Eculizumab

Identification

Logo pink
Are you a
new drug developer?
Contact us to learn more about our customized products and solutions.
Logo pink
Stay in the know!
As part of our commitment to providing the most up-to-date drug information, we will be releasing #DrugBankUpdates with our newly added curated drug pages.
#DrugBankUpdates
Name
Eculizumab
Accession Number
DB01257
Type
Biotech
Groups
Approved, Investigational
Biologic Classification
Protein Based Therapies
Monoclonal antibody (mAb)
Description

Eculizumab is a monoclonal antibody that targets complement protein C5.7,1 Binding to this protein prevents the activation of a complement terminal complex, which is used to treat a number of autoimmune conditions.7,1,2

Eculizumab was granted FDA approval on 16 March 2007.7

Protein structure
Db01257
Protein chemical formula
Not Available
Protein average weight
148000.0 Da
Sequences
Not Available
Synonyms
  • Eculizumab
External IDs
5G1.1 / H5G1-1 / H5G1.1 / H5G11
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
SolirisInjection, solution, concentrate300 mg/30mLIntravenousAlexion Pharmaceuticals Inc.2007-04-02Not applicableUs
SolirisInjection, solution, concentrate300 mgIntravenousAlexion Europe Sas2007-06-20Not applicableEu
SolirisSolution10 mgIntravenousAlexion Pharma Gmbh2009-05-25Not applicableCanada
Additional Data Available
  • Application Number
    Application Number

    A unique ID assigned by the FDA when a product is submitted for approval by the labeller.

    Learn more
  • Product Code
    Product Code

    A governmentally-recognized ID which uniquely identifies the product within its regulatory market.

    Learn more
Categories
UNII
A3ULP0F556
CAS number
219685-50-4

Pharmacology

Indication

Eculizumab is indicated to treat paroxysmal nocturnal hemoglobinuria (PNH) to reduce hemolysis, atypical hemolytic uremic syndrome to inhibit complement-mediated thrombotic microangiopathy7,2, and neuromyelitis optica spectrum disorder (NMOSD).6

Associated Conditions
Pharmacodynamics

Eculizumab is a monoclonal antibody that prevents the activation of terminal complement in some autoimmune conditions.7,1,2 Eculizumab has a long duration of action.7 Patients taking this medication should be vaccinated against Neisseria meningiditis as serious meningococcal infections have occurred in the past.7,2

Mechanism of action

Eculizumab is a monoclonal antibody that targets complement protein C5, preventing cleavage to C5a and C5b, and the formation of the terminal complement complex C5b-9.7,1,2 Inhibition of this complex prevents complement mediated intravascular hemolysis in paroxysmal nocturnal hemoglobunuria, complement mediated microangiopathy in atypical hemolytic uremic syndrome, and immune mediated inflammation and damage of the central nervous system in neuromyelitis optica spectrum disorder.7,6,2

TargetActionsOrganism
AComplement C5
antibody
Humans
Additional Data Available
Adverse Effects

Comprehensive structured data on known drug adverse effects with statistical prevalence. MedDRA and ICD10 ids are provided for adverse effect conditions and symptoms.

Learn more
Additional Data Available
Contraindications

Structured data covering drug contraindications. Each contraindication describes a scenario in which the drug is not to be used. Includes restrictions on co-administration, contraindicated populations, and more.

Learn more
Additional Data Available
Blackbox Warnings

Structured data representing warnings from the black box section of drug labels. These warnings cover important and dangerous risks, contraindications, or adverse effects.

Learn more
Absorption

Eculizumab is administered by intravenous infusion so the bioavailability is 100%.7 This drug reaches a Cmax of 194±76µg/mL and Ctrough of 97±60µg/mL.7 The AUC was calculated to be 24,467.6µg*h/mL.4

Volume of distribution

The volume of distribution of eculizumab is 5-8L.7

Protein binding

Though protein binding data is scarce, eculizumab is unlikely to be protein bound as it is a monoclonal antibody.

Metabolism

Eculizumab is a monoclonal antibody and is expected to be metabolized to small peptides and amino acids.4,5

Route of elimination

Monoclonal antibodies are not eliminated in the urine, and only a small amount is excreted in bile.5 Most monoclonal antibodies are catabolized in lysosomes to amino acids.5

Half life

The half life of eculizumab is 270-375h7 or 272±82h.3

Clearance

Pharmacokinetic properties in healthy patients have not been determined.4 In patients with rhematoid arthritis, there is an average clearance of 0.26mL/kg/h.4

Toxicity

Overdoses of eculizumab are unlikely as it is administered under specialist supervision.8 In case of overdose, contact local poison control.8

Affected organisms
  • Humans and other mammals
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.
DrugInteraction
2-MethoxyethanolThe risk or severity of adverse effects can be increased when Eculizumab is combined with 2-Methoxyethanol.
9-(N-methyl-L-isoleucine)-cyclosporin AThe risk or severity of adverse effects can be increased when Eculizumab is combined with 9-(N-methyl-L-isoleucine)-cyclosporin A.
AbataceptThe risk or severity of adverse effects can be increased when Eculizumab is combined with Abatacept.
AbciximabThe risk or severity of adverse effects can be increased when Abciximab is combined with Eculizumab.
AbetimusThe risk or severity of adverse effects can be increased when Eculizumab is combined with Abetimus.
AbituzumabThe risk or severity of adverse effects can be increased when Eculizumab is combined with Abituzumab.
AbrilumabThe risk or severity of adverse effects can be increased when Eculizumab is combined with Abrilumab.
ActeosideThe risk or severity of adverse effects can be increased when Eculizumab is combined with Acteoside.
AdalimumabThe risk or severity of adverse effects can be increased when Adalimumab is combined with Eculizumab.
AdecatumumabThe risk or severity of adverse effects can be increased when Eculizumab is combined with Adecatumumab.
Additional Data Available
  • Extended Description
    Extended Description

    Extended description of the mechanism of action and particular properties of each drug interaction.

    Learn more
  • Severity
    Severity

    A severity rating for each drug interaction, from minor to major.

    Learn more
  • Evidence Level
    Evidence Level

    A rating for the strength of the evidence supporting each drug interaction.

    Learn more
  • Action
    Action

    An effect category for each drug interaction. Know how this interaction affects the subject drug.

    Learn more
Food Interactions
Not Available

References

General References
  1. Thomas TC, Rollins SA, Rother RP, Giannoni MA, Hartman SL, Elliott EA, Nye SH, Matis LA, Squinto SP, Evans MJ: Inhibition of complement activity by humanized anti-C5 antibody and single-chain Fv. Mol Immunol. 1996 Dec;33(17-18):1389-401. [PubMed:9171898]
  2. Dmytrijuk A, Robie-Suh K, Cohen MH, Rieves D, Weiss K, Pazdur R: FDA report: eculizumab (Soliris) for the treatment of patients with paroxysmal nocturnal hemoglobinuria. Oncologist. 2008 Sep;13(9):993-1000. doi: 10.1634/theoncologist.2008-0086. Epub 2008 Sep 10. [PubMed:18784156]
  3. Rother RP, Rollins SA, Mojcik CF, Brodsky RA, Bell L: Discovery and development of the complement inhibitor eculizumab for the treatment of paroxysmal nocturnal hemoglobinuria. Nat Biotechnol. 2007 Nov;25(11):1256-64. [PubMed:17989688]
  4. Wijnsma KL, Ter Heine R, Moes DJAR, Langemeijer S, Schols SEM, Volokhina EB, van den Heuvel LP, Wetzels JFM, van de Kar NCAJ, Bruggemann RJ: Pharmacology, Pharmacokinetics and Pharmacodynamics of Eculizumab, and Possibilities for an Individualized Approach to Eculizumab. Clin Pharmacokinet. 2019 Jul;58(7):859-874. doi: 10.1007/s40262-019-00742-8. [PubMed:30758736]
  5. Ryman JT, Meibohm B: Pharmacokinetics of Monoclonal Antibodies. CPT Pharmacometrics Syst Pharmacol. 2017 Sep;6(9):576-588. doi: 10.1002/psp4.12224. Epub 2017 Jul 29. [PubMed:28653357]
  6. FDA: Eculizumab New Indication [Link]
  7. FDA Approved Drug Products: Eculizumab Intravenous Infusion [Link]
  8. Alexion Pharma: Soliris Product Monograph [Link]
External Links
PubChem Substance
46505429
ChEMBL
CHEMBL1201828
Therapeutic Targets Database
DAP000967
PharmGKB
PA164776637
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
Wikipedia
Eculizumab
ATC Codes
L04AA25 — Eculizumab
AHFS Codes
  • 92:32.00 — Complement Inhibitors

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
0RecruitingTreatmentEnd Stage Liver Diseases1
1CompletedOtherHealthy Volunteers1
1CompletedTreatmentDense Deposit Disease / Membranoproliferative Glomerulonephritis1
1CompletedTreatmentHealthy Volunteers1
1CompletedTreatmentKidney; Complications, Allograft1
1Not Yet RecruitingTreatmentComplement Abnormality / HELLP Syndrome (HELLP), Third Trimester / Maternal Injury / Morbidity;Newborn / Severe Preeclampsia1
1, 2CompletedTreatmentNeuromyelitis Optica1
1, 2CompletedTreatmentTransplant, Kidney1
1, 2TerminatedPreventionTransplant, Kidney1
1, 2TerminatedTreatmentTransplant, Kidney1
1, 2Unknown StatusTreatmentChronic Hemolysis1
1, 2WithdrawnTreatmentSubclinical Acute Antibody-mediated Rejection in Kidney Transplantation1
2Active Not RecruitingPreventionAntiphospholipid Antibody Syndrome / End Stage Renal Disease (ESRD)1
2Active Not RecruitingTreatmentParoxysmal Nocturnal Haemoglobinuria (PNH)1
2CompletedPreventionAsthma, Allergic1
2CompletedPreventionDiabetes Mellitus (DM)1
2CompletedPreventionEnd-Stage Renal Disease (ESRD) / Graft Reperfusion Injury / Renal Failure1
2CompletedTreatmentAge-Related Macular Degeneration (ARMD)1
2CompletedTreatmentAlloimmune Platelet Refractoriness / Thrombocytopenia1
2CompletedTreatmentAtypical Hemolytic Uremic Syndrome (aHUS)5
2CompletedTreatmentAtypical Hemolytic-Uremic Syndrome2
2CompletedTreatmentCold type haemolytic anaemia1
2CompletedTreatmentDermatomyositis1
2CompletedTreatmentGullain Barre Syndrome1
2CompletedTreatmentMembranoproliferative Glomerulonephritis1
2CompletedTreatmentParoxysmal Nocturnal Haemoglobinuria (PNH)2
2CompletedTreatmentHemodialysis-dependent chronic kidney disease (HDD-CKD)1
2RecruitingTreatmentAtypical Hemolytic Uremic Syndrome (aHUS) / Multiple Organ Dysfunction Syndrome / Thrombotic Microangiopathies1
2TerminatedPreventionComplement Activity / Delayed Graft Function / Transplantation, Kidney1
2TerminatedPreventionDelayed Function of Renal Transplant1
2TerminatedTreatmentAntibody Mediated Rejection1
2TerminatedTreatmentAntibody-mediated Rejection / Humoral Rejection1
2TerminatedTreatmentMyasthenia Gravis1
2Unknown StatusTreatmentGullian Barre Syndrome1
2WithdrawnTreatmentAnti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis1
2, 3CompletedPreventionDelayed Graft Function1
2, 3CompletedTreatmentShiga-like Toxin-producing Escherichia Coli1
2, 3Not Yet RecruitingTreatmentNeuromyelitis Optica / Neuromyelitis Optica Spectrum Disorder1
3Active Not RecruitingTreatmentAdult Patients With Paroxysmal Nocturnal Hemoglobinuria (PNH) Who Are Currently Being Treated With Eculizumab / Paroxysmal Nocturnal Haemoglobinuria (PNH)1
3Active Not RecruitingTreatmentNeuromyelitis Optica / Neuromyelitis Optica Spectrum Disorder1
3Active Not RecruitingTreatmentParoxysmal Nocturnal Haemoglobinuria (PNH)1
3Approved for MarketingNot AvailableParoxysmal Hemoglobinuria1
3CompletedEducational/Counseling/TrainingParoxysmal Hemoglobinuria1
3CompletedPreventionLeukemias1
3CompletedTreatmentHemolytic Uremic Syndrome of Childhood1
3CompletedTreatmentParoxysmal Hemoglobinuria2
3CompletedTreatmentParoxysmal Hemoglobinuria, Nocturnal2
3CompletedTreatmentRefractory Generalized Myasthenia Gravis2
3RecruitingTreatmentMyasthenia Gravis / Myasthenia Gravis, Generalized / Myasthenia Gravis, Juvenile Form1
3RecruitingTreatmentParoxysmal Nocturnal Haemoglobinuria (PNH)4
3TerminatedTreatmentNeuromyelitis Optica / Neuromyelitis Optica Spectrum Disorder1
4Active Not RecruitingTreatmentAntibody-mediated Rejection / Cardiac Allograft Vasculopathy / Heart Graft Dysfunction / Hyperacute Rejection of Cardiac Transplant / Symptomatic left ventricular ejection fraction ≤ 35% Chronic heart failure1
4Active Not RecruitingTreatmentAtypical Hemolytic Uremic Syndrome (aHUS)1
4CompletedTreatmentParoxysmal Hemoglobinuria1
Not AvailableRecruitingNot AvailableCD55 - Cluster of Differentiation Antigen 55 Deficiency / Complement Regulatory Factor Defect / Primary Intestinal Lymphangiectasis / Protein-Losing Enteropathies1
Not AvailableRecruitingNot AvailableDisorder Related to Bone Marrow Transplantation / Thrombotic Microangiopathies1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
  • Alexion Pharmaceuticals Inc.
  • Ben Venue Laboratories Inc.
Dosage forms
FormRouteStrength
Injection, solution, concentrateIntravenous300 mg
Injection, solution, concentrateIntravenous300 mg/30mL
SolutionIntravenous10 mg
Prices
Unit descriptionCostUnit
Soliris 300 mg/30 ml vial210.0USD ml
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)
CA2189015No2010-04-132015-04-30Canada
Additional Data Available
  • Filed On
    Filed On

    The date on which a patent was filed with the relevant government.

    Learn more

Properties

State
Liquid
Experimental Properties
Not 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
Humans
Pharmacological action
Yes
Actions
Antibody
General Function
Receptor binding
Specific Function
Activation of C5 by a C5 convertase initiates the spontaneous assembly of the late complement components, C5-C9, into the membrane attack complex. C5b has a transient binding site for C6. The C5b-C...
Gene Name
C5
Uniprot ID
P01031
Uniprot Name
Complement C5
Molecular Weight
188303.705 Da
References
  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [PubMed:17139284]
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. [PubMed:17016423]
  3. Singer AL, Locke JE, Stewart ZA, Lonze BE, Hamilton JP, Scudiere JR, Anders RA, Rother RP, Brodsky RA, Cameron AM: Successful liver transplantation for Budd-Chiari syndrome in a patient with paroxysmal nocturnal hemoglobinuria treated with the anti-complement antibody eculizumab. Liver Transpl. 2009 May;15(5):540-3. doi: 10.1002/lt.21714. [PubMed:19399743]
  4. Kelly R, Richards S, Hillmen P, Hill A: The pathophysiology of paroxysmal nocturnal hemoglobinuria and treatment with eculizumab. Ther Clin Risk Manag. 2009;5:911-21. Epub . [PubMed:20011245]
  5. Dmytrijuk A, Robie-Suh K, Cohen MH, Rieves D, Weiss K, Pazdur R: FDA report: eculizumab (Soliris) for the treatment of patients with paroxysmal nocturnal hemoglobinuria. Oncologist. 2008 Sep;13(9):993-1000. doi: 10.1634/theoncologist.2008-0086. Epub 2008 Sep 10. [PubMed:18784156]
  6. Rother RP, Rollins SA, Mojcik CF, Brodsky RA, Bell L: Discovery and development of the complement inhibitor eculizumab for the treatment of paroxysmal nocturnal hemoglobinuria. Nat Biotechnol. 2007 Nov;25(11):1256-64. [PubMed:17989688]
  7. Luzzatto L, Risitano AM, Notaro R: Paroxysmal nocturnal hemoglobinuria and eculizumab. Haematologica. 2010 Apr;95(4):523-6. doi: 10.3324/haematol.2009.017848. [PubMed:20378572]
  8. Hillmen P, Young NS, Schubert J, Brodsky RA, Socie G, Muus P, Roth A, Szer J, Elebute MO, Nakamura R, Browne P, Risitano AM, Hill A, Schrezenmeier H, Fu CL, Maciejewski J, Rollins SA, Mojcik CF, Rother RP, Luzzatto L: The complement inhibitor eculizumab in paroxysmal nocturnal hemoglobinuria. N Engl J Med. 2006 Sep 21;355(12):1233-43. [PubMed:16990386]
  9. Hillmen P, Muus P, Duhrsen U, Risitano AM, Schubert J, Luzzatto L, Schrezenmeier H, Szer J, Brodsky RA, Hill A, Socie G, Bessler M, Rollins SA, Bell L, Rother RP, Young NS: Effect of the complement inhibitor eculizumab on thromboembolism in patients with paroxysmal nocturnal hemoglobinuria. Blood. 2007 Dec 1;110(12):4123-8. Epub 2007 Aug 16. [PubMed:17702897]
  10. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [PubMed:11752352]

Drug created on May 16, 2007 10:57 / Updated on November 20, 2019 12:25