Anakinra

FDA Drug Information • Also known as: Kineret

Brand Names: Kineret
Drug Class: Interleukin-1 Receptor Antagonist [EPC]
Route: SUBCUTANEOUS
Dosage Form: INJECTION, SOLUTION
Product Type: HUMAN PRESCRIPTION DRUG

Description

11 DESCRIPTION KINERET (anakinra) is a recombinant , nonglycosylated form of the human interleukin-1 receptor antagonist (IL-1Ra). KINERET differs from native human IL-1Ra in that it has the addition of a single methionine residue at its amino terminus. KINERET consists of 153 amino acids and has a molecular weight of 17.3 kilodaltons. It is produced by recombinant DNA technology using an E coli bacterial expression system. KINERET is supplied in single use prefilled glass syringes with 29 gauge needles as a sterile, clear, colorless-to-white, preservative free solution for daily subcutaneous (SC) administration. The solution may contain trace amounts of small, translucent-to-white amorphous proteinaceous particles. Each prefilled glass syringe contains: 0.67 mL (100 mg) of anakinra in a solution (pH 6.5) containing anhydrous citric acid (1.29 mg), disodium EDTA (0.12 mg), polysorbate 80 (0.70 mg), and sodium chloride (5.48 mg) in Water for Injection, USP. The prefilled syringe contains an outer rigid plastic needle shield attached to an inner needle cover. The syringe or needle shield components are not made with natural rubber latex.

What Is Anakinra Used For?

1 INDICATIONS AND USAGE KINERET is an interleukin-1 receptor antagonist indicated for: Rheumatoid Arthritis (RA) Reduction in signs and symptoms and slowing the progression of structural damage in moderately to severely active rheumatoid arthritis, in patients 18 years of age or older who have failed 1 or more disease modifying antirheumatic drugs (DMARDs) ( 1.1 ) Cryopyrin-Associated Periodic Syndromes (CAPS) Treatment of Neonatal-Onset Multisystem Inflammatory Disease (NOMID) ( 1.2 ) Deficiency of Interleukin-1 Receptor Antagonist (DIRA) Treatment of Deficiency of Interleukin-1 Receptor Antagonist (DIRA) ( 1.3 ) 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)

Dosage and Administration

2 DOSAGE AND ADMINISTRATION Rheumatoid Arthritis (RA) The recommended dose of KINERET for the treatment of patients with rheumatoid arthritis is 100 mg/day administered daily by subcutaneous injection. The dose should be administered at approximately the same time every day ( 2.1 ) Physicians should consider a dose of 100 mg of KINERET administered every other day for RA patients who have severe renal insufficiency or end stage renal disease (defined as creatinine clearance < 30 mL/min, as estimated from serum creatinine levels) ( 2.4 ) Cryopyrin-Associated Periodic Syndromes (CAPS) The recommended starting dose of KINERET is 1-2 mg/kg daily for NOMID patients. The dose can be individually adjusted to a maximum of 8 mg/kg daily to control active inflammation. ( 2.2 ) Physicians should consider administration of the prescribed KINERET dose every other day for NOMID patients who have severe renal insufficiency or end stage renal disease (defined as creatinine clearance < 30 mL/min, as estimated from serum creatinine levels) ( 2.4 ) 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. ( 2.3 ) Physicians should consider administration of the prescribed KINERET dose every other day for patients with DIRA who have severe renal insufficiency or end stage renal disease (defined as creatinine clearance < 30 mL/min, as estimated from serum creatinine levels) ( 2.4 ) See full prescribing information for administration instructions ( 2.4 ) 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...

Side Effects (Adverse Reactions)

6 ADVERSE REACTIONS Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in clinical practice. Rheumatoid Arthritis (RA) Most common adverse reactions (incidence ≥ 5%) are injection site reaction, worsening of rheumatoid arthritis, upper respiratory tract infection, headache, nausea, diarrhea, sinusitis, arthralgia, flu like-symptoms, and abdominal pain ( 6.1 ) NOMID The most common AEs during the first 6 months of treatment (incidence > 10%) are injection site reaction, headache, vomiting, arthralgia, pyrexia, and nasopharyngitis ( 6.2 ) DIRA The most common AEs are upper respiratory tract infections, rash, pyrexia, influenza like illness, and gastroenteritis ( 6.3 ) To report SUSPECTED ADVERSE REACTIONS, contact Swedish Orphan Biovitrum at 1-866-547-0644 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 6.1 Clinical Studies Experience in RA The most serious adverse reactions were: Serious Infections – [see Warnings and Precautions ( 5.1 )] Neutropenia, particularly when used in combination with TNF blocking agents The most common adverse reaction with KINERET is injection-site reactions. These reactions were the most common reason for withdrawing from studies. The data described herein reflect exposure to KINERET in 3025 patients, including 2124 exposed for at least 6 months and 884 exposed for at least one year. Studies 1 and 4 used the recommended dose of 100 mg per day. The patients studied were representative of the general population of patients with rheumatoid arthritis. Injection-site Reactions The most common and consistently reported treatment-related adverse event associated with KINERET is injection-site reaction (ISR). In Studies 1 and 4, 71% of patients developed an ISR, which was typically reported within the first 4 weeks of therapy. The majority of ISRs were reported as mild (72.6% mild, 24.1% moderate and 3.2% severe). The ISRs typically lasted for 14 to 28 days and were characterized by 1 or more of the following: erythema, ecchymosis, inflammation, and pain. Injection-site Reactions The most common and consistently reported treatment-related adverse event associated with KINERET is injection-site reaction (ISR). In Studies 1 and 4, 71% of patients developed an ISR, which was typically reported within the first 4 weeks of therapy. The majority of ISRs were reported as mild (72.6% mild, 24.1% moderate and 3.2% severe). The ISRs typically lasted for 14 to 28 days and were characterized by 1 or more of the following: erythema, ecchymosis, inflammation, and pain. Injection-site Reactions The most common and consistently reported treatment-related adverse event associated with KINERET is injection-site reaction (ISR). In Studies 1 and 4, 71% of patients developed an ISR, which was typically reported within the first 4 weeks of therapy. The majority of ISRs were reported as mild (72.6% mild, 24.1% moderate and 3.2% severe). The ISRs typically lasted for 14 to 28 days and were characterized by 1 or more of the following: erythema, ecchymosis, inflammation, and pain. Infections In Studies 1 and 4 combined, the incidence of infection was 39% in the KINERET-treated patients and 37% in placebo-treated patients during the first 6 months of blinded treatment. The incidence of serious infections in Studies 1 and 4 was 2% in KINERET-treated patients and 1% in patients receiving placebo over 6 months. The incidence of serious infection over 1 year was 3% in KINERET-treated patients and 2% in patients receiving placebo. These infections consisted primarily of bacterial events such as cellulitis, pneumonia, and bone and joint infections. Majority of patients (73%) continued on study drug after the infection resolved. No serious opportunistic infections were reported. Patients with asthma appeared to be at higher risk of...

Drug Interactions

7 DRUG INTERACTIONS No drug-drug interaction studies in human subjects have been conducted. Toxicologic and toxicokinetic studies in rats did not demonstrate any alterations in the clearance or toxicologic profile of either methotrexate or KINERET when the two agents were administered together. A higher rate of serious infections has been observed in RA patients treated with concurrent KINERET and etanercept therapy than in patients treated with etanercept alone. Use of KINERET in combination with TNF blocking agents is not recommended ( 7 ) 7.1 TNF Blocking Agents A higher rate of serious infections has been observed in patients treated with concurrent KINERET and etanercept therapy than in patients treated with etanercept alone [see Warnings and Precautions ( 5.2 )] . Two percent of patients treated concurrently with KINERET and etanercept developed neutropenia (ANC < 1 x 10 9 /L). Use of KINERET in combination with TNF blocking agents is not recommended.

Contraindications

4 CONTRAINDICATIONS 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 )] . Known hypersensitivity to E coli -derived proteins, Kineret, or to any component of the product. ( 4 )

Pregnancy and Breastfeeding

8.1 Pregnancy Risk Summary Available data from retrospective studies and case reports on KINERET use in pregnant women are insufficient to identify a drug associated risk of major birth defects, miscarriage, or maternal and fetal adverse events. There are risks to the mother and fetus associated with active rheumatoid arthritis or Cryopyrin-Associated Periodic Syndromes (CAPS). In animal reproduction studies, subcutaneous administration of anakinra to pregnant rats and rabbits during organogenesis demonstrated no evidence of fetal harm at doses up to 25 times the maximum recommended human dose (MRHD). The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2-4% and 15-20%, respectively. Clinical Considerations Disease-associated maternal and/or embryo/fetal risk Published data suggest the risk of adverse pregnancy outcomes in women with rheumatoid arthritis or CAPS is associated with increased disease activity. Adverse pregnancy outcomes include preterm delivery (before 37 weeks of gestation), low birth weight (<2500 grams), and small for gestational age at birth. Data Human Data The available data from retrospective studies and case reports of anakinra-exposed pregnancies have not identified an increased frequency or pattern of birth defects, miscarriage, or adverse maternal or fetal outcomes. An international multi-center retrospective study of pregnancy outcomes with interleukin-1 inhibitors reported on 23 anakinra-exposed pregnancies. There were 21 live births of healthy infants, 1 miscarriage, and 1 infant with left renal agenesis. The estimated background rate of detected renal malformations is 0.2-2% of all newborns. Another retrospective study reported on 10 anakinra-exposed...

Overdosage

10 OVERDOSAGE There have been no cases of overdose reported with KINERET in clinical trials of RA or NOMID. In sepsis trials no serious toxicities attributed to KINERET were seen when administered at mean calculated doses of up to 35 times those given patients with RA over a 72-hour treatment period.

How Supplied

16 HOW SUPPLIED/STORAGE AND HANDLING KINERET is supplied in single-use preservative free, prefilled glass syringes with 29 gauge needles. Each prefilled glass syringe contains 100 mg of anakinra per 0.67 mL. The full syringe contains 100 mg anakinra. KINERET is dispensed in a 1 x 7 syringe dispensing pack containing 7 syringes (NDC 66658-234-07). Storage KINERET should be stored in the refrigerator at 2°C to 8°C (36°F to 46°F). DO NOT FREEZE OR SHAKE. Protect from light. Rx only

About This Information

This drug information is sourced from FDA-approved labeling via the openFDA database. It is intended for educational and reference purposes only. This is not medical advice. Always consult your healthcare provider before making decisions about medication. Drug information may be updated by the FDA; check with your pharmacist for the most current information.

What are side effects?

Side effects are unwanted reactions that can occur when taking a medication. They range from mild (headache, nausea) to severe (allergic reactions, organ damage). Not everyone experiences side effects, and severity varies. Report any concerning side effects to your doctor.

What are drug interactions?

Drug interactions occur when a medication is affected by another drug, food, or supplement. Interactions can make medications less effective or cause dangerous side effects. Always tell your doctor about all medications and supplements you take.