Sarilumab

FDA Drug Information • Also known as: Kevzara

Brand Names: Kevzara
Dosage Form: INJECTION, SOLUTION
Product Type: DRUG FOR FURTHER PROCESSING

⚠ Boxed Warning (Black Box)

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. 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 )

Description

11 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, clear and colorless to pale yellow, preservative-free solution of approximately pH 6.0. KEVZARA is supplied in a single-dose pre-filled syringe and 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.

What Is Sarilumab Used For?

1 INDICATIONS AND USAGE 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 ) patients who weigh 63 kg or greater with active polyarticular juvenile idiopathic arthritis (pJIA). ( 1.3 ) 1.1 Rheumatoid Arthritis (RA) KEVZARA ® is indicated for treatment of adult patients with moderately to severely active rheumatoid arthritis who have had an inadequate response or intolerance to one or more disease-modifying antirheumatic drugs (DMARDs). 1.2 Polymyalgia Rheumatica (PMR) KEVZARA is indicated for treatment of adult patients with polymyalgia rheumatica who have had an inadequate response to corticosteroids or who cannot tolerate corticosteroid taper. 1.3 Polyarticular Juvenile Idiopathic Arthritis (pJIA) KEVZARA is indicated for treatment of active polyarticular juvenile idiopathic arthritis (pJIA) in patients who weigh 63 kg or greater.

Dosage and Administration

2 DOSAGE AND ADMINISTRATION General Considerations for Administration KEVZARA initiation is not recommended in patients with ANC less than 2,000/mm 3 , platelets less than 150,000/mm 3 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 ) Recommended Dosage in pJIA The recommended dosage is 200 mg given subcutaneously once every 2 weeks for pJIA patients who weigh 63 kg or greater using the 200 mg/1.14 mL pre-filled syringe. ( 2.4 ) For pJIA, KEVZARA can be used as monotherapy or in combination with conventional DMARDs. ( 2.4 ) Dosage Modifications for Cytopenias, Abnormal Liver Enzymes, Infections See FPI for complete information. ( 2.6 ) 2.1 General Considerations Prior to Administration Not Recommended for Concomitant Use with Biological DMARDS The concurrent use of KEVZARA with biological DMARDs such as tumor necrosis factor (TNF) antagonists, IL-1R antagonists, anti-CD20 monoclonal antibodies and selective co-stimulation modulators has not been studied. Avoid using KEVZARA with biological DMARDs because of the possibility of increased immunosuppression and increased risk of infection. Recommended Evaluations Prior to Treatment Complete blood count (CBC): Treatment initiation with KEVZARA is not recommended in patients with an absolute neutrophil count (ANC) below 2000 per mm 3 , or platelet count below 150,000 per mm 3 . Monitor laboratory parameters [see Warnings and Precautions (5.2) ]. Liver function tests (LFT): Treatment initiation with KEVZARA is not recommended in patients with or who have alanine transaminase (ALT) or aspartate aminotransferase (AST) above 1.5 times the upper limit of normal (ULN). Monitor laboratory parameters [see Dosage and Administration (2.6) and Warnings and Precautions (5.2) ] . Lipid parameters (total cholesterol, LDL cholesterol, HDL cholesterol and/or triglycerides): Assess lipid parameters at baseline. Monitor laboratory parameters [see Warnings and Precautions (5.2) ]. Active and latent tuberculosis infection evaluation: Prior to initiating KEVZARA, test patients for active and latent tuberculosis (TB). KEVZARA should not be administered to patients with active TB. If positive for latent infection, consider treating for TB prior to KEVZARA use [see Warnings and Precautions (5.1) ]. Evaluate for infections: Avoid KEVZARA use in patients with active infections [see Warnings and Precautions (5.1) ] . 2.2 Recommended Dosage for Rheumatoid Arthritis The recommended dosage...

Side Effects (Adverse Reactions)

6 ADVERSE REACTIONS 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) ] 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 ) Polyarticular Juvenile Idiopathic Arthritis: nasopharyngitis, neutropenia, upper respiratory tract infection and injection site erythema. ( 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 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. Rheumatoid Arthritis 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 . 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...

Drug Interactions

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) ]. 7.3 Live Vaccines Avoid concurrent use of live vaccines during treatment with KEVZARA [see Warnings and Precautions (5.7) ] .

Contraindications

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) ] . KEVZARA is contraindicated in patients with known hypersensitivity to sarilumab or any of the inactive ingredients. ( 4 )

Pregnancy and Breastfeeding

8.1 Pregnancy Risk Summary The limited human data with KEVZARA 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 (see Clinical Considerations ) . 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 (see Clinical Considerations and Data ) . 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) (see Data ) . 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 (see Data ) . 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. KEVZARA should be used in pregnancy only if the potential benefit justifies the potential risk to the fetus. Clinical Considerations 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 KEVZARA in utero [see...

How Supplied

16 HOW SUPPLIED/STORAGE AND HANDLING KEVZARA (sarilumab) injection is supplied as a clear and colorless to pale yellow solution in 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 Storage and Stability Refrigerate at 36°F to 46°F (2°C to 8°C) in 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.

About This Information

This drug information is sourced from FDA-approved labeling via the openFDA database. It is intended for educational and reference purposes only. This is not medical advice. Always consult your healthcare provider before making decisions about medication. Drug information may be updated by the FDA; check with your pharmacist for the most current information.

What are side effects?

Side effects are unwanted reactions that can occur when taking a medication. They range from mild (headache, nausea) to severe (allergic reactions, organ damage). Not everyone experiences side effects, and severity varies. Report any concerning side effects to your doctor.

What are drug interactions?

Drug interactions occur when a medication is affected by another drug, food, or supplement. Interactions can make medications less effective or cause dangerous side effects. Always tell your doctor about all medications and supplements you take.