Enspryng
(satralizumab-mwge)Dosage & Administration
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Enspryng Prescribing Information
ENSPRYNG is indicated for the treatment of neuromyelitis optica spectrum disorder (NMOSD) in adult patients who are anti-aquaporin-4 (AQP4) antibody positive.
Assessments Prior to the First Dose of ENSPRYNG
Hepatitis B Virus Screening
Prior to initiating ENSPRYNG, perform Hepatitis B virus (HBV) screening. ENSPRYNG is contraindicated in patients with active HBV confirmed by positive results for surface antigen [HBsAg] and anti-HBV tests. For patients who are negative for HBsAg and positive for HB core antibody [HBcAb+] or are carriers of HBV [HBsAg+], consult liver disease experts before starting and during treatment with ENSPRYNG [see Contraindications (4) and Warnings and Precautions (5.1)].
Tuberculosis Screening
Prior to initiating ENSPRYNG, evaluate for active tuberculosis and test for latent infection. For patients with active tuberculosis or positive tuberculosis screening without a history of appropriate treatment, consult infectious disease experts before initiating treatment with ENSPRYNG [see Contraindications (4) and Warnings and Precautions (5.1)].
Liver Transaminase Screening
Liver transaminases and serum bilirubin should be assessed prior to initiation of treatment with ENSPRYNG [see Warnings and Precautions (5.2)].
Caution should be exercised when considering initiation of ENSPRYNG treatment in patients whose aspartate aminotransferase (AST) or alanine aminotransferase (ALT) levels are greater than 1.5 times the upper limit of normal (ULN).
Vaccinations
Because vaccination with live-attenuated or live vaccines is not recommended during treatment with ENSPRYNG, 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 [see Warnings and Precautions (5.1)].
Recommended Dosage
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 [see Warnings and Precautions (5.1)].
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.
Missed Dose
If a dose of ENSPRYNG is missed for any reason other than increases in liver enzymes [see Dosage and Administration (2.4)], administer as described in Table 1.
| Last Dose Administered | Recommended Dosage for Delayed or Missed Doses |
|---|---|
| |
| Less than 8 weeks during the maintenance period or missed a loading dose | Administer 120 mg by subcutaneous injection as soon as possible, and do not wait until the next planned dose. Maintenance period After the delayed or missed dose is administered, reset the dose schedule to every 4 weeks. Loading period If the second loading dose is delayed or missed, administer as soon as possible and administer the 3rd and final loading dose 2 weeks later. If the third loading dose is delayed or missed, administer as soon as possible and administer the 1st maintenance dose 4 weeks later. |
| 8 weeks to less than 12 weeks | 120 mg by subcutaneous injection at 0 * and 2 weeks, followed by 120 mg every 4 weeks. |
| 12 weeks or longer | 120 mg by subcutaneous injection at 0 *, 2, and 4 weeks followed by 120 mg every 4 weeks. |
Important Administration Instructions
- 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.
Safety Monitoring During Treatment
Liver Transaminases
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 [see Warnings and Precautions (5.2)].
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 in Table 2.
If treatment is restarted, the liver parameters must be closely monitored, and if any subsequent increase in ALT/AST and/or bilirubin above the ULN is observed, ENSPRYNG should be discontinued, and another reinitiation is not recommended.Table 2 Recommended Dosage for Restart of Treatment After Liver Transaminase Elevation Last Dose Administered Recommended Dosage for Restart of Treatment - *
- "0 weeks" refers to time of the first administration after the missed dose.
Less than 12 weeks Restart at a dosage of 120 mg by subcutaneous injection every 4 weeks. 12 weeks or longer Restart at a dose of 120 mg by subcutaneous injection at Weeks 0 *, 2, and 4, followed by a dosage of 120 mg every 4 weeks.
Neutrophil Counts
Monitor neutrophils 4 to 8 weeks after initiation of therapy and thereafter at regular clinically determined intervals. If the neutrophil count is below 1.0 × 109/L and confirmed by repeat testing, ENSPRYNG should be interrupted until the neutrophil count is > 1.0 × 109/L [see Warnings and Precautions (5.3)].
Injection: 120 mg/mL clear, and colorless to slightly yellow solution in single-dose prefilled syringe.
Pregnancy
Pregnancy Exposure Registry
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.
Risk Summary
There are no adequate data on the developmental risk associated with the use of ENSPRYNG in pregnant women. In an animal reproduction study, no adverse effects on maternal animals or fetal development were observed in pregnant monkeys and their offspring, with administration of satralizumab-mwge at doses up to 50 mg/kg/week (see Data).
In the U.S. general population, the estimated background risk of major birth defect and miscarriage in clinically recognized pregnancies is 2 – 4% and 15 – 20%, respectively. The estimated background risk of major birth defects and miscarriage for the indicated population is unknown.
Clinical Considerations
Fetal/neonatal adverse reactions
Monoclonal antibodies are increasingly transported across the placenta as pregnancy progresses, with the largest amount transferred during the third trimester. Risks and benefits should be considered prior to administering live or live-attenuated vaccines to infants exposed to ENSPRYNG in utero [see Warnings and Precautions (5.1)].
Data
Animal Data
Weekly subcutaneous administration of satralizumab-mwge (0, 2, or 50 mg/kg) to monkeys throughout pregnancy resulted in no adverse effects on postnatal development of the offspring; however, immune function was impaired in offspring at both doses. Plasma exposures (Cave) in dams at the low and high doses were approximately 3 and 100 times, respectively, that in humans at the recommended monthly maintenance dose of 120 mg.
Lactation
Risk Summary
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.
Geriatric 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 [see Clinical Pharmacology (12.3)]. 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.
ENSPRYNG is contraindicated in patients with:
- A known hypersensitivity to satralizumab or any of the inactive ingredients [see Warnings and Precautions (5.4)]
- Active Hepatitis B infection [see Warnings and Precautions (5.1)]
- Active or untreated latent tuberculosis [see Warnings and Precautions (5.1)]
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 [see Adverse Reactions (6.1)].
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 [see Dosage and Administration (2.4)].
Decreased Neutrophil Counts
Decreases in neutrophil counts were observed in patients treated with ENSPRYNG at a higher incidence than placebo [see Adverse Reactions (6.1)].
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.