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Product Monograph Including Patient Medication Information PRODUCT MONOGRAPH INCLUDING PATIENT MEDICATION INFORMATION PrLORBRENA® Lorlatinib tablets Tablets, 25 and 100 mg, oral Tyrosine Kinase Inhibitor “LORBRENA, indicated for: monotherapy for the first-line treatment of adult patients with anaplastic lymphoma kinase (ALK)-positive locally advanced (not amenable to curative therapy) or metastatic non-small cell lung cancer (NSCLC) has been issued marketing authorization without conditions monotherapy for the treatment of adult patients with anaplastic lymphoma kinase (ALK)-positive metastatic non-small cell lung cancer (NSCLC) who have progressed on: crizotinib and at least one other ALK inhibitor, or patients who have progressed on ceritinib or alectinib has been issued market authorization with conditions, pending the results of trials to verify its clinical benefit. Patients should be advised of the nature of the authorization. For further information for LORBRENA please refer to Health Canada’s Notice of Compliance with conditions - drug products web site: https://www.canada.ca/en/health-canada/services/drugs-health-products/drug-products/notice- compliance/conditions.html” Pfizer Canada ULC Date of Initial Authorization: FEB 20, 2019 17300 Trans-Canada Highway Kirkland, Quebec Date of Revision: H9J2M5 JUN 4, 2021 Submission Control Number: 247174 ®Pfizer Inc. Pfizer Canada ULC, Licensee LORBRENA (lorlatinib) Page 1 of 50 RECENT MAJOR LABEL CHANGES 1 Indications 06/2021 4 Dosage and Administration 06/2021 2 Contraindications 01/2020 6 Warnings and Precautions 01/2020 6 Warnings and Precautions 06/2021 TABLE OF CONTENTS Sections or subsections that are not applicable at the time of authorization are not listed. RECENT MAJOR LABEL CHANGES ........................................................................................... 2 TABLE OF CONTENTS ............................................................................................................. 2 PART I: HEALTH PROFESSIONAL INFORMATION ..................................................................... 4 1 INDICATIONS.............................................................................................................. 4 1.1 Pediatrics................................................................................................................... 4 1.2 Geriatrics................................................................................................................... 4 2 CONTRAINDICATIONS................................................................................................. 4 3 SERIOUS WARNINGS AND PRECAUTIONS BOX ............................................................ 5 4 DOSAGE AND ADMINISTRATION................................................................................. 5 4.1 Dosing Considerations .............................................................................................. 5 4.2 Recommended Dose and Dosage Adjustment ......................................................... 5 4.4 Administration ........................................................................................................ 10 4.5 Missed Dose............................................................................................................ 10 5 OVERDOSAGE........................................................................................................... 10 6 DOSAGE FORMS, STRENGTHS, COMPOSITION AND PACKAGING ............................... 10 7 WARNINGS AND PRECAUTIONS................................................................................ 11 7.1 Special Populations................................................................................................. 14 7.1.1 Pregnant Women.............................................................................................. 14 7.1.2 Breast-feeding................................................................................................... 15 7.1.3 Pediatrics........................................................................................................... 15 7.1.4 Geriatrics........................................................................................................... 15 LORBRENA (lorlatinib) Page 2 of 50 8 ADVERSE REACTIONS................................................................................................ 15 8.1 Adverse Reaction Overview.................................................................................... 15 8.2 Clinical Trial Adverse Reactions .............................................................................. 17 8.2.1 Clinical Trial Adverse Reactions – Pediatrics..................................................... 22 8.3 Less Common Clinical Trial Adverse Reactions....................................................... 22 8.3.1 Less Common Clinical Trial Adverse Reactions – Pediatrics ............................. 22 8.4 Abnormal Laboratory Findings: Hematologic, Clinical Chemistry and Other Quantitative Data.............................................................................................................. 22 8.5 Post-Market Adverse Reactions.............................................................................. 24 9 DRUG INTERACTIONS ............................................................................................... 25 9.2 Drug Interactions Overview.................................................................................... 25 9.4 Drug-Drug Interactions ........................................................................................... 25 9.5 Drug-Food Interactions........................................................................................... 27 9.6 Drug-Herb Interactions........................................................................................... 27 10 CLINICAL PHARMACOLOGY....................................................................................... 27 10.1 Mechanism of Action........................................................................................ 27 10.2 Pharmacodynamics........................................................................................... 27 10.3 Pharmacokinetics.............................................................................................. 28 11 STORAGE, STABILITY AND DISPOSAL......................................................................... 30 12 SPECIAL HANDLING INSTRUCTIONS........................................................................... 30 PART II: SCIENTIFIC INFORMATION ...................................................................................... 31 13 PHARMACEUTICAL INFORMATION ........................................................................... 31 14 CLINICAL TRIALS ....................................................................................................... 31 14.1 Trial Design and Study Demographics .............................................................. 31 14.2 Study Results..................................................................................................... 34 15 MICROBIOLOGY ....................................................................................................... 39 16 NON-CLINICAL TOXICOLOGY..................................................................................... 39 PATIENT MEDICATION INFORMATION ................................................................................. 41 LORBRENA (lorlatinib) Page 3 of 50 PART I: HEALTH PROFESSIONAL INFORMATION 1 INDICATIONS LORBRENA (lorlatinib) is indicated as: monotherapy for the first-line treatment of adult patients with anaplastic lymphoma kinase (ALK)-positive locally advanced (not amenable to curative therapy) or metastatic non-small cell lung cancer (NSCLC) monotherapy for the treatment of adult patients with anaplastic lymphoma kinase NOC/c (ALK)-positive metastatic non-small cell lung cancer (NSCLC) who have progressed on: crizotinib and at least one other ALK inhibitor, or patients who have progressed on ceritinib or alectinib. The marketing authorization with conditions was based on a primary efficacy endpoint of tumor objective response rate and duration of response; no overall survival benefit has been demonstrated (see 14 CLINICAL TRIALS). 1.1 Pediatrics Pediatrics (<18 years of age): No data are available to Health Canada; therefore, Health Canada has not authorized an indication for pediatric use. 1.2 Geriatrics Geriatrics (≥ 65 years of age): Of the patients in Study B7461001 (N=295) and Study B7461006 (N=149) who received 100 mg LORBRENA orally once daily, 54 (18%) and 59 (40%), respectively, were aged 65 years or older. No clinically important differences in safety or efficacy were observed between patients aged 65 years or older and younger patients (see 10 CLINICAL PHARMACOLOGY). 2 CONTRAINDICATIONS LORBRENA (lorlatinib) 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 6 DOSAGE FORMS, STRENGTHS, COMPOSITION AND PACKAGING. Concomitant use of strong CYP3A inducers with LORBRENA is contraindicated due to the potential for serious hepatoxicity (aspartate aminotransferase [AST] and alanine aminotransferase [ALT] elevations (see 4 DOSAGE AND ADMINISTRATION and 9 DRUG INTERACTIONS). LORBRENA (lorlatinib) Page 4 of 50 3 SERIOUS WARNINGS AND PRECAUTIONS BOX Serious Warnings and Precautions Hypercholesterolemia/Hypertriglyceridemia (see 7 WARNINGS AND PRECAUTIONS, Metabolism
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