Enspryng^® (Solution) Instructions for Use

Marketing Authorization Holder

F. Hoffmann-La Roche, Ltd (Switzerland)

Manufactured By

Chugai Pharma Manufacturing, Co.Ltd. (Japan)

Packaging and Quality Control Release

F.Hoffmann-La Roche, Ltd (Switzerland)

ATC Code

L04AC19 (Satralizumab)

Active Substance

Satralizumab (Rec.INN registered by WHO)

Dosage Form

Enspryng®

Solution for subcutaneous administration 120 mg/1 ml: syringe-tube with a built-in needle

Dosage Form, Packaging, and Composition

Solution for subcutaneous administration from a clear to highly opalescent liquid, from colorless to slightly yellowish.

Excipients : L-histidine – 3.1 mg, L-aspartic acid – to pH 6.0, L-arginine – 26.1 mg, poloxamer 188 – 0.5 mg, water for injection – to 1 ml.

1 ml – syringe-tubes (1) with a built-in needle – cardboard packs.

Clinical-Pharmacological Group

Immunosuppressive drug – monoclonal antibodies

Pharmacotherapeutic Group

Immunosuppressants, interleukin inhibitors

Pharmacological Action

Satralizumab is a humanized monoclonal antibody from the immunoglobulin G2 (IgG2) subclass that binds to both soluble and membrane-bound human interleukin-6 receptor (IL-6R), and thus prevents signal transmission along the downstream pathway through these receptors. Interleukin-6 (IL-6) is a multifunctional cytokine that is produced by various cell types and is involved in various inflammatory processes.

Some functions of IL-6 are involved in the pathogenesis of neuromyelitis optica and neuromyelitis optica spectrum disorders, including the production of pathological autoantibodies to AQP4 (aquaporin 4, a protein of the water channel family, which is mainly expressed by astrocytes in the CNS). Satralizumab blocks the action of the interleukin-6 (IL-6) protein, which is involved in the processes leading to damage and swelling of nerve system cells, thereby reducing the risk of relapse or onset of neuromyelitis optica spectrum disorders.

Pharmacokinetics

The metabolism of satralizumab has not been specifically studied, since monoclonal antibodies are eliminated, predominantly, through catabolism.

Indications

As monotherapy or in combination with immunosuppressive therapy in adults and adolescents from 12 to 18 years of age for the treatment of neuromyelitis optica and neuromyelitis optica spectrum disorders with antibodies (IgG) to aquaporin-4.

ICD codes

Dosage Regimen

Administer Enspryng^® by subcutaneous injection only.

The recommended loading dose is 120 mg administered every 2 weeks for the first three injections.

Initiate the maintenance dose of 120 mgevery 4 weeks following the completion of the loading doses.

Adhere strictly to the prescribed dosing schedule to maintain therapeutic effect.

If a dose is missed, administer the injection as soon as possible.

Thereafter, resume the regular every 4-week dosing schedule from the most recent administration.

This therapy is indicated for long-term treatment of neuromyelitis optica spectrum disorders.

Regularly monitor patients for clinical response and potential adverse effects throughout the treatment course.

Do not administer live vaccines concurrently with satralizumab therapy.

Complete all necessary immunizations according to current guidelines prior to initiating treatment.

Adverse Reactions

Blood and lymphatic system disorders common – hypofibrinogenemia.

Psychiatric disorders common – insomnia.

Nervous system disorders very common – headache; common – migraine.

Respiratory, thoracic and mediastinal disorders: common – allergic rhinitis.

Skin and subcutaneous tissue disorders common – rash, itching.

Musculoskeletal and connective tissue disorders very common – arthralgia; common – musculoskeletal stiffness.

General disorders and administration site conditions very common – injection-related reactions (redness, itching, pain or swelling at the injection site); common – peripheral edema.

Laboratory and instrumental data very common – decreased white blood cell count; common – increased bilirubin level; decreased platelet count; increased activity of liver enzymes; increased levels of total cholesterol and triglycerides.

Contraindications

Hypersensitivity to satralizumab; pregnancy; breastfeeding period; children under 12 years of age; concomitant use with live, including attenuated, vaccines.

With caution: impaired liver function; impaired renal function; history of intestinal ulcer or diverticulitis.

Use in Pregnancy and Lactation

Use during pregnancy and breastfeeding is contraindicated.

Use in Hepatic Impairment

Use with caution in patients with impaired liver function.

Use in Renal Impairment

Use with caution in patients with impaired renal function.

Pediatric Use

Contraindicated for use in children under 12 years of age.

Special Precautions

Administration of satralizumab should be postponed in patients with active infections until active infections are brought under control.

Before starting therapy with satralizumab, all patients should be checked for latent tuberculosis. Patients with latent tuberculosis should receive standard antibacterial therapy before starting treatment with satralizumab.

Satralizumab should not be used concomitantly with live, including attenuated, vaccines, since the clinical safety of such a combination has not been established. It is recommended to complete all necessary immunizations according to current immunization guidelines before starting therapy with satralizumab.

Mild or moderate increases in liver transaminase activity have been observed with the use of satralizumab. ALT and AST activity should be monitored before starting treatment and during the course of therapy with satralizumab.

Cases of hepatitis B reactivation have been observed with the use of immunosuppressive therapy. Testing for hepatitis B virus should be performed before starting treatment with satralizumab. If the test result is positive, a hepatologist should be consulted before starting treatment and monitored in accordance with local standards to prevent hepatitis B reactivation.

A decrease in neutrophil count has been observed with the use of satralizumab. Neutrophil count should be monitored 4-8 weeks after the start of therapy, then – depending on clinical indications.

Cases of other inflammatory diseases of the CNS have been noted during therapy with IL-6 receptor inhibitors. Attention should be paid to symptoms indicating the development of a demyelinating disease of the CNS (visual and/or coordination disturbances, weakness and trembling in the limbs, numbness and tingling).

Immunomodulatory agents may increase the risk of malignancies.

Satralizumab should be used with caution in patients with a history of intestinal ulcer or diverticulitis. In case of acute abdominal pain, patients should be checked immediately for early detection of gastrointestinal perforation.

The drug should not be used in children from 0 to 12 years of age, since the safety and efficacy of use in this category of patients have not been established.

Drug Interactions

Patients taking individually controlled doses of drugs metabolized by CYP3A4, 1A2 or 2C9 (for example, atorvastatin, calcium channel blockers, theophylline, warfarin, phenytoin, cyclosporine or benzodiazepines) should be under medical supervision; if necessary, the dose of these substances may be adjusted.

Storage Conditions

Store at 2°C (36°F) to 8°C (46°F). Keep in original packaging, protected from light. Keep out of reach of children.

Dispensing Status

Rx Only

Important Safety Information

This information is for educational purposes only and does not replace professional medical advice. Always consult your doctor before use. Dosage and side effects may vary. Use only as prescribed.