Anakinra Property

storage temp. 

Store at 4°C, do not freeze

solubility 

Soluble in DMSO

form 

Liquid

color 

Colorless to light yellow

CAS DataBase Reference

143090-92-0

Hazard and Precautionary Statements (GHS)

Anakinra Chemical Properties,Usage,Production

Description

Anakinra was launched in the US as a new daily subcutaneous injection therapy for the reduction of signs and symptoms of moderately to severely active rheumatoid arthritis (RA) in adults who have failed to respond to one or more disease-modifying antirheumatic drugs. Anakinra, N²-L-methionylinterleukin-1 receptor antagonist (human isoform x reduced), is the first recombinant non-glycosylated human IL-1 receptor antagonist (IL-lra). It was isolated from human monocytes, cloned and expressed in Escherichia coll. IL-1ra is an endogenous cytokine that blocks the binding of the pro-inflammatory cytokine ILl to its receptor thereby balancing the cartilage destruction and bone resorption mediated by IL-1. In RA patients, the amount of endogenous IL-lra in the synovial joint is not sufficient to neutralize the detrimental effects of an excessive level of IL-1. In collageninduced arthritic mice, continuous i.p. infusion of IL-1ra suppressed the established arthritis, reduced cartilaginous destruction and restored the synthetic function in articular cartilage chondrocytes. In clinical trials with RA patients, anakinra was found to attenuate disease severity and to reduce joint destruction over 6 to 12 months. Treatment with anakinra was generally well tolerated, although skin reactions at the injection site were reported. Experiments in rat showed that subcutaneous or intradermal injection of high doses of anakinra or its vehicle caused a non-immunologically mediated cutaneous mast cell degranulation.

Originator

Amgen/University of Colorado (US)

Uses

Anti-inflammatory (nonsteroidal); suppressant (inflammatory bowel disease).

Indications

Anakinra (Kineret) is the first antirheumatic agent that acts by blocking the action of IL-1. This drug was recently approved for the treatment of moderately to severely active rheumatoid arthritis in adults who have not responded to therapy with one or more DMARDs. Anakinra may be used alone or in combination with DMARDs other than the TNF antagonists. Clinical trials have shown anakinra to be more effective than placebo, either alone or in conjunction with methotrexate.

brand name

Antril (Synergen);Kineret.

Biological Functions

IL-1Rα plays an important role for regulating synovial proinflammatory IL-1 activity by preventing IL-1 from binding to IL-1R1. Analysis of synovial fluid suggests that the rheumatoid synovium is characterized by an overexpression of IL-1. The resulting imbalance between IL-1 and IL-1Rα has been implicated in perpetuating the pro-inflammatory response and destructive tide of events in rheumatoid arthritis. If IL-1 is prevented from binding to IL-1R1, the inflammatory response decreases. The levels of the naturally occurring IL-lRα in synovium and synovial fluid from rheumatoid arthritis patients are insufficient to compete with the elevated amount of locally produced IL-1.

Pharmacology

Anakinra is a nonglycosylated form of the human IL-1 receptor antagonist (IL-1ra). It is produced in a recombinant Escherichia coli expression system and has an additional methionine residue at its amino terminus. In rheumatoid arthritis patients, the amount of naturally occurring IL-1ra in the synovial fluid is not sufficient to counteract the high levels of locally produced IL-1. Anakinra acts as a competitive antagonist of the type 1 IL-1 receptor and decreases the pain and inflammation produced by IL-1. It is administered as a daily subcutaneous injection.

Clinical Use

Anakinra is the first IL-1Rα to be approved for use in adults with moderate to severe active rheumatoid arthritis who have not responded adequately to conventional DMARD therapy. It may be used either alone or in combination with methotrexate. Anakinra is supplied in single-use, prefilled, glass syringes as sterile, clear, preservative-free solution that is administered daily as a self-administered subcutaneous injection under the skin. Some potential side effects include injection site reactions, decreased white blood cell counts, headache, and an increase in upper respiratory infections. There may be a slightly higher rate of respiratory infections in people who have asthma or chronic obstructive pulmonary disease. Persons with an active infection are advised not to use anakinra. Its elimination half-life after sc administration is 4 to 6 hours.

Side effects

The most common adverse reactions to anakinra are redness, bruising, pain, and inflammation at the injection site. Neutropenia may occur, and the risk of serious infection is somewhat elevated, particularly in asthmatic patients.Antibodies to anakinra can develop with long-term therapy, but no correlation between antibody development and clinical response or adverse effects has been observed.

Drug interactions

Potentially hazardous interactions with other drugs
Adalimumab, certolizumab, etanercept, golimumab and infliximab: avoid concomitant use.
Live vaccines: avoid concomitant use.

Metabolism

Renally metabolised and excreted.

Precautions

No drug interaction studies have been conducted in humans.Animal studies indicate no change in the clearanceor toxicity of either methotrexate or anakinrawhen the two agents are administered together. Concomitantadministration of a TNF blocker appears toincrease the risk of serious infection. The response tovaccines may be diminished in patients taking anakinra.