IUPAC nomenclature is a systematic way of naming organic chemical compounds. ... CAS registry numbers are unique numerical identifiers for chemical compounds, polymers, biological sequences and alloys. ... The Anatomical Therapeutic Chemical Classification System is used for the classification of drugs. ... A section of the Anatomical Therapeutic Chemical Classification System. ... PubChem is a database of chemical molecules . ... DrugBank is a database available at the University of Alberta that provides information about thousands of products. ... A chemical formula (also called molecular formula) is a concise way of expressing information about the atoms that constitute a particular chemical compound. ... The molecular mass of a substance (less accurately called molecular weight and abbreviated as MW) is the mass of one molecule of that substance, relative to the unified atomic mass unit u (equal to 1/12 the mass of one atom of carbon-12). ... In pharmacology, bioavailability is used to describe the fraction of an administered dose of medication that reaches the systemic circulation, one of the principal pharmacokinetic properties of drugs. ... Santorio Santorio (1561-1636) in his steelyard balance, from Ars de statica medecina, first published 1614 Metabolism (from μεταβολισμος (metabolismos)) is the biochemical modification of chemical compounds in living organisms anggjgjhnd cell (b). ... The elimination half-life of a drug (or any xenobiotic agent) refers to the timecourse necessary for the quantity of the xenobiotic agent in the body (or plasma concentration) to be reduced to half of its original level through various elimination processes. ... Excretion is the biological process by which an organism chemically separates waste products from its body. ... The pregnancy category of a pharmaceutical agent is an assessment of the risk of fetal injury due to the pharmaceutical, if it is used as directed by the mother. ... The regulation of therapeutic goods, that is drugs and therapeutic devices, varies by jurisdiction. ... In pharmacology and toxicology, a route of administration is the path by which a drug, fluid, poison or other substance is brought into contact with the body 1. ...

Basic chemical, pharmacological and marketing data

Anakinra is an IL-1 receptor antagonist. The anakinra molecule is a recombinant, non glycosolated version of human IL-1RA (RA for receptor antagonist). It consists of 153 amino acids and has a molecular weight of 17,257.6 g/mol (approx. 17.3 kilodaltons) and differs from native human IL-1RA in that it has the addition of a single methionine residue on its amino terminus. Interleukin-1 (IL-1) is secreted by the macrophages, monocytes and dendritic cells. ...

The substance is a biologic response modifier. It is prepared from cultures of genetically modified Escherichia coli using recombinant DNA technology. Binomial name Escherichia coli T. Escherich, 1885 E. coli at 10,000x magnification Escherichia coli, usually abbreviated to E. coli, discovered by Theodor Escherich, a pediatrician and bacteriologist, is one of the main species of bacteria that live in the lower intestines of mammals. ...

Anakinra blocks the biologic activity of naturally occuring IL-1, including inflammation and cartilage degradation associated with rheumatoid arthritis, by competetively inhibiting the binding of IL-1 to the Interleukin-1 type receptor, which is expressed in many tissues and organs. IL-1 is produced in response to inflammatory stimuli and mediates various physiologic responses, including inflammatory and immunologic reactions. IL-1 additionally stimulates bone resorption and induces tissue damage like cartilage degration as a result of loss of proteoglycans. In patients with rheumatoid arthritis the natural IL-1 receptor antagonist is not found in effective concentrations in synovium and synovial fluid to counteract the elevated IL-1 concentrations in these patients. Inflammation is the first response of the immune system to infection or irritation and may be referred to as the innate cascade. ... Rheumatoid arthritis (RA) is a chronic, inflammatory autoimmune disorder that causes the immune system to attack the joints. ... Receptor may refer to: In telecommunication, a receiver. ... Physiology (in Greek physis = nature and logos = word) is the study of the mechanical, physical, and biochemical functions of living organisms. ... Inflammation is the first response of the immune system to infection or irritation and may be referred to as the innate cascade. ... This page is a candidate to be copied to Wiktionary. ... Proteoglycans represent a special class of glycoprotein that are heavily glycosylated. ... Synovium means with egg, because the (synovial) fluid in joints that have a cavity between the bearing surfaces is like egg-white. ... Synovial fluid is a thin, stringy fluid found in the cavities of synovial joints. ...

Anakinra had an absolute bioavailability of 95% for healthy adults (n = 11) after a 70 mg subcutaneous bolus injection. Peak plasma concentrations of Kineret® generally occurred 3 to 7 hours after s.c. administration of clinically relevant doses (1 to 2 mg/kg: n = 18) for patients with rheumatoid arthritis. The terminal half-life ranged from 4 to 6 hours. After daily s.c. dosing for up to 24 weeks, no unexpected accumulations of Kineret® were observed in the plasma samples of rheumatoid arthritis patients.

This drug is sold under the tradename "Kineret®" and is produced by the pharmaceutical company Amgen. It is delivered as injection concentrate containing 100mg each single dose. A trade name, also known as a trading name or a business name, is the legal name of a business, or the name which a business trades under for commercial purposes. ... Amgen Inc. ...

Indications

Anakinra is indicated as monotherapeutic agent or in combination with other disease-modifying agents (DMARDs) other than tumor necrosis factor (TNF-) blocking agents (e.g., adalimumab, etanercept, infliximab) for the management of signs and symptoms of rheumatoid arthritis and to inhibit the progression of structural damage associated with the disease in adults with moderately to severely active disease who have had an absence of clinical improvement of symptoms or inedequate response in therapy with one or more DMARDs. In medicine, tumor necrosis factor alpha (TNFα, cachexin or cachectin) is an important cytokine involved in systemic inflammation and the acute phase response. ... Adalimumab (Humira®) is the third TNF antagonist (after infliximab and etanercept) to be approved in the US. Like infliximab and etanercept, adalimumab binds to TNFα, preventing it from activating TNF receptors; adalimumab was constructed from a fully human monoclonal antibody, while infliximab is a mouse-human chimeric antibody and etanercept... Etanercept (Enbrel®, co-marketed by Amgen and Wyeth) is a human recombinant, soluble tumor necrosis factor-alpha (TNFα) receptor. ... It has been suggested that Infliximab (Remicade) be merged into this article or section. ...

Kineret® showed moderate but statistically significant therapeutic efficacy; in most studies methotrexate was administered concomitantly. In the methotrexate plus anakinra group 38% of 250 patients reached an inprovement/relief of symptoms of at least 20% within 24 weeks. In the control group of 251 patients under methotrexate treatment alone response was only seen in 22%. The clinical response was measured according to ACR-criteria (20, 50, and 70). Methotrexate (rINN) (IPA: ), abbreviated MTX and formerly known as amethopterin, is an antimetabolite drug used in treatment of cancer and autoimmune diseases. ...

There are no direct studies comparing anakinra with TNF-inhibitors, but indirect data suggests that anakinra may be inferior to TNF-inhibitors.

Contraindications and Precautions

• Hypersensitivity to anakinra, other E. coli derived proteins or to any other ingredient (absolute contraindication).
• Preexisting malignant diseases (e.g., solid cancers, leukemia) : absolutely contraindicated (anakinra may be a human carcinogen and the supression of immune function may worsen already existing malignancies).
• Patients with neutropenia due to any reason : absolutely contraindicated. Neutrophil counts should be obtained before initiating therapy and regulary thereafter (see recommended laboratory tests).
• Severly impaired renal function (Creatinine-clearance less than 30 ml/minute) : Absolutely contraindicated.
• Preexisting active tuberculosis (disease may be worsened – see side-effects).
• Concomitant application of live-virus vaccines (see Interactions).
• Lactation : It is not known, if anakinra is distributed into human milk, nursing mothers should either discontinue the drug or breast-feeding taking into account the importance of the drug to the mother.
• Pediatric Patients : No well controlled human data exists in patients under age 18. Therefore, therapy is contraindicated in those patients.

Precautions: Hypersensitivity is an immune response that damages the bodys own tissues. ... When normal cells are damaged beyond repair, they are eliminated by apoptosis. ... Leukemia or leukaemia (see spelling differences) is a cancer of the blood or bone marrow characterized by an abnormal proliferation of blood cells, usually white blood cells (leukocytes). ... It has been suggested that Agranulocytosis be merged into this article or section. ... In medicine (nephrology) renal function is an indication of the state of the kidney and its role in physiology. ... Tuberculosis (commonly abbreviated as TB) is an infection caused by the bacterium Mycobacterium tuberculosis, which most commonly affects the lungs (pulmonary TB) but can also affect the central nervous system (meningitis), lymphatic system, circulatory system (Miliary tuberculosis), genitourinary system, bones and joints. ... Kittens nursing Lactation describes the secretion of milk from the mammary glands, the process of providing that milk to the young, and the period of time that a mother lactates to feed her young. ...

• Geriatric Patients (over 65 yrs of age) : Risk of infections is increased.
• Asthma bronchiale : Caution : Increased risk of severe infections.
• Women with childbearing potential should use effective anticonceptive methods.

Preganancy : Animal studies showed no adverse effects. Human data is not available. The drug should be applied to pregnant women only if clearly indicated.

• Mild to moderately impaired renal function : Caution.

Side-Effects

• GIT : Frequently, nausea (8%), diarrhea (7%), unspecific abdominal pain (5%).
• Allergy : Rare cases of allergic reactions including severe anaphylaxis have been noticed. If necessary, the usual symptomatic therapy with corticosteroids, epinephrine, and i.v. fluid correction should be initiated as soon as possible. Rare cases of allergic skin rash have also been seen.
• Respiratory tract : Frequently, infections of upper respiratory tract (13%), sinusitis (7%), flu-like syndrome (6%), Infrequently, pneumonia and tuberculosis.
• Skin : Frequently ecchymoses, infrequently skin mycosis, Lupus-erythematodes-like syndrome, urticaria, and isolated cases of melanoma (see malignancies).
• Immune system : Frequently, infections (40%, severe in 2%). Infrequently, production of antibodies with neutralizing activity.
• Blood and blood formin organs : Frequently, decrease in neutrophil counts (8% under anakinra, placebo 2%), infrequent significant neutropenia (0.4% under anakinra), moderate eosinophilia, moderate thrombocytopenia, and malignant lymphomas (0.12 cases/patient year)(see malignancies).
• Musculosceletal system : Infrequent are arthritic symptoms, arthritic symptoms associated with inflammation, bony infections.
• Pain, inflammation, and erythema at injection sites : Very frequently (70% of patients), usually during first 4 weeks of therapy, reversible wihin 1 to 2 weeks. These reactions are reasons, why many patients discontinue therapy.

Look up git in Wiktionary, the free dictionary. ... An allergy can refer to several kinds of immune reactions including Type I hypersensitivity in which a persons body is hypersensitised and develops IgE type antibodies to typical proteins. ... In medicine, anaphylaxis is a severe and rapid systemic allergic reaction. ... In physiology, corticosteroids are a class of steroid hormones that are produced in the adrenal cortex. ... It has been suggested that this article or section be merged with adrenalin. ... A typical rash A rash is a change in the skin which affects its appearance or texture. ... In humans the respiratory tract is the part of the anatomy that has to do with the process of respiration or breathing. ... Sinusitis is inflammation, either bacterial, fungal, viral, allergic or autoimmune, of the paranasal sinuses. ... Pneumonia is an illness of the lungs and respiratory system in which the microscopic, alveoli (air-filled sacs) responsible for absorbing oxygen from the atmosphere become inflamed and flooded with fluid. ... Tuberculosis (commonly abbreviated as TB) is an infection caused by the bacterium Mycobacterium tuberculosis, which most commonly affects the lungs (pulmonary TB) but can also affect the central nervous system (meningitis), lymphatic system, circulatory system (Miliary tuberculosis), genitourinary system, bones and joints. ... A close-up of human skin. ... A bruise or contusion or ecchymoses is a kind of injury, usually caused by blunt impact, in which the capillaries are damaged, allowing blood to seep into the surrounding tissue. ... The Term mycosis (plural: mycoses) refers to conditions in which fungi pass the resistance barriers of the human body and establish infections. ... The Immune System (also known as the Immunlological System) is made up of all the mechanisms through which a multicellular organism defends itself from internal invaders such as bacteria, virus or parasites. ... Wikipedia does not yet have an article with this exact name. ... Eosinophilia is the state of having high eosinophil granulocytes in the blood. ... Thrombocytopenia (or -paenia, or thrombopenia in short) is the presence of relatively few platelets in blood. ... Lymphoma is a variety of cancer that originates in the lymphatic system. ...

Recommended Laboratoy Tests

In patients receiving Kineret® a decrease in neutrophil counts may be found. In the placebo-controlled studies 8% of patients receiving anakinra had decreases in neutrophil counts of at least 1 World Health Organization (WHO) toxicity grade compared with 2% in the placebo control group. Kineret®-treated patients experienced defined neutropenia (ANC < 1 x 109/L) in 0.4%.

Neutrophil counts should be assessed prior to initiating Kineret® treatment, and while receiving Kineret®, monthly for 3 months, and thereafter quarterly for a period up to 1 year.

Malignancies

Among 5,300 rheumatoid arthritis patients treated with Kineret® in clinical trials for a mean of 15 months (approximately 6,400 patient years of treatment), 8 cases of lymphomas were observed resulting in a rate of 0.12 cases/100 patient years. This is 3.6 fold higher than the rate of lymphomas expected in the general population. However, it should be noted that the 'natural' incidence of lymphomas in patients with rheumatoid arthritis is considerably increased and may even be higher in patients with severe activity of rheumatoid arthritis.

Additionally, 37 solid tumors of different origination have been found. Of these, the number of 3 melanomas reported in study 4 is statistically significant (1 case expected), but a clear association to anakinra therapy remains unclear.

At this stage it cannot be ruled out that anakinra is a human carcinogen.

Interactions

• TNF-Blocking Agents:

An increased incidence of serious infections and an increased risk of neutropenia have been seen when anakinra and etanercept were used concomitantly in patients with rheumatoid arthritis. Similar interactions can be anticipated for the comination therapy of ankinra together with other agents blocking TNF (alpha) (e.g., adalimumab, infliximab). Therefore, combined drug therapy with anakinra and any TNF-blocking agent is not recommended and should be avoided. Moreover, in a 24-week clinical study a regime with anakinra and etanercept did not provide any additional benefit to the patients. Generally, an interaction is a kind of action which occurs as two or more objects have an effect upon one another. ...

• Methotrexate:

Methotrexate has been coadministered with anakinra in quite extended clinical studies. Neither specific drug interactions nor increased toxicity of anakinra and/or methotrexate have been noticed. In animal models (rats) studying the effects of both drugs when coadminstered, no effects on clearing of both drugs form plasma or the respective toxicologic properties have been seen. Therefore, the concomitant use of both disease modifiers in patients with rheumatoid arthritis can be regarded as safe.

• Vaccines:

Live-virus vaccines should not be given to patients during anakinra treatment. Information is not available, if anakinra would affect the rate of secondary transmission of vaccine virus (e.g., measles or poliomyelitis viruses) following administration of a live virus vaccine or regarding any other effect of vaccination on patients receiving the drug. Due to the fact that anakinra decreases the immune response to antigens in general, vaccine efficacy may be reduced in patients receiving anakinra.

Dosage Regime

The usual dosage is 100mg subcutaneosly (s.c.) once a day. Dose reduction to 100mg s.c. every other day should be considered in patients with severe renal impairment, if these are treated in exceptional cases (see contraindications and precautions). No additional benefits of doses exceeding 100mg daily have been seen.

Duration of treatment

In the preclinical and clinical studies the usual duration of therapy was 24 weeks. It is also possible to extend therapy to 48 weeks in patients with satisfying remission after 24 weeks to maintain clinical remission. Under continued therapy anakinra has been shown to slow progression of disease over a period of at least 12 month evidenced by X-ray studies or other clinical examinations. Some experience with 48 to 60 weeks (15 months) treatment duaration has already been gained and no evidence has been seen regarding additional toxicity.

References and External Links

• AHFS Database Online
• Arzneimittel Datenbank (in German)
• Kineret homepage
• http://www.rheuma-online.de/medikamente/anakinra-kineret/anakinra-zb-kineret/tumorrisiko.html (on the risk of cancerogenity (in German))