PRODUCT MONOGRAPH INCLUDING PATIENT . - Novo Nordisk
PRODUCT MONOGRAPHINCLUDING PATIENT MEDICATION INFORMATIONPROZEMPIC semaglutide injection2 mg/pen (1.34 mg/mL)4 mg/pen (1.34 mg/mL)Pre-filled pen delivering doses of 0.25 mg or 0.5 mgandPre-filled pen delivering doses of 1 mgATC code: A10BJ06Antihyperglycemic AgentGlucagon-like Peptide-1 (GLP-1) Receptor AgonistNovo Nordisk Canada101 – 2476 Argentia RoadMississauga, OntarioL5N 6M1Date of Initial Approval:January 4, 2018Date of Revision:August 21, 2020Submission Control No: 231580Product Monograph OZEMPIC semaglutide injectionPage 1 of 56
RECENT MAJOR LABEL CHANGESIndications, (1) JUL, 2020Clinical Trials, Study Results (15.2) JUL, 2020TABLE OF CONTENTSRECENT MAJOR LABEL CHANGES .2TABLE OF CONTENTS .2PART I: HEALTH PROFESSIONAL INFORMATION .41INDICATIONS.41.1 Pediatrics .41.2 Geriatrics .42CONTRAINDICATIONS .43SERIOUS WARNINGS AND PRECAUTIONS BOX .54DOSAGE AND ADMINISTRATION.54.1 Dosing Considerations .54.2 Recommended Dose and Dosage Adjustment .54.3 Administration .64.4 Missed Dose .65OVERDOSAGE .66DOSAGE FORMS, STRENGTHS, COMPOSITION AND PACKAGING .77DESCRIPTION .88WARNINGS AND PRECAUTIONS .88.1 Special Populations .118.1.1 Pregnant Women . 118.1.2 Breastfeeding. 118.1.3 Pediatrics . 118.1.4 Geriatrics . 118.1.5 Renal Insufficiency . 118.1.6 Hepatic Insufficiency . 119ADVERSE REACTIONS.129.1 Adverse Reaction Overview .129.2 Clinical Trial Adverse Reactions .129.3 Less Common Clinical Trial Adverse Reactions .159.4 Post-Market Adverse Reactions .1510DRUG INTERACTIONS.1610.1Overview .1610.2Drug-Drug Interactions .1610.3Drug-Food Interactions .1710.4Drug-Herb Interactions .17Product Monograph OZEMPIC semaglutide injectionPage 2 of 56
10.510.6Drug-Laboratory Test Interactions .17Drug-Lifestyle Interactions .1711ACTION AND CLINICAL PHARMACOLOGY.1811.1Mechanism of Action .1811.2Pharmacodynamics.1811.3Pharmacokinetics .2212STORAGE, STABILITY AND DISPOSAL.2413SPECIAL HANDLING INSTRUCTIONS .24PART II: SCIENTIFIC INFORMATION .2514PHARMACEUTICAL INFORMATION .2515CLINICAL TRIALS .2515.1Trial Design and Study Demographics .2515.2Study Results .2816MICROBIOLOGY .3517NON-CLINICAL TOXICOLOGY .35PATIENT MEDICATION INFORMATION.39Product Monograph OZEMPIC semaglutide injectionPage 3 of 56
PART I: HEALTH PROFESSIONAL INFORMATION1INDICATIONSOZEMPIC is indicated for the once-weekly treatment of adult patients with type 2 diabetesmellitus to improve glycemic control, in combination with: diet and exercise in patients for whom metformin is inappropriate due to contraindicationor intolerance.metformin, when diet and exercise plus maximal tolerated dose of metformin do notachieve adequate glycemic control.metformin and a sulfonylurea, when diet and exercise plus dual therapy with metforminand a sulfonylurea do not achieve adequate glycemic control.metformin or a sulfonylurea and a sodium-glucose cotransporter 2 inhibitor (SGLT2i),when diet and exercise plus metformin or a sulfonylurea, in addition to an SGLT2i, donot achieve adequate glycemic control.basal insulin with metformin, when diet and exercise plus basal insulin with metformin donot achieve adequate glycemic control (see CLINICAL TRIALS).OZEMPIC has not been studied in combination with prandial insulin (short acting). OZEMPIC is not a substitute for insulin.OZEMPIC should not be used in patients with type 1 diabetes mellitus (formerly known asinsulin-dependent diabetes mellitus or IDDM) or for the treatment of diabetic ketoacidosis.See DOSAGE AND ADMINISTRATION for information on adjustment of doses of concomitantmedications when adding OZEMPIC to the treatment regimen.1.1PediatricsPediatrics ( 18 years of age): The safety and efficacy of OZEMPIC have not been studied inpediatric populations. OZEMPIC is not indicated for use in pediatric patients.1.2GeriatricsGeriatrics ( 65 years of age): OZEMPIC was studied in a limited number of patients 75years of age or older.2 CONTRAINDICATIONSOZEMPIC is contraindicated in patients with a personal or family history of medullarythyroid carcinoma (MTC) or in patients with Multiple Endocrine Neoplasia syndrome type 2(MEN 2). See WARNINGS AND PRECAUTIONS.OZEMPIC is contraindicated in patients with hypersensitivity to OZEMPIC or to any of theproduct components. See WARNINGS AND PRECAUTIONS.OZEMPIC should not be used during pregnancy or breastfeeding.Product Monograph OZEMPIC semaglutide injectionPage 4 of 56
3SERIOUS WARNINGS AND PRECAUTIONS BOXSerious Warnings and PrecautionsRisk of Thyroid C-cell Tumours Semaglutide causes treatment-dependent thyroid C-cell tumours at clinically relevantexposures in both sexes of rats and mice (see NON-CLINICAL TOXICOLOGY). It isunknown whether semaglutide causes thyroid C-cell tumors, including medullarythyroid carcinoma (MTC), in humans, as human relevance could not be ruled out byclinical or nonclinical studies. OZEMPIC is contraindicated in patients with a personal or family history of MTC andin patients with Multiple Endocrine Neoplasia syndrome type 2 (MEN 2). It is unknownwhether monitoring with serum calcitonin or thyroid ultrasound will mitigate humanrisk of thyroid C-cell tumors. Patients should be counseled regarding the risk andsymptoms of thyroid tumors (see CONTRAINDICATIONS, WARNINGS ANDPRECAUTIONS, ADVERSE REACTIONS and NON-CLINICAL TOXICOLOGY ).44.1DOSAGE AND ADMINISTRATIONDosing ConsiderationsOZEMPIC is to be administered once weekly, at any time of the day, with or without meals.OZEMPIC should not be administered daily.The day of weekly administration can be changed if necessary as long as the time between twodoses is at least 2 days ( 48 hours).OZEMPIC can be used as monotherapy when metformin is not tolerated or is contraindicated,or as combination therapy with one or more antidiabetic drugs (metformin, sulfonylurea [SU],basal insulin, SGLT2i). OZEMPIC should not be given in combination with other GLP-1analogs. Combination with DPP-4 inhibitors has not been studied.When OZEMPIC is added to existing metformin therapy, the current dose of metformin can becontinued unchanged.An increased risk of hypoglycemia was seen with concomitant use of SU or basal insulin withOZEMPIC . When OZEMPIC is added to existing therapy of a sulfonylurea or insulin, areduction in the dose of sulfonylurea or insulin should be considered to reduce the risk ofhypoglycemia. In clinical trials, insulin dose was decreased by 20% at onset of OZEMPIC treatment. See WARNINGS AND PRECAUTIONS.4.2Recommended Dose and Dosage AdjustmentThe recommended starting dose of OZEMPIC is 0.25 mg once weekly. OZEMPIC 0.25 mg isnot a therapeutic dose. After 4 weeks, the dose should be increased to 0.5 mg once weekly. Ifadditional glycemic control is needed after 4 weeks, the dose may be increased to 1 mg onceweekly to further improve glycemic control. The maximum recommended dose is 1 mg onceProduct Monograph OZEMPIC semaglutide injectionPage 5 of 56
weekly.Dosage in Patients with Renal InsufficiencyNo dosage adjustment is required for patients with renal insufficiency. See ACTION ANDCLINICAL PHARMACOLOGY, Pharmacokinetics.Geriatrics ( 65 years old)No dose adjustment is required based on age. See ACTION AND CLINICALPHARMACOLOGY, Pharmacokinetics.Pediatrics ( 18 years old)Safety and efficacy of OZEMPIC in pediatrics aged below 18 years have not been studied. SeeACTION AND CLINICAL PHARMACOLOGY, Pharmacokinetics.Patients with hepatic insufficiencyThe safety and efficacy of OZEMPIC in patients with hepatic insufficiency has not beenstudied. Therefore, OZEMPIC should be used with caution in this patient population (SeeACTION AND CLINICAL PHARMACOLOGY, Pharmacokinetics.)4.3AdministrationOZEMPIC is to be injected subcutaneously in the abdomen, in the thigh or in the upper arm.The injection site can be changed without dose adjustment.Inspect OZEMPIC visually before use. It should appear clear and colourless. Do not useOZEMPIC if particulate matter and colouration is seen.When using OZEMPIC with insulin, instruct patients to administer as separate injections and tonever mix the products.It is acceptable to inject OZEMPIC and insulin in the same body region but the injectionsshould not be adjacent to each other. Rotate injection sites with each dose. Do not use thesame site for each injection. OZEMPIC should not be administered intravenously orintramuscularly.4.4Missed DoseIf a dose is missed, it should be administered as soon as possible within 5 days after the misseddose. If more than 5 days have passed, the missed dose should be skipped and the next doseshould be administered on the regularly scheduled day. In each case, patients can then resumetheir regular once weekly dosing schedule.5OVERDOSAGEOverdoses of up to 4 mg in a single dose, and up to 4 mg in a week have been reported inclinical trials. The most commonly reported adverse event was nausea. All patients recoveredwithout complications. Ensure patients are instructed that OZEMPIC is a weekly medication,and should not be administered daily.There is no specific antidote for overdose with OZEMPIC . In the event of overdose,appropriate supportive treatment should be initiated according to the patient’s clinical signs andProduct Monograph OZEMPIC semaglutide injectionPage 6 of 56
symptoms. A prolonged period of observation and treatment for these symptoms may benecessary, taking into account the long half-life of OZEMPIC of approximately 1 week.For management of a suspected drug overdose, contact your regional poison control centre.6DOSAGE FORMS, STRENGTHS, COMPOSITION AND PACKAGINGTable – Dosage Forms, Strengths, Composition and PackagingRoute ofAdministrationSubcutaneousDosage Form /Strength/CompositionInjectable, 1.34 mg/mLNon-medicinal IngredientsDisodium phosphate dihydrate, propyleneglycol, phenol, and water for injections.OZEMPIC is provided in a pre-filled, multi-dose, disposable pen, which contains the drugsolution, semaglutide in a 1.5 mL or 3 mL cartridge.Each 1 mL of OZEMPIC solution contains 1.34 mg of semaglutide and the following nonmedicinal ingredients disodium phosphate dihydrate, propylene glycol, phenol, and water forinjections.The primary packaging contains a 1.5 mL or 3 mL glass cartridge (Type I glass) closed at theone end with a rubber plunger (chlorobutyl) and at the other end with an aluminium cap with arubber disc (bromobutyl/polyisoprene) inserted. The cartridge is assembled into a pre-filledmulti-dose disposable pen made of polypropylene, polyoxymethylene, polycarbonate andacrylonitrile butadiene styrene.There are two variants of the pre-filled multi-dose pen for OZEMPIC .OZEMPIC 0.25 mg, 0.5mg/dose contains 1.5 mL solution, equivalent to 2 mg semaglutide.OZEMPIC 1 mg/dose contains 3 mL solution, equivalent to 4 mg semaglutide.Patients should not administer the full volume of the pen at any time.NovoFine Plus needles are included in the OZEMPIC package.Pack sizes of:Carton of 1 Pen Pen delivers doses of 0.25 mg or 0.5 mg 6 NovoFine Plus needles Intended to be used for dose escalation and maintenance treatment at the0.5 mg doseCarton of 1 Pen Pen delivers 1 mg doses 4 NovoFine Plus needles Intended to be used for maintenance treatment at the 1 mg dose onlyProduct Monograph OZEMPIC semaglutide injectionPage 7 of 56
7DESCRIPTIONOZEMPIC contains semaglutide, a glucagon-like peptide-1 (GLP-1) receptor agonist (or GLP-1analog) with 94% sequence homology to human GLP-1. The peptide backbone is produced byyeast fermentation and includes three amino acid substitutions to allow for attachment of analbumin-binding C-18 fatty diacid with a hydrophilic spacer and to increase stabilisation againstdegradation by the enzyme dipeptidyl-peptidase 4 (DPP-4). The molecular weight ofsemaglutide is approximately 4 kilodalton.OZEMPIC is a clear and colourless solution with a pH of 7.4. OZEMPIC is provided in a prefilled multi-dose disposable pen, which contains the drug solution, semaglutide, in a 1.5 mL or3 mL cartridge, equivalent to 2 mg or 4 mg semaglutide. See DOSAGE FORMS, STRENGTHS,COMPOSITION AND PACKAGING.8WARNINGS AND PRECAUTIONSPlease see the Serious Warnings and Precautions Box at the beginning of Part I: HealthProfessional Information.GeneralOZEMPIC should not be used in patients with type 1 diabetes mellitus or for the treatment ofpatients with diabetic ketoacidosis.OZEMPIC should not be administered intramuscularly.Carcinogenesis and MutagenesisRisk of Thyroid C-Cell TumorsIn mice and rats, semaglutide caused a treatment-duration-dependent increase in the incidenceof thyroid C-cell tumors (adenomas and carcinomas) after lifetime exposure at clinically relevantplasma exposures (see NON-CLINICAL TOXICOLOGY). It is unknown whether semaglutidecauses thyroid C-cell tumors, including MTC, in humans as human relevance could not bedetermined. Thyroid C-cell tumors in rodents are a known class effect for GLP-1 receptoragonists.In clinical trials, there were no cases of MTC observed in patients treated with OZEMPIC .Counsel patients regarding the potential risk for MTC with the use of OZEMPIC and informthem of symptoms of thyroid tumors (e.g. a mass in the neck, dysphagia, dyspnea, persistenthoarseness).It is unknown whether monitoring with serum calcitonin or thyroid ultrasound will mitigate thepotential risk of MTC, and such monitoring may increase the risk of unnecessary procedures,due to low test specificity for serum calcitonin and a high background incidence of thyroiddisease. Patients with thyroid nodules noted on physical examination or neck imaging obtainedfor other reasons should be referred to an endocrinologist for further evaluation. Althoughroutine monitoring of serum calcitonin is of uncertain value in patients treated with OZEMPIC ifserum calcitonin is measured and found to be elevated, the patient should be referred to anendocrinologist for further evaluation. (see Clinical Trial Adverse ReactionsOZEMPIC is contraindicated in patients with a personal or family history of medullary thyroidcarcinoma (MTC) or in patients with Multiple Endocrine Neoplasia syndrome type 2 (MEN 2).Product Monograph OZEMPIC semaglutide injectionPage 8 of 56
CardiovascularHeart Rate IncreaseOZEMPIC causes an increase in heart rate (see ACTION AND CLINICAL PHARMACOLOGY).Caution should be observed in patients who have cardiac conditions that might be worsened byan increase in heart rate, such as tachyarrhythmias (see DRUG INTERACTIONS).PR Interval ProlongationOZEMPIC causes a prolongation of the PR interval of the electrocardiogram (see ACTIONAND CLINICAL PHARMACOLOGY). Caution should be observed in patients with pre-existingconduction system abnormalities (e.g., marked first-degree AV block or second- or third-degreeAV block) or a history of rhythm disturbances (e.g., tachyarrhythmias).Heart FailureThere is no therapeutic experience in patients with congestive heart failure New York HeartAssociation (NYHA) class IV.Endocrine and MetabolismHypoglycemia with Concomitant Use of Insulin Secretagogues or InsulinPatients receiving OZEMPIC in conjunction with sulfonylurea or basal insulin may have anincreased risk of hypoglycemia. The risk of hypoglycemia may be lowered by a reduction in thedose of sulfonylurea (or other concomitantly administered insulin secretagogues) or insulinwhen initiating treatment with OZEMPIC . See DOSAGE AND ADMINISTRATION, andADVERSE REACTIONS.Other incretin drugsConcomitant use of OZEMPIC with other GLP-1 analogs and DPP-4 inhibitors has not beenstudied. It is unknown if concomitant use of drugs acting via similar pathways affects theefficacy and safety of OZEMPIC .Hepatic/Biliary/Pa
Novo Nordisk Canada 101 – 2476 Argentia Road . Mississauga, Ontario . L5N 6M1 . Date of Initial Approval: January 4, 2018 . Date of Revision: August 21, 2020 . Submission Control No: 231580 . Product Monograph OZEMPIC semaglutide injection Page 2 of 56 RECENT MAJOR LABEL CHANGES Indications, (1) JUL, 2020 Clinical Trials, Study Results (15 .
INCLUDING PATIENT MEDICATION INFORMATION . PrVictoza liraglutide injection . 6 mg/mL . Solution for Injection in a pre-filled pen . Human Glucagon Like Peptide-1 (GLP-1) Novo Nordisk Canada Inc. 101-2476 Argentia Road Mississauga, Ontario
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In the US, people with diabetes using Novo Nordisk insulin, who have lost health insurance coverage because of a change in job status due to the COVID-19 pandemic, may now be eligible for enrolment in Novo Nordisk’s Diabetes Patient Assistance
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