Anakinra

Identification

Name
Anakinra
Accession Number
DB00026  (BTD00060, BIOD00060)
Type
Biotech
Groups
Approved
Biologic Classification
Protein Based Therapies
Interleukin-based products
Description

Anakinra 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 structure
Db00026
Protein chemical formula
C759H1186N208O232S10
Protein average weight
17257.6 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
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
KineretInjection, solution100 mgSubcutaneousSWEDISH ORPHAN BIOVITRUM AB (PUBL)2002-03-08Not applicableEu
KineretInjection, solution100 mg/.67mLSubcutaneousSWEDISH ORPHAN BIOVITRUM AB (PUBL)2009-12-15Not applicableUs
KineretInjection, solution100 mgSubcutaneousSWEDISH ORPHAN BIOVITRUM AB (PUBL)2002-03-08Not applicableEu
KineretSolution150 mgSubcutaneousSWEDISH ORPHAN BIOVITRUM AB (PUBL)2002-05-29Not applicableCanada
KineretInjection, solution100 mgSubcutaneousSWEDISH ORPHAN BIOVITRUM AB (PUBL)2002-03-08Not applicableEu
Categories
UNII
9013DUQ28K
CAS number
143090-92-0

Pharmacology

Indication

For the treatment of adult rheumatoid arthritis and treatment of Neonatal-Onset Multisystem Inflammatory Disease (NOMID).

Structured Indications
Pharmacodynamics

Used 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 action

Anakinra 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.

TargetActionsOrganism
AInterleukin-1 receptor type 1
antagonist
Human
Absorption

When 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 distribution
Not Available
Protein binding
Not Available
Metabolism
Not Available
Route of elimination
Not Available
Half life

Healthy 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.

Toxicity

Most 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
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
DrugInteractionDrug group
AbataceptThe risk or severity of adverse effects can be increased when Anakinra is combined with Abatacept.Approved
AdalimumabThe risk or severity of adverse effects can be increased when Adalimumab is combined with Anakinra.Approved
AfelimomabThe risk or severity of adverse effects can be increased when Afelimomab is combined with Anakinra.Investigational
BCG vaccineThe therapeutic efficacy of BCG vaccine can be decreased when used in combination with Anakinra.Investigational
CanakinumabThe risk or severity of adverse effects can be increased when Anakinra is combined with Canakinumab.Approved, Investigational
Certolizumab pegolThe risk or severity of adverse effects can be increased when Certolizumab pegol is combined with Anakinra.Approved
Clostridium tetani toxoid antigen (formaldehyde inactivated)The therapeutic efficacy of Clostridium tetani toxoid antigen (formaldehyde inactivated) can be decreased when used in combination with Anakinra.Approved
Corynebacterium diphtheriae toxoid antigen (formaldehyde inactivated)The therapeutic efficacy of Corynebacterium diphtheriae toxoid antigen (formaldehyde inactivated) can be decreased when used in combination with Anakinra.Approved
DenosumabThe risk or severity of adverse effects can be increased when Denosumab is combined with Anakinra.Approved
EtanerceptThe risk or severity of adverse effects can be increased when Etanercept is combined with Anakinra.Approved, Investigational
FingolimodAnakinra may increase the immunosuppressive activities of Fingolimod.Approved, Investigational
G17DTThe therapeutic efficacy of G17DT can be decreased when used in combination with Anakinra.Investigational
GI-5005The therapeutic efficacy of GI-5005 can be decreased when used in combination with Anakinra.Investigational
GolimumabThe risk or severity of adverse effects can be increased when Golimumab is combined with Anakinra.Approved
Hepatitis A VaccineThe therapeutic efficacy of Hepatitis A Vaccine can be decreased when used in combination with Anakinra.Approved
Hepatitis B Vaccine (Recombinant)The therapeutic efficacy of Hepatitis B Vaccine (Recombinant) can be decreased when used in combination with Anakinra.Approved, Withdrawn
InfliximabThe risk or severity of adverse effects can be increased when Infliximab is combined with Anakinra.Approved
INGN 201The therapeutic efficacy of INGN 201 can be decreased when used in combination with Anakinra.Investigational
INGN 225The therapeutic efficacy of INGN 225 can be decreased when used in combination with Anakinra.Investigational
LeflunomideThe risk or severity of adverse effects can be increased when Anakinra is combined with Leflunomide.Approved, Investigational
NatalizumabThe risk or severity of adverse effects can be increased when Anakinra is combined with Natalizumab.Approved, Investigational
PimecrolimusThe risk or severity of adverse effects can be increased when Pimecrolimus is combined with Anakinra.Approved, Investigational
PirfenidoneThe risk or severity of adverse effects can be increased when Pirfenidone is combined with Anakinra.Approved, Investigational
Rabies virus inactivated antigen, AThe risk or severity of adverse effects can be increased when Anakinra is combined with Rabies virus inactivated antigen, A.Approved
Rabies virus inactivated antigen, AThe therapeutic efficacy of Rabies virus inactivated antigen, A can be decreased when used in combination with Anakinra.Approved
RindopepimutThe therapeutic efficacy of Rindopepimut can be decreased when used in combination with Anakinra.Investigational
RituximabThe risk or severity of adverse effects can be increased when Anakinra is combined with Rituximab.Approved
RoflumilastRoflumilast may increase the immunosuppressive activities of Anakinra.Approved
Rotavirus VaccineThe therapeutic efficacy of Rotavirus Vaccine can be decreased when used in combination with Anakinra.Approved
Rubella virus vaccineThe therapeutic efficacy of Rubella virus vaccine can be decreased when used in combination with Anakinra.Approved
Salmonella typhi ty21a live antigenThe therapeutic efficacy of Salmonella typhi ty21a live antigen can be decreased when used in combination with Anakinra.Approved
Sipuleucel-TThe therapeutic efficacy of Sipuleucel-T can be decreased when used in combination with Anakinra.Approved
SRP 299The therapeutic efficacy of SRP 299 can be decreased when used in combination with Anakinra.Investigational
TacrolimusThe risk or severity of adverse effects can be increased when Tacrolimus is combined with Anakinra.Approved, Investigational
TecemotideThe therapeutic efficacy of Tecemotide can be decreased when used in combination with Anakinra.Investigational
TG4010The therapeutic efficacy of TG4010 can be decreased when used in combination with Anakinra.Investigational
TocilizumabThe risk or severity of adverse effects can be increased when Anakinra is combined with Tocilizumab.Approved
TofacitinibThe risk or severity of adverse effects can be increased when Anakinra is combined with Tofacitinib.Approved, Investigational
TrastuzumabTrastuzumab may increase the neutropenic activities of Anakinra.Approved, Investigational
Yellow fever vaccineThe therapeutic efficacy of Yellow fever vaccine can be decreased when used in combination with Anakinra.Approved
Zoster vaccineThe therapeutic efficacy of Zoster vaccine can be decreased when used in combination with Anakinra.Approved
Food Interactions
Not Available

References

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
UniProt
P18510
Genbank
M55646
KEGG Drug
D02934
PubChem Substance
46507944
ChEMBL
CHEMBL1201570
Therapeutic Targets Database
DAP000095
PharmGKB
PA10799
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
Wikipedia
Anakinra
ATC Codes
L04AC03 — Anakinra
AHFS Codes
  • 92:36.00 — Disease-modifying Antirheumatic Agents
FDA label
Download (62.3 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
0Not Yet RecruitingTreatmentAcute Pericarditis1
0RecruitingTreatmentAdenocarcinoma of the Pancreas1
1Active Not RecruitingTreatmentMalignant Neoplasm of Pancreas1
1CompletedNot AvailablePostprandial Fatigue1
1CompletedBasic ScienceHealthy Control Subjects1
1CompletedTreatmentFamilial Cold Autoinflammatory Syndrome (FCAS)1
1CompletedTreatmentHealthy Volunteers1
1CompletedTreatmentUnspecified Adult Solid Tumor, Protocol Specific1
1Enrolling by InvitationOtherHuman Immunodeficiency Virus (HIV) Infections / Neurologic Disorders1
1RecruitingTreatmentAdvanced Cancers1
1RecruitingTreatmentMacrophage Activation Syndrome1
1RecruitingTreatmentPulmonary Arterial Hypertension (PAH)1
1TerminatedTreatmentAllergic Disease / Anakinra / Atopic Dermatitis (AD) / Dermatitis, Eczematous / Kineret1
1, 2Active Not RecruitingTreatmentIndolent Plasma Cell Myeloma / Plasma Cell Myeloma / Smoldering Plasma Cell Myeloma1
1, 2CompletedOtherHeart Failure, Unspecified1
1, 2CompletedTreatmentAutoimmune Inner Ear Disease / Sensorineural Hearing Loss1
1, 2CompletedTreatmentAutoimmune/Connective Tissue Diseases / Immune System Diseases1
1, 2CompletedTreatmentCorneal Neovascularization1
1, 2CompletedTreatmentDiabetes, Diabetes Mellitus Type 12
1, 2CompletedTreatmentHeart Failure, Unspecified1
1, 2CompletedTreatmentKnee Injuries1
1, 2CompletedTreatmentPosterior Blepharitis1
1, 2Not Yet RecruitingTreatmentDiabetes, Diabetes Mellitus Type 11
1, 2RecruitingTreatmentMucocutaneous Lymph Node Syndrome1
1, 2TerminatedTreatmentArthropathy, Neurogenic / Nervous System Malformations / Optic discs blurred / Urticarias1
1, 2TerminatedTreatmentHearing Loss, Sudden1
1, 2TerminatedTreatmentPulmonary Hypertension (PH)1
2Active Not RecruitingTreatmentHeart Failure With Normal Ejection Fraction1
2Active Not RecruitingTreatmentMetastatic Colorectal Cancers1
2CompletedTreatmentAcute Myocardial Infarction (AMI) / Heart Failure, Unspecified1
2CompletedTreatmentAdult-Onset Still's Disease1
2CompletedTreatmentESRD1
2CompletedTreatmentHidradenitis Suppurativa (HS)2
2CompletedTreatmentJuvenile Chronic Arthritis1
2CompletedTreatmentMultiple Myeloma and Plasma Cell Neoplasm1
2CompletedTreatmentOsteoarthritis (OA)1
2CompletedTreatmentPrimary Sjogren / Tiredness1
2CompletedTreatmentRheumatoid Arthritis1
2CompletedTreatmentType 2 Diabetes Mellitus1
2Not Yet RecruitingTreatmentAnterior Cruciate Ligament Tear1
2Not Yet RecruitingTreatmentEnd-Stage Renal Disease (ESRD)1
2Not Yet RecruitingTreatmentMacrophage Activation Syndrome / Sepsis1
2Not Yet RecruitingTreatmentTraumatic Brain Injury (TBI)1
2RecruitingSupportive CareMultiple Myeloma (MM)1
2RecruitingTreatmentAcrodermatitis Continua of Hallopeau / Palmoplantar Pustulosis / Pustular Dermatosis / Pustular Psoriasis / Sneddon-Wilkinson1
2RecruitingTreatmentAcute Gouty Arthritis1
2RecruitingTreatmentBiotherapy / Uveitis1
2RecruitingTreatmentChildren / Mucocutaneous Lymph Node Syndrome1
2RecruitingTreatmentHeart Failure, Systolic / Renal Disease, End Stage1
2RecruitingTreatmentRefractory Hemochromatosis Rheumatism1
2TerminatedTreatmentRheumatoid Arthritis1
2TerminatedTreatmentType I Diabetes1
2Unknown StatusTreatmentAmyotrophic Lateral Sclerosis (ALS)1
2Unknown StatusTreatmentDiabetes Mellitus (DM)1
2Unknown StatusTreatmentInsulin Resistance / Type 2 Diabetes Mellitus1
2, 3CompletedTreatmentDermatomyositis / Inclusion Body Myositis (IBM) / Polymyositis1
2, 3CompletedTreatmentDiabetes, Diabetes Mellitus Type 11
2, 3CompletedTreatmentHeart Failure, Unspecified2
2, 3CompletedTreatmentMyalgic Encephalomyelitis (ME)1
2, 3CompletedTreatmentSystemic-Onset Juvenile Idiopathic Arthritis1
2, 3RecruitingTreatmentAcute Alcoholic Hepatitis1
2, 3RecruitingTreatmentAcute Myocardial Infarction (AMI)1
2, 3RecruitingTreatmentAcute Myocarditis1
2, 3RecruitingTreatmentChronic Kidney Disease (CKD) / Gout Acute1
3CompletedNot AvailableHypersecretion; Cortisol / Metabolic Syndromes1
3CompletedTreatmentBMI >30 kg/m2 / Hypogonadism / Metabolic Syndromes1
3CompletedTreatmentFamilial Mediterranean Fever (FMF )1
3CompletedTreatmentRheumatoid Arthritis1
3CompletedTreatmentST Segment Elevation Acute Myocardial Infarction1
3Not Yet RecruitingTreatmentGiant Cells Arteritis1
3RecruitingTreatmentStill's Disease, Adult-Onset / Still's Disease, Juvenile-Onset1
4Active Not RecruitingTreatmentKnee Injuries1
4CompletedTreatmentIdiopathic Recurrent Pericarditis1
4CompletedTreatmentRheumatoid Arthritis2
4Unknown StatusTreatmentRheumatoid Arthritis / Type 2 Diabetes Mellitus1
Not AvailableActive Not RecruitingNot AvailableCryopyrin-associated Periodic Syndromes (CAPS)1
Not AvailableActive Not RecruitingOtherAdiposity1
Not AvailableCompletedNot AvailableRheumatoid Arthritis2
Not AvailableCompletedBasic ScienceType 2 Diabetes Mellitus1
Not AvailableCompletedTreatmentCoronary Artery Disease / Inflammatory Reaction / Rheumatoid Arthritis1
Not AvailableCompletedTreatmentEnd Stage Renal Disease (ESRD)1
Not AvailableCompletedTreatmentHeart Failure, Unspecified1
Not AvailableRecruitingDiagnosticLate Dumping Syndrome / Post-gastrointestinal bypass surgery / Postprandial Hypoglycemia1
Not AvailableUnknown StatusNot AvailableGlucose tolerance impaired / Impaired Insulin Secretion / Type 2 Diabetes Mellitus1
Not AvailableUnknown StatusTreatmentInflammatory Reaction / Pain1
Not AvailableWithdrawnBasic ScienceType 2 Diabetes Mellitus1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Dosage forms
FormRouteStrength
Injection, solutionSubcutaneous100 mg
Injection, solutionSubcutaneous100 mg/.67mL
SolutionSubcutaneous150 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)
CA2141953No2008-04-082013-09-17Canada
CA1341322No2001-11-272018-11-27Canada

Properties

State
Liquid
Experimental Properties
PropertyValueSource
hydrophobicity-0.412Not Available
isoelectric point5.46Not Available

Taxonomy

Description
Not Available
Kingdom
Organic Compounds
Super Class
Organic Acids
Class
Carboxylic Acids and Derivatives
Sub Class
Amino Acids, Peptides, and Analogues
Direct Parent
Peptides
Alternative Parents
Not Available
Substituents
Not Available
Molecular Framework
Not Available
External Descriptors
Not 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-dependen...
Gene Name
IL1R1
Uniprot ID
P14778
Uniprot Name
Interleukin-1 receptor type 1
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]

Drug created on June 13, 2005 07:24 / Updated on November 19, 2017 20:34