range of 3.1 - 28.2 hours).
Clearance

Clearance is variable and increases with increasing creatinine clearance and body weight. However, gender and age were not significant factors.

ToxicityMost common adverse reactions (incidence ≥ 5%) are injection site reaction, worsening of rheumatoid arthritis, upper respiratory tract infection, headache, nausea, diarrhea, sinusitis, arthralgia, flu like-symptoms, and abdominal pain when anakinra is used in RA patients. In NOMID patients, the most common AEs during the first 6 months of treatment (incidence >10%) are injection site reaction, headache, vomiting, arthralgia, pyrexia, and nasopharyngitis.
Affected organisms
  • Humans and other mammals
PathwaysNot Available
SNP Mediated EffectsNot Available
SNP Mediated Adverse Drug ReactionsNot Available
Pharmacoeconomics
ManufacturersNot Available
Packagers
Dosage forms
FormRouteStrength
Injection, solutionsubcutaneous100 mg/.67mL
Solutionsubcutaneous150 mg
Solution for injectionSubcutaneous use100 mg
Prices
Unit descriptionCostUnit
Kineret 1 Box = 7 Syringes, 4.69ml Box449.9USD box
Kineret 100 mg/0.67 ml syr61.8USD syringe
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)
CA1341322 No2001-11-272018-11-27Canada
CA2141953 No2008-04-082013-09-17Canada
Properties
StateLiquid
Experimental Properties
PropertyValueSource
hydrophobicity-0.412Not Available
isoelectric point5.46Not Available
References
Synthesis ReferenceNot Available
General References
  1. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [PubMed:11752352 ]
  2. Lequerre T, Quartier P, Rosellini D, Alaoui F, De Bandt M, Mejjad O, Kone-Paut I, Michel M, Dernis E, Khellaf M, Limal N, Job-Deslandre C, Fautrel B, Le Loet X, Sibilia J: Interleukin-1 receptor antagonist (anakinra) treatment in patients with systemic-onset juvenile idiopathic arthritis or adult onset Still disease: preliminary experience in France. Ann Rheum Dis. 2008 Mar;67(3):302-8. Epub 2007 Oct 18. [PubMed:17947302 ]
External Links
ATC CodesL04AC03
AHFS Codes
  • 92:00.00
PDB Entries
FDA labelDownload (62.3 KB)
MSDSNot Available
Interactions
Drug Interactions
Drug
AbataceptThe risk or severity of adverse effects can be increased when Anakinra is combined with Abatacept.
AdalimumabThe risk or severity of adverse effects can be increased when Adalimumab is combined with Anakinra.
AfelimomabThe risk or severity of adverse effects can be increased when Afelimomab is combined with Anakinra.
CanakinumabThe risk or severity of adverse effects can be increased when Anakinra is combined with Canakinumab.
Certolizumab pegolThe risk or severity of adverse effects can be increased when Certolizumab pegol is combined with Anakinra.
DenosumabThe risk or severity of adverse effects can be increased when Denosumab is combined with Anakinra.
EtanerceptThe risk or severity of adverse effects can be increased when Etanercept is combined with Anakinra.
FingolimodAnakinra may increase the immunosuppressive activities of Fingolimod.
GolimumabThe risk or severity of adverse effects can be increased when Golimumab is combined with Anakinra.
InfliximabThe risk or severity of adverse effects can be increased when Infliximab is combined with Anakinra.
LeflunomideThe risk or severity of adverse effects can be increased when Anakinra is combined with Leflunomide.
NatalizumabThe risk or severity of adverse effects can be increased when Anakinra is combined with Natalizumab.
PimecrolimusThe risk or severity of adverse effects can be increased when Pimecrolimus is combined with Anakinra.
PirfenidoneThe risk or severity of adverse effects can be increased when Pirfenidone is combined with Anakinra.
Rabies vaccineThe risk or severity of adverse effects can be increased when Anakinra is combined with Rabies vaccine.
RoflumilastRoflumilast may increase the immunosuppressive activities of Anakinra.
Sipuleucel-TThe therapeutic efficacy of Sipuleucel-T can be decreased when used in combination with Anakinra.
TacrolimusThe risk or severity of adverse effects can be increased when Tacrolimus is combined with Anakinra.
TofacitinibAnakinra may increase the immunosuppressive activities of Tofacitinib.
TrastuzumabTrastuzumab may increase the neutropenic activities of Anakinra.
Food InteractionsNot Available

Targets

Kind
Protein
Organism
Human
Pharmacological action
yes
Actions
antagonist
General Function:
Transmembrane signaling receptor activity
Specific Function:
Receptor for IL1A, IL1B and IL1RN. After binding to interleukin-1 associates with the corecptor IL1RAP to form the high affinity interleukin-1 receptor complex which mediates interleukin-1-dependent activation of NF-kappa-B, MAPK and other pathways. Signaling involves the recruitment of adapter molecules such as TOLLIP, MYD88, and IRAK1 or IRAK2 via the respective TIR domains of the receptor/co...
Gene Name:
IL1R1
Uniprot ID:
P14778
Molecular Weight:
65401.91 Da
References
  1. Tang YH, Zhang SP, Liang Y, Deng CQ: [Effects of Panax notoginseng saponins on mRNA expressions of interleukin-1 beta, its correlative factors and cysteinyl-aspartate specific protease after cerebral ischemia-reperfusion in rats]. Zhong Xi Yi Jie He Xue Bao. 2007 May;5(3):328-32. [PubMed:17498496 ]
  2. Dayer JM: The pivotal role of interleukin-1 in the clinical manifestations of rheumatoid arthritis. Rheumatology (Oxford). 2003 May;42 Suppl 2:ii3-10. [PubMed:12817089 ]
  3. Vamvakopoulos J, Green C, Metcalfe S: Genetic control of IL-1beta bioactivity through differential regulation of the IL-1 receptor antagonist. Eur J Immunol. 2002 Oct;32(10):2988-96. [PubMed:12355453 ]
  4. Do H, Vasilescu A, Carpentier W, Meyer L, Diop G, Hirtzig T, Coulonges C, Labib T, Spadoni JL, Therwath A, Lathrop M, Matsuda F, Zagury JF: Exhaustive genotyping of the interleukin-1 family genes and associations with AIDS progression in a French cohort. J Infect Dis. 2006 Dec 1;194(11):1492-504. Epub 2006 Oct 26. [PubMed:17083033 ]
  5. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [PubMed:11752352 ]
  6. So A, De Smedt T, Revaz S, Tschopp J: A pilot study of IL-1 inhibition by anakinra in acute gout. Arthritis Res Ther. 2007;9(2):R28. [PubMed:17352828 ]
  7. Vannier E, Kaser A, Atkins MB, Fantuzzi G, Dinarello CA, Mier JW, Tilg H: Elevated circulating levels of soluble interleukin-1 receptor type II during interleukin-2 immunotherapy. Eur Cytokine Netw. 1999 Mar;10(1):37-42. [PubMed:10210771 ]
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Drug created on June 13, 2005 07:24 / Updated on August 17, 2016 12:23