KINERET- anakinra injection, solution
Swedish Orphan Biovitrum AB (publ)
1 INDICATIONS AND USAGE
1.1 Active Rheumatoid Arthritis
KINERET is indicated for the reduction in signs and symptoms and slowing the progression of structural damage in moderately to severely active rheumatoid arthritis (RA), in patients 18 years of age or older who have failed 1 or more disease modifying antirheumatic drugs (DMARDs). KINERET can be used alone or in combination with DMARDs other than Tumor Necrosis Factor (TNF) blocking agents [see Warnings and Precautions (5.2)].
1.2 Cryopyrin-Associated Periodic Syndromes (CAPS)
KINERET is indicated for the treatment of Neonatal-Onset Multisystem Inflammatory Disease (NOMID).
1.3 Deficiency of Interleukin-1 Receptor Antagonist (DIRA)
KINERET is indicated for the treatment of Deficiency of Interleukin-1 Receptor Antagonist (DIRA)
2 DOSAGE AND ADMINISTRATION
2.1 Active Rheumatoid Arthritis
The recommended dose of KINERET for the treatment of patients with rheumatoid arthritis is 100 mg/day administered daily by subcutaneous injection. Higher doses did not result in a higher response. The dose should be administered at approximately the same time every day.
2.2 Cryopyrin-Associated Periodic Syndromes (CAPS)
The recommended starting dose of KINERET is 1-2 mg/kg for NOMID patients. The dose can be individually adjusted to a maximum of 8 mg/kg daily to control active inflammation.
Adjust doses in 0.5 to 1 mg/kg increments. Once daily administration is generally recommended, but the dose may be split into twice daily administrations. Each syringe is intended for a single use. A new syringe must be used for each dose. Any unused portion after each dose should be discarded.
2.3 Deficiency of Interleukin-1 Receptor Antagonist (DIRA)
The recommended starting dose of KINERET is 1-2 mg/kg daily for patients with DIRA. The dose can be individually adjusted to a maximum of 8 mg/kg daily to control active inflammation. Adjust doses in 0.5 to 1 mg/kg increments.
Each syringe is intended for a single use. A new syringe must be used for each dose. Any unused portion after each dose should be discarded.
2.4 Renal Impairment
Physicians should consider administration of the prescribed dose of KINERET every other day for patients who have severe renal insufficiency or end stage renal disease (defined as creatinine clearance < 30 mL/min, as estimated from serum creatinine levels) [see Use in Specific Populations (8.6) and Clinical Pharmacology (12.3)].
Instructions on appropriate use should be given by the healthcare provider to the patient or caregiver. Patients or caregivers should not be allowed to administer KINERET until the patient or caregiver has demonstrated a thorough understanding of procedures and an ability to inject the product correctly. The prescribed dose of KINERET should be administered according to the instructions for use and any unused portions discarded. After administration of KINERET it is essential to follow the proper procedure for disposal of syringes and any residual drug. See the “Information for Patients” insert for detailed instructions on the handling and injection of KINERET.
Do not use KINERET beyond the expiration date shown on the carton. Visually inspect the solution for particulate matter and discoloration before administration. There may be trace amounts of small, translucent-to-white amorphous particles of protein in the solution. The prefilled syringe should not be used if the solution is discolored or cloudy, or if foreign particulate matter is present. If the number of translucent-to-white amorphous particles in a given syringe appears excessive, do not use this syringe.
3 DOSAGE FORMS AND STRENGTHS
Injection: 100 mg/0.67 mL solution in a single-use prefilled syringe for subcutaneous injection. Graduated syringe allows for doses between 20 and 100 mg.
KINERET is contraindicated in patients with known hypersensitivity to E coli -derived proteins, KINERET, or any components of the product [see Hypersensitivity Reactions (5.3)].
5 WARNINGS AND PRECAUTIONS
5.1 Serious Infections
KINERET has been associated with an increased incidence of serious infections (2%) vs. Placebo (< 1%) in clinical trials in RA. Administration of KINERET in RA should be discontinued if a patient develops a serious infection. In KINERET treated NOMID and DIRA patients the risk of a disease flare when discontinuing KINERET treatment should be weighed against the potential risk of continued treatment. Treatment with KINERET should not be initiated in patients with active infections. The safety and efficacy of KINERET in immunosuppressed patients or in patients with chronic infections have not been evaluated.
Drugs that affect the immune system by blocking tumor necrosis factor (TNF) have been associated with an increased risk of reactivation of latent tuberculosis (TB). It is possible that taking drugs such as KINERET that blocks IL-1 increases the risk of TB or other atypical or opportunistic infections. Health care providers should follow current CDC guidelines both to evaluate for and to treat possible latent tuberculosis infections before initiating therapy with KINERET.
5.2 Use with TNF Blocking Agents
In a 24-week study of concurrent KINERET and etanercept therapy in RA patients, the rate of serious infections in the combination arm (7%) was higher than with etanercept alone (0%). The combination of KINERET and etanercept did not result in higher ACR response rates compared to etanercept alone [see Clinical Studies (14)]. Use of KINERET in combination with TNF blocking agents is not recommended.
5.3 Hypersensitivity Reactions
Hypersensitivity reactions, including anaphylactic reactions and angioedema, have been reported with KINERET. If a severe hypersensitivity reaction occurs, administration of KINERET should be discontinued and appropriate therapy initiated.
KINERET is the recombinant form of IL-1Ra that DIRA patients are lacking. Patients with DIRA may have an increased risk of allergic reactions, particularly in the first several weeks after starting KINERET treatment. Patients should be closely monitored during this time period. If a severe allergic reaction occurs, appropriate treatment should be initiated and discontinuation of KINERET should be considered.
The impact of treatment with KINERET on active and/or chronic infections and the development of malignancies is not known [see Adverse Reactions (6)].
In a placebo-controlled clinical trial (n = 126), no difference was detected in anti-tetanus antibody response between the KINERET and placebo treatment groups when the tetanus/diphtheria toxoids vaccine was administered concurrently with KINERET. No data are available on the effects of vaccination with other inactivated antigens in patients receiving KINERET. No data are available on either the effects of live vaccination or the secondary transmission of infection by live vaccines in patients receiving KINERET. Therefore, live vaccines should not be given concurrently with KINERET.
5.6 Neutrophil Count
Patients receiving KINERET may experience a decrease in neutrophil counts. Neutrophil counts should therefore be assessed prior to initiating KINERET treatment, and while receiving KINERET, monthly for 3 months, and thereafter quarterly for a period up to 1 year.
In the placebo-controlled studies, 8% of RA patients receiving KINERET had decreases in neutrophil counts of at least one World Health Organization (WHO) toxicity grade compared with 2% in the placebo control group. Nine KINERET-treated patients (0.4%) experienced neutropenia (ANC < 1 x 109 /L). This is discussed in more detail in the Adverse Reactions (6): Hematologic Events (6.1) section.
In 43 NOMID patients followed for up to 60 months 2 patients experienced neutropenia that resolved over time during continued KINERET treatment. [see Adverse Reactions (6.2)]
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