sarilumab (Rx)

Brand and Other Names:Kevzara
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Dosing & Uses

AdultPediatric

Dosage Forms & Strengths

solution for injection (prefilled syringe)

  • 150mg/1.14mL
  • 200mg/1.14mL

Rheumatoid Arthritis

Indicated for adults with moderately to severely active rheumatoid arthritis (RA) who have had an inadequate response or intolerance to ≥1 disease-modifying antirheumatic drugs (DMARDs)

200 mg SC q2wk

Dosage Modifications

Serious infection: Hold dose until infection is controlled

ANC

  • >1000 cells/mm³: Maintain current dose
  • 500-1000 cells/mm³: Hold treatment until ANC >1000; resume at 150 mg q2wk and increase to 200 mg q2wk as clinically appropriate
  • <500 cells/mm³: Discontinue

Platelets

  • 50,000-100,000 cells/mm³: Hold treatment until platelets >100,000; resume at 150 mg q2wk and increase to 200 mg q2wk as clinically appropriate
  • <50,000 cells/mm³: If confirmed by repeat testing, discontinue

ALT

  • ALT >ULN to ≤3 x ULN: Consider dosage modification of concomitant DMARDs as clinically appropriate
  • ALT 3-5 x ULN: Hold treatment until ALT <3 x ULN; resume at 150 mg q2wk and increase to 200 mg q2wk as clinically appropriate
  • ALT >5 x ULN: Discontinue

Renal impairment

  • Mild-to-moderate: No dose adjustment required
  • Severe: Not studied

Hepatic impairment

  • Not studied

Dosing Considerations

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

Initiation not recommended with ANC <2000/mm³, platelets <150,000/mm³, or ALT or AST >1.5 x ULN

Test for latent tuberculosis (TB) before initiating; if positive, consider treating for TB before using sarilumab

Avoid coadministering with DMARDs because of increased risk for immunosuppression and infection

Avoid with active infections

Also see Black Box Warnings

Safety and efficacy not established

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Interactions

Interaction Checker

and sarilumab

No Results

     activity indicator 
    No Interactions Found
    Interactions Found

    Contraindicated

      Serious - Use Alternative

        Significant - Monitor Closely

          Minor

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            Adverse Effects

            >10%

            ALT >ULN to ≤3 x ULN (38-43%)

            AST >ULN to ≤3 x ULN (27-30%)

            1-10%

            Injection site reaction (7%)

            ANC <1000 cells/³ (4-6%)

            Upper respiratory tract infection (3-4%)

            Urinary tract infection (3%)

            Hypertriglyceridemia (1-3%)

            Leukopenia (0.9-2%)

            <1%

            Hypersensitivity reactions

            ANC <500 cells/³

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            Warnings

            Black Box Warnings

            Serious infections

            • Use of sarilumab increases risk for developing serious infections that may lead to hospitalization or death
            • Opportunistic infections reported
            • Most patients who developed infections were taking concomitant immunosuppressants (eg, methotrexate, corticosteroids)
            • Avoid use in patients with active infection
            • Closely monitor for signs and symptoms of infection during treatment; if a serious infection develops, interrupt sarilumab therapy until the infection is controlled
            • Consider the risks and benefits of using sarilumab before initiating in patients with chronic or recurrent infection; a history of opportunistic infections, underlying conditions, in addition to RA, that may predispose them to infection, have been exposed to tuberculosis, or lived in or traveled to areas of endemic tuberculosis or endemic mycoses
            • Reported infections include
              • Active tuberculosis, which may present with pulmonary or extrapulmonary disease; test for latent TB before and during therapy; treatment for latent infection should be initiated before sarilumab is started; 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
              • Invasive fungal infections (eg, candidiasis, pneumocystis); patients with invasive fungal infections may present with disseminated, rather than localized, disease
              • Bacterial, viral, and other infections due to opportunistic pathogens

            Contraindications

            Documented hypersensitivity to drug or inactive ingredients

            Cautions

            Serious and sometimes fatal infections due to bacterial, mycobacterial, invasive fungal, viral, or other opportunistic pathogens have been reported (see Black Box Warnings)

            GI perforations 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

            Immunosuppression may result in an increased risk of malignancies

            Hypersensitivity reactions reported

            Not recommended with active hepatic disease or hepatic impairment

            Laboratory abnormalities

            • Neutropenia, thrombocytopenia, elevated liver enzymes, and lipid abnormalities reported (see Dosage Modifications)
            • Assess platelet count prior to initiation of therapy and monitor platelets 4 to 8 weeks after start of therapy and every 3 months thereafter
            • Assess ALT/AST levels prior to initiation of therapy and monitor ALT and 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
            • Assess lipid parameters approximately 4-8 weeks following initiation of therapy, then at approximately 6-month intervals; manage patients according to clinical guidelines for the management of hyperlipidemia

            Drug interaction overview

            • Live virus vaccines
              • Avoid concurrent use of live virus vaccines, owing to potentially increased risk of infections
              • The interval between live vaccinations and initiation of sarilumab therapy should be in accordance with current vaccination guidelines regarding immunosuppressive agents
            • CYP450 substrates
              • The formation of CYP450 enzymes can be altered by increased levels of certain cytokines (eg, IL-1, IL-6, IL-10, TNF-alpha, IFN) during chronic inflammation
              • Elevated IL-6 concentration may down-regulate CYP activity, such as in patients with RA, and, hence, increase drug levels compared with subjects without RA
              • Blockade of IL-6 signaling by IL-6 antagonists (eg, sarilumab) might reverse the inhibitory effect of IL-6 and restore CYP activity, leading to decreased drug concentrations
              • Caution when initiating or discontinuing sarilumab if coadministered with CYP450 substrates, especially those with a narrow therapeutic index
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            Pregnancy

            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.

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            Pharmacology

            Mechanism of Action

            Human monoclonal antibody that binds to both soluble and membrane-bound IL-6 receptors (sIL-6R and mIL-6R), and has been shown to inhibit IL-6-mediated signaling through these receptors

            IL-6 is produced by synovial and endothelial cells leading to local production of IL-6 in joints affected by inflammatory processes (eg, rheumatoid arthritis)

            IL-6 is a pleiotropic proinflammatory cytokine produced by a variety of cell types including T- and B-cells, lymphocytes, monocytes, and fibroblasts

            IL-6 has been shown to be involved in diverse physiological processes (eg, T-cell activation, induction of immunoglobulin secretion, initiation of hepatic acute-phase protein synthesis, and stimulation of hematopoietic precursor cell proliferation and differentiation

            Absorption

            Peak plasma time: 2-4 days

            Peak plasma concentration: 20 mg/L

            Minimum plasma concentration: 6.35 mg/L

            AUC: 202 mg·day/L

            Steady state: Reached in 14-16 weeks

            Distribution

            Vd: 7.2 L

            Metabolism

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

            Elimination

            Half-life: 10 days (200 mg q2wk); 8 days (150 mg q2wk)

            Excretion: Monoclonal antibodies are not eliminated via renal or hepatic pathways

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            Administration

            SC Preparation

            Allow the prefilled syringe to sit at room temperature for 30 minutes prior to SC injection; do not warm in any other way

            Visually inspect syringe for particulate matter and discoloration prior to administration

            Solution should be clear and colorless to pale yellow; do not use if the solution is cloudy, discolored, or contains particles, or if any part of the prefilled syringe appears to be damaged

            SC Administration

            Patient may self-inject or the patient's caregiver may administer after properly instructed

            Instruct patients to inject the full amount in the syringe (1.14 mL), which provides 200 mg or 150 mg

            Rotate injection sites with each injection; do not inject into skin that is tender, damaged, or has bruises or scars

            Storage

            Refrigerate at 36-46°F (2-8°C) in original carton to protect from light

            Do not freeze

            Do not shake

            If needed, may store 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 within 14 days or discard

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            Formulary

            FormularyPatient Discounts

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            The above information is provided for general informational and educational purposes only. Individual plans may vary and formulary information changes. Contact the applicable plan provider for the most current information.

            Tier Description
            1 This drug is available at the lowest co-pay. Most commonly, these are generic drugs.
            2 This drug is available at a middle level co-pay. Most commonly, these are "preferred" (on formulary) brand drugs.
            3 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs.
            4 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
            5 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
            6 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
            NC NOT COVERED – Drugs that are not covered by the plan.
            Code Definition
            PA Prior Authorization
            Drugs that require prior authorization. This restriction requires that specific clinical criteria be met prior to the approval of the prescription.
            QL Quantity Limits
            Drugs that have quantity limits associated with each prescription. This restriction typically limits the quantity of the drug that will be covered.
            ST Step Therapy
            Drugs that have step therapy associated with each prescription. This restriction typically requires that certain criteria be met prior to approval for the prescription.
            OR Other Restrictions
            Drugs that have restrictions other than prior authorization, quantity limits, and step therapy associated with each prescription.
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