Anakinra (Monograph)

Brand name: Kineret
Drug class: Interleukin-mediated Agents, Miscellaneous

Medically reviewed by Drugs.com on Apr 10, 2025. Written by ASHP.

Introduction

Recombinant human interleukin-1 (IL-1) receptor antagonist; biologic disease-modifying antirheumatic drug (DMARD).^{1 11}

Uses for Anakinra

Rheumatoid Arthritis

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 in adults with moderately to severely active disease who have failed one or more DMARDs.^{1 3 4 5 12 13}

Guidelines do not include anakinra due to infrequent use in patients with rheumatoid arthritis.²⁰⁰³

Cryopyrin-associated Periodic Syndromes (CAPS)

Used for the treatment of neonatal-onset multisystem inflammatory disease (NOMID), which is a form of cryopyrin-associated periodic syndromes (CAPS).^{1 18 19 20}

Guidelines recommend use of anakinra, rilonacept, or canakinumab for patients with CAPS.²⁰⁰⁴

Deficiency of Interleukin-1 Receptor Antagonist

Used for the treatment of deficiency of interleukin-1 receptor antagonist (DIRA).^{1 21}

Guidelines recommend use of anakinra or another IL-1 antagonist for treatment of this condition.²⁰⁰⁴

Hidradenitis Suppurativa

Has been used in the management of hidradenitis suppurativa^{† [off-label]}.^{44 45 2023}

Familial Mediterranean Fever

Has been used in the management of familial Mediterranean fever^{† [off-label]}.⁴⁶

Anakinra Dosage and Administration

General

Pretreatment Screening

• Screen patients for active infections; do not initiate anakinra in patients with an active infection.¹

• Evaluate for and treat possible latent tuberculosis infections prior to initiating anakinra treatment; follow CDC guidelines.¹

• Assess absolute neutrophil count (ANC) prior to starting anakinra.¹

Patient Monitoring

• Monitor patients for hypersensitivity reactions and discontinue anakinra if a hypersensitivity reaction occurs.¹ Patients with deficiency of interleukin-1 receptor antagonist (DIRA) may have an increased risk of allergic reactions, particularly in the first several weeks of initiating anakinra; closely monitor patients during this time.¹

• Assess ANC monthly for 3 months, and then quarterly for up to 1 year during treatment with anakinra.¹

Administration

Sub-Q Administration

Administer sub-Q.¹

Administer sub-Q injections into the thighs, abdomen, outer area of the upper arms, or upper outer areas of the buttocks.¹ Rotate injection sites.¹ Do not administer into areas where the skin is tender, swollen, bruised, red, or hard, or into scars or stretch marks, or close to a vein.¹ See full prescribing information for additional administration instructions.¹

Allow anakinra prefilled syringe to reach room temperature (about 30 minutes) prior to administration.¹ Do not remove the needle cover until the prefilled syringe has reached room temperature.¹

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 once daily at approximately the same time each day.¹

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

Cryopyrin-associated Periodic Syndromes

Sub-Q

Recommended starting dosage in patients with neonatal-onset multisystem inflammatory disease (NOMID) is 1–2 mg/kg daily.¹ Individually adjust the dosage in 0.5–1 mg/kg increments up to a maximum of 8 mg/kg daily to control active inflammation.¹

Once-daily administration generally is recommended; however, the dose may be split into twice-daily administration.¹

Each syringe is intended for single use only; a new syringe must be used for each dose and any unused portions should be discarded.¹

Deficiency of Interleukin-1 Receptor Antagonist

Sub-Q

Recommended starting dosage is 1–2 mg/kg daily.¹ Individually adjust the dosage in 0.5–1 mg/kg increments up to a maximum of 8 mg/kg daily to control active inflammation.¹

Each syringe is intended for single use only; a new syringe must be used for each dose and any unused portions should be discarded.¹

Special Populations

Hepatic Impairment

Manufacturer makes no specific dosage recommendations.¹

Renal Impairment

Consider decreasing dosage to the prescribed dose administered every other day in patients with severe renal insufficiency or end-stage renal disease (Cl_cr <30 mL/minute, as estimated from S_cr).¹

Geriatric Patients

Manufacturer makes no specific dosage recommendations.¹

Cautions for Anakinra

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 in clinical trials in rheumatoid arthritis.^{1 9 12} Opportunistic infections (fungal, mycobacterial, bacterial) reported rarely.¹ Patients with asthma may be at a higher risk.¹ Risk of serious infection and neutropenia increased in patients receiving concomitant anakinra and etanercept compared with etanercept alone.¹

Do not initiate anakinra therapy in patients with active infections.¹ Discontinue the drug in patients with rheumatoid arthritis who develop a serious infection.¹ In patients with neonatal-onset multisystem inflammatory disease (NOMID) or deficiency of interleukin-1 receptor antagonist (DIRA), weigh the risk of a disease flare when discontinuing anakinra with the potential risk of continued treatment.¹

Safety and efficacy have not been evaluated in immunosuppressed patients or patients with chronic infections.¹

Evaluate for latent tuberculosis infection prior to initiating anakinra, and treat according to CDC guidelines.¹

Use with TNF Blocking Agents

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 compared with etanercept alone.¹

Hypersensitivity Reactions

Hypersensitivity reactions, including anaphylactic reactions and angioedema, reported.¹ Serious cutaneous reactions, including DRESS, also reported in patients with autoinflammatory conditions treated with anakinra.¹ If a severe hypersensitivity reaction occurs, discontinue anakinra immediately and institute appropriate interventions as indicated.¹

Patients with DIRA may have an increased risk of allergic reactions, particularly in the first several weeks after initiating anakinra.¹ Closely monitor patients during this time.¹ Initiate appropriate treatment and consider discontinuing anakinra if a severe allergic reaction occurs.¹

Immunosuppression

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

Immunizations

Do not administer live-virus vaccines to patients receiving anakinra.¹ No data are available on the effects of live vaccination or the secondary transmission of infection by live vaccines in patients receiving anakinra.¹

In a clinical trial, no difference was observed in anti-tetanus antibody response after administration of tetanus/diphtheria toxoid vaccine in patients receiving anakinra.¹ No data are available on the effects of vaccination with other inactivated antigens in patients receiving anakinra.¹

Neutropenia

Neutropenia (ANC <1000/mm³) and/or reduced neutrophil counts reported.¹ Evaluate ANC before therapy is initiated.¹ After anakinra is started, monitor ANC monthly for 3 months and then quarterly for up to 1 year.¹

Specific Populations

Pregnancy

Available data insufficient to identify a drug-associated risk of major birth defects, miscarriage, or maternal or fetal adverse events.¹ No evidence of fetal harm observed in animal studies.¹ There are risks to mother and fetus associated with active rheumatoid arthritis or CAPS, including preterm delivery, low birth weight, and the neonate being small for its gestational age at birth.¹

Lactation

Not known whether anakinra is distributed into milk or if the drug affects milk production.¹ Consider the benefits of breastfeeding along with the woman's clinical need for anakinra and any potential adverse effects on the breast-fed infant from the drug or underlying maternal condition.¹

Pediatric Use

Evaluated for treatment of neonatal-onset multisystem inflammatory disease (NOMID) in 36 pediatric patients ranging in age from <2 years up to 17 years.¹

Evaluated for treatment of deficiency of interleukin-1 receptor antagonist (DIRA) in 9 pediatric patients 1 month to 9 years of age.¹

Evaluated in a limited number of children 2–17 years of age with polyarticular course juvenile rheumatoid arthritis^{† [off-label]}; efficacy and safety not established (insufficient numbers of children have been enrolled in trials).¹ Adverse effects observed in children similar to those in adults.¹ Manufacturer states that use in pediatric patients with juvenile rheumatoid arthritis is not recommended.¹

Geriatric Use

No substantial differences in safety and efficacy in rheumatoid arthritis 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

Hepatic Impairment

Not studied in patients with severe hepatic impairment.¹

Renal Impairment

Risk of toxic reactions increased; consider dosage reduction.¹

Elimination reduced in patients with renal insufficiency.¹

Common Adverse Effects

Rheumatoid arthritis (≥5%): injection site reaction,^{1 3 5 9 10 12 13} worsening of rheumatoid arthritis,¹ upper respiratory tract infection,¹ headache,^{1 13} nausea,¹ diarrhea,¹ sinusitis,^{1 11} arthralgia,¹ influenza-like symptoms,^{1 11} and abdominal pain.^{1 13}

NOMID (>10%): injection site reaction, headache, vomiting, arthralgia, pyrexia, and nasopharyngitis.¹

DIRA: upper respiratory tract infections, rash, pyrexia, influenza-like illness, and gastroenteritis.¹

Drug Interactions

Used concomitantly with methotrexate, sulfasalazine, hydroxychloroquine, gold, penicillamine, leflunomide, and/or azathioprine in clinical studies of rheumatoid arthritis;^{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 vaccines, except for tetanus and diphtheria toxoids.¹

Specific Drugs

Anakinra 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 in patients with rheumatoid arthritis ranges from 4–6 hours.¹

The median half-life of anakinra in patients with neonatal-onset multisystem inflammatory disease (NOMID) is 5.7 hours (range: 3.1–28.2 hours).¹

Special Populations

In patients with renal impairment, plasma clearance was reduced by 16–75% depending on Cl_cr.^{1 15} Less than 2.5% of dose removed by hemodialysis or CAPD.¹

Gender and age (adjusted for Cl_cr 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 alpha and beta.^{1 3 4 5 9 10 11 12}

• 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}

• Most patients with cryopyrin-associated periodic syndromes (CAPS) such as neonatal-onset multisystem inflammatory disease (NOMID) have spontaneous mutations in the CIAS1/NLRP3 gene which encodes for cryopyrin (an inflammasome component).¹ Systemic inflammation and manifestations of NOMID are controlled in part by the activated inflammasome causing proteolytic maturation and IL-1β secretion.¹

• In patients with the autosomal recessive monogenic autoinflammatory disease called deficiency of IL-1 receptor antagonist (DIRA), mutations in the IL1RN gene cause loss of secretion of the IL-1 receptor antagonist.¹ When IL-1 receptor antagonist levels are insufficient, unopposed IL-1α and IL-1β pro-inflammatory signaling causes systemic inflammation, including in the skin and bone.¹

Advice to Patients

• Provide patients with the FDA-approved patient labeling (Patient Information and Instructions for Use).¹

• Advise patients to inform clinician about existing or recurrent infections prior to initiating therapy.¹ Advise patients to contact their clinician if they develop any symptoms of infection during anakinra therapy.¹

• Instruct patients and/or caregivers regarding proper dosage and administration of anakinra.¹ Assess the patient's ability to inject subcutaneously for proper anakinra administration.¹ Discuss proper disposal and caution against reuse of needles, syringes, and drug product.¹ Provide or advise patients to obtain a puncture-resistant container for disposal of used syringes.¹

• Advise patients and/or caregivers about recognition and reporting of adverse effects of anakinra (e.g., hypersensitivity reactions, infection, skin reactions).¹ Advise patients with deficiency of interleukin-1 receptor antagonist (DIRA) and their caregivers that patients may have a higher risk of allergic reactions, particularly in the first several weeks of treatment, and that they should be monitored closely.¹ Advise patients to discontinue anakinra and seek immediate medical attention if they experience symptoms suggesting an allergic reaction (e.g., rash, hives, and swelling of the face, lips, tongue, and throat that may cause difficulty breathing or swallowing).¹

• Advise patients of the risk of developing an injection-site reaction, which may include pain, erythema, swelling, pruritus, bruising, mass, inflammation, dermatitis, edema, urticaria, vesicles, warmth, and hemorrhage.¹ Advise patients or their caregivers to remove the prefilled syringe from refrigeration and leave at room temperature for 30 minutes before injecting.¹ Advise patients to avoid injecting into areas that are already swollen or red.¹ Advise patients to report any persistent injection-site reaction to their clinician.¹

• Advise patients to inform their clinicians if they are or plan to become pregnant or plan to breast-feed.¹

• Advise patients to inform their clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs.¹

• Inform patients of other important precautionary information.¹

Additional Information

The American Society of Health-System Pharmacists, Inc. represents that the information provided in the accompanying monograph was formulated with a reasonable standard of care, and in conformity with professional standards in the field. Readers are advised that decisions regarding use of drugs are complex medical decisions requiring the independent, informed decision of an appropriate health care professional, and that the information contained in the monograph is provided for informational purposes only. The manufacturer's labeling should be consulted for more detailed information. The American Society of Health-System Pharmacists, Inc. does not endorse or recommend the use of any drug. The information contained in the monograph is not a substitute for medical care.

Preparations

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.

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