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Sarilumab

Medically reviewed by Drugs.com. Last updated on Apr 20, 2020.

Pronunciation

(sar IL ue mab)

Index Terms

  • REGN88
  • SAR153191

Dosage Forms

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Solution Auto-injector, Subcutaneous [preservative free]:

Kevzara: 150 mg/1.14 mL (1.14 mL); 200 mg/1.14 mL (1.14 mL)

Solution Prefilled Syringe, Subcutaneous [preservative free]:

Kevzara: 150 mg/1.14 mL (1.14 mL); 200 mg/1.14 mL (1.14 mL)

Brand Names: U.S.

  • Kevzara

Pharmacologic Category

  • Antirheumatic, Disease Modifying
  • Interleukin-6 Receptor Antagonist
  • Monoclonal Antibody

Pharmacology

Sarilumab is an interleukin-6 (IL-6) receptor antagonist which binds to both soluble and membrane-bound IL-6 receptors. Endogenous IL-6 is induced by inflammatory stimuli and mediates a variety of immunological responses. IL-6 produced by synovial and endothelial cells leads to local production of IL-6 in joints affected by inflammatory processes such as rheumatoid arthritis. Inhibition of IL-6 receptors by sarilumab leads to a reduction in CRP levels.

Distribution

Vdss: 7.3 L

Excretion

Elimination is predominantly through the linear, non-saturable proteolytic pathway at high concentrations; at lower concentrations, elimination is predominately through non-linear saturable target-mediated pathway.

Time to Peak

2 to 4 days

Half-Life Elimination

Concentration dependent:

200 mg every 2 weeks: Up to 10 days

150 mg every 2 weeks: Up to 8 days

Special Populations Note

There was a trend toward higher apparent clearance of sarilumab in the presence of anti-sarilumab antibodies.

Use: Labeled Indications

Rheumatoid arthritis: Treatment of moderate to severe active rheumatoid arthritis in adults who have had an inadequate response or intolerance to one or more disease-modifying antirheumatic drugs.

Contraindications

Hypersensitivity to sarilumab or any component of the formulation

Dosing: Adult

Note: Do not initiate if ANC is <2,000/mm3, platelets are <150,000/mm3, or if ALT or AST are >1.5 times ULN.

Rheumatoid arthritis: SubQ: 200 mg once every 2 weeks. Note: May use as monotherapy or in combination with nonbiologic disease-modifying antirheumatic drugs (DMARDs). Do not use in combination with biologic DMARDs.

Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.

Dosing: Geriatric

Refer to adult dosing.

Dosing: Adjustment for Toxicity

Hematologic toxicity:

ANC >1,000/mm3: No dosage adjustment necessary.

ANC 500 to 1,000/mm3: Interrupt therapy; when ANC >1,000/mm3, resume at 150 mg once every 2 weeks (may increase to 200 mg once every 2 weeks as clinically appropriate).

ANC <500/mm3: Discontinue.

Platelets 50,000 to 100,000/mm3: Interrupt therapy; when platelet count is >100,000/mm3, resume at 150 mg once every 2 weeks (may increase to 200 mg once every 2 weeks as clinically appropriate).

Platelets <50,000/mm3: If confirmed by repeat testing, discontinue.

Nonhematologic toxicity:

Hypersensitivity (anaphylaxis or other clinically significant hypersensitivity reaction): Stop immediately and discontinue permanently.

Infection (serious): Interrupt treatment until the infection is controlled.

Administration

SubQ: Administer subcutaneously. Rotate injection sites; may inject into the thigh, abdomen (avoiding the 2-inch area around the navel), or outer area of upper arm. Allow prefilled syringe and prefilled pen to sit at room temperature for 30 or 60 minutes, respectively, prior to use; do not warm in any other way. Solution should be clear and colorless to pale yellow; do not shake. Administer the full amount in the prefilled syringe or prefilled pen; do not administer if window on pen is solid yellow (indicates pen has been used). Do not inject into skin that is tender, damaged, or has bruises or scars.

Storage

Store at 2°C to 8°C (36°F to 46°F) in original carton to protect from light. Do not freeze or shake. May store at ≤25°C (77°F) for ≤14 days. Do not store at >25°C (77°F). After removal from the refrigerator, use within 14 days or discard.

Drug Interactions

BCG (Intravesical): Immunosuppressants may diminish the therapeutic effect of BCG (Intravesical). Avoid combination

Belimumab: May enhance the immunosuppressive effect of Biologic Disease-Modifying Antirheumatic Drugs (DMARDs). Avoid combination

Biologic Disease-Modifying Antirheumatic Drugs (DMARDs): May enhance the immunosuppressive effect of other Biologic Disease-Modifying Antirheumatic Drugs (DMARDs). Avoid combination

Cladribine: May enhance the immunosuppressive effect of Immunosuppressants. Avoid combination

Coccidioides immitis Skin Test: Immunosuppressants may diminish the diagnostic effect of Coccidioides immitis Skin Test. Monitor therapy

CYP3A4 Substrates (High risk with Inducers): Sarilumab may decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Monitor therapy

Denosumab: May enhance the adverse/toxic effect of Immunosuppressants. Specifically, the risk for serious infections may be increased. Monitor therapy

Echinacea: May diminish the therapeutic effect of Immunosuppressants. Management: Consider avoiding Echinacea in patients receiving therapeutic immunosuppressants. If coadministered, monitor for reduced efficacy of the immunosuppressant during concomitant use. Consider therapy modification

Fingolimod: Immunosuppressants may enhance the immunosuppressive effect of Fingolimod. Management: Avoid the concomitant use of fingolimod and other immunosuppressants when possible. If combined, monitor patients closely for additive immunosuppressant effects (eg, infections). Consider therapy modification

Inebilizumab: May enhance the immunosuppressive effect of Immunosuppressants. Monitor therapy

Leflunomide: Immunosuppressants may enhance the adverse/toxic effect of Leflunomide. Specifically, the risk for hematologic toxicity such as pancytopenia, agranulocytosis, and/or thrombocytopenia may be increased. Management: Consider not using a leflunomide loading dose in patients receiving other immunosuppressants. Patients receiving both leflunomide and another immunosuppressant should be monitored for bone marrow suppression at least monthly. Consider therapy modification

Natalizumab: Immunosuppressants may enhance the adverse/toxic effect of Natalizumab. Specifically, the risk of concurrent infection may be increased. Avoid combination

Nivolumab: Immunosuppressants may diminish the therapeutic effect of Nivolumab. Management: Avoid use of immunosuppressants (including systemic corticosteroids) prior to initiation of nivolumab. Use of immunosuppressants after administration of nivolumab (eg, for immune-related toxicity) is unlikely to affect nivolumab efficacy. Consider therapy modification

Ocrelizumab: May enhance the immunosuppressive effect of Immunosuppressants. Monitor therapy

Ozanimod: Immunosuppressants may enhance the immunosuppressive effect of Ozanimod. Monitor therapy

Pidotimod: Immunosuppressants may diminish the therapeutic effect of Pidotimod. Monitor therapy

Pimecrolimus: May enhance the adverse/toxic effect of Immunosuppressants. Avoid combination

Roflumilast: May enhance the immunosuppressive effect of Immunosuppressants. Management: Consider avoiding concomitant use of roflumilast and immunosuppressants as recommended by the Canadian product monograph. Inhaled or short-term corticosteroids are unlikely to be problematic. Consider therapy modification

Siponimod: Immunosuppressants may enhance the immunosuppressive effect of Siponimod. Monitor therapy

Sipuleucel-T: Immunosuppressants may diminish the therapeutic effect of Sipuleucel-T. Management: Evaluate patients to see if it is medically appropriate to reduce or discontinue therapy with immunosuppressants prior to initiating sipuleucel-T therapy. Consider therapy modification

Smallpox and Monkeypox Vaccine (Live): Immunosuppressants may diminish the therapeutic effect of Smallpox and Monkeypox Vaccine (Live). Monitor therapy

Tacrolimus (Topical): May enhance the adverse/toxic effect of Immunosuppressants. Avoid combination

Talimogene Laherparepvec: Immunosuppressants may enhance the adverse/toxic effect of Talimogene Laherparepvec. Specifically, the risk for disseminated herpetic infection may be increased. Avoid combination

Tertomotide: Immunosuppressants may diminish the therapeutic effect of Tertomotide. Monitor therapy

Vaccines (Inactivated): Immunosuppressants may diminish the therapeutic effect of Vaccines (Inactivated). Management: Complete all age-appropriate vaccinations at least 2 weeks prior to starting an immunosuppressant. If vaccinated less than 2 weeks before starting or during immunosuppressant therapy, revaccinate at least 3 months after immunosuppressant discontinuation. Consider therapy modification

Vaccines (Live): Immunosuppressants may enhance the adverse/toxic effect of Vaccines (Live). Immunosuppressants may diminish the therapeutic effect of Vaccines (Live). Management: Avoid use of live organism vaccines with immunosuppressants; live-attenuated vaccines should not be given for at least 3 months after immunosuppressants. Avoid combination

Adverse Reactions

The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified.

Incidence as reported for combination therapy unless otherwise noted. Combination therapy refers to use in rheumatoid arthritis with nonbiological disease-modifying antirheumatic drugs.

>10%: Hepatic: Increased serum alanine aminotransferase (≤3 X ULN: 5% to 43%), increased serum aspartate aminotransferase (≤3 X ULN: 30%)

1% to 10%:

Dermatologic: Injection site pruritus (2%)

Endocrine & metabolic: Hypertriglyceridemia (1%)

Gastrointestinal: Oral herpes simplex infection (<2%)

Genitourinary: Urinary tract infection (3%)

Hematologic & oncologic: Decreased platelet count (1%), leukopenia (2%), neutropenia (10%)

Immunologic: Antibody development (monotherapy) (9%; neutralizing: 7%)

Local: Erythema at injection site (4%), injection site reaction (7%)

Respiratory: Nasopharyngitis (≤4%), upper respiratory tract infection (3%)

<1%:

Gastrointestinal: Gastrointestinal perforation

Hypersensitivity: Hypersensitivity reaction

Frequency not defined:

Dermatologic: Cellulitis

Endocrine & metabolic: Increased HDL cholesterol, increased LDL cholesterol

Hematologic & oncologic: Malignant neoplasm

Respiratory: Pneumonia

Postmarketing:

Infection: Candidiasis, opportunistic infection, serious infection

Respiratory: Infection due to an organism in genus Pneumocystis, tuberculosis

ALERT: U.S. Boxed Warning

Risk of serious infections:

Patients treated with sarilumab are at increased risk for developing serious infections that may lead to hospitalization or death. Opportunistic infections have also been reported in patients receiving sarilumab. Most patients who developed infections were taking concomitant immunosuppressants such as methotrexate or corticosteroids.

Avoid use of sarilumab 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 sarilumab use and during therapy. Treatment for latent infection should be initiated prior to sarilumab 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 sarilumab. If a serious infection develops, interrupt sarilumab until the infection is controlled.

Consider the risks and benefits of treatment with sarilumab prior to initiating therapy in patients with chronic or recurrent infection.

Warnings/Precautions

Concerns related to adverse effects:

• GI perforation: Has been reported, typically secondary to diverticulitis or concomitant use of NSAIDs or corticosteroid therapy. Monitor for new-onset abdominal symptoms.

• Hematologic effects: Neutropenia and thrombocytopenia may occur; may require treatment interruption, dose modification, or discontinuation. Monitor neutrophils and platelets. Do not initiate treatment in patients with an ANC <2,000/mm3 or platelet count <150,000/mm3; discontinue treatment for ANC <500/mm3 or platelet count <50,000/mm3.

• Hepatotoxicity: Sarilumab is associated with transaminase elevations; monitor liver function tests prior to therapy initiation and during treatment. Do not initiate treatment in patients who have ALT or AST >1.5 x ULN; discontinue treatment for ALT >5 x ULN. Transaminase elevations are typically reversible and generally do not result in clinically evident hepatic injury; patients receiving concomitant hepatotoxic drugs (eg, methotrexate) are at an increased risk of developing elevated transaminases.

• Hyperlipidemia: Therapy is associated with increases in triglycerides, LDL, and/or HDL; monitor lipids approximately 4 to 8 weeks after initiation, then approximately every 6 months.

• Hypersensitivity reactions: Hypersensitivity reactions such as injection-site rash, rash, and urticaria have been reported. Patients should seek medical attention if symptoms of hypersensitivity reaction occur. Stop administration immediately in patients who develop anaphylaxis or other hypersensitivity reaction to sarilumab.

• Infection: [US Boxed Warning]: Serious and potentially fatal infections (including active tuberculosis, invasive fungal, bacterial, viral, and other opportunistic infections) have been reported in patients receiving sarilumab. Most of the serious infections have occurred in patients on concomitant immunosuppressive therapy. Closely monitor patients for signs/symptoms of infection during treatment. If serious infection develops, withhold sarilumab until infection is controlled. Prior to treatment initiation, carefully consider risk versus benefit in patients with chronic or recurrent infections, tuberculosis exposure, history of or current opportunistic infection, underlying conditions predisposing to infection, or patients residing in or with travel to areas of endemic tuberculosis or endemic mycosis. The most common serious infections occurring have included pneumonia and cellulitis; opportunistic infections reported have included tuberculosis, candidiasis, and pneumocystis. Patients may present with disseminated infection. Do not administer sarilumab to a patient with an active infection, including localized infection.

• Malignancy: Use of sarilumab may increase malignancy risk; impact on the development and course of malignancies is not fully defined; however, malignancies were observed in clinical trials.

• Tuberculosis: [US Boxed Warning]: Tuberculosis (TB) (pulmonary or extrapulmonary) has been reported in patients receiving sarilumab; both reactivation of latent infection and new infections have been reported. Evaluate patients for TB risk factors and test for latent infection prior to initiating treatment. Treat patients with latent TB before initiating sarilumab; consider anti-TB therapy prior to initiation of sarilumab in patients with a history of latent or active TB if adequate course of treatment cannot be confirmed, and for patients with risk factors for TB despite a negative test. Some patients who test negative prior to therapy may develop active infection; monitor for signs and symptoms of TB during and after treatment in all patients.

• Viral reactivation: Viral reactivation has been observed with immunosuppressive biologic therapy. Herpes zoster has been reported in patients receiving sarilumab. The risk for hepatitis B reactivation with sarilumab therapy is unknown; monitor for signs/symptoms of viral reactivation.

Disease-related concerns:

• Hepatic impairment: Use is not recommended in patients with active hepatic disease or hepatic impairment.

Special populations:

• Elderly: Infection has been reported at a higher incidence in elderly patients compared with younger adults; use with caution in elderly patients.

Other warnings/precautions:

• Immunizations: Patients should be up to date with all immunizations before initiating sarilumab therapy. Avoid concurrent use of live vaccines. No data is available concerning secondary transmission of infection from patients receiving live vaccines to patients receiving sarilumab.

Monitoring Parameters

Latent TB screening prior to therapy initiation; neutrophils, platelets, ALT/AST (prior to therapy, 4 to 8 weeks after start of therapy, and every 3 months thereafter); additional liver function tests (eg, bilirubin) as clinically indicated; lipid panel (4 to 8 weeks following initiation and approximately every 6 months during therapy); signs/symptoms of infection (prior to, during, and after therapy), hypersensitivity reaction, and GI perforation.

Reproductive Considerations

The effectiveness of oral contraceptives may be decreased during therapy and for several weeks after sarilumab is discontinued.

Pregnancy Considerations

Sarilumab is a humanized monoclonal antibody (IgG1). Potential placental transfer of human IgG is dependent upon the IgG subclass and gestational age, generally increasing as pregnancy progresses. The lowest exposure would be expected during the period of organogenesis (Palmeira 2012; Pentsuk 2009).

Based on animal data and the mechanism of action, maternal use of sarilumab may delay parturition.

Immune response in infants exposed to sarilumab in utero may be affected. Consider risks/benefits prior to administering live or live-attenuated vaccines to infants exposed to sarilumab during pregnancy.

A pregnancy registry has been established to monitor outcomes of women exposed to sarilumab during pregnancy. Health care providers or pregnant patients are encouraged to register (877-311-8972).

Patient Education

What is this drug used for?

• It is used to treat rheumatoid arthritis.

• It may be given to you for other reasons. Talk with the doctor.

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:

• Injection site irritation

• Common cold symptoms

• Nose irritation

• Throat irritation

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:

• Urinary tract infection like blood in the urine, burning or painful urination, passing a lot of urine, fever, lower abdominal pain, or pelvic pain

• Weight loss

• Diarrhea

• Severe loss of strength and energy

• Bruising

• Bleeding

• Infection

• Abdominal pain

• Vomiting blood

• Black, tarry, or bloody stools

• Shortness of breath

• Chest pain

• Dizziness

• Passing out

• Skin sores

• Sweating a lot

• Muscle pain

• Muscle weakness

• 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, swallowing, or talking; unusual hoarseness; or swelling of the mouth, face, lips, tongue, or throat.

Note: This is not a comprehensive list of all side effects. Talk to your doctor if you have questions.

Consumer Information Use and Disclaimer: This information should not be used to decide whether or not to take this medicine or any other medicine. Only the healthcare provider has the knowledge and training to decide which medicines are right for a specific patient. This information does not endorse any medicine as safe, effective, or approved for treating any patient or health condition. This is only a limited summary of general information about the medicine's uses from the patient education leaflet and is not intended to be comprehensive. This limited summary does NOT include all information available about the possible uses, directions, warnings, precautions, interactions, adverse effects, or risks that may apply to this medicine. This information is not intended to provide medical advice, diagnosis or treatment and does not replace information you receive from the healthcare provider. For a more detailed summary of information about the risks and benefits of using this medicine, please speak with your healthcare provider and review the entire patient education leaflet.

Further information

Always consult your healthcare provider to ensure the information displayed on this page applies to your personal circumstances.

Frequently Asked Questions