Kineret

Anakinra (Kineret) is a synthetic (man-made), injectable, interleukin-1 (IL-1) receptor antagonist that blocks the effects of human interleukin-1. It is used in the treatment of rheumatoid arthritis.

Dosage Forms And Strengths

100 mg/0.67 mL solution for subcutaneous injection. Graduated syringe allows for doses between 20 and 100 mg.

Storage And Handling

Kineret is supplied in single-use preservative free, prefilled glass syringes with 27 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 4 x 7 syringe dispensing pack containing 28 syringes (NDC 66658-234-28). Kineret is also dispensed in a 1 x 7 syringe dispensing pack containing 7 syringes (NDC 66658-234-07).

Kineret should be stored in the refrigerator at 2° to 8°C (36° to 46°F). DO NOT FREEZE OR SHAKE. Protect from light.

Manufactured by: Swedish Orphan Biovitrum AB (publ) SE-112 76 Stockholm, Sweden License No. 1859. Revised Date: 10/2013

Kineret is a prescription medication used to treat adults with moderate to severe rheumatoid arthritis (RA) when other drugs have not worked. It is also used to treat neonatal onset multisystem inflammatory disease (NOMID). NOMID is a rare disorder that causes persistent inflammation and tissue damage primarily affecting the nervous system, skin, and joints.

Kineret belongs to a group of drugs called biological response modifiers, which inactivate a substance that causes some of the symptoms of RA and NOMID. By binding to IL-1, Kineret can help reduce the symptoms of rheumatoid arthritis, along with the physical damage to the joints, and help patients with NOMID.

This medication comes in an injectable form to be given once daily, just under the skin.

Common side effects of Kineret include redness at the injection site, nausea, and headache.

• Sobi, Inc.

Kineret is part of the drug class:

• Interleukin inhibitors

Tell your healthcare provider if you are breastfeeding or plan to breastfeed. It is not known if Kineret passes into your breast milk. You and your healthcare provider should decide if you will take Kineret or breastfeed.

You should not use this medicine if you are allergic to anakinra or to other medicines that contain E. coli bacteria proteins. You also should not use anakinra if you have an active infection.

To make sure anakinra is safe for you, tell your doctor if you have:

• kidney disease;

• an active or chronic infection;

• a history of recurrent infections;

• fever, chills, or open sores on your skin;

• a weak immune system (caused by disease or by using certain medicines):

• asthma; or

• a history of tuberculosis.

It is not known whether this medicine will harm an unborn baby. Tell your doctor if you are pregnant or plan to become pregnant.

It is not known whether anakinra passes into breast milk or if it could harm a nursing baby. Tell your doctor if you are breast-feeding a baby.

Do not give this medicine to a child without medical advice. Anakinra is not approved for the treatment of rheumatoid arthritis in anyone younger than 18 years old.

Call your doctor for instructions if you miss a dose of anakinra.

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 averages 4–6 hours.1

Special Populations

In patients with renal impairment, plasma clearance was reduced by 16–75% depending on Clcr.1 15 Less than 2.5% of dose removed by hemodialysis or CAPD.1 (See Renal Impairment under Dosage and Administration.)

Gender and age (adjusted for Clcr and body weight) do not have substantial effect on mean plasma clearance.1

Pharmacokinetics not studied in patients with hepatic impairment.1

• 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-1.1 3 4 5 9 10 12 11

• 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

Anakinra injection is used alone or together with other medicines to treat signs and symptoms of moderately to severely active rheumatoid arthritis in adult patients who have not been helped by other medicines (e.g., DMARDs). This medicine is also used to treat a rare genetic disorder called neonatal-onset multisystem inflammatory disease (NOMID). NOMID is the most severe form of a condition called cryopyrin-associated periodic syndrome (CAPS).

This medicine is available only with your doctor's prescription.

• If your symptoms or health problems do not get better or if they become worse, call your doctor.
• Do not share your drugs with others and do not take anyone else's drugs.
• Keep a list of all your drugs (prescription, natural products, vitamins, OTC) with you. Give this list to your doctor.
• Talk with the doctor before starting any new drug, including prescription or OTC, natural products, or vitamins.
• Some drugs may have another patient information leaflet. Check with your pharmacist. If you have any questions about Kineret, please talk with your doctor, nurse, pharmacist, or other health care provider.
• If you think there has been an overdose, call your poison control center or get medical care right away. Be ready to tell or show what was taken, how much, and when it happened.

This information should not be used to decide whether or not to take this medicine or any other medicine. Only the healthcare provider has the knowledge and training to decide which medicines are right for a specific patient. This information does not endorse any medicine as safe, effective, or approved for treating any patient or health condition. This is only a brief summary of general information about Kineret. It does NOT include all information about the possible uses, directions, warnings, precautions, interactions, adverse effects, or risks that may apply to this medicine. This information is not specific medical advice and does not replace information you receive from the healthcare provider. You must talk with the healthcare provider for complete information about the risks and benefits of using Kineret.

Review Date: October 4, 2017

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)].

Cryopyrin-Associated Periodic Syndromes (CAPS)

Kineret is indicated for the treatment of Neonatal-Onset Multisystem Inflammatory Disease (NOMID).

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 patients the risk of a NOMID 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.

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.

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.

Immunosuppression

The impact of treatment with Kineret on active and/or chronic infections and the development of malignancies is not known [see Adverse Reactions (6)].

Immunizations

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.

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)]

Pregnancy

Teratogenic effects: Pregnancy Category B: There are no adequate and well-controlled studies of Kineret in pregnant women. Reproductive studies have been performed in rats and rabbits at doses up to 25 times the maximum recommended human dose (on a mg/kg basis at a maternal dose of 200 mg/kg/day) and have revealed no evidence of impaired fertility or harm to the fetus due to Kineret. Because animal reproduction studies are not always predictive of human response, Kineret should be used during pregnancy only if clearly needed.

Nursing Mothers

It is not known whether Kineret is secreted in human milk. Because many drugs are secreted in human milk, caution should be exercised if Kineret is administered to nursing women.

Pediatric Use

The NOMID study included 36 pediatric patients: 13 below 2 years, 18 between 2 and 11 years, and 5 between 12 and 17 years of age. A subcutaneous Kineret starting dose of 1–2 mg/kg/day was administered in all age groups. An average maintenance dose of 3–4 mg/kg/day was adequate to maintain clinical response throughout the study irrespective of age but a higher dose was, on occasion, required in severely affected patients. The prefilled syringe does not allow doses lower than 20 mg to be administered.

Kineret was studied in a single randomized, blinded multi-center trial in 86 patients with polyarticular course Juvenile Rheumatoid Arthritis (JRA; ages 2-17 years) receiving a dose of 1 mg/kg subcutaneously daily, up to a maximum dose of 100 mg. The 50 patients who achieved a clinical response after a 12-week open-label run-in were randomized to Kineret (25 patients) or placebo (25 patients), administered daily for an additional 16 weeks. A subset of these patients continued open-label treatment with Kineret for up to 1 year in a companion extension study. An adverse event profile similar to that seen in adult RA patients was observed in these studies. These study data are insufficient to demonstrate efficacy and, therefore, Kineret is not recommended for pediatric use in Juvenile Rheumatoid Arthritis.

Geriatric Use

A total of 752 RA patients ≥ 65 years of age, including 163 patients ≥ 75 years of age, were studied in clinical trials. No differences in safety or effectiveness were observed between these patients and younger patients, but greater sensitivity of some older individuals cannot be ruled out. Because there is a higher incidence of infections in the elderly population in general, caution should be used in treating the elderly.

This drug is known to be substantially excreted by the kidney, and the risk of toxic reactions to this drug may be greater in patients with impaired renal function.

Renal Impairment

This drug is known to be substantially excreted by the kidney, and the risk of toxic reactions to this drug may be greater in patients with impaired renal function [see Clinical Pharmacology (12.3)].

Hepatic Impairment

No formal studies have been conducted examining the pharmacokinetics of Kineret administered subcutaneously in patients with hepatic impairment.

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 4 x 7 syringe dispensing pack containing 28 syringes (NDC 66658-234-28). Kineret is also 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