Description

Simple

A medication used to treat inflammatory conditions in the muscles and joints, such as rheumatoid arthritis, in children and adults.

Clinical

A disease-modifying antirheumatic drug (DMARD) used for the management of moderate-to-severe active rheumatoid arthritis and active polyarticular juvenile idiopathic arthritis as monotherapy or in combination with other DMARDs.

Overview

Abatacept is a soluble fusion protein, which links the extracellular domain of human cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) to the modified Fc (hinge, CH2, and CH3 domains) portion of human immunoglobulin G1 (IgG1). Structurally, abatacept is a glycosylated fusion protein with a MALDI-MS molecular weight of 92,300 Da and it is a homodimer of two homologous polypeptide chains of 357 amino acids each. It is produced through recombinant DNA technology in mammalian CHO cells. The drug has activity as a selective co-stimulation modulator with inhibitory activity on T lymphocytes. Although approved for the treatment of rheumatoid arthritis, Repligen has entered a slightly different formulation of CTLA4-Ig into clinical trials (RG2077).

Pharmacology

Indication

For the management of the signs and symptoms of moderate-to-severe active rheumatoid arthritis, inducing major clinical response, slowing the progression of structural damage, and improving physical function in adult patients. It is indicated both as a monotherapy and for use in combination with a c... Read more

Pharmacodynamic

Abatacept is the first in a new class of drugs known as Selective Co-stimulation Modulators. Known as a recombinant fusion protein, the drug consists of the extracellular domain of human cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) linked to a modified Fc portion of human immunoglobulin G Read more

Mechanism of action

Abatacept is a selective costimulation modulator, like CTLA-4, the drug has shown to inhibit T-cell (T lymphocyte) activation by binding to CD80 and CD86, thereby blocking interaction with CD28. Blockade of this interaction has been shown to inhibit the delivery of the second co-stimulatory signal r... Read more

Absorption

When a single 10 mg/kg intravenous infusion of abatacept is administered in healthy subjects, the peak plasma concentration (Cmax) was 292 mcg/mL. When multiple doses of 10 mg/kg was given to rheumatoid arthritis (RA) patients, the Cmax was 295 mcg/mL. The bioavailability of abatacept following subc... Read more

Protein binding

Information currently not available.

Volume of distribution

0.07 L/kg [RA Patients, IV administration]0.09 L/kg [Healthy Subjects, IV administration]0.11 L/kg [RA patients, subcutaneous administration]

Clearance

0.23 mL/h/kg [Healthy Subjects after 10 mg/kg Intravenous Infusion]0.22 mL/h/kg [RA Patients after multiple 10 mg/kg Intravenous Infusions]0.4 mL/h/kg [juvenile idiopathic arthritis patients].The mean systemic clearance is 0.28 mL/h/kg when a subcutaneously administered to adult RA patients.The clea... Read more

Half life

16.7 (12-23) days in healthy subjects;
13.1 (8-25) days in RA subjects;
14.3 days when subcutaneously administered to adult RA patients.

Route of elimination

kidney and liver

Toxicity

Most common adverse events (≥10%) are headache, upper respiratory tract infection, nasopharyngitis, and nausea. Doses up to 50 mg/kg have been administered without apparent toxic effect.

Adverse Effects

Contraindications

Information currently not available.

Food Interactions

    Information currently not available.

Interactions

Type in a drug name to check for interaction with Abatacept
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  • Paracetamol(acetaminophen)
  • Paxil(paroxetine)
  • Pamelor(nortriptyline)
  • Panadol(acetaminophen)
  • Patanol(olopatadine ophthalmic)
  • Pataday(olopatadine ophthalmic)
  • Parnate(tranylcypromine)
  • Pazeo(olopatadine ophthalmic)
(R)-warfarin
The metabolism of (R)-warfarin can be increased when combined with Abatacept.
(S)-Warfarin
The metabolism of (S)-Warfarin can be increased when combined with Abatacept.
2-Methoxyethanol
The risk or severity of adverse effects can be increased when Abatacept is combined with 2-Methoxyethanol.
4-hydroxycoumarin
The metabolism of 4-hydroxycoumarin can be increased when combined with Abatacept.
4-Methoxyamphetamine
The metabolism of 4-Methoxyamphetamine can be increased when combined with Abatacept.
5-methoxy-N,N-dimethyltryptamine
The metabolism of 5-methoxy-N,N-dimethyltryptamine can be increased when combined with Abatacept.
6-O-benzylguanine
The metabolism of 6-O-benzylguanine can be increased when combined with Abatacept.
8-azaguanine
The metabolism of 8-azaguanine can be increased when combined with Abatacept.
8-chlorotheophylline
The metabolism of 8-chlorotheophylline can be increased when combined with Abatacept.
9-(N-methyl-L-isoleucine)-cyclosporin A
The risk or severity of adverse effects can be increased when Abatacept is combined with 9-(N-methyl-L-isoleucine)-cyclosporin A.
9-aminocamptothecin
The metabolism of 9-aminocamptothecin can be increased when combined with Abatacept.
9-Deazaguanine
The metabolism of 9-Deazaguanine can be increased when combined with Abatacept.
9-Methylguanine
The metabolism of 9-Methylguanine can be increased when combined with Abatacept.
Abetimus
The risk or severity of adverse effects can be increased when Abatacept is combined with Abetimus.
Acebutolol
The metabolism of Acebutolol can be increased when combined with Abatacept.
Acefylline
The metabolism of Acefylline can be increased when combined with Abatacept.
Acenocoumarol
The metabolism of Acenocoumarol can be increased when combined with Abatacept.
Acetaminophen
The metabolism of Acetaminophen can be increased when combined with Abatacept.
Acetohexamide
The metabolism of Acetohexamide can be increased when combined with Abatacept.
Acetylsalicylic acid
The metabolism of Acetylsalicylic acid can be increased when combined with Abatacept.
10 References
  1. 1 . Dall'Era M, Davis J: CTLA4Ig: a novel inhibitor of costimulation. Lupus. 2004;13(5):372-6.PubMed: 15230295
  2. 2 . Moreland L, Bate G, Kirkpatrick P: Abatacept. Nat Rev Drug Discov. 2006 Mar;5(3):185-6.PubMed: 16557658
  3. 3 . Weisman MH, Durez P, Hallegua D, Aranda R, Becker JC, Nuamah I, Vratsanos G, Zhou Y, Moreland LW: Reduction of inflammatory biomarker response by abatacept in treatment of rheumatoid arthritis. J Rheumatol. 2006 Nov;33(11):2162-6. Epub 2006 Oct 1.PubMed: 17014006
  4. 4 . Weyand CM, Goronzy JJ: T-cell-targeted therapies in rheumatoid arthritis. Nat Clin Pract Rheumatol. 2006 Apr;2(4):201-10.PubMed: 16932686
  5. 5 . Scheinfeld N: Abatacept: A review of a new biologic agent for refractory rheumatoid arthritis for dermatologists. J Dermatolog Treat. 2006;17(4):229-34.PubMed: 16971318
  6. 6 . Maxwell LJ, Singh JA: Abatacept for rheumatoid arthritis: a Cochrane systematic review. J Rheumatol. 2010 Feb;37(2):234-45. doi: 10.3899/jrheum.091066. Epub 2010 Jan 15.PubMed: 20080922
  7. 7 . Maxwell L, Singh JA: Abatacept for rheumatoid arthritis. Cochrane Database Syst Rev. 2009 Oct 7;(4):CD007277. doi: 10.1002/14651858.CD007277.pub2.PubMed: 19821401
  8. 8 . Nogid A, Pham DQ: Role of abatacept in the management of rheumatoid arthritis. Clin Ther. 2006 Nov;28(11):1764-78.PubMed: 17212998
  9. 9 . Hervey PS, Keam SJ: Abatacept. BioDrugs. 2006;20(1):53-61; discussion 62.PubMed: 16573350
  10. 10 . Reynolds J, Shojania K, Marra CA: Abatacept: a novel treatment for moderate-to-severe rheumatoid arthritis. Pharmacotherapy. 2007 Dec;27(12):1693-701.PubMed: 18041889