Kineret (Anakinra)
برای این دارو، اطلاعات عمومی (فارسی) یافت نشد . برای افزودن اطلاعات فارسی به این دارو کلیک نمایید.
Kineret (Anakinra)

Kineret®
(anakinra) for Injection

DRUG 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 27 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 disodium EDTA (0.12 mg), sodium chloride (5.48 mg), sodium citrate (1.29 mg), and polysorbate 80 (0.70 mg) in Water for Injection, USP.

What are the possible side effects of anakinra (Kineret)?

If you experience an allergic reaction (difficulty breathing; closing of the throat; swelling of your lips, tongue, or face; or hives), stop using anakinra, and seek emergency medical attention.

In rare cases, people receiving anakinra have developed serious infections. Notify your doctor immediately if you develop a fever, flu-like symptoms, or any other sign of infection.

Other less serious side effects may be more likely to occur. Continue to use anakinra and notify your doctor if you experience

  • nausea or diarrhea;
  • a headache;
  • sinus irritation or...

Read All Potential Side Effects and See Pictures of Kineret »

What are the precautions when taking anakinra (Kineret)?

Before using anakinra, tell your doctor or pharmacist if you are allergic to it; or to proteins made from a certain bacteria (E. coli); or to latex; or if you have any other allergies. This product may contain inactive ingredients, which can cause allergic reactions or other problems. Talk to your pharmacist for more details.

Before using this medication, tell your doctor or pharmacist your medical history, especially of: recent/current infection, immune system problems (such as HIV disease), kidney disease, asthma.

Anakinra can make you more likely to get infections or may worsen any current infections. Therefore, wash your hands well to prevent the spread of infection. Avoid contact with people who have infections that may spread to others (such as chickenpox, measles,...

Read All Potential Precautions of Kineret »

Last reviewed on RxList: 1/16/2013
This monograph has been modified to include the generic and brand name in many instances.

INDICATIONS

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].

Cryopyrin-Associated Periodic Syndromes (CAPS)

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

DOSAGE AND ADMINISTRATION

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.

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 1.0 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.

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 and CLINICAL PHARMACOLOGY].

Administration

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.

HOW SUPPLIED

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).

Storage

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. Revised: December 2012

Last reviewed on RxList: 1/16/2013
This monograph has been modified to include the generic and brand name in many instances.

SIDE EFFECTS

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.

Clinical Studies Experience in RA

The most serious adverse reactions were:

  • Serious Infections – [see WARNINGS AND PRECAUTIONS]
  • 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.

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 developing serious infections when treated with Kineret (8 of 177 patients, 4.5%) compared to placebo (0 of 50 patients, 0%).

In open-label extension studies, the overall rate of serious infections was stable over time and comparable to that observed in controlled trials. In clinical studies and postmarketing experience, cases of opportunistic infections have been observed and included fungal, mycobacterial and bacterial pathogens. Infections have been noted in all organ systems and have been reported in patients receiving Kineret alone or in combination with immunosuppressive agents.

In patients who received both Kineret and etanercept for up to 24 weeks, the incidence of serious infections was 7%. The most common infections consisted of bacterial pneumonia (4 cases) and cellulitis (4 cases). One patient with pulmonary fibrosis and pneumonia died due to respiratory failure.

Malignancies

Among 5300 RA patients treated with Kineret in clinical trials for a mean of 15 months (approximately 6400 patient years of treatment), 8 lymphomas were observed for a rate of 0.12 cases/100 patient years. This is 3.6 fold higher than the rate of lymphomas expected in the general population, based on the National Cancer Institute's Surveillance, Epidemiology and End Results (SEER) database.3 An increased rate of lymphoma, up to several fold, has been reported in the RA population, and may be further increased in patients with more severe disease activity. Thirty-seven malignancies other than lymphoma were observed. Of these, the most common were breast, respiratory system, and digestive system. There were 3 melanomas observed in Study 4 and its long-term open-label extension, greater than the 1 expected case. The significance of this finding is not known. While patients with RA, particularly those with highly active disease, may be at a higher risk (up to several fold) for the development of lymphoma, the role of IL-1 blockers in the development of malignancy is not known.

Hematologic Events

In placebo-controlled studies with Kineret, 8% of patients receiving Kineret had decreases in total white blood counts of at least one WHO toxicity grade, compared with 2% of placebo patients. Nine Kineret-treated patients (0.4%) developed neutropenia (ANC < 1 x 109/L). 9 % of patients receiving Kineret had increases in eosinophil differential percentage of at least one WHO toxicity grade, compared with 3 % of placebo patients. Of patients treated concurrently with Kineret and etanercept 2% developed neutropenia (ANC < 1 x 109/L). While neutropenic, one patient developed cellulitis which recovered with antibiotic therapy. 2% of patients receiving Kineret had decreases in platelets, all of WHO toxicity grade one, compared to 0% of placebo patients.

Hypersensitivity Reactions

Hypersensitivity reactions including anaphylactic reactions, angioedema, urticaria, rash, and pruritus have been reported with Kineret.

Immunogenicity

As with all therapeutic proteins, there is potential for immunogenicity. In Studies 1 and 4, from which data is available for up to 36 months, 49% of patients tested positive for anti-anakinra binding antibodies at one or more time points using a biosensor assay. Of the 1615 patients with available data at Week 12 or later, 30 (2%) tested positive for neutralizing antibodies in a cell-based bioassay. Of the 13 patients with available follow-up data, 5 patients remained positive for neutralizing antibodies at the end of the studies. No correlation between antibody development and adverse events was observed.

The detection of antibody formation is highly dependent on the sensitivity and specificity of the assays. Additionally, the observed incidence of antibody (including neutralizing antibody) positivity in an assay may be influenced by several factors, including sample handling, concomitant medications, and underlying disease. For these reasons, comparison of the incidence of antibodies to Kineret with the incidence of antibodies to other products may be misleading.

Other Adverse Events

Table 1 reflects adverse events in Studies 1 and 4, that occurred with a frequency of ≥ 5% in Kineret-treated patients over a 6-month period.

Table 1: Percent of RA Patients Reporting Adverse Events (Studies 1 and 4)

Preferred term Placebo
(n = 733)
Kineret 100 mg/day
(n = 1565)
Injection Site Reaction 29% 71%
Worsening of RA 29% 19%
Upper Respiratory Tract Infections 17% 14%
Headache 9% 12%
Nausea 7% 8%
Diarrhea 5% 7%
Sinusitis 7% 7%
Arthralgia 6% 6%
Flu Like Symptoms 6% 6%
Abdominal Pain 5% 5%

Clinical Study Experience in NOMID

The data described herein reflect an open-label study in 43 NOMID patients exposed to Kineret for up to 60 months adding up to a total exposure of 159.8 patient years.

Patients were treated with a starting dose of 1 to 2 mg/kg/day and an average maintenance dose of 3-4 mg/kg/day adjusted depending on the severity of disease. Among pediatric NOMID patients, doses up to 7.6 mg/kg/day have been maintained for up to 15 months.

There were 24 serious adverse events (SAEs) reported in 14 of the 43 treated patients. The most common type of SAEs reported were infections [see WARNINGS AND PRECAUTIONS]. Five SAEs were related to lumbar puncture, which was part of the study procedure.

There were no permanent discontinuations of study drug treatment due to AEs. Doses were adjusted in 5 patients because of AEs; all were dose increases in connection with disease flares.

The reporting frequency of AEs was highest during the first 6 months of treatment. The incidence of AEs did not increase over time, and no new types of AEs emerged.

The most commonly reported AEs during the first 6 months of treatment (incidence > 10%) were injection site reaction (ISR), headache, vomiting, arthralgia, pyrexia, and nasopharyngitis (Table 2).

The most commonly reported AEs during the 60-month study period, calculated as the number of events/patient years of exposure, were arthralgia, headache, pyrexia, upper respiratory tract infection, nasopharyngitis, and rash (Table 2).

The AE profiles for different age groups < 2 years, 2-11 years, and 12-17 years corresponded to the AE profile for patients ≥ 18 years, with the exception of infections and related symptoms being more frequent in patients < 2 years.

Infections

The reporting rate for infections was higher during the first 6 months of treatment (2.3 infections/patient-year) compared to after the first 6 months (1.7 infections/patient year). The most common infections were upper respiratory tract infection, sinusitis, ear infections, and nasopharyngitis.

There were no deaths or permanent treatment discontinuations due to infections. In one patient Kineret administration was temporarily stopped during an infection and in 5 patients the dose of Kineret was increased due to disease flares in connection with infections. Thirteen infections in 7 patients were classified as serious, the most common being pneumonia and gastroenteritis occurring in 3 and 2 patients, respectively. No serious opportunistic infections were reported.

The reporting frequency for infections was highest in patients < 12 years of age.

Hematologic Events

After start of Kineret treatment neutropenia was reported in 2 patients. One of these patients experienced an upper respiratory tract infection and an otitis media infection. Both episodes of neutropenia resolved over time with continued Kineret treatment.

Injection Site Reactions

In total, 17 injection site reactions (ISRs) were reported in 10 patients during the 60-month study period. Out of the 17 ISRs, 11 (65%) occurred during the first month and 13 (76%) were reported during the first 6 months. No ISR was reported after Year 2 of treatment. The majority of ISRs were reported as mild (76% mild, 24% moderate). No patient permanently or temporarily discontinued Kineret treatment due to injection site reactions.

Immunogenicity

The immunogenicity of Kineret in NOMID patients was not evaluated.

Table 2: Most common ( > 10% of patients) treatment-emergent adverse events during the first 6 months of Kineret treatment

Preferred term Safety population (N=43)
Total exposure in patient years= 20.8
N (%) Number of events /patient year
Injection site reaction 7 (16.3%) 0.5
Headache 6 (14.0%) 0.7
Vomiting 6 (14.0%) 0.6
Arthralgia 5 (11.6%) 0.6
Pyrexia 5 (11.6%) 0.4
Nasopharyngitis 5 (11.6%) 0.3

The most common adverse reactions occurring after the first 6-month period of treatment with Kineret (up to 60 months of treatment) included: arthralgia, headache, pyrexia, upper respiratory tract infection, nasopharyngitis, and rash.

REFERENCES

3. National Cancer Institute. Surveillance, Epidemiology, and End Results Database (SEER) Program. SEER Incidence Crude Rates, 11 Registries, 1992-1999.

Read the Kineret (anakinra) Side Effects Center for a complete guide to possible side effects »

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.

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]. Two percent of patients treated concurrently with Kineret and etanercept developed neutropenia (ANC < 1 x 109/L). Use of Kineret in combination with TNF blocking agents is not recommended.

Last reviewed on RxList: 1/16/2013
This monograph has been modified to include the generic and brand name in many instances.

WARNINGS

Included as part of the PRECAUTIONS section.

PRECAUTIONS

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]. 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.

The needle cover of the prefilled syringe contains dry natural rubber (a derivative of latex), which may cause allergic reactions in individuals sensitive to latex.

Immunosuppression

The impact of treatment with Kineret on active and/or chronic infections and the development of malignancies is not known [see ADVERSE REACTIONS].

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]

Patient Counseling Information

Instruct patients and their caregivers on the proper dosage and administration of Kineret and provide all patients with the “Patient information and Instructions for Use” insert. While this Patient Information and Instructions for Use provides information about the product and its use, it is not intended to take the place of regular discussions between the patient and healthcare provider. The ability to inject subcutaneously should be assessed to ensure proper administration of Kineret. Inform patients and their caregivers that the needle cover on the prefilled syringe contains dry natural rubber (a derivative of latex), which should not be handled by persons sensitive to latex. Thoroughly instruct patients and their caregivers on the importance of proper disposal and caution against the reuse of needles, syringes, and drug product. A puncture-resistant container for the disposal of used syringes should be available to the patient. The full container should be disposed of according to the directions provided by the healthcare provider.

Infections: Inform patients that Kineret may lower the ability of their immune system to fight infections. Advise patients of the importance of contacting their doctor if they develop any symptoms of infection.

Injection-site reactions: Physicians should explain to patients that almost a quarter of patients in the clinical trial experienced a reaction at the injection site. Injection-site reactions may include pain, erythema, swelling, purities, brusing, mass, inflammation, dermatitis, edema, urticaria, vesicles, warmth, and hemorrhage. Patients should be cautioned to avoid injecting into an area that is already swollen or red. Any persistent reaction should be brought to the attention of the prescribing physician.

Allergic or other drug reactions: Inform patients about the signs and symptoms of allergic and other adverse drug reactions and the appropriate actions they should take if they experience any of these signs and symptoms.

See FDA-approved patient labeling (Patient Information and Instruction for Use)

Nonclinical Toxicology

Carcinogenesis, Mutagenesis, and Impairment of Fertility

Long-term animal studies to evaluate the carcinogenic potential of Kineret were not conducted. Using a standard in vivo and in vitro battery of mutagenesis assays, Kineret did not induce gene mutations in either bacteria or mammalian cells. Kineret had no effects on fertility and reproductive performance indices in male and female rats at 200 mg/kg/day (approximately 25 times the maximum recommended dose).

Use In Specific Populations

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].

Hepatic Impairment

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

Last reviewed on RxList: 1/16/2013
This monograph has been modified to include the generic and brand name in many instances.

OVERDOSE

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.

CONTRAINDICATIONS

Kineret is contraindicated in patients with known hypersensitivity to E coli-derived proteins, Kineret, or any components of the product [see section Hypersensitivity Reactions].

Last reviewed on RxList: 1/16/2013
This monograph has been modified to include the generic and brand name in many instances.

CLINICAL PHARMACOLOGY

Mechanism of Action

Kineret blocks the biologic activity of IL-1 alpha and beta by competitively inhibiting IL-1 binding to the interleukin-1 type I receptor (IL-1RI), which is expressed in a wide variety of tissues and organs.

IL-1 production is induced in response to inflammatory stimuli and mediates various physiologic responses including inflammatory and immunological responses. IL-1 has a broad range of activities including cartilage degradation by its induction of the rapid loss of proteoglycans, as well as stimulation of bone resorption. The levels of the naturally occurring IL-1Ra in synovium and synovial fluid from RA patients are not sufficient to compete with the elevated amount of locally produced IL-1.

Spontaneous mutations in the CIAS1/NLRP3 gene have been identified in a majority of patients with cryopyrin-associated periodic syndromes such as NOMID. CIAS1/NLRP3 encodes for cryopyrin, a component of the inflammasome. The activated inflammasome results in proteolytic maturation and secretion of IL-1β, which has an important role in the systemic inflammation and manifestations of NOMID.

Pharmacokinetics

The absolute bioavailability of Kineret after a 70 mg subcutaneous bolus injection in healthy subjects (n = 11) is 95%. In subjects with RA, maximum plasma concentrations of Kineret occurred 3 to 7 hours after subcutaneous administration of Kineret at clinically relevant doses (1 to 2 mg/kg; n = 18); the terminal half-life ranged from 4 to 6 hours. In RA patients, no unexpected accumulation of Kineret was observed after daily subcutaneous doses for up to 24 weeks.

The influence of demographic covariates on the pharmacokinetics of Kineret was studied using population pharmacokinetic analysis encompassing 341 patients receiving daily subcutaneous injection of Kineret at doses of 30, 75, and 150 mg for up to 24 weeks. The estimated Kineret clearance increased with increasing creatinine clearance and body weight. After adjusting for creatinine clearance and body weight, gender and age were not significant factors for mean plasma clearance.

In NOMID patients, at a median SC dose of 3 mg/kg once daily and a median treatment time of 3.5 years, the median (range) steady-state serum exposure of anakinra was Cmax 3628 (655–8511) ng/mL (n=16) and C24h 203 (53–1979) ng/mL (n=16). The median (range) half-life of anakinra was 5.7 (3.1–28.2) hours (n=12). There was no obvious gender difference.

Patients With Renal Impairment: The mean plasma clearance of Kineret in subjects with mild (creatinine clearance 50-80 mL/min) and moderate (creatinine clearance 30-49 mL/min) renal insufficiency was reduced by 16% and 50%, respectively. In severe renal insufficiency and end stage renal disease (creatinine clearance < 30 mL/min1), mean plasma clearance declined by 70% and 75%, respectively. Less than 2.5% of the administered dose of Kineret was removed by hemodialysis or continuous ambulatory peritoneal dialysis. Based on these observations, a dose schedule change should be considered for subjects with severe renal insufficiency or end stage renal disease [see DOSAGE AND ADMINISTRATION].

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

Clinical Studies

Clinical Studies in RA

The safety and efficacy of Kineret have been evaluated in three randomized, double-blind, placebo-controlled trials of 1790 patients ≥ 18 years of age with active rheumatoid arthritis (RA). An additional fourth study was conducted to assess safety. In the efficacy trials, Kineret was studied in combination with other disease-modifying antirheumatic drugs (DMARDs) other than Tumor Necrosis Factor (TNF) blocking agents (Studies 1 and 2) or as a monotherapy (Study 3).

Study 1 involved 899 patients with active RA who had been on a stable dose of methotrexate (MTX) (10 to 25 mg/week) for at least 8 weeks. All patients had at least 6 swollen/painful and 9 tender joints and either a C-reactive protein (CRP) of ≥ 1.5 mg/dL or an erythrocyte sedimentation rate (ESR) of ≥ 28 mm/hr. Patients were randomized to Kineret or placebo in addition to their stable doses of MTX. The first 501 patients were evaluated for signs and symptoms of active RA. The total 899 patients were evaluated for progression of structural damage.

Study 2 evaluated 419 patients with active RA who had received MTX for at least 6 months including a stable dose (15 to 25 mg/week) for at least 3 consecutive months prior to enrollment. Patients were randomized to receive placebo or one of five doses of Kineret subcutaneous daily for 12 to 24 weeks in addition to their stable doses of MTX.

Study 3 evaluated 472 patients with active RA and had similar inclusion criteria to Study 1 except that these patients had received no DMARD for the previous 6 weeks or during the study. Patients were randomized to receive either Kineret or placebo. Patients were DMARD-naïve or had failed no more than 3 DMARDs.

Study 4 was a placebo-controlled, randomized trial designed to assess the safety of Kineret in 1414 patients receiving a variety of concurrent medications for their RA including some DMARD therapies, as well as patients who were DMARD-free. The TNF blocking agents etanercept and infliximab were specifically excluded. Concurrent DMARDs included MTX, sulfasalazine, hydroxychloroquine, gold, penicillamine, leflunomide, and azathioprine. Unlike Studies 1, 2 and 3, patients predisposed to infection due to a history of underlying disease such as pneumonia, asthma, controlled diabetes, and chronic obstructive pulmonary disease (COPD) were also enrolled [see ADVERSE REACTIONS].

In Studies 1, 2 and 3, the improvement in signs and symptoms of RA was assessed using the American College of Rheumatology (ACR) response criteria (ACR20, ACR50, ACR70). In these studies, patients treated with Kineret were more likely to achieve an ACR20 or higher magnitude of response (ACR50 and ACR70) than patients treated with placebo (Table 3). The treatment response rates did not differ based on gender or ethnic group. The results of the ACR component scores in Study 1 are shown in Table 4.

Most clinical responses, both in patients receiving placebo and patients receiving Kineret, occurred within 12 weeks of enrollment.

Table 3: Percent of Patients with ACR Responses in Studies 1 and 3

Response Study 1 (Patientson MTX) Study 3 (No DMARDs)
Placebo
(n= 251)
Kineret 100 mg/day
(n = 250)
Placebo
(n = 119)
Kineret 75 mg/day
(n = 115)
150 mg/day
(n = 115)
ACR20
  Month 3 24% 34%a 23% 33% 33%
  Month 6 22% 38%c 27% 34% 43%a
ACR50
  Month 3 6% 13%b 5% 10% 8%
  Month 6 8% 17%b 8% 11% 19%a
ACR70
  Month 3 0% 3%a 0% 0% 0%
  Month 6 2% 6%a 1% 1% 1%
ap < 0.05, Kineret versus placebo
bp < 0.01, Kineret versus placebo
cp < 0.001, Kineret versus placebo

Table 4: Median ACR Component Scores in Study 1

Parameter (median) Placebo/MTX
(n = 251)
Kineret/MTX 100 mg/day
(n = 250)
Baseline Month 6 Baseline Month 6
Patient Reported Outcomes
  Disability indexa 1.38 1.13 1.38 1.00
  Patient global assessmentb 51.0 41.0 51.0 29.0
  Painb 56.0 44.0 63.0 34.0
Objective Measures
  ESR (mm/hr) 35.0 32.0 36.0 19.0
  CRP (mg/dL) 2.2 1.6 2.2 0.5
Physician's Assessments
  Tender/painful jointsc 20.0 11.0 23.0 9.0
  Physician global assessmentb 59.0 31.0 59.0 26.0
  Swollen jointsd 18.0 10.5 17.0 9.0
aHealth Assessment Questionnaire; 0 = best, 3 = worst; includes eight categories: dressing and grooming, arising, eating, walking, hygiene, reach, grip, and activities.
bVisual analog scale; 0 = best, 100 = worst
cScale 0 to 68
dScale 0 to 66

A 24-week study was conducted in 242 patients with active RA on background methotrexate who were randomized to receive either etanercept alone or the combination of Kineret and etanercept. The ACR50 response rate was 31% for patients treated with the combination of Kineret and etanercept and 41% for patients treated with etanercept alone, indicating no added clinical benefit of the combination over etanercept alone. Serious infections were increased with the combination compared to etanercept alone [see WARNINGS AND PRECAUTIONS].

In Study 1, the effect of Kineret on the progression of structural damage was assessed by measuring the change from baseline at month 12 in the Total Modified Sharp Score (TSS) and its subcomponents, erosion score, and joint space narrowing (JSN) score.2 Radiographs of hands/wrists and forefeet were obtained at baseline, 6 months and 12 months and scored by readers who were unaware of treatment group. A difference between placebo and Kineret for change in TSS, erosion score (ES) and JSN score was observed at 12 months (Table 5).

Table 5: Mean Radiographic Changes Over 12 Months in Study 1

  Placebo/MTX (N = 450) Kineret 100 mg/day /MTX (N = 449) Placebo/MTX vs. Kineret/MTX
Baseline Change at Month 12 Baseline Change at Month 12 95% Confidence Interval* p-value**
TSS 52 2.6 50 1.7 0.9 [0.3, 1.6] < 0.001
Erosion 28 1.6 25 1.1 0.5 [0.1, 1.0] 0.024
JSN 24 1.1 25 0.7 0.4 [0.1, 0.7] < 0.001
* Differences and 95% confidence intervals for the differences in change scores between Placebo/MTX and Kineret/MTX
** Based on Wilcoxon rank-sum test

The disability index of the Health Assessment Questionnaire (HAQ) was administered monthly for the first six months and quarterly thereafter during Study 1. Health outcomes were assessed by the Short Form-36 (SF-36) questionnaire. The 1-year data on HAQ in Study 1 showed more improvement with Kineret than placebo. The physical component summary (PCS) score of the SF-36 also showed more improvement with Kineret than placebo but not the mental component summary (MCS).

Clinical Studies in NOMID

The efficacy of Kineret was evaluated in a prospective, long-term, open-label and uncontrolled study which incorporated a withdrawal period in a subset of 11 patients. This study included 43 NOMID patients 0.7 to 46 years of age treated for up to 60 months. Patients were given an initial Kineret dose of 1–2.4 mg/kg body weight. During the study, the dose was adjusted by 0.5 to 1 mg/kg increments to a protocol-specified maximum of 10 mg/kg daily, titrated to control signs and symptoms of disease. The maximum dose actually studied was 7.6 mg/kg/day. The average maintenance dose was 3 to 4 mg/kg daily. In general, the dose was given once daily, but for some patients, the dose was split into twice daily administrations for better control of disease activity.

NOMID symptoms were assessed with a disease-specific Diary Symptom Sum Score (DSSS), which included the prominent disease symptoms fever, rash, joint pain, vomiting, and headache. In addition, serum amyloid A (SAA), hsCRP, and ESR levels were monitored. Changes in clinical and laboratory parameters from baseline to Months 3 to 6 and from Month 3 (before withdrawal) to the end of the withdrawal period were assessed in the subset of patients who underwent withdrawal. The estimated changes from baseline in DSSS are summarized through Month 60 in Table 6. Results were consistent across all subgroups, including age, gender, presence of CIAS1 mutation, and disease phenotype. Improvements occurred in all individual disease symptoms comprising the DSSS (Table 7), as well as in the serum markers of inflammation. For the 11 patients who went through a withdrawal phase, disease symptoms and serum markers of inflammation worsened after withdrawal and promptly responded to reinstitution of Kineret therapy. Upon withdrawal of treatment, the median time until disease flare criteria were met was 5 days.

Table 6: Estimated change from baseline in DSSS in NOMID patients (N=29)

Time point Estimated mean change from baseline in DSSS* 95% confidence interval
Month 3-6 -3.5 -3.7 to -3.3
Month 12 -3.6 -3.9 to -3.3
Month 36 -3.5 -3.8 to -3.2
Month 60 -3.5 -3.8 to -3.1
*Mean (SD) baseline value was 4.5 (3.2)

Table 7: Individual diary key symptom scores by visit (ITT diary population)

Visit (month) Number of patients Fever score Rash score Joint pain score* Vomiting score* Headache score*
Baseline 29 0.5 (0.8) 1.9 (1.1) 1.2 (1.1) 0.1 (0.2) 0.9 (1.0)
1 28 0.1 (0.1) 0.3 (0.5) 0.2 (0.3) 0.0 (0.0) 0.2 (0.3)
3 26 0.1 (0.2) 0.1 (0.2) 0.2 (0.4) 0.0 (0.1) 0.1 (0.2)
6 25 0.0 (0.1) 0.1 (0.1) 0.2 (0.4) 0.0 (0.1) 0.2 (0.3)
12 24 0.1 (0.1) 0.1 (0.2) 0.1 (0.2) 0.0 (0.1) 0.1 (0.2)
36 19 0.0 (0.2) 0.0 (0.2) 0.1 (0.3) 0.0 (0.0) 0.2 (0.6)
60 15 0.0 (0.0) 0.1 (0.3) 0.3 (0.7) 0.0 (0.0) 0.1 (0.3)
*mean (SD)

Kineret treatment also appeared to be associated with improvement of, or stability in, assessments of other NOMID disease manifestations, such as CNS, audiogram, and visual acuity data, up to Month 60.

REFERENCES

1. Cockcroft DW and Gault HM. Prediction of creatinine clearance from serum creatinine. Nephron 1976; 16:31-41.

2. Sharp JT, Young DY, Bluhm GB, et al. How many joints in the hands and wrists should be included in a score of radiologic abnormalities used to assess rheumatoid arthritis? Arthritis Rheum. 1985; 28:1326-1335.

Last reviewed on RxList: 1/16/2013
This monograph has been modified to include the generic and brand name in many instances.

PATIENT INFORMATION

No information provided. Please refer to the WARNINGS AND PRECAUTIONS section.

Last reviewed on RxList: 1/16/2013
This monograph has been modified to include the generic and brand name in many instances.

>

PATIENT INFORMATION

No information provided. Please refer to the WARNINGS AND PRECAUTIONS section.

Last reviewed on RxList: 1/16/2013
This monograph has been modified to include the generic and brand name in many instances.

Disclaimer

Kineret Consumer

IMPORTANT: HOW TO USE THIS INFORMATION: This is a summary and does NOT have all possible information about this product. This information does not assure that this product is safe, effective, or appropriate for you. This information is not individual medical advice and does not substitute for the advice of your health care professional. Always ask your health care professional for complete information about this product and your specific health needs.

ANAKINRA - INJECTION

(an-a-KIN-ra)

COMMON BRAND NAME(S): Kineret

USES: This medication is used alone or with other medications to treat rheumatoid arthritis. It helps to slow joint damage and reduces the joint pain/swelling caused by rheumatoid arthritis so that you can move better. Anakinra is a man-made form of a natural protein (interleukin-1 receptor antagonist) made by the body. It helps to block the effects of another protein (interleukin-1) which can cause joint pain/swelling/stiffness.

HOW TO USE: Read the Patient Information Leaflet if available from your pharmacist before you start using anakinra and each time you get a refill. If you have any questions, consult your doctor or pharmacist.

If you are giving the shots yourself, you will be trained by a health care professional on how to properly prepare and inject this product. If any of the information is unclear, consult your health care professional.

This medication is injected under the skin (subcutaneously), usually once a day or as directed by your doctor.

Dosage is based on your medical condition and response to treatment.

Do not shake this medication. Before using, check this product visually for particles or discoloration. If either is present, do not use the liquid. Let the medication warm to room temperature for 60 to 90 minutes before injecting it.

Before injecting each dose, clean the injection site with rubbing alcohol. It is important to change the location of the injection site daily to avoid problem areas under the skin. Do not inject this medication in an area that is tender, red, bruised, or hard or which has scars or stretch marks.

Use this medication regularly to get the most benefit from it. To help you remember, use it at the same time each day.

Do not reuse the syringe. Learn how to store and discard needles and medical supplies safely. Consult your pharmacist for more details.

Tell your doctor if your condition does not improve after 4 weeks or if it worsens.

Disclaimer

Kineret Consumer (continued)

SIDE EFFECTS: Redness, bruising, swelling, and pain at the injection site may occur. These skin reactions are usually mild and may last 2 to 4 weeks. If any of these effects persist or worsen, tell your doctor or pharmacist promptly.

Remember that your doctor has prescribed this medication because he or she has judged that the benefit to you is greater than the risk of side effects. Many people using this medication do not have serious side effects.

Anakinra has caused very serious infections (such as skin/bone/joint infections, pneumonia). Tell your doctor immediately if you develop signs of an infection, including: fever/chills, persistent sore throat, cough with mucus, spreading redness/swelling/tenderness of the skin, bone pain.

A very serious allergic reaction to this drug is rare. However, seek immediate medical attention if you notice any symptoms of a serious allergic reaction, including: rash, itching/swelling (especially of the face/tongue/throat), severe dizziness, trouble breathing.

This is not a complete list of possible side effects. If you notice other effects not listed above, contact your doctor or pharmacist.

In the US -

Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

In Canada - Call your doctor for medical advice about side effects. You may report side effects to Health Canada at 1-866-234-2345.

Read the Kineret (anakinra) Side Effects Center for a complete guide to possible side effects »

PRECAUTIONS: Before using anakinra, tell your doctor or pharmacist if you are allergic to it; or to proteins made from a certain bacteria (E. coli); or to latex; or if you have any other allergies. This product may contain inactive ingredients, which can cause allergic reactions or other problems. Talk to your pharmacist for more details.

Before using this medication, tell your doctor or pharmacist your medical history, especially of: recent/current infection, immune system problems (such as HIV disease), kidney disease, asthma.

Anakinra can make you more likely to get infections or may worsen any current infections. Therefore, wash your hands well to prevent the spread of infection. Avoid contact with people who have infections that may spread to others (such as chickenpox, measles, flu). Consult your doctor if you have been exposed to an infection or for more details.

Do not have immunizations/vaccinations without the consent of your doctor. Avoid contact with people who have recently received live vaccines (such as flu vaccine inhaled through the nose).

Older adults may be at greater risk for infections while using this drug.

During pregnancy, this medication should be used only when clearly needed. Discuss the risks and benefits with your doctor.

It is unknown if this medication passes into breast milk. Consult your doctor before breast-feeding.

Disclaimer

Kineret Consumer (continued)

DRUG INTERACTIONS: The effects of some drugs can change if you take other drugs or herbal products at the same time. This can increase your risk for serious side effects or may cause your medications not to work correctly. These drug interactions are possible, but do not always occur. Your doctor or pharmacist can often prevent or manage interactions by changing how you use your medications or by close monitoring.

To help your doctor and pharmacist give you the best care, be sure to tell your doctor and pharmacist about all the products you use (including prescription drugs, nonprescription drugs, and herbal products) before starting treatment with this product. While using this product, do not start, stop, or change the dosage of any other medicines you are using without your doctor's approval.

Some products that may interact with this drug include: abatacept, TNF blockers (such as adalimumab, certolizumab, etanercept, infliximab).

This document does not contain all possible interactions. Keep a list of all the products you use. Share this list with your doctor and pharmacist to lessen your risk for serious medication problems.

OVERDOSE: If overdose is suspected, contact a poison control center or emergency room immediately. US residents can call the US National Poison Hotline at 1-800-222-1222. Canada residents can call a provincial poison control center.

NOTES: Do not share this medication with others.

Laboratory and/or medical tests (such as absolute neutrophil count) should be performed periodically to monitor your progress or check for side effects. Consult your doctor for more details.

MISSED DOSE: If you miss a dose, use it as soon as you remember. If it is near the time of the next dose, skip the missed dose and resume your usual dosing schedule. Do not double the dose to catch up.

STORAGE: Store in the refrigerator between 36-46 degrees F (2-8 degrees C) away from light. Do not freeze. Keep all medicines away from children and pets.

Do not flush medications down the toilet or pour them into a drain unless instructed to do so. Properly discard this product when it is expired or no longer needed. Consult your pharmacist or local waste disposal company for more details about how to safely discard your product.

Information last revised May 2010. Copyright(c) 2010 First Databank, Inc.

Kineret Patient Information Including Side Effects

Brand Names: Kineret

Generic Name: anakinra (injectable) (Pronunciation: an na KIN rah)

What is anakinra (Kineret)?

Anakinra reduces the actions of chemicals in the body that are involved in inflammatory and immune responses.

Anakinra is used to treat the symptoms of moderate to severe rheumatoid arthritis in patients who have had an inadequate response to one or more antirheumatic drugs. Anakinra may be used in combination with other antirheumatic medications.

Anakinra may also be used for purposes other than those listed in this medication guide.

What are the possible side effects of anakinra (Kineret)?

If you experience an allergic reaction (difficulty breathing; closing of the throat; swelling of your lips, tongue, or face; or hives), stop using anakinra, and seek emergency medical attention.

In rare cases, people receiving anakinra have developed serious infections. Notify your doctor immediately if you develop a fever, flu-like symptoms, or any other sign of infection.

Other less serious side effects may be more likely to occur. Continue to use anakinra and notify your doctor if you experience

  • nausea or diarrhea;
  • a headache;
  • sinus irritation or infection; or
  • redness, bruising, pain, or swelling at the injection site.

Side effects other than those listed here may also occur. Talk to your doctor about any side effect that seems unusual or that is especially bothersome. You may report side effects to FDA at 1-800-FDA-1088.

Read the Kineret (anakinra) Side Effects Center for a complete guide to possible side effects »

What is the most important information I should know about anakinra (Kineret)?

In rare cases, people receiving anakinra have developed serious infections. Notify your doctor immediately if you develop a fever, flu-like symptoms, or any other sign of infection. Treatment with anakinra should not be started in patients with active infections or those taking other medicines that may suppress the immune system. The use of anakinra in combination with etanercept (Enbrel), infliximab (Remicade), adalimumab (Humira), or other medicines used to treat rheumatoid arthritis, may also increase the risk of a serious infection.

Side Effects Centers

Kineret Patient Information including How Should I Take

What should I discuss with my healthcare provider before using anakinra (Kineret)?

In rare cases, people receiving anakinra have developed serious infections. Notify your doctor immediately if you develop a fever, flu-like symptoms, or any other sign of infection. Treatment with anakinra should not be started in patients with active infections or those taking other medicines that may suppress the immune system. The use of anakinra in combination with etanercept (Enbrel), infliximab (Remicade), adalimumab (Humira), or other medicines used to treat rheumatoid arthritis, may also increase the risk of a serious infection.

Do not use anakinra without first talking to your doctor if you

  • are currently taking etanercept (Enbrel), infliximab (Remicade), or adalimumab (Humira) to treat rheumatoid arthritis;
  • have an active infection or a history of recurrent infection;
  • have recently been exposed to varicella (chickenpox) virus;
  • have a bone marrow disease;
  • have a suppressed immune system due to a medical condition or treatment with medication;
  • have recently received a live vaccine; or
  • have kidney disease.

You may not be able to use anakinra, or you may require a dosage adjustment or special monitoring during treatment.

Anakinra is in the FDA pregnancy category B. This means that it is not expected to harm an unborn baby. Do not use anakinra without first talking to your doctor if you are pregnant or could become pregnant during treatment.

It is not known whether anakinra passes into breast milk. Do not use anakinra without first talking to your doctor if you are breast-feeding a baby.

The safety and effectiveness of anakinra have not been established for pediatric patients.

How should I use anakinra (Kineret)?

Use anakinra exactly as directed by your doctor. If you do not understand these directions, ask your doctor, nurse, or pharmacist to explain them to you.

Anakinra is used as a subcutaneous (under the skin) injection only. Your doctor or nurse will give you detailed instructions on how and where to inject anakinra. Do not inject this medication if you are unsure how.

Anakinra is usually injected once a day. The dose should be injected at approximately the same time every day.

The medication may be allowed to reach room temperature by removing it from the refrigerator about 60 to 90 minutes before administration. This may reduce discomfort during or following the injection.

The medication can be injected into the outer thighs, stomach, back of the upper arms, or buttocks. Rotate the injection site daily to reduce the possibility of soreness or redness. The area of the body being injected does not need to change daily, however each injection site should be at least one inch from the previous day's injection site.

Do not inject anakinra if it is discolored, cloudy, or if it has particles in it. Do not shake the prefilled syringe and do not use anakinra beyond the expiration date shown on the carton. If the solution appears foamy, allow it to sit for a few minutes until it clears.

This medication does not contain a preservative. Therefore, throw away any medication remaining in the syringe after a dose. Do not save the medication for later use.

Never reuse a needle or syringe. Dispose of all needles and syringes in an appropriate, puncture-resistant disposal container.

Your doctor may want you to have blood tests or other medical evaluations during treatment with anakinra to monitor progress and side effects.

Anakinra should be used on a regular basis to get the most benefit.

Store anakinra in the refrigerator (36 to 46 degrees Fahrenheit/2 to 8 degrees Celsius) away from moisture, heat and light. Do not allow anakinra to freeze.

Side Effects Centers

Kineret Patient Information including If I Miss a Dose

What happens if I miss a dose (Kineret)?

Notify your healthcare provider if you miss a dose of this medication.

What happens if I overdose (Kineret)?

Serious or life-threatening side effects are unlikely to occur from an overdose of anakinra. Contact your doctor or seek medical attention if an overdose of anakinra is suspected.

What should I avoid while using anakinra (Kineret)?

Anakinra has been associated with an increased incidence of infection. Avoid contact with people who have colds, the flu, or other contagious illnesses [e.g., varicella (chickenpox) and others] and do not receive vaccines that contain live strains of a virus (e.g., live oral polio vaccine) during treatment with anakinra. In addition, avoid contact with individuals who have recently been vaccinated with a live vaccine. There is a chance that the virus can be passed on to you.

What other drugs will affect anakinra (Kineret)?

Do not receive "live" vaccines during treatment with anakinra without first talking to your doctor. Administration of a live vaccine may result in an inadequate immune response or infection.

Before using anakinra, talk to your doctor if you are taking

  • etanercept (Enbrel);
  • infliximab (Remicade);
  • adalimumab (Humira); or
  • a medicine that may decrease the effects of the immune system.

You may not be able to use anakinra, or you may require a dosage adjustment or special monitoring during treatment if you are taking any of the medicines listed above.

Drugs other than those listed here may also interact with anakinra. Talk to your doctor and pharmacist before taking any prescription or over-the-counter medicines, including herbal products.

Where can I get more information?

Your pharmacist has more information about anakinra written for health professionals that you may read.


Remember, keep this and all other medicines out of the reach of children, never share your medicines with others, and use this medication only for the indication prescribed.

Every effort has been made to ensure that the information provided by Cerner Multum, Inc. ('Multum') is accurate, up-to-date, and complete, but no guarantee is made to that effect. Drug information contained herein may be time sensitive. Multum information has been compiled for use by healthcare practitioners and consumers in the United States and therefore Multum does not warrant that uses outside of the United States are appropriate, unless specifically indicated otherwise. Multum's drug information does not endorse drugs, diagnose patients or recommend therapy. Multum's drug information is an informational resource designed to assist licensed healthcare practitioners in caring for their patients and/or to serve consumers viewing this service as a supplement to, and not a substitute for, the expertise, skill, knowledge and judgment of healthcare practitioners. The absence of a warning for a given drug or drug combination in no way should be construed to indicate that the drug or drug combination is safe, effective or appropriate for any given patient. Multum does not assume any responsibility for any aspect of healthcare administered with the aid of information Multum provides. The information contained herein is not intended to cover all possible uses, directions, precautions, warnings, drug interactions, allergic reactions, or adverse effects. If you have questions about the drugs you are taking, check with your doctor, nurse or pharmacist.

Copyright 1996-2012 Cerner Multum, Inc. Version: 2.06. Revision date: 12/15/2010.

Your use of the content provided in this service indicates that you have read,understood and agree to the End-User License Agreement,which can be accessed by clicking on this link.

Healthwise

Side Effects Centers

توزیع کنندگان این دارو
شرکت های تولید کننده یا وارد کننده دارو

دارونـــما
نوآوری برای سلامت

طراحی و اجرا M.Ramezani
ارتباط با ما Info@darunama.com