Anakinra (1 brand name, 1 dosage form, 1 route)
Available dosage forms: VIAL.
Routes of administration: SUBCUTANEOUS.
Brand Names
- KINERET
Contraindications
KINERET is contraindicated in patients with known hypersensitivity to E coli-derived proteins, KINERET, or any components of the product [see Hypersensitivity Reactions (5.3)].
Adverse Reactions
Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in clinical practice.
Drug Interactions
No drug-drug interaction studies in human subjects have been conducted. Toxicologic and toxicokinetic studies in rats did not demonstrate any alterations in the clearance or toxicologic profile of either methotrexate or KINERET when the two agents were administered together.
Mechanism of Action
KINERET blocks the biologic activity of IL-1 alpha and beta 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. IL-1 production is induced in response to inflammatory stimuli and mediates various physiologic responses including inflammatory and immunological responses. IL-1 has a broad range of activities including cartilage degradation by its induction of the rapid loss of proteoglycans, as well as stimulation of bone resorption. The levels of the naturally occurring IL-1Ra in synovium and synovial fluid from RA patients are not sufficient to compete with the elevated amount of locally produced IL-1. Spontaneous mutations in the CIAS1/NLRP3 gene have been identified in a majority of patients with cryopyrin-associated periodic syndromes such as NOMID. CIAS1/NLRP3 encodes for cryopyrin, a component of the inflammasome. The activated inflammasome results in proteolytic maturation and secretion of IL-1β, which has an important role in the systemic inflammation and manifestations of NOMID. DIRA is an autosomal recessive monogenic autoinflammatory disease caused by mutations in the IL1RN gene leading to loss of secretion of the interleukin-1 receptor antagonist (IL-1Ra). The deficiency of IL-1Ra results in unopposed IL-1α and IL-1β pro-inflammatory signaling causing systemic inflammation with skin and bone involvement.
Overdosage
There have been no cases of overdose reported with KINERET in clinical trials of RA or NOMID. In sepsis trials no serious toxicities attributed to KINERET were seen when administered at mean calculated doses of up to 35 times those given patients with RA over a 72-hour treatment period.