Anakinra

Sample preparation Inject a 50 (xL aliquot of plasma or tissue homogenate supernatant. 

Mobile phase 10 mM pH 6.5 citrate buffer containing 140 mM NaCl and 0.5 mM EDTA 

Carmichael, D.P. Bloedow, D.C. Kidney as a major clearance organ for recombinant human interleukin-1 receptor antagonist, J.Pharm.Sci., 1995,84, 575-580. 

5 2-(A(-morpholuio)ethanesulfonic acid monohydrate. B was 20 mM pH 5.5 2-(N-morpholino)ethanesulfonic acid monohydrate containing 1.0 M NaCl. 

Nahata, M.C. Morosco, R.S. Sabados, B.K. Weber, T.R. Stability and compatibility of anakinra with intravenous cimetidine hydrochloride or famotidine in 0.9% sodium chloride injection, J.Clin.Pharm. Ther., 1995,20, 97-99. 

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Recombinant human DL-1 receptor antagonist (Anakinra, Kineret ) blocks the biological activity of interleukin-1 by competitively inhibiting IL-1 binding to the interleukin-1 type I receptor (IL-1RI), which is expressed in a wide variety of tissues and organs. Thereby it reduces the pro-inflammatory activities of IL-1 including cartilage destiuction and bone resorption. Side effects include an increased risk of infections and neutropenia. 

IL-1 receptor antagonist Anakinra A naturally occurring complete antagonist, effective in rheumatoid arthritis. 

Anakinra/Kineret, an IL-1 receptor antagonist approved for use in rheumatoid arthritis, was recently evaluated in a small phase II trial. When initiated within 6 hours after stroke onset, Anakinra treatment yielded promising preliminary results it was deemed safe with demonstrable biologic activity and likely favorable clinical outcome." ... 

Anakinra (Kineret) 100-150 mg daily SC injection 2-4 weeks HA, N, V, D, ISR Monitor for infection ... 

Anakinra is a recombinant form of human IL-1 receptor antagonist. Anakinra inhibits the activity of IL-1 by binding to it and preventing cell signaling.28 Patients must administer a subcutaneous injection every day, which may be less desirable than other treatment options. Anakinra may be used in combination with other DMARDs in patients not responding to or unable to tolerate DMARDs or TNF antagonists.21 Anakinra should not be used in combination with TNF antagonists due to the increased risk of infection.21... 

Several pro-inflammatory cytokines, such as TNFa, IL-1, IL-6, are important in the initiation and maintenance of various autoimmune diseases, such as RA, CD, and psoriasis. Thus, targeted therapies, which have been developed to inhibit their activity, have resulted in clinical improvement of these patients. Currently, there are three TNFa inhibitors (etanercept, infliximab, and adalimumab) and one IL-1 receptor antagonist (anakinra) that have been approved for the treatment of at least one of these diseases. In addition, a number of other anti-cytokine therapies are in clinical development. The TNFa antagonists will be reviewed here. 

Kepivance, Palifermin, KSA-2 Kineret , Anakinra IL-IRa Amgen, Inc Amgen, Inc... 

Anakinra - recombinant version of human lL-1 Rheumatoid arthritis patients failing to respond... 

In addition to the small molecular weight drugs, various antibodies (adalimumab, ritux-imab, omalizumab), a recombinant form of human IL-l-receptor antagonist (anakinra) and a recombinant fusion protein comprising the... 

Coadministration with anakinra in RA patients resulted in a 7% rate of serious infection. 

The recommended dose of anakinra is 100 mg/day administered at approximately the same time daily by subcutaneous injection. Higher doses did not result in a higher response. Administer the dose at approximately the same time every day. 

Pharmacology Anakinra is a recombinant, nonglycosylated form of the human interleukin-1 receptor antagonist (IL-1 Ra). Anakinra differs from native human IL-IRa in that it has a single methionine residue at its amino terminus. It is produced by recombinant DNA technology using an Escherichia coli bacterial expression system. 

Anakinra blocks the biologic activity of IL-1 by competitively inhibiting IL-1 binding to the interleukin-1 type I receptor (IL-1RI), which is expressed in a wide variety of tissues and organs. 

Pharmacokinetics The absolute bioavailability after a 70 mg subcutaneous bolus injection in healthy subjects (n = 11) is 95%. In subjects with RA, maximum plasma concentrations occurred 3 to 7 hours after subcutaneous administration of anakinra at clinically relevant doses (1 to 2 mg/kg n = 18) the terminal half-life ranged from 4 to 6 hours. In RA patients, no unexpected accumulation was observed after daily subcutaneous doses for up to 24 weeks. The estimated clearance increased with increasing Ccr and body weight. 

Patients with known hypersensitivity to E. co//-derived proteins, anakinra, or any component of the product. 

Infections Anakinra has been associated with an increased incidence of serious infections (2%) vs placebo (less than 1%). Discontinue administration if a patient develops a serious infection. Do not initiate treatment with anakinra in patients with active infections. The safety and efficacy of anakinra in immunocompromised patients or in patients with chronic infections have not been evaluated. Coadministration of anakinra and etanercept has not demonstrated increased clinical benefit. Carefully monitor patients when considering initiation of anakinra therapy concurrently with etanercept therapy. 

Immunosuppression The impact of treatment with anakinra on active and/or chronic infections and the development of malignancies is not known. 

Vaccinations Do not give live vaccines concurrently with anakinra. No data are available on the secondary transmission of infections by live vaccines in patients receiving anakinra. Because anakinra interferes with normal immune response mechanisms to new antigens such as vaccines, vaccination may not be effective in... 

Hematologic events Patients may experience a decrease in neutrophil counts. Hypersensitivity reactions Hypersensitivity reactions associated with anakinra administration are rare. If a severe hypersensitivity reaction occurs, discontinue anakinra administration and initiate appropriate therapy. 

Lactation It is not known whether anakinra is secreted in human milk. Because many drugs are secreted in human milk, exercise caution if anakinra is administered to nursing women. 

Monitoring Assess neutrophil counts prior to initiating anakinra treatment, and while receiving anakinra, monthly for 3 months, and thereafter quarterly for a period up to 1 year. 

The most serious adverse reactions were serious infection and neutropenia, particularly when used in combination with TNF-blocking agents. The most common adverse reaction with anakinra is injection site reactions, the majority of which were reported as mild. These typically lasted for 14 to 28 days and were characterized by 1 or more of the following reactions Erythema, ecchymosis, inflammation, and pain. Adverse reactions occurring in at least 5% of RA patients include injection site reaction, worsening of RA, infection (eg, upper respiratory infection, sinusitis, influenza-like symptoms, other infections), headache, nausea, diarrhea, sinusitis. 

Serious infections were seen in clinical studies with concurrent use of anakinra and another TNF -blocking agent, etanercept, with no added clinical benefit compared with etanercept alone. The combination of infliximab and anakinra is not recommended. 

Concurrent administration of etanercept (another TNF -blocking agent) and anakinra (an interleukin-1 antagonist) has been associated with an increased risk of serious infections, and increased risk of neutropenia and no additional benefit compared with these medicinal products alone. Other TNF -blocking agents (including infliximab) used in combination with anakinra also may result in similar toxicities. 

Kineret (anakinra rIL-1 receptor antagonist produced in E. coli) Vaccines Amgen Rheumatoid arthritis 2001 (USA)... 

Anakinra is the first biologic drug that has been developed specifically as an interleukin (IL)-l receptor antagonist and is derived from an endogenous IL-IRa. The drug blocks the activity of IL-1 in synovial joints, reducing the infiammatory and joint destructive processes associated with rheumatoid arthritis. It is administered subcutaneously and is generally well tolerated. Injection-site reactions are the most commonly reported adverse event. 

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