Kevzara

Tell your doctor about all prescription, nonprescription, illegal, recreational, herbal, nutritional, or dietary drugs you're taking while using Kevzara, especially:

• Coumadin (warfarin)
• Theophylline
• Oral contraceptives
• Statin medicines
• Other drugs to treat RA, including Rituxan (rituximab), Enbrel (etanercept), Remicade (infliximab), Kineret (anakinra), Humira (adalimumab), Orencia (abatacept), Cimzia (certolizumab), Simponi (golimumab), Actemra (tocilizumab), or Xeljanz (tofacitinib)

Sarilumab reduces the effects of a substance in the body that can cause inflammation.

Sarilumab is used to treat moderate to severe rheumatoid arthritis in adults. Sarilumab is sometimes given together with other arthritis medicines.

Sarilumab is usually given after other medications have been tried without successful treatment of symptoms.

Sarilumab may also be used for purposes not listed in this medication guide.

General

Sarilumab is available in the following dosage form(s) and strength(s):

Injection: 150 mg/1.14 mL or 200 mg/1.14 mL solution in a single-dose pre-filled syringe.1

Dosage

It is essential that the manufacturer's labeling be consulted for more detailed information on dosage and administration of this drug. Dosage summary:

• Sarilumab may be used as monotherapy or in combination with methotrexate (MTX) or other conventional DMARDs.1

• The recommended dosage of sarilumab is 200 mg once every two weeks, administered as a subcutaneous injection.1

• Sarilumab initiation is not recommended in patients with ANC less than 2000/mm3, platelets less than 150,000/mm3 or liver transaminases above 1.5 times ULN.1

• Modify dosage to manage neutropenia, thrombocytopenia, and/or elevated liver transaminases.1

Contraindications

Sarilumab is contraindicated in patients with known hypersensitivity to sarilumab or any of the inactive ingredients.1

Warnings/Precautions

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 sarilumab for rheumatoid arthritis (RA). The most frequently observed serious infections with sarilumab included pneumonia and cellulitis. Among opportunistic infections, tuberculosis, candidiasis, and pneumocystis were reported with sarilumab. Some patients presented with disseminated rather than localized disease and were often taking concomitant immunosuppressants such as methotrexate or corticosteroids, which in addition to RA may predispose them to infections. While not reported in sarilumab clinical studies, other serious infections (e.g., histoplasmosis, cryptococcus, aspergillosis) have been reported in patients receiving other immunosuppressive agents for the treatment of RA.1

Avoid use of sarilumab in patients with an active infection, including localized infections. Consider the risks and benefits of treatment prior to initiating sarilumab in patients who have: 1

• chronic or recurrent infection;1

• a history of serious or opportunistic infections;1

• underlying conditions, in addition to RA, that may predispose them to infection;1

• been exposed to tuberculosis; or1

• lived in or traveled to areas of endemic tuberculosis or endemic mycoses.1

Closely monitor patients for the development of signs and symptoms of infection during treatment with sarilumab, as signs and symptoms of acute inflammation may be lessened due to suppression of the acute phase reactants.1

Hold treatment with sarilumab if a patient develops a serious infection or an opportunistic infection.1

Perform prompt and complete diagnostic testing appropriate for an immunocompromised patient who develops a new infection during treatment with sarilumab; initiate appropriate antimicrobial therapy, and closely monitor the patient.1

Evaluate patients for tuberculosis (TB) risk factors and test for latent infection prior to initiating treatment with sarilumab. Treat patients with latent TB with standard antimycobacterial therapy before initiating sarilumab. Consider anti-TB therapy prior to initiation of sarilumab in patients with a past history of latent or active TB in whom an adequate course of treatment cannot be confirmed, and for patients with a negative test for latent TB but having risk factors for TB infection. When considering anti-TB therapy, consultation with a physician with expertise in TB may be appropriate.1

Closely monitor patients for the development of signs and symptoms of TB including patients who tested negative for latent TB infection prior to initiating therapy.1

Viral reactivation has been reported with immunosuppressive biologic therapies. Cases of herpes zoster were observed in clinical studies with sarilumab. The risk of hepatitis B reactivation with sarilumab is unknown since patients who were at risk for reactivation were excluded.1

Laboratory Abnormalities

Treatment with sarilumab was associated with a higher incidence of decrease in absolute neutrophil count (ANC), including neutropenia.1

• Assess neutrophil count prior to initiation of sarilumab and monitor neutrophil count 4 to 8 weeks after start of therapy and every 3 months thereafter.1

• Based on the pharmacodynamics of the changes in ANC, use results obtained at the end of the dosing interval when considering dose modification.1

Treatment with sarilumab was associated with a reduction in platelet counts in clinical studies.1

• Assess platelet count prior to initiation of sarilumab and monitor platelets 4 to 8 weeks after start of therapy and every 3 months thereafter.1

Treatment with sarilumab was associated with a higher incidence of transaminase elevations. These elevations were transient and did not result in any clinically evident hepatic injury in clinical studies. Increased frequency and magnitude of these elevations were observed when potentially hepatotoxic drugs (e.g., MTX) were used in combination with sarilumab.1

• Assess ALT/AST levels prior to initiation of sarilumab and monitor ALT/AST levels 4 to 8 weeks after start of therapy and every 3 months thereafter. When clinically indicated, consider other liver function tests such as bilirubin.1

Treatment with sarilumab was associated with increases in lipid parameters such as LDL cholesterol, HDL cholesterol and/or triglycerides.1

• Assess lipid parameters approximately 4 to 8 weeks following initiation of treatment with sarilumab, then at approximately 6 month intervals.1

• Manage patients according to clinical guidelines for the management of hyperlipidemia.1

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.1

Immunosuppression

Treatment with immunosuppressants may result in an increased risk of malignancies. The impact of treatment with sarilumab on the development of malignancies is not known but malignancies were reported in clinical studies.1

Hypersensitivity Reactions

Hypersensitivity reactions have been reported in association with sarilumab. 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 sarilumab immediately. Do not administer sarilumab to patients with known hypersensitivity to sarilumab.1

Active Hepatic Disease and Hepatic Impairment

Treatment with sarilumab is not recommended in patients with active hepatic disease or hepatic impairment, as treatment with sarilumab was associated with transaminase elevations.1

Live Vaccines

Avoid concurrent use of live vaccines during treatment with sarilumab due to potentially increased risk of infections; clinical safety of live vaccines during sarilumab treatment has not been established. No data are available on the secondary transmission of infection from persons receiving live vaccines to patients receiving sarilumab. The interval between live vaccinations and initiation of sarilumab therapy should be in accordance with current vaccination guidelines regarding immunosuppressive agents.1

Specific Populations

Pregnancy Exposure Registry: There is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to sarilumab during pregnancy. Physicians are encouraged to register patients and pregnant women are encouraged to register themselves by calling 1-877-311-8972.1

Risk Summary: The limited human data with sarilumab in pregnant women are not sufficient to inform drug-associated risk for major birth defects and miscarriage. Monoclonal antibodies, such as sarilumab, are actively transported across the placenta during the third trimester of pregnancy and may affect immune response in the in utero exposed infant. From animal data, and consistent with the mechanism of action, levels of IgG, in response to antigen challenge, may be reduced in the fetus/infant of treated mothers. In an animal reproduction study, consisting of a combined embryo-fetal and pre- and postnatal development study with monkeys that received intravenous administration of sarilumab, there was no evidence of embryotoxicity or fetal malformations with exposures up to approximately 84 times the maximum recommended human dose (MRHD). The literature suggests that inhibition of IL-6 signaling may interfere with cervical ripening and dilatation and myometrial contractile activity leading to potential delays of parturition. The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriages in clinically recognized pregnancies is 2 to 4% and 15 to 20%, respectively. Sarilumab should be used in pregnancy only if the potential benefit justifies the potential risk to the fetus.1

Fetal/Neonatal Adverse Reactions: Monoclonal antibodies are increasingly transported across the placenta as pregnancy progresses, with the largest amount transferred during the third trimester. Risks and benefits should be considered prior to administering live or live-attenuated vaccines to infants exposed to sarilumab in utero From the animal data, and consistent with the mechanism of action, levels of IgG, in response to antigen challenge, may be reduced in the fetus/infant of treated mothers.1

Animal Data

In a combined embryo-fetal and pre- and postnatal development study, pregnant cynomolgus monkeys received sarilumab at intravenous doses of 0, 5, 15, or 50 mg/kg/week from confirmation of pregnancy at gestation day (GD) 20, throughout the period of organogenesis (up to approximately GD 50), and continuing to natural birth of infants at around GD 165. Maintenance of pregnancy was not affected at any doses. Sarilumab was not embryotoxic or teratogenic with exposures up to approximately 84 times the MRHD (based on AUC with maternal intravenous doses up to 50 mg/kg/week). Sarilumab had no effect on neonatal growth and development evaluated up to one month after birth. Sarilumab was detected in the serum of neonates up to one month after birth, suggesting that the antibody had crossed the placenta.1

Following antigen challenge, decreased IgG titers attributed to the immunosuppressive action of sarilumab were evident in studies with older monkeys, with exposures up to approximately 80 times the MRHD (based on AUC with intravenous doses up to 50 mg/kg/week) and juvenile mice treated with an analogous antibody, which binds to murine IL-6Rα to inhibit IL-6 mediated signaling, at subcutaneous doses up to 200 mg/kg/week. These findings suggest the potential for decreased IgG titers, following antigen challenge, in infants of mothers treated with sarilumab.1

Parturition is associated with significant increases of IL-6 in the cervix and myometrium. The literature suggests that inhibition of IL-6 signaling may interfere with cervical ripening and dilatation and myometrial contractile activity leading to potential delays of parturition. For mice deficient in IL-6 (ll6-/- null mice), parturition was delayed relative to wild-type (ll6+/+) mice. Administration of recombinant IL-6 to ll6-/- null mice restored the normal timing of delivery.1

No information is available on the presence of sarilumab in human milk, the effects of the drug on the breastfed infant, or the effects of the drug on milk production. Maternal IgG is present in human milk. If sarilumab is transferred into human milk, the effects of local exposure in the gastrointestinal tract and potential limited systemic exposure in the infant to sarilumab are unknown. The lack of clinical data during lactation precludes clear determination of the risk of sarilumab to an infant during lactation; therefore, the developmental and health benefits of breastfeeding should be considered along with the mother's clinical need for sarilumab and the potential adverse effects on the breastfed child from sarilumab or from the underlying maternal condition.1

Safety and efficacy of sarilumab in pediatric patients have not been established.1

Of the total number of patients in clinical studies of sarilumab, 15% were 65 years of age and over, while 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 infection among sarilumab and placebo-treated patients 65 years of age and older was higher than those under the age of 65. As there is a higher incidence of infections in the elderly population in general, caution should be used when treating the elderly.1

The safety and efficacy of sarilumab have not been studied in patients with hepatic impairment, including patients with positive HBV or HCV serology.1

No dose adjustment is required in patients with mild to moderate renal impairment. Sarilumab has not been studied in patients with severe renal impairment.1

Common Adverse Effects

Most common adverse reactions (incidence at least 3%) are neutropenia, increased ALT, injection site erythema, upper respiratory infections and urinary tract infections.1

AHFS First Release. For additional information until a more detailed monograph is developed and published, the manufacturer's labeling should be consulted. It is essential that the manufacturer's labeling be consulted for more detailed information on usual uses, dosage and administration, cautions, precautions, contraindications, potential drug interactions, laboratory test interferences, and acute toxicity.

WARNING/CAUTION: Even though it may be rare, some people may have very bad and sometimes deadly side effects when taking a drug. Tell your doctor or get medical help right away if you have any of the following signs or symptoms that may be related to a very bad side effect:

• Signs of an allergic reaction, like rash; hives; itching; red, swollen, blistered, or peeling skin with or without fever; wheezing; tightness in the chest or throat; trouble breathing or talking; unusual hoarseness; or swelling of the mouth, face, lips, tongue, or throat.
• Signs of a urinary tract infection (UTI) like blood in the urine, burning or pain when passing urine, feeling the need to pass urine often or right away, fever, lower stomach pain, or pelvic pain.
• Very bad belly pain.
• Throwing up blood or throw up that looks like coffee grounds.
• Black, tarry, or bloody stools.
• Shortness of breath.
• Chest pain.
• Dizziness or passing out.
• Warm, red, or painful skin or sores on the body.
• Sweating a lot.
• Muscle pain or weakness.
• Coughing up blood.

All drugs may cause side effects. However, many people have no side effects or only have minor side effects. Call your doctor or get medical help if any of these side effects or any other side effects bother you or do not go away:

• Irritation where the shot is given.
• Signs of a common cold.
• Stuffy nose.
• Runny nose.
• Sore throat.

These are not all of the side effects that may occur. If you have questions about side effects, call your doctor. Call your doctor for medical advice about side effects.

You may report side effects to the FDA at 1-800-FDA-1088. You may also report side effects at http://www.fda.gov/medwatch.

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)]

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.

All patients in the safety data described below had moderately to severely active rheumatoid arthritis.

The safety of Kevzara in combination with conventional DMARDs was evaluated based on data from seven studies, of which two were placebo-controlled, consisting of 2887 patients (long-term safety population). Of these, 2170 patients received Kevzara for at least 24 weeks, 1546 for at least 48 weeks, 1020 for at least 96 weeks, and 624 for at least 144 weeks.

The pre-rescue placebo-controlled population includes patients from the two Phase 3 efficacy studies (Studies 1 and 2) from weeks 0 to 16 for Study 1 and weeks 0 to 12 for Study 2, and was used to assess common adverse reactions and laboratory abnormalities prior to patients being permitted to switch from placebo to Kevzara. In this population, 582 patients, 579 patients, and 579 patients received Kevzara 200 mg, Kevzara 150 mg, or placebo once every two weeks, respectively, in combination with conventional DMARDs.

The 52-week placebo-controlled population includes patients from one Phase 2 study of 12 week duration and two Phase 3 efficacy studies (one of 24 week duration and the other of 52 week duration). This placebo-controlled population includes all subjects from the double-blind, placebo-controlled periods from each study and was analyzed under their original randomization assignment. In this population, 661 patients, 660 patients, and 661 patients received Kevzara 200 mg, Kevzara 150 mg, or placebo once every two weeks, respectively, in combination with conventional DMARDs.

Most safety data are described for the pre-rescue population. For rarer events, the 52-week placebo-controlled population is used.

The most common serious adverse reactions were infections [see Warnings and Precautions (5.1)].

The most frequent adverse reactions (occurring in at least 3% of patients treated with Kevzara in combination with DMARDs) observed with Kevzara in the clinical studies were neutropenia, increased ALT, injection site erythema, upper respiratory infections, and urinary tract infections.

In the pre-rescue placebo-controlled population, premature discontinuation due to adverse reactions occurred in 8%, 6% and 3% of patients treated with Kevzara 200 mg, Kevzara 150 mg, and placebo, respectively.

The most common adverse reaction (greater than 1%) that resulted in discontinuation of therapy with Kevzara was neutropenia.

The use of Kevzara as monotherapy was assessed in 132 patients, of which 67 received Kevzara 200 mg and 65 patients received Kevzara 150 mg without concomitant DMARDs. The safety profile was generally consistent with that in the population receiving concomitant DMARDs.

Overall Infections

In the pre-rescue placebo-controlled population, the rate of infections in the 200 mg and 150 mg Kevzara + DMARD group was 110 and 105 events per 100 patient-years, respectively, compared to 81 events per 100 patient-years in the placebo + DMARD group. The most commonly reported infections (2% to 4% of patients) were upper respiratory tract infections, urinary tract infections, and nasopharyngitis.

In the 52-week placebo-controlled population, 0.8% of patients (5 patients) treated with Kevzara 200 mg + DMARD, 0.6% (4 patients) treated with Kevzara 150 mg + DMARD and 0.5% (3 patients) treated with placebo + DMARD had an event of herpes zoster [see Warnings and Precautions (5.1)].

The overall rate of infections with Kevzara + DMARD in the long-term safety population was consistent with rates in the controlled periods of the studies.

Serious Infections

In the pre-rescue population, the rate of serious infections in the 200 mg and 150 mg Kevzara + DMARD group was 3.8 and 4.4 events per 100 patient-years, respectively, compared to 2.5 events per 100 patient-years in the placebo + DMARD group. In the 52-week placebo-controlled population, the rate of serious infections in the 200 mg and 150 mg Kevzara + DMARD group was 4.3 and 3.0 events per 100 patient-years, respectively, compared to 3.1 events per 100 patient-years in the placebo + DMARD group.

In the long-term safety population, the overall rate of serious infections was consistent with rates in the controlled periods of the studies. The most frequently observed serious infections included pneumonia and cellulitis. Cases of opportunistic infection have been reported [see Warnings and Precautions (5.1)].

Gastrointestinal Perforation

In the 52-week placebo-controlled population, one patient on Kevzara therapy experienced a gastrointestinal (GI) perforation (0.11 events per 100 patient-years).

In the long-term safety population, the overall rate of GI perforation was consistent with rates in the controlled periods of the studies. Reports of GI perforation were primarily reported as complications of diverticulitis including lower GI perforation and abscess. Most patients who developed GI perforations were taking concomitant nonsteroidal anti-inflammatory medications (NSAIDs) or corticosteroids. The contribution of these concomitant medications relative to Kevzara in the development of GI perforations is not known [see Warnings and Precautions (5.3)].

Hypersensitivity Reactions

In the pre-rescue placebo-controlled population, the proportion of patients who discontinued treatment due to hypersensitivity reactions was higher among those treated with Kevzara (0.3% in 200 mg, 0.2% in 150 mg) than placebo (0%). The rate of discontinuations due to hypersensitivity in the long-term safety population was consistent with the placebo-controlled period.

Injection Site Reactions

In the pre-rescue placebo-controlled population, injection site reactions were reported in 7% of patients receiving Kevzara 200 mg, 6% receiving Kevzara 150 mg, and 1% receiving placebo. These injection site reactions (including erythema and pruritus) were mild in severity for the majority of patients and necessitated drug discontinuation in 2 (0.2%) patients receiving Kevzara.

Laboratory Abnormalities

Decreased neutrophil count

In the pre-rescue placebo-controlled population, decreases in neutrophil counts less than 1000 per mm3 occurred in 6% and 4% of patients in the 200 mg Kevzara + DMARD and 150 mg Kevzara + DMARD group, respectively, compared to no patients in the placebo + DMARD groups. Decreases in neutrophil counts less than 500 per mm3 occurred in 0.7% of patients in both the 200 mg Kevzara + DMARD and 150 mg Kevzara + DMARD groups. Decrease in ANC was not associated with the occurrence of infections, including serious infections.

In the long-term safety population, the observations on neutrophil counts were consistent with what was seen in the placebo-controlled clinical studies [see Warnings and Precautions (5.2)].

Decreased platelet count

In the pre-rescue placebo-controlled population, decreases in platelet counts less than 100,000 per mm3 occurred in 1% and 0.7% of patients on 200 mg and 150 mg Kevzara + DMARD, respectively, compared to no patients on placebo + DMARD, without associated bleeding events.

In the long-term safety population, the observations on platelet counts were consistent with what was seen in the placebo-controlled clinical studies [see Warnings and Precautions (5.2)].

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)].

Lipid Abnormalities

Lipid parameters (LDL, HDL, and triglycerides) were first assessed at 4 weeks following initiation of Kevzara + DMARDs in the placebo-controlled population. Increases were observed at this time point with no additional increases observed thereafter. Changes in lipid parameters from baseline to Week 4 are summarized below:

• Mean LDL increased by 12 mg/dL in the Kevzara 150 mg every two weeks + DMARD group and 16 mg/dL in the Kevzara 200 mg every two weeks + DMARD group.
• Mean triglycerides increased by 20 mg/dL in the Kevzara 150 mg every two weeks + DMARD group and 27 mg/dL in the Kevzara 200 mg every two weeks + DMARD group.
• Mean HDL increased by 3 mg/dL in both the Kevzara 150 mg every two weeks + DMARD and Kevzara 200 mg every two weeks + DMARD groups.

In the long-term safety population, the observations in lipid parameters were consistent with what was observed in the placebo-controlled clinical studies.

Malignancies

In the 52-week placebo-controlled population, 9 malignancies (exposure-adjusted event rate of 1.0 event per 100 patient-years) were diagnosed in patients receiving Kevzara+ DMARD compared to 4 malignancies in patients in the control group (exposure-adjusted event rate of 1.0 event per 100 patient-years).

In the long-term safety population, the rate of malignancies was consistent with the rate observed in the placebo-controlled period [see Warnings and Precautions (5.4)].

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.

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.

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 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 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.

NDC 0024-5910-01
Rx Only

Kevzara®
(sarilumab)
injection

200 mg/1.14 mL (175.4 mg/mL)
2 Single-Dose Pre-filled Syringes
For Subcutaneous Injection Use Only

REGENERON
SANOFI GENZYME

Store in a refrigerator at 36°F to 46°F (2°C to 8°C) in the original
carton to protect from light. Do NOT freeze. Do NOT shake.

If needed, patients/caregivers may store Kevzara at room
temperature up to 77°F (25°C) up to 14 days in the outer carton.
Do not store above 77°F (25°C). After removal from the
refrigerator, use Kevzara within 14 days or discard.

Date removed from the refrigerator ____/____/____

ATTENTION: Enclosed Medication Guide is required for each patient

200 mg/1.14 mL

Kevzara (sarilumab) reduces the effects of a substance in the body that can cause inflammation.

Kevzara is used to treat moderate to severe rheumatoid arthritis in adults.

Kevzara is sometimes given together with other arthritis medicines. It is usually given after other medications have been tried without successful treatment of symptoms.

Seek emergency medical attention or call the Poison Help line at 1-800-222-1222.

Avoid being near people who are sick or have infections. Tell your doctor at once if you develop signs of infection.

Do not receive a "live" vaccine while using Kevzara, or you could develop a serious infection. Live vaccines include measles, mumps, rubella (MMR), polio, rotavirus, typhoid, yellow fever, varicella (chickenpox), zoster (shingles), and nasal flu (influenza) vaccine.

Get emergency medical help if you have signs of an allergic reaction to Kevzara: hives; chest pain, difficulty breathing, feeling like you might pass out; swelling of your face, lips, tongue, or throat.

Serious and sometimes fatal infections may occur during treatment with Kevzara. Stop using this medicine and call your doctor right away if you have signs of infection such as:

• fever, chills, sweating, body aches;

• cough with bloody mucus;

• feeling short of breath;

• diarrhea, stomach pain, weight loss;

• sores on your skin;

• pain or burning when you urinate; or

• feeling very tired.

Also call your doctor at once if you have signs of perforation (a hole or tear) in your stomach or intestines:

• fever;

• ongoing stomach pain; or

• a change in bowel habits.

Common Kevzara side effects may include:

• runny or stuffy nose, sinus pain, sore throat;

• abnormal liver function tests;

• painful urination; or

• skin redness where an injection was given.

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.

Pregnancy

Limited human data in pregnant women are not sufficient to inform drug-associated risk for major birth defects and miscarriage

Monoclonal antibodies are increasingly transported across the placenta as pregnancy progresses, with the largest amount transferred during the third trimester

Risks and benefits should be considered prior to administering live or live-attenuated vaccines to infants exposed in utero

From the animal data, and consistent with the mechanism of action, levels of IgG, in response to antigen challenge, may be reduced in the fetus/infant of treated mothers

Pregnancy registry

• There is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to sarilumab during pregnancy
• Physicians are encouraged to register patients and pregnant women are encouraged to register themselves by calling 1-877-311-8972

Lactation

Unknown if distributed in human breast milk

Consider the developmental and health benefits of breastfeeding along with the mother’s clinical need for the drug, and any potential adverse effects on the breastfed infant from the drug or from the underlying maternal condition

Pregnancy Categories

A:Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.

B:May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.

C:Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.

D:Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.

X:Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.

NA:Information not available.