Version May 2024
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.
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.
COVID-19, hospitalized patients (off-label use) (alternative agent): Note: Use as an alternative to IV tocilizumab for hospitalized patients with significant oxygen requirements (eg, high-flow oxygen, noninvasive ventilation, mechanical ventilation, extracorporeal membrane oxygenation) and for those with lower but increasing oxygen requirements and evidence of systemic inflammation (eg, C-reactive protein ≥75 mg/L) (Ref).
IV (off-label route): 400 mg once, as part of an appropriate combination regimen (Ref).
Polymyalgia rheumatica: Note: For use as adjunctive therapy with a tapering course of systemic corticosteroids or as monotherapy following discontinuation of corticosteroids.
SUBQ: 200 mg once every 2 weeks.
Rheumatoid arthritis: Note: For use as adjunctive therapy in patients who have not met treatment goals despite maximally tolerated methotrexate therapy; may also be used off label as an alternative to methotrexate in disease-modifying antirheumatic drug (DMARD)-naive patients with moderate to high disease activity (Ref). May be used in combination with nonbiologic DMARDs.
SUBQ: 200 mg once every 2 weeks.
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
CrCl 30 to 90 mL/minute: No dosage adjustment necessary.
CrCl <30 mL/minute: There are no dosage adjustments provided in the manufacturer's labeling (has not been studied).
Hepatic impairment prior to treatment initiation: There are no dosage adjustments provided in the manufacturer's labeling (has not been studied). Sarilumab is not recommended for use in patients with active hepatic disease or hepatic impairment.
Hepatotoxicity during treatment:
Polymyalgia rheumatica:
ALT or AST >3 × ULN: Discontinue sarilumab.
Rheumatoid arthritis:
ALT or AST >1 to ≤3 × ULN: Adjust concomitant DMARDs as appropriate.
ALT or AST >3 to ≤5 × ULN: Interrupt therapy; when ALT or AST is <3 × ULN, resume at 150 mg once every 2 weeks (may increase to 200 mg once every 2 weeks as clinically appropriate).
ALT or AST >5 × ULN: Discontinue sarilumab.
Hematologic toxicity:
Polymyalgia rheumatica:
ANC <1,000/mm3: Discontinue sarilumab.
Platelets <100,000/mm3: Discontinue sarilumab.
Rheumatoid arthritis:
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 sarilumab.
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 sarilumab.
Nonhematologic toxicity:
Hypersensitivity (anaphylaxis or other clinically significant hypersensitivity reaction): Stop immediately and discontinue sarilumab permanently.
Infection (serious or opportunistic): Interrupt treatment until the infection is controlled.
Refer to adult dosing.
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 in adults.
>10%: Hepatic: Increased serum alanine aminotransferase (≤3 x ULN: 5% to 43%), increased serum aspartate aminotransferase (≤3 x ULN: 30%)
1% to 10%:
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: Injection-site reaction (7%; including erythema at injection site [4%] and injection-site pruritus [2%])
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
Hypersensitivity to sarilumab or any component of the formulation
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 tuberculosis [TB] disease [active TB], 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, TB exposure, history of or current opportunistic infection, underlying conditions predisposing to infection, or patients residing in or with travel to areas of endemic TB or endemic mycosis. The most common serious infections occurring have included pneumonia and cellulitis; opportunistic infections reported have included TB, 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 TB infection (latent TB) and new infections have been reported. Evaluate patients for TB risk factors and test for TB infection prior to initiating treatment. Treat patients with TB infection before initiating sarilumab; consider anti-TB therapy prior to initiation of sarilumab in patients with a history of TB infection or disease (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:
• Older adult: 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.
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)
No
Solution Auto-injector (Kevzara Subcutaneous)
150MG/1.14ML (per mL): $2,285.85
200MG/1.14ML (per mL): $2,285.85
Solution Prefilled Syringe (Kevzara Subcutaneous)
150MG/1.14ML (per mL): $2,285.85
200MG/1.14ML (per mL): $2,285.85
Disclaimer: A representative AWP (Average Wholesale Price) price or price range is provided as reference price only. A range is provided when more than one manufacturer's AWP price is available and uses the low and high price reported by the manufacturers to determine the range. The pricing data should be used for benchmarking purposes only, and as such should not be used alone to set or adjudicate any prices for reimbursement or purchasing functions or considered to be an exact price for a single product and/or manufacturer. Medi-Span expressly disclaims all warranties of any kind or nature, whether express or implied, and assumes no liability with respect to accuracy of price or price range data published in its solutions. In no event shall Medi-Span be liable for special, indirect, incidental, or consequential damages arising from use of price or price range data. Pricing data is updated monthly.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product
Solution Auto-injector, Subcutaneous:
Kevzara: 150 mg/1.14 mL (1.14 mL); 200 mg/1.14 mL (1.14 mL)
Solution Prefilled Syringe, Subcutaneous:
Kevzara: 150 mg/1.14 mL ([DSC]); 200 mg/1.14 mL (1.14 mL)
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.
IV (off-label route): Using SUBQ formulation, dilute in 100 mL NS and administer over 1 hour (Ref).
An FDA-approved patient medication guide, which is available with the product information and as follows, must be dispensed with this medication:
Kevzara https://www.accessdata.fda.gov/drugsatfda_docs/label/2023/761037s013lbl.pdf#page=31
Polymyalgia rheumatica: Treatment of polymyalgia rheumatica in adults who have had an inadequate response to corticosteroids or who cannot tolerate a corticosteroid taper.
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.
COVID-19, hospitalized patients
Sarilumab may be confused with adalimumab, certolizumab pegol, golimumab, siltuximab, tocilizumab.
None known.
Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the Lexicomp drug interactions program by clicking on the “Launch drug interactions program” link above.
Abrocitinib: May enhance the immunosuppressive effect of Immunosuppressants (Therapeutic Immunosuppressant Agents). Risk X: Avoid combination
Anifrolumab: Biologic Disease-Modifying Antirheumatic Drugs (DMARDs) may enhance the immunosuppressive effect of Anifrolumab. Risk X: Avoid combination
Antithymocyte Globulin (Equine): Immunosuppressants (Therapeutic Immunosuppressant Agents) may enhance the adverse/toxic effect of Antithymocyte Globulin (Equine). Specifically, these effects may be unmasked if the dose of immunosuppressive therapy is reduced. Immunosuppressants (Therapeutic Immunosuppressant Agents) may enhance the immunosuppressive effect of Antithymocyte Globulin (Equine). Specifically, infections may occur with greater severity and/or atypical presentations. Risk C: Monitor therapy
Baricitinib: Immunosuppressants (Therapeutic Immunosuppressant Agents) may enhance the immunosuppressive effect of Baricitinib. Risk X: Avoid combination
BCG Products: Immunosuppressants (Therapeutic Immunosuppressant Agents) may enhance the adverse/toxic effect of BCG Products. Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Therapeutic Immunosuppressant Agents) may diminish the therapeutic effect of BCG Products. Risk X: Avoid combination
Belimumab: May enhance the immunosuppressive effect of Biologic Disease-Modifying Antirheumatic Drugs (DMARDs). Management: Consider alternatives to the use of belimumab with other biologic therapies. Monitor closely for increased toxicities related to additive immunosuppression (ie, infection, malignancy) if combined. Risk D: Consider therapy modification
Biologic Disease-Modifying Antirheumatic Drugs (DMARDs): May enhance the immunosuppressive effect of other Biologic Disease-Modifying Antirheumatic Drugs (DMARDs). Risk X: Avoid combination
Brincidofovir: Immunosuppressants (Therapeutic Immunosuppressant Agents) may diminish the therapeutic effect of Brincidofovir. Risk C: Monitor therapy
Brivudine: May enhance the adverse/toxic effect of Immunosuppressants (Therapeutic Immunosuppressant Agents). Risk X: Avoid combination
Chikungunya Vaccine (Live): Immunosuppressants (Therapeutic Immunosuppressant Agents) may enhance the adverse/toxic effect of Chikungunya Vaccine (Live). Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Therapeutic Immunosuppressant Agents) may diminish the therapeutic effect of Chikungunya Vaccine (Live). Risk X: Avoid combination
Cladribine: Immunosuppressants (Therapeutic Immunosuppressant Agents) may enhance the immunosuppressive effect of Cladribine. Risk X: Avoid combination
Coccidioides immitis Skin Test: Immunosuppressants (Therapeutic Immunosuppressant Agents) may diminish the diagnostic effect of Coccidioides immitis Skin Test. Management: Consider discontinuing therapeutic immunosuppressants several weeks prior to coccidioides immitis skin antigen testing to increase the likelihood of accurate diagnostic results. Risk D: Consider therapy modification
COVID-19 Vaccine (Adenovirus Vector): Immunosuppressants (Therapeutic Immunosuppressant Agents) may diminish the therapeutic effect of COVID-19 Vaccine (Adenovirus Vector). Management: Administer a 2nd dose using an mRNA COVID-19 vaccine (at least 4 weeks after the primary vaccine dose) and a bivalent booster dose (at least 2 months after the additional mRNA dose or any other boosters). Risk D: Consider therapy modification
COVID-19 Vaccine (Inactivated Virus): Immunosuppressants (Therapeutic Immunosuppressant Agents) may diminish the therapeutic effect of COVID-19 Vaccine (Inactivated Virus). Risk C: Monitor therapy
COVID-19 Vaccine (mRNA): Immunosuppressants (Therapeutic Immunosuppressant Agents) may diminish the therapeutic effect of COVID-19 Vaccine (mRNA). Management: Give a 3-dose primary series for all patients aged 6 months and older taking immunosuppressive medications or therapies. Booster doses are recommended for certain age groups. See CDC guidance for details. Risk D: Consider therapy modification
COVID-19 Vaccine (Subunit): Immunosuppressants (Therapeutic Immunosuppressant Agents) may diminish the therapeutic effect of COVID-19 Vaccine (Subunit). Risk C: Monitor therapy
COVID-19 Vaccine (Virus-like Particles): Immunosuppressants (Therapeutic Immunosuppressant Agents) may diminish the therapeutic effect of COVID-19 Vaccine (Virus-like Particles). Risk C: Monitor therapy
CycloSPORINE (Systemic): Interleukin-6 (IL-6) Inhibiting Therapies may decrease the serum concentration of CycloSPORINE (Systemic). Risk C: Monitor therapy
CYP Substrates (Narrow Therapeutic Index/Sensitive with Inducers): Interleukin-6 (IL-6) Inhibiting Therapies may decrease the serum concentration of CYP Substrates (Narrow Therapeutic Index/Sensitive with Inducers). Risk C: Monitor therapy
CYP2C9 Substrates (Narrow Therapeutic Index/Sensitive with Inducers): Interleukin-6 (IL-6) Inhibiting Therapies may decrease the serum concentration of CYP2C9 Substrates (Narrow Therapeutic Index/Sensitive with Inducers). Risk C: Monitor therapy
CYP3A4 Substrates (Narrow Therapeutic Index/Sensitive with Inducers): Interleukin-6 (IL-6) Inhibiting Therapies may decrease the serum concentration of CYP3A4 Substrates (Narrow Therapeutic Index/Sensitive with Inducers). Risk C: Monitor therapy
Dengue Tetravalent Vaccine (Live): Immunosuppressants (Therapeutic Immunosuppressant Agents) may enhance the adverse/toxic effect of Dengue Tetravalent Vaccine (Live). Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Therapeutic Immunosuppressant Agents) may diminish the therapeutic effect of Dengue Tetravalent Vaccine (Live). Risk X: Avoid combination
Denosumab: Immunosuppressants (Therapeutic Immunosuppressant Agents) may enhance the immunosuppressive effect of Denosumab. Management: Consider the risk of serious infections versus the potential benefits of coadministration of denosumab and immunosuppressants. If combined, monitor for signs/symptoms of serious infections. Risk D: Consider therapy modification
Deucravacitinib: May enhance the immunosuppressive effect of Immunosuppressants (Therapeutic Immunosuppressant Agents). Risk X: Avoid combination
Efgartigimod Alfa: May diminish the therapeutic effect of Fc Receptor-Binding Agents. Risk C: Monitor therapy
Etrasimod: May enhance the immunosuppressive effect of Immunosuppressants (Therapeutic Immunosuppressant Agents). Risk X: Avoid combination
Filgotinib: May enhance the immunosuppressive effect of Immunosuppressants (Therapeutic Immunosuppressant Agents). Risk X: Avoid combination
HMG-CoA Reductase Inhibitors (Statins): Interleukin-6 (IL-6) Inhibiting Therapies may decrease the serum concentration of HMG-CoA Reductase Inhibitors (Statins). Risk C: Monitor therapy
Inebilizumab: Immunosuppressants (Therapeutic Immunosuppressant Agents) may enhance the immunosuppressive effect of Inebilizumab. Risk C: Monitor therapy
Influenza Virus Vaccines: Immunosuppressants (Therapeutic Immunosuppressant Agents) may diminish the therapeutic effect of Influenza Virus Vaccines. Management: Administer influenza vaccines at least 2 weeks prior to initiating immunosuppressants if possible. If vaccination occurs less than 2 weeks prior to or during therapy, revaccinate 2 to 3 months after therapy discontinued if immune competence restored. Risk D: Consider therapy modification
Leflunomide: Immunosuppressants (Therapeutic Immunosuppressant Agents) may enhance the immunosuppressive effect of Leflunomide. Management: Increase the frequency of chronic monitoring of platelet, white blood cell count, and hemoglobin or hematocrit to monthly, instead of every 6 to 8 weeks, if leflunomide is coadministered with immunosuppressive agents. Risk D: Consider therapy modification
Mumps- Rubella- or Varicella-Containing Live Vaccines: Immunosuppressants (Therapeutic Immunosuppressant Agents) may enhance the adverse/toxic effect of Mumps- Rubella- or Varicella-Containing Live Vaccines. Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Therapeutic Immunosuppressant Agents) may diminish the therapeutic effect of Mumps- Rubella- or Varicella-Containing Live Vaccines. Risk X: Avoid combination
Nadofaragene Firadenovec: Immunosuppressants (Therapeutic Immunosuppressant Agents) may enhance the adverse/toxic effect of Nadofaragene Firadenovec. Specifically, the risk of disseminated adenovirus infection may be increased. Risk X: Avoid combination
Natalizumab: Immunosuppressants (Therapeutic Immunosuppressant Agents) may enhance the immunosuppressive effect of Natalizumab. Risk X: Avoid combination
Ocrelizumab: Immunosuppressants (Therapeutic Immunosuppressant Agents) may enhance the immunosuppressive effect of Ocrelizumab. Risk C: Monitor therapy
Ofatumumab: Immunosuppressants (Therapeutic Immunosuppressant Agents) may enhance the immunosuppressive effect of Ofatumumab. Risk C: Monitor therapy
Pidotimod: Immunosuppressants (Therapeutic Immunosuppressant Agents) may diminish the therapeutic effect of Pidotimod. Risk C: Monitor therapy
Pimecrolimus: Immunosuppressants (Therapeutic Immunosuppressant Agents) may enhance the immunosuppressive effect of Pimecrolimus. Risk X: Avoid combination
Pneumococcal Vaccines: Immunosuppressants (Therapeutic Immunosuppressant Agents) may diminish the therapeutic effect of Pneumococcal Vaccines. Risk C: Monitor therapy
Poliovirus Vaccine (Live/Trivalent/Oral): Immunosuppressants (Therapeutic Immunosuppressant Agents) may enhance the adverse/toxic effect of Poliovirus Vaccine (Live/Trivalent/Oral). Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Therapeutic Immunosuppressant Agents) may diminish the therapeutic effect of Poliovirus Vaccine (Live/Trivalent/Oral). Risk X: Avoid combination
Polymethylmethacrylate: Immunosuppressants (Therapeutic Immunosuppressant Agents) may enhance the potential for allergic or hypersensitivity reactions to Polymethylmethacrylate. Management: Use caution when considering use of bovine collagen-containing implants such as the polymethylmethacrylate-based Bellafill brand implant in patients who are receiving immunosuppressants. Consider use of additional skin tests prior to administration. Risk D: Consider therapy modification
Rabies Vaccine: Immunosuppressants (Therapeutic Immunosuppressant Agents) may diminish the therapeutic effect of Rabies Vaccine. Management: Complete rabies vaccination at least 2 weeks before initiation of immunosuppressant therapy if possible. If combined, check for rabies antibody titers, and if vaccination is for post exposure prophylaxis, administer a 5th dose of the vaccine. Risk D: Consider therapy modification
Ritlecitinib: Immunosuppressants (Therapeutic Immunosuppressant Agents) may enhance the immunosuppressive effect of Ritlecitinib. Risk X: Avoid combination
Rozanolixizumab: May diminish the therapeutic effect of Fc Receptor-Binding Agents. Risk C: Monitor therapy
Ruxolitinib (Topical): Immunosuppressants (Therapeutic Immunosuppressant Agents) may enhance the immunosuppressive effect of Ruxolitinib (Topical). Risk X: Avoid combination
Sipuleucel-T: Immunosuppressants (Therapeutic Immunosuppressant Agents) may diminish the therapeutic effect of Sipuleucel-T. Management: Consider reducing the dose or discontinuing the use of immunosuppressants prior to initiating sipuleucel-T therapy. Risk D: Consider therapy modification
Sphingosine 1-Phosphate (S1P) Receptor Modulator: May enhance the immunosuppressive effect of Immunosuppressants (Therapeutic Immunosuppressant Agents). Risk C: Monitor therapy
Tacrolimus (Topical): Immunosuppressants (Therapeutic Immunosuppressant Agents) may enhance the immunosuppressive effect of Tacrolimus (Topical). Risk X: Avoid combination
Talimogene Laherparepvec: Immunosuppressants (Therapeutic Immunosuppressant Agents) may enhance the adverse/toxic effect of Talimogene Laherparepvec. Specifically, the risk of infection from the live, attenuated herpes simplex virus contained in talimogene laherparepvec may be increased. Risk X: Avoid combination
Tertomotide: Immunosuppressants (Therapeutic Immunosuppressant Agents) may diminish the therapeutic effect of Tertomotide. Risk X: Avoid combination
Theophylline: Interleukin-6 (IL-6) Inhibiting Therapies may decrease the serum concentration of Theophylline. Risk C: Monitor therapy
Tofacitinib: Immunosuppressants (Therapeutic Immunosuppressant Agents) may enhance the immunosuppressive effect of Tofacitinib. Management: Coadministration of tofacitinib with potent immunosuppressants is not recommended. Use with non-biologic disease-modifying antirheumatic drugs (DMARDs) was permitted in psoriatic arthritis clinical trials. Risk X: Avoid combination
Typhoid Vaccine: Immunosuppressants (Therapeutic Immunosuppressant Agents) may enhance the adverse/toxic effect of Typhoid Vaccine. Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Therapeutic Immunosuppressant Agents) may diminish the therapeutic effect of Typhoid Vaccine. Risk X: Avoid combination
Ublituximab: Immunosuppressants (Therapeutic Immunosuppressant Agents) may enhance the immunosuppressive effect of Ublituximab. Risk C: Monitor therapy
Upadacitinib: Immunosuppressants (Therapeutic Immunosuppressant Agents) may enhance the immunosuppressive effect of Upadacitinib. Risk X: Avoid combination
Vaccines (Inactivated/Non-Replicating): Immunosuppressants (Therapeutic Immunosuppressant Agents) may diminish the therapeutic effect of Vaccines (Inactivated/Non-Replicating). Management: Give inactivated vaccines at least 2 weeks prior to initiation of immunosuppressants when possible. Patients vaccinated less than 14 days before initiating or during therapy should be revaccinated at least 2 to 3 months after therapy is complete. Risk D: Consider therapy modification
Vaccines (Live): Immunosuppressants (Therapeutic Immunosuppressant Agents) may enhance the adverse/toxic effect of Vaccines (Live). Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Therapeutic Immunosuppressant Agents) may diminish the therapeutic effect of Vaccines (Live). Risk X: Avoid combination
Yellow Fever Vaccine: Immunosuppressants (Therapeutic Immunosuppressant Agents) may enhance the adverse/toxic effect of Yellow Fever Vaccine. Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Therapeutic Immunosuppressant Agents) may diminish the therapeutic effect of Yellow Fever Vaccine. Risk X: Avoid combination
The effectiveness of oral contraceptives may be decreased during therapy and for several weeks after sarilumab is discontinued.
Sarilumab is a humanized monoclonal antibody (IgG1). Human IgG crosses the placenta. Fetal exposure is dependent upon the IgG subclass, maternal serum concentrations, placental integrity, newborn birth weight, and GA, generally increasing as pregnancy progresses. The lowest exposure would be expected during the period of organogenesis and the highest during the third trimester (Clements 2020; Palmeira 2012; Pentsuk 2009).
Based on animal data and the mechanism of action, maternal use of sarilumab may delay parturition. Outcome data following use of sarilumab for rheumatoid arthritis during pregnancy are limited (Dernoncourt 2023; Mizutani 2022).
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.
Sarilumab is currently under study for the treatment of COVID-19. The risk of severe morbidity and mortality from COVID-19 infection is increased in symptomatic pregnant patients compared to nonpregnant patients. Pregnant and recently pregnant patients with moderate or severe infection are at increased risk of complications such as hypertensive disorders of pregnancy, postpartum hemorrhage, or other infections compared to pregnant patients without COVID-19. Symptomatic pregnant patients may require ICU admission, mechanical ventilation, or ventilatory support (ECMO). Other adverse pregnancy outcomes include preterm birth and stillbirth. The risk of coagulopathy, cesarean delivery, and maternal death may be increased; neonates have an increased risk for NICU admission. Maternal age and comorbidities such as diabetes, hypertension, lung disease, and obesity may also increase the risk of severe illness in pregnant and recently pregnant patients (ACOG 2023; NIH 2022)
In general, the treatment of COVID-19 infection during pregnancy is the same as in nonpregnant patients. However, because data for most therapeutic agents in pregnant patients are limited, treatment options should be evaluated as part of a shared decision-making process. Data are insufficient to make recommendations for use of sarilumab in pregnant patients (NIH 2022). Information related to the treatment of COVID-19 during pregnancy continues to emerge; refer to current guidelines for the treatment of pregnant patients.
Sarilumab is present in breast milk (Saito 2023).
Sarilumab is a humanized monoclonal antibody (IgG1). Human IgG is present in breast milk; concentrations are dependent upon IgG subclass and postpartum age (Anderson 2021).
Outcome data following use of sarilumab for rheumatoid arthritis in a breastfeeding patient are limited (Mizutani 2022). According to the manufacturer, the decision to breastfeed during therapy should consider the risk of infant exposure, the benefits of breastfeeding to the infant, and the benefits of treatment to the mother.
Breast milk has not been found to be a source of COVID-19 infection and maternal infection is not a contraindication to breastfeeding. The decision to breastfeed during treatment for COVID-19 should be evaluated as part of a shared decision-making process. However, lactating patients with COVID-19 infection can transmit the virus through respiratory droplets and all precautions should be taken to avoid spreading the virus to the infant (eg, hand hygiene, mask wearing); alternatively, breast milk can be expressed and fed to the infant by someone without confirmed or suspected COVID-19 (ACOG 2023; NIH 2022).
Information related to COVID-19 and breastfeeding is available from the World Health Organization (https://www.who.int/news/item/28-04-2020-new-faqs-address-healthcare-workers-questions-on-breastfeeding-and-covid-19).
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.
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
Half-life elimination: Concentration dependent:
200 mg every 2 weeks: Up to 10 days
150 mg every 2 weeks: Up to 8 days
Time to peak: 2 to 4 days
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.
There was a trend toward higher apparent clearance of sarilumab in the presence of anti-sarilumab antibodies.
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