Drug Detail:Kevzara (Sarilumab [ sar-il-ue-mab ])
Drug Class: Antirheumatics Interleukin inhibitors
Highlights of Prescribing Information
KEVZARA (sarilumab) injection, for subcutaneous use
Initial U.S. Approval: 2017
WARNING: RISK OF SERIOUS INFECTIONS
See full prescribing information for complete boxed warning.
- Serious infections leading to hospitalization or death including bacterial, viral, invasive fungal, and other opportunistic infections have occurred in patients receiving KEVZARA. (5.1)
- If a serious infection develops, interrupt KEVZARA until the infection is controlled. (5.1)
- Cases of tuberculosis (TB) have been reported. Prior to starting KEVZARA, test for latent TB; if positive, start treatment for TB. (5.1)
- Closely monitor patients for signs and symptoms of infection during treatment with KEVZARA. (5.1)
Recent Major Changes
| Indications and Usage (1.2) | 02/2023 |
| Dosage and Administration (2.3, 2.5) | 02/2023 |
Indications and Usage for Kevzara
KEVZARA® is an interleukin-6 (IL-6) receptor antagonist indicated for treatment of:
- adult patients with moderately to severely active rheumatoid arthritis (RA) who have had an inadequate response or intolerance to one or more disease-modifying antirheumatic drugs (DMARDs). (1.1)
- adult patients with polymyalgia rheumatica (PMR) who have had an inadequate response to corticosteroids or who cannot tolerate corticosteroid taper. (1.2)
Kevzara Dosage and Administration
General Considerations for Administration
- KEVZARA initiation is not recommended in patients with ANC less than 2,000/mm3, platelets less than 150,000/mm3 or liver transaminases above 1.5 times ULN. See Full Prescribing Information (FPI) for complete information. (2.1)
Recommended Dosage in RA
- The recommended dosage is 200 mg subcutaneously, once every 2 weeks. (2.2)
- For RA, KEVZARA may be used as monotherapy or in combination with methotrexate (MTX) or other conventional DMARDs. (2.2)
Recommended Dosage in PMR
- The recommended dosage is 200 mg subcutaneously, once every two weeks in combination with a tapering course of corticosteroids. (2.3)
- For PMR, KEVZARA can be used as monotherapy following discontinuation of corticosteroids. (2.3)
Dosage Modifications for Cytopenias, Abnormal Liver Enzymes, Infections
- See FPI for complete information. (2.5)
Dosage Forms and Strengths
- Injection: 150 mg/1.14 mL or 200 mg/1.14 mL solution in a single-dose pre-filled syringe (3)
- Injection: 150 mg/1.14 mL or 200 mg/1.14 mL solution in a single-dose pre-filled pen (3)
Contraindications
KEVZARA is contraindicated in patients with known hypersensitivity to sarilumab or any of the inactive ingredients. (4)
Warnings and Precautions
- Serious Infections: Avoid KEVZARA use during an active infection. (5.1)
- Neutropenia, Thrombocytopenia, Elevated Liver Enzymes, Lipid Abnormalities: Monitor laboratory parameters. (5.2)
- Gastrointestinal (GI) Perforation: Risk may be increased with concurrent diverticulitis or concomitant use of NSAIDs or corticosteroids. Promptly evaluate acute abdominal signs or symptoms. (5.3)
- Hypersensitivity reactions. (5.5)
- Live vaccines: Avoid use with KEVZARA. (5.7, 7.3)
Adverse Reactions/Side Effects
Most common adverse reactions are:
- Rheumatoid Arthritis (incidence ≥3 %): neutropenia, increased ALT, injection site erythema, upper respiratory infections and urinary tract infections. (6.1)
- Polymyalgia Rheumatica (incidence ≥ 5%): neutropenia, leukopenia and injection site pruritus. (6.1)
To report SUSPECTED ADVERSE REACTIONS, contact sanofi-aventis at 1-800-633-1610 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch
Use In Specific Populations
- Lactation: Discontinue drug or nursing taking into consideration importance of drug to mother. (8.2)
See 17 for PATIENT COUNSELING INFORMATION and Medication Guide.
Revised: 2/2023
Full Prescribing Information
WARNING: RISK OF SERIOUS INFECTIONS
Patients treated with KEVZARA are at increased risk for developing serious infections that may lead to hospitalization or death [see Warnings and Precautions (5.1), Adverse Reactions (6.1)]. Opportunistic infections have also been reported in patients receiving KEVZARA. Most patients who developed infections were taking concomitant immunosuppressants such as methotrexate or corticosteroids.
Avoid use of KEVZARA in patients with an active infection.
Reported infections include:
- Active tuberculosis, which may present with pulmonary or extrapulmonary disease. Patients should be tested for latent tuberculosis before KEVZARA use and during therapy. Treatment for latent infection should be initiated prior to KEVZARA use.
- Invasive fungal infections, such as candidiasis, and pneumocystis. Patients with invasive fungal infections may present with disseminated, rather than localized, disease.
- Bacterial, viral and other infections due to opportunistic pathogens.
Closely monitor patients for signs and symptoms of infection during treatment with KEVZARA. If a serious infection develops, interrupt KEVZARA until the infection is controlled.
Consider the risks and benefits of treatment with KEVZARA prior to initiating therapy in patients with chronic or recurrent infection.
1. Indications and Usage for Kevzara
2. Kevzara Dosage and Administration
2.2 Recommended Dosage for Rheumatoid Arthritis
The recommended dosage of KEVZARA is 200 mg once every two weeks given as a subcutaneous injection (see Dosage and Administration 2.1).
KEVZARA may be used as monotherapy or in combination with methotrexate (MTX) or other conventional DMARDs.
Modify the dosage as recommended in Table 1 if the patient develops neutropenia, thrombocytopenia, or liver enzyme abnormalities [see Dosage and Administration (2.5), Warnings and Precautions (5.2) and Adverse Reactions (6.1)].
2.3 Recommended Dosage for Polymyalgia Rheumatica
The recommended dosage of KEVZARA is 200 mg once every two weeks given as a subcutaneous injection, in combination with a tapering course of systemic corticosteroids [see Dosage and Administration (2.1)]. KEVZARA can be used as monotherapy following discontinuation of corticosteroids.
Discontinue KEVZARA if the patient develops neutropenia (using ANC results obtained at the end of the dosing interval), thrombocytopenia, or liver enzyme abnormalities [see Dosage and Administration (2.5), Warnings and Precautions (5.2) and Adverse Reactions (6.1)].
2.4 Preparation and Administration Instructions
- KEVZARA is intended for use under the guidance of a healthcare professional. A patient may self-inject KEVZARA or the patient's caregiver may administer KEVZARA. Provide proper training to patients and/or caregivers on the preparation and administration of KEVZARA prior to use according to the Instructions for Use (IFU).
- Allow the pre-filled syringe to sit at room temperature for 30 minutes prior to subcutaneous injection. Do not warm KEVZARA in any other way.
- If using a pre-filled pen, allow the pre-filled pen to sit at room temperature for 60 minutes prior to subcutaneous injection. Do not warm KEVZARA in any other way.
- Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration. KEVZARA solution should be clear and colorless to pale yellow. Do not use if the solution is cloudy, discolored or contains particles, or if any part of the pre-filled syringe or pre-filled pen appears to be damaged.
- Instruct patients to inject the full amount in the syringe or pen (1.14 mL), which provides 200 mg or 150 mg of KEVZARA, according to the directions provided in the IFU.
- Rotate injection sites with each injection. Do not inject into skin that is tender, damaged, or has bruises or scars.
2.5 Dosage Modifications for Cytopenias, Abnormal Liver Enzymes, or Infections
Dosage Modifications for Patients with Rheumatoid Arthritis
- Laboratory Abnormalities: Modify dosage in case of neutropenia, thrombocytopenia, or liver enzyme elevations as shown in Table 1 [see Warnings and Precautions (5.2) and Clinical Pharmacology (12.2)]. For treatment initiation criteria, refer to the dosage recommendations for RA [see Dosage and Administration (2.1, 2.2)].
| Low Absolute Neutrophil Count (ANC) | |
| Lab Value (cells/mm3) | Recommendation |
| ANC greater than 1,000 | Maintain current dosage of KEVZARA. |
| ANC 500 to 1,000 | Hold treatment with KEVZARA until ANC greater than 1,000. KEVZARA can then be resumed at 150 mg every two weeks and increased to 200 mg every two weeks as clinically appropriate. |
| ANC less than 500 | Discontinue KEVZARA. |
| Low Platelet Count | |
| Lab Value (cells/mm3) | Recommendation |
| 50,000 to 100,000 | Hold treatment with KEVZARA until platelets greater than 100,000. KEVZARA can then be resumed at 150 mg every two weeks and increased to 200 mg every two weeks as clinically appropriate. |
| Less than 50,000 | If confirmed by repeat testing, discontinue KEVZARA. |
| Liver Enzyme Abnormalities | |
| Lab Value | Recommendation |
| ALT or AST greater than ULN to 3 times ULN | Consider dosage modification of concomitant DMARDs as clinically appropriate. |
| ALT or AST greater than 3 times ULN to 5 times ULN | Hold treatment with KEVZARA until ALT or AST less than 3 times ULN. KEVZARA can then be resumed at 150 mg every two weeks and increased to 200 mg every two weeks as clinically appropriate. |
| ALT or AST greater than 5 times ULN | Discontinue KEVZARA. |
- Infections: If a patient with RA develops a serious infection or an opportunistic infection, hold treatment with KEVZARA until the infection is controlled [see Warnings and Precautions (5.1)].
3. Dosage Forms and Strengths
Injection: 150 mg/1.14 mL or 200 mg/1.14 mL colorless to pale-yellow solution in a single-dose pre-filled syringe.
Injection: 150 mg/1.14 mL or 200 mg/1.14 mL colorless to pale-yellow solution in a single-dose pre-filled pen.
4. Contraindications
KEVZARA is contraindicated in patients with known hypersensitivity to sarilumab or any of the inactive ingredients [see Warnings and Precautions (5.5) and Adverse Reactions (6.1)].
5. Warnings and Precautions
5.1 Serious Infections
Serious and sometimes fatal infections due to bacterial, mycobacterial, invasive fungal, viral, or other opportunistic pathogens have been reported in patients receiving immunosuppressive agents including KEVZARA. The most frequently observed serious infections with KEVZARA included pneumonia and cellulitis [see Adverse Reactions (6.1)]. Among opportunistic infections, tuberculosis, candidiasis, and pneumocystis were reported with KEVZARA. Some patients presented with disseminated rather than localized disease and were often taking concomitant immunosuppressants such as methotrexate or corticosteroids. While not reported in KEVZARA clinical studies, other serious infections (e.g., histoplasmosis, cryptococcus, aspergillosis) have been reported in patients receiving other immunosuppressive agents for the treatment of RA.
Avoid use of KEVZARA in patients with an active infection, including localized infections. Consider the risks and benefits of treatment prior to initiating KEVZARA in patients who have:
- chronic or recurrent infection;
- a history of serious or opportunistic infections;
- underlying conditions that may predispose them to infection;
- been exposed to tuberculosis; or
- lived in or traveled to areas of endemic tuberculosis or endemic mycoses.
Closely monitor patients for the development of signs and symptoms of infection during treatment with KEVZARA, as signs and symptoms of acute inflammation may be lessened due to suppression of the acute phase reactants [see Dosage and Administration (2.5), Adverse Reactions (6.1)].
Hold treatment with KEVZARA if a patient develops a serious infection or an opportunistic infection.
Perform prompt and complete diagnostic testing appropriate for an immunocompromised patient who develops a new infection during treatment with KEVZARA; initiate appropriate antimicrobial therapy, and closely monitor the patient.
5.3 Gastrointestinal Perforation
Gastrointestinal perforations have been reported in clinical studies, primarily as complications of diverticulitis. GI perforation risk may be increased with concurrent diverticulitis or concomitant use of NSAIDs or corticosteroids. Promptly evaluate patients presenting with new onset abdominal symptoms [see Adverse Reactions (6.1)].
5.4 Immunosuppression
Treatment with immunosuppressants may result in an increased risk of malignancies. The impact of treatment with KEVZARA on the development of malignancies is not known but malignancies were reported in clinical studies [see Adverse Reactions (6.1)].
5.5 Hypersensitivity Reactions
Hypersensitivity reactions have been reported in association with KEVZARA [see Adverse Reactions (6.1)]. Hypersensitivity reactions that required treatment discontinuation were reported in 0.3% of patients in controlled RA trials. Injection site rash, rash, and urticaria were the most frequent hypersensitivity reactions. Advise patients to seek immediate medical attention if they experience any symptoms of a hypersensitivity reaction. If anaphylaxis or other hypersensitivity reaction occurs, stop administration of KEVZARA immediately. Do not administer KEVZARA to patients with known hypersensitivity to sarilumab [see Contraindications (4) and Adverse Reactions (6.1)].
5.6 Active Hepatic Disease and Hepatic Impairment
Treatment with KEVZARA is not recommended in patients with active hepatic disease or hepatic impairment, as treatment with KEVZARA was associated with transaminase elevations [see Adverse Reactions (6.1), Use in Specific Populations (8.6)].
5.7 Live Vaccines
Avoid concurrent use of live vaccines during treatment with KEVZARA due to potentially increased risk of infections; clinical safety of live vaccines during KEVZARA treatment has not been established. No data are available on the secondary transmission of infection from persons receiving live vaccines to patients receiving KEVZARA. The interval between live vaccinations and initiation of KEVZARA therapy should be in accordance with current vaccination guidelines regarding immunosuppressive agents [see Drug Interactions (7.3)].
6. Adverse Reactions/Side Effects
The following serious adverse reactions are described elsewhere in labeling:
- Serious infections [see Warnings and Precautions (5.1)]
- Neutropenia, thrombocytopenia, elevated liver enzymes, lipid abnormalities [see Warnings and Precautions (5.2)]
- Gastrointestinal perforation [see Warnings and Precautions (5.3)]
- Immunosuppression [see Warnings and Precautions (5.4)]
- Hypersensitivity reactions [see Warnings and Precautions (5.5)]
6.1 Clinical Trials Experience
Because clinical studies are conducted under widely varying conditions, adverse reaction rates observed in the clinical studies of a drug cannot be directly compared to rates in the clinical studies of another drug and may not reflect the rates observed in practice.
Laboratory Abnormalities
Elevated liver enzymes
Liver enzyme elevations in the pre-rescue placebo-controlled population (KEVZARA + DMARD or placebo + DMARD) are summarized in Table 2. In patients experiencing liver enzyme elevation, modification of treatment regimen, such as interruption of KEVZARA or reduction in dose, resulted in decrease or normalization of liver enzymes [see Dosage and Administration (2.4)]. These elevations were not associated with clinically relevant increases in direct bilirubin, nor were they associated with clinical evidence of hepatitis or hepatic impairment [see Warnings and Precautions (5.2)].
| Placebo + DMARD N=579 | KEVZARA 150 mg + DMARD N=579 | KEVZARA 200 mg + DMARD N=582 |
|
|---|---|---|---|
| ULN = Upper Limit of Normal | |||
|
|||
| AST | |||
| Greater than ULN to 3 times ULN or less | 15% | 27% | 30% |
| Greater than 3 times ULN to 5 times ULN | 0% | 1% | 1% |
| Greater than 5 times ULN | 0% | 0.7% | 0.2% |
| ALT | |||
| Greater than ULN to 3 times ULN or less | 25% | 38% | 43% |
| Greater than 3 times ULN to 5 times ULN | 1% | 4% | 3% |
| Greater than 5 times ULN | 0% | 1% | 0.7% |
Other Adverse Reactions
Adverse reactions occurring in 2% or more of patients on KEVZARA + DMARD and greater than those observed in patients on placebo + DMARD are summarized in Table 3.
| Preferred Term | Placebo + DMARD (N=579) | KEVZARA 150 mg + DMARD (N=579) | KEVZARA 200 mg + DMARD (N=582) |
|---|---|---|---|
|
|||
| Neutropenia | 0.2% | 7% | 10% |
| Alanine aminotransferase increased | 2% | 5% | 5% |
| Injection site erythema | 0.9% | 5% | 4% |
| Injection site pruritus | 0.2% | 2% | 2% |
| Upper respiratory tract infection | 2% | 4% | 3% |
| Urinary tract infection | 2% | 3% | 3% |
| Hypertriglyceridemia | 0.5% | 3% | 1% |
| Leukopenia | 0% | 0.9% | 2% |
Medically relevant adverse reactions occurring at an incidence less than 2% in patients with rheumatoid arthritis treated with KEVZARA in controlled studies was oral herpes.
7. Drug Interactions
7.1 Use with Other Drugs
Population pharmacokinetic analyses did not detect any effect of methotrexate (MTX) on sarilumab clearance. KEVZARA has not been investigated in combination with JAK inhibitors or biological DMARDs such as TNF antagonists [see Dosage and Administration (2.2)].
7.2 Interactions with CYP450 Substrates
Various in vitro and limited in vivo human studies have shown that cytokines and cytokine modulators can influence the expression and activity of specific cytochrome P450 (CYP) enzymes and therefore have the potential to alter the pharmacokinetics of concomitantly administered drugs that are substrates of these enzymes. Elevated interleukin-6 (IL-6) concentration may down-regulate CYP activity such as in patients with RA and hence increase drug levels compared to subjects without RA. Blockade of IL-6 signaling by IL-6Rα antagonists such as KEVZARA might reverse the inhibitory effect of IL-6 and restore CYP activity, leading to altered drug concentrations.
The modulation of IL-6 effect on CYP enzymes by KEVZARA may be clinically relevant for CYP substrates with a narrow therapeutic index, where the dose is individually adjusted. Upon initiation or discontinuation of KEVZARA, in patients being treated with CYP substrate medicinal products, perform therapeutic monitoring of effect (e.g., warfarin) or drug concentration (e.g., theophylline) and adjust the individual dose of the medicinal product as needed.
Exercise caution when co-administering KEVZARA with CYP3A4 substrate drugs where decrease in effectiveness is undesirable, e.g., oral contraceptives, lovastatin, atorvastatin, etc. The effect of KEVZARA on CYP450 enzyme activity may persist for several weeks after stopping therapy [see Clinical Pharmacology (12.3)].
8. Use In Specific Populations
8.5 Geriatric Use
Of the total number of patients with RA exposed to KEVZARA in clinical studies [see Clinical Studies (14.1)], 450 patients (15%) were 65 years of age and over, while 48 patients (1.6%) were 75 years and over. In clinical studies, no overall differences in safety and efficacy were observed between older and younger patients. The frequency of serious infections among KEVZARA and placebo-treated patients 65 years of age and older was higher than those under the age of 65.
Of the total number of patients with PMR exposed to KEVZARA in the clinical study (Study 3) [see Clinical Studies (14.2)], 16 patients (27.1%) were under 65 years of age, 33 patients (55.9%) were 65 to 75 years of age, and 10 patients (17.0%) were 75 years and over. The median age in the PMR study was 69.0 years and all patients were on baseline corticosteroid. There were no differences in the incidence of serious infections between the KEVZARA group and placebo group. In Study 3, no overall differences in safety were observed between older and younger patients.
As there is a higher incidence of infections in the elderly population in general, caution should be used when treating the elderly.
11. Kevzara Description
Sarilumab is a human recombinant monoclonal antibody of the IgG1 subclass that binds to the IL-6 receptor and has an approximate molecular weight of 150 kDa. Sarilumab is produced by recombinant DNA technology in Chinese Hamster Ovary cell suspension culture.
KEVZARA (sarilumab) injection for subcutaneous administration is supplied as a sterile, colorless to pale yellow, preservative-free solution of approximately pH 6.0. KEVZARA is supplied in a single-dose pre-filled syringe or pre-filled pen. Each syringe or pen delivers 1.14 mL of solution containing 150 mg or 200 mg of sarilumab, arginine (8.94 mg), histidine (3.71 mg), polysorbate 20 (2.28 mg), sucrose (57 mg) and Water for Injection, USP.
12. Kevzara - Clinical Pharmacology
12.1 Mechanism of Action
Sarilumab binds to both soluble and membrane-bound IL-6 receptors (sIL-6R and mIL-6R), and has been shown to inhibit IL-6-mediated signaling through these receptors. IL-6 is a pleiotropic pro-inflammatory cytokine produced by a variety of cell types including T- and B-cells, lymphocytes, monocytes, and fibroblasts. IL-6 has been shown to be involved in diverse physiological processes such as T-cell activation, induction of immunoglobulin secretion, initiation of hepatic acute phase protein synthesis, and stimulation of hematopoietic precursor cell proliferation and differentiation. IL-6 is also produced by synovial and endothelial cells leading to local production of IL-6 in joints affected by inflammatory processes such as rheumatoid arthritis.
12.2 Pharmacodynamics
Following single-dose subcutaneous administration of sarilumab 200-mg and 150-mg in patients with RA, rapid reduction of CRP levels was observed. Levels were reduced to normal within 2 weeks after treatment initiation. Following single-dose sarilumab administration, in patients with RA, absolute neutrophil counts decreased to the nadir between 3 to 4 days and thereafter recovered towards baseline [see Warnings and Precautions (5.2)]. Treatment with sarilumab resulted in decreases in fibrinogen and serum amyloid A, and increases in hemoglobin and serum albumin.
12.3 Pharmacokinetics
Rheumatoid Arthritis
12.6 Immunogenicity
As with all therapeutic proteins, there is potential for immunogenicity. The detection of antibody formation is highly dependent on the sensitivity and specificity of the assay. Additionally, the observed incidence of antibody (including neutralizing antibody) positivity in an assay may be influenced by several factors, including assay methodology, sample handling, timing of sample collection, concomitant medications, and underlying disease. For these reasons, comparison of the incidence of antibodies to sarilumab in the studies described below with the incidence of antibodies in other studies or to other products may be misleading.
In the RA pre-rescue population, 4.0% of patients treated with KEVZARA 200 mg + DMARD, 5.7% of patients treated with KEVZARA 150 mg + DMARD and 1.9% of patients treated with placebo + DMARD, exhibited an anti-drug antibody (ADA) response. Neutralizing antibodies (NAb) were detected in 1.0% of patients on KEVZARA 200 mg + DMARD, 1.6% of patients on KEVZARA 150 mg + DMARD, and 0.2% of patients on placebo + DMARD.
In RA patients treated with KEVZARA monotherapy, 9.2% of patients exhibited an ADA response with 6.9% of patients also exhibiting NAbs. Prior to administration of KEVZARA, 2.3% of patients exhibited an ADA response.
No correlation was observed between ADA development and either loss of efficacy or adverse reactions in RA patients.
In the PMR population, 1 patient (1.8%) in the KEVZARA 200 mg + 14-week corticosteroid taper group exhibited an ADA response. None of the patients in the placebo +52-week corticosteroid taper group exhibited an ADA response. Neutralizing antibodies were detected in the PMR patient with ADA response on KEVZARA 200 mg; the patient did not demonstrate a clinical response. Because of the low occurrence of anti-drug antibodies, the effect of these antibodies on the safety, and/or effectiveness of sarilumab is unknown.
13. Nonclinical Toxicology
13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility
No long-term animal studies have been performed to establish the carcinogenicity potential of sarilumab. Literature indicates that the IL-6 pathway can mediate anti-tumor responses by promoting increased immune cell surveillance of the tumor microenvironment. However, available published evidence also supports that IL-6 signaling through the IL-6 receptor may be involved in pathways that lead to tumorigenesis. The malignancy risk in humans from an antibody that disrupts signaling through the IL-6 receptor, such as sarilumab, is presently unknown.
Fertility and reproductive performance were unaffected in male and female mice treated with an analogous antibody, which binds to murine IL-6Rα to inhibit IL-6 mediated signaling, at subcutaneous doses of 10, 25, and 100 mg/kg twice per week.
14. Clinical Studies
14.1 Rheumatoid Arthritis
Clinical Response
The percentages of KEVZARA every two weeks + MTX/DMARD-treated patients achieving ACR20, ACR50 and ACR70 responses in Studies 1 and 2 are shown Table 4. In both studies, patients treated with either 200 mg or 150 mg of KEVZARA every two weeks + MTX/DMARD had higher ACR20, ACR50, and ACR70 response rates versus placebo + MTX/DMARD-treated patients at Week 24.
In Studies 1 and 2, a greater proportion of patients treated with KEVZARA 200 mg or 150 mg every two weeks plus MTX/DMARD achieved a low level of disease activity as measured by a Disease Activity Score 28-C-Reactive Protein (DAS28-CRP) <2.6 compared with placebo + MTX/DMARD at the end of the studies (Table 4). In Study 1, the proportion of patients achieving DAS28-CRP <2.6 who had at least 3 or more active joints at the end of Week 24 was 33.1%, 37.8% and 20%, in the KEVZARA 200 mg + MTX/DMARD arm, KEVZARA 150 mg + MTX/DMARD arm, and placebo arm respectively.
| Percentage of Patients | ||||||
|---|---|---|---|---|---|---|
| Study 1 | Study 2 | |||||
| Placebo + MTX N=398 | KEVZARA 150 mg + MTX N=400 | KEVZARA 200 mg + MTX N=399 | Placebo + DMARD(s)†
N=181 | KEVZARA 150 mg + DMARD(s)†
N=181 | KEVZARA 200 mg + DMARD(s)†
N=184 |
|
|
||||||
| ACR20 | ||||||
| Week 12 | 34.7% | 54.0% | 64.9% | 37.6% | 54.1% | 62.5% |
| Difference from placebo (95% CI)‡ | 19.4% (12.6%, 26.1%) | 30.2% (23.6%, 36.8%) | 16.6% (6.7%, 26.5%) | 25.3% (15.7%, 34.8%) |
||
| Week 24§ | 33.4% | 58.0% | 66.4% | 33.7% | 55.8% | 60.9% |
| Difference from placebo (95% CI)‡ | 24.6% (18.0%, 31.3%) | 33.0% (26.5%, 39.5%) | 22.1% (12.6%, 31.6%) | 27.4% (17.7%, 37.0%) |
||
| Week 52 | 31.7% | 53.5% | 58.6% | |||
| Difference from placebo (95% CI)‡ | 21.9% (15.2%, 28.5%) | 27.0% (20.5%, 33.6%) | NA¶ | NA¶ | NA¶ | |
| ACR50 | ||||||
| Week 12 | 12.3% | 26.5% | 36.3% | 13.3% | 30.4% | 33.2% |
| Difference from placebo (95% CI)‡ | 14.2% (8.9%, 19.6%) | 24.1% (18.4%, 29.8%) | 17.1% (9.2%, 25.1%) | 20.1% (12.0%, 28.3%) |
||
| Week 24 | 16.6% | 37.0% | 45.6% | 18.2% | 37.0% | 40.8% |
| Difference from placebo (95% CI)‡ | 20.4% (14.5%, 26.3%) | 29.1% (23.0%, 35.1%) | 18.8% (10.2%, 27.4%) | 22.8% (14.0%, 31.6%) |
||
| Week 52 | 18.1% | 40.0% | 42.9% | |||
| Difference from placebo (95% CI)‡ | 21.9% (15.8%, 28.0%) | 24.8% (18.7%, 30.9%) | NA¶ | NA¶ | NA¶ | |
| ACR70 | ||||||
| Week 12 | 4.0% | 11.0% | 17.5% | 2.2% | 13.8% | 14.7% |
| Difference from placebo (95% CI)‡ | 7.0% (3.4%, 10.6%) | 13.5% (9.4%, 17.7%) | 11.6% (6.2%, 17.0%) | 12.5% (7.1%, 17.9%) |
||
| Week 24 | 7.3% | 19.8% | 24.8% | 7.2% | 19.9% | 16.3% |
| Difference from placebo (95% CI)‡ | 12.5% (7.8%, 17.1%) | 17.5% (12.6%, 22.5%) | 12.7% (6.1%, 19.3%) | 9.2% (2.8%, 15.7%) |
||
| Week 52 | 9.0% | 24.8% | 26.8% | |||
| Difference from placebo (95% CI)‡ | 15.7% (10.6%, 20.8%) | 17.8% (12.6%, 23.0%) | NA¶ | NA¶ | NA¶ | |
| Major clinical response# | ||||||
| Responders | 3.0% | 12.8% | 14.8% | NA¶ | NA¶ | NA¶ |
| Difference from placebo (95% CI)‡ | 9.7% (6.1%, 13.4%) | 11.8% (7.9%, 15.6%) | ||||
| DAS28-CRP < 2.6Þ | ||||||
| Week 12 | ||||||
| Percentage of patients | 4.8% | 18.0% | 23.1% | 3.9% | 17.1% | 17.9% |
| Difference from placebo (95% CI)‡ | 13.3% (9.0%, 17.5%) | 18.3% (13.7%, 23.0%) | 13.3% (7.3%, 19.3%) | 14.1% (8.0%, 20.3%) |
||
| Week 24 | ||||||
| Percentage of patients | 10.1% | 27.8% | 34.1% | 7.2% | 24.9% | 28.8% |
| Difference from placebo (95% CI)‡ | 17.7% (12.5%, 23.0%) | 24.0% (18.5%, 29.5%) | 17.7% (10.5%, 24.9%) | 21.7% (14.3%, 29.1%) |
||
The percent ACR20 response by visit in Study 1 is shown in Figure 1. A similar response curve was observed in Study 2.
| Figure 1: Percent of ACR20 Response by Visit for Study 1 (Adults with Moderately to Severely Active RA) |
|---|
 |
The results of the components of the ACR response criteria at Week 12 for Studies 1 and 2 are shown in Table 5.
| Study 1 | Study 2 | |||||
|---|---|---|---|---|---|---|
| Component means (range/units) | Placebo + MTX (N=398) | KEVZARA 150 mg + MTX (N=400) | KEVZARA 200 mg + MTX (N=399) | Placebo + DMARD(s) (N=181) | KEVZARA 150 mg + DMARD(s) (N=181) | KEVZARA 200 mg + DMARD(s) (N=184) |
|
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| Tender Joints (0–68) | ||||||
| Baseline | 26.80 | 27.21 | 26.50 | 29.42 | 27.66 | 29.55 |
| Week 12 | 16.25 | 12.88 | 11.78 | 19.18 | 13.38 | 13.10 |
| Change from baseline | -10.51 | -14.42 | -14.94 | -9.79 | -14.11 | -15.92 |
| Swollen Joints (0–66) | ||||||
| Baseline | 16.68 | 16.60 | 16.77 | 20.21 | 19.60 | 19.97 |
| Week 12 | 9.66 | 7.50 | 6.79 | 12.50 | 8.82 | 8.28 |
| Change from baseline | -7.02 | -9.03 | -10.12 | -7.25 | -10.77 | -10.89 |
| Pain VAS* (0–100 mm) | ||||||
| Baseline | 63.71 | 65.48 | 66.71 | 71.57 | 71.02 | 74.86 |
| Week 12 | 49.25 | 41.47 | 36.93 | 54.77 | 43.45 | 41.66 |
| Change from baseline | -14.45 | -23.73 | -29.77 | -16.12 | -27.95 | -32.77 |
| Physician global VAS* (0–100 mm) | ||||||
| Baseline | 62.86 | 63.43 | 63.59 | 68.39 | 68.10 | 67.76 |
| Week 12 | 39.25 | 31.32 | 28.47 | 43.73 | 33.65 | 30.18 |
| Change from baseline | -23.63 | -31.85 | -34.84 | -24.60 | -34.92 | -36.92 |
| Patient global VAS* (0–100 mm) | ||||||
| Baseline | 63.70 | 64.43 | 66.49 | 68.77 | 67.71 | 70.89 |
| Week 12 | 49.37 | 41.52 | 38.05 | 53.67 | 41.99 | 41.74 |
| Change from baseline | -13.92 | -22.88 | -28.39 | -15.05 | -26.05 | -28.83 |
| HAQ-DI (0–3) | ||||||
| Baseline | 1.61 | 1.63 | 1.69 | 1.80 | 1.72 | 1.82 |
| Week 12 | 1.34 | 1.15 | 1.13 | 1.49 | 1.23 | 1.33 |
| Change from baseline | -0.27 | -0.47 | -0.57 | -0.29 | -0.50 | -0.49 |
| CRP (mg/L) | ||||||
| Baseline | 20.46 | 22.57 | 22.23 | 26.02 | 23.60 | 30.77 |
| Week 12 | 19.61 | 9.24 | 3.30 | 21.72 | 9.21 | 4.58 |
| Change from baseline | -0.58 | -13.59 | -18.31 | -3.39 | -14.24 | -25.91 |
Radiographic Response
In Study 1, structural joint damage was assessed radiographically and expressed as the van der Heijde-modified Total Sharp Score (mTSS) and its components, the erosion score and joint space narrowing score. Radiographs of hands and feet were obtained at baseline, 24 weeks, and 52 weeks and scored independently by at least two well-trained readers who were blinded to treatment group and visit number.
Both doses of KEVZARA + MTX were superior to placebo + MTX in the change from baseline in mTSS over 52 weeks (see Table 6). Less progression of both erosion and joint space narrowing scores over 52 weeks was reported in the KEVZARA + MTX treatment groups compared to the placebo + MTX group.
Treatment with KEVZARA + MTX was associated with significantly less radiographic progression of structural damage as compared with placebo + MTX. At Week 52, 55.6% of patients receiving KEVZARA 200 mg + MTX and 47.8% of patients receiving KEVZARA 150 mg + MTX had no progression of structural damage (as defined by a change in the Total Sharp Score of zero or less) compared with 38.7% of patients receiving placebo.
| Study 1 | |||
|---|---|---|---|
| Placebo + MTX (N=398) | KEVZARA 150 mg + MTX (N=400) | KEVZARA 200 mg + MTX (N=399) |
|
|
|||
| Modified Total Sharp Score (mTSS) | |||
| Mean change | 2.78 | 0.90 | 0.25 |
| LS† mean difference (95% CI‡) | -1.88 (-2.74, -1.01) | -2.52 (-3.38, -1.66) | |
| Erosion score | |||
| Mean change | 1.46 | 0.42 | 0.05 |
| LS† mean difference (95% CI‡) | -1.03 (-1.53, -0.53) | -1.40 (-1.90, -0.90) | |
| Joint space narrowing score | |||
| Mean change | 1.32 | 0.47 | 0.20 |
| LS† mean difference (95% CI‡) | -0.85 (-1.34, -0.35) | -1.12 (-1.61, -0.63) | |
Physical Function Response
In Studies 1 and 2, physical function and disability were assessed by the Health Assessment Questionnaire Disability Index (HAQ-DI). Patients receiving KEVZARA 200 mg every two weeks + MTX/DMARD and KEVZARA 150 mg every two weeks + MTX/DMARD demonstrated greater improvement from baseline in physical function compared to placebo + MTX/DMARD at Week 16 and Week 12 in Studies 1 and 2, respectively (Table 7).
| Study 1 | Study 2 | |||||
|---|---|---|---|---|---|---|
| Week 16 | Week 12 | |||||
| Placebo + MTX (N=398) | KEVZARA 150 mg + MTX (N=400) | KEVZARA 200 mg + MTX (N=399) | Placebo + DMARD(s) (N=181) | KEVZARA 150 mg + DMARD(s) (N=181) | KEVZARA 200 mg + DMARD(s) (N=184) |
|
|
||||||
| HAQ-DI | ||||||
| Change from baseline | -0.30 | -0.54 | -0.58 | -0.29 | -0.50 | -0.49 |
| Difference from placebo (95% CI)* | -0.24 (-0.31, -0.16) | -0.26 (-0.34, -0.18) | -0.20 (-0.32, -0.09) | -0.21 (-0.33, -0.10) |
||
| % of patients with clinically meaningful improvement† | 42.5% | 53.8% | 57.4% | 35.9% | 47% | 51.1% |
14.2 Polymyalgia Rheumatica
The efficacy and safety of KEVZARA in PMR were assessed in a randomized, double-blind, placebo-controlled, 52-week, multicenter study (Study 3) (NCT03600818) in adults with PMR diagnosed according to American College of Rheumatology/European Union League against Rheumatism (ACR/EULAR) classification criteria. Patients had at least one episode of unequivocal PMR flare while attempting to taper corticosteroids.
In Study 3, patients with active PMR were randomized to receive KEVZARA 200 mg every two weeks with a pre-defined 14-week taper of prednisone (n= 60) or placebo every two weeks with a pre-defined 52-week taper of prednisone (n=58). One participant was randomized but not treated in the KEVZARA 200 mg arm. Patients experiencing a disease flare or unable to adhere to the assigned prednisone tapering schedule could receive corticosteroids as rescue therapy.
The primary endpoint was the proportion of patients with sustained remission at Week 52. Sustained remission was defined as achievement of disease remission no later than Week 12, absence of disease flare from Week 12 through Week 52, sustained reduction of CRP (to <10 mg/L) from Week 12 through Week 52, and successful adherence to prednisone taper from Week 12 through Week 52. An additional endpoint was total cumulative corticosteroid dose over 52 weeks.
Clinical Response
The proportion of participants achieving sustained remission at Week 52 was higher in the KEVZARA arm compared to the placebo arm; this difference was statistically significant. At 52 weeks, a higher proportion of patients in the KEVZARA arm achieved each component of the sustained remission endpoint compared to the placebo An analysis was conducted that removed all acute phase reactants (CRP and ESR) criteria from the definition of the sustained remission, given sarilumab's direct impact on acute phase reactants. The results of this analysis were consistent with the primary analysis (see Table 8).
| Placebo (N=58) | KEVZARA (N=60) |
||
|---|---|---|---|
|
|||
| Sustained remission at Week 52 | |||
| Number of patients with sustained remission, n (%) | 6 (10.3) | 17 (28.3) | |
| Proportion difference (95% CI) vs. placebo | 18.0 (4.2, 31.8; p=0.0193) | ||
| Components of sustained remission at Week 52 | |||
| Absence of signs and symptoms and CRP < 10 mg/L (disease remission*) no later than Week 12, n (%) | 22 (37.9) | 28 (46.7) | |
| Absence of disease flare† from Week 12 through Week 52, n (%) | 19 (32.8) | 33 (55.0) | |
| Sustained reduction of CRP (<10 mg/L) from Week 12 through Week 52, n (%) | 26 (44.8) | 40 (66.7) | |
| Successful adherence to prednisone taper from Week 12 through Week 52, n (%) | 14 (24.1) | 30 (50.0) | |
| Sensitivity analysis removing acute phase reactants (CRP and ESR) from sustained remission at Week 52 | |||
| Number of patients with sustained remission, n (%) | 8 (13.8) | 19 (31.7) | |
| Proportion difference (95% CI) for sarilumab vs. placebo | 17.9 (3.1, 32.6) | ||
16. How is Kevzara supplied
KEVZARA (sarilumab) injection is supplied as a colorless to pale yellow solution in a single-dose pre-filled syringes and single-dose pre-filled pens.
| Strength | Package Size | NDC Number |
|---|---|---|
| 150 mg/1.14 mL | 2 syringes per pack | 0024-5908-01 |
| 200 mg/1.14 mL | 2 syringes per pack | 0024-5910-01 |
| Strength | Package Size | NDC Number |
|---|---|---|
| 150 mg/1.14 mL | 2 pre-filled pens per pack | 0024-5920-01 |
| 200 mg/1.14 mL | 2 pre-filled pens per pack | 0024-5922-01 |
17. Patient Counseling Information
Advise the patients to read the FDA-approved patient labeling (Medication Guide and Instructions for Use).
| MEDICATION GUIDE KEVZARA® (KEV-za-ra) (sarilumab) injection, for subcutaneous use |
|||
|---|---|---|---|
| This Medication Guide has been approved by the U.S. Food and Drug Administration | Revised: February 2023 | ||
| What is the most important information I should know about KEVZARA? KEVZARA can cause serious side effects including:
|
|||
|
|
||
See "What are the possible side effects of KEVZARA?" for more information about side effects. |
|||
| What is KEVZARA?
KEVZARA is an injectable prescription medicine called an interleukin-6 (IL-6) receptor blocker. KEVZARA is used:
It is not known if KEVZARA is safe and effective in children. |
|||
| Who should not use KEVZARA?
Do not use KEVZARA if you are allergic to sarilumab or any of the ingredients in KEVZARA. See the end of this Medication Guide for a complete list of ingredients in KEVZARA. |
|||
Before using KEVZARA, talk to your healthcare provider about all of your medical conditions, including if you:
Tell your healthcare provider about all the medicines you take, including prescription and over-the-counter medicines, vitamins, and herbal supplements.
Know the medicines you take. Keep a list of them to show to your healthcare provider and pharmacist when you get a new medicine. |
|||
How should I use KEVZARA?
|
|||
| What are the possible side effects of KEVZARA? KEVZARA can cause serious side effects, including:
|
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|
|
||
Common side effects of KEVZARA include:
These are not all of the possible side effects of KEVZARA. |
|||
How should I store KEVZARA?
|
|||
| General Information about the safe and effective use of KEVZARA.
Medicines are sometimes prescribed for purposes other than those listed in a Medication Guide. Do not use KEVZARA for a condition for which it was not prescribed. Do not give KEVZARA to other people, even if they have the same symptoms you have. It may harm them. You can ask your healthcare provider or pharmacist for information about KEVZARA that is written for health professionals. |
|||
| What are the ingredients in KEVZARA? Active Ingredient: sarilumab Inactive Ingredients: arginine, histidine, polysorbate 20, sucrose, and Water for Injection, USP. REGENERON sanofi Manufactured by: sanofi-aventis U.S. LLC Bridgewater, NJ 08807, A SANOFI COMPANY U.S. License # 1752. Marketed by: sanofi-aventis U.S. LLC (Bridgewater, NJ 08807) and Regeneron Pharmaceuticals, Inc. (Tarrytown, NY 10591) KEVZARA® is a registered trademark of Sanofi Biotechnology ©2023 Regeneron Pharmaceuticals, Inc. / sanofi-aventis U.S. LLC For more information, go to www.KEVZARA.com or call 1-844-KEVZARA (1-844-538-9272). |
|||
Instructions For UseKEVZARA® (KEV-za-ra)(sarilumab)injection, for subcutaneous useSingle-dose Pre-filled Syringe (150 mg/1.14 mL)
Important information:
KEVZARA is available as a single-dose pre-filled syringe (called "syringe" in these instructions). The pre-filled syringe contains 150 mg of KEVZARA for injection under the skin (subcutaneous injection) 1 time every 2 weeks.
Do not try to inject KEVZARA until you have been shown the right way to give the injections by your healthcare provider.
| Do | Do not |
|---|---|
|
|
Keep these instructions for future use.
If you have any further questions, ask your healthcare provider or call 1-844-KEVZARA (1-844-538-9272).
KEVZARA pre-filled syringe parts
What you will need for your injection:
- A new KEVZARA 150 mg/1.14 mL pre-filled syringe
- Alcohol wipe
- Cotton ball or gauze
- Sharps disposal container. See "How should I dispose of (throw away) KEVZARA pre-filled syringes?" at the end of this Instructions for Use.
Step A: Get ready for an injection
| 1. Prepare all of the equipment you will need on a clean, flat working surface. | |
|  |
| 2. Look at the label. | |
|  |
| 3. Look at the medicine. | |
|  |
| 4. Lay the syringe on a flat surface and allow it to warm up at room temperature for at least 30 minutes. | |
|  |
| 5. Select the injection site. | |
|  |
| 6. Prepare the injection site. | |
|
Step B: Give the injection
Complete Step B after completing all steps in Step A "Get ready for an injection".
| 1. Pull off the needle cap. | |
|  |
| 2. Pinch the skin. | |
|  |
| 3. Insert the needle into the fold of skin at about a 45 degree angle. |  |
| 4. Push the plunger down. | |
|  |
| 5. Before you remove the needle, check that the syringe is empty. | |
|  |
| 6. Dispose of the syringe. | |
|  |
How should I dispose of (throw away) KEVZARA pre-filled syringes?
- Put the used syringe in an FDA-cleared sharps disposal container right away after use. Do not throw away (dispose of) the syringe in your household trash.
- If you do not have an FDA-cleared sharps disposal container, you may use a household container that is:
- made of a heavy-duty plastic,
- can be closed with a tight-fitting, puncture-resistant lid, without sharps being able to come out,
- upright and stable during use,
- leak-resistant, and
- properly labeled to warn of hazardous waste inside the container.
- When your sharps disposal container is almost full, you will need to follow your community guidelines for the right way to dispose of your sharps disposal container. There may be state or local laws about how you should throw away used needles and syringes. For more information about safe sharps disposal, and for specific information about sharps disposal in the state that you live in, go to the FDA's website at: http://www.fda.gov/safesharpsdisposal
- Do not reuse the syringe.
- Do not dispose of your used sharps disposal container in your household trash unless your community guidelines permit this. Do not recycle your used sharps disposal container.
Important: Always keep the sharps disposal container out of the reach of children.
This Instructions for Use has been approved by the U.S. Food and Drug Administration.
REGENERON
SANOFI GENZYME
Manufactured by:
sanofi-aventis U.S. LLC
Bridgewater, NJ 08807
A SANOFI COMPANY
U.S. License # 1752
Marketed by: sanofi-aventis U.S. LLC (Bridgewater, NJ 08807)
and Regeneron Pharmaceuticals, Inc. (Tarrytown, NY 10591)
KEVZARA® is a registered trademark of Sanofi Biotechnology
©2017 Regeneron Pharmaceuticals, Inc. / sanofi-aventis U.S. LLC
Issued: May 2017
Instructions For UseKEVZARA® (KEV-za-ra)(sarilumab)injection, for subcutaneous useSingle-dose Pre-filled Syringe (200 mg/1.14 mL)
Important information:
KEVZARA is available as a single-dose pre-filled syringe (called "syringe" in these instructions). The pre-filled syringe contains 200 mg of KEVZARA for injection under the skin (subcutaneous injection) 1 time every 2 weeks.
Do not try to inject KEVZARA until you have been shown the right way to give the injections by your healthcare provider.
| Do | Do not |
|---|---|
|
|
Keep these instructions for future use.
If you have any further questions, ask your healthcare provider or call 1-844-KEVZARA (1-844-538-9272).
KEVZARA pre-filled syringe parts
What you will need for your injection:
- A new KEVZARA 200 mg/1.14 mL pre-filled syringe
- Alcohol wipe
- Cotton ball or gauze
- Sharps disposal container. See "How should I dispose of (throw away) KEVZARA pre-filled syringes?" at the end of this Instructions for Use.
Step A: Get ready for an injection
| 1. Prepare all of the equipment you will need on a clean, flat working surface. | |
|  |
| 2. Look at the label. | |
|  |
| 3. Look at the medicine. | |
|  |
| 4. Lay the syringe on a flat surface and allow it to warm up at room temperature for at least 30 minutes. | |
|  |
| 5. Select the injection site. | |
|  |
| 6. Prepare the injection site. | |
|
Step B: Give the injection
Complete Step B after completing all steps in Step A "Get ready for an injection"
| 1. Pull off the needle cap. | |
|  |
| 2. Pinch the skin. | |
|  |
| 3. Insert the needle into the fold of skin at about a 45 degree angle. | |
 |
|
| 4. Push the plunger down. | |
|  |
| 5. Before you remove the needle, check that the syringe is empty. | |
|  |
| 6. Dispose of the syringe. | |
|  |
How should I dispose of (throw away) KEVZARA pre-filled syringes?
- Put the used syringe in an FDA-cleared sharps disposal container right away after use. Do not throw away (dispose of) the syringe in your household trash.
- If you do not have an FDA-cleared sharps disposal container, you may use a household container that is:
- made of a heavy-duty plastic,
- can be closed with a tight-fitting, puncture-resistant lid, without sharps being able to come out,
- upright and stable during use,
- leak-resistant, and
- properly labeled to warn of hazardous waste inside the container.
- When your sharps disposal container is almost full, you will need to follow your community guidelines for the right way to dispose of your sharps disposal container. There may be state or local laws about how you should throw away used needles and syringes. For more information about safe sharps disposal, and for specific information about sharps disposal in the state that you live in, go to the FDA's website at: http://www.fda.gov/safesharpsdisposal
- Do not reuse the syringe.
- Do not dispose of your used sharps disposal container in your household trash unless your community guidelines permit this. Do not recycle your used sharps disposal container.
Important: Always keep the sharps disposal container out of the reach of children.
This Instructions for Use has been approved by the U.S. Food and Drug Administration.
REGENERON
SANOFI GENZYME
Manufactured by:
sanofi-aventis U.S. LLC
Bridgewater, NJ 08807
A SANOFI COMPANY
U.S. License # 1752
Marketed by: sanofi-aventis U.S. LLC, (Bridgewater, NJ 08807)
and Regeneron Pharmaceuticals, Inc. (Tarrytown, NY 10591)
KEVZARA® is a registered trademark of Sanofi Biotechnology
©2017 Regeneron Pharmaceuticals, Inc. / sanofi-aventis U.S. LLC
Issued: May 2017
Instructions For UseKEVZARA® (KEV-za-ra)(sarilumab)injection, for subcutaneous useSingle-dose pre-filled pen (150 mg/1.14 mL)
Important information:
KEVZARA is available as a single-dose pre-filled pen (called "pen" in these instructions). The pre-filled pen contains 150 mg of KEVZARA for injection under the skin (subcutaneous injection) 1 time every 2 weeks.
Do not try to inject KEVZARA until you have been shown the right way to give the injections by your healthcare provider.
| Do | Do not |
|---|---|
|
|
Keep these instructions for future use.
If you have any further questions, ask your healthcare provider or call 1-844-KEVZARA (1-844-538-9272).
KEVZARA pre-filled pen parts
What you will need for your injection:
- An unused KEVZARA 150 mg/1.14 mL pre-filled pen
- Alcohol wipe
- Cotton ball or gauze
- Sharps disposal container. See "How should I throw away (dispose of) KEVZARA pre-filled pens?" at the end of this Instructions for Use.
Step A: Get ready for an injection
| 1. Prepare all of the equipment you will need on a clean, flat working surface. | |
|
|
| 2. Look at the label. | |
|  |
| 3. Look at the window. | |
|  |
| 4. Lay the pen on a flat surface and allow it to warm up at room temperature for at least 60 minutes. | |
|  |
| 5. Select the injection site. | |
|  |
| 6. Prepare the injection site. | |
|
|
Step B: Give the injection
Complete Step B after completing all steps in Step A "Get ready for an injection"
| 1. Twist or pull off the orange cap. | |
|  |
| 2. Put the yellow needle cover on your skin at about a 90 degree angle. | |
|  |
| 3. Press down and hold the pen firmly against your skin. | |
|  |
| 4. Keep holding the pen firmly against your skin. | |
|  |
| 5. There will be a second click when the injection is complete. Check to see if the entire window has turned solid yellow before you remove the pen. | |
|  |
| 6. Remove the pen from your skin. | |
|  |
| 7. Dispose of the pen | |
|  |
How should I throw away (dispose of) KEVZARA pre-filled pens?
- Put the used pen in an FDA-cleared sharps disposal container right away after use. Do not throw away (dispose of) the pen in your household trash.
- If you do not have an FDA-cleared sharps disposal container, you may use a household container that is:
- made of a heavy-duty plastic,
- can be closed with a tight-fitting, puncture-resistant lid, without sharps being able to come out,
- upright and stable during use,
- leak-resistant, and
- properly labeled to warn of hazardous waste inside the container.
- When your sharps disposal container is almost full, you will need to follow your community guidelines for the right way to dispose of your sharps disposal container. There may be state or local laws about how you should throw away used needles and syringes. For more information about safe sharps disposal, and for specific information about sharps disposal in the state that you live in, go to the FDA's website at: http://www.fda.gov/safesharpsdisposal
- Do not reuse the pen.
- Do not dispose of your used sharps disposal container in your household trash unless your community guidelines permit this. Do not recycle your used sharps disposal container.
Important: Always keep the sharps disposal container out of the reach of children.
This Instructions for Use has been approved by the U.S. Food and Drug Administration.
REGENERON
SANOFI GENZYME
Manufactured by:
sanofi-aventis U.S. LLC
Bridgewater, NJ 08807
A SANOFI COMPANY
U.S. License # 1752
Marketed by: sanofi-aventis U.S. LLC (Bridgewater, NJ 08807)
and Regeneron Pharmaceuticals, Inc. (Tarrytown, NY 10591)
KEVZARA® is a registered trademark of Sanofi Biotechnology
©2018 Regeneron Pharmaceuticals, Inc. / sanofi-aventis U.S. LLC
Issued: April 2018a
Instructions For UseKEVZARA® (KEV-za-ra)(sarilumab)injection, for subcutaneous useSingle-dose pre-filled pen (200 mg/1.14 mL)
Important information:
KEVZARA is available as a single-dose pre-filled pen (called "pen" in these instructions). The pre-filled pen contains 200 mg of KEVZARA for injection under the skin (subcutaneous injection) 1 time every 2 weeks.
Do not try to inject KEVZARA until you have been shown the right way to give the injections by your healthcare provider.
| Do | Do not |
|---|---|
|
|
Keep these instructions for future use.
If you have any further questions, ask your healthcare provider or call 1-844-KEVZARA (1-844-538-9272).
KEVZARA pre-filled pen parts
What you will need for your injection:
- An unused KEVZARA 200 mg/1.14 mL pre-filled pen
- Alcohol wipe
- Cotton ball or gauze
- Sharps disposal container. See "How should I throw away (dispose of) KEVZARA pre-filled pens?" at the end of this Instructions for Use.
Step A: Get ready for an injection
| 1. Prepare all of the equipment you will need on a clean, flat working surface. | |
|
|
| 2. Look at the label. | |
|  |
| 3. Look at the window. | |
|  |
| 4. Lay the pen on a flat surface and allow it to warm up at room temperature for at least 60 minutes. | |
|  |
| 5. Select the injection site. | |
|  |
| 6. Prepare the injection site. | |
|
|
Step B: Give the injection
Complete Step B after completing all steps in Step A "Get ready for an injection"
| 1. Twist or pull off the orange cap. | |
|  |
| 2. Put the yellow needle cover on your skin at about a 90 degree angle. | |
|  |
| 3. Press down and hold the pen firmly against your skin. | |
|  |
| 4. Keep holding the pen firmly against your skin. | |
|  |
| 5. There will be a second click when the injection is complete. Check to see if the entire window has turned solid yellow before you remove the pen. | |
|  |
| 6. Remove the pen from your skin. | |
|  |
| 7. Dispose of the pen | |
|  |
How should I throw away (dispose of) KEVZARA pre-filled pens?
- Put the used pen in an FDA-cleared sharps disposal container right away after use. Do not throw away (dispose of) the pen in your household trash.
- If you do not have an FDA-cleared sharps disposal container, you may use a household container that is:
- made of a heavy-duty plastic,
- can be closed with a tight-fitting, puncture-resistant lid, without sharps being able to come out,
- upright and stable during use,
- leak-resistant, and
- properly labeled to warn of hazardous waste inside the container.
- When your sharps disposal container is almost full, you will need to follow your community guidelines for the right way to dispose of your sharps disposal container. There may be state or local laws about how you should throw away used needles and syringes. For more information about safe sharps disposal, and for specific information about sharps disposal in the state that you live in, go to the FDA's website at: http://www.fda.gov/safesharpsdisposal
- Do not reuse the pen.
- Do not dispose of your used sharps disposal container in your household trash unless your community guidelines permit this. Do not recycle your used sharps disposal container.
Important: Always keep the sharps disposal container out of the reach of children.
This Instructions for Use has been approved by the U.S. Food and Drug Administration.
REGENERON
SANOFI GENZYME
Manufactured by:
sanofi-aventis U.S. LLC
Bridgewater, NJ 08807
A SANOFI COMPANY
U.S. License # 1752
Marketed by: sanofi-aventis U.S. LLC (Bridgewater, NJ 08807)
and Regeneron Pharmaceuticals, Inc. (Tarrytown, NY 10591)
KEVZARA® is a registered trademark of Sanofi Biotechnology
©2018 Regeneron Pharmaceuticals, Inc. / sanofi-aventis U.S. LLC
Issued: April 2018a
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sarilumab injection, solution |
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sarilumab injection, solution |
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| KEVZARA
sarilumab injection, solution |
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| KEVZARA
sarilumab injection, solution |
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| Labeler - sanofi-aventis U.S. LLC (824676584) |
| Establishment | |||
| Name | Address | ID/FEI | Business Operations |
|---|---|---|---|
| Sanofi Winthrop Industrie | 297730488 | ANALYSIS(0024-5908, 0024-5910, 0024-5920, 0024-5922) , MANUFACTURE(0024-5908, 0024-5910, 0024-5920, 0024-5922) , PACK(0024-5908, 0024-5910, 0024-5920, 0024-5922) , LABEL(0024-5908, 0024-5910, 0024-5920, 0024-5922) | |
| Establishment | |||
| Name | Address | ID/FEI | Business Operations |
|---|---|---|---|
| Sanofi-Aventis Deutschland GmbH | 313218430 | ANALYSIS(0024-5920, 0024-5922) , MANUFACTURE(0024-5920, 0024-5922) , PACK(0024-5920, 0024-5922) , LABEL(0024-5920, 0024-5922) | |
| Establishment | |||
| Name | Address | ID/FEI | Business Operations |
|---|---|---|---|
| Regeneron Pharmaceuticals, Inc. | 945589711 | API MANUFACTURE(0024-5908, 0024-5910, 0024-5920, 0024-5922) , ANALYSIS(0024-5908, 0024-5910, 0024-5920, 0024-5922) , MANUFACTURE(0024-5908, 0024-5910, 0024-5920, 0024-5922) | |
| Establishment | |||
| Name | Address | ID/FEI | Business Operations |
|---|---|---|---|
| Genzyme Corporation | 050424395 | LABEL(0024-5908, 0024-5910, 0024-5920, 0024-5922) , PACK(0024-5908, 0024-5910, 0024-5920, 0024-5922) | |
| Establishment | |||
| Name | Address | ID/FEI | Business Operations |
|---|---|---|---|
| Genzyme Ireland Limited | 985127419 | ANALYSIS(0024-5908, 0024-5910) , MANUFACTURE(0024-5908, 0024-5910) | |
| Establishment | |||
| Name | Address | ID/FEI | Business Operations |
|---|---|---|---|
| Nelson Laboratories, LLC | 151663234 | ANALYSIS(0024-5908, 0024-5910) | |
