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Kineret

Generic Name: Anakinra
Class: Disease-modifying Antirheumatic Drugs
Chemical Name: N2-l-methionyl-interleukin 1 receptor antagonist (human isoform × reduced)
Molecular Formula: C759H1186N208O232S10
CAS Number: 143090-92-0

Introduction

Recombinant human interleukin-1 (IL-1) receptor antagonist; biologic response modifier and disease-modifying antirheumatic drug (DMARD).1 11

Uses for Kineret

Rheumatoid Arthritis in Adults

Used alone or in combination with 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 progression of structural damage associated with the disease in adults with moderately to severely active disease who have had an inadequate response to therapy with one or more DMARDs.1 3 4 5 12 13 (See Interactions.)

Slideshow: Drug Treatment for Rheumatoid Arthritis - What Are Your Options?

Kineret Dosage and Administration

General

  • Monitor neutrophil counts prior to and during anakinra therapy.1 12 (See Neutropenia under Cautions.)

Administration

Sub-Q Administration

Administer sub-Q at approximately the same time each day.1

Administer sub-Q injections into the thighs, abdomen, upper arms, or buttocks.17 Rotate injection sites.17 Do not make injections into areas where the skin is tender, bruised, red, or hard; into scars or stretch marks; or close to a vein.17

Allow anakinra prefilled syringe to reach room temperature (about 60–90 minutes) prior to administration.17 Do not remove the needle cover until the prefilled syringe has reached room temperature.17

Intended for use under the guidance and supervision of a clinician, but may be self-administered if the clinician determines that the patient and/or their caregiver is competent to prepare and safely administer the drug.1

Dosage

Adults

Rheumatoid Arthritis
Sub-Q

100 mg (entire contents [0.67 mL] of one prefilled syringe) daily.1

Prescribing Limits

Adults

Rheumatoid Arthritis
Sub-Q

Dosages >100 mg daily do not appear to provide additional benefit.1

Special Populations

Renal Impairment

Rheumatoid Arthritis
Sub-Q

Consider decreasing dosage to 100 mg every other day in patients with severe renal insufficiency or end-stage renal disease (Clcr <30 mL/minute, as estimated from Scr).1 15 (See the Special Populations sections under Pharmacokinetics and under Cautions.)

Cautions for Kineret

Contraindications

  • Known hypersensitivity to Escherichia coli-derived proteins, anakinra, or any ingredient in the formulation.1

Warnings/Precautions

Warnings

Infectious Complications

Increased incidence of serious infections reported.1 9 12 (See Infection under Cautions.) Do not initiate anakinra therapy in patients with active infections.1 Discontinue the drug in patients who develop a serious infection.1 Safety and efficacy have not been evaluated in immunosuppressed patients or patients with chronic infections.1

Interactions

Concomitant use of TNF blocking agents (e.g., adalimumab, etanercept, infliximab) not recommended.1 Increased incidence of serious infections and lack of additional clinical benefit with combined anakinra and etanercept therapy.1

Sensitivity Reactions

Hypersensitivity Reactions

Anaphylaxis and anaphylactoid reactions reported rarely.1 11

If a severe hypersensitivity reaction occurs, discontinue anakinra immediately and institute appropriate interventions as indicated (e.g., epinephrine, corticosteroids, maintenance of an adequate airway, oxygen, IV fluids, antihistamines, maintenance of BP).1

Latex Sensitivity

The needle cover of the prefilled syringe contains dry natural rubber (latex); individuals sensitive to latex should not handle the needle cover.1

Major Toxicities

Infection

The incidence of infection, including serious infections, is increased in patients receiving anakinra.1 Infections of bacterial origin (e.g., cellulitis, pneumonia, bone and joint) most common.1 Opportunistic infections (fungal, mycobacterial, bacterial, viral) reported rarely.1 Patients with asthma may be at a higher risk for developing serious infections.1

Risk of serious infection and neutropenia increased in patients receiving concomitant anakinra and etanercept compared with etanercept alone.1 5

Hematologic Effects

Small reductions reported in WBC, ANC, and platelet counts; small increases in eosinophil counts reported.1 13

General Precautions

Immunologic Effects

Effect of anakinra in patients with active and/or chronic infections or on the subsequent development of malignancy not fully elucidated.1

Anti-anakinra antibodies reported after therapy; not associated with increased adverse events.1 Effect of neutralizing antibodies on clinical response not fully elucidated.1 3 11 13

Do not administer live-virus vaccines to patients receiving anakinra.1 (See Vaccines under Interactions.)

Neutropenia

Neutropenia (ANC < 1000/mm2) and/or reduced neutrophil counts reported.1 Monitor ANC before therapy is initiated, monthly for 3 months, and then every 3 months for a period up to 1 year during anakinra therapy.1 12

Malignancies and Lymphoproliferative Disorders

Increased incidence of lymphoma compared with general population reported in patients with rheumatoid arthritis receiving anakinra.1 However, patients with rheumatoid arthritis, especially those with highly active disease, may be at increased risk of lymphoma.1 Role of human interleukin-1 receptor antagonist (IL-1Ra)-induced immunosuppression in the development of malignancies is unknown.1

Increased incidence of malignancies involving the breast and respiratory and digestive systems has been reported.1 Increased incidence of melanoma also reported; clinical importance unknown.1

Specific Populations

Pregnancy

Category B.1

Lactation

Not known whether anakinra is distributed into milk.1 Caution if used in nursing women.1

Pediatric Use

Evaluated in a limited number of children 2–17 years of age with polyarticular course juvenile rheumatoid arthritis; efficacy not established (insufficient numbers of children have been enrolled in trials).1 Adverse effects observed in children similar to those in adults.1 Use of anakinra in pediatric patients is not recommended.1 The currently available prefilled syringes are not designed to deliver pediatric doses accurately.1

Geriatric Use

No substantial differences in safety and efficacy relative to younger adults, but increased sensitivity cannot be ruled out.1

Geriatric patients may be at increased risk of serious infection; use with caution.1

Geriatric patients may be at increased risk of toxic reactions due to impaired renal function; use with caution.1 (See Renal Impairment under Cautions.)

Hepatic Impairment

Not studied in patients with severe hepatic impairment.1

Renal Impairment

Risk of toxic reactions increased; consider dosage reduction.1 (See Renal Impairment under Dosage and Administration.)

Elimination reduced in patients with renal insufficiency.1 (See Special Populations under Pharmacokinetics.)

Common Adverse Effects

Injection-site reaction,1 3 5 9 10 12 13 infections (principally bacterial origin),1 3 11 13 headache,1 13 nausea,1 neutropenia,1 diarrhea,1 influenza-like symptoms,1 11 abdominal pain.1 13

Interactions for Kineret

Used concomitantly with methotrexate, sulfasalazine, hydroxychloroquine, gold, penicillamine, leflunomide, and/or azathioprine in clinical studies;1 3 13 specific drug interactions not evaluated in humans.1 11

Vaccines

Live virus vaccines should not be administered to patients receiving anakinra.1 Information is not available regarding whether anakinra would affect the rate of secondary transmission of vaccine virus following administration of a live virus vaccine or regarding any other effect of vaccination on patients receiving the drug.1

Information not available regarding effects of vaccination with inactivated vaccine.1

Specific Drugs

Drug

Interaction

Comments

Abatacept

Concomitant use not recommended; clinical experience insufficient to establish safety and efficacy16

Methotrexate

Pharmacokinetic interaction unlikely;1 no alterations in clearance or toxicologic profile of anakinra or methotrexate with concomitant administration in rats1

Tetanus toxoid

Immunologic response preserved in 1 study1

TNF blocking agents (e.g., adalimumab, etanercept, infliximab)

Increased incidence of adverse effects (serious infections, neutropenia) and no added clinical benefit reported with combined anakinra and etanercept therapy compared with etanercept alone1 14

Concomitant use not recommended1 14

Kineret Pharmacokinetics

Absorption

Bioavailability

Absolute bioavailability is 95% after sub-Q administration; peak plasma concentrations attained within 3–7 hours.1

Distribution

Extent

Not known whether anakinra crosses the placenta or is distributed into milk.1

Elimination

Metabolism

Metabolic fate of anakinra not fully elucidated; no unexpected accumulation after daily sub-Q dosing for up to 24 weeks.1 15

Elimination Route

Excreted principally in urine.1 15

Half-life

Terminal half-life averages 4–6 hours.1

Special Populations

In patients with renal impairment, plasma clearance was reduced by 16–75% depending on Clcr.1 15 Less than 2.5% of dose removed by hemodialysis or CAPD.1 (See Renal Impairment under Dosage and Administration.)

Gender and age (adjusted for Clcr and body weight) do not have substantial effect on mean plasma clearance.1

Pharmacokinetics not studied in patients with hepatic impairment.1

Stability

Storage

Parenteral

Injection

2–8°C; do not freeze or shake.1 Protect from light.1

Actions

  • A biosynthetic (recombinant DNA origin) form of human interleukin-1 (IL-1) receptor antagonist (IL-1Ra).

  • A biologic response modifier that blocks the biologic activity of endogenous IL-1.1 3 4 5 9 10 12 11

  • Competitively inhibits binding of IL-1 to the interleukin-1 type I receptor (IL-1RI) expressed in many tissues and organs.1 10 Decreases inflammation and cartilage degradation associated with rheumatoid arthritis.1 2 5 10 12

Advice to Patients

  • Importance of providing patient a copy of manufacturer’s patient information.1

  • Importance of patient informing clinician about existing or recurrent infections prior to initiating therapy.1 17

  • Importance of instructing patient and/or caregiver regarding proper dosage and administration of anakinra, including the use of aseptic technique and safe disposal of needles and syringes, in patients whose clinician has determined that the drug can safely and effectively be self-administered in the patient’s home by the patient, family member, or other responsible individual.1

  • Importance of advising patient and/or caregiver about recognition and reporting of adverse effects of anakinra (e.g., sensitivity reactions, infection).1

  • Importance of informing clinician if allergy to latex exists.11

  • Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.1

  • Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs.1

  • Importance of informing patients of other important precautionary information.1 (See Cautions.)

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Anakinra (Recombinant DNA Origin)

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Parenteral

Injection, for subcutaneous use

100 mg/0.67 mL

Kineret (preservative-free; available in prefilled disposable syringes)

Amgen

Comparative Pricing

This pricing information is subject to change at the sole discretion of DS Pharmacy. This pricing information was updated 09/2014. Actual costs to patients will vary depending on the use of specific retail or mail-order locations and health insurance copays.

Kineret 100MG/0.67ML Solution (BIOVITRUM AB): 5/$433.00 or 19/$1,702.91

AHFS DI Essentials. © Copyright, 2004-2014, Selected Revisions August 26, 2014. American Society of Health-System Pharmacists, Inc., 7272 Wisconsin Avenue, Bethesda, Maryland 20814.

† Use is not currently included in the labeling approved by the US Food and Drug Administration.

References

1. Amgen Inc. Kineret (anakinra) injection prescribing information. Thousand Oaks, CA; 2006 Dec 15.

2. Schiff MH. Role of interleukin 1 and interleukin 1 receptor antagonist in the mediation of rheumatoid arthritis. Ann Rheum Dis. 2000; 59(Suppl 1):i103-8. [IDIS 455654] [PubMed 11053099]

3. Bresnihan B, Alvaro-Gracia JM, Cobby M, et al., Treatment of rheumatoid arthritis with recombinant human interleukin-1 receptor antagonist. Arthritis Rheum1998; 41:2196-204.

4. Jiang Y, Genant HK, Watt I, et al.A multicenter, double-blind, dose-ranging, randomized, placebo-controlled study of recombinant human interleukin-1 receptor antagonist in patients with rheumatoid arthritis: radiologic progression and correlation of Genant and Larsen scores. Arthritis Rheum 2000; 43:1001-9. [PubMed 10817552]

5. Anon. Anakinra (kineret) for rheumatoid arthritis. Med Lett Drugs Ther. 2002; 44:18-9.

6. Arnett FC, Edworthy SM, Bloch DA et al. The American Rheumatology Association 1987: revised criteria for the classification of rheumatoid arthritis. Arthritis Rheum. 1988; 31:315-24. [PubMed 3358796]

7. Hochberg MC, Chang RW, Dwosh I et al. The American College of Rheumatology 1991 revised criteria for the classification of global functional status in rheumatoid arthritis. Arthritis Rheum. 1992; 35:498-502. [PubMed 1575785]

8. Felson DT, Anderson JJ, Boers M et al. American College of Rheumatology preliminary definition of improvement in rheumatoid arthritis. Arthritis Rheum. 1995; 38:727-35. [PubMed 7779114]

9. Bresnihan B.The safety and efficacy of interleukin-1 receptor antagonist in the treatment of rheumatoid arthritis. Semin Arthritis Rheum. 2001; 30(Suppl 2):17-20. [PubMed 11357167]

10. Bresnihan B. The prospect of treating rheumatoid arthritis with recombinant human interleukin-1 receptor antagonist. BioDrugs. 2001; 15:87-97. [PubMed 11437678]

11. Amgen Inc,Thousand Oaks, CA: Personal communication.

12. Calabrese LH. Anakinra treatment of patients with rheumatoid arthritis. Ann Pharmacother. 2002; 36:1204-9. [IDIS 485217] [PubMed 12086555]

13. Cohen S, Hurd E, Cush J, Schiff M et al. Treatment of rheumatoid arthritis with anakinra, a recombinant human interleukin-1 receptor antagonist, in combination with methotrexate: results of a twenty-four-week, multicenter, randomized, double-blind, placebo-controlled trial. Arthritis Rheum. 2002; 46:614-24. [PubMed 11920396]

14. Spencer-Green G. Dear healthcare professional letter: Important Drug Warning. Abbott Park, IL: Abbott Laboratories; 2004 Nov.

15. Yang BB, Baughman S, Sullivan JT. Pharmacokinetics of anakinra in subjects with different levels of renal function. Clin Pharmacol Ther. 2003; 74:85-94. [PubMed 12844139]

16. Bristol-Myers Squibb. Orencia (abatacept) prescribing information. Princeton, NJ; 2005 Dec.

17. Amgen Inc. Kineret (anakinra) patient information. Thousand Oaks, CA; 2006 Dec 15.

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