PRODUCT MONOGRAPH INCLUDING PATIENT MEDICATION INFORMATION ADDERALL XR® mixed salts amphetamine extended-release capsules Capsule 5 mg, 10 mg, 15 mg, 20 mg, 25 mg, 30 mg Oral Central Nervous System Stimulant Takeda Canada Inc. Date of Initial Approval: 22 Adelaide Street West, Suite 3800 Jan 23, 2004 Toronto, Ontario M5H 4E3 Date of Revision: Dec 21, 2020 Submission Control No: 241496 ADDERALL XR® and ADDERALL® are registered trademarks of Takeda Pharmaceuticals U.S.A., Inc. TAKEDA™ and the TAKEDA Logo® are trademarks of Takeda Pharmaceutical Company Limited, used under license. Product Monograph ADDERALL XR® (mixed salts amphetamine extended-release capsules) Template Date: June 2017 Page 1 of 42 RECENT MAJOR LABEL CHANGES None. Not applicable sections or subsections are omitted from this Product Monograph. Remaining sections and subsections are not renumbered. TABLE OF CONTENTS RECENT MAJOR LABEL CHANGES............................................................................ 2 TABLE OF CONTENTS.................................................................................................. 2 PART I: HEALTH PROFESSIONAL INFORMATION .................................................... 4 1 INDICATIONS ...................................................................................................... 4 1.1 Pediatrics..................................................................................................... 5 1.2 Geriatrics ..................................................................................................... 5 2 CONTRAINDICATIONS....................................................................................... 5 3 SERIOUS WARNINGS AND PRECAUTIONS BOX ............................................ 5 4 DOSAGE AND ADMINISTRATION ..................................................................... 6 4.1 Dosing Considerations................................................................................. 6 4.2 Recommended Dose and Dosage Adjustment............................................ 6 4.3 Administration.............................................................................................. 7 4.5 Missed Dose................................................................................................ 7 5 OVERDOSAGE.................................................................................................... 7 6 DOSAGE FORMS, STRENGTHS, COMPOSITION AND PACKAGING ............. 8 7 WARNINGS AND PRECAUTIONS...................................................................... 9 7.1 Special Populations ................................................................................... 14 7.1.1 Pregnant Women ................................................................................... 14 7.1.2 Breast-feeding........................................................................................ 14 7.1.3 Pediatrics ............................................................................................... 14 7.1.4 Geriatrics................................................................................................ 14 8 ADVERSE REACTIONS .................................................................................... 15 8.1 Adverse Reaction Overview ...................................................................... 15 8.2 Clinical Trial Adverse Reactions ................................................................ 15 8.5 Clinical Trial Adverse Reactions (Pediatrics)............................................. 18 8.6 Post-Market Adverse Reactions ................................................................ 20 9 DRUG INTERACTIONS ..................................................................................... 20 9.2 Overview.................................................................................................... 20 9.3 Drug-Drug Interactions .............................................................................. 20 9.6 Drug-Laboratory Test Interactions ............................................................. 22 10 CLINICAL PHARMACOLOGY........................................................................... 22 10.1 Mechanism of Action .............................................................................. 22 10.2 Pharmacodynamics................................................................................ 22 Product Monograph ADDERALL XR® (mixed salts amphetamine extended-release capsules) Template Date: June 2017 Page 2 of 42 10.3 Pharmacokinetics................................................................................... 23 11 STORAGE, STABILITY AND DISPOSAL ......................................................... 27 PART II: SCIENTIFIC INFORMATION ......................................................................... 28 13 PHARMACEUTICAL INFORMATION ............................................................... 28 14 CLINICAL TRIALS............................................................................................. 29 14.2 Study Results ......................................................................................... 29 14.3 Comparative Bioavailability Studies ....................................................... 30 16 NON-CLINICAL TOXICOLOGY......................................................................... 32 PATIENT MEDICATION INFORMATION ..................................................................... 34 Product Monograph ADDERALL XR® (mixed salts amphetamine extended-release capsules) Template Date: June 2017 Page 3 of 42 PART I: HEALTH PROFESSIONAL INFORMATION 1 INDICATIONS ADDERALL XR (mixed salts amphetamine extended-release capsules) is indicated for the treatment of Attention Deficit Hyperactivity Disorder (ADHD) in: Children (6 – 12 years of age) Adolescents (13 – 17 years of age) Adults (18 years of age or older) A diagnosis of ADHD (DSM-IV) implies the presence of hyperactive-impulsive and/or inattentive symptoms that caused impairment and that were present before age 7 years. The symptoms must be persistent, must be more severe than is typically observed in individuals at a comparable level of development, must cause clinically significant impairment (e.g., in social, academic, or occupational functioning), and must be present in two or more settings (e.g., school or work, and at home). The symptoms must not be better accounted for by another mental disorder. For the Inattentive Type, at least six of the following symptoms must have persisted for at least 6 months: lack of attention to details/careless mistakes, lack of sustained attention, poor listener, failure to follow through on tasks, poor organization, avoids tasks requiring sustained mental effort, loses things, easily distracted, forgetful. For the Hyperactive- Impulsive Type, at least six of the following symptoms must have persisted for at least 6 months: fidgeting/squirming, leaving seat, inappropriate running/climbing, difficulty with quiet activities, “on the go”, excessive talking, blurting answers, can’t wait turn, intrusive. For a Combined Type diagnosis, both inattentive and hyperactive impulsive criteria must be met. Special Diagnostic Considerations The specific etiology of ADHD is unknown, and there is no single diagnostic test. Adequate diagnosis requires the use not only of medical but of special psychological, educational, and social resources. Learning may or may not be impaired. The diagnosis must be based upon a complete history and evaluation of the patient and not solely on the presence of the required number of DSM-IV characteristics. Need for Comprehensive Treatment Program ADDERALL XR is indicated as an integral part of a total treatment program for ADHD that may include other measures (psychological, educational, social) for patients with this syndrome. Drug treatment may not be indicated for all patients with this syndrome. Drug treatment is not intended for use in the patient who exhibits symptoms secondary to environmental factors and/or other primary psychiatric disorders, including psychosis. Appropriate educational placement is essential in patients with this diagnosis and psychosocial intervention is often helpful. When remedial measures alone are insufficient, the decision to prescribe drug treatment will depend upon the physician's assessment of the chronicity and severity of the patient’s symptoms. Long-Term Use The effectiveness of ADDERALL XR for long-term use, i.e., for more than 3 weeks in children aged 6 to 12 years and 4 weeks in adolescents aged 13 to 17 years, and adults, has not been systematically evaluated in controlled trials. Therefore, the physician who elects to use ADDERALL XR for extended periods should periodically re-evaluate the long-term usefulness of Product Monograph ADDERALL XR® (mixed salts amphetamine extended-release capsules) Template Date: June 2017 Page 4 of 42 the drug for the individual patient (see DOSAGE AND ADMINISTRATION). 1.1 Pediatrics Pediatrics (<6 years old): ADDERALL XR should not be used in children under six years, since safety and efficacy in this age group have not been studied. 1.2 Geriatrics ADDERALL XR has not been studied in the geriatric population. 2 CONTRAINDICATIONS ADDERALL XR (mixed salts amphetamine extended-release capsules) is contraindicated in patients who are hypersensitive to this drug or to any ingredient in the formulation, including any non-medicinal ingredient, or component of the container. For a complete listing, see DOSAGE FORMS, STRENGTHS, STRENGTHS, COMPOSITION AND PACKAGING. ADDERALL