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Pronunciation
(an a KIN ra)
Generic Available (U.S.)
No
Index Terms
Brand Names: U.S.
Brand Names: Canada
Pharmacologic Category
Pharmacologic Category Synonyms
Use: Labeled Indications
Treatment of moderately- to severely-active rheumatoid arthritis in adult patients who have failed one or more disease-modifying antirheumatic drugs (DMARDs); may be used alone or in combination with DMARDs (other than tumor necrosis factor-blocking agents)
Pregnancy Risk Factor
B
Pregnancy Considerations
Animal reproduction studies have not revealed any evidence of impaired fertility or harm to fetus. There are no adequate and well-controlled studies in pregnant women. 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.
Lactation
Excretion in breast milk unknown/use caution
Breast-Feeding Considerations
Endogenous interleukin-1 receptor antagonist can be found in breast milk; specific excretion of anakinra is not known.
Contraindications
Hypersensitivity to E. coli-derived proteins, anakinra, or any component of the formulation
Warnings/Precautions
Concerns related to adverse effects:
• Anaphylaxis/hypersensitivity reactions: May cause hypersensitivity, anaphylaxis, or anaphylactoid reactions; discontinue use if severe hypersensitivity occurs; medications for the treatment of hypersensitivity reactions should be available for immediate use.
• Infections: Caution should be exercised when considering the use in patients with a history of new/recurrent infections, with conditions that predispose them to infections, or with chronic, latent, or localized infections. Patients who develop a new infection while undergoing treatment should be monitored closely. If a patient develops a serious infection, therapy should be discontinued.
• Malignancy: Use 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.
Disease-related concerns:
• Asthma: Use with caution in patients with asthma; may have increased risk of serious infection.
• Hematologic disorders: Use with caution in patients with a history of significant hematologic abnormalities; therapy has been associated with uncommon, but significant decreases in hematologic parameters (particularly neutrophil counts). Patients must be advised to seek medical attention if they develop signs and symptoms suggestive of blood dyscrasias; discontinue if significant hematologic abnormalities are confirmed.
• Renal impairment: Use caution in patients with renal impairment; consider extended dosing intervals for severe renal dysfunction (Clcr <30 mL/minute).
Concurrent drug therapy issues:
• TNF-blocking agents: Use is not recommended in combination with tumor necrosis factor antagonists.
Special populations:
• Elderly: Use caution due to the potential higher risk for infections.
Dosage form specific issues:
• Latex: The packaging (needle cover) contains latex.
Other warnings/precautions:
• 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.
Adverse Reactions
>10%:
Central nervous system: Headache (12%)
Local: Injection site reaction (majority mild, typically lasting 14-28 days, characterized by erythema, ecchymosis, inflammation, and pain; up to 71%)
Miscellaneous: Infection (39% versus 37% in placebo; serious infection 2% to 3%)
1% to 10%:
Gastrointestinal: Nausea (8%), diarrhea (7%)
Hematologic: Neutropenia (8%; grades 3/4: 0.4%)
<1%: Cellulitis, leukopenia, hypersensitivity reactions (including anaphylaxis, angioedema, pruritus, rash, urticaria), opportunistic infection, malignancies (including lymphoma, melanoma), pneumonia (bacterial), pulmonary fibrosis, thrombocytopenia
Metabolism/Transport Effects
None known.
Drug Interactions
Anti-TNF Agents: May enhance the adverse/toxic effect of Anakinra. An increased risk of serious infection during concomitant use has been reported. Risk X: Avoid combination
BCG: Immunosuppressants may diminish the therapeutic effect of BCG. Risk X: 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. Risk X: Avoid combination
Coccidioidin Skin Test: Immunosuppressants may diminish the diagnostic effect of Coccidioidin Skin Test. Risk C: Monitor therapy
Denosumab: May enhance the adverse/toxic effect of Immunosuppressants. Specifically, the risk for serious infections may be increased. Risk C: Monitor therapy
Echinacea: May diminish the therapeutic effect of Immunosuppressants. Risk D: 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. Risk D: Consider therapy modification
Natalizumab: Immunosuppressants may enhance the adverse/toxic effect of Natalizumab. Specifically, the risk of concurrent infection may be increased. Risk X: Avoid combination
Pimecrolimus: May enhance the adverse/toxic effect of Immunosuppressants. Risk X: Avoid combination
Roflumilast: May enhance the immunosuppressive effect of Immunosuppressants. Risk D: Consider therapy modification
Sipuleucel-T: Immunosuppressants may diminish the therapeutic effect of Sipuleucel-T. Risk C: Monitor therapy
Tacrolimus (Topical): May enhance the adverse/toxic effect of Immunosuppressants. Risk X: Avoid combination
Trastuzumab: May enhance the neutropenic effect of Immunosuppressants. Risk C: Monitor therapy
Vaccines (Inactivated): Immunosuppressants may diminish the therapeutic effect of Vaccines (Inactivated). Risk C: Monitor therapy
Vaccines (Live): Immunosuppressants may enhance the adverse/toxic effect of Vaccines (Live). Vaccinial infections may develop. 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. Risk X: Avoid combination
Storage
Store in refrigerator at 2°C to 8°C (36°F to 46°F); do not freeze. Do not shake. Protect from light.
Mechanism of Action
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.
Pharmacodynamics/Kinetics
Bioavailability: SubQ: 95%
Half-life elimination: Terminal: 4-6 hours; Severe renal impairment (Clcr <30 mL/minute): ~7 hours; ESRD: 9.7 hours (Yang, 2003)
Time to peak: SubQ: 3-7 hours
Dosage
Adults: SubQ: Rheumatoid arthritis: 100 mg once daily (administer at approximately the same time each day)
Dosage adjustment in renal impairment: Clcr <30 mL/minute and/or end-stage renal disease: 100 mg every other day
Dosage adjustment in hepatic impairment: There are no dosage adjustments recommended in manufacturer's labeling.
Administration: Other
SubQ: Rotate injection sites (thigh, abdomen, upper arm, buttocks); injection should be given at least 1 inch away from previous injection site. Allow solution to warm to room temperature prior to use (60-90 minutes). Do not shake. Provided in single-use, preservative free syringes with 27-gauge needles; discard any unused portion.
Monitoring Parameters
CBC with differential (baseline, then monthly for 3 months, then every 3 months for a period up to 1 year); serum creatinine
Patient Education
If self-injecting, follow instructions for injection and disposal of needles exactly. If redness, swelling, or irritation appears at the injection site, contact prescriber. You may experience headache. Immediately report skin rash, unusual muscle or bone weakness, or signs of respiratory flu or other infection (eg, chills, fever, sore throat, easy bruising or bleeding, mouth sores, unhealed sores).
Geriatric Considerations
Clinical trials with older adults (65% to 75%) demonstrated no clinical differences between elderly patients and younger adults in safety and efficacy. Since elderly may be more liable to infections in general, use with caution. Also, since many elderly patients may have Clcr <30 mL/minute, close monitoring should be followed with calculation of creatinine clearance prior to initiating therapy with anakinra.
Additional Information
Anakinra is produced by recombinant DNA/E. coli technology.
Dental Health: Effects on Dental Treatment
No significant effects or complications reported
Dental Health: Vasoconstrictor/Local Anesthetic Precautions
No information available to require special precautions
Mental Health: Effects on Mental Status
None reported
Mental Health: Effects on Psychiatric Treatment
May cause leukopenia and rarely neutropenia; use caution with clozapine and carbamazepine. May cause nausea and diarrhea; monitor with concurrent SSRI, lithium, or valproic acid use.
Nursing: Physical Assessment/Monitoring
Monitor effectiveness of therapy (eg, pain, range of motion, mobility, ADL function, inflammation). Teach patient proper injection technique and syringe/needle disposal.
Dosage Forms
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Injection, solution [preservative free]:
Kineret®: 100 mg/0.67 mL (0.67 mL) [contains edetate disodium, natural rubber/natural latex in packaging, polysorbate 80]
Pricing: U.S. (www.drugstore.com)
Solution (Kineret)
100 mg/0.67 mL (4.69): $433.00
References
Cohen S, Hurd E, Cush J, 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(3):614-24.
Fleischmann RM, Schechtman J, Bennett R, et al, “Anakinra, a Recombinant Human Interleukin-1 Receptor Antagonist (r-metHuIL-1ra), in Patients With Rheumatoid Arthritis: A Large, International, Multicenter, Placebo-Controlled Trial,” Arthritis Rheum, 2003, 48(4):927-34.
Fleischmann RM, Tesser J, Schiff MH, et al, Safety of Extended Treatment With Anakinra in Patients With Rheumatoid Arthritis, Ann Rheum Dis, 2006,65(8):1006-12.
Genovese MC, Cohen S, Moreland L, et al, “Combination Therapy With Etanercept and Anakinra in the Treatment of Patients With Rheumatoid Arthritis Who Have Been Treated Unsuccessfully With Methotrexate,” Arthritis Rheum, 2004, 50(5):1412-9.
Yang B, Baughman S, and Sullivan JT, “Pharmacokinetics of Anakinra in Subjects With Different Levels of Renal Function,” Clin Pharmacol Ther, 2003, 74(1):85-94.
International Brand Names
Lexi-Comp.com
Last full review/revision December 2011
Content last modified December 2011
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