Satralizumab-mwge
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Alara Ece Dagsali, M.D.
Disclaimer
WikiDoc MAKES NO GUARANTEE OF VALIDITY. WikiDoc is not a professional health care provider, nor is it a suitable replacement for a licensed healthcare provider. WikiDoc is intended to be an educational tool, not a tool for any form of healthcare delivery. The educational content on WikiDoc drug pages is based upon the FDA package insert, National Library of Medicine content and practice guidelines / consensus statements. WikiDoc does not promote the administration of any medication or device that is not consistent with its labeling. Please read our full disclaimer here.
Overview
Satralizumab-mwge is a interleukin inhibitors that is FDA approved for the {{{indicationType}}} of ENSPRYNG is indicated for the treatment of neuromyelitis optica spectrum disorder (NMOSD) in adult patients who are anti-aquaporin-4 (AQP4) antibody positive.. Common adverse reactions include The following clinically significant adverse reactions are described elsewhere in the labeling:
- Infections
- Elevated Liver Enzymes
- Decreased Neutrophil Counts
- Hypersensitivity Reactions.
Adult Indications and Dosage
FDA-Labeled Indications and Dosage (Adult)
ENSPRYNG is indicated for the treatment of neuromyelitis optica spectrum disorder (NMOSD) in adult patients who are anti-aquaporin-4 (AQP4) antibody positive.
For subcutaneous use only.
Prior to every use of ENSPRYNG, advise patients to consult with their healthcare professional (HCP) if they suspect an active infection, including localized infections. In case of active infection, delay use of ENSPRYNG until the infection is resolved
The recommended loading dosage of ENSPRYNG for the first three administrations is 120 mg by subcutaneous injection at Weeks 0, 2, and 4, followed by a maintenance dosage of 120 mg every 4 weeks.
Off-Label Use and Dosage (Adult)
Guideline-Supported Use
There is limited information regarding Off-Label Guideline-Supported Use of Satralizumab-mwge in adult patients.
Non–Guideline-Supported Use
There is limited information regarding Off-Label Non–Guideline-Supported Use of Satralizumab-mwge in adult patients.
Pediatric Indications and Dosage
FDA-Labeled Indications and Dosage (Pediatric)
There is limited information regarding Satralizumab-mwge FDA-Labeled Indications and Dosage (Pediatric) in the drug label.
Off-Label Use and Dosage (Pediatric)
Guideline-Supported Use
There is limited information regarding Off-Label Guideline-Supported Use of Satralizumab-mwge in pediatric patients.
Non–Guideline-Supported Use
There is limited information regarding Off-Label Non–Guideline-Supported Use of Satralizumab-mwge in pediatric patients.
Contraindications
ENSPRYNG is contraindicated in patients with:
- A known hypersensitivity to satralizumab or any of the inactive ingredients
- Active Hepatitis B infection
- Active or untreated latent tuberculosis
Warnings
Infections An increased risk of infections, including serious and potentially fatal infections, has been observed in patients treated with IL-6 receptor antagonists, including ENSPRYNG.
The most common infections reported in a randomized clinical trial of patients treated with ENSPRYNG who were not on other chronic immunosuppressant therapies (Study 1), and that occurred more often than in patients receiving placebo, were nasopharyngitis (12%) and cellulitis (10%). The most common infections in patients who were on an additional concurrent immunosuppressant, and that occurred more often than in patients receiving placebo, were nasopharyngitis (31%), upper respiratory infection (19%), and pharyngitis (12%).
Delay ENSPRYNG administration in patients with an active infection, including localized infections, until the infection is resolved.
Hepatitis B Virus (HBV) Reactivation
Risk of HBV reactivation has been observed with other immunosuppressant therapies. Patients with chronic HBV infection were excluded from clinical trials. Perform HBV screening in all patients before initiation of treatment with ENSPRYNG. Do not administer ENSPRYNG to patients with active hepatitis. For patients who are chronic carriers of HBV [HBsAg+] or are negative for HBsAg and positive for HB core antibody [HBcAb+], consult liver disease experts before starting and during treatment with ENSPRYNG.
Tuberculosis
Tuberculosis has occurred in patients treated with other interleukin-6 receptor antagonists. Patients should be evaluated for tuberculosis risk factors and tested for latent infection prior to initiating ENSPRYNG. Consider anti-tuberculosis therapy prior to initiation of ENSPRYNG in patients with a history of latent or active tuberculosis in whom an adequate course of treatment cannot be confirmed, and for patients with a negative test for latent tuberculosis but having risk factors for tuberculosis infection. Consult infectious disease experts regarding whether initiating anti-tuberculosis therapy is appropriate before starting treatment. Patients should be monitored for the development of symptoms and signs of tuberculosis with ENSPRYNG, even if initial tuberculosis testing is negative.
Vaccinations
Live or live-attenuated vaccines should not be given concurrently with ENSPRYNG because clinical safety has not been established. Administer all immunizations according to immunization guidelines at least 4 weeks prior to initiation of ENSPRYNG for live or live-attenuated vaccines and, whenever possible, at least 2 weeks prior to initiation of ENSPRYNG for non-live vaccines.
Elevated Liver Enzymes Mild and moderate elevations of liver enzymes have been observed in patients treated with ENSPRYNG at a higher incidence than in patients receiving placebo.
ALT and AST levels should be monitored every 4 weeks for the first 3 months of treatment, followed by every 3 months for one year, and thereafter, as clinically indicated.
Decreased Neutrophil Counts Decreases in neutrophil counts were observed in patients treated with ENSPRYNG at a higher incidence than placebo.
Neutrophil counts should be monitored 4 to 8 weeks after initiation of therapy, and thereafter at regular clinically determined intervals [see Dosage and Administration (2.4)].
Hypersensitivity Reactions Hypersensitivity reactions, including rash, urticaria, and fatal anaphylaxis, have occurred with other interleukin-6 receptor antagonists.
Adverse Reactions
Clinical Trials Experience
Because clinical studies are conducted under widely varying conditions, adverse reaction rates observed in the clinical studies of a drug cannot be directly compared to rates in the clinical studies of another drug and may not reflect the rates observed in clinical practice.
The safety of ENSPRYNG was evaluated in two randomized, placebo-controlled clinical trials [Study 1 evaluated ENSPRYNG without concurrent immunosuppressive therapy (IST) and Study 2 evaluated ENSPRYNG with concurrent IST], which included 41 anti-AQP4 seropositive patients treated with ENSPRYNG in Study 1 and 26 anti-AQP4 seropositive patients treated with ENSPRYNG in Study 2. In the double-blind, controlled period, the median exposure time on ENSPRYNG treatment was approximately 2 years in Study 1 and approximately 3 years in Study 2. The median exposure time on placebo treatment was approximately 1 year in both Study 1 and Study 2.
Adverse reactions that occurred in Study 1 and Study 2 in more than 5% of patients treated with ENSPRYNG, and at a greater incidence than in patients who received placebo, are shown in Table 3 and Table 4, respectively. The most common adverse reactions (15% or greater with ENSPRYNG in either) were nasopharyngitis, headache, upper respiratory tract infection, gastritis, rash, arthralgia, extremity pain, fatigue, and nausea.
Postmarketing Experience
There is limited information regarding Satralizumab-mwge Postmarketing Experience in the drug label.
Drug Interactions
There is limited information regarding Satralizumab-mwge Drug Interactions in the drug label.
Use in Specific Populations
Pregnancy
Pregnancy Category (FDA):
There is no FDA guidance on usage of Satralizumab-mwge in women who are pregnant.
Pregnancy Category (AUS):
There is no Australian Drug Evaluation Committee (ADEC) guidance on usage of Satralizumab-mwge in women who are pregnant.
Labor and Delivery
There is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to ENSPRYNG during pregnancy. Healthcare providers are encouraged to register patients and pregnant women are encouraged to register themselves by calling 1-833-277-9338.
Nursing Mothers
No information is available on the presence of satralizumab-mwge in human milk, the effects of the satralizumab-mwge on the breastfed infant, or the effects of the satralizumab-mwge on milk production. Satralizumab-mwge was excreted in the milk of lactating monkeys administered satralizumab-mwge throughout pregnancy. Human IgG is excreted in human milk and the potential for absorption in the infant is unknown. The developmental and health benefits of breastfeeding should be considered along with the mother's clinical need for ENSPRYNG and any potential adverse effects on the breastfed infant from ENSPRYNG or from the underlying maternal condition.
Pediatric Use
Safety and effectiveness in pediatric patients have not been established.
Geriatic Use
Clinical studies of ENSPRYNG did not include sufficient numbers of patients aged 65 years and older to determine whether they respond differently from younger patients. However, population pharmacokinetic analyses in patients with NMOSD did not show that age affected the pharmacokinetics of satralizumab-mwge. In general, caution should be used when dosing the elderly, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant diseases or other drug therapy.
Gender
There is no FDA guidance on the use of Satralizumab-mwge with respect to specific gender populations.
Race
There is no FDA guidance on the use of Satralizumab-mwge with respect to specific racial populations.
Renal Impairment
There is no FDA guidance on the use of Satralizumab-mwge in patients with renal impairment.
Hepatic Impairment
There is no FDA guidance on the use of Satralizumab-mwge in patients with hepatic impairment.
Females of Reproductive Potential and Males
There is no FDA guidance on the use of Satralizumab-mwge in women of reproductive potentials and males.
Immunocompromised Patients
There is no FDA guidance one the use of Satralizumab-mwge in patients who are immunocompromised.
Administration and Monitoring
Administration
- ENSPRYNG is intended for patient self-administration by subcutaneous injection under the guidance of a health care professional (HCP). After proper training in subcutaneous injection technique, a patient may self-inject ENSPRYNG or the patient's caregiver may administer ENSPRYNG, if the HCP determines that it is appropriate. See ENSPRYNG "Instructions for Use" (IFU) for more detailed instructions on the preparation and administration of ENSPRYNG.
- Patients or caregivers should seek immediate medical attention if the patient develops symptoms of a serious allergic reaction and should not administer further doses until evaluated by a HCP [see Contraindications (4) and Warning and Precautions (5.4)].
Prior to use, remove the prefilled syringe from the refrigerator and allow to sit at room temperature outside of the carton for 30 minutes. Do not warm ENSPRYNG in any other way.
- Inspect visually for particulate matter and discoloration prior to administration. ENSPRYNG solution should be clear and colorless to slightly yellow. Do not use ENSPRYNG if the solution is cloudy, discolored, or contains particles, or if any part of the prefilled syringe appears to be damaged.
- Instruct patients to inject the full amount in the syringe (1 mL), which provides 120 mg of ENSPRYNG, according to the directions provided in the IFU.
- Administer ENSPRYNG by subcutaneous injection in the abdomen or thigh. Rotate injection sites with each administration. Do not give injection into moles, scars, or areas where the skin is tender, bruised, red, hard, or not intact.
Monitoring
- Monitor ALT and AST levels every 4 weeks for the first 3 months of treatment with ENSPRYNG, followed by every 3 months for one year, and thereafter as clinically necessary.
- If an ALT or AST elevation of greater than 5 times the ULN occurs, discontinue ENSPRYNG as follows:
- If associated with any bilirubin elevation, discontinue ENSPRYNG, and reinitiation is not recommended.
- If not associated with any bilirubin elevation above the ULN, when the ALT or AST level has returned to the normal range and following a benefit-risk assessment of the patient, treatment with ENSPRYNG can be restarted per the schedule.
IV Compatibility
There is limited information regarding the compatibility of Satralizumab-mwge and IV administrations.
Overdosage
There is limited information regarding Satralizumab-mwge overdosage. If you suspect drug poisoning or overdose, please contact the National Poison Help hotline (1-800-222-1222) immediately.
Pharmacology
There is limited information regarding Satralizumab-mwge Pharmacology in the drug label.
Mechanism of Action
The precise mechanism by which satralizumab-mwge exerts therapeutic effects in NMOSD is unknown but is presumed to involve inhibition of IL-6-mediated signaling through binding to soluble and membrane-bound IL-6 receptors.
Structure
There is limited information regarding Satralizumab-mwge Structure in the drug label.
Pharmacodynamics
The relationship between any of the pharmacodynamic effects of ENSPRYNG and clinical outcomes in NMOSD is unknown.
Pharmacokinetics
The pharmacokinetics of ENSPRYNG have been characterized both in Japanese and Caucasian healthy volunteers, and in NMOSD patients. The pharmacokinetics in NMOSD patients using the recommended dose were characterized using population pharmacokinetic analysis methods based on a database of 154 patients.
The concentration-time course of ENSPRYNG in patients with NMOSD was accurately described by a two-compartment population pharmacokinetic model with parallel linear and target-mediated (Michaelis-Menten) elimination and first-order subcutaneous absorption. ENSPRYNG clearance and volume parameters allometrically scaled by body weight (through power function with the fixed power coefficient of 0.75 and 1 for clearance and volume parameters, respectively). Body weight was shown to be a significant covariate, with clearance and Vc for patients weighing 123 kg (97.5th percentile of the weight distribution) increased by 71.3% and 105%, respectively, compared to a patient weighing 60 kg.
Steady state pharmacokinetics were achieved after the loading period (8 weeks) as follows [mean (±SD)]: Cmin: 19.7 (12.2) mcg/mL, Cmax: 31.5 (14.9) mcg/mL, and AUC: 737 (386) mcg.mL/day.
Absorption
The bioavailability of satralizumab-mwge was 85%.
Distribution
Satralizumab-mwge undergoes biphasic distribution. The central volume of distribution was 3.46 L and the peripheral volume of distribution was 2.07 L. The inter-compartmental clearance was 0.336 L/day.
Elimination
The total clearance of satralizumab-mwge is concentration-dependent. Linear clearance (accounting for approximately half of the total clearance at steady state using the recommended dose in NMOSD patients) is estimated to be 0.0601 L/day. The associated terminal t1/2 is approximately 30 days (range 22 – 37 days) based on data pooled from Study 1 and Study 2.
Metabolism
The metabolism of satralizumab-mwge has not been directly studied, as antibodies are cleared principally by catabolism.
Excretion
Monoclonal antibodies, including satralizumab-mwge, are not eliminated via renal or hepatic pathways.
Specific Populations
Population pharmacokinetic analyses in patients with NMOSD showed that age, gender, and race did not meaningfully influence the pharmacokinetics of satralizumab-mwge.
Patients with Renal or Hepatic Impairment
No formal studies of the effect of renal impairment or hepatic impairment on the pharmacokinetics of satralizumab-mwge were conducted.
Drug Interaction Studies
No formal drug-drug interaction studies have been performed with ENSPRYNG.
Based on population pharmacokinetic analyses of the available data, the impact of commonly used small molecule drugs on the pharmacokinetics of satralizumab-mwge remains inconclusive.
Suppression of IL-6 signaling by treatment with ENSPRYNG, from the low baseline levels seen in Study 1 and Study 2, is expected to have a minor impact on exposure of concomitant medications metabolized by CYP450 enzymes. The clinical significance of this is unknown.
Nonclinical Toxicology
Carcinogenesis
Carcinogenicity studies of satralizumab-mwge were not conducted.
Mutagenesis
Genetic toxicology studies of satralizumab-mwge were not conducted. As an antibody, satralizumab-mwge is not expected to interact directly with DNA.
Impairment of Fertility
In monkeys administered satralizumab-mwge (0, 2, 10, or 50 mg/kg) weekly by subcutaneous injection for 26 weeks, no effects on sperm, estrus cycle, or male and female reproductive organs were observed. At the high dose, plasma exposures (Cave) were approximately 100 times that in humans at the recommended monthly maintenance dose of 120 mg.
Clinical Studies
The efficacy of ENSPRYNG for the treatment of NMOSD in adult patients was established in two studies. Study 1 was a randomized (2:1), placebo-controlled trial in 95 patients without concurrent IST (Study 1, NCT02073279) in which 64 patients were anti-AQP4 antibody positive and 31 patients were anti-AQP4 antibody negative.
Study 2 was a randomized (1:1), placebo-controlled trial in 76 adult patients with concurrent IST (Study 2, NCT02028884). Of these, 52 adult patients were anti-AQP4 antibody positive and 24 adult patients were anti-AQP4 antibody negative.
Patients met the following eligibility criteria:
Study 1: Clinical evidence of 1 relapse in the previous 12 months Study 2: Clinical evidence of at least 2 relapses in the previous 2 years, at least one of which must have occurred in the previous year EDSS score of 0 to 6.5 (both studies) Study 1: Patients were excluded if previously treated with IST within an interval specified for each such therapy Study 2: One of the following baseline treatments at a stable dose as a monotherapy for 8 weeks prior to baseline: azathioprine, mycophenolate mofetil, oral corticosteroids In Study 1, 41 anti-AQP4 antibody positive adult patients were randomized to and received ENSPRYNG and 23 received placebo. Females accounted for 76% of the ENSPRYNG group and 96% of the placebo group. The remaining baseline demographic characteristics were balanced between the treatment groups. The mean age was 44 years. Fifty percent were White, 22% were Black or African-American, and 20% were Asian. The mean EDSS score was 3.8.
In Study 2, 26 anti-AQP4 antibody positive adult patients were randomized to and received ENSPRYNG and 26 received placebo. All patients were receiving either concurrent azathioprine (42%), oral corticosteroids (52%), or mycophenolate mofetil (6%) during the trial. The baseline demographic and disease characteristics were balanced between the treatment groups. Females accounted for 100% of the study population. Forty-six percent of patients were White and 52% were Asian. The mean age was 46 years. The mean EDSS score was 4.0.
All potential relapses were adjudicated by a blinded Clinical Endpoint Committee (CEC). The primary efficacy endpoint for both studies was the time to the first CEC-confirmed relapse.
In Study 1, the time to the first CEC-confirmed relapse was significantly longer in ENSPRYNG-treated patients compared to patients who received placebo (risk reduction 55%; hazard ratio 0.45; p = 0.0184). In the anti-AQP4 antibody positive population, there was a 74% risk reduction; hazard ratio 0.26; p = 0.0014. There was no evidence of a benefit in the anti-AQP4 antibody negative patients.
In Study 2, the time to the first CEC-confirmed relapse was significantly longer in patients treated with ENSPRYNG compared to patients who received placebo (risk reduction 62%; hazard ratio 0.38; p = 0.0184). In the anti-AQP4 antibody positive population, there was a 78% risk reduction; hazard ratio 0.22; p = 0.0143 (Table 5; Figure 2). There was no evidence of a benefit in the anti-AQP4 antibody negative patients.
How Supplied
ENSPRYNG (satralizumab-mwge) injection is available as a sterile, preservative-free, clear, colorless to slightly yellow solution in single-dose prefilled syringe (PFS) with needle safety device.
ENSPRYNG PFS is not made with natural rubber latex. Each ENSPRYNG carton contains one single-dose 120 mg/mL prefilled syringe (NDC 50242-007-01).
Storage
- Refrigerate at 2°C to 8°C (36°F to 46°F) in original carton to protect from light. Do not freeze. Do not shake.
- Prior to administration, ENSPRYNG, if unopened, can be removed from and returned to the refrigerator, if necessary. The total combined time out of refrigeration should not exceed 8 days at a temperature that does not exceed 30°C (86°F).
Images
Drug Images
{{#ask: Page Name::Satralizumab-mwge |?Pill Name |?Drug Name |?Pill Ingred |?Pill Imprint |?Pill Dosage |?Pill Color |?Pill Shape |?Pill Size (mm) |?Pill Scoring |?NDC |?Drug Author |format=template |template=DrugPageImages |mainlabel=- |sort=Pill Name }}
Package and Label Display Panel
{{#ask: Label Page::Satralizumab-mwge |?Label Name |format=template |template=DrugLabelImages |mainlabel=- |sort=Label Page }}
Patient Counseling Information
Infections
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 ENSPRYNG. Instruct patients to contact their healthcare provider immediately when symptoms suggesting infection (e.g., fever, chills, constant cough, or sore throat) appear during treatment [see Warning and Precautions (5.1)].
Vaccinations
Advise patients to complete any required vaccinations at least 4 weeks prior to initiation of ENSPRYNG for live or live-attenuated vaccines and, whenever possible, at least 2 weeks prior to initiation of ENSPRYNG for non-live vaccines [see Warnings and Precautions 5.1].
Elevated Liver Enzymes
Inform patients on the importance of liver enzyme testing.
Decreased Neutrophil Counts
Inform patients on the importance of neutrophil count testing [see Warnings and Precautions (5.3)].
Hypersensitivity Reactions
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 [see Warnings and Precautions (5.4)].
Instruction on Injection Technique
Instruct patients and caregivers to read the Instructions for Use before the patient starts using ENSPRYNG, and each time the patient gets a refill as there may be new information they need to know.
Perform the first injection under the guidance of a qualified healthcare professional. If a patient or caregiver is to administer subcutaneous ENSPRYNG, instruct him/her in injection techniques and assess his/her ability to inject subcutaneously to ensure proper administration of subcutaneous ENSPRYNG and the suitability for home use.
Instruct patients to remove the prefilled syringe from the refrigerator prior to use and allow to sit at room temperature outside of the carton for 30 minutes. Do not warm ENSPRYNG in any other way.
Advise patients to consult their healthcare provider if the full dose is not received.
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 technique as well as proper prefilled syringe disposal, and caution against reuse of these items.
Pregnancy Exposure Registry
Encourage patients to enroll in the ENSPRYNG Pregnancy Registry if they become pregnant while taking ENSPRYNG. The Registry monitors fetal outcomes of pregnant women exposed to ENSPRYNG.
Precautions with Alcohol
Alcohol-Satralizumab-mwge interaction has not been established. Talk to your doctor about the effects of taking alcohol with this medication.
Brand Names
ENSPRYNG
Look-Alike Drug Names
There is limited information regarding Satralizumab-mwge Look-Alike Drug Names in the drug label.
Drug Shortage Status
Price
References
The contents of this FDA label are provided by the National Library of Medicine.