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Oct.11.2023

Sarilumab

Indications/Dosage

Labeled

  • polymyalgia rheumatica
  • rheumatoid arthritis

Off-Label

  • coronavirus disease 2019 (COVID-19)
  • severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection
† Off-label indication

INVESTIGATIONAL USE: For the treatment of coronavirus disease 2019 (COVID-19)†, due to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection†, in certain hospitalized patients who are receiving systemic corticosteroids and require supplemental oxygen, including high-flow oxygen, noninvasive or invasive mechanical ventilation, or extracorporeal membrane oxygenation (ECMO)

Intravenous dosage

Adults

The National Institutes of Health (NIH) COVID-19 treatment guidelines recommend a single 400 mg IV dose in combination with dexamethasone (with or without remdesivir) to treat hospitalized adults requiring supplemental oxygen, IF the patient is exhibiting signs of systemic inflammation and rapidly increasing oxygen needs while on dexamethasone. Further, sarilumab may be given with dexamethasone to treat patients on high-flow oxygen, noninvasive ventilation, mechanical ventilation, or ECMO. Sarilumab is to be used as an alternative when other immunomodulators are not available or not feasible to administer.[65314]

For the treatment of moderately to severely active rheumatoid arthritis in persons who have had an inadequate response or intolerance to disease modifying antirheumatic drugs

Subcutaneous dosage

Adults

200 mg subcutaneously every 2 weeks as monotherapy or in combination with methotrexate or other conventional DMARDs (cDMARDs). Do not use with other biological DMARDs because of the possibility of increased immunosuppression and increased risk of infection; such combinations have not been studied.[61976]

For the treatment of polymyalgia rheumatica (PMR) in patients who have had an inadequate response to corticosteroid therapy or who cannot tolerate corticosteroid taper

Subcutaneous dosage

Adults

200 mg subcutaneously every 2 weeks. May use as monotherapy following discontinuation of corticosteroid therapy or in combination with a tapering course of systemic corticosteroids. Do not use with other biological DMARDs because of the possibility of increased immunosuppression and increased risk of infection; such combinations have not been studied.[61976]

Therapeutic Drug Monitoring

Prior to initiation of treatment

Check the patient's complete blood count (CBC), liver function tests (LFTs, including ALT/AST concentrations), and serum lipid profile. Test for active and latent tuberculosis (TB) and evaluate for any other active infection. Initiation of treatment is NOT recommended for patients with an absolute neutrophile count (ANC) less than 2,000/mm3, a platelet count less than 150,000/mm3, an ALT or AST greater than 1.5-times the upper limit of normal (ULN), or an active infection (including active TB).[61976]

 

During treatment

Monitor ANC, platelet count, and LFTs 4 to 8 weeks after treatment initiation and then every 3 months during therapy. Monitor serum lipid profile 4 to 8 weeks after starting treatment and then approximately every 6 months during therapy.[61976]

 

Dosage modifications in patients with rheumatoid arthritis (RA) for neutropenia, thrombocytopenia, elevated liver enzymes, or infection

ANC 500 to 1,000/mm3: Hold treatment and when ANC more than 1,000 cells/mm3, restart with 150 mg subcutaneously every 2 weeks; increase to 200 mg subcutaneously every 2 weeks as clinically appropriate.

ANC less than 500/mm3: Discontinue treatment.

Platelet count 50,000 to 100,000/mm3: Hold treatment and when platelet count is more than 100,000/mm3, restart with 150 mg subcutaneously every 2 weeks; increase to 200 mg subcutaneously every 2 weeks as clinically appropriate.

Platelet count less than 50,000/mm3: Repeat test; discontinue treatment if confirmed.

ALT or AST 3-times ULN or less: Consider dosage modification of concomitant DMARDs as clinically appropriate.

ALT or AST 3 to 5-times ULN: Hold treatment and when ALT/AST less than 3-times ULN, restart with 150 mg subcutaneously every 2 weeks; increase to 200 mg subcutaneously every 2 weeks as clinically appropriate.

ALT or AST more than 5-times ULN: Discontinue treatment.

Serous or opportunistic infection: Hold treatment until the infection is controlled.[61976]

 

Dosage modifications in patients with polymyalgia rheumatica (PMR) for neutropenia, thrombocytopenia, elevated liver enzymes, or infection

ANC less than 1,000/mm3 at the end of the dosing interval: Discontinue treatment.

Platelet count less than 100,000/mm3: Discontinue treatment.

ALT or AST 3-times ULN or higher: Discontinue treatment.

Serous or opportunistic infection: Hold treatment until the infection is controlled.[61976]

Maximum Dosage Limits

  • Adults

    200 mg per dose subcutaneously; investigational doses of 400 mg IV have been used for COVID-19.

  • Geriatric

    200 mg per dose subcutaneously; investigational doses of 400 mg IV have been used for COVID-19.

  • Adolescents

    Safety and efficacy have not been established.

  • Children

    Safety and efficacy have not been established.

  • Infants

    Safety and efficacy have not been established.

  • Neonates

    Safety and efficacy have not been established.

Patients with Hepatic Impairment Dosing

Prior to treatment initiation: Do not initiate treatment with sarilumab if baseline AST or ALT is more than 1.5-times the upper limit of normal (ULN).

 

-Hepatic enzyme elevations occurring during treatment for rheumatoid arthritis (RA):

AST or ALT up to 3-times the ULN: Dose modify concomitant DMARDs, if appropriate.

AST or ALT 3- to 5-times the ULN: Interrupt sarilumab dosing until AST/ALT is less than 3 times the ULN. Then, resume sarilumab at 150 mg subcutaneously every 2 weeks, and then increase to 200 mg subcutaneously every 2 weeks as clinically appropriate.

AST or ALT more than 5-times the ULN: Discontinue sarilumab.

 

-Hepatic enzyme elevations occurring during treatment for polymyalgia rheumatica (PMR):

AST or ALT 3-times ULN or more: Discontinue sarilumab.[61976]

Patients with Renal Impairment Dosing

CrCl 30 mL/minute or more: No dosage adjustment needed.

CrCl less than 30 mL/minute: Sarilumab has not been studied in patients with severe renal impairment.[61976]

† Off-label indication
Revision Date: 10/11/2023, 03:34:46 PM

References

61976 - Kevzara (sarilumab) package insert. Bridgewater, NJ: Sanofi-Aventis US. LLC; 2023 Feb.65314 - COVID-19 Treatment Guidelines Panel. Coronavirus Disease 2019 (COVID-19) Treatment Guidelines. Accessed December 26, 2023. Available at https://www.covid19treatmentguidelines.nih.gov/

How Supplied

Sarilumab Solution for injection

KEVZARA 150mg/1.14mL Pre-Filled Pen Solution for Injection (00024-5920) (Sanofi U.S. LLC) null

Sarilumab Solution for injection

KEVZARA 150mg/1.14mL Prefilled Syringe Solution for Injection (00024-5908) (Sanofi U.S. LLC) null

Sarilumab Solution for injection

KEVZARA 200mg/1.14mL Pre-Filled Pen Solution for Injection (00024-5922) (Sanofi U.S. LLC) nullKEVZARA 200mg/1.14mL Pre-Filled Pen Solution for Injection package photo

Sarilumab Solution for injection

KEVZARA 200mg/1.14mL Prefilled Syringe Solution for Injection (00024-5910) (Sanofi U.S. LLC) nullKEVZARA 200mg/1.14mL Prefilled Syringe Solution for Injection package photo

Description/Classification

Description

Sarilumab is an injectable interleukin-6 (IL-6) receptor antagonist. It is indicated for the treatment of adults with moderate to severe rheumatoid arthritis (RA) who have had an inadequate response or intolerance to 1 or more disease-modifying antirheumatic drugs (DMARDs). Sarilumab is also approved to treat adults with polymyalgia rheumatica (PMR) who have had an inadequate response to corticosteroids or who cannot tolerate corticosteroid taper. Prior to initiating treatment, obtain a complete blood count (CBC), liver function test (LFT), and serum lipid profile. Additionally, evaluate the patient for tuberculosis (active and latent infections) and any other active infection. The prescribing label contains a Boxed Warning regarding an increased risk for developing serious infections with sarilumab use.[61976]

 

Updates for coronavirus disease 2019 (COVID-19):

According to the National Institutes of Health (NIH) COVID-19 treatment guidelines, sarilumab may be used as an alternative to other immunomodulators for the treatment of COVID-19 in hospitalized patients:

  • on conventional oxygen who are exhibiting signs of systemic inflammation and rapidly increasing oxygen needs while on dexamethasone
  • on high-flow oxygen, noninvasive or invasive mechanical ventilation, or extracorporeal membrane oxygenation (ECMO)

Sarilumab must be given in combination with dexamethasone (with or without remdesivir), and is only recommended for use when other immunomodulators are unavailable or cannot be administered. For the treatment of COVID-19, sarilumab must be administered as an intravenous infusion; the dose is obtained by diluting the commercially available subcutaneous formulation with 0.9% Sodium Chloride for Injection.[65314]

Classifications

  • Antineoplastic and Immunomodulating Agents
    • Agents that Suppress the Immune System
      • Interleukin-6 (IL-6) Inhibitors
  • Musculo-Skeletal System
    • Antiinflammatory Agents and Antirheumatic Agents
      • Specific Anti-Rheumatic Agents
        • Anti-Rheumatic Monoclonal Antibodies
Revision Date: 10/13/2023, 10:38:10 AM

References

61976 - Kevzara (sarilumab) package insert. Bridgewater, NJ: Sanofi-Aventis US. LLC; 2023 Feb.65314 - COVID-19 Treatment Guidelines Panel. Coronavirus Disease 2019 (COVID-19) Treatment Guidelines. Accessed December 26, 2023. Available at https://www.covid19treatmentguidelines.nih.gov/

Administration Information

General Administration Information

For storage information, see the specific product information within the How Supplied section.

Route-Specific Administration

Injectable Administration

  • Available only as a subcutaneous formulation.
  • Visually inspect parenteral products for particulate matter and discoloration prior to administration whenever solution and container permit. The injection solution should be clear and colorless to pale yellow. Do not use the injection if it is cloudy, discolored or contains particles, or if any part of the prefilled syringe or prefilled pen appears to be damaged.[61976]

Intravenous Administration

COVID-19 per the National Institutes of Health (NIH) treatment guidelines:

NOTE: Sarilumab is not approved by the FDA for intravenous administration.

  • Obtain a 400 mg dose using the prefilled syringes for subcutaneous injection. DO NOT use the prefilled pens.
  • Using aseptic technique, dilute the 400 mg dose in 100 mL of 0.9% Sodium Chloride for Injection.
  • Administer the diluted solution via intravenous infusion over 1 hour.
  • Storage: The diluted solution should be administered within 4 hours of preparation. The infusion may be stored at room temperature until administered.[65314]

Subcutaneous Administration

  • The injection may be given by the patient or patient's caregiver after proper training in subcutaneous injection technique and a healthcare practitioner determines that it is appropriate.

 

Prefilled Syringe:

  • Remove the prefilled syringe from the refrigerator and allow it to sit at room temperature outside of the carton for 30 minutes. Do not warm sarilumab in any other way.
  • Do not uncap the needle until ready to inject. Do not get rid of any air bubbles in the syringe.
  • Pick an injection site such as the front of a thigh or the abdomen except for the 2-inch area around the navel. If a caregiver or healthcare professional will administer, they can also use the patient's outer area of an upper arm. Do not inject into skin that is tender, damaged, or has bruises or scars.
  • Rotate injection sites with each injection.
  • Remove the needle cap immediately before injection, and gently pinch a cleaned area of skin between the thumb and index finger. Using a dart-like motion, insert the needle at a 45-degree angle. Gently push the plunger all the way down to inject the full amount in the prefilled syringe.
  • Check that the syringe is empty and then pull the needle out at the same angle it was inserted. Do not rub the injection site.
  • Dispose of the used syringe in an FDA-cleared sharps disposal container right away after use. Do not recap after use. Do not re-use the syringe.
  • Storage: The prefilled syringes should be stored in the refrigerator in the original container to protect sarilumab from light. The prefilled syringes may be stored in the carton at room temperature up to 25 degrees C (77 degrees F) for up to 14 days. Dispose of any prefilled syringes left at room temperature for more than 14 days.[61976]

 

Prefilled Pen:

  • Remove the prefilled pen from the refrigerator and allow it to sit at room temperature outside of the carton for 60 minutes. Do not warm sarilumab in any other way.
  • Do not remove the orange cap until ready to inject.
  • Pick an injection site such as the front of a thigh or the abdomen except for the 2-inch area around the navel. If a caregiver or healthcare professional will administer, they can also use the patient's outer area of an upper arm. Do not inject into skin that is tender, damaged, or has bruises or scars.
  • Rotate injection sites with each injection.
  • Twist or pull off the orange cap immediately before injection, and do not touch the yellow needle cover. Place the yellow needle cover on the skin at a 90-degree angle, making sure the window is visible. Press down and hold firmly against the skin. There will be an audible 'click' when the injection starts. Continue to hold the pen firmly against the skin until the entire window becomes solid yellow and the full dose is administered; the complete injection may take up to 15 seconds. There will be a second 'click' when the injection is complete.
  • Remove the pen from the skin and the needle will automatically cover. Do not rub the injection site.
  • Dispose of the used pen in an FDA-cleared sharps disposal container right away after use. Do not replace the orange cap after use. Do not re-use the pen.
  • Storage: The prefilled pens should be stored in the refrigerator in the original container to protect sarilumab from light. The prefilled pens may be stored in the carton at room temperature up to 25 degrees C (77 degrees F) in the carton for up to 14 days. Dispose of any prefilled pens left at room temperature for more than 14 days.[61976]

Clinical Pharmaceutics Information

From Trissel's 2‚Ñ¢ Clinical Pharmaceutics Database

Sarilumab

pH Range
pH is 6.0.
ReferencesKevzara (sarilumab) injection package insert. Bridgewater, NJ. Sanofi-Aventis U.S. LLC. 2023; Feb
    Revision Date: 10/20/2021, 02:34:56 PMCopyright 2004-2024 by Lawrence A. Trissel. All Rights Reserved.

    References

    61976 - Kevzara (sarilumab) package insert. Bridgewater, NJ: Sanofi-Aventis US. LLC; 2023 Feb.65314 - COVID-19 Treatment Guidelines Panel. Coronavirus Disease 2019 (COVID-19) Treatment Guidelines. Accessed December 26, 2023. Available at https://www.covid19treatmentguidelines.nih.gov/

    Adverse Reactions

    Moderate

    • antibody formation
    • candidiasis
    • constipation
    • elevated hepatic enzymes
    • erythema
    • hypercholesterolemia
    • hyperlipidemia
    • hypertriglyceridemia
    • leukopenia
    • neutropenia
    • thrombocytopenia

    Mild

    • fatigue
    • infection
    • injection site reaction
    • myalgia
    • pharyngitis
    • pruritus

    Severe

    • anaphylactoid reactions
    • GI perforation
    • new primary malignancy
    • rash
    • urticaria

    Patients treated with sarilumab are at increased risk for developing a serious infection, including bacterial or viral infections or reactivation of viral infections, that may lead to hospitalization or death. Opportunistic infections have also been reported in patients receiving sarilumab. Most patients who developed an infection were taking concomitant immunosuppressants such as methotrexate or corticosteroids. During and after treatment with sarilumab, closely monitor all patients for the development of signs and symptoms of infection including the possible development of tuberculosis (TB) in patients who tested negative for latent TB infection before sarilumab use. If a serious infection develops, interrupt sarilumab until the infection is controlled. Infections of various types have been reported during clinical trials. During the rheumatoid arthritis placebo-controlled clinical trials of sarilumab plus conventional DMARD, upper respiratory tract infections were reported in 3% and 4% of patients receiving sarilumab 200 mg and 150 mg, respectively (2% placebo). Urinary tract infections were reported in 3% of both sarilumab treatment groups (2% placebo). Naso-pharyngitis also was reported. The rate of serious infections in the 200 mg and 150 mg group was 3.8 to 4.3 and 3 to 4.4 events per 100 patient-years, respectively, compared to 2.5 to 3.1 events per 100 patient-years for placebo. Serious infections reported included pneumonia, cellulitis, and opportunistic infections. Viral reactivation has been reported with the use of immunosuppressive biologic therapies. Herpes zoster was reported in 0.8% and 0.6% of those receiving sarilumab 200 mg and 150 mg, respectively (0.5% placebo). Oral herpes simplex infection occurred in less than 2% of rheumatoid arthritis patients who received sarilumab in clinical trials. In the polymyalgia rheumatica placebo-controlled clinical trial, 3 patients who received sarilumab 200 mg discontinued treatment due to an infection (COVID-19, intervertebral discitis, and pneumonia). However, the overall infection rate was lower in sarilumab group (37.3%) than in the placebo group (50%), and the rate of serious infections was similar (5.1% vs. 5.2%). Herpes zoster was noted in 2 patients who received sarilumab (3.2%) and 1 patient in the placebo group (1.7%). No cases of hepatitis B reactivation were observed in the trials; however, patients who screened positive for hepatitis were excluded from clinical trials. Among opportunistic infections, TB (pulmonary or extrapulmonary disease), candidiasis, and Pneumocystosis infections were reported with sarilumab. Patients have presented with disseminated rather than localized disease and were often taking concomitant immunosuppressants such as methotrexate or corticosteroids. Carefully consider the risks and benefits of sarilumab in patients with chronic or recurrent infection.[61976]

    Gastrointestinal perforation has been reported during sarilumab clinical trials. Reports of GI perforation were primarily noted as complications of diverticulitis including lower GI perforation and abscesses. One patient experienced a GI perforation during sarilumab clinical trials for rheumatoid arthritis (0.11 events per 100 patient-years). In the long-term safety population, the overall rate of GI perforation was consistent with rates of the controlled periods of the studies. Most patients that developed GI perforations were taking concomitant nonsteroidal anti-inflammatory medications (NSAIDs) or corticosteroids. The contribution of these concomitant medications to the development of GI perforations is not known. In the polymyalgia rheumatica clinical trial, 6.8% of drug recipients experienced constipation.[61976]

    Sarilumab may cause neutropenia; neutrophil counts should be assessed before and during treatment. During the rheumatoid arthritis placebo-controlled clinical trials of sarilumab plus conventional DMARD, neutropenia was reported in 10% of those who received sarilumab 200 mg and 7% of those who received sarilumab 150 mg. Decreases in neutrophil counts to less than 1,000/mm3 occurred in 6% and 4% of the patients in the sarilumab 200 mg and 150 mg groups, respectively (0% placebo). Severe decreases in neutrophil counts to less than 500/mm3 were reported in 0.7% of both sarilumab treatment groups. Neutropenia was not associated with the occurrence of infections, including serious infections. In the polymyalgia rheumatica clinical trial, 15.3% of adults treated with sarilumab 200 mg developed neutropenia, and 3 patients (5.1%) required permanent treatment discontinuation because of neutropenia. Two patients (3.4%) developed neutrophil counts less than 500/mm3 without any infections. In both cases, the neutrophil counts resolved once sarilumab therapy was stopped. Leukopenia has also been reported. In the rheumatoid arthritis trial, leukopenia was reported in 0.9% of patients receiving sarilumab 150 mg and 2% of patients receiving the 200 mg dose. Leukopenia was also reported in the polymyalgia rheumatica clinical trial, occurring in 6.8% of drug recipients.[61976]

    Sarilumab may cause thrombocytopenia; platelet counts should be assessed before and during treatment. During the rheumatoid arthritis placebo-controlled clinical trials of sarilumab plus conventional DMARD, decreases in platelet counts to less than 100,000/mm3 occurred in 1% and 0.7% of those receiving sarilumab 200 mg and 150 mg, respectively (0% placebo). In the polymyalgia rheumatica clinical trial, decreases in platelet counts between 75,000 and 100,000/mm3 occurred in 2 patients (3.4%) who received sarilumab 200 mg, compared to no patient in the placebo group. Treatment-related reductions in platelet counts were not associated with bleeding events in clinical trials.[61976]

    Sarilumab is associated with elevated hepatic enzymes. Liver function tests should be assessed before and during sarilumab treatment. In those experiencing elevated liver enzymes, modification of the treatment regimen (i.e., dose reduction or interruption) usually results in a decrease or normalization of the liver enzyme. During the rheumatoid arthritis placebo-controlled clinical trials of sarilumab plus conventional DMARD, an AST greater than the upper limit of normal (ULN) to 3-times ULN or less were reported in 30% of patients receiving sarilumab 200 mg and 27% of those receiving 150 mg compared to 15% of those receiving placebo. AST elevations of more than 3-times the ULN to 5-times the ULN were reported in 1% (0% for placebo), and AST more than 5-times ULN were reported in 0.2% to 0.7% (0% for placebo) of those receiving any dose of sarilumab. Similarly, ALT more than the ULN up to 3-times ULN were reported in 43% of patients receiving sarilumab 200 mg and 38% of those receiving 150 mg vs. 25% of those receiving placebo. ALT elevations of more than 3-times the ULN to 5-times the ULN were reported in 3% to 4% of those receiving any dose of sarilumab (1% for placebo), and ALT greater than 5-times ULN were reported in 0.7% to 1% of those receiving sarilumab (0% for placebo). These increases in liver enzymes were not associated with clinically relevant increases in direct bilirubin or evidence of hepatitis or hepatic impairment. In the polymyalgia rheumatica clinical trial, no patient who received treatment with sarilumab 200 mg/dose experienced an ALT or AST greater than 3-times the ULN.[61976]

    An injection site reaction may occur with the use of sarilumab. In the rheumatoid arthritis clinical trials, injection site reactions were reported in 7% and 6% of those who received sarilumab 200 mg and sarilumab 150 mg, respectively. Injection site reactions included pruritus (2%) and erythema (4% to 5%). Mild injection site pruritis was also noted in 3 patients (5.1%) who received sarilumab 200 mg during the polymyalgia rheumatica clinical trial.[61976]

    Hypersensitivity reactions have been reported with the administration of sarilumab. In the rheumatoid arthritis clinical trials, reactions that required treatment discontinuation were reported in 0.2 to 0.3% of patients. Injection site rash, rash (unspecified), and urticaria were reported most frequently. In the polymyalgia rheumatica clinical trial, pruritic rash (5.1%) was among the most common adverse reactions. Advise patients to seek medical attention if they experience any symptoms of a hypersensitivity reaction. If anaphylactoid reactions or other hypersensitivity reaction occurs, immediately stop the administration of sarilumab.[61976]

    Sarilumab may cause hyperlipidemia, including hypercholesterolemia and hypertriglyceridemia. Lipid parameters should be assessed during sarilumab treatment. During the rheumatoid arthritis placebo-controlled trials of sarilumab plus conventional DMARD, lipid parameters were measured 4 weeks following sarilumab initiation. Among those receiving sarilumab 150 mg, the mean LDL cholesterol increased by 12 mg/dL, mean triglycerides increased by 20 mg/dL, and mean HDL increased by 3 mg/dL. Among those receiving sarilumab 200 mg, the mean LDL increased by 16 mg/dL, mean triglycerides increased by 27 mg/dL, and mean HDL increased by 3 mg/dL. In the long-term safety population, the observations in lipid parameters were consistent with what was observed in the rheumatoid arthritis trials. In the polymyalgia rheumatica clinical trial, cholesterol levels of 299.27 mg/dL or greater were observed in 8 patients (13.8%) who received sarilumab 200 mg compared to 4 patients (6.9%) in the placebo group. Triglyceride levels of at least 407.4 mg/dL were observed in 3 sarilumab patients (5.2%) and 1 placebo patient (1.7%). At treatment Week 52, mean increases from baseline for LDL and triglycerides were observed in the sarilumab group, though both remained within the normal range. There was no difference in mean HDL levels between the sarilumab and placebo.[61976]

    In the polymyalgia rheumatica clinical trial, myalgia (6.8%) and fatigue (5.1%) were among the most common adverse reactions in PMR patients who received treatment with sarilumab 200 mg.[61976]

    In rheumatoid arthritis patients treated with sarilumab monotherapy, 9.2% of patients exhibited an anti-drug antibody (ADA) response with 6.9% of patients also exhibiting neutralizing antibodies (NAbs). Prior to the administration of sarilumab, 2.3% of patients exhibited an ADA response. In the pre-rescue population, 4% of patients treated with sarilumab 200 mg plus DMARD and 5.7% of patients treated with sarilumab 150 mg plus DMARD exhibited an ADA response, compared with 1.9% of patients receiving placebo plus DMARD. Neutralizing antibodies were detected in 1% of patients on sarilumab 200 mg plus DMARD and 1.6% of patients on sarilumab 150 mg plus DMARD (versus 0.2% of patients on placebo plus DMARD). No correlation was observed between antibody formation and adverse events or loss of efficacy. In the polymyalgia rheumatica population, 1 patient (1.8%) who received sarilumab 200 mg plus 14-week corticosteroid taper exhibited an ADA response, compared with no patient in the placebo plus 52-week corticosteroid taper group. Neutralizing antibodies were detected in the sarilumab recipient, and that patient did not demonstrate a clinical response. Due to the low occurrence of ADA, the effect of these antibodies on safety and effectiveness of sarilumab is unknown.[61976]

    Sarilumab may increase the risk for a new primary malignancy. In the 52-week placebo-controlled trial, 9 malignancies (exposure-adjusted event rate of 1 event per 100 patient-years) were reported in patients receiving sarilumab and a DMARD compared to 4 malignancies (exposure-adjusted event rate of 1 event per 100 patient-years) in the control group. In the long-term safety population, the rate of malignancies was consistent with the rate observed in the placebo-controlled period.[61976]

    Revision Date: 03/03/2023, 06:01:32 PM

    References

    61976 - Kevzara (sarilumab) package insert. Bridgewater, NJ: Sanofi-Aventis US. LLC; 2023 Feb.

    Contraindications/Precautions

    Absolute contraindications are italicized.

    • breast-feeding
    • children
    • corticosteroid therapy
    • diabetes mellitus
    • diverticulitis
    • fungal infection
    • geriatric
    • GI perforation
    • hepatic disease
    • hepatitis
    • human immunodeficiency virus (HIV) infection
    • hypercholesterolemia
    • hyperlipidemia
    • hypertriglyceridemia
    • immunosuppression
    • infants
    • infection
    • influenza
    • labor
    • neonates
    • neoplastic disease
    • neutropenia
    • obstetric delivery
    • pregnancy
    • sepsis
    • thrombocytopenia
    • tuberculosis
    • vaccination

    Sarilumab is contraindicated for use in patients with known hypersensitivity to sarilumab or any of its inactive ingredients. Hypersensitivity reactions were reported in sarilumab clinical trials.[61976]

    Patients who receive sarilumab are at increased risk for developing serious infections that may lead to hospitalization or death. Infections include active tuberculosis (TB) and invasive fungal infections including candidiasis and pneumocystis. Bacterial, viral, and other infections due to opportunistic pathogens have been reported. Most patients who developed serious infections were taking concomitant immunosuppressants such as methotrexate or corticosteroids. Patients with an invasive fungal infection may present with disseminated disease, and TB may present as pulmonary or extrapulmonary disease. Evaluate patients for TB risk factors before starting sarilumab. Also, test patients for latent TB before and during sarilumab receipt. Initiate treatment for latent infection before sarilumab use. Consider anti-TB therapy prior to sarilumab initiation for 2 patient groups: patients with a past history of latent or active TB in whom an adequate course of treatment cannot be confirmed and patients with a negative test for latent TB but with risk factors for tuberculosis infection. Consultation with a physician with expertise in the treatment of TB is recommended to aid in the decision whether initiating anti-TB therapy is appropriate for an individual patient. Carefully consider the risks and benefits of sarilumab before initiating therapy in patients with chronic or recurrent infection, who have been exposed to TB, with a history of a serious or opportunistic infection, with underlying conditions that may predispose them to infection (e.g., patients with advanced or uncontrolled diabetes mellitus, human immunodeficiency virus (HIV) infection, or immunosuppression), or who have resided or traveled in areas of endemic tuberculosis or endemic mycoses. Do not start treatment with sarilumab in patients with an absolute neutrophil count (ANC) less than 2,000/mm3. For rheumatoid arthritis (RA) patients who experience reduced neutrophil counts while taking sarilumab, discontinuation is advised if the ANC drops below 500/mm3 and treatment interruption is advised for an ANC between 500 and 1,000/mm3. For polymyalgia rheumatica patients, sarilumab discontinuation is recommended if the ANC drops below 1,000/mm3 at the end of the dosing interval. Closely monitor patients for the development of signs and symptoms of infection; signs and symptoms of acute inflammation may be lessened due to suppression of the acute phase reactants. Consider the possible development of TB in patients who tested negative for latent TB infection prior to taking sarilumab. Viral reactivation has been observed during immunosuppressive biologic therapies. Do not administer sarilumab to a patient with an active infection including localized infections. If a serious infection such as sepsis or influenza or an opportunistic infection develops, interrupt sarilumab receipt until the infection is controlled. If a new infection develops during sarilumab receipt, complete a prompt and complete diagnostic workup appropriate for an immunocompromised patient, initiate appropriate antimicrobial therapy, and closely monitor the patient.[61976]

    Initiation of sarilumab therapy is not recommended in patients with thrombocytopenia defined as a platelet count less than 150,000/mm3 or for neutropenia defined as an absolute neutrophil count (ANC) below 2,000/mm3. Thrombocytopenia and neutropenia have occurred with sarilumab, and drug interruption, dose reduction, or discontinuation may be needed. Assess platelet count and ANC before sarilumab receipt, 4 to 8 weeks after sarilumab initiation, and every 3 months thereafter.[61976]

    Sarilumab is not recommended in patients with active hepatic disease or hepatic impairment. Initiation of sarilumab is not recommended in patients who have ALT or AST more than 1.5 times the upper limit of normal (ULN). Hepatic enzyme elevations observed in clinical trials with sarilumab did not result in any clinically evident hepatic injury. Elevated transaminases have been noted with sarilumab, and drug interruption, dose reduction, or discontinuation may be needed. Assess liver function tests (LFTs) before sarilumab receipt, 4 to 8 weeks after start of therapy, and every 3 months thereafter. Consider assessing other liver function tests such as bilirubin when clinically indicated. The safety and efficacy of sarilumab have not been studied in patients with hepatic impairment including patients with positive hepatitis B virus (HBV) or hepatitis C virus (HCV) serology. The risk of hepatitis B reactivation with sarilumab is unknown since patients who were at risk for reactivation were excluded from clinical trials.[61976]

    Gastrointestinal (GI) perforations have been reported in clinical studies, primarily as complications of diverticulitis. Use with caution in patients with diverticulitis. GI perforation risk may be increased with concurrent diverticulitis or concomitant use of NSAIDs or in those receiving corticosteroid therapy. Promptly evaluate patients presenting with new onset abdominal symptoms.[61976]

    Sarilumab is an immunosuppressant; therefore, sarilumab may affect host defenses against neoplastic disease. The impact of sarilumab on the development of malignancies is unknown, but malignancies were observed in clinical studies. Consider the risks and benefits of sarilumab before treatment initiation in patients with a known malignancy. Also, consider the risks and benefits of sarilumab continuation in patients who develop a malignancy.[61976]

    Cautious use of sarilumab may be warranted for patients with hyperlipidemia, hypercholesterolemia, or hypertriglyceridemia. Increased total cholesterol, increased HDL-C, increased LDL-C, and increased triglycerides may occur with sarilumab. Assess lipid parameters approximately 4 to 8 weeks after sarilumab initiation and subsequently at approximately 6 month intervals. Manage patients according to clinical guidelines [e.g., National Cholesterol Educational Program (NCEP)] for the management of hyperlipidemia.[61976]

    Live virus vaccines should not be given concurrently with sarilumab due to the potential increase in risk of infection. The safety of live virus vaccination in patients receiving sarilumab has not been established. No data exist on the secondary transmission of infection from persons receiving live vaccines to patients receiving sarilumab. The interval between live vaccinations and initiation of sarilumab should be in accordance with current vaccination guidelines regarding immunosuppressive agents.[61976]

    Limited available data are not sufficient to determine whether the use of sarilumab during human pregnancy is associated with risk for major birth defects or miscarriage. Monoclonal antibodies, like sarilumab, are increasingly transported across the placenta as pregnancy progresses, with the largest amount transferred during the third trimester. This may affect immune response in the in utero exposed infant. Concentrations of immunoglobulin G (IgG), in response to antigen challenge, may be reduced in the fetus/infant of treated mothers. Consider risks and benefits prior to administering live or live-attenuated vaccines to neonates or infants who were exposed to sarilumab in utero. In an animal reproduction study, consisting of a combined embryo-fetal and pre- and postnatal development study with monkeys that received intravenous administration of sarilumab, there was no evidence of embryotoxicity or fetal malformations with exposures up to approximately 84 times the maximum recommended human dose (MRHD). Animal data suggest sarilumab may affect labor and obstetric delivery. Inhibition of IL-6 signaling may interfere with cervical ripening and dilatation and myometrial contractile activity, leading to potential delays in parturition. For mice deficient in IL-6, parturition was delayed relative to wild-type mice without this deficiency. Administration of recombinant IL-6 to the deficient mice restored the normal timing of delivery.[61976]

    There is no information available on the presence of sarilumab in human milk or its effects on the breast-fed infant or milk production. Maternal immunoglobulin G (IgG) is present in human milk. The effects of local exposure on the gastrointestinal tract and potential limited systemic exposure to the infant are unknown. Consider the developmental and health benefits of breast-feeding along with the mother's clinical need for sarilumab and the potential adverse effects on the breast-fed infant from sarilumab or the underlying maternal condition.[61976]

    During the rheumatoid arthritis clinical trials, the rate of serious infections among geriatric adults was higher compared to that of adults less than 65 years of age. There were no overall differences in safety observed between older and younger adults in the polymyalgia rheumatica trial. Because there is a higher incidence of infections in the older adult in general, cautious use of sarilumab is advised.[61976]

    The safety and efficacy of sarilumab have not been established in pediatric patients (adolescents, children or infants).[61976]

    Revision Date: 03/02/2023, 08:49:08 AM

    References

    61976 - Kevzara (sarilumab) package insert. Bridgewater, NJ: Sanofi-Aventis US. LLC; 2023 Feb.

    Mechanism of Action

    Sarilumab binds to both soluble and membrane-bound interleukin-6 (IL-6) receptors (sIL-6R and mIL-6R), and has been shown to inhibit IL-6-mediated signaling through these receptors. IL-6 is a pleiotropic pro-inflammatory cytokine produced by a variety of cell types including T-cells and B-cells, lymphocytes, monocytes, and fibroblasts. IL-6 has been shown to be involved in diverse physiological processes such as T-cell activation, induction of immunoglobulin secretion, initiation of hepatic acute phase protein synthesis, and stimulation of hematopoietic precursor cell proliferation and differentiation. IL-6 is also produced by synovial and endothelial cells leading to local production of IL-6 in joints affected by inflammatory processes such as rheumatoid arthritis.[61976]

    Revision Date: 04/06/2020, 04:48:59 PM

    References

    61976 - Kevzara (sarilumab) package insert. Bridgewater, NJ: Sanofi-Aventis US. LLC; 2023 Feb.

    Pharmacokinetics

    Sarilumab is administered subcutaneously. The volume of distribution at steady state is 7.3 L. Sarilumab is eliminated by parallel linear and non-linear pathways. At higher concentrations, the elimination is predominately through the linear, non-saturable proteolytic pathway. At lower concentrations, non-linear saturable target-mediated elimination predominates. The half-life is concentration-dependent. At steady-state following administration of 150 mg or 200 mg subcutaneously every 2 weeks, the half-life is up to 8 or 10 days, respectively. After the last steady-state dose of 150 mg and 200 mg, the median times to non-detectable concentration are 28 and 43 days, respectively. Sarilumab is expected to be degraded into small peptides and amino acids via catabolic pathways, similar to endogenous IgG. Monoclonal antibodies are not eliminated via renal or hepatic pathways.[61976]

     

    Decreases in C-reactive protein to within normal ranges were seen as early as week 2 after single-dose administration of sarilumab 150 mg or 200 mg during trials in adult patients with rheumatoid arthritis. Treatment with sarilumab resulted in decreases in serum amyloid A and fibrinogen and increases in hemoglobin and serum albumin.[61976]

     

    Affected cytochrome P450 (CYP450) isoenzymes and drug transporters: various CYP450 isoenzymes

    The formation of CYP450 enzymes may be suppressed by increased concentrations of cytokines, such as IL-6, during chronic inflammation. Thus, it is expected that the formation of CYP450 enzymes could be normalized during sarilumab receipt leading to increased metabolism of drugs that are CYP450 substrates. Exercise caution when coadministering sarilumab with CYP3A4 substrate drugs where a decrease in effectiveness is undesirable. The effect of sarilumab on CYP450 enzyme activity may persist for several weeks after stopping the medication.[61976]

    Route-Specific Pharmacokinetics

    Subcutaneous Route

    When administered subcutaneously to rheumatoid arthritis patients, the time to maximum concentration (Tmax) was 2 to 4 days. At steady state, the exposure (AUC) increased 2-fold with an increase in dose from 150 mg to 200 mg every 2 weeks. Steady-state was reached in 14 to 16 weeks with a 2- to 3-fold accumulation compared to single-dose exposure. For the 150 mg every 2 week regimen, the estimated mean (+/- SD) steady-state AUC was 202 +/- 120 mg x day/L, the minimum concentration (Cmin) was 6.35 +/- 7.54 mg/L, and the maximal concentration (Cmax) was 20 +/- 9.2 mg/L. For the 200 mg every 2 week regimen, the estimated mean (+/- SD) steady-state AUC, Cmin, and Cmax were 395 +/- 207 mg x day/L, 16.5 +/- 14.1 mg/L, and 35.6 +/- 15.2 mg/L, respectively. Data from a population pharmacokinetic analysis of 58 patients found sarilumab exposures were generally higher in those with polymyalgia rheumatica as compared to those with rheumatoid arthritis. For the dosing regimen of 200 mg every 2 weeks, the estimated mean (+/- SD) steady-state AUC, Cmin, and Cmax in polymyalgia rheumatica patients were 551 +/- 321 mg x day/L, 27 +/-21.5 mg/L, and 46.5 +/- 23 mg/L, respectively. Accumulation was observed, with an accumulation ratio of approximately 6-fold based on the mean trough concentrations.[61976]

    Special Populations

    Renal Impairment

    Mild (CrCl 60 to 90 mL/minute) and moderate (CrCl 30 to 60 mL/minute) renal impairment does affect the exposure of sarilumab; however, the effect is not sufficient enough to warrant dose adjustment. Patients with severe renal impairment have not been studied.[61976]

    Geriatric

    Age does not affect the pharmacokinetic profile of sarilumab.[61976]

    Gender Differences

    Gender does not affect the pharmacokinetic profile of sarilumab.[61976]

    Ethnic Differences

    Race does not affect the pharmacokinetic profile of sarilumab.[61976]

    Obesity

    Although body weight influenced the pharmacokinetics of sarilumab, no dose adjustments are recommended.[61976]

    Revision Date: 03/03/2023, 05:25:20 PM

    References

    61976 - Kevzara (sarilumab) package insert. Bridgewater, NJ: Sanofi-Aventis US. LLC; 2023 Feb.

    Pregnancy/Breast-feeding

    infants, labor, neonates, obstetric delivery, pregnancy

    Limited available data are not sufficient to determine whether the use of sarilumab during human pregnancy is associated with risk for major birth defects or miscarriage. Monoclonal antibodies, like sarilumab, are increasingly transported across the placenta as pregnancy progresses, with the largest amount transferred during the third trimester. This may affect immune response in the in utero exposed infant. Concentrations of immunoglobulin G (IgG), in response to antigen challenge, may be reduced in the fetus/infant of treated mothers. Consider risks and benefits prior to administering live or live-attenuated vaccines to neonates or infants who were exposed to sarilumab in utero. In an animal reproduction study, consisting of a combined embryo-fetal and pre- and postnatal development study with monkeys that received intravenous administration of sarilumab, there was no evidence of embryotoxicity or fetal malformations with exposures up to approximately 84 times the maximum recommended human dose (MRHD). Animal data suggest sarilumab may affect labor and obstetric delivery. Inhibition of IL-6 signaling may interfere with cervical ripening and dilatation and myometrial contractile activity, leading to potential delays in parturition. For mice deficient in IL-6, parturition was delayed relative to wild-type mice without this deficiency. Administration of recombinant IL-6 to the deficient mice restored the normal timing of delivery.[61976]

    breast-feeding

    There is no information available on the presence of sarilumab in human milk or its effects on the breast-fed infant or milk production. Maternal immunoglobulin G (IgG) is present in human milk. The effects of local exposure on the gastrointestinal tract and potential limited systemic exposure to the infant are unknown. Consider the developmental and health benefits of breast-feeding along with the mother's clinical need for sarilumab and the potential adverse effects on the breast-fed infant from sarilumab or the underlying maternal condition.[61976]

    Revision Date: 03/02/2023, 08:45:40 AM

    References

    61976 - Kevzara (sarilumab) package insert. Bridgewater, NJ: Sanofi-Aventis US. LLC; 2023 Feb.

    Interactions

    Level 2 (Major)

    • Abatacept
    • Adalimumab
    • Anakinra
    • Bacillus Calmette-Guerin Vaccine, BCG
    • Baricitinib
    • Canakinumab
    • Certolizumab pegol
    • Chikungunya Vaccine, Live
    • Etanercept
    • Golimumab
    • Infliximab
    • Intranasal Influenza Vaccine
    • Live Vaccines
    • Measles Virus; Mumps Virus; Rubella Virus; Varicella Virus Vaccine, Live
    • Measles/Mumps/Rubella Vaccines, MMR
    • Ofatumumab
    • Rituximab
    • Rituximab; Hyaluronidase
    • Rotavirus Vaccine
    • Secukinumab
    • Smallpox and Monkeypox Vaccine, Live, Nonreplicating
    • Smallpox Vaccine, Vaccinia Vaccine
    • Tocilizumab
    • Tofacitinib
    • Tumor Necrosis Factor modifiers
    • Typhoid Vaccine
    • Upadacitinib
    • Ustekinumab
    • Varicella-Zoster Virus Vaccine, Live
    • Yellow Fever Vaccine, Live

    Level 3 (Moderate)

    • Alfentanil
    • Amlodipine; Atorvastatin
    • Apixaban
    • Atorvastatin
    • Carbamazepine
    • Cholera Vaccine
    • Cisapride
    • Cyclosporine
    • Dengue Tetravalent Vaccine, Live
    • Desogestrel; Ethinyl Estradiol
    • Dextromethorphan; Quinidine
    • Dienogest; Estradiol valerate
    • Drospirenone
    • Drospirenone; Estetrol
    • Drospirenone; Estradiol
    • Drospirenone; Ethinyl Estradiol
    • Drospirenone; Ethinyl Estradiol; Levomefolate
    • Elagolix; Estradiol; Norethindrone acetate
    • Estradiol; Levonorgestrel
    • Estradiol; Norethindrone
    • Estradiol; Norgestimate
    • Ethinyl Estradiol; Norelgestromin
    • Ethinyl Estradiol; Norethindrone Acetate
    • Ethinyl Estradiol; Norgestrel
    • Ethosuximide
    • Ethynodiol Diacetate; Ethinyl Estradiol
    • Etonogestrel; Ethinyl Estradiol
    • Everolimus
    • Ezetimibe; Simvastatin
    • Fentanyl
    • Fosphenytoin
    • Leuprolide; Norethindrone
    • Levonorgestrel
    • Levonorgestrel; Ethinyl Estradiol
    • Levonorgestrel; Ethinyl Estradiol; Ferrous Bisglycinate
    • Levonorgestrel; Ethinyl Estradiol; Ferrous Fumarate
    • Lovastatin
    • Norethindrone
    • Norethindrone Acetate; Ethinyl Estradiol; Ferrous fumarate
    • Norethindrone; Ethinyl Estradiol
    • Norethindrone; Ethinyl Estradiol; Ferrous fumarate
    • Norgestimate; Ethinyl Estradiol
    • Norgestrel
    • Oral Contraceptives
    • Phenytoin
    • Pimozide
    • Quinidine
    • Relugolix; Estradiol; Norethindrone acetate
    • Rivaroxaban
    • SARS-CoV-2 (COVID-19) vaccines
    • SARS-CoV-2 Virus (COVID-19) Adenovirus Vector Vaccine
    • SARS-CoV-2 Virus (COVID-19) mRNA Vaccine
    • SARS-CoV-2 Virus (COVID-19) Recombinant Spike Protein Nanoparticle Vaccine
    • Segesterone Acetate; Ethinyl Estradiol
    • Simvastatin
    • Tacrolimus
    • Theophylline, Aminophylline
    • Thioridazine
    • Tizanidine
    • Warfarin
    Abatacept: (Major) Avoid the concomitant use of sarilumab with biological DMARDs, including selective costimulation modulators such as abatacept; coadministration has not been studied and may result in additive immunosuppression and increased risk of infection. [61976] Adalimumab: (Major) Avoid the concomitant use of sarilumab with biological DMARDs, such as tumor necrosis factor (TNF) modifiers; coadministration has not been studied and may result in additive immunosuppression and increased risk of infection. [61976] Alfentanil: (Moderate) Monitor for evidence of reduced effect if alfentanil coadministration with sarilumab is necessary; alfentanil dosage adjustment may be needed. Inhibition of IL-6 signaling by sarilumab may restore CYP450 activities to higher levels leading to increased metabolism of drugs that are CYP450 substrates compared to metabolism prior to treatment. Therefore, CYP450 substrates with a narrow therapeutic index, such as alfentanil, may have fluctuations in drug levels and therapeutic effect when sarilumab therapy is started or discontinued. This effect on CYP450 enzyme activity may persist for several weeks after stopping sarilumab. In vitro, sarilumab has the potential to affect expression of multiple CYP enzymes, including CYP1A2, CYP2B6, CYP2C9, CYP2C19, CYP2D6, and CYP3A4. Alfentanil is a CYP3A4 substrate and a narrow therapeutic index drug. [61976] Amlodipine; Atorvastatin: (Moderate) Utilize caution with concomitant use of sarilumab and CYP3A4 substrate drugs, such as atorvastatin, where a decrease in effectiveness is undesirable. Monitor lipid panels and adjust therapy as indicated. Inhibition of IL-6 signaling by sarilumab may restore CYP450 activities to higher levels leading to increased metabolism of drugs that are CYP450 substrates as compared to metabolism prior to treatment. This effect on CYP450 enzyme activity may persist for several weeks after stopping sarilumab. A 45% decrease in exposure to another "statin" was noted in a drug interaction study. In vitro, sarilumab has the potential to affect expression of multiple CYP enzymes, including CYP1A2, CYP2B6, CYP2C9, CYP2C19, CYP2D6, and CYP3A4. Atorvastatin is a CYP3A4 substrate. [61976] Anakinra: (Major) Avoid using sarilumab with other biological DMARDs including interleukin-1 receptor antagonists such as anakinra; coadministration has not been studied and may result in additive immunosuppression and increased risk of infection. [61976] Apixaban: (Moderate) Monitor for a decrease in efficacy of apixaban if used with sarilumab. Until more data are available, consider using an anticoagulant without dependence on CYP450 enzymes for metabolism (e.g., heparins, edoxaban). The formation of CYP450 enzymes may be suppressed by increased concentrations of cytokines such as IL-6 during chronic inflammation. It is expected that the activity of CYP450 enzymes could increase to normal concentrations during treatment with an IL-6 antagonist such as sarilumab; these effects on CYP450 enzyme activity may persist for several weeks after stopping sarilumab. In vitro, sarilumab has the potential to affect expression of multiple CYP enzymes [including CYP1A2, CYP2B6, CYP2C9, CYP2C19, CYP2D6, and CYP3A4]. Apixaban is an in vitro substrate for CYP3A4. [52739] [61976] [65210] Atorvastatin: (Moderate) Utilize caution with concomitant use of sarilumab and CYP3A4 substrate drugs, such as atorvastatin, where a decrease in effectiveness is undesirable. Monitor lipid panels and adjust therapy as indicated. Inhibition of IL-6 signaling by sarilumab may restore CYP450 activities to higher levels leading to increased metabolism of drugs that are CYP450 substrates as compared to metabolism prior to treatment. This effect on CYP450 enzyme activity may persist for several weeks after stopping sarilumab. A 45% decrease in exposure to another "statin" was noted in a drug interaction study. In vitro, sarilumab has the potential to affect expression of multiple CYP enzymes, including CYP1A2, CYP2B6, CYP2C9, CYP2C19, CYP2D6, and CYP3A4. Atorvastatin is a CYP3A4 substrate. [61976] Bacillus Calmette-Guerin Vaccine, BCG: (Major) Avoid concurrent use of live vaccines during treatment with sarilumab due to potentially increased risk of infections; clinical safety of live vaccines during sarilumab treatment has not been established. No data are available on the secondary transmission of infection from persons receiving live vaccines to patients receiving sarilumab. The interval between live vaccinations and initiation of sarilumab therapy should be in accordance with current vaccination guidelines regarding immunosuppressive agents. [51778] [61976] Baricitinib: (Major) Avoid the concomitant use of sarilumab with other biological DMARDs such as baricitinib; coadministration has not been studied and may result in additive immunosuppression and increased risk of infection. [61976] [63229] Canakinumab: (Major) Avoid using sarilumab with other biological DMARDs including interleukin-1 receptor antagonists such as canakinumab; coadministration has not been studied and may result in additive immunosuppression and increased risk of infection. [61976] Carbamazepine: (Moderate) Monitor carbamazepine concentrations and watch for decreased efficacy of carbamazepine if coadministration with sarilumab is necessary; adjust carbamazepine dosage as necessary. Inhibition of IL-6 signaling by sarilumab may restore CYP450 activities to higher levels leading to increased metabolism of drugs that are CYP450 substrates compared to metabolism prior to treatment. Therefore, CYP450 substrates with a narrow therapeutic index, such as carbamazepine, may have fluctuations in drug levels and therapeutic effect when sarilumab therapy is started or discontinued. This effect on CYP450 enzyme activity may persist for several weeks after stopping sarilumab. In vitro, sarilumab has the potential to affect expression of multiple CYP enzymes, including CYP1A2, CYP2B6, CYP2C9, CYP2C19, CYP2D6, and CYP3A4. Carbamazepine is a substrate of both CYP1A2 and CYP3A4 and a narrow therapeutic index drug. [61976] Certolizumab pegol: (Major) Avoid the concomitant use of sarilumab with biological DMARDs, such as tumor necrosis factor (TNF) modifiers; coadministration has not been studied and may result in additive immunosuppression and increased risk of infection. [61976] Chikungunya Vaccine, Live: (Major) Avoid concurrent use of live vaccines during treatment with sarilumab due to potentially increased risk of infections; clinical safety of live vaccines during sarilumab treatment has not been established. No data are available on the secondary transmission of infection from persons receiving live vaccines to patients receiving sarilumab. The interval between live vaccinations and initiation of sarilumab therapy should be in accordance with current vaccination guidelines regarding immunosuppressive agents. [51778] [61976] Cholera Vaccine: (Moderate) Patients receiving immunosuppressant medications may have a diminished response to the live cholera vaccine. When feasible, administer indicated vaccines prior to initiating immunosuppressant medications. Counsel patients receiving immunosuppressant medications about the possibility of a diminished vaccine response and to continue to follow precautions to avoid exposure to cholera bacteria after receiving the vaccine. [60871] Cisapride: (Moderate) Monitor for decreased efficacy of cisapride if coadministration with sarilumab is necessary. Inhibition of IL-6 signaling by sarilumab may restore CYP450 activities to higher levels leading to increased metabolism of drugs that are CYP450 substrates compared to metabolism prior to treatment. Therefore, CYP450 substrates with a narrow therapeutic index, such as cisapride, may have fluctuations in drug levels and therapeutic effect when sarilumab therapy is started or discontinued. This effect on CYP450 enzyme activity may persist for several weeks after stopping sarilumab. In vitro, sarilumab has the potential to affect expression of multiple CYP enzymes, including CYP1A2, CYP2B6, CYP2C9, CYP2C19, CYP2D6, and CYP3A4. Cisapride is a CYP3A4 substrate and a narrow therapeutic index drug. [61976] Cyclosporine: (Moderate) Monitor cyclosporine levels and adjust the dose of cyclosporine as appropriate if coadministration with sarilumab is necessary. Inhibition of IL-6 signaling by sarilumab may restore CYP450 activities to higher levels leading to increased metabolism of drugs that are CYP450 substrates compared to metabolism prior to treatment. Therefore, CYP450 substrates with a narrow therapeutic index, such as cyclosporine, may have fluctuations in drug levels and therapeutic effect when sarilumab therapy is started or discontinued. This effect on CYP450 enzyme activity may persist for several weeks after stopping sarilumab. In vitro, sarilumab has the potential to affect expression of multiple CYP enzymes, including CYP1A2, CYP2B6, CYP2C9, CYP2C19, CYP2D6, and CYP3A4. Cyclosporine is a CYP3A4 substrate and a narrow therapeutic index drug. [61976] Dengue Tetravalent Vaccine, Live: (Moderate) Patients receiving immunosuppressant medications may have a diminished response to the dengue virus vaccine. When feasible, administer indicated vaccines at least 2 weeks prior to initiating immunosuppressant medications. If vaccine administration is necessary, consider revaccination following restoration of immune competence. Counsel patients receiving immunosuppressant medications about the possibility of a diminished vaccine response and to continue to follow precautions to avoid exposure after receiving the vaccine. [60092] [64100] [65107] Desogestrel; Ethinyl Estradiol: (Moderate) Utilize caution with concomitant use of sarilumab and CYP3A4 substrate drugs, such as combined hormonal oral contraceptives, where a decrease in effectiveness is undesirable. Inhibition of IL-6 signaling by sarilumab may restore CYP450 activities to higher levels leading to increased metabolism of drugs that are CYP450 substrates as compared to metabolism prior to treatment. This effect on CYP450 enzyme activity may persist for several weeks after stopping sarilumab. In vitro, sarilumab has the potential to affect expression of multiple CYP enzymes, including CYP1A2, CYP2B6, CYP2C9, CYP2C19, CYP2D6, and CYP3A4. [61976] Dextromethorphan; Quinidine: (Moderate) Monitor quinidine levels and adjust the dose of quinidine as appropriate if coadministration with sarilumab is necessary. Inhibition of IL-6 signaling by sarilumab may restore CYP450 activities to higher levels leading to increased metabolism of drugs that are CYP450 substrates compared to metabolism prior to treatment. Therefore, CYP450 substrates with a narrow therapeutic index, such as quinidine, may have fluctuations in drug levels and therapeutic effect when sarilumab therapy is started or discontinued. This effect on CYP450 enzyme activity may persist for several weeks after stopping sarilumab. In vitro, sarilumab has the potential to affect expression of multiple CYP enzymes, including CYP1A2, CYP2B6, CYP2C9, CYP2C19, CYP2D6, and CYP3A4. Quinidine is a CYP3A4 substrate and narrow therapeutic index drug. [61976] Dienogest; Estradiol valerate: (Moderate) Utilize caution with concomitant use of sarilumab and CYP3A4 substrate drugs, such as combined hormonal oral contraceptives, where a decrease in effectiveness is undesirable. Inhibition of IL-6 signaling by sarilumab may restore CYP450 activities to higher levels leading to increased metabolism of drugs that are CYP450 substrates as compared to metabolism prior to treatment. This effect on CYP450 enzyme activity may persist for several weeks after stopping sarilumab. In vitro, sarilumab has the potential to affect expression of multiple CYP enzymes, including CYP1A2, CYP2B6, CYP2C9, CYP2C19, CYP2D6, and CYP3A4. [61976] Drospirenone: (Moderate) Utilize caution with concomitant use of sarilumab and CYP3A4 substrate drugs, such as combined hormonal oral contraceptives, where a decrease in effectiveness is undesirable. Inhibition of IL-6 signaling by sarilumab may restore CYP450 activities to higher levels leading to increased metabolism of drugs that are CYP450 substrates as compared to metabolism prior to treatment. This effect on CYP450 enzyme activity may persist for several weeks after stopping sarilumab. In vitro, sarilumab has the potential to affect expression of multiple CYP enzymes, including CYP1A2, CYP2B6, CYP2C9, CYP2C19, CYP2D6, and CYP3A4. [61976] Drospirenone; Estetrol: (Moderate) Utilize caution with concomitant use of sarilumab and CYP3A4 substrate drugs, such as combined hormonal oral contraceptives, where a decrease in effectiveness is undesirable. Inhibition of IL-6 signaling by sarilumab may restore CYP450 activities to higher levels leading to increased metabolism of drugs that are CYP450 substrates as compared to metabolism prior to treatment. This effect on CYP450 enzyme activity may persist for several weeks after stopping sarilumab. In vitro, sarilumab has the potential to affect expression of multiple CYP enzymes, including CYP1A2, CYP2B6, CYP2C9, CYP2C19, CYP2D6, and CYP3A4. [61976] Drospirenone; Estradiol: (Moderate) Utilize caution with concomitant use of sarilumab and CYP3A4 substrate drugs, such as combined hormonal oral contraceptives, where a decrease in effectiveness is undesirable. Inhibition of IL-6 signaling by sarilumab may restore CYP450 activities to higher levels leading to increased metabolism of drugs that are CYP450 substrates as compared to metabolism prior to treatment. This effect on CYP450 enzyme activity may persist for several weeks after stopping sarilumab. In vitro, sarilumab has the potential to affect expression of multiple CYP enzymes, including CYP1A2, CYP2B6, CYP2C9, CYP2C19, CYP2D6, and CYP3A4. [61976] Drospirenone; Ethinyl Estradiol: (Moderate) Utilize caution with concomitant use of sarilumab and CYP3A4 substrate drugs, such as combined hormonal oral contraceptives, where a decrease in effectiveness is undesirable. Inhibition of IL-6 signaling by sarilumab may restore CYP450 activities to higher levels leading to increased metabolism of drugs that are CYP450 substrates as compared to metabolism prior to treatment. This effect on CYP450 enzyme activity may persist for several weeks after stopping sarilumab. In vitro, sarilumab has the potential to affect expression of multiple CYP enzymes, including CYP1A2, CYP2B6, CYP2C9, CYP2C19, CYP2D6, and CYP3A4. [61976] Drospirenone; Ethinyl Estradiol; Levomefolate: (Moderate) Utilize caution with concomitant use of sarilumab and CYP3A4 substrate drugs, such as combined hormonal oral contraceptives, where a decrease in effectiveness is undesirable. Inhibition of IL-6 signaling by sarilumab may restore CYP450 activities to higher levels leading to increased metabolism of drugs that are CYP450 substrates as compared to metabolism prior to treatment. This effect on CYP450 enzyme activity may persist for several weeks after stopping sarilumab. In vitro, sarilumab has the potential to affect expression of multiple CYP enzymes, including CYP1A2, CYP2B6, CYP2C9, CYP2C19, CYP2D6, and CYP3A4. [61976] Elagolix; Estradiol; Norethindrone acetate: (Moderate) Utilize caution with concomitant use of sarilumab and CYP3A4 substrate drugs, such as combined hormonal oral contraceptives, where a decrease in effectiveness is undesirable. Inhibition of IL-6 signaling by sarilumab may restore CYP450 activities to higher levels leading to increased metabolism of drugs that are CYP450 substrates as compared to metabolism prior to treatment. This effect on CYP450 enzyme activity may persist for several weeks after stopping sarilumab. In vitro, sarilumab has the potential to affect expression of multiple CYP enzymes, including CYP1A2, CYP2B6, CYP2C9, CYP2C19, CYP2D6, and CYP3A4. [61976] Estradiol; Levonorgestrel: (Moderate) Utilize caution with concomitant use of sarilumab and CYP3A4 substrate drugs, such as combined hormonal oral contraceptives, where a decrease in effectiveness is undesirable. Inhibition of IL-6 signaling by sarilumab may restore CYP450 activities to higher levels leading to increased metabolism of drugs that are CYP450 substrates as compared to metabolism prior to treatment. This effect on CYP450 enzyme activity may persist for several weeks after stopping sarilumab. In vitro, sarilumab has the potential to affect expression of multiple CYP enzymes, including CYP1A2, CYP2B6, CYP2C9, CYP2C19, CYP2D6, and CYP3A4. [61976] Estradiol; Norethindrone: (Moderate) Utilize caution with concomitant use of sarilumab and CYP3A4 substrate drugs, such as combined hormonal oral contraceptives, where a decrease in effectiveness is undesirable. Inhibition of IL-6 signaling by sarilumab may restore CYP450 activities to higher levels leading to increased metabolism of drugs that are CYP450 substrates as compared to metabolism prior to treatment. This effect on CYP450 enzyme activity may persist for several weeks after stopping sarilumab. In vitro, sarilumab has the potential to affect expression of multiple CYP enzymes, including CYP1A2, CYP2B6, CYP2C9, CYP2C19, CYP2D6, and CYP3A4. [61976] Estradiol; Norgestimate: (Moderate) Utilize caution with concomitant use of sarilumab and CYP3A4 substrate drugs, such as combined hormonal oral contraceptives, where a decrease in effectiveness is undesirable. Inhibition of IL-6 signaling by sarilumab may restore CYP450 activities to higher levels leading to increased metabolism of drugs that are CYP450 substrates as compared to metabolism prior to treatment. This effect on CYP450 enzyme activity may persist for several weeks after stopping sarilumab. In vitro, sarilumab has the potential to affect expression of multiple CYP enzymes, including CYP1A2, CYP2B6, CYP2C9, CYP2C19, CYP2D6, and CYP3A4. [61976] Etanercept: (Major) Avoid the concomitant use of sarilumab with biological DMARDs, such as tumor necrosis factor (TNF) modifiers; coadministration has not been studied and may result in additive immunosuppression and increased risk of infection. [61976] Ethinyl Estradiol; Norelgestromin: (Moderate) Utilize caution with concomitant use of sarilumab and CYP3A4 substrate drugs, such as combined hormonal oral contraceptives, where a decrease in effectiveness is undesirable. Inhibition of IL-6 signaling by sarilumab may restore CYP450 activities to higher levels leading to increased metabolism of drugs that are CYP450 substrates as compared to metabolism prior to treatment. This effect on CYP450 enzyme activity may persist for several weeks after stopping sarilumab. In vitro, sarilumab has the potential to affect expression of multiple CYP enzymes, including CYP1A2, CYP2B6, CYP2C9, CYP2C19, CYP2D6, and CYP3A4. [61976] Ethinyl Estradiol; Norethindrone Acetate: (Moderate) Utilize caution with concomitant use of sarilumab and CYP3A4 substrate drugs, such as combined hormonal oral contraceptives, where a decrease in effectiveness is undesirable. Inhibition of IL-6 signaling by sarilumab may restore CYP450 activities to higher levels leading to increased metabolism of drugs that are CYP450 substrates as compared to metabolism prior to treatment. This effect on CYP450 enzyme activity may persist for several weeks after stopping sarilumab. In vitro, sarilumab has the potential to affect expression of multiple CYP enzymes, including CYP1A2, CYP2B6, CYP2C9, CYP2C19, CYP2D6, and CYP3A4. [61976] Ethinyl Estradiol; Norgestrel: (Moderate) Utilize caution with concomitant use of sarilumab and CYP3A4 substrate drugs, such as combined hormonal oral contraceptives, where a decrease in effectiveness is undesirable. Inhibition of IL-6 signaling by sarilumab may restore CYP450 activities to higher levels leading to increased metabolism of drugs that are CYP450 substrates as compared to metabolism prior to treatment. This effect on CYP450 enzyme activity may persist for several weeks after stopping sarilumab. In vitro, sarilumab has the potential to affect expression of multiple CYP enzymes, including CYP1A2, CYP2B6, CYP2C9, CYP2C19, CYP2D6, and CYP3A4. [61976] Ethosuximide: (Moderate) Monitor for reduced efficacy of ethosuximide, monitor drug concentrations, and adjust the dose of ethosuximide as appropriate if coadministration with sarilumab is necessary. Inhibition of IL-6 signaling by sarilumab may restore CYP450 activities to higher levels leading to increased metabolism of drugs that are CYP450 substrates compared to metabolism prior to treatment. Therefore, CYP450 substrates with a narrow therapeutic index, such as ethosuximide, may have fluctuations in drug levels and therapeutic effect when sarilumab therapy is started or discontinued. This effect on CYP450 enzyme activity may persist for several weeks after stopping sarilumab. In vitro, sarilumab has the potential to affect expression of multiple CYP enzymes, including CYP1A2, CYP2B6, CYP2C9, CYP2C19, CYP2D6, and CYP3A4. Ethosuximide is a CYP3A4 substrate and narrow therapeutic index drug. [61976] Ethynodiol Diacetate; Ethinyl Estradiol: (Moderate) Utilize caution with concomitant use of sarilumab and CYP3A4 substrate drugs, such as combined hormonal oral contraceptives, where a decrease in effectiveness is undesirable. Inhibition of IL-6 signaling by sarilumab may restore CYP450 activities to higher levels leading to increased metabolism of drugs that are CYP450 substrates as compared to metabolism prior to treatment. This effect on CYP450 enzyme activity may persist for several weeks after stopping sarilumab. In vitro, sarilumab has the potential to affect expression of multiple CYP enzymes, including CYP1A2, CYP2B6, CYP2C9, CYP2C19, CYP2D6, and CYP3A4. [61976] Etonogestrel; Ethinyl Estradiol: (Moderate) Utilize caution with concomitant use of sarilumab and CYP3A4 substrate drugs, such as combined hormonal oral contraceptives, where a decrease in effectiveness is undesirable. Inhibition of IL-6 signaling by sarilumab may restore CYP450 activities to higher levels leading to increased metabolism of drugs that are CYP450 substrates as compared to metabolism prior to treatment. This effect on CYP450 enzyme activity may persist for several weeks after stopping sarilumab. In vitro, sarilumab has the potential to affect expression of multiple CYP enzymes, including CYP1A2, CYP2B6, CYP2C9, CYP2C19, CYP2D6, and CYP3A4. [61976] Everolimus: (Moderate) Monitor for clinical response in patients taking everolimus concurrently with sarilumab. For indications where therapeutic drug monitoring is appropriate, monitor everolimus trough concentrations and adjust the dose of everolimus accordingly. Inhibition of IL-6 signaling by sarilumab may restore CYP450 activities to higher levels leading to increased metabolism of drugs that are CYP450 substrates compared to metabolism prior to treatment. Therefore, CYP450 substrates with a narrow therapeutic index, such as everolimus, may have fluctuations in drug levels and therapeutic effect when sarilumab therapy is started or discontinued. This effect on CYP450 enzyme activity may persist for several weeks after stopping sarilumab. In vitro, sarilumab has the potential to affect expression of multiple CYP enzymes, including CYP1A2, CYP2B6, CYP2C9, CYP2C19, CYP2D6, and CYP3A4. Everolimus is a CYP3A4 substrate and narrow therapeutic index drug. [61976] Ezetimibe; Simvastatin: (Moderate) Utilize caution with concomitant use of sarilumab and CYP3A4 substrate drugs, such as simvastatin, where a decrease in effectiveness is undesirable. Monitor lipid panels and adjust therapy as indicated. Inhibition of IL-6 signaling by sarilumab may restore CYP450 activities to higher levels leading to increased metabolism of drugs that are CYP450 substrates as compared to metabolism prior to treatment. This effect on CYP450 enzyme activity may persist for several weeks after stopping sarilumab. A 45% decrease in simvastatin exposure was noted 1 week after a single sarilumab dose. In vitro, sarilumab has the potential to affect expression of multiple CYP enzymes, including CYP1A2, CYP2B6, CYP2C9, CYP2C19, CYP2D6, and CYP3A4. Simvastatin is a CYP3A4 substrate. [61976] Fentanyl: (Moderate) Monitor for evidence of reduced pain control or opioid withdrawal if fentanyl coadministration with sarilumab is necessary; fentanyl dosage adjustment may be needed. Inhibition of IL-6 signaling by sarilumab may restore CYP450 activities to higher levels leading to increased metabolism of drugs that are CYP450 substrates compared to metabolism prior to treatment. Therefore, CYP450 substrates with a narrow therapeutic index, such as fentanyl, may have fluctuations in drug levels and therapeutic effect when sarilumab therapy is started or discontinued. This effect on CYP450 enzyme activity may persist for several weeks after stopping sarilumab. In vitro, sarilumab has the potential to affect expression of multiple CYP enzymes, including CYP1A2, CYP2B6, CYP2C9, CYP2C19, CYP2D6, and CYP3A4. Fentanyl is a CYP3A4 substrate and narrow therapeutic index drug. [61976] Fosphenytoin: (Moderate) Monitor fosphenytoin concentrations and watch for decreased efficacy of fosphenytoin if coadministration with sarilumab is necessary; adjust fosphenytoin dosage as necessary. Inhibition of IL-6 signaling by sarilumab may restore CYP450 activities to higher levels leading to increased metabolism of drugs that are CYP450 substrates compared to metabolism prior to treatment. Therefore, CYP450 substrates with a narrow therapeutic index, such as fosphenytoin, may have fluctuations in drug levels and therapeutic effect when sarilumab therapy is started or discontinued. This effect on CYP450 enzyme activity may persist for several weeks after stopping sarilumab. In vitro, sarilumab has the potential to affect expression of multiple CYP enzymes, including CYP1A2, CYP2B6, CYP2C9, CYP2C19, CYP2D6, and CYP3A4. Fosphenytoin is a substrate of both CYP2C9 and CYP2C19 and narrow therapeutic index drug. [61976] Golimumab: (Major) Avoid the concomitant use of sarilumab with biological DMARDs, such as tumor necrosis factor (TNF) modifiers; coadministration has not been studied and may result in additive immunosuppression and increased risk of infection. [61976] Infliximab: (Major) Avoid the concomitant use of sarilumab with biological DMARDs, such as tumor necrosis factor (TNF) modifiers; coadministration has not been studied and may result in additive immunosuppression and increased risk of infection. [61976] Intranasal Influenza Vaccine: (Major) Avoid concurrent use of live vaccines during treatment with sarilumab due to potentially increased risk of infections; clinical safety of live vaccines during sarilumab treatment has not been established. No data are available on the secondary transmission of infection from persons receiving live vaccines to patients receiving sarilumab. The interval between live vaccinations and initiation of sarilumab therapy should be in accordance with current vaccination guidelines regarding immunosuppressive agents. [51778] [61976] Leuprolide; Norethindrone: (Moderate) Utilize caution with concomitant use of sarilumab and CYP3A4 substrate drugs, such as combined hormonal oral contraceptives, where a decrease in effectiveness is undesirable. Inhibition of IL-6 signaling by sarilumab may restore CYP450 activities to higher levels leading to increased metabolism of drugs that are CYP450 substrates as compared to metabolism prior to treatment. This effect on CYP450 enzyme activity may persist for several weeks after stopping sarilumab. In vitro, sarilumab has the potential to affect expression of multiple CYP enzymes, including CYP1A2, CYP2B6, CYP2C9, CYP2C19, CYP2D6, and CYP3A4. [61976] Levonorgestrel: (Moderate) Utilize caution with concomitant use of sarilumab and CYP3A4 substrate drugs, such as combined hormonal oral contraceptives, where a decrease in effectiveness is undesirable. Inhibition of IL-6 signaling by sarilumab may restore CYP450 activities to higher levels leading to increased metabolism of drugs that are CYP450 substrates as compared to metabolism prior to treatment. This effect on CYP450 enzyme activity may persist for several weeks after stopping sarilumab. In vitro, sarilumab has the potential to affect expression of multiple CYP enzymes, including CYP1A2, CYP2B6, CYP2C9, CYP2C19, CYP2D6, and CYP3A4. [61976] Levonorgestrel; Ethinyl Estradiol: (Moderate) Utilize caution with concomitant use of sarilumab and CYP3A4 substrate drugs, such as combined hormonal oral contraceptives, where a decrease in effectiveness is undesirable. Inhibition of IL-6 signaling by sarilumab may restore CYP450 activities to higher levels leading to increased metabolism of drugs that are CYP450 substrates as compared to metabolism prior to treatment. This effect on CYP450 enzyme activity may persist for several weeks after stopping sarilumab. In vitro, sarilumab has the potential to affect expression of multiple CYP enzymes, including CYP1A2, CYP2B6, CYP2C9, CYP2C19, CYP2D6, and CYP3A4. [61976] Levonorgestrel; Ethinyl Estradiol; Ferrous Bisglycinate: (Moderate) Utilize caution with concomitant use of sarilumab and CYP3A4 substrate drugs, such as combined hormonal oral contraceptives, where a decrease in effectiveness is undesirable. Inhibition of IL-6 signaling by sarilumab may restore CYP450 activities to higher levels leading to increased metabolism of drugs that are CYP450 substrates as compared to metabolism prior to treatment. This effect on CYP450 enzyme activity may persist for several weeks after stopping sarilumab. In vitro, sarilumab has the potential to affect expression of multiple CYP enzymes, including CYP1A2, CYP2B6, CYP2C9, CYP2C19, CYP2D6, and CYP3A4. [61976] Levonorgestrel; Ethinyl Estradiol; Ferrous Fumarate: (Moderate) Utilize caution with concomitant use of sarilumab and CYP3A4 substrate drugs, such as combined hormonal oral contraceptives, where a decrease in effectiveness is undesirable. Inhibition of IL-6 signaling by sarilumab may restore CYP450 activities to higher levels leading to increased metabolism of drugs that are CYP450 substrates as compared to metabolism prior to treatment. This effect on CYP450 enzyme activity may persist for several weeks after stopping sarilumab. In vitro, sarilumab has the potential to affect expression of multiple CYP enzymes, including CYP1A2, CYP2B6, CYP2C9, CYP2C19, CYP2D6, and CYP3A4. [61976] Live Vaccines: (Major) Avoid concurrent use of live vaccines during treatment with sarilumab due to potentially increased risk of infections; clinical safety of live vaccines during sarilumab treatment has not been established. No data are available on the secondary transmission of infection from persons receiving live vaccines to patients receiving sarilumab. The interval between live vaccinations and initiation of sarilumab therapy should be in accordance with current vaccination guidelines regarding immunosuppressive agents. [51778] [61976] Lovastatin: (Moderate) Utilize caution with concomitant use of sarilumab and CYP3A4 substrate drugs, such as lovastatin, where a decrease in effectiveness is undesirable. Monitor lipid panels and adjust therapy as indicated. Inhibition of IL-6 signaling by sarilumab may restore CYP450 activities to higher levels leading to increased metabolism of drugs that are CYP450 substrates as compared to metabolism prior to treatment. This effect on CYP450 enzyme activity may persist for several weeks after stopping sarilumab. A 45% decrease in exposure to another "statin" was noted in a drug interaction study. In vitro, sarilumab has the potential to affect expression of multiple CYP enzymes, including CYP1A2, CYP2B6, CYP2C9, CYP2C19, CYP2D6, and CYP3A4. Lovastatin is a CYP3A4 substrate. [61976] Measles Virus; Mumps Virus; Rubella Virus; Varicella Virus Vaccine, Live: (Major) Avoid concurrent use of live vaccines during treatment with sarilumab due to potentially increased risk of infections; clinical safety of live vaccines during sarilumab treatment has not been established. No data are available on the secondary transmission of infection from persons receiving live vaccines to patients receiving sarilumab. The interval between live vaccinations and initiation of sarilumab therapy should be in accordance with current vaccination guidelines regarding immunosuppressive agents. [51778] [61976] Measles/Mumps/Rubella Vaccines, MMR: (Major) Avoid concurrent use of live vaccines during treatment with sarilumab due to potentially increased risk of infections; clinical safety of live vaccines during sarilumab treatment has not been established. No data are available on the secondary transmission of infection from persons receiving live vaccines to patients receiving sarilumab. The interval between live vaccinations and initiation of sarilumab therapy should be in accordance with current vaccination guidelines regarding immunosuppressive agents. [51778] [61976] Norethindrone Acetate; Ethinyl Estradiol; Ferrous fumarate: (Moderate) Utilize caution with concomitant use of sarilumab and CYP3A4 substrate drugs, such as combined hormonal oral contraceptives, where a decrease in effectiveness is undesirable. Inhibition of IL-6 signaling by sarilumab may restore CYP450 activities to higher levels leading to increased metabolism of drugs that are CYP450 substrates as compared to metabolism prior to treatment. This effect on CYP450 enzyme activity may persist for several weeks after stopping sarilumab. In vitro, sarilumab has the potential to affect expression of multiple CYP enzymes, including CYP1A2, CYP2B6, CYP2C9, CYP2C19, CYP2D6, and CYP3A4. [61976] Norethindrone: (Moderate) Utilize caution with concomitant use of sarilumab and CYP3A4 substrate drugs, such as combined hormonal oral contraceptives, where a decrease in effectiveness is undesirable. Inhibition of IL-6 signaling by sarilumab may restore CYP450 activities to higher levels leading to increased metabolism of drugs that are CYP450 substrates as compared to metabolism prior to treatment. This effect on CYP450 enzyme activity may persist for several weeks after stopping sarilumab. In vitro, sarilumab has the potential to affect expression of multiple CYP enzymes, including CYP1A2, CYP2B6, CYP2C9, CYP2C19, CYP2D6, and CYP3A4. [61976] Norethindrone; Ethinyl Estradiol: (Moderate) Utilize caution with concomitant use of sarilumab and CYP3A4 substrate drugs, such as combined hormonal oral contraceptives, where a decrease in effectiveness is undesirable. Inhibition of IL-6 signaling by sarilumab may restore CYP450 activities to higher levels leading to increased metabolism of drugs that are CYP450 substrates as compared to metabolism prior to treatment. This effect on CYP450 enzyme activity may persist for several weeks after stopping sarilumab. In vitro, sarilumab has the potential to affect expression of multiple CYP enzymes, including CYP1A2, CYP2B6, CYP2C9, CYP2C19, CYP2D6, and CYP3A4. [61976] Norethindrone; Ethinyl Estradiol; Ferrous fumarate: (Moderate) Utilize caution with concomitant use of sarilumab and CYP3A4 substrate drugs, such as combined hormonal oral contraceptives, where a decrease in effectiveness is undesirable. Inhibition of IL-6 signaling by sarilumab may restore CYP450 activities to higher levels leading to increased metabolism of drugs that are CYP450 substrates as compared to metabolism prior to treatment. This effect on CYP450 enzyme activity may persist for several weeks after stopping sarilumab. In vitro, sarilumab has the potential to affect expression of multiple CYP enzymes, including CYP1A2, CYP2B6, CYP2C9, CYP2C19, CYP2D6, and CYP3A4. [61976] Norgestimate; Ethinyl Estradiol: (Moderate) Utilize caution with concomitant use of sarilumab and CYP3A4 substrate drugs, such as combined hormonal oral contraceptives, where a decrease in effectiveness is undesirable. Inhibition of IL-6 signaling by sarilumab may restore CYP450 activities to higher levels leading to increased metabolism of drugs that are CYP450 substrates as compared to metabolism prior to treatment. This effect on CYP450 enzyme activity may persist for several weeks after stopping sarilumab. In vitro, sarilumab has the potential to affect expression of multiple CYP enzymes, including CYP1A2, CYP2B6, CYP2C9, CYP2C19, CYP2D6, and CYP3A4. [61976] Norgestrel: (Moderate) Utilize caution with concomitant use of sarilumab and CYP3A4 substrate drugs, such as combined hormonal oral contraceptives, where a decrease in effectiveness is undesirable. Inhibition of IL-6 signaling by sarilumab may restore CYP450 activities to higher levels leading to increased metabolism of drugs that are CYP450 substrates as compared to metabolism prior to treatment. This effect on CYP450 enzyme activity may persist for several weeks after stopping sarilumab. In vitro, sarilumab has the potential to affect expression of multiple CYP enzymes, including CYP1A2, CYP2B6, CYP2C9, CYP2C19, CYP2D6, and CYP3A4. [61976] Ofatumumab: (Major) Avoid using sarilumab with other biological agents, including anti-CD20 monoclonal antibodies such as ofatumumab; coadministration has not been studied and may result in additive immunosuppression and an increased risk of infection. [61976] Oral Contraceptives: (Moderate) Utilize caution with concomitant use of sarilumab and CYP3A4 substrate drugs, such as combined hormonal oral contraceptives, where a decrease in effectiveness is undesirable. Inhibition of IL-6 signaling by sarilumab may restore CYP450 activities to higher levels leading to increased metabolism of drugs that are CYP450 substrates as compared to metabolism prior to treatment. This effect on CYP450 enzyme activity may persist for several weeks after stopping sarilumab. In vitro, sarilumab has the potential to affect expression of multiple CYP enzymes, including CYP1A2, CYP2B6, CYP2C9, CYP2C19, CYP2D6, and CYP3A4. [61976] Phenytoin: (Moderate) Monitor phenytoin concentrations and watch for decreased efficacy of phenytoin if coadministration with sarilumab is necessary; adjust phenytoin dosage as necessary. Inhibition of IL-6 signaling by sarilumab may restore CYP450 activities to higher levels leading to increased metabolism of drugs that are CYP450 substrates compared to metabolism prior to treatment. Therefore, CYP450 substrates with a narrow therapeutic index, such as phenytoin, may have fluctuations in drug levels and therapeutic effect when sarilumab therapy is started or discontinued. This effect on CYP450 enzyme activity may persist for several weeks after stopping sarilumab. In vitro, sarilumab has the potential to affect expression of multiple CYP enzymes, including CYP1A2, CYP2B6, CYP2C9, CYP2C19, CYP2D6, and CYP3A4. Phenytoin is a substrate of both CYP2C9 and CYP2C19 and narrow therapeutic index drug. [61976] Pimozide: (Moderate) Monitor for an altered patient response to pimozide if coadministration with sarilumab is necessary. Inhibition of IL-6 signaling by sarilumab may restore CYP450 activities to higher levels leading to increased metabolism of drugs that are CYP450 substrates compared to metabolism prior to treatment. Therefore, CYP450 substrates with a narrow therapeutic index, such as pimozide, may have fluctuations in drug levels and therapeutic effect when sarilumab therapy is started or discontinued. This effect on CYP450 enzyme activity may persist for several weeks after stopping sarilumab. In vitro, sarilumab has the potential to affect expression of multiple CYP enzymes, including CYP1A2, CYP2B6, CYP2C9, CYP2C19, CYP2D6, and CYP3A4. Pimozide a substrate of both CYP2D6 and CYP3A4 and narrow therapeutic index drug. [61976] Quinidine: (Moderate) Monitor quinidine levels and adjust the dose of quinidine as appropriate if coadministration with sarilumab is necessary. Inhibition of IL-6 signaling by sarilumab may restore CYP450 activities to higher levels leading to increased metabolism of drugs that are CYP450 substrates compared to metabolism prior to treatment. Therefore, CYP450 substrates with a narrow therapeutic index, such as quinidine, may have fluctuations in drug levels and therapeutic effect when sarilumab therapy is started or discontinued. This effect on CYP450 enzyme activity may persist for several weeks after stopping sarilumab. In vitro, sarilumab has the potential to affect expression of multiple CYP enzymes, including CYP1A2, CYP2B6, CYP2C9, CYP2C19, CYP2D6, and CYP3A4. Quinidine is a CYP3A4 substrate and narrow therapeutic index drug. [61976] Relugolix; Estradiol; Norethindrone acetate: (Moderate) Utilize caution with concomitant use of sarilumab and CYP3A4 substrate drugs, such as combined hormonal oral contraceptives, where a decrease in effectiveness is undesirable. Inhibition of IL-6 signaling by sarilumab may restore CYP450 activities to higher levels leading to increased metabolism of drugs that are CYP450 substrates as compared to metabolism prior to treatment. This effect on CYP450 enzyme activity may persist for several weeks after stopping sarilumab. In vitro, sarilumab has the potential to affect expression of multiple CYP enzymes, including CYP1A2, CYP2B6, CYP2C9, CYP2C19, CYP2D6, and CYP3A4. [61976] Rituximab: (Major) Avoid using sarilumab with other biological agents, including anti-CD20 monoclonal antibodies such as rituximab; coadministration has not been studied and may result in additive immunosuppression and an increased risk of infection. [49773] [61976] Rituximab; Hyaluronidase: (Major) Avoid using sarilumab with other biological agents, including anti-CD20 monoclonal antibodies such as rituximab; coadministration has not been studied and may result in additive immunosuppression and an increased risk of infection. [49773] [61976] Rivaroxaban: (Moderate) Monitor for a decrease in efficacy of rivaroxaban if used with sarilumab. Until more data are available, consider using an anticoagulant without dependence on CYP450 enzymes for metabolism (e.g., heparins, edoxaban). The formation of CYP450 enzymes may be suppressed by increased concentrations of cytokines such as IL-6 during chronic inflammation. It is expected that the activity of CYP450 enzymes could increase to normal concentrations during treatment with an IL-6 antagonist such as sarilumab; these effects on CYP450 enzyme activity may persist for several weeks after stopping sarilumab. In vitro, sarilumab has the potential to affect expression of multiple CYP enzymes [including CYP1A2, CYP2B6, CYP2C9, CYP2C19, CYP2D6, and CYP3A4]. Rivaroxaban is a substrate for CYP3A4/5. [44854] [61976] [65210] Rotavirus Vaccine: (Major) Avoid concurrent use of live vaccines during treatment with sarilumab due to potentially increased risk of infections; clinical safety of live vaccines during sarilumab treatment has not been established. No data are available on the secondary transmission of infection from persons receiving live vaccines to patients receiving sarilumab. The interval between live vaccinations and initiation of sarilumab therapy should be in accordance with current vaccination guidelines regarding immunosuppressive agents. [51778] [61976] SARS-CoV-2 (COVID-19) vaccines: (Moderate) Patients receiving immunosuppressant medications may have a diminished response to the SARS-CoV-2 virus vaccine. When feasible, administer indicated vaccines prior to initiating immunosuppressant medications. Counsel patients receiving immunosuppressant medications about the possibility of a diminished vaccine response and to continue to follow precautions to avoid exposure to SARS-CoV-2 virus after receiving the vaccine. [65107] [66080] SARS-CoV-2 Virus (COVID-19) Adenovirus Vector Vaccine: (Moderate) Patients receiving immunosuppressant medications may have a diminished response to the SARS-CoV-2 virus vaccine. When feasible, administer indicated vaccines prior to initiating immunosuppressant medications. Counsel patients receiving immunosuppressant medications about the possibility of a diminished vaccine response and to continue to follow precautions to avoid exposure to SARS-CoV-2 virus after receiving the vaccine. [65107] [66080] SARS-CoV-2 Virus (COVID-19) mRNA Vaccine: (Moderate) Patients receiving immunosuppressant medications may have a diminished response to the SARS-CoV-2 virus vaccine. When feasible, administer indicated vaccines prior to initiating immunosuppressant medications. Counsel patients receiving immunosuppressant medications about the possibility of a diminished vaccine response and to continue to follow precautions to avoid exposure to SARS-CoV-2 virus after receiving the vaccine. [65107] [66080] SARS-CoV-2 Virus (COVID-19) Recombinant Spike Protein Nanoparticle Vaccine: (Moderate) Patients receiving immunosuppressant medications may have a diminished response to the SARS-CoV-2 virus vaccine. When feasible, administer indicated vaccines prior to initiating immunosuppressant medications. Counsel patients receiving immunosuppressant medications about the possibility of a diminished vaccine response and to continue to follow precautions to avoid exposure to SARS-CoV-2 virus after receiving the vaccine. [65107] [66080] Secukinumab: (Major) Avoid using sarilumab with other biological DMARDs, such as secukinumab; coadministration has not been studied and may result in additive immunosuppression and increased risk of infection. [61976] Segesterone Acetate; Ethinyl Estradiol: (Moderate) Utilize caution with concomitant use of sarilumab and CYP3A4 substrate drugs, such as combined hormonal oral contraceptives, where a decrease in effectiveness is undesirable. Inhibition of IL-6 signaling by sarilumab may restore CYP450 activities to higher levels leading to increased metabolism of drugs that are CYP450 substrates as compared to metabolism prior to treatment. This effect on CYP450 enzyme activity may persist for several weeks after stopping sarilumab. In vitro, sarilumab has the potential to affect expression of multiple CYP enzymes, including CYP1A2, CYP2B6, CYP2C9, CYP2C19, CYP2D6, and CYP3A4. [61976] Simvastatin: (Moderate) Utilize caution with concomitant use of sarilumab and CYP3A4 substrate drugs, such as simvastatin, where a decrease in effectiveness is undesirable. Monitor lipid panels and adjust therapy as indicated. Inhibition of IL-6 signaling by sarilumab may restore CYP450 activities to higher levels leading to increased metabolism of drugs that are CYP450 substrates as compared to metabolism prior to treatment. This effect on CYP450 enzyme activity may persist for several weeks after stopping sarilumab. A 45% decrease in simvastatin exposure was noted 1 week after a single sarilumab dose. In vitro, sarilumab has the potential to affect expression of multiple CYP enzymes, including CYP1A2, CYP2B6, CYP2C9, CYP2C19, CYP2D6, and CYP3A4. Simvastatin is a CYP3A4 substrate. [61976] Smallpox and Monkeypox Vaccine, Live, Nonreplicating: (Major) Avoid concurrent use of live vaccines during treatment with sarilumab due to potentially increased risk of infections; clinical safety of live vaccines during sarilumab treatment has not been established. No data are available on the secondary transmission of infection from persons receiving live vaccines to patients receiving sarilumab. The interval between live vaccinations and initiation of sarilumab therapy should be in accordance with current vaccination guidelines regarding immunosuppressive agents. [51778] [61976] Smallpox Vaccine, Vaccinia Vaccine: (Major) Avoid concurrent use of live vaccines during treatment with sarilumab due to potentially increased risk of infections; clinical safety of live vaccines during sarilumab treatment has not been established. No data are available on the secondary transmission of infection from persons receiving live vaccines to patients receiving sarilumab. The interval between live vaccinations and initiation of sarilumab therapy should be in accordance with current vaccination guidelines regarding immunosuppressive agents. [51778] [61976] Tacrolimus: (Moderate) Monitor tacrolimus levels and adjust the dose of tacrolimus as appropriate if coadministration with sarilumab is necessary. Inhibition of IL-6 signaling by sarilumab may restore CYP450 activities to higher levels leading to increased metabolism of drugs that are CYP450 substrates compared to metabolism prior to treatment. Therefore, CYP450 substrates with a narrow therapeutic index, such as tacrolimus, may have fluctuations in drug levels and therapeutic effect when sarilumab therapy is started or discontinued. This effect on CYP450 enzyme activity may persist for several weeks after stopping sarilumab. In vitro, sarilumab has the potential to affect expression of multiple CYP enzymes, including CYP1A2, CYP2B6, CYP2C9, CYP2C19, CYP2D6, and CYP3A4. Tacrolimus is a CYP3A4 substrate and narrow therapeutic index drug. [61976] Theophylline, Aminophylline: (Moderate) Monitor drug concentrations and watch for decreased efficacy of aminophylline or theophylline if coadministration with sarilumab is necessary; a dosage increase of these methylxanthines may be necessary. Inhibition of IL-6 signaling by sarilumab may restore CYP450 activities to higher levels leading to increased metabolism of drugs that are CYP450 substrates compared to metabolism prior to treatment. Therefore, CYP450 substrates with a narrow therapeutic index may have fluctuations in drug levels and therapeutic effect when sarilumab therapy is started or discontinued. This effect on CYP450 enzyme activity may persist for several weeks after stopping sarilumab. In vitro,sarilumab has the potential to affect expression of multiple CYP enzymes, including CYP1A2, CYP2B6, CYP2C9, CYP2C19, CYP2D6, and CYP3A4. Aminophylline and Theophylline are CYP1A2 substrates and narrow therapeutic index drugs. [61976] Thioridazine: (Moderate) Monitor for an altered patient response to thioridazine if coadministration with sarilumab is necessary. Inhibition of IL-6 signaling by sarilumab may restore CYP450 activities to higher levels leading to increased metabolism of drugs that are CYP450 substrates compared to metabolism prior to treatment. Therefore, CYP450 substrates with a narrow therapeutic index, such as thioridazine, may have fluctuations in drug levels and therapeutic effect when sarilumab therapy is started or discontinued. This effect on CYP450 enzyme activity may persist for several weeks after stopping sarilumab. In vitro, sarilumab has the potential to affect expression of multiple CYP enzymes, including CYP1A2, CYP2B6, CYP2C9, CYP2C19, CYP2D6, and CYP3A4. Thioridazine is a CYP2D6 substrate and narrow therapeutic index drug. [61976] Tizanidine: (Moderate) Monitor for reduced efficacy of tizanidine if coadministered with sarilumab. Inhibition of IL-6 signaling by sarilmuab may restore CYP450 activities to higher levels leading to increased metabolism of drugs that are CYP450 substrates compared to metabolism prior to treatment. Therefore, CYP450 substrates with a narrow therapeutic index, such as tizanidine, may have fluctuations in drug levels and therapeutic effect when sarilumab therapy is started or discontinued. This effect on CYP450 enzyme activity may persist for several weeks after stopping sarilumab. In vitro, sarilumab has the potential to affect expression of multiple CYP enzymes, including CYP1A2, CYP2B6, CYP2C9, CYP2C19, CYP2D6, and CYP3A4. Tizanidine is a CYP1A2 substrate and narrow therapeutic index drug. [61976] Tocilizumab: (Major) Avoid using sarilumab with other biological DMARDs, such as tocilizumab; coadministration has not been studied and may result in additive immunosuppression and increased risk of infection. [38283] [61976] Tofacitinib: (Major) Avoid the concomitant use of sarilumab with other biological DMARDs such as tofacitinib; coadministration has not been studied and may result in additive immunosuppression and increased risk of infection. [52315] [61976] Tumor Necrosis Factor modifiers: (Major) Avoid the concomitant use of sarilumab with biological DMARDs, such as tumor necrosis factor (TNF) modifiers; coadministration has not been studied and may result in additive immunosuppression and increased risk of infection. [61976] Typhoid Vaccine: (Major) Avoid concurrent use of live vaccines during treatment with sarilumab due to potentially increased risk of infections; clinical safety of live vaccines during sarilumab treatment has not been established. No data are available on the secondary transmission of infection from persons receiving live vaccines to patients receiving sarilumab. The interval between live vaccinations and initiation of sarilumab therapy should be in accordance with current vaccination guidelines regarding immunosuppressive agents. [51778] [61976] Upadacitinib: (Major) Avoid the concomitant use of sarilumab with other biological DMARDs, such as upadacitinib; coadministration has not been studied and may result in additive immunosuppression and an increased risk of infection. [61976] [64572] Ustekinumab: (Major) Avoid the concomitant use of sarilumab with other biological DMARDs such as ustekinumab; coadministration has not been studied and may result in additive immunosuppression and increased risk of infection. [61976] Varicella-Zoster Virus Vaccine, Live: (Major) Avoid concurrent use of live vaccines during treatment with sarilumab due to potentially increased risk of infections; clinical safety of live vaccines during sarilumab treatment has not been established. No data are available on the secondary transmission of infection from persons receiving live vaccines to patients receiving sarilumab. The interval between live vaccinations and initiation of sarilumab therapy should be in accordance with current vaccination guidelines regarding immunosuppressive agents. [51778] [61976] Warfarin: (Moderate) Monitor the INR if sarilumab is coadministered with warfarin due to the potential for decreased warfarin efficacy; adjust the dose of warfarin as necessary. Inhibition of IL-6 signaling by sarilumab may restore CYP450 activities to higher levels leading to increased metabolism of drugs that are CYP450 substrates as compared to metabolism prior to treatment. Therefore, CYP450 substrates with a narrow therapeutic index, such as warfarin, may have fluctuations in drug levels and therapeutic effect when sarilumab therapy is started or discontinued. This effect on CYP450 enzyme activity may persist for several weeks after stopping sarilumab. [28549] [61976] Yellow Fever Vaccine, Live: (Major) Avoid concurrent use of live vaccines during treatment with sarilumab due to potentially increased risk of infections; clinical safety of live vaccines during sarilumab treatment has not been established. No data are available on the secondary transmission of infection from persons receiving live vaccines to patients receiving sarilumab. The interval between live vaccinations and initiation of sarilumab therapy should be in accordance with current vaccination guidelines regarding immunosuppressive agents. [51778] [61976]
    Revision Date: 01/11/2024, 04:54:00 PM

    References

    28549 - Coumadin (warfarin tablets) package insert. Princeton, NJ: Bristol-Myers Squibb Company; 2017 Aug.38283 - Actemra (tocilizumab) injection package insert. South San Francisco, CA: Genentech, Inc.; 2022 Dec.44854 - Xarelto (rivaroxaban) package insert. Titusville, NJ: Janssen Pharmaceuticals, Inc.; 2023 Feb.49773 - Rituxan (rituximab) injection package insert. South San Francisco, CA: Genentech, Inc.; 2018 Apr.51778 - Centers for Disease Control and Prevention. Recommendations of the Advisory Committee on Immunization Practices (ACIP): Use of vaccines and immune globulins in persons with altered immunocompetence. MMWR 1993;42:1-1852315 - Xeljanz and Xeljanz XR (tofacitinib) package insert. New York, NY: Pfizer, Inc.; 2021 Dec.52739 - Eliquis (apixaban) package insert. Bristol-Myers Squibb Company; Princeton, NJ. 2021 Apr.60092 - Rubin LG, Levin MJ, Ljungman P, et al. 2013 IDSA clinical practice guideline for vaccination of the immunocompromised host. Clin Infect Dis. 2014; 58: e44-100.60871 - Vaxchora (Cholera Vaccine, live, oral) package insert. Redwood City, CA: Emergent Travel Health Inc.; 2022 Dec.61976 - Kevzara (sarilumab) package insert. Bridgewater, NJ: Sanofi-Aventis US. LLC; 2023 Feb.63229 - Olumiant (baricitinib) tablets package insert. Indianapolis, IN: Lilly USA, LLC; 2022 Jun.64100 - Dengvaxia (dengue tetravalent vaccine, live) package insert. Swiftwater, PA: Sanofi Pasteur Inc.; 2023 August.64572 - Rinvoq (upadacitinib) package insert. North Chicago, IL: Abbvie Inc.; 2023 Nov.65107 - Kroger A, Bahta L, Hunter P. General Best Practice Guidelines for Immunization. Best Practices Guidance of the Advisory Committee on Immunization Practices (ACIP).Available on the world wide web at https://www.cdc.gov/vaccines/hcp/acip-recs/general-recs/downloads/general-recs.pdf. Revised April 27, 2022. Accessed on July 14, 2022.65210 - University of Liverpool. COVID-19 Drug Interactions. Retrived April 6, 2020. Available on the World Wide Web at https://www.covid19-druginteractions.org/.66080 - Food and Drug Administration (FDA). Fact Sheet for Healthcare Providers Administering Vaccine: Emergency Use Authorization (EUA) of Pfizer-BioNTech COVID-19 Vaccine to Prevent Coronavirus Disease 2019 (COVID-19) for 12 years and older. Purple cap and purple border. Retrieved November 22, 2022.

    Monitoring Parameters

    • CBC with differential
    • LFTs
    • platelet count
    • serum lipid profile
    • tuberculin skin test

    US Drug Names

    • KEVZARA
    ;