PRODUCT MONOGRAPH INCLUDING PATIENT …

1 PRODUCT MONOGRAPH Master TemplateTemplate date: September 2020 FORXIGA (dapagliflozin propanediol monohydrate)Page 1 of 75 COPYRIGHT 2014-2021 ASTRAZENECA CANADA INCPRODUCT MONOGRAPHINCLUDING PATIENT MEDICATION INFORMATIONFORXIGA Dapagliflozin propanediol monohydrateTablets, 5 mg and 10 mg, OralATC Code: A10BK01 Sodium-glucose co-transporter 2 (SGLT2) inhibitorsAstraZeneca Canada Middlegate RoadMississauga, OntarioL4Y of Initial Authorization:Dec 10, 2014 Date of Revision:Aug 06, 2021 Submission Control Number: 248367 FORXIGA is a registered trademark of AstraZeneca AB, used under license byAstraZeneca Canada MONOGRAPH Master TemplateTemplate date: September 2020 FORXIGA (dapagliflozin propanediol monohydrate)Page 2 of 75 COPYRIGHT 2014-2021 ASTRAZENECA CANADA INCRECENT MAJOR LABEL CHANGES1 INDICATIONS08/20212 CONTRAINDICATIONS08/20214 DOSAGE AND ADMINISTRATION, Dosing Considerations08/20214 DOSAGE AND ADMINISTRATION, Recommended Dose and Dosage Adjustment08/20217 WARNINGS AND PRECAUTIONS08/20217 WARNINGS AND PRECAUTIONS, Geriatrics08/2021 TABLE OF CONTENTSS ections or subsections that are not applicable atthe time of authorization are not MAJOR LABEL OF I: HEALTH PROFESSIONAL WARNINGS AND PRECAUTIONS AND Dose and Dosage FORMS, STRENGTHS, COMPOSITION AND AND Reaction Trial Adverse Common Clinical Trial Adverse Reactions.

2 22 PRODUCT MONOGRAPH Master TemplateTemplate date: September 2020 FORXIGA (dapagliflozin propanediol monohydrate)Page 3 of 75 COPYRIGHT 2014-2021 ASTRAZENECA CANADA Laboratory Findings: Hematologic, Clinical Chemistry and Other Quantitative Adverse Interactions Test of , STABILITY AND HANDLING II: SCIENTIFIC Design and Study 66 PATIENT MEDICATION 68 PRODUCT MONOGRAPH Master TemplateTemplate date: September 2020 FORXIGA (dapagliflozin propanediol monohydrate)Page 4 of 75 COPYRIGHT 2014-2021 ASTRAZENECA CANADA INCPART I: HEALTH PROFESSIONALINFORMATION1 INDICATIONSType 2 Diabetes Mellitus (T2DM)Monotherapy:FORXIGA (dapagliflozin propanediol monohydrate) is indicated for use as an adjunct to diet and exercise to improveglycemic control in adultpatients with T2DM for whom metformin is inappropriate due to contraindications or combination:FORXIGA is indicated in adult patients with T2DM to improve glycemic control in combination with metformin a sulfonylurea metformin and a sulfonylurea sitagliptin (alone or with metformin) insulin (alone or with metformin)when metformin alone or the existing therapy listed above, along with diet and exercise, do not provide adequate glycemic control.

3 Add-On Combination in patients with Cardiovascular Risk Factors or Established Cardiovascular Disease: FORXIGA is indicated as anadjunct to diet, exercise, and standard of care therapy to reduce the risk of hospitalization for heart failure in adults with type 2 diabetes mellitus and CV risk factors or established CV disease. Heart FailureFORXIGA is indicated in adults, as an adjunct to standard of care therapy, for the treatment of heart failure with reduced ejection fraction (HFrEF) to reduce the risk of cardiovascular (CV) death, hospitalization for heart failure and urgentheart failure Kidney DiseaseFORXIGA isindicated to reduce the risk of sustained eGFR decline,end-stage kidney disease, and cardiovascular and renal deathin adults with chronic kidney disease (CKD).

4 (<18 years of age):Safety and efficacy of FORXIGA have not been established in patients under 18 years of age; therefore, Health Canada has not authorized an indication for pediatric 2 Diabetes Mellitus (T2DM)Geriatrics( 65 years of age):FORXIGA should be used with caution in this population as a higherproportion of patients 65 years of age treated with FORXIGA had adverse reactions related to volume PRODUCT MONOGRAPH Master TemplateTemplate date: September 2020 FORXIGA (dapagliflozin propanediol monohydrate)Page 5 of 75 COPYRIGHT 2014-2021 ASTRAZENECA CANADA INCdepletion and renalimpairment or failure, compared to patients treated with placebo. See Geriatricsand 8 ADVERSE REACTIONS. 2 CONTRAINDICATIONS FORXIGA 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.

5 For a complete listing, see 6 DOSAGE FORMS, STRENGTHS, COMPOSITION AND PACKAGING. FORXIGAis contraindicated in patients on dialysis. See 7 WARNINGS AND SERIOUS WARNINGS ANDPRECAUTIONS BOXS erious Warnings and PrecautionsDiabetic Ketoacidosis in patients with Diabetes Clinical trial and post-market cases of diabetic ketoacidosis (DKA), a serious life-threatening condition requiring urgent hospitalization, have been reported in patients with T2DM treated with FORXIGA and other sodium-glucose co-transporter 2 (SGLT2) inhibitors. A number of these cases have been atypical with blood glucose values below mmol/L (250 mg/dL). Some cases of DKA have been fatal. See 8 ADVERSE REACTIONS. patients should be assessed for DKA immediately if non-specific symptoms such as difficulty breathing, nausea, vomiting, abdominal pain, confusion, anorexia, excessive thirst and unusual fatigue or sleepiness occur,regardless of blood glucose level.

6 If DKA is suspected or diagnosed, FORXIGA should be discontinued immediately. FORXIGA should not be used for the treatment of DKA or in patients with a history of DKA. FORXIGA is not indicated, andshould not be used, inpatients with type 1 DOSAGE AND Considerations FORXIGA may be taken at any time of the day with or without food. Assess renal function prior to initiation of FORXIGA therapy and regularly thereafter. See 7 WARNINGS AND PRECAUTIONS. Assess volume status and, if necessary, correct volume depletion prior to initiation of FORXIGA therapy. See 7 WARNINGS AND PRECAUTIONS. Concomitant use with insulin or aninsulin secretagogue ( , sulfonylurea): When FORXIGA is used as add-on therapy with insulin or an insulin secretagogue ( , sulfonylurea), a lower dose of insulin or the insulin secretagogue may be considered to reduce the risk of hypoglycemia.

7 See 7 WARNINGS AND PRECAUTIONSand 8 ADVERSE MONOGRAPH Master TemplateTemplate date: September 2020 FORXIGA (dapagliflozin propanediol monohydrate)Page 6 of 75 COPYRIGHT 2014-2021 ASTRAZENECA CANADA Dose and Dosage AdjustmentType 2 Diabetes Mellitus (T2DM)To improve glycemic control, the recommended starting dose of FORXIGA is 5 mg taken orally oncedaily. In patients tolerating FORXIGA 5 mg once daily and who require additional glycemic control, the dose can be increasedto 10 mg reduce the risk of hospitalization due to HF, the recommended doseof FORXIGA is 10 mg once Failure To reduce the risk of CV death,hospitalization for HF and urgent HF visit in patients with HFrEF, the recommended dose ofFORXIGA is 10 mg taken orally once the DAPA-HF study, FORXIGA wasused in conjunction withother heart failure Kidney DiseaseIn patients with chronic kidney disease, the recommended dose of FORXIGA is 10 mg taken orally once for Special PopulationsRenal impairment:The glucose-lowering efficacy of FORXIGA is dependent on renal function and declines with decreasing renal function.

8 Monitoring of renal function is requiredprior toinitiation of FORXIGA therapy and regularly thereafter. In patients with eGFR less than 60 mL/ , more frequent monitoring of renal dysfunction is recommended. See 7 WARNINGS AND on estimated glomerular filtration rate (eGFR; mL/ ), the dosage recommendations are: eGFR 25 to less than 45 FORXIGA is likely to be ineffective in improving glycemic control in adults with T2DM with an eGFR <45 mL/ Therefore, FORXIGA is not recommended for useto improve glycemic controlin T2DM patients with an eGFR persistently <45 mL/ less than 25 Initiation of treatment with FORXIGA is not recommended in patients with an eGFR less than 25 mL/ On dialysisFORXIGA is contraindicated in patients on dialysis. See 2 impairment:No dosage adjustment for FORXIGA is requiredfor patients with mild or moderate hepatic impairment.

9 FORXIGA exposure is increasedin patients with severe hepatic impairment. See 10 CLINICALPHARMACOLOGY. Therefore, FORXIGA is not recommended for use in this MONOGRAPH Master TemplateTemplate date: September 2020 FORXIGA (dapagliflozin propanediol monohydrate)Page 7 of 75 COPYRIGHT 2014-2021 ASTRAZENECA CANADA INCP ediatrics (<18 years of age):Safety and effectiveness of FORXIGA in pediatric and adolescent patients have not been established; therefore, Health Canada has not authorized an indication for pediatric ( 65 years of age):No dosage adjustment forFORXIGA is required based on age; however renal function and risk of volume depletion should be taken into account. See DoseIf a dose of FORXIGAis missed, it should be taken as soon as the PATIENT remembers.

10 A double dose of FORXIGA should not be taken on the same OVERDOSAGEIt is reasonable to employ supportive measures, as dictated bythe PATIENT s clinical status. The removal of dapagliflozin by hemodialysis has not been management of a suspected drug overdose, contact yourregional poison control DOSAGE FORMS, STRENGTHS, COMPOSITION ANDPACKAGINGT able 1 Dosage Forms, Strengths, Composition and PackagingFORXIGA is available as afilm-coated tablet for oral administration containing the equivalent of 5 mg or 10 mg dapagliflozinas dapagliflozin propanediol 5 mgtablets are yellow, biconvex, round, film coated tablets with 5 engraved on one side and 1427 engraved on the other (dapagliflozin) 10 mg tablets are yellow, biconvex, diamond, film coated tablets with 10 engraved on one side and 1428 engraved on the other 5 mg and 10 mg tablets are provided in blisters in cartons of WARNINGS AND PRECAUTIONSP lease see 3 SERIOUS WARNINGS AND PRECAUTIONS of AdministrationDosage Form / Strength / CompositionNon-medicinal IngredientsOralTablets 5 mg, 10 mgTablet: anhydrous lactose, crospovidone, magnesiumstearate, microcrystalline cellulose, silicon coat: polyvinyl alcohol, titanium dioxide, polyethylene glycol, talc and yellow iron MONOGRAPH Master TemplateTemplate date.