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  • Page 1 of 61

    PRODUCT MONOGRAPH

    INCLUDING PATIENT MEDICATION INFORMATION

    Pr DUPIXENT™

    dupilumab injection

    solution for subcutaneous injection

    300 mg single-use syringe (300 mg/2 mL)

    200 mg single-use syringe (200 mg/1.14 mL)

    Immunomodulator, Interleukin inhibitor

    Sanofi-aventis Canada Inc.

    2905 Place Louis-R-Renaud

    Laval, Quebec H7V0A3

    Distributed by Sanofi Genzyme,

    a division of sanofi-aventis Canada Inc.

    800-2700 Matheson Blvd East

    Mississauga, ON L4W 4V9

    Submission Control No: 221043

    Date of Initial Approval: November 30, 2017

    Date of Approval: September 25, 2019

    s-a version 3.0 dated September 25, 2019

  • Page 2 of 61

    Table of Contents

    PART I: HEALTH PROFESSIONAL INFORMATION ......................................................... 3 SUMMARY PRODUCT INFORMATION ....................................................................... 3 DESCRIPTION................................................................................................................... 3

    INDICATIONS AND CLINICAL USE ............................................................................. 3 CONTRAINDICATIONS .................................................................................................. 4 WARNINGS AND PRECAUTIONS ................................................................................. 4

    ADVERSE REACTIONS ................................................................................................... 6 DRUG INTERACTIONS ................................................................................................... 9 DOSAGE AND ADMINISTRATION ............................................................................. 10 OVERDOSAGE ............................................................................................................... 11

    ACTION AND CLINICAL PHARMACOLOGY ........................................................... 12 STORAGE AND STABILITY ......................................................................................... 16

    SPECIAL HANDLING INSTRUCTIONS ...................................................................... 16 DOSAGE FORMS, COMPOSITION AND PACKAGING ............................................ 17

    PART II: SCIENTIFIC INFORMATION ............................................................................... 18 PHARMACEUTICAL INFORMATION ......................................................................... 18 CLINICAL TRIALS ......................................................................................................... 19

    DETAILED PHARMACOLOGY .................................................................................... 26 TOXICOLOGY ................................................................................................................ 26

    REFERENCES ................................................................................................................. 27

    PART III: PATIENT MEDICATION INFORMATION ....................................................... 28

    INSTRUCTIONS FOR USE ...................................................................................................... 34 DUPIXENT 300 mg SINGLE-DOSE PRE-FILLED SYRINGE WITH NEEDLE

    SHIELD ............................................................................................................................ 34

    INSTRUCTIONS FOR USE ...................................................................................................... 43 DUPIXENT 200 mg SINGLE-DOSE PRE-FILLED SYRINGE WITH NEEDLE

    SHIELD ............................................................................................................................ 43 DUPIXENT 300 mg SINGLE-DOSE PRE-FILLED SYRINGE ..................................... 53

  • Page 3 of 61

    Pr DUPIXENT™

    dupilumab injection

    solution for subcutaneous injection

    300 mg single-use syringe (300 mg/2 mL)

    200 mg single-use syringe (200 mg/1.14 mL)

    PART I: HEALTH PROFESSIONAL INFORMATION

    SUMMARY PRODUCT INFORMATION

    Route of

    Administration

    Dosage Form /

    Strength

    Clinically Relevant Nonmedicinal

    Ingredients

    Subcutaneous

    injection

    Solution in a pre-filled

    syringe with needle

    shield (PFS-S) or pre-

    filled syringe (PFS)

    150 mg/mL; or pre-

    filled syringe with

    needle shield (PFS-S)

    175 mg/mL

    L-arginine hydrochloride, L-histidine,

    polysorbate 80, sodium acetate, sucrose,

    acetic acid for pH adjustment, water for

    injection.

    For a complete listing see Dosage Forms,

    Composition and Packaging section.

    DESCRIPTION

    DUPIXENT is a recombinant human IgG4 monoclonal antibody that inhibits interleukin-4

    (IL-4) and interleukin-13 (IL-13) signaling by specifically binding to the IL-4Rα subunit

    shared by the IL-4 and IL-13 receptor complexes. DUPIXENT inhibits IL-4 signaling via the

    Type I receptor (IL-4Rα/γc), and both IL-4 and IL-13 signaling through the Type II receptor

    (IL-4Rα/IL-13Rα).

    INDICATIONS AND CLINICAL USE

    DUPIXENT™ (dupilumab injection) is indicated for the treatment of patients aged 12 years and

    older with moderate-to-severe atopic dermatitis whose disease is not adequately controlled with

    topical prescription therapies or when those therapies are not advisable.

    DUPIXENT can be used with or without topical corticosteroids.

  • Page 4 of 61

    Geriatrics (≥65 years of age):

    Of the 1472 patients with atopic dermatitis exposed to DUPIXENT in a phase 2 dose-ranging

    study or phase 3 placebo-controlled studies, a total of 67 were 65 years or older. Although no

    differences in safety or efficacy were observed between older and younger patients, the number

    of patients aged 65 and over is not sufficient to determine whether they respond differently from

    younger patients (see ACTION AND CLINICAL PHARMACOLOGY, Special Populations and

    Conditions). No dose adjustment is recommended for elderly patients.

    Pediatrics (

  • Page 5 of 61

    become infected while receiving treatment with DUPIXENT and do not respond to anti-

    helminth treatment, discontinue treatment with DUPIXENT until infection resolves.

    Conjunctivitis and Keratitis

    Conjunctivitis and keratitis occurred more frequently in subjects who received DUPIXENT.

    Conjunctivitis was the most frequently reported eye disorder. Most subjects with

    conjunctivitis recovered or were recovering during the treatment period (see ADVERSE

    REACTIONS). Keratitis was reported in 65 years of age): Of the 1472 patients with atopic dermatitis exposed to DUPIXENT in a phase 2 dose-ranging

    study or phase 3 placebo-controlled studies, a total of 67 were 65 years or older. Although no

    differences in safety or efficacy were observed between older and younger patients, the number

  • Page 6 of 61

    of patients aged 65 and over is not sufficient to determine whether they respond differently from

    younger patients.

    ADVERSE REACTIONS

    Clinical Trial Adverse Drug Reactions

    Because clinical trials are conducted under very specific conditions the adverse reaction

    rates observed in the clinical trials may not reflect the rates observed in practice and

    should not be compared to the rates in the clinical trials of another drug. Adverse drug

    reaction information from clinical trials is useful for identifying drug-related adverse

    events and for approximating rates.

    Adults

    In the overall exposure pool, a total of 2526 patients with atopic dermatitis were treated with

    DUPIXENT in controlled and uncontrolled clinical trials. Of these, 739 patients were exposed

    for at least 1 year.

    The safety of DUPIXENT monotherapy was evaluated through week 16 based on data from

    three randomized, double-blind, placebo-controlled multicenter studies (SOLO 1, SOLO 2, and a

    phase 2, dose-ranging study) that included 1564 adult patients with moderate-to-severe atopic

    dermatitis (AD). The study population had a mean age of 38.2 years, 41.1 % was female, 67.9 %

    white, 21.9 % Asian, 7.1% black, and reported co-morbid atopic conditions such as asthma

    (39.6%), allergic rhinitis (49.0%), food allergy (37.3%), and allergic conjunctivitis (23.1%).

    The safety of DUPIXENT with concomitant topical corticosteroids (TCS) was evaluated based

    on data from one randomized, double-blind, placebo-controlled multicenter study (CHRONOS).

    A total of 740 patients were treated up to 52 weeks. The study population had a mean age of 37.1

    years, 39.7% was female, 66.2% white, 27.2% Asian, 4.6% black, and reported co-morbid atopic

    conditions such as asthma (39.3%), allergic rhinitis (42.8%), food allergy (33.4%), and allergic

    conjunctivitis (23.2%).

    In the monotherapy studies, the proportion of patients who discontinued treatment due to adverse

    events was 1.9% of the placebo group and 1.9% of the DUPIXENT 300 mg every other week

    (Q2W) group.

    In the concomitant TCS study, the proportion of patients wh