Satralizumab-mwge (Monograph)

Brand name: Enspryng
Drug class: Immunomodulatory Agents

Medically reviewed by Drugs.com on Feb 26, 2023. Written by ASHP.

Introduction

Satralizumab-mwge, a recombinant humanized IgG2 monoclonal antibody, is an interleukin-6 (IL-6) receptor antagonist.¹

Uses for Satralizumab-mwge

Neuromyelitis Optica Spectrum Disorder

Satralizumab-mwge is used for the treatment of neuromyelitis optica spectrum disorder (NMOSD) in adult patients who are anti-aquaporin-4 (AQP4) antibody positive.¹ Satralizumab is designated an orphan drug by the FDA for treatment of this disease.²

Satralizumab-mwge is more effective than placebo or immunosuppressant therapy alone in reducing the relapse rate and prolonging the time to relapse in patients with anti-AQP4 antibody positive NMOSD.^{1 3 4}

There is currently no evidence of benefit in anti-AQP4 antibody negative patients.^{1 3 4}

Satralizumab-mwge Dosage and Administration

General

Pretreatment Screening

• Assess for active infection; delay administration until infection resolves.¹

• Screen for active or latent tuberculosis.¹

• Screen for hepatitis B (hepatitis B surface antigen [HBsAg] and hepatitis B core antibody [HBcAb]); do not administer to patients with active hepatitis B.¹

• Assess AST/ALT and serum bilirubin; carefully consider treatment in patients with baseline hepatic transaminase concentrations greater than 1.5 times the upper limit of normal.¹

• Assess complete blood count.¹

Patient Monitoring

• Monitor for signs or symptoms of active infection prior to each dose.¹

• Monitor for signs and symptoms of tuberculosis throughout treatment.¹

• Evaluate AST/ALT every 4 weeks for the first 3 months of treatment, followed by every 3 months for 1 year, then as clinically necessary.¹

• Monitor serum bilirubin throughout treatment as clinically necessary.¹

• Monitor neutrophil count 4–8 weeks after initiation of treatment and then at regular clinically determined intervals.¹

Other General Considerations

• Administer all live or live-attenuated vaccines at least 4 weeks before treatment and non-live vaccines at least 2 weeks prior to treatment.¹ Do not administer live vaccines during treatment.¹

• Consult liver disease expert prior to and during satralizumab therapy in patients who are HBsAg-negative and positive for HBcAb or are carriers of HBV (HBsAg-positive).¹

• Consult infectious disease expert prior to starting treatment in patients with active tuberculosis or positive tuberculosis screening without history of appropriate treatment.¹

Administration

Subcutaneous Administration

Administer by subcutaneous injection.¹

Administer into abdomen or thigh.¹ Do not inject within 5 cm (2 inches) of the umbilicus.¹ Do not inject into moles, scars, or areas where the skin is tender, bruised, red, hard, or broken.¹ Rotate injection sites; administer next injection at least 2.5 cm (1 inch) from the previous site.¹

Intended for self-administration after appropriate instruction is given.¹ Perform first injection under the guidance of a healthcare professional.¹

Commercially available as a prefilled single-use syringe.¹ Store in the refrigerator in the original carton to protect from light.¹ Do not freeze or shake syringes.¹ Allow prefilled syringes to reach room temperature for about 30 minutes prior to use.¹

Discard prefilled syringes after use.¹

Dosage

Adults

Neuromyelitis Optica Spectrum Disorder

Sub-Q

Initially (loading dosage), 120 mg at weeks 0, 2, and 4.¹

Maintenance dosage: 120 mg every 4 weeks.¹

If a dose is missed, administer as soon as possible without waiting until the next scheduled dose.¹ Administer subsequent doses according to Table 1.

Dosage Modification for Toxicity

If adverse reactions occur during satralizumab therapy, temporary interruption and/or discontinuation may be necessary.¹

Hepatic Toxicity

If an elevation in alanine aminotransferase (ALT) or aspartate aminotransferase (AST) greater than 5 times the upper limit of normal occurs in combination with any elevation in bilirubin, permanently discontinue satralizumab.¹

If an elevation in ALT or AST greater than 5 times the upper limit of normal occurs without elevation in bilirubin above the upper limit of normal, interrupt satralizumab therapy until liver enzymes return to the normal range.¹ Satralizumab may then be restarted following a benefit-risk assessment as follows.¹ If the last dose of satralizumab was administered less than 12 weeks previously, restart satralizumab at a dosage of 120 mg by subcutaneous injection every 4 weeks.¹ If the delay in satralizumab dosing is 12 weeks or longer, restart the initiation regimen of 120 mg subcutaneously at 0, 2, and 4 weeks, followed by a dosage of 120 mg every 4 weeks.¹ If any subsequent elevation in ALT or AST and/or bilirubin above the ULN occurs, permanently discontinue satralizumab.¹

Neutropenia

If the neutrophil count falls below 1 × 10⁹/L and is confirmed by repeat testing, interrupt satralizumab therapy until the neutrophil count is greater than 1 × 10⁹/L.¹ Satralizumab may then be restarted according to the dosage recommendations in Table 1.¹

Special Populations

Hepatic Impairment

Manufacturer makes no specific dosage recommendations for patients with hepatic impairment.¹ Use caution when considering initiating satralizumab in patients with baseline ALT or AST greater than 1.5 times the upper limit of normal.¹

Patients who develop hepatotoxicity during treatment may require dose interruption or permanent discontinuation.¹

Renal Impairment

Manufacturer makes no specific dosage recommendations for patients with renal impairment.¹

Geriatric Patients

Manufacturer makes no specific dosage recommendations for geriatric patients.¹

Cautions for Satralizumab-mwge

Contraindications

• Known hypersensitivity to satralizumab-mwge or any of the inactive ingredients.¹

• Active HBV infection.¹

• Active or untreated latent tuberculosis.¹

Warnings/Precautions

Infectious Complications

Increased risk of infections (e.g., nasopharyngitis, upper respiratory tract infection).¹ Do not administer in patients with active infection; delay therapy until infection resolves.¹

Although not reported with satralizumab, reactivation of HBV infection has occurred in patients treated with other immunosuppressant therapies.¹ Satralizumab is contraindicated in patients with active hepatitis.¹ Screen all patients for HBV prior to initiating therapy.¹ Consult a liver disease expert prior to and during satralizumab therapy in patients who are HBsAg-negative and positive for HBcAb or are chronic carriers of HBV (HBsAg-positive).¹

Although not reported with satralizumab, tuberculosis has occurred in patients treated with other interleukin-6 receptor antagonists.¹ Evaluate patients for tuberculosis risk factors and test for latent infection prior to initiating satralizumab.¹ Consult an infectious disease expert to determine whether antituberculosis therapy is appropriate prior to starting satralizumab treatment in patients with active tuberculosis or positive tuberculosis screening without history of appropriate treatment, and in patients with negative tuberculosis screening but who have risk factors for tuberculosis infection.¹ Monitor all patients for signs and symptoms of tuberculosis during satralizumab therapy, even if initial tuberculosis screening is negative.¹

Satralizumab may interfere with the safety and effectiveness of vaccines; complete any necessary immunizations at least 4 weeks prior to initiation of satralizumab for live or live-attenuated vaccines, and whenever possible, at least 2 weeks prior to initiation of satralizumab for inactivated vaccines.¹

Elevated Liver Enzymes

Increased risk of mild to moderate liver enzyme elevation reported.¹ Elevations were not associated with increases in total bilirubin.¹

Monitor AST and ALT every 4 weeks for the first 3 months of treatment, followed by every 3 months for 1 year, then as clinically necessary.¹

Discontinue satralizumab therapy if ALT or AST elevation greater than 5 times the upper limit of normal occur; consider restarting treatment once liver enzymes normalize.¹ Do not reinitiate treatment if liver enzyme elevation is associated with any increase in bilirubin.¹

Neutropenia

Neutropenia reported in 10-15% of patients.¹

Monitor neutrophil counts 4 to 8 weeks after initiation of therapy and then at regular clinically determined intervals.¹

Hypersensitivity Reactions

Although not reported with satralizumab, hypersensitivity reactions, including rash, urticaria, and fatal anaphylaxis, have occurred with other interleukin-6 receptor antagonists.¹ Monitor for hypersensitivity reactions during treatment with satralizumab.¹

Immunogenicity

Potential for immunogenicity.¹ Anti-satralizumab antibodies observed in up to 73% of patients; clinical relevance unknown.¹

No dosage adjustments or treatment interruptions recommended.¹

Specific Populations

Pregnancy

No adequate data in pregnant women; may impair infant immune function based on animal studies.¹ Consider the risks and benefits of administering live or live-attenuated vaccines to infants exposed to satralizumab in utero.¹

Pregnancy registry available: 1-833-277-9338.¹

Lactation

Not known whether distributed into human milk or if the drug has any effect on milk production or the breast-fed infant.¹

Consider known benefits of breast-feeding along with the mother's clinical need for satralizumab and any potential adverse effects of the drug or disease on the infant.¹

Pediatric Use

Safety and efficacy not established.¹

Geriatric Use

Insufficient experience in geriatric patients to determine whether they respond differently than younger adults.¹

Hepatic Impairment

Pharmacokinetics not studied.¹

Renal Impairment

Pharmacokinetics not studied.¹

Common Adverse Effects

Adverse effects occurring in ≥15% of patients: nasopharyngitis, headache, upper respiratory tract infection, gastritis, rash, arthralgia, extremity pain, fatigue, and nausea.¹

Drug Interactions

No formal drug interaction studies performed to date.¹ Minor impact on exposure of concomitant CYP450 substrates expected due to suppression of IL-6 signaling; clinical relevance unknown.¹

Vaccines

Safety and effectiveness of live or live-attenuated vaccines administered concomitantly with satralizumab not established; administration of these vaccines not recommended during satralizumab therapy.¹

Complete any necessary immunizations at least 4 weeks prior to initiation of satralizumab for live or live-attenuated vaccines, and whenever possible, at least 2 weeks prior to initiation of satralizumab for inactivated vaccines.¹

The effects of maternal exposure to satralizumab on infant immune function and response to vaccines is unknown.¹ Consider the risks and benefits of administering live or live-attenuated vaccines to infants exposed to satralizumab in utero.¹

Satralizumab-mwge Pharmacokinetics

Absorption

Bioavailability

Following sub-Q administration, bioavailability is 85%.¹

Steady state pharmacokinetics achieved after the 8 week loading period.¹

Special Populations

Pharmacokinetics do not appear to be affected by age, sex, or race.¹

Distribution

Undergoes biphasic distribution; central volume of distribution is 3.46 L and peripheral volume of distribution is 2.07 L.¹

Extent

Not known whether drug is distributed into human milk.¹ May cross placenta.¹

Special Populations

Central volume of distribution and clearance are increased in patients with higher body weight; clinical relevance is unknown.¹

Elimination

Metabolism

Not directly studied; antibodies are cleared by catabolism.¹

Clearance is concentration dependent; undergoes linear and target-mediated elimination.¹

Elimination Route

Monoclonal antibodies, including satralizumab-mwge, are not eliminated via renal or hepatic pathways.¹

Half-life

Approximately 30 days.¹

Stability

Storage

Parenteral

Prefilled Syringe

2–8°C in original carton; protect from light until time of use.¹ Do not freeze or shake.¹ Unopened syringes can be removed from and returned to the refrigerator if necessary; do not exceed a total nonrefrigerated time of 8 days or a temperature of 30°C.¹

Actions

• A recombinant humanized IgG2 monoclonal antibody that binds to soluble and membrane-bound IL-6 receptors and inhibits IL-6 mediated signaling.^{1 3 4}

• IL-6 levels are elevated in serum and cerebrospinal fluid in patients with NMOSD and correlate with AQP4-IgG levels and disease severity.^{6 8}

• IL-6 facilitates disruption of the blood-brain barrier, promotes production of AQP4-IgG and proinflammatory helper T cells, and blocks activation of regulatory T cells.^{6 8 9}

• Although the exact mechanism in NMOSD is unclear, inhibition of IL-6 mediated signaling is thought to result in the drug’s immunomodulatory effects.^{6 8}

Advice to Patients

• Advise the patients to read the FDA-approved patient labeling (Medication Guide and Instructions for Use).¹

• Inform patients that an increased risk of infections, including serious and potentially fatal infections, has been observed in patients treated with IL-6 receptor antagonists, including satralizumab-mwge. Instruct patients to contact their healthcare provider immediately when symptoms suggesting infection (e.g., fever, chills, constant cough, sore throat) appear during treatment.¹

• Advise patients to complete any required vaccinations at least 4 weeks prior to initiation of satralizumab-mwge for live or live-attenuated vaccines and, whenever possible, at least 2 weeks prior to initiation of satralizumab-mwge for non-live vaccines.¹

• Inform patients about the importance of liver enzyme testing.¹

• Inform patients about the importance of neutrophil count testing.¹

• Inform patients about the signs and symptoms of hypersensitivity reactions and anaphylaxis and advise them to contact their healthcare provider immediately if these symptoms occur.¹

• Instruct patients and caregivers to read the instructions for use in the manufacturer's labeling before the patient starts using satralizumab-mwge, and each time the patient gets a refill as there may be new information they need to know.¹

• Perform the first injection under the guidance of a qualified healthcare professional. If a patient or caregiver is to administer subcutaneous satralizumab-mwge, instruct him/her in injection techniques and assess his/her ability to inject subcutaneously to ensure proper administration and the suitability for home use.¹

• Instruct patients to remove the prefilled syringe from the refrigerator prior to use and allow it to sit at room temperature outside of the carton for 30 minutes. Do not warm satralizumab-mwge in any other way.¹

• Advise patients to consult their healthcare provider if the full dose is not received.¹

• A puncture-resistant container for disposal of syringes should be used and should be kept out of the reach of children. Instruct patients or caregivers in the disposal technique, as well as proper prefilled syringe disposal, and caution against reuse of these items.¹

• Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs and dietary or herbal supplements, as well as any concomitant illnesses.¹

• Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.¹

• Importance of informing patients of other important precautionary information.¹

Additional Information

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

Preparations

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

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

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