Class: Disease-modifying Antirheumatic Drugs
- Interleukin-1 Inhibitors
Chemical Name: N2-l-methionyl-interleukin 1 receptor antagonist (human isoform × reduced)
Molecular Formula: C759H1186N208O232S10
CAS Number: 143090-92-0
Recombinant human interleukin-1 (IL-1) receptor antagonist; biologic response modifier and disease-modifying antirheumatic drug (DMARD).
Uses for Anakinra
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. (See Interactions.)
Anakinra Dosage and Administration
Monitor neutrophil counts prior to and during anakinra therapy. (See Neutropenia under Cautions.)
Administer sub-Q at approximately the same time each day.
Administer sub-Q injections into the thighs, abdomen, upper arms, or buttocks. Rotate injection sites. 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.
Allow anakinra prefilled syringe to reach room temperature (about 60–90 minutes) prior to administration. Do not remove the needle cover until the prefilled syringe has reached room temperature.
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.
100 mg (entire contents [0.67 mL] of one prefilled syringe) daily.
Dosages >100 mg daily do not appear to provide additional benefit.
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). (See the Special Populations sections under Pharmacokinetics and under Cautions.)
Cautions for Anakinra
Known hypersensitivity to Escherichia coli-derived proteins, anakinra, or any ingredient in the formulation.
Increased incidence of serious infections reported. (See Infection under Cautions.) Do not initiate anakinra therapy in patients with active infections. Discontinue the drug in patients who develop a serious infection. Safety and efficacy have not been evaluated in immunosuppressed patients or patients with chronic infections.
Concomitant use of TNF blocking agents (e.g., adalimumab, etanercept, infliximab) not recommended. Increased incidence of serious infections and lack of additional clinical benefit with combined anakinra and etanercept therapy.
Anaphylaxis and anaphylactoid reactions reported rarely.
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).
The needle cover of the prefilled syringe contains dry natural rubber (latex); individuals sensitive to latex should not handle the needle cover.
The incidence of infection, including serious infections, is increased in patients receiving anakinra. Infections of bacterial origin (e.g., cellulitis, pneumonia, bone and joint) most common. Opportunistic infections (fungal, mycobacterial, bacterial, viral) reported rarely. Patients with asthma may be at a higher risk for developing serious infections.
Risk of serious infection and neutropenia increased in patients receiving concomitant anakinra and etanercept compared with etanercept alone.
Small reductions reported in WBC, ANC, and platelet counts; small increases in eosinophil counts reported.
Effect of anakinra in patients with active and/or chronic infections or on the subsequent development of malignancy not fully elucidated.
Anti-anakinra antibodies reported after therapy; not associated with increased adverse events. Effect of neutralizing antibodies on clinical response not fully elucidated.
Do not administer live-virus vaccines to patients receiving anakinra. (See Vaccines under Interactions.)
Neutropenia (ANC < 1000/mm2) and/or reduced neutrophil counts reported. 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.
Malignancies and Lymphoproliferative Disorders
Increased incidence of lymphoma compared with general population reported in patients with rheumatoid arthritis receiving anakinra. However, patients with rheumatoid arthritis, especially those with highly active disease, may be at increased risk of lymphoma. Role of human interleukin-1 receptor antagonist (IL-1Ra)-induced immunosuppression in the development of malignancies is unknown.
Increased incidence of malignancies involving the breast and respiratory and digestive systems has been reported. Increased incidence of melanoma also reported; clinical importance unknown.
Not known whether anakinra is distributed into milk. Caution if used in nursing women.
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). Adverse effects observed in children similar to those in adults. Use of anakinra in pediatric patients is not recommended. The currently available prefilled syringes are not designed to deliver pediatric doses accurately.
No substantial differences in safety and efficacy relative to younger adults, but increased sensitivity cannot be ruled out.
Geriatric patients may be at increased risk of serious infection; use with caution.
Geriatric patients may be at increased risk of toxic reactions due to impaired renal function; use with caution. (See Renal Impairment under Cautions.)
Not studied in patients with severe hepatic impairment.
Risk of toxic reactions increased; consider dosage reduction. (See Renal Impairment under Dosage and Administration.)
Elimination reduced in patients with renal insufficiency. (See Special Populations under Pharmacokinetics.)
Common Adverse Effects
Injection-site reaction, infections (principally bacterial origin), headache, nausea, neutropenia, diarrhea, influenza-like symptoms, abdominal pain.
Interactions for Anakinra
Used concomitantly with methotrexate, sulfasalazine, hydroxychloroquine, gold, penicillamine, leflunomide, and/or azathioprine in clinical studies; specific drug interactions not evaluated in humans.
Live virus vaccines should not be administered to patients receiving anakinra. 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.
Information not available regarding effects of vaccination with inactivated vaccine.
Concomitant use not recommended; clinical experience insufficient to establish safety and efficacy
Pharmacokinetic interaction unlikely; no alterations in clearance or toxicologic profile of anakinra or methotrexate with concomitant administration in rats
Immunologic response preserved in 1 study
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 alone
Concomitant use not recommended
Absolute bioavailability is 95% after sub-Q administration; peak plasma concentrations attained within 3–7 hours.
Not known whether anakinra crosses the placenta or is distributed into milk.
Metabolic fate of anakinra not fully elucidated; no unexpected accumulation after daily sub-Q dosing for up to 24 weeks.
Excreted principally in urine.
Terminal half-life averages 4–6 hours.
In patients with renal impairment, plasma clearance was reduced by 16–75% depending on Clcr. Less than 2.5% of dose removed by hemodialysis or CAPD. (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.
Pharmacokinetics not studied in patients with hepatic impairment.
2–8°C; do not freeze or shake. Protect from light.
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.
Competitively inhibits binding of IL-1 to the interleukin-1 type I receptor (IL-1RI) expressed in many tissues and organs. Decreases inflammation and cartilage degradation associated with rheumatoid arthritis.
Advice to Patients
Importance of providing patient a copy of manufacturer’s patient information.
Importance of patient informing clinician about existing or recurrent infections prior to initiating therapy.
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.
Importance of advising patient and/or caregiver about recognition and reporting of adverse effects of anakinra (e.g., sensitivity reactions, infection).
Importance of informing clinician if allergy to latex exists.
Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.
Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs.
Importance of informing patients of other important precautionary information. (See Cautions.)
Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.
Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.
Injection, for subcutaneous use
100 mg/0.67 mL
Kineret (preservative-free; available in prefilled disposable syringes)
AHFS DI Essentials™. © Copyright 2021, Selected Revisions August 26, 2014. American Society of Health-System Pharmacists, Inc., 4500 East-West Highway, Suite 900, Bethesda, Maryland 20814.
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