U.S. FDA APPROVED  DRUGS DURING 2020

Sr.No-  36

ADVERSE REACTIONS-

The most common adverse reactions (incidence at least 15%) are nasopharyngitis, headache, upper respiratory tract infection, gastritis, rash, arthralgia, extremity pain, fatigue, and nausea. 

CONTRAINDICATIONS

• Known hypersensitivity to satralizumab or any of the inactive ingredients 

• Active Hepatitis B infection (

• Active or untreated latent tuberculosis 

WARNINGS AND PRECAUTIONS

 • Infections:                                                                                                                           Delay ENSPRYNG administration in patients with an active infection until the infection is resolved. Vaccination with live or liveattenuated vaccines is not recommended during treatment. 

• Elevated Liver Enzymes:                                                                                                      Monitor ALT and AST levels during treatment; interruption of ENSPRYNG may be required.   • Decreased Neutrophil Counts:                                                                                         Monitor neutrophils during treatment. 

 PATIENT COUNSELING INFORMATION

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

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.

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

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 and Instructions for 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. ENSPRYNG™ [satralizumab-mwge]

Manufactured by: Genentech, Inc. A Member of the Roche Group 1 DNA Way South San Francisco, CA 94080-4990 U.S. License No.: 1048

 CLINICAL PHARMACOLOGY

1. 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.

2. Pharmacodynamics-                                                                                                         The relationship between any of the pharmacodynamic effects of ENSPRYNG and clinical outcomes in NMOSD is unknown.

3. 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.

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%. Reference ID: 4657149

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.

 USE IN SPECIFIC POPULATIONS

1. Pregnancy Risk Summary -                                                                                                  There are no adequate data on the developmental risk associated with the use of ENSPRYNG in pregnant women.

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.

2. 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.

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.

3.Pediatric Use-                                                                                                                      Safety and effectiveness in pediatric patients have not been established.

4.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 

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.