Kineret (Anakinra) - Drug Interactions, Contraindications, Overdosage, etc

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. In a study in which patients with active RA were treated for up to 24 weeks with concurrent Kineret® and etanercept therapy, a 7% rate of serious infections was observed, which was higher than that observed with etanercept alone (0%) (see also WARNINGS). Two percent of patients treated concurrently with Kineret® and etanercept developed neutropenia (ANC < 1 × 10⁹/L).

OVERDOSAGE

There have been no cases of overdose reported with Kineret® in clinical trials of RA. 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.

CONTRAINDICATIONS

Kineret® is contraindicated in patients with known hypersensitivity to E coli -derived proteins, Kineret®, or any components of the product.

REFERENCES

1. Hannum CH, Wilcox CJ, Arend WP, et al. Interleukin-1 receptor antagonist activity of a human interleukin-1 inhibitor. Nature. 1990; 343:336-40.
2. Van Lent PLEM, Fons AJ, Van De Loo AEM, et al, Major role for interleukin 1 but not for tumor necrosis factor in early cartilage damage in immune complex in mice. J Rheumatol. 1995; 22:2250-2258.
3. Deleuran BW, Shu CQ, Field M, et al. Localization of interleukin-1 alpha, type 1 interleukin-1 receptor and interleukin-1 receptor antagonist in the synovial membrane and cartilage/pannus junction in rheumatoid arthritis. Br J Rheumatol. 1992; 31:801-809.
4. Chomarat P, Vannier E, Dechanet J, et al. Balance of IL-1 receptor antagonist/IL-1 B in rheumatoid synovium and its regulation by IL-4 and IL-10. J Immunol. 1995; 1432-1439.
5. Firestein GS, Boyle DL, Yu C, et al. Synovial interleukin-1 receptor antagonist and interleukin-1 balance in rheumatoid arthritis. Arthritis Rheum. 1994; 37:644-652.
6. Cockcroft DW and Gault HM. Prediction of creatinine clearance from serum creatinine. Nephron 1976; 16:31-41.
7. Bresnihan B, Alvaro-Gracia JM, Cobby M, et al. Treatment of rheumatoid arthritis with recombinant human interleukin-1 receptor antagonist. Arthritis Rheum. 1998; 41:2196-2204.
8. Sharp JT, Young DY, Bluhm GB, et al. How many joints in the hands and wrists should be included in a score of radiologic abnormalities used to assess rheumatoid arthritis? Arthritis Rheum. 1985; 28:1326-1335.
9. National Cancer Institute. Surveillance, Epidemiology, and End Results Database (SEER) Program. SEER Incidence Crude Rates, 11 Registries, 1992-1999.

This product, its production, and/or its use may be covered by one or more U.S. Patents, including U.S. Patent Nos. 6,599,873 and 5,075,222 as well as other patents or patents pending.

AMGEN®

Manufactured by:

Amgen Manufacturing, Limited,

a subsidiary of Amgen Inc

One Amgen Center Drive

Thousand Oaks, CA 91320-1799

© 2001 - 2004 Amgen. All rights reserved.

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Issue Date: 04/23/2004