Adalimumab

Identification

Summary

Adalimumab is a monoclonal anti-tumor necrosis factor alpha antibody used in the treatment of a wide variety of inflammatory conditions such as rheumatoid arthritis, Crohn's disease, and ankylosing spondylitis.

Brand Names

Humira

Generic Name

Adalimumab

DrugBank Accession Number

DB00051

Background

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

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
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 ¹³, ^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)

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Associated Conditions

Contraindications & Blackbox Warnings

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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 ¹³, ^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) ¹³.

Target	Actions	Organism
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 ¹³.

Volume of distribution

The distribution volume (Vss) ranged from 4.7-6.0 L ¹³. Adalimumab concentrations in the synovial fluid from five rheumatoid arthritis patients ranged from 31-96% of those in serum ¹³.

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 ¹³.

Clearance

12 mL/hr [RA patients with dose 0.25-10 mg/kg] ¹³. 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 ¹³.

Adverse Effects

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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 ¹³.

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.

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.

Drug	Interaction
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Abatacept	The risk or severity of infection can be increased when Adalimumab is combined with Abatacept.
Abciximab	The risk or severity of adverse effects can be increased when Adalimumab is combined with Abciximab.
Abemaciclib	The metabolism of Abemaciclib can be increased when combined with Adalimumab.
Acalabrutinib	The metabolism of Acalabrutinib can be increased when combined with Adalimumab.
Acebutolol	The metabolism of Acebutolol can be increased when combined with Adalimumab.
Acenocoumarol	The metabolism of Acenocoumarol can be increased when combined with Adalimumab.
Acetaminophen	The metabolism of Acetaminophen can be increased when combined with Adalimumab.
Acetohexamide	The metabolism of Acetohexamide can be increased when combined with Adalimumab.
Acetylsalicylic acid	The metabolism of Acetylsalicylic acid can be increased when combined with Adalimumab.
Acyclovir	The metabolism of Acyclovir can be increased when combined with Adalimumab.

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Food Interactions

No interactions found.

Products

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International/Other Brands

Amjevita (Amgen, Inc.) / Cyltezo (Boehringer Ingelheim Pharmaceuticals, Inc.) / Humira Pen (Abbott Laboratories)

Brand Name Prescription Products

Name	Dosage	Strength	Route	Labeller	Marketing Start	Marketing End
Abrilada	Solution	10 mg / 0.2 mL	Subcutaneous	Pfizer Canada Ulc	Not applicable	Not applicable
Abrilada	Solution	40 mg / 0.8 mL	Subcutaneous	Pfizer Canada Ulc	Not applicable	Not applicable
Abrilada	Solution	20 mg / 0.4 mL	Subcutaneous	Pfizer Canada Ulc	Not applicable	Not applicable
Abrilada	Kit; Solution	40 mg / 0.8 mL	Subcutaneous	Pfizer Canada Ulc	Not applicable	Not applicable
Abrilada	Solution	40 mg / 0.8 mL	Subcutaneous	Pfizer Canada Ulc	Not applicable	Not applicable
Amgevita	Solution	50 mg / mL	Subcutaneous	Amgen	2021-02-19	Not applicable
Amgevita	Injection, solution	20 mg	Subcutaneous	Amgen Europe B.V.	2020-12-16	Not applicable
Amgevita	Injection, solution	40 mg	Subcutaneous	Amgen Europe B.V.	2020-12-16	Not applicable
Amgevita	Injection, solution	40 mg	Subcutaneous	Amgen Europe B.V.	2020-12-16	Not applicable
Amgevita	Injection, solution	40 mg	Subcutaneous	Amgen Europe B.V.	2020-12-16	Not applicable

Mixture Products

Name	Ingredients	Route	Labeller	Marketing Start	Marketing End
Humira	Adalimumab (40 mg/0.8mL) + Isopropyl alcohol (0.70 mL/1mL)	Subcutaneous; Topical	AbbVie Inc.	2006-06-23	Not applicable
Humira	Adalimumab (80 mg/0.8mL) + Adalimumab (40 mg/0.4mL) + Isopropyl alcohol (0.70 mL/1mL)	Subcutaneous; Topical	AbbVie Inc.	2016-10-17	Not applicable
Humira	Adalimumab (20 mg/0.2mL) + Isopropyl alcohol (0.70 mL/1mL)	Subcutaneous; Topical	AbbVie Inc.	2017-04-28	Not applicable
Humira	Adalimumab (40 mg/0.8mL) + Isopropyl alcohol (0.70 mL/1mL)	Subcutaneous; Topical	A-S Medication Solutions	2006-06-23	Not applicable
Humira	Adalimumab (40 mg/0.4mL) + Isopropyl alcohol (.70 mL/1mL)	Subcutaneous; Topical	AbbVie Inc.	2015-11-23	Not applicable
Humira	Adalimumab (80 mg/0.8mL) + Isopropyl alcohol (0.70 mL/1mL)	Subcutaneous; Topical	AbbVie Inc.	2017-04-21	Not applicable
Humira	Adalimumab (40 mg/0.8mL) + Isopropyl alcohol (0.70 mL/1mL)	Subcutaneous; Topical	A-S Medication Solutions	2006-06-23	2019-12-31
Humira	Adalimumab (10 mg/0.2mL) + Isopropyl alcohol (0.70 mL/1mL)	Subcutaneous; Topical	AbbVie Inc.	2014-09-23	2021-01-31
Humira	Adalimumab (80 mg/0.8mL) + Adalimumab (40 mg/0.4mL) + Isopropyl alcohol (0.70 mL/1mL)	Subcutaneous; Topical	AbbVie Inc.	2016-10-17	Not applicable
Humira	Adalimumab (80 mg/0.8mL) + Adalimumab (40 mg/0.4mL) + Isopropyl alcohol (0.7 mL/1mL)	Subcutaneous; Topical	AbbVie Inc.	2017-04-21	Not applicable

Chemical Identifiers

UNII: FYS6T7F842
CAS number: 331731-18-1

References

General References

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. [Article]
Mease PJ: Adalimumab in the treatment of arthritis. Ther Clin Risk Manag. 2007 Mar;3(1):133-48. [Article]
Scheinfeld N: Adalimumab (HUMIRA): a review. J Drugs Dermatol. 2003 Aug;2(4):375-7. [Article]
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. [Article]
Fonder MA, Cummins DL, Ehst BD, Anhalt GJ, Meyerle JH: Adalimumab therapy for recalcitrant pyoderma gangrenosum. J Burns Wounds. 2006 Nov 20;5:e8. [Article]
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. [Article]
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. [Article]
Patent: Methods related to adalimumab [Link]
Sandoz received US FDA approval for bio similar, Hyrimoz [Link]
HUMIRA website [Link]
Abbvie Website [Link]
FDA Approved Drug Products: HUMIRA (adalimumab) injection [Link]
HUMIRA FDA LABEL [File]

External Links

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

FDA label

Download (3.64 MB)

MSDS

Download (157 KB)

Clinical Trials

Clinical Trials

Phase	Status	Purpose	Conditions	Count
4	Active Not Recruiting	Treatment	CD	1
4	Active Not Recruiting	Treatment	Crohn's Disease (CD)	1
4	Active Not Recruiting	Treatment	Crohn's Disease (CD) / Inflammatory Bowel Diseases (IBD) / Stricture; Bowel	1
4	Active Not Recruiting	Treatment	Crohn's Disease (CD) / Inflammatory Bowel Diseases (IBD) / Ulcerative Colitis	1
4	Active Not Recruiting	Treatment	Rheumatoid Arthritis	3
4	Completed	Not Available	Rheumatoid Arthritis	2
4	Completed	Basic Science	Psoriasis (PsO)	1
4	Completed	Basic Science	Rheumatoid Arthritis	2
4	Completed	Diagnostic	Enterocolitis / Spondyloarthritis (SpA)	1
4	Completed	Prevention	Cardiovascular Disease (CVD) / Rheumatoid Arthritis	1

Pharmacoeconomics

Manufacturers

Not Available

Packagers

Abbott Laboratories Ltd.
Vetter Pharma Fertigung GmbH and Co. KG

Dosage Forms

Form	Route	Strength
Kit; solution	Subcutaneous	40 mg / 0.8 mL
Solution	Subcutaneous	10 mg / 0.2 mL
Injection, solution		20 mg/0.4ml
Injection, solution	Parenteral; Subcutaneous	20 MG
Injection, solution	Parenteral; Subcutaneous	40 MG
Solution	Subcutaneous	50 mg / mL
Injection, solution	Parenteral	40 MG
Injection, solution	Parenteral	40 MG/0.8ML
Injection, solution	Subcutaneous	20 mg/0.4ml
Solution	Subcutaneous	50 mg
Solution	Subcutaneous	40 mg/0.8ml
Injection, solution	Subcutaneous	20 MG
Injection, solution	Subcutaneous	40 MG
Solution	Subcutaneous	20 mg / 0.4 mL
Injection	Subcutaneous
Injection	Subcutaneous	40 MG/0.4ML
Injection, solution	Parenteral; Subcutaneous	80 MG
Injection, solution	Subcutaneous	80 mg
Solution	Subcutaneous	10 mg / 0.1 mL
Solution	Subcutaneous	20 mg / 0.2 mL
Solution	Subcutaneous	40 mg / 0.8 mL
Solution	Subcutaneous	40 mg / 0.4 mL
Solution	Subcutaneous	80 mg / 0.8 mL
Injection, solution	Parenteral	40 MG/0.4ML
Injection, solution
Injection, solution	Parenteral	80 MG/0.8ML
Injection, solution	Subcutaneous
Injection, solution	Subcutaneous	20.0 mg/0.2mL
Injection, solution	Subcutaneous	40.0 mg
Injection, solution	Subcutaneous	40 mg/0.4ml
Injection	Subcutaneous	40 mg
Injection	Subcutaneous	40 mg/0.8ml
Injection	Subcutaneous	40.0 mg
Injection, solution	Subcutaneous	80.0 mg/0.8mL
Solution	Subcutaneous	40 mg
Solution	Subcutaneous	100 mg
Injection, solution	Parenteral; Subcutaneous	40 MG/0.8ML
Injection, solution	Subcutaneous	40 mg/0.8mL
Injection, solution		40 mg/0.8ml

Prices

Unit description	Cost	Unit
Humira (1 Box = Two 40 mg/0.8ml Syringes) Box	1995.1USD	box
Humira 2 20 mg/0.4ml Kit 1 Box = Two 20 mg/0.4ml Syringes	1995.1USD	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 syringe	959.19USD	syringe
Humira 40 mg/0.8 ml pen	959.19USD	pen
Humira crohn's starter pack	959.19USD	each
Humira psoriasis starter pack	959.19USD	each

DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.

Patents

Patent Number	Pediatric Extension	Approved	Expires (estimated)	Region
CA2243459	No	2002-09-17	2017-02-10

Properties

State

Liquid

Experimental Properties

Property	Value	Source
isoelectric point	8.25	http://www.druglib.com/activeingredient/adalimumab/chembio/

Targets

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Details1. Tumor necrosis factor

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

Lorenz HM: Technology evaluation: adalimumab, Abbott laboratories. Curr Opin Mol Ther. 2002 Apr;4(2):185-90. [Article]
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. [Article]
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. [Article]
Bang LM, Keating GM: Adalimumab: a review of its use in rheumatoid arthritis. BioDrugs. 2004;18(2):121-39. [Article]

Drug created at June 13, 2005 13:24 / Updated at November 28, 2021 11:56

Adalimumab

Identification

Pharmacology

Interactions

Products

Categories

Chemical Identifiers

References

Clinical Trials

Pharmacoeconomics

Properties

Targets

References