"Nov. 6, 2012 -- The FDA has approved Pfizer's Xeljanz (tofacitinib), a first-of-its-kind treatment for rheumatoid arthritis.
Xeljanz is approved for use by patients not helped by methotrexate, the usual first treatment for RA. It's a "...
Kineret Side Effects Center
Medical Editor: John P. Cunha, DO, FACOEP
Kineret (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. Kineret may be used in combination with other antirheumatic medications. It is a man-made form of a natural protein (interleukin-1 receptor antagonist) made by the body. Common side effects include redness, bruising, swelling, and pain at the injection site. These skin reactions are usually mild and may last 2 to 4 weeks.The recommended dose of Kineret to treat rheumatoid arthritis is 100 mg/day administered daily by subcutaneous injection. Kineret may interact with "live" vaccines, etanercept, infliximab, adalimumab, or medicine that may decrease the effects of the immune system. Tell your doctor all medications you use. During pregnancy, Kineret should be used only when prescribed. It is unknown if this medication passes into breast milk. Consult your doctor before breast-feeding. Our Kineret (anakinra) Side Effects Drug Center provides a comprehensive view of available drug information on the potential side effects when taking this medication.
This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.
What is Patient Information in Detail?
Easy-to-read and understand detailed drug information and pill images for the patient or caregiver from Cerner Multum.
Kineret in Detail - Patient Information: Side Effects
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 entire detailed patient monograph for Kineret (Anakinra) »
What is Patient Information Overview?
A concise overview of the drug for the patient or caregiver from First DataBank.
Kineret Overview - Patient Information: Side Effects
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 entire patient information overview for Kineret (Anakinra)»
What is Prescribing information?
The FDA package insert formatted in easy-to-find categories for health professionals and clinicians.
Kineret FDA Prescribing Information: 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.
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.
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.
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.
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.
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)
(n = 733)
|Kineret 100 mg/day
(n = 1565)
|Injection Site Reaction||29%||71%|
|Worsening of RA||29%||19%|
|Upper Respiratory Tract Infections||17%||14%|
|Flu Like Symptoms||6%||6%|
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.
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.
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.
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|
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.
3. National Cancer Institute. Surveillance, Epidemiology, and End Results Database (SEER) Program. SEER Incidence Crude Rates, 11 Registries, 1992-1999.
Read the entire FDA prescribing information for Kineret (Anakinra) »
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