(an a KIN ra)
- Interleukin-1 Receptor Antagonist
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Solution Prefilled Syringe, Subcutaneous [preservative free]:
Kineret: 100 mg/0.67 mL (0.67 mL) [contains disodium edta, polysorbate 80]
Brand Names: U.S.
- Antirheumatic, Disease Modifying
- Interleukin-1 Receptor Antagonist
Antagonist of the interleukin-1 (IL-1) receptor. Endogenous IL-1 is induced by inflammatory stimuli and mediates a variety of immunological responses, including degradation of cartilage (loss of proteoglycans) and stimulation of bone resorption.
Time to Peak
SubQ: 3 to 7 hours
Terminal: 4 to 6 hours; Severe renal impairment (CrCl <30 mL/minute): ~7 hours; ESRD: 9.7 hours (Yang 2003)
Special Populations: Renal Function Impairment
Mean plasma clearance in patients with mild (CrCl 50 to 80 mL/minute), moderate (CrCl 30 to 49 mL/minute), severe (CrCl <30 mL/minute), and end-stage renal disease (ESRD) was decreased by 16%, 50%, 70%, and 75%, respectively.
Use: Labeled Indications
Neonatal-onset multisystem inflammatory disease: Treatment of neonatal-onset multisystem inflammatory disease (NOMID).
Rheumatoid arthritis: Reduction in signs and symptoms and slowing the progression of structural damage of moderately to severely active rheumatoid arthritis (RA) in patients 18 years and older who have failed 1 or more disease-modifying antirheumatic drugs (DMARDs).
Off Label Uses
Familial Mediterranean fever
Evidence from a small number of patients in a short-term controlled trial and noncontrolled trials suggests that anakinra may reduce the frequency of attacks in patients with familial Mediterranean fever (FMF) who are resistant or intolerant to colchicine. Additional data are necessary to further define the role of anakinra in this condition.
Based on European League Against Rheumatism (EULAR) guidelines for the management of FMF, interleukin-1 (IL-1) blockers are recommended for patients unresponsive or resistant to the maximum dose of colchicine.
Gout, treatment of acute flares (when conventional therapy is ineffective, contraindicated, or not tolerated)
Data from a case series and several retrospective chart reviews have suggested anakinra may be beneficial for the treatment of acute flare of gout in patients who are refractory to, intolerant of, or have contraindications to conventional therapy (eg, colchicine, NSAIDs, corticosteroids) [Ghosh 2013], [Ottaviani 2013], [So 2007]. Additional data may be necessary to further define the role of anakinra in this condition.
Based on European League Against Rheumatism (EULAR) evidence-based recommendations for the management of gout, interleukin-1 (IL-1) blockers (eg, anakinra) may be considered for treating acute gout flares in patients with frequent flares and who have contraindications to other anti-gout therapies including colchicine, NSAIDS, and corticosteroids. Following flare treatment with interleukin-1 (IL-1) blockers, urate-lowering therapy should be adjusted to meet uricemia target levels.
Juvenile idiopathic arthritis
Data from two retrospective studies in patients with juvenile idiopathic arthritis suggested that anakinra, as first-line treatment, may be beneficial for this condition [Hedrich 2012], [Nigrovic 2011]. Furthermore, a multicenter, randomized, double-blind, placebo-controlled trial enrolling a small number of patients supports the use of anakinra, as adjunctive therapy, in patients with this condition [Quartier 2011]. Additional trials may be necessary to further define the role of anakinra in patients with juvenile idiopathic arthritis.
Based on the American College of Rheumatology guidelines for the treatment of juvenile idiopathic arthritis, anakinra is effective and is recommended as initial therapy or as adjunct therapy in children and adolescents with systemic juvenile idiopathic arthritis who have failed an adequate trial of glucocorticoids and/or nonsteroidal anti-inflammatory drugs (NSAIDs).
Evidence from small controlled and noncontrolled trials and several case reports/series indicate that anakinra may be effective in preventing recurrences in patients with recurrent pericarditis refractory to conventional therapy. Larger controlled trials are needed.
European Society of Cardiology (ESC) guidelines on the diagnosis and management of pericardial diseases recommend that intravenous immunoglobulin, anakinra, or azathioprine be considered in cases of infection-negative, corticosteroid-dependent recurrent pericarditis in patients not responsive to colchicine.
Hypersensitivity to E. coli-derived proteins, anakinra, or any component of the formulation
Neonatal-onset multisystem inflammatory disease (NOMID): SubQ: Initial: 1 to 2 mg/kg daily in 1 to 2 divided doses; adjust dose in 0.5 to 1 mg/kg increments as needed; usual maintenance dose: 3 to 4 mg/kg daily (maximum: 8 mg/kg daily). Note: Once-daily administration is preferred; however, the dose may also be divided and administered twice daily.
Familial Mediterranean fever (off-label use): SubQ: 100 mg once daily (Ben-Zvi 2016)
Gout, treatment of acute flares (when conventional therapy is ineffective, contraindicated, or not tolerated) (off-label use): SubQ: 100 mg once daily (Ghosh 2013; Ottaviani 2013; So 2007). Most patients received therapy for 3 days (So 2007). Additional data may be necessary to further define the role of anakinra in this condition.
Pericarditis (recurrent) (off-label use): SubQ: 100 mg once daily. Dosing based on limited data with treatment periods up to 6 months (Brucata 2016; Cantarini 2010). Additional data is necessary to further define the role of anakinra in the treatment of this condition.
Rheumatoid arthritis (RA): SubQ: 100 mg once daily (administer at approximately the same time each day)
Refer to adult dosing.
Neonatal-onset multisystem inflammatory disease (NOMID): Infants, Children, and Adolescents: SubQ: Refer to adult dosing.
Juvenile idiopathic arthritis, systemic (off-label use): Children and Adolescents: SubQ: Initial: 1 to 2 mg/kg once daily; maximum initial dose: 100 mg; if no response after 1 to 2 weeks, may titrate up to 4 mg/kg once daily (maximum: 200 mg/day) (Dewitt 2012; Hedrich 2012; Lequerré 2008; Nigrovi 2011; Quartier 2011; Ringold 2013).
Dosing: Renal Impairment
CrCl ≥30 mL/minute: No dosage adjustment necessary.
CrCl <30 mL/minute or end-stage renal disease (ESRD): Consider administering the prescribed dose every other day.
Hemodialysis: Not dialyzable (<2.5%)
Continuous ambulatory peritoneal dialysis (CAPD): Not dialyzable (<2.5%)
Dosing: Hepatic Impairment
There are no dosage adjustments provided in the manufacturer's labeling (has not been studied).
SubQ: Allow solution to warm to room temperature prior to use (30 minutes). Inject into outer area of upper arms, abdomen (do not use within 2 inches of belly button), front of middle thighs, or upper outer buttocks. Rotate injection sites; do not administer into tender, swollen, bruised, red, or hard skin or skin with scars or stretch marks.
Store in refrigerator at 2°C to 8°C (36°F to 46°F); do not freeze. Do not shake. Protect from light. Discard any unused portion.
Abatacept: Anakinra may enhance the adverse/toxic effect of Abatacept. Avoid combination
Anti-TNF Agents: May enhance the adverse/toxic effect of Anakinra. An increased risk of serious infection during concomitant use has been reported. Avoid combination
BCG (Intravesical): Immunosuppressants may diminish the therapeutic effect of BCG (Intravesical). Avoid combination
Canakinumab: Interleukin-1 Receptor Antagonist may enhance the adverse/toxic effect of Canakinumab. Whether such a combination will also alter the therapeutic response to one or both agents is unclear. Avoid combination
Coccidioides immitis Skin Test: Immunosuppressants may diminish the diagnostic effect of Coccidioides immitis Skin Test. Monitor therapy
Denosumab: May enhance the adverse/toxic effect of Immunosuppressants. Specifically, the risk for serious infections may be increased. Monitor therapy
Echinacea: May diminish the therapeutic effect of Immunosuppressants. Consider therapy modification
Fingolimod: Immunosuppressants may enhance the immunosuppressive effect of Fingolimod. Management: Avoid the concomitant use of fingolimod and other immunosuppressants when possible. If combined, monitor patients closely for additive immunosuppressant effects (eg, infections). Consider therapy modification
Leflunomide: Immunosuppressants may enhance the adverse/toxic effect of Leflunomide. Specifically, the risk for hematologic toxicity such as pancytopenia, agranulocytosis, and/or thrombocytopenia may be increased. Management: Consider not using a leflunomide loading dose in patients receiving other immunosuppressants. Patients receiving both leflunomide and another immunosuppressant should be monitored for bone marrow suppression at least monthly. Consider therapy modification
Natalizumab: Immunosuppressants may enhance the adverse/toxic effect of Natalizumab. Specifically, the risk of concurrent infection may be increased. Avoid combination
Nivolumab: Immunosuppressants may diminish the therapeutic effect of Nivolumab. Consider therapy modification
Ocrelizumab: May enhance the immunosuppressive effect of Immunosuppressants. Monitor therapy
Pidotimod: Immunosuppressants may diminish the therapeutic effect of Pidotimod. Monitor therapy
Pimecrolimus: May enhance the adverse/toxic effect of Immunosuppressants. Avoid combination
Roflumilast: May enhance the immunosuppressive effect of Immunosuppressants. Consider therapy modification
Sipuleucel-T: Immunosuppressants may diminish the therapeutic effect of Sipuleucel-T. Monitor therapy
Tacrolimus (Topical): May enhance the adverse/toxic effect of Immunosuppressants. Avoid combination
Tertomotide: Immunosuppressants may diminish the therapeutic effect of Tertomotide. Monitor therapy
Tofacitinib: Anakinra may enhance the adverse/toxic effect of Tofacitinib. Avoid combination
Trastuzumab: May enhance the neutropenic effect of Immunosuppressants. Monitor therapy
Vaccines (Inactivated): Immunosuppressants may diminish the therapeutic effect of Vaccines (Inactivated). Management: Vaccine efficacy may be reduced. Complete all age-appropriate vaccinations at least 2 weeks prior to starting an immunosuppressant. If vaccinated during immunosuppressant therapy, revaccinate at least 3 months after immunosuppressant discontinuation. Consider therapy modification
Vaccines (Live): Immunosuppressants may enhance the adverse/toxic effect of Vaccines (Live). Immunosuppressants may diminish the therapeutic effect of Vaccines (Live). Management: Avoid use of live organism vaccines with immunosuppressants; live-attenuated vaccines should not be given for at least 3 months after immunosuppressants. Avoid combination
Central nervous system: Headache (12% to 14%)
Gastrointestinal: Vomiting (NOMID: 14%)
Immunologic: Antibody development (RA: 49%; neutralizing: 2%; no correlation of antibody development and adverse effects)
Infection: Infection (RA: 39%; serious infection: 2% to 3%; including cellulitis, pneumonia, and bone and joint infections)
Local: Injection site reaction (RA: 71%; mild: 73%; moderate: 24%; severe: 2% to 3%; NOMID: 16%; mild: 76%; moderate: 24%)
Neuromuscular & skeletal: Arthralgia (NOMID: 12%)
Respiratory: Nasopharyngitis (NOMID: 12%)
Miscellaneous: Fever (NOMID: 12%)
1% to 10%:
Gastrointestinal: Nausea (RA: 8%), diarrhea (RA: 7%)
Hematologic & oncologic: Eosinophilia (RA: 9%), decreased white blood cell count (RA: 8%), change in platelet count (RA; decreased: 2%
Frequency not defined:
Dermatologic: Skin rash (NOMID)
Endocrine & metabolic: Hypercholesterolemia (RA)
Respiratory: Upper respiratory tract infection (NOMID)
<1%, postmarketing, and/or case reports: Hepatitis (noninfectious), hypersensitivity reaction (including anaphylaxis, angioedema, pruritus, skin rash, urticaria), increased serum transaminases, metastases (malignant lymphoma, malignant melanoma), opportunistic infection, thrombocytopenia (including severe)
Concerns related to adverse effects:
• Anaphylaxis/hypersensitivity reactions: Hypersensitivity reactions, including anaphylactic reactions and angioedema, have been reported; discontinue use if severe hypersensitivity occurs; medications for the treatment of hypersensitivity reactions should be available for immediate use.
• Infections: Associated with an increased risk of serious infections in rheumatoid arthritis studies. Anakinra should not be initiated in patients with an active infection. If a patient receiving anakinra for rheumatoid arthritis develops a serious infection, therapy should be discontinued; if a patient receiving anakinra for neonatal-onset multisystem inflammatory disease (NOMID) develops a serious infection, the risk of a NOMID flare should be weighed against the risks associated with continued treatment. Safety and efficacy have not been evaluated in immunosuppressed patients or patients with chronic infections; the impact on active or chronic infections has not been determined. Immunosuppressive therapy (including anakinra) may lead to reactivation of latent tuberculosis or other atypical or opportunistic infections; test patients for latent TB prior to initiation, and treat latent TB infection prior to use.
• Injection site reactions: Injection site reactions commonly occur (within first 4 weeks of therapy) and are generally mild with a duration of 14 to 28 days.
• Malignancy: May affect defenses against malignancies; impact on the development and course of malignancies is not fully defined. As compared to the general population, an increased risk of lymphoma has been noted in clinical trials; however, rheumatoid arthritis has been previously associated with an increased rate of lymphoma.
• Neutropenia: A decrease in neutrophil count may occur during treatment. Assess neutrophil count at baseline, monthly for 3 months, then every 3 months for up to 1 year. In a limited number of patients with NOMID, neutropenia resolved over time with continued anakinra administration.
• Asthma: Use with caution in patients with asthma; may have increased risk of serious infection.
• Renal impairment: Use caution in patients with renal impairment; extended dosing intervals (every other day) are recommended for severe renal insufficiency (CrCl <30 mL/minute) and ESRD.
Concurrent drug therapy issues:
• Drug-drug interactions: Potentially significant interactions may exist, requiring dose or frequency adjustment, additional monitoring, and/or selection of alternative therapy. Consult drug interactions database for more detailed information.
• Elderly: Use caution due to the potential higher risk for infections.
Dosage form specific issues:
• Polysorbate 80: Some dosage forms may contain polysorbate 80 (also known as Tweens). Hypersensitivity reactions, usually a delayed reaction, have been reported following exposure to pharmaceutical products containing polysorbate 80 in certain individuals (Isaksson 2002; Lucente 2000; Shelley 1995). Thrombocytopenia, ascites, pulmonary deterioration, and renal and hepatic failure have been reported in premature neonates after receiving parenteral products containing polysorbate 80 (Alade 1986; CDC 1984). See manufacturer's labeling.
• Immunizations: Patients should be brought up to date with all immunizations before initiating therapy; live vaccines should not be given concurrently. There is no data available concerning the effects of therapy on vaccination or secondary transmission of live vaccines in patients receiving therapy.
CBC with differential (baseline, then monthly for 3 months, then every 3 months for a period up to 1 year); TB test (baseline); serum creatinine; signs/symptoms of infection
Pregnancy Risk Factor
Adverse events have not been observed in animal reproduction studies.
Information related to the use of anakinra during pregnancy is limited (Makol 2011; Ostensen 2011). Specific guidelines for use in pregnancy are not available (Saag [ACR] 2008); use should not be continued during pregnancy until more data is available (Makol 2011; Ostensen 2011).
Women exposed to anakinra during pregnancy may contact the Organization of Teratology Information Services (OTIS), Rheumatoid Arthritis and Pregnancy Study at 1-877-311-8972.
• Discuss specific use of drug and side effects with patient as it relates to treatment. (HCAHPS: During this hospital stay, were you given any medicine that you had not taken before? Before giving you any new medicine, how often did hospital staff tell you what the medicine was for? How often did hospital staff describe possible side effects in a way you could understand?)
• Patient may experience headache, nausea, vomiting, diarrhea, joint pain, pharyngitis, rhinorrhea, rhinitis, or abdominal pain. Have patient report immediately to prescriber signs of infection, bruising, bleeding, severe injection site irritation, severe dizziness, passing out, tachycardia, abnormal heartbeat, or sweating a lot (HCAHPS).
• Educate patient about signs of a significant reaction (eg, wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat). Note: This is not a comprehensive list of all side effects. Patient should consult prescriber for additional questions.
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More about anakinra
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- Drug class: antirheumatics
Other brands: Kineret