Adalimumab

Identification

Name
Adalimumab
Accession Number
DB00051
Description

Adalimumab is a subcutaneously administered biological disease modifier for the treatment of rheumatoid arthritis and other chronic debilitating diseases mediated by tumor necrosis factor 2, 3. It was originally launched by Abbvie in the U.S. and approved in 2002 by the FDA 1. This drug is frequently known as Humira. It is produced by recombinant DNA technology using a mammalian cell expression system. This drug is available in a prefilled syringe form and convenient pen form for subcutaneous self-administered doses 1. A new biosimilar to adalimumab, named adalimumab-adaz, was approved by the FDA on October 31, 2018. This biosimilar is known as Hyrimoz, and is a trademark of Novartis AG 9.

Type
Biotech
Groups
Approved, Experimental
Biologic Classification
Protein Based Therapies
Monoclonal antibody (mAb)
Protein Structure
Db00051
Protein Chemical Formula
C6428H9912N1694O1987S46
Protein Average Weight
144190.3 Da
Sequences
> Adalimumab Light chain:
DIQMTQSPSSLSASVGDRVTITCRASQGIRNYLAWYQQKPGKAPKLLIYAASTLQSGVPS
RFSGSGSGTDFTLTISSLQPEDVATYYCQRYNRAPYTFGQGTKVEIKRTVAAPSVFIFPP
SDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLT
LSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC
> Adalimumab Heavy chain:
EVQLVESGGGLVQPGRSLRLSCAASGFTFDDYAMHWVRQAPGKGLEWVSAITWNSGHIDY
ADSVEGRFTISRDNAKNSLYLQMNSLRAEDTAVYYCAKVSYLSTASSLDYWGQGTLVTVS
SASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQS
SGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLG
GPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQY
NSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRD
ELTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSR
WQQGNVFSCSVMHEALHNHYTQKSLSLSPGK
Download FASTA Format
Synonyms
  • Adalimumab (genetical recombination)
  • adalimumab-adaz
  • adalimumab-adbm
  • adalimumab-afzb
  • adalimumab-atto
  • adalimumab-bwwd
  • adalimumab-fkjp
External IDs
  • ABP-501
  • BCD-057
  • BI-695501
  • BI695501
  • CHS-1420
  • D2E7
  • GP-2017
  • GP2017
  • LU-200134
  • LU200134
  • M-923
  • M923
  • MSB-11022
  • MSB11022
  • ONS-3010
  • SB-5
  • SB5

Pharmacology

Indication

The following are conditions for which adalimumab has been indicated 12, Label, 10, 5, 6, 11.

Rheumatoid Arthritis (Moderate to Severe)

Juvenile Idiopathic Arthritis (Moderately to Severely Active)

Psoriatic Arthritis (Active)

Ankylosing Spondylitis (Active)

Crohn’s Disease (Moderately to Severely Active)

Ulcerative Colitis (Moderately to Severely Active)

Plaque Psoriasis (Moderate to Severe Chronic)

Non-infectious Intermediate, Posterior and Panuveitis

Hidradenitis Suppurativa (Moderate to Severe)

Pyoderma Gangrenosum (off-label)

Associated Conditions
Contraindications & Blackbox Warnings
Learn about our commercial Contraindications & Blackbox Warnings data.
Learn More
Pharmacodynamics

After treatment with adalimumab, a decrease in levels of acute phase reactant proteins of inflammation (C­ reactive protein [CRP] and erythrocyte sedimentation rate [ESR]) and serum cytokines (IL-6) was measured compared to baseline in patients diagnosed with rheumatoid arthritis. A decrease in CRP levels was also observed in patients diagnosed with Crohn’s disease. Serum levels of matrix metalloproteinases (MMP-1 and MMP-3) that lead to the tissue remodeling responsible for cartilage destruction were also found to be decreased after administration of adalimumab 12, Label. A reduction in signs and symptoms of disease, the induction of a clinical response, an inhibition of structural damage, and improvements in physical function in adult and pediatric patients with various inflammatory conditions have been demonstrated 1, 3, Label.

Mechanism of action

Adalimumab binds with specificity to tumor necrosis factor-alpha (TNF-alpha) 2, 3 and inhibits its interaction with the p55 and p75 cell surface TNF receptors. Adalimumab also lyses surface tumor necrosis factor expressing cells in vitro when in the presence of complement. Adalimumab does not bind or inactivate lymphotoxin (Tumor necrosis factor-beta). TNF is a naturally occurring cytokine that plays a role in normal inflammatory and immune responses 3. Increased levels of TNF are found in the joint synovial fluid of rheumatoid arthritis, psoriatic arthritis, and ankylosing spondylitis patients, and play an imperative role in pathologic inflammation and the joint destruction that are major complications of these diseases. Increased levels of TNF are also measured in psoriasis plaques. In plaque psoriasis, treatment with adalimumab may decrease the epidermal thickness and inflammatory cell infiltration. The relationship between these pharmacodynamics and the mechanism(s) by which adalimumab achieves its clinical effects is not known. Additionally, adalimumab alters biological responses that are induced/regulated by TNF, including changes in the levels of adhesion molecules responsible for leukocyte migration during inflammation (ELAM-1, VCAM-1, and ICAM-1 with an IC50 of 1-2 X 10-10M) 12.

TargetActionsOrganism
ATumor necrosis factor
antibody
Humans
Absorption

The maximum serum concentration (Cmax) and the time to reach the maximum concentration (Tmax) were 4.7 ± 1.6 μg/mL and 131 ± 56 hours respectively, following a single 40 mg subcutaneous administration of adalimumab to healthy adult subjects. The average absolute bioavailability of adalimumab estimated from three clinical studies after a single 40 mg subcutaneous dose of adalimumab was 64%. The pharmacokinetics of adalimumab showed a linear pattern over the dose range of 0.5 to 10.0 mg/kg following a single intravenous dose 12.

Volume of distribution

The distribution volume (Vss) ranged from 4.7-6.0 L 12. Adalimumab concentrations in the synovial fluid from five rheumatoid arthritis patients ranged from 31-96% of those in serum 12.

Protein binding
Not Available
Metabolism

Most likely removed by opsonization via the reticuloendothelial system 7.

Route of elimination
Not Available
Half-life

The mean terminal half-life was approximately 2 weeks, ranging from 10 to 20 days across studies 12.

Clearance

12 mL/hr [RA patients with dose 0.25-10 mg/kg] 12. Population pharmacokinetic analyses in patients with rheumatoid arthritis showed a trend toward a higher apparent clearance of adalimumab in the presence of anti-adalimumab antibodies, and a lower clearance with increasing age in patients aged 40 years old to greater than 75 years old 12.

Adverse Effects
Learn about our commercial Adverse Effects data.
Learn More
Toxicity

Carcinogenesis, Mutagenesis, Impairment of Fertility

Long-term animal studies of adalimumab products have not been performed to study the carcinogenic potential or the drug's effect on fertility 12.

Refer to the "Adverse Effects" section for more information on adverse effects and "Blackbox Warnings" section for important black box information/warnings.

Rare side effects include: worsening or initiation of congestive heart failure, a lupus-like syndrome, lymphoma, medically significant cytopenias, and worsening or initiation of multiple sclerosis/neurological diseases. There has been reported pancytopenia and increased liver transaminases with the use of adalimumab, which suggests that laboratory value monitoring blood counts and liver function, at least intermittently, are important 4.

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
AbataceptThe risk or severity of infection can be increased when Adalimumab is combined with Abatacept.
AbciximabThe risk or severity of adverse effects can be increased when Adalimumab is combined with Abciximab.
AbirateroneThe metabolism of Abiraterone can be increased when combined with Adalimumab.
AcalabrutinibThe metabolism of Acalabrutinib can be increased when combined with Adalimumab.
AcebutololThe metabolism of Acebutolol can be increased when combined with Adalimumab.
AcenocoumarolThe metabolism of Acenocoumarol can be increased when combined with Adalimumab.
AcetaminophenThe metabolism of Acetaminophen can be increased when combined with Adalimumab.
AcetohexamideThe metabolism of Acetohexamide can be increased when combined with Adalimumab.
Acetylsalicylic acidThe metabolism of Acetylsalicylic acid can be increased when combined with Adalimumab.
AcyclovirThe metabolism of Acyclovir can be increased when combined with Adalimumab.
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

Products

International/Other Brands
Amjevita (Amgen, Inc.) / Cyltezo (Boehringer Ingelheim Pharmaceuticals, Inc.) / Humira Pen (Abbott Laboratories)
Brand Name Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
HadlimaSolutionSubcutaneousSamsung Bioepis Co., Ltd.Not applicableNot applicableCanada flag
Hadlima PushtouchSolutionSubcutaneousSamsung Bioepis Co., Ltd.Not applicableNot applicableCanada flag
HumiraInjection, solution40 mgSubcutaneousAbb Vie Deutschland Gmb H & Co. Kg2003-09-08Not applicableEU flag
HumiraInjection, solution40 mgSubcutaneousAbb Vie Deutschland Gmb H & Co. Kg2003-09-08Not applicableEU flag
HumiraInjection, solution40 mgSubcutaneousAbb Vie Deutschland Gmb H & Co. Kg2003-09-08Not applicableEU flag
HumiraSolution20 mgSubcutaneousAbbvie2020-08-18Not applicableCanada flag
HumiraSolution40 mgSubcutaneousAbbvie2004-09-24Not applicableCanada flag
HumiraInjection, solution40 mgSubcutaneousAbb Vie Deutschland Gmb H & Co. Kg2003-09-08Not applicableEU flag
HumiraInjection, solution40 mgSubcutaneousAbb Vie Deutschland Gmb H & Co. Kg2003-09-08Not applicableEU flag
HumiraInjection, solution40 mgSubcutaneousAbb Vie Deutschland Gmb H & Co. Kg2003-09-08Not applicableEU flag
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
Mixture Products
NameIngredientsDosageRouteLabellerMarketing StartMarketing EndRegionImage
HumiraAdalimumab (20 mg/0.4mL) + Isopropyl alcohol (0.70 mL/1mL)Subcutaneous; TopicalAbbVie Inc.2008-02-21Not applicableUS flag
HumiraAdalimumab (40 mg/0.8mL) + Isopropyl alcohol (0.70 mL/1mL)Subcutaneous; TopicalA-S Medication Solutions2006-06-232019-12-31US flag
HumiraAdalimumab (40 mg/0.8mL) + Isopropyl alcohol (0.70 mL/1mL)Subcutaneous; TopicalAbbVie Inc.2002-12-31Not applicableUS flag
HumiraAdalimumab (80 mg/0.8mL) + Adalimumab (40 mg/0.4mL) + Isopropyl alcohol (0.7 mL/1mL)Subcutaneous; TopicalAbbVie Inc.2017-04-21Not applicableUS flag
HumiraAdalimumab (80 mg/0.8mL) + Isopropyl alcohol (0.70 mL/1mL)Subcutaneous; TopicalAbbVie Inc.2016-10-17Not applicableUS flag
HumiraAdalimumab (40 mg/0.4mL) + Isopropyl alcohol (0.70 mL/1mL)Subcutaneous; TopicalAbbVie Inc.2016-03-09Not applicableUS flag
HumiraAdalimumab (40 mg/0.8mL) + Isopropyl alcohol (0.70 mL/1mL)Subcutaneous; TopicalAbbVie Inc.2006-06-23Not applicableUS flag
HumiraAdalimumab (10 mg/0.1mL) + Isopropyl alcohol (0.7 mL/1mL)Subcutaneous; TopicalAbbVie Inc.2017-04-28Not applicableUS flag
HumiraAdalimumab (80 mg/0.8mL) + Adalimumab (40 mg/0.4mL) + Isopropyl alcohol (0.7 mL/1mL)Subcutaneous; TopicalAbbVie Inc.2017-04-21Not applicableUS flag
HumiraAdalimumab (40 mg/0.8mL) + Isopropyl alcohol (0.70 mL/1mL)Subcutaneous; TopicalA-S Medication Solutions2006-06-23Not applicableUS flag

Categories

ATC Codes
L04AB04 — Adalimumab
Drug Categories
Chemical TaxonomyProvided by Classyfire
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

Chemical Identifiers

UNII
FYS6T7F842
CAS number
331731-18-1

References

General References
  1. Kivitz A, Segurado OG: HUMIRA pen: a novel autoinjection device for subcutaneous injection of the fully human monoclonal antibody adalimumab. Expert Rev Med Devices. 2007 Mar;4(2):109-16. doi: 10.1586/17434440.4.2.109. [PubMed:17359217]
  2. Mease PJ: Adalimumab in the treatment of arthritis. Ther Clin Risk Manag. 2007 Mar;3(1):133-48. [PubMed:18360621]
  3. Scheinfeld N: Adalimumab (HUMIRA): a review. J Drugs Dermatol. 2003 Aug;2(4):375-7. [PubMed:12884458]
  4. Scheinfeld N: Adalimumab: a review of side effects. Expert Opin Drug Saf. 2005 Jul;4(4):637-41. doi: 10.1517/14740338.4.4.637. [PubMed:16011443]
  5. Fonder MA, Cummins DL, Ehst BD, Anhalt GJ, Meyerle JH: Adalimumab therapy for recalcitrant pyoderma gangrenosum. J Burns Wounds. 2006 Nov 20;5:e8. [PubMed:17149453]
  6. Hinterberger L, Muller CS, Vogt T, Pfohler C: Adalimumab: a treatment option for pyoderma gangrenosum after failure of systemic standard therapies. Dermatol Ther (Heidelb). 2012 Dec;2(1):6. doi: 10.1007/s13555-012-0006-6. Epub 2012 May 12. [PubMed:23205329]
  7. 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]
  8. Patent: Methods related to adalimumab [Link]
  9. Sandoz received US FDA approval for bio similar, Hyrimoz [Link]
  10. HUMIRA website [Link]
  11. Abbvie Website [Link]
  12. HUMIRA FDA LABEL [File]
UniProt
P01857
Genbank
J00228
KEGG Drug
D02597
PubChem Substance
46504982
RxNav
327361
ChEMBL
CHEMBL1201580
Therapeutic Targets Database
DAP000392
PharmGKB
PA10004
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
Wikipedia
Adalimumab
AHFS Codes
  • 92:36.00 — Disease-modifying Antirheumatic Agents
  • 92:20.00 — Immunomodulatory Agents
  • 56:92.00 — Miscellaneous GI Drugs
FDA label
Download (3.64 MB)
MSDS
Download (157 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
4Active Not RecruitingBasic SciencePsoriasis1
4Active Not RecruitingBasic ScienceRheumatoid Arthritis1
4Active Not RecruitingPreventionCardiovascular Heart Disease / Rheumatoid Arthritis1
4Active Not RecruitingTreatmentAnkylosing Spondylitis (AS)1
4Active Not RecruitingTreatmentCD1
4Active Not RecruitingTreatmentCrohn's Disease (CD)1
4Active Not RecruitingTreatmentCrohn's Disease (CD) / Inflammatory Bowel Diseases (IBD) / Stricture; Bowel1
4Active Not RecruitingTreatmentRheumatoid Arthritis2
4Active Not RecruitingTreatmentUlcerative Colitis1
4CompletedNot AvailableRheumatoid Arthritis3

Pharmacoeconomics

Manufacturers
Not Available
Packagers
  • Abbott Laboratories Ltd.
  • Vetter Pharma Fertigung GmbH and Co. KG
Dosage Forms
FormRouteStrength
Injection, solutionCutaneous; Parenteral20 MG
Injection, solutionCutaneous; Parenteral40 MG
SolutionSubcutaneous50 mg
SolutionSubcutaneous
Injection, solutionCutaneous20 MG
Injection, solutionCutaneous40 MG
Injection, solutionCutaneous40 MG/0.8ML
Injection, solutionCutaneous; Parenteral80 MG
Injection, solutionSubcutaneous40 mg
SolutionSubcutaneous10 mg
SolutionSubcutaneous20 mg
SolutionSubcutaneous40 mg
SolutionSubcutaneous80 mg
Injection20 mg/0.2ml
Injection40 mg/0.8ml
Injection40 mg/0.4ml
Injection, solution40 mg/0.8ml
Solution
SolutionSubcutaneous100 mg
Injection, solutionCutaneous; Parenteral40 MG/0.8ML
Injection, solutionSubcutaneous40 mg/0.8mL
Prices
Unit descriptionCostUnit
Humira (1 Box = Two 40 mg/0.8ml Syringes) Box1995.1USD box
Humira 2 20 mg/0.4ml Kit 1 Box = Two 20 mg/0.4ml Syringes1995.1USD box
Humira Pen 2 40 mg/0.8ml Kit (1 Box = 1 Kit Containing Two 40 mg/0.8ml Pens)1995.1USD box
Humira 20 mg/0.4 ml syringe959.19USD syringe
Humira 40 mg/0.8 ml pen959.19USD pen
Humira crohn's starter pack959.19USD each
Humira psoriasis starter pack959.19USD each
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)Region
CA2243459No2002-09-172017-02-10Canada flag
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
PropertyValueSource
isoelectric point8.25http://www.druglib.com/activeingredient/adalimumab/chembio/

Targets

Kind
Protein
Organism
Humans
Pharmacological action
Yes
Actions
Antibody
General Function
Tumor necrosis factor receptor binding
Specific Function
Cytokine that binds to TNFRSF1A/TNFR1 and TNFRSF1B/TNFBR. It is mainly secreted by macrophages and can induce cell death of certain tumor cell lines. It is potent pyrogen causing fever by direct ac...
Gene Name
TNF
Uniprot ID
P01375
Uniprot Name
Tumor necrosis factor
Molecular Weight
25644.15 Da
References
  1. Lorenz HM: Technology evaluation: adalimumab, Abbott laboratories. Curr Opin Mol Ther. 2002 Apr;4(2):185-90. [PubMed:12044041]
  2. Flendrie M, Creemers MC, Welsing PM, den Broeder AA, van Riel PL: Survival during treatment with tumour necrosis factor blocking agents in rheumatoid arthritis. Ann Rheum Dis. 2003 Nov;62 Suppl 2:ii30-3. [PubMed:14532145]
  3. Aguillon JC, Contreras J, Dotte A, Cruzat A, Catalan D, Salazar L, Molina MC, Guerrero J, Lopez M, Soto L, Salazar-Onfray F, Cuchacovich M: [New immunological weapons for medicine in the 21st Century: biological therapy based on the use of the latest generation monoclonal antibodies]. Rev Med Chil. 2003 Dec;131(12):1445-53. [PubMed:15022409]
  4. Bang LM, Keating GM: Adalimumab: a review of its use in rheumatoid arthritis. BioDrugs. 2004;18(2):121-39. [PubMed:15046527]

Drug created on June 13, 2005 07:24 / Updated on September 22, 2020 02:11

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