Sarilumab (Monograph)

Brand name: Kevzara
Drug class: Interleukin-mediated Agents, Miscellaneous

Medically reviewed by Drugs.com on Jan 10, 2025. Written by ASHP.

Introduction

Biologic response modifier and a disease-modifying antirheumatic drug (DMARD); a recombinant human IgG₁ kappa monoclonal antibody specific for interleukin-6 (IL-6) receptor.

Uses for Sarilumab

Rheumatoid Arthritis

Management of moderately to severely active rheumatoid arthritis in adults who have had an inadequate response or intolerance to one or more DMARDs.

Can be used alone or in combination with methotrexate or other nonbiologic DMARDs (e.g., hydroxychloroquine, leflunomide, sulfasalazine).

Guidelines generally support use of IL-6 inhibitors as add-on therapy to methotrexate in patients who do not meet treatment goals with methotrexate alone.

Polymyalgia Rheumatica

Management of adults with polymyalgia rheumatica who have had an inadequate response to corticosteroids or who cannot tolerate corticosteroid taper.

Used in combination with corticosteroids during the taper and then as monotherapy following discontinuation of the corticosteroid.

Polyarticular Juvenile Idiopathic Arthritis

Treatment of active polyarticular juvenile idiopathic arthritis in patients weighing ≥63 kg.

Sarilumab Dosage and Administration

General

Pretreatment Screening

• Evaluate for tuberculosis infection prior to initiation of sarilumab; initiate antimycobacterial therapy if indicated.

• Evaluate neutrophil and platelet counts prior to initiation of sarilumab. Do not initiate therapy in patients with ANC <2000/mm³ or platelet count <150,000/mm³.

• Evaluate ALT/AST concentrations prior to initiation of sarilumab. Do not initiate sarilumab if the ALT or AST concentration is >1.5 times the upper limit of normal (ULN).

• Evaluate lipoprotein concentrations (total cholesterol, LDL cholesterol, HDL cholesterol and/or triglycerides) prior to initiation of sarilumab.

• Evaluate patients for any active infections.

• Prior to treatment, all patients should be brought up to date with all immunizations in agreement with current immunization guidelines.

Patient Monitoring

• Monitor closely for signs or symptoms of infection.

• Evaluate for tuberculosis infection periodically during therapy; initiate antimycobacterial therapy if indicated.

• Monitor neutrophil and platelet counts 4-8 weeks after therapy initiation, and then every 3 months.

• Monitor ALT/AST concentrations 4–8 weeks after therapy initiation, and then every 3 months. Monitor other liver function tests (e.g., bilirubin) when clinically indicated.

• Monitor lipoprotein concentrations 4–8 weeks after therapy initiation, then approximately every 6 months.

Other General Considerations

• May continue methotrexate, other nonbiologic DMARDs, and corticosteroids in adults receiving sarilumab for the management of rheumatoid arthritis.

• Do not use concomitantly with other biologic DMARDs, such as TNF blocking agents, interleukin-1 (IL-1) receptor antagonists, anti-CD20 monoclonal antibodies, and selective costimulation modulators.

Administration

Sub-Q Administration

Administer by sub-Q injection using single-dose prefilled syringe or prefilled pen.

Intended for use under the guidance and supervision of a clinician, but may be self-administered if the clinician determines that the patient and/or their caregiver is competent to safely administer the drug after appropriate training. Ability of pediatric patients to self-inject the prefilled pen not evaluated.

Administer sub-Q injections into anterior thigh or abdomen (except for the 2-inch area around the umbilicus); may be administered into the upper arm by a caregiver or clinician. Rotate injection sites. Do not make injections into areas where the skin is tender, bruised, or damaged or into scars.

Allow prefilled syringe to sit at room temperature for at least 30 minutes prior to administration; remove prefilled pen from refrigeration at least 60 minutes prior to administration. Do not warm sarilumab any other way (e.g., microwave, hot water). Do not shake syringe.

Administer entire contents of prefilled syringe or pen as a single dose.

Dosage

Pediatric Patients

Polyarticular Juvenile Idiopathic Arthritis

Sub-Q

Patients weighing ≥63 kg: 200 mg once every 2 weeks. Maximum dose is 200 mg. Can be used as monotherapy or in combination with conventional DMARDs.

Dosage Modification or Discontinuance for Toxicity in Patients with Polyarticular Juvenile Idiopathic Arthritis

Dose reduction of sarilumab not evaluated in patients with polyarticular juvenile idiopathic arthritis. Discontinue if ALT >5 times ULN, platelet count ≤50,000 cells/mm³, or neutrophil count <500 cells/mm³ associated with infection. Withhold if ALT >3 to ≤5 times ULN, platelet count >50,000 to ≤100,000 cells/mm³, and neutrophil count ≥500 to <1000 cells/mm³, and until clinical condition evaluated. Dosing of concomitant medications should be modified or discontinued, if appropriate.

Adults

Rheumatoid Arthritis

Sub-Q

200 mg once every 2 weeks.

Polymyalgia Rheumatica

Sub-Q

200 mg once every 2 weeks in combination with a tapering course of systemic corticosteroids. Can be used as monotherapy following discontinuation of corticosteroids.

Dosage Modifications or Discontinuance due to Toxicity in Patients with Rheumatoid Arthritis

Sub-Q

If a serious infection or opportunistic infection develops, interrupt sarilumab until the infection is controlled.

If certain dose-related laboratory changes (i.e., neutropenia, thrombocytopenia, elevated liver enzyme concentrations) occur, reduce sarilumab dosage to 150 mg every 2 weeks or temporarily interrupt or discontinue therapy (see Tables 1-3).

Dosage Modification or Discontinuance for Toxicity in Patients with Polymyalgia Rheumatica

Sub-Q

If a serious infection or an opportunistic infection develops, interrupt sarilumab until the infection is controlled.

If certain dose-related laboratory changes (i.e., neutropenia, thrombocytopenia, elevated liver enzyme concentrations) occur, discontinue sarilumab therapy. (See Tables 4-6.) Dosage modifications have not been studied in patients with polymyalgia rheumatica with these conditions.

Special Populations

Hepatic Impairment

Use not recommended.

Renal Impairment

Dosage adjustment not necessary in mild or moderate renal impairment; not evaluated in severe renal impairment.

Geriatric Patients

Manufacturer makes no specific dosage recommendations.

Cautions for Sarilumab

Contraindications

• Known hypersensitivity to sarilumab or any ingredient in the formulation.

Warnings/Precautions

Warnings

Infectious Complications

Serious, sometimes fatal infections (including bacterial, mycobacterial, invasive fungal, viral, or other opportunistic infections) reported in patients with rheumatoid arthritis, particularly in those receiving concomitant therapy with other immunosuppressive agents (e.g., methotrexate, corticosteroids; See Boxed Warning). Opportunistic infections may include tuberculosis, cryptococcal infection, aspergillosis, candidiasis, and pneumocystosis. Infections may be disseminated.

Do not initiate sarilumab in patients with active infections, including localized infections. Consider potential risks and benefits of the drug prior to initiating therapy in patients with a history of chronic, recurring, serious, or opportunistic infections; patients with underlying conditions that may predispose them to infections; and patients who have been exposed to tuberculosis or who have resided or traveled in regions where tuberculosis or mycoses are endemic.

Closely monitor patients during treatment with sarilumab for the development of signs or symptoms of infection.

If new infection occurs during therapy, perform thorough diagnostic evaluation (appropriate for immunocompromised patient), initiate appropriate anti-infective therapy, and closely monitor patient. If serious or opportunistic infection develops, interrupt sarilumab until the infection is controlled.

Evaluate all patients for latent tuberculosis and for risk factors for tuberculosis prior to and periodically during therapy. When indicated, initiate an appropriate antimycobacterial regimen for the treatment of latent tuberculosis infection prior to sarilumab therapy. Consider initiation of antimycobacterial therapy prior to initiation of sarilumab in individuals with a history of latent or active tuberculosis in whom an adequate course of antimycobacterial treatment cannot be confirmed and in individuals with a negative test for latent tuberculosis who have risk factors for tuberculosis. Consultation with a tuberculosis specialist is recommended when deciding whether to initiate antimycobacterial therapy.

Monitor all patients, including those with a negative test for latent tuberculosis, for active tuberculosis.

Viral reactivation can occur in patients receiving immunosuppressive therapies. Herpes zoster exacerbation reported in patients receiving sarilumab. Risk of reactivation of HBV infection not known.

Other Warnings and Precautions

Hypersensitivity Reactions

Hypersensitivity reactions (e.g., injection site rash, rash, urticaria), including hypersensitivity reactions requiring treatment discontinuance, reported. Sarilumab is contraindicated in patients with known hypersensitivity to the drug.

If a hypersensitivity reaction occurs, immediately stop administration of the drug.

Hematologic Effects

Possible neutropenia or thrombocytopenia.

In clinical trials, decreases in neutrophil counts were not associated with infection, including serious infection, and decreases in platelet counts were not associated with bleeding.

Monitor neutrophil and platelet counts prior to and 4–8 weeks after initiation of therapy, then every 3 months thereafter.

Dosage adjustment, treatment interruption, or discontinuance of the drug may be necessary.

Hepatic Effects

Elevated aminotransferase concentrations may occur. In clinical trials, changes were reversible following reduction of sarilumab dosage or interruption of sarilumab therapy and were not associated with clinical evidence of hepatic injury.

Incidence and magnitude of aminotransferase elevations were increased with concomitant use of hepatotoxic drugs (e.g., methotrexate).

Monitor serum ALT and AST prior to and 4–8 weeks after initiation of therapy, then every 3 months thereafter. Monitor other liver function tests when clinically indicated.

Dosage adjustment, treatment interruption, or discontinuance of sarilumab or concomitantly administered DMARDs may be necessary. Not recommended in patients with active hepatic disease or hepatic impairment.

Effects on Serum Lipid

Increased serum concentrations of total cholesterol, triglycerides, LDL-cholesterol, and/or HDL-cholesterol reported.

Evaluate lipoprotein concentrations (total cholesterol, LDL cholesterol, HDL cholesterol and/or triglycerides) prior to initiation of sarilumab. Monitor lipoprotein concentrations 4–8 weeks after initiation of therapy and approximately every 6 months thereafter.

Manage lipid disorders as clinically appropriate.

GI Perforation

GI perforation reported, usually as a complication of diverticulitis. Risk may be increased in patients with concurrent diverticulitis or receiving concomitant therapy with NSAIAs or corticosteroids.

Promptly evaluate patients with new-onset abdominal symptoms.

Malignancies

Immunosuppressive therapy may increase risk of malignancies. Whether treatment with sarilumab affects development of malignancies remains to be determined. Malignancies reported in clinical trials.

Immunization

Do not administer live vaccines to patients receiving sarilumab.

Immunogenicity

Antibodies to sarilumab, including neutralizing antibodies, reported. Increased drug clearance reported in patients with neutralizing antibodies; however, effects of antibody development on clinical response or adverse reactions not observed.

Specific Populations

Pregnancy

Limited data in pregnant women insufficient to inform drug-associated risk for major birth defects and miscarriage. No evidence of embryotoxicity or fetal malformations in animal studies.

As pregnancy progresses, monoclonal antibodies are increasingly transported across the placenta; largest amount transferred during the third trimester. Infants exposed to sarilumab in utero may have impaired immune responses.

IL-6 is increased in cervical and myometrial tissues during parturition; sarilumab may delay parturition by interfering with cervical ripening and myometrial contractions.

Use during pregnancy only when potential benefits justify potential fetal risks.

Lactation

Not known whether sarilumab is distributed into milk or absorbed systemically following ingestion. Because IgG is distributed into human milk, sarilumab may distribute into milk. Potential effects on milk production or on breast-fed infants are unknown.

Consider benefits of breast-feeding and the importance of sarilumab to the woman as well as potential adverse effects on the breast-fed infant from the drug or underlying maternal condition.

Pediatric Use

Efficacy and safety of sarilumab for active polyarticular juvenile idiopathic arthritis established in pediatric patients weighing ≥63 kg. Efficacy and safety not established in pediatric patients with polyarticular juvenile idiopathic arthritis <2 years of age. Not approved in pediatric patients weighing <63 kg due to lack of appropriate dosage form.

Neonates and infants exposed to sarilumab in utero may have impaired immune responses; consider risks and benefits of administering live vaccines to such infants.

Geriatric Use

Geriatric patients in general may have a higher incidence of infections than younger adults. In clinical trials of sarilumab, no overall differences in safety and efficacy between geriatric and younger patients, but incidence of serious infections was increased in geriatric patients ≥65 years of age. Use sarilumab with caution in this age group.

Hepatic Impairment

Safety and efficacy not established in patients with hepatic impairment, including those with serologic evidence of HBV or HCV infection. Use in patients with active hepatic disease or hepatic impairment is not recommended.

Renal Impairment

In patients with mild to moderate renal impairment (Cl_cr 30 to <90 mL/minute), population pharmacokinetic data suggest increased exposure, but sarilumab is not expected to undergo substantial renal elimination and dosage adjustment is not necessary.

Not evaluated in patients with severe renal impairment.

Common Adverse Effects

Adverse effects (≥3%) in patients with rheumatoid arthritis: Neutropenia, increased ALT concentrations, injection site erythema, upper respiratory tract infection, urinary tract infection.

Adverse effects (≥5%) in patients with polymyalgia rheumatica: Neutropenia, leukopenia, injection site pruritus.

Adverse effects in patients with polyarticular juvenile idiopathic arthritis: Nasopharyngitis, neutropenia, upper respiratory tract infection, injection site erythema.

Drug Interactions

May alter expression of CYP isoenzymes.

Drugs Metabolized by Hepatic Microsomal Enzymes

Possible increased metabolism of drugs metabolized by CYP isoenzymes. Because IL-6 may down-regulate CYP isoenzymes, inhibition of IL-6 by sarilumab in patients with rheumatoid arthritis may restore CYP enzyme activity to higher levels. Effects on CYP enzyme activity may persist for several weeks after drug discontinuance.

Drugs metabolized by CYP isoenzymes that have a low therapeutic index and require individualized dosing: Carefully monitor therapeutic effect and serum concentrations following initiation or discontinuance of sarilumab; adjust dosage as needed.

Other CYP3A4 substrates: Caution advised when a reduction in efficacy would be undesirable.

Vaccines

Avoid live vaccines. Safety not established. Possible increased risk of infections.

Information not available regarding secondary transmission of infection from individuals receiving live vaccines to patients receiving sarilumab.

Consult current vaccination guidelines regarding interval between administration of live vaccines and initiation of immunosuppressive (e.g., sarilumab) therapy.

Specific Drugs

Sarilumab Pharmacokinetics

Absorption

Bioavailability

Following sub-Q injection, bioavailability is approximately 80%.

Following sub-Q injection every 2 weeks in patients with rheumatoid arthritis, peak serum concentrations are attained in approximately 2–4 days, steady-state concentrations are attained within 14–16 weeks, and systemic accumulation is 2- to 3-fold.

Following sub-Q injection every 2 weeks in patients with polymyalgia rheumatica, median time to steady state is estimated to be 28 weeks with an accumulation ratio of approximately 6-fold.

In patients with polyarticular juvenile idiopathic arthritis, steady state reached in 12 to 28 weeks.

Plasma Concentrations

With increase in dosage from 150 mg every 2 weeks to 200 mg every 2 weeks in patients with rheumatoid arthritis, steady-state concentrations increase by approximately 2-fold. In general, pharmacokinetic exposures were higher in patients with polymyalgia rheumatica compared to patients with rheumatoid arthritis.

Distribution

Extent

Not known whether distributed into human milk.

Elimination

Metabolism

Metabolic pathway not characterized.

Expected to be degraded into small peptides and amino acids via catabolic pathways in the same manner as endogenous IgG.

Half-life

Up to 8 days at dosage of 150 mg every 2 weeks; up to 10 days at dosage of 200 mg every 2 weeks in patients with rheumatoid arthritis.

Exhibits concentration-dependent clearance. At low sarilumab concentrations, target-mediated nonlinear clearance plays a major role in determining total drug clearance; at higher concentrations, nonlinear pathway is saturated and clearance is determined mainly by linear clearance.

Special Populations

Pharmacokinetics not formally studied in renal or hepatic impairment.

Population pharmacokinetic data indicate that age, gender, and race do not alter pharmacokinetics.

Increased clearance in patients who develop antisarilumab antibodies.

Stability

Storage

Parenteral

Injection

2–8°C. Keep in original carton and protect from light. Do not freeze.

May store at room temperatures up to 25°C in the original carton for up to 14 days if refrigeration unavailable; do not return to refrigerator after allowing drug to warm to room temperature.

Actions

• Binds specifically to both soluble and membrane-bound IL-6 receptors and inhibits IL-6-mediated signaling through these receptors, thereby resulting in a reduction in inflammatory mediator production.

• IL-6, a pleiotropic proinflammatory cytokine, is produced by various cell types (e.g., T cells, B lymphocytes, monocytes, fibroblasts, synoviocytes, endothelial cells) and has a broad spectrum of biologic activities, including involvement in T-cell activation, induction of immunoglobulin secretion, initiation of hepatic acute phase protein synthesis, stimulation of hematopoietic precursor cell proliferation and differentiation, and induction of osteoclast differentiation and activation.

• IL-6 is overexpressed in synovial tissue in patients with rheumatoid arthritis and is thought to contribute to synovial proliferation and joint destruction in patients with the disease. Elevated levels of IL-6 in serum and synovial fluid correlate with clinical and laboratory measures of disease activity in patients with rheumatoid arthritis.

Advice to Patients

• Provide a copy of the manufacturer’s patient information (medication guide and instructions for use) for sarilumab to all patients. Stress importance of patients and/or caregivers reading the patient information prior to initiation of therapy and each time the prescription is refilled.

• Instruct patients regarding proper dosage and administration of sarilumab, including the use of aseptic technique, and proper disposal of the prefilled syringes and pens if it is determined that the patient is competent to safely administer the drug.

• Risk of increased susceptibility to infection. Inform clinician immediately if any signs or symptoms suggestive of infection (e.g., fever, sweating, or chills; cough, dyspnea, or blood in phlegm; diarrhea; weight loss; burning upon urination or frequent urination; warm, red, or painful skin) develop.

• Risk of GI perforation, usually as a complication of diverticulitis and in those receiving NSAIAs or corticosteroids concomitantly. Inform a clinician immediately if severe, persistent abdominal pain occurs.

• Risk of hypersensitivity reactions. Contact a clinician prior to administering the next dose if manifestations of an allergic reaction (e.g., urticaria, rash, flushing) occur; seek immediate medical attention if manifestations of a serious allergic reaction (e.g., difficulty breathing, chest pain, feelings of faintness or dizziness, abdominal pain or vomiting, swelling of the lips, tongue, or face) occur.

• Inform clinicians of existing or contemplated concomitant therapy, including prescription (e.g., biologic DMARDs, immunizations) and OTC drugs and dietary or herbal supplements, as well as any concomitant illnesses (e.g., active infection, liver disease, diverticulitis, stomach ulcers) or any history of tuberculosis or other chronic or recurring infections.

• Stress importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.

• Inform patients of other important precautionary information.

Additional Information

The American Society of Health-System Pharmacists, Inc. represents that the information provided in the accompanying monograph was formulated with a reasonable standard of care, and in conformity with professional standards in the field. Readers are advised that decisions regarding use of drugs are complex medical decisions requiring the independent, informed decision of an appropriate health care professional, and that the information contained in the monograph is provided for informational purposes only. The manufacturer’s labeling should be consulted for more detailed information. The American Society of Health-System Pharmacists, Inc. does not endorse or recommend the use of any drug. The information contained in the monograph is not a substitute for medical care.

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

Reload page with references included

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Frequently asked questions

• What are the new drugs for rheumatoid arthritis (RA)?
• How long does it take for Kevzara to work?
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