ID-6772 - PCPs or Endos Speaker Deck for RTD.pptx

ID-6772 - PCPs or Endos Speaker Deck for RTD

1. DECLARE- ing the Importance of Early Intervention in T2D Management ID-6772/Dec-25

2. Disclaimer The meeting and material are sponsored by PT. AstraZeneca Indonesia. This is a promotional meeting. The speaker in this meeting receive honoraria from PT. AstraZeneca Indonesia. Pertemuan ilmiah dan materi dalam pertemuan ini disponsori oleh PT. AstraZeneca Indonesia. Pertemuan ilmiah ini adalah pertemuan yang bersifat promosi. Pembicara dalam pertemuan ilmiah ini menerima honoraria dari PT. AstraZeneca Indonesia .

3. 08 December 2023 3 T2D Prevalence in Indonesia ~74% are undiagnosed 28% Microvascular complications 16,4% Macrovascular complications

4. HF and CKD are the earliest and most common complications of T2D 1,2 * Data based on a study of 46,720 Medicare patients (aged ≥65 years) with T2D who developed HF between 1994 and 1999. 29 CKD = chronic kidney disease; CV = cardiovascular; HF = heart failure; MI = myocardial infarction; PAD = peripheral artery disease; T2D = Type 2 diabetes 1. Bergenstal RM et al. Am J Med . 2010;123(4):374.e9–e18.2. Birkeland KI et al. Oral presentation at the 55th European Association for the Study of Diabetes Annual Meeting; 16–20 September 2019; Barcelona, Spain. Presentation #126.3. Bertoni AG et al. Diabetes Care. 2004;27(3):699–703. 4. Alicic RZ et al. Clin J Am Soc Nephrol. 2017;12(12):2032–2045. . 5. Drawz PE et al. Kidney Int Suppl. 2013;3(4):372–379. 6. Gansevoort RT et al. J Am Soc Nephrol. 2009;20(3):465–468. INITIAL CV AND RENAL DISEASE MANIFESTATION IN PATIENTS WITH T2D 2 60 % cardiorenal diseases (HF or CKD) Adapted from Birkeland KI et al. 2019. Up to 40% of patients with T2D who were diagnosed with HF died within 5 years of diagnosis 3* Up to 40% of patients with T2D develop CKD 4 HF 24 % PAD 10 % MI 13 % Stroke 18 % CKD 36 % Early intervention is critical to protect against cardio and renal outcomes 5,6

5. While HbA1c control is important, is it enough to fully protect T2DM patients from complications & death? Gaede P et al. . Diabetologia , 61(8), 1724–1733 . Conventional Intensive Systolic BP (mm Hg) <160 <140 b Diastolic BP (mm Hg) <95 <85 HbA1c (%) <7.5 <6.5 c Triglycerides (mmol/L) <2.2 <1.7 d Total cholesterol (mmol/L) <6.5 <5.0 e HDL cholesterol (mmol/L) >0.9 >1.1 ACE inhibitor irrespective of BP No Yes Aspirin in patients with known ischemia Yes Yes Aspirin in patients with peripheral vascular disease No Yes Vitamin C and E supplement No Yes Despite optimal management of risk factor in intensive therapy Residual risk of cardiorenal complications Leading to high residual risk of death Residual Risk Residual Risk Residual Risk

6. Meet Ms. A, your patient newly diagnosed with T2D In your patients newly diagnosed with T2D, early intervention is critical to protect the heart and kidneys 1,2 Hypothetical patient profile. ARB = angiotensin receptor blocker; BMI = body mass index; BP = blood pressure; eGFR = estimated glomerular filtration rate; HbA 1c = haemoglobin A 1c ; LDL-C = low density lipoprotein cholesterol; T2D = Type 2 diabetes. 1. Alicic RZ et al. Clin J Am Soc Nephrol. 2017;12(12):2032–2045. 2. Drawz PE et al. Kidney Int Suppl. 2013;3(4):372–379. HbA 1c 7.8% BP 140/90 mmHg eGFR 75 mL/min/1.73m 2 BMI 29 kg/m 2 LDL-C 152 mg/dL Metformin, ARB

7. Start with more. XIGDUO goes beyond HbA 1c 1 * Data are mean change from baseline; p<0.0001 vs placebo + metformin; † XIGDUO and FORXIGA are not indicated for the management of weight loss or high blood pressure. Weight change was an exploratory endpoint in clinical trials. Blood pressure change was primarily assessed as a safety and tolerability measure. HbA 1c = haemoglobin A 1c . 1. Bailey CJ et al. Lancet . 2010;375(9733):2223-2233. 2. XIGDUO Product Information 2022 Dapagliflozin 10 mg once daily and metformin were administrated as individual tablets XIGDUO combination tablets are considered to be bioequivalent to co-administration of corresponding doses of dapagliflozin and metformin administered together as individual tablets Administration of 5 mg dapagliflozin twice daily gave similar overall exposures (AUCSS) over a 24-hour period as 10 mg dapagliflozin administered once daily. As expected, 5 mg dapagliflozin administered twice daily compared with 10 mg dapagliflozin once daily resulted in lower peak dapagliflozin plasma concentrations ( C max ) and higher rough plasma dapagliflozin concentrations ( C min ) XIGDUO XR (dapagliflozin and metformin HCl extended release) is indicated as substitution therapy for treatment of type 2 diabetes mellitus in adjunct to diet and exercise to improve glycemic control in adult patients already controlled with dapagliflozin and metformin XR given concurrently at the same dose level. 0.6 0.7 0.8 0.9 0.5 0.4 0.3 0.2 0.1 Change in HbA 1c from baseline (%) -0.84% (n=135) 2.8x -0.30% (n=137) XIGDUO Placebo + metformin HbA 1C REDUCTION IN THIS STUDY, XIGDUO DEMONSTRATED: Significant reductions in HbA 1c -0.84% decrease from baseline at 24 weeks 1* (Mean baseline HbA 1c = 7.92%) -0.30% reduction in HbA 1c seen with placebo from baseline at 24 weeks 1 (Mean baseline HbA 1c = 8.11%) Significant reductions in weight -2.9 kg weight loss from baseline at 24 weeks 1* (Mean baseline body weight = 86.3 kg) -0.9 kg weight loss seen with placebo from baseline at 24 weeks 1 (Mean baseline body weight = 87.7 kg) ADDITIONAL BENEFITS † Blood pressure reductions -5.1 mmHg reduction in systolic blood pressure from baseline at 24 weeks 1 (Mean baseline systolic blood pressure = 125 mmHg) -0.2 mmHg reduction in systolic blood pressure seen with placebo from baseline at 24 weeks 1 (Mean baseline systolic blood pressure = 127.7 mmHg)

8. * DAPA dose was uptitrated to a maximum of 10 mg over an 18-week period based on glycaemic response and tolerability. Nauck MA, et al . Diabetes Care 2011;34:2015 –22 . Significant A1c reduction with XIGDUO Primary Endpoint Result: HbA 1c HbA 1c reductions with DAPA were noninferior to those with glipizide as add-on to MET at 52 weeks Dapagliflozin Add-on to Metformin vs a Sulphonylurea *No statistical treatment-group comparisons were made. Del Prato, S, et al. Diabetes, Obesity and Meta bolism 2015;17:581-590 Primary Endpoint Result (Extension) DAPA was associated with greater durability of HbA 1c reduction vs glipizide . By Week 208, the DAPA group had a reduced HbA 1c vs the glipizide group Dapagliflozin Add-on to Metformin vs a Sulphonylurea

9. Key Secondary Endpoint: Weight 1 DAPA was associated with weight loss whereas glipizide treatment resulted in weight gain Weight (kg) -3.5 -1.5 -1.0 -0.5 1.5 88.4 BL DAPA + MET (n=400) Glipizide + MET (n=401) -2.0 -2.5 -3.0 1.0 0.0 87.6 BL –3.22 kg +1.44 kg -4.65 kg difference P <0.0001 Additional Endpoint Result: BP 2 Mean SBP was reduced from baseline to Week 52 in the DAPA group but not in the glipizide group. This reduction in SBP was maintained during the extension period in the DAPA group Additional benefits Beyond A1c * DAPA dose was uptitrated to a maximum of 10 mg over an 18-week period based on glycaemic response and tolerability. Safety DAPA treatment was generally safe and well tolerated 1 DAPA was more frequently associated with UTIs and genital infections than glipizide 1 Most of the events were reported in the first year and responded to standard treatment 2 Adjusted proportions of patients experiencing at least one hypoglycaemic event was more than 10-fold lower with DAPA vs glipizide: At 52 weeks: 3.5% vs 40.8%; difference – 37.2%; p<0.0001 1 At 208 weeks: 5.4% vs 51.5% 2 1. Nauck MA, et al . Diabetes Care 2011;34:2015 –22; 2. Del Prato, S, et al . Diabetes, Obesity and Meta bolism 2015;17:581-590

10. Metformin IR Multiple daily dosing -- poor compliance Frequent GI side effects Metformin XR QD -- regimen simplification Less GI side effects Timmins P, et al. Clin Pharmacokinet . 2005;44(7):721-9 Donnelly LA ,et l. Diabetes Obes Metab . 2009 Apr;11(4):338-42. Harris SB. Expert Rev Clin Pharmacol . 2016;9(11):1453-62 15 From Metformin IR to Metformin XR * p=0.0001 81% 62% Metformin hydrochloride Inner solid particulate phase Outer solid continuous phase IR : Intermediate release; XR : Extended Release ; GI : Gastrointestinal; QD: quaque die (Once A day)

11. 11 2023 ADA Standards of Care in Diabetes Use of Glucose-Lowering Medications in the Management of T2D a In people with HF, CKD, established CVD or multiple risk factors for CVD, the decision to use a GLP-1 RA or SGLT2i with proven benefit should be independent of background use of metformin; b A strong recommendation is warranted for people with CVD and a weaker recommendation for those with indicators of high CV risk. Moreover, a higher absolute risk reduction and thus lower numbers needed to treat are seen at higher levels of baseline risk and should be factored into the shared decision-making process; c For GLP-1 RA, CVOTs demonstrate their efficacy in reducing composite MACE, CV death, all-cause mortality, MI, stroke, and renal endpoints in individuals with T2D with established/high risk of CVD; d For SGLT2i, CV/renal outcomes trials demonstrate their efficacy in reducing the risk of composite MACE, CV death, all-cause mortality, MI, hHF, and renal outcomes in individuals with T2D with established/high risk of CVD; e Low-dose TZD may be better tolerated and similarly effective. Adapted from American Diabetes Association. Diabetes Care . 2023;46(suppl 1):S1-S298. Healthy Lifestyle Behaviors; Diabetes Self-Management Education and Support (DSMES); Social Determinants of Health (SDOH) Goal: Achievement and Maintenance of Glycemic and Weight Management Goals To avoid therapeutic inertia reassess and modify treatment regularly (3-6 months) Efficacy for weight loss Neutral: DPP-4i, Metformin Intermediate: GLP-1 RA (not listed above), SGLT2i High: Dulaglutide, Liraglutide Very High: Semaglutide , Tirzepatide In general, higher efficacy approaches have greater likelihood of achieving glycemic goals Efficacy for glucose lowering Intermediate: DPP-4i High: GLP-1 RA (not listed above), Metformin, SGLT2i, Sulfonylurea, TZD Very High: Dulaglutide (high dose), Semaglutide , Tirzepatide Insulin Combination Oral, Combination Injectable (GLP-1 RA/Insulin) Glycemic Management: Choose approaches that provide the efficacy to achieve goals: Metformin OR Agent(s) including COMBINATION therapy that provide adequate EFFICACY to achieve and maintain treatment goals Consider avoidance of hypoglycemia a priority in high-risk individuals Achievement and Maintenance of Weight Management Goals: Set individualized weight management goals General lifestyle advice: medical, nutrition therapy/eating patterns/physical activity Intensive evidence-based structural weight management program Consider medication for weight loss Consider metabolic surgery When choosing glucose-lowering therapies: Consider regimen with high-to-very-high dual glucose and weight efficacy Identify barriers to goals: Consider DSMES referral to support self-efficacy in achievement of goals Consider technology (e.g., diagnostic CGM) to identify therapeutic gaps and tailor therapy Identify and address SDOH that impact achievement of goals If A1C above target If additional cardiorenal risk reduction or glycemic lowering needed +HF SGLT2i d with proven HF benefit in this population + ASCVD b Defined differently across CVOTs but all included individuals with established CVD (e.g., MI, stroke, any revascularization procedure). Variability included: conditions such as TIA, UA, amputation, symptomatic or asymptomatic CAD. +Indicators of high risk While definitions vary, most comprise ≥55 years of age with 2 or more additional risk factors (including obesity, HTN, smoking, dyslipidemia, or albuminuria) +CKD (on maximally tolerated dose of ACEI/ARB) GLP-1 RA with proven CVD benefit if SGLT2i not tolerated or contraindicated SGLT2i d with primary evidence of reducing CKD progression Use SGLT2i in people with an eGFR ≥20 mL/min/1.73 m 2 ; once initiated should be continued until initiation of dialysis or transplantation PREFERABLY OR If A1C above target, for patients on SGLT2i, consider incorporating a GLP-1 RA and vice versa +ASCVD/INDICATORS of HIGH RISK GLP-1 RA c with proven CVD benefit SGLT2i d with proven CVD benefit EITHER/ OR For patients on a GLP-1 RA, consider adding SGLT2i with proven CVD benefit and vice versa TZD e +HF Current or prior symptoms with HF with documente d HFrEF or HFpEF +CKD eGFR <60 mL/min/1.73 m 2 OR albuminuria (ACR ≥30 mg/g). These measurements may vary over time; thus, a repeat measure is required to document CKD. If A1C above target Goal: Cardiorenal Risk Reduction in High-Risk Patients with T2D (in addition to comprehensive CV risk management) a

12. The highest representativeness of the general T2D patients. 1 Sustained ≥40% decrease in eGFR to eGFR <60 mL/min/1.73 m2 and/or ESKD and/or renal death hHF randomisation 2 PRIMARY ENDPOINTS 2 1:1 Dapagliflozin 1:1 (10 mg/day) + SOC* PLACEBO + SOC* P A TIENT POPUL A TION 2 17,160 T2D patients aged 60% 40% 40% SECONDARY ENDPOINTS 2 Renal composite: sustained ≥40% decrease in eGFR to eGFR <60 mL/min/1.73 m2 and/or ESKD and/or renal or CV death All-cause mortality Safety endpoint Composite of CV death, MI, stroke (MACE) Co-primary efficacy endpoints Composite of CV death or hospitalisation MACE PRE-SPECIFIED EXPLORATORY ENDPOINTS INCLUDED 2 : CV Risk factor 2 Established CV disease 2 (n=10,186) (n=6,974) 4.2 years median follow-up time Average eGFR 2 (85.2 mL/min/1.73m 2 ) *Add on to background CV and oGLD therapies per treating physician. 2 CV=cardiovascular; CVOT=cardiovascular outcome trial; DECLARE-TIMI 58=Dapagliflozin Effect on Cardiovascular Events–Thrombolysis in Myocardial Infarction 58; eGFR=estimated glomerular filtration rate; ESKD=end-stage kidney disease; hHF = hospitalisation for heart failure; MACE, major adverse cardiovascular events; MI=myocardial infarction; oGLD , other glucose-lowering drugs; SOC=standard of care; T2D=type 2 diabetes References : 1. Birkeland KI, et al. Diabetes Obes Metab. 2019;21:968–974. 2. Wiviott SD et al. N Engl J Med 2019; 380:347–357.

13. Act early—FORXIGA reduces the risk of hHF and new onset or further progression of nephropathy 1 * hHF alone was a separate, nominally significant exploratory endpoint in DECLARE; the primary endpoint composite of CV death/ hHF was driven by hHF ; † Nominally significant, prespecified exploratory renal composite outcome of a sustained decrease of ≥40% in eGFR to <60 mL/min/1.73m 2 of body surface area, new ESKD, or death from renal causes. ARR = absolute risk reduction; CI = confidence interval; CV = cardiovascular; DECLARE = Dapagliflozin Effect on Cardiovascular Events; ESKD = end-stage kidney disease; HbA 1c = haemoglobin A 1c ; hHF = hospitalisation for heart failure; HR = hazard ratio; RRR = relative risk reduction; T2D = Type 2 diabetes. 1. Wiviott SD et al. N Engl J Med . 2019;380(4):347–357. In patients with T2D and multiple CV risk factors or established CV disease FORXIGA is proven to reduce the risk of hHF * and shown to reduce the risk of progression to nephropathy in patients with T2D and multiple CV risk factors or established CV disease vs placebo DECLARE EXPLORATORY ENDPOINTS DECLARE was a randomised , double-blind, multinational, placebo-controlled, phase 3 trial. Patients were randomly assigned in a 1:1 ratio to receive 10 mg of FORXIGA daily or matching placebo. The use of other glucose-lowering agents (other than an open-label SGLT2i, pioglitazone, or rosiglitazone) was at the discretion of the treating physician. Patients were 40 years of age or older and had T2D (HbA 1c level of ≥6.5% and <12.0%) and a creatinine clearance of ≥60 mL/min. in progression to nephropathy † (1.5% vs 2.8%) HR 0.53; 95% CI, 0.43, 0.66 1.3 % ARR 47 RRR % Exploratory Endpoint vs Placebo in hHF 0.8 % ARR 27 RRR % (2.5% vs 3.3%) HR 0.73; 95% CI, 0.61, 0.88 Exploratory Endpoint vs Placebo DECLARE —a CVOT of patients with T2D representative of those you treat every day N=17,160 ~60 % had T2D + multiple CV risk factors ~40 % had T2D + established CV disease 17% RRR (0.9% ARR) in the primary composite endpoint of CV death or hHF vs placebo

14. 14 FORXIGA did not only consistently reduce the risk of microalbuminuria deterioration, but also more patients reversed back to micro/ normo albuminuria a Exploratory outcome macro, macroalbuminuria; micro, microalbuminuria; normo , normoalbuminuria Raz I, et al. Presented at 79 th Scientific Sessions of the American Diabetes Association; June 7 th –11 th , 2019; San Francisco, CA, USA; 244-OR Primary prevention Normo Micro Macro ↓ 21% 0.79 (0.72, 0.87) a Progression Micro Normo Macro ↓ 46% 0.54 (0.45, 0.65) a Micro Macro Micro Normo ↓ 27% 0.73 (0.67, 0.79) a Regression Micro Macro Micro Normo ↑ 54% 1.54 (1.40, 1.69) a

15. 15 PRIMARY COMPOSITE ENDPOINT: DECLINING KIDNEY FUNCTION, ESKD, AND RENAL OR CV DEATH 1* HR 0.61 (95% CI, 0.51, 0.72) p<0.001 Placebo (n=2152) 4 8 12 16 20 24 Cumulative incidence (%) 4 8 12 16 20 24 28 32 FORXIGA 10 mg (n=2152) Time from randomisation Median follow-up of 2.4 years 5.3 % ARR 39 RRR % NNT=19 PATIENTS Consistent efficacy in patients with or without T2D 2† *Primary composite endpoint of ≥50% sustained decline in eGFR, reaching ESKD, and renal or CV death 1 . ESKD defined as the need for maintenance dialysis (peritoneal or haemodialysis ) for at least 28 days and renal transplantation or sustained eGFR <15 mL/min/1.73m 2 for at least 28 days 1 ; † There was no significant interaction of the effect on the primary composite endpoint by diabetes status (p for interaction = 0.24). 2 ARR, absolute risk reduction; CI, confidence interval; CKD, chronic kidney disease; CV, cardiovascular; DAPA-CKD, Dapagliflozin And Prevention of Adverse outcomes in Chronic Kidney Disease; eGFR, estimated glomerular filtration rate; ESKD, end-stage kidney disease; HR, hazard ratio; NNT, number needed to treat; RRR, relative risk reduction; T2D, type 2 diabetes. References: 1. Heerspink HJL et al. N Engl J Med. 2020;383(15):1436–46. 2. Wheeler DC et al. Lancet Diabetes Endocrinol. 2021;9(1):22–1. Adapted from Heerspink HJL et al. 2020. Treatment with FORXIGA has shown to reduce the risk of the composite of declining kidney function, ESKD, and renal or CV death in patients with or without T2D 1,2

16. Different views but many times the same Patient! 16 Inclusion criterion: CrCl ≥60 mL/min 1 949 mg/g Median UACR 3 13 mg/g Median UACR 2 1 2 3 4 5 CKD stage: ≥100 90 80 70 60 50 40 30 20 eGFR (mL/min/1.73 m 2 ) 10 Inclusion criterion: eGFR ≥25 to ≤75 mL/min/1.73 m 2 3 85 mL/min/1.73 m 2 Mean eGFR 1 43 mL/min/1.73 m 2 Mean eGFR 3 Disclaimer: in Indonesia, Forxiga is approved for CKD patients with eGFR >30 mL/min/1.73m 2 Mean eGFR and median UACR values are at baseline. FORXIGA is not recommended in patients on dialysis and should not be initiated in patients with eGFR <25 mL/min/1.73 m 2 4 CKD, chronic kidney disease; CrCl , creatinine clearance; CV, cardiovascular; eGFR, estimated glomerular filtration rate; T2D, Type 2 diabetes; UACR, urine albumin:creatinine ratio 1. Mosenzon O, et al. Lancet Diabetes Endocrinol 2019;7:606–617; 2. Raz I, et al. Diabetes Obes Metab 2018;20:1102–1110; 3. Wheeler DC, et al. Nephrol Dial Transplant 2020;35:1700–1711; 4. Forxiga Approved PI 2023 FORXIGA - Cardiorenal protection spans from prevention (in T2D) to treatment in CKD

17. Secondary prevention population SGLT2i prevent heart failure and renal disease, and reduce atherosclerotic events (major adverse cardiovascular events) Primary prevention population SGLT2i prevent heart failure and renal disease but do not reduce major adverse cardiovascular events Major adverse cardiovascular events Hospitalisation for heart failure Renal protection Cardiorenal efficacy of FORXIGA Diabetes established cardiovascular disease Diabetes and multiple risk factors Based on a meta- analysis of subgroups of 3 CVOTs (CANVAS, EMPA-REG and DECLARE): Dapagliflozin did not show superiority for MACE vs placebo in the primary DECLARE analysis . Renal endpoints and the mono-component of hHF were exploratory endpoints Defined as MACE. MACE = major adverse cardiovascular events; SGLT2i = sodium-glucose cotransporter inhibitors. Verma S et al. Lancet . 2019;393:3-5. Benefits of FORXIGA

18. 18 Why to take a chance in a patient suffering with complex Cardio-Renal Metabolic disease and not achieving its Goals? HF: Heart Failure; HFrEF : Heart Failure with a reduced Ejection Fraction; CKD: Chronic Kidney Diease ; RCT: Randomised Control Trial References: 1. Forxiga Approved Product Information Indonesia; 2. Wiviott SD et al. N Engl J Med. 2019;380(4):347-357. ; 3. McMurray JJV et al. N Engl J Med . 2019;381(21):1995-2008 .; 4. Heerspink HJL et al. Epub 2020 Sep 24. PMID: 32970396.; 5. Sonesson C, et al. Cardiovascular diabetology . 2016 Dec;15(1):1-2.; 6. CDSCO-guidelines for BA/BE studies. **No infor mation from the Product Information *Generic products aren’t required to be tested in RCT

19. Bioequivalence and Therapeutic equivalence are not similar 1 19 Pharmaceutical Equivalence (Stability & Dissolution Testing) 1. Vandana Roy, Indian J Med Res .  2018 May; 147(5): 442–444. 2. Chow SC. Wiley Interdiscip Rev Comput Stat.  2014;6(4):304-312. Bioequivalence (Blood Concentration of Drug in Healthy Volunteers) Therapeutic Equivalence (Outcome in Actual Patients) ≠ ≠ Bioequivalence A mere bio-equivalent Generic may not necessarily lead to the same therapeutic effect as the Innovator. Without an outcome based Clinical Trial Therapeutic equivalence cannot be established by a generic .

20. Bioequivalent drug may not achieve optimum patient goals 1 Reference(s): 1. Chow SC. Wiley Interdiscip Rev Comput Stat.   2014;6(4):304-312. Generics’ bioavailability may range from -20% to +25%

21. Higher serum K + levels and comorbidities increase risk associated with hyperkalaemia 1 Hyperkalaemia can be a chronic condition and an ongoing threat 2-4 1. Collins AJ, Pitt B, Reaven N, et al.. Am J Nephrol . 2017;46:213–221; 2. Rowan CG, et al. Poster #296 presented at National Kidney Foundation Spring clinical Meetings, Austin, USA, April 11–15, 2023. 3. Thomsen RW, Nicolaisen SK, Hasvold P, et al. Elevated potassium levels in patients with chronic kidney disease: occurrence, risk factors, and clinical outcomes—a Danish population-based cohort study. Nephrol Dial Transplant. 2018;33(9):1610–1620. 4. Dunn JD, Benton WW, Orozco- Torrentera E, Adamson RT. The burden of hyperkalemia in patients with cardiovascular and renal disease. Am J Manag Care. 2015;21(15 Suppl ): s307–s315. Over half of patients with CKD experienced hyperkalaemia recurrence within 6 months

22. *KDIGO guideline relating to the management of blood pressure and to the management of diabetes in patients with chronic kidney disease. 1,2 † 2022 KDIGO Clinical Practice Guideline for Diabetes Management in Chronic Kidney Disease. 2 ACEi , angiotensin-converting enzyme inhibitor; ARB, angiotensin receptor blocker; KDIGO, Kidney Disease Improving Global Outcomes; RASi , Renin–angiotensin system inhibitor. 1. Kidney Disease: Improving Global Outcomes (KIDGO) Blood Pressure Work Group. KDIGO 2021 Clinical Practice Guideline for Management of Blood Pressure in Chronic Kidney Disease. Kidney Int. 2021;99(3S):S1–S87.2. Kidney Disease: Improving Global Outcomes (KDIGO) Diabetes Work Group. KDIGO 2022 Clinical Practice Guideline for Diabetes Management in Chronic Kidney Disease. Kidney Int. 2022;102(5S):S1–S127. For management of ACEi /ARB-associated hyperkalaemia, KDIGO guideline* supports use of K + binder over ACEi /ARB decrease or discontinuation 1 ,2 K + binders may be considered to decrease serum K + levels after other measures have failed, rather than decreasing or discontinuing ACEi or ARB treatment 2 2022 KDIGO guideline update † Hyperkalaemia should no longer be a barrier to optimize RAASi therapy 1,2

23. LOKELMA a Novel K binder Designed to capture K 1,2 Lokelma Highly selective For K + Provide early capture of K +†1,2 LOKELMA works throughout the entire gastrointestinal tract SZC preferentially captures for K + in exchange for Na + and H + , even in the presence of Ca 2+ and Mg 2+ No effect on serum Ca 2+ and Mg 2+ concentrations Highly selective for K + ; binding site width and K + ionic diameter are similar Insoluble, highly stable, and does not expand in water Not systemically absorbed References: 1 . Indonesia LOKELMA Prescribing Information 2023. 2 Stavros F, Yang A, Leon A, Nuttall M, Rasmussen HS. PLoS One. 2014;9:e114686.

24. Choose LOKELMA for rapid serum K + reduction as early as 1 hour One dose of LOKELMA significantly reduced serum K + levels at 1 hour vs baseline ( P <0.001) 1 Median time to normokalaemia was 2.2 hours (interquartile range, 1.0 to 22.3 hours) 1 Stay with LOKELMA for sustained K + control for up to 1 year 88% of patients achieved normokalaemia at 48 hours Discontinuing LOKELMA resulted in increased K + levels LOKELMA sustained normokalaemia with continued treatment up to one year 2 1. Kosiborod , M et al. JAMA . 2014;312(21):2223-2233 2. Roger SD, Spinowitz BS, Lerma EV, et al. Efficacy and safety of sodium zirconium cyclosilicate for treatment of hyperkalemia : an 11-month open-label extension of HARMONIZE. Am J Nephrol . 2019;50(6):473–480.

25. Take Home Messages HF and CKD are the earliest and most common complications of T2D 1,2 XIGDUO goes beyond HbA 1c. 3 FORXIGA reduces the risk of hHF and new onset or further progression of nephropathy. 4 FORXIGA did not only consistently reduce the risk of microalbuminuria deterioration, but also more patients reversed back to micro/ normo albuminuria 5 Hyperkalemia should no longer be a barrier to optimizing RAASi therapy. 6,7 Choose LOKELMA for rapid serum K+ reduction as early as 1 hour. 8 LOKELMA proven to sustain normokalaemia with continued treatment up to one year as a solution to optimizing RAASi therapy. 9 25 1. Bergenstal RM et al. Am J Med . 2010;123(4):374.e9–e18.2. Birkeland KI et al. Oral presentation at the 55th European Association for the Study of Diabetes Annual Meeting; 16–20 September 2019; Barcelona, Spain. Presentation #126 3. Bailey CJ et al. Lancet . 2010;375(9733):2223-2233 4. Wiviott SD et al. N Engl J Med . 2019;380(4):347–357. 5. Raz I, et al. Presented at 79th Scientific Sessions of the American Diabetes Association; June 7th–11th, 2019; San Francisco, CA, USA; 244-OR 6. Kidney Disease: Improving Global Outcomes (KIDGO) Blood Pressure Work Group. KDIGO 2021 Clinical Practice Guideline for Management of Blood Pressure in Chronic Kidney Disease. Kidney Int. 2021;99(3S):S1–S87. 7. Kidney Disease: Improving Global Outcomes (KDIGO) Diabetes Work Group. KDIGO 2022 Clinical Practice Guideline for Diabetes Management in Chronic Kidney Disease. Kidney Int. 2022;102(5S):S1–S127. 8. Kosiborod , M et al. JAMA. 2014;312(21):2223-2233 9. Roger SD, Spinowitz BS, Lerma EV, et al. Efficacy and safety of sodium zirconium cyclosilicate for treatment of hyperkalemia: an 11-month open-label extension of HARMONIZE. Am J Nephrol. 2019;50(6):473–480.

26. ABBREVIATED PRESCRIBING INFORMATION FORXIGA™ (Dapagliflozin), Film-coated tablets 5 mg & Film-coated tablets 10 mg. Each tablet contains dapagliflozin propanediol monohydrate equivalent to dapaglifozin . See local Prescribing Information for full details prior to prescribing – Prescribing Information may vary from country to country PRESENTATION: FORXIGA (dapagliflozin) 5 mg tablets are yellow, biconvex, round, film coated tablets with “5” engraved on one side and “1427” engraved on the other side; FORXIGA (dapagliflozin) 10 mg tablets are yellow, biconvex, diamond, film coated tablets with “10” engraved on one side and “1428”engraved on the other side. INDICATION: Type 2 diabetes mellitus: FORXIGA is indicated in patients with type 2 diabetes mellitus to improve glycemic control in combination with metformin, insulin (alone or with up to two oral antidiabetic medications), pioglitazone, sitagliptin (with or without metformin) and glycazide , glimepiride or glyburide (with or without metformin), when the existing therapy, along with diet and exercise, does not provide adequate glycemic control. For study results with respect to combination of therapies, effects on glycaemic control and cardiovascular events, and the populations studied, see sections Special warnings and Precautions for Use, Undesirable effects and Pharmacodynamics. Heart failure: FORXIGA is indicated in adults for the treatment of symptomatic chronic stable heart failure (NYHA functional class (II-III)) with reduced ejection fraction (left ventricular ejection fraction (LVEF) ≤40%), as an adjunct to standard of care therapy. Chronic Kidney Disease Forxiga is indicated in adults for the treatment of chronic kidney disease (eGFR 30-75 ml/min/1.73 m2) in reducing the risk of composite of ≥50% sustained eGFR decline, end-stage renal disease, and renal or cv death. DOSAGE: Type 2 diabetes mellitus: The recommended dose is 10 mg dapagliflozin once daily for add-on combination therapy with metformin, insulin (alone or with up to two oral antidiabetic medications), sitagliptin (with or without metformin) and glycazide , glimepiride or glyburide (with or without metformin). When dapagliflozin is used in combination with an insulin secretagogue, such as a sulphonylurea , a lower dose of insulin secretagogue may be considered to reduce the risk of hypoglycaemia . Heart failure: The recommended dose is 10 mg dapagliflozin once daily for heart failure. In the DAPA-HF study, dapaglifozin was administered in conjunction with other heart failre therapies (see section pharmacodynamic properties). Based on DAPA-HF study, dapagliflozin is not recommended for patients with acute decompensated heart failure, symptomatic hypotension or systolic BP < 95 mmHg, type 1 diabetes mellitus, or severe renal impairment (GFR < 30 mL/min). Chronic kidney disease The recommended dose is 10 mg dapagliflozin once daily. In the DAPA-CKD study, dapagliflozin was administered in conjunction with other chronic kidney disease therapies. Special population: No dose adjustment is required in patients with GFR ≥ 45 mL/min, mild or moderate hepatic impairment. Dapagliflozin is not recommended in patients with severe renal impairment (GFR < 30 mL/min). METHOD OF ADMINISTRATION Forxiga can be taken orally once daily at any time of day with or without food. Tablets are to be swallowed whole. CONTRAINDICATION: hypersensitivity to the active substance(s) or to any of the excipients. WARNINGS AND PRECAUTIONS: General: FORXIGA should not be used in patients with type 1 diabetes mellitus or for the treatment of diabetic ketoacidosis. Treatment of diabetes mellitus: The glycaemic efficacy of dapagliflozin is dependent on renal function, and efficacy is reduced in patients who have moderate renal impairment and is likely absent in patient with severe renal impairment. Forxiga should not be initiated in patients with a GFR < 60 mL/min and should be discontinued at GFR persistently below 45 mL/min. Forxiga has not been studied in severe renal impairment (GFR < 30 mL/min) or end stage renal disease (ESRD). Chronic kidney disease There is no experience with dapagliflozin for the treatment of chronic kidney disease in patients without diabetes who do not have albuminuria. Type 1 diabetes mellitus: Dapagliflozin has not been studied for the treatment of heart failure in patients with type 1 diabetes mellitus. Treatment of these patients with dapagliflozin is not recommended. Treatment of heart failure: There is limited experience with dapagliflozin for the treatment of heart failure in patients with severe renal impairment (GFR < 30 mL/min). Ketoacidosis: There have been reports of ketoacidosis (DKA), including diabetic ketoacidosis, in patients with type 2 diabetes mellitus taking Forxiga and other SGLT2 inhibitors. Forxiga is not indicated for the treatment of patients with type 1 diabetes mellitus. Patients treated with FORXIGA who present with signs and symptoms consistent with ketoacidosis, including nausea, vomiting, abdominal pain, malaise and shortness of breath, should be assessed for ketoacidosis, even if blood glucose levels are below 14 mmol/l (250 mg/dl). If ketoacidosis is suspected, discontinuation or temporary interruption of FORXIGA should be considered and the patient should be promptly evaluated Urinary tract infections: Urinary glucose excretion may be associated with an increased risk of urinary tract infection; therefore, temporary interruption of dapagliflozin should be considered when treating pyelonephritis or urosepsis. Use in patients with hepatic impairment: Dapagliflozin exposure is increased in patients with severe hepatic impairment. Use in patients at risk for volume depletion and/or hypotension: Caution should be exercised in patients for whom a dapagliflozin induced drop in blood pressure could pose a risk, such as patients on anti hypertensive therapy with a history of hypotension or elderly patients. For patients receiving dapagliflozin, In case of intercurrent conditions that may lead to volume depletion (e.g. gastrointestinal illness), careful monitoring of volume status (e.g. physical examination, blood pressure measurements, laboratory tests including electrolytes) is recommended. Elderly patients: Elderly patients may be at a greater risk for volume depletion and are more likely to be treated with diuretics. Elderly patients are more likely to have impaired renal function, and/or to be treated with anti-hypertensive medicinal products that may cause changes in renal function such as angiotensin-converting enzyme inhibitors (ACE-I) and angiotensin II type 1 receptor blockers (ARB). Cardiac failure : Experience with dapagliflozin in NYHA class IV is limited. Elevated haematocrit : Haemotocrit increase was observed with dapagliflozin treatment; therefore, caution in patients with already elevated haematocrit is warranted. Combinations not studied: Dapagliflozin has not been studied in combination with glucagon-like peptide 1 (GLP-1) analogues. Urine laboratory assessments: Due to its mechanism of action, patients taking Forxiga will test positive for glucose in their urine. Lactose: The tablets contain lactose anhydrous. Patients with rare hereditary problems of galactose intolerance, the total lactase deficiency, or glucose-galactose malabsorption should not take this medicinal product. INTERACTIONS : In pharmacodynamics interaction, dapagliflozin may add the diuretic effect of thiazide and loop diuretics, so it may increase the risk of dehydration and hypotension. For using dapaglifozin in combination with insulin secretagogues, such as sulphonylureas , require a lower dose of an insulin secretagogue to reduce the risk of hypoglycaemia . On the other side, pharmacokinetics of dapagliflozin are not altered by metformin, pioglitazone, sitagliptin, glimepiride, voglibose , hydrochlorothiazide, bumetanide, valsartan, or simvastatin. Monitoring glycemic control with 1.5-AG assay is not recommended, use alternative methods to monitor glycemic control. Dapagliflozin may increase renal lithium excretion and the blood lithium levels may be decreased. Serum concentration of lithium should be monitored more frequently after dapagliflozin initiation and dose changes. Please refer the patient to the lithium prescribing doctor in order to monitor serum concentration of lithium UNDESIRABLE EFFECTS: very common (≥ 1/10) : Hypoglycaemia , common (≥ 1/100 to < 1/10) Vulvovaginitis, balanitis and related genital infections, Urinary tract infection, Dizziness, Rash, Back pain Dysuria, Polyuria, Haematocrit increase, Creatinine renal clearance decrease during initial treatment, Dyslipidaemia , uncommon (≥ 1/1,000 to < 1/100) : Fungal infection, Volume depletion, Thirst, Constipation, Dry mouth, Nocturia, , Vulvovaginal pruritus, Pruritus genital, Blood creatinine increase during initial treatment,Blood urea increased, Weight decreased, rare (≥ 1/10000 to < 1/1000) Diabetic ketoacidosis , very rare (< 1/10000) , not known (cannot be estimated from the available data). Pack size 5 mg FORXIGA tablet: Box of 2 blisters @ 14 film-coated tablets (Reg. No: DKI1735301317A1). Box of 3 blisters @ 10 film-coated tablets (Reg. No: DKI1735301317A1). 10 mg FORXIGA tablet: Box of 2 blisters @ 14 film-coated tablets (Reg. No: DKI1735301317B1). Box of 3 blisters @ 10 film-coated tablets (Reg. No: DKI1735301317B1). HARUS DENGAN RESEP DOKTER Further information is available on request from PT AstraZeneca Indonesia Perkantoran Hijau Arkadia Tower G, 16th fl , Jl. T.B. Simatupang Kav . 88, Jakarta – 12520 Tel: [phone] FORXIGA is a trademark of AstraZeneca group of companies. © AstraZeneca 2022. Promomats ID : ID-6171 Date of preparation : 23 August 2023 Date of Expiry : 23 August 2025 Based on Doc ID : Doc ID-005173760 (approval 15 th May 2023)

27. ABBREVIATED PRESCRIBING INFORMATION XIGDUO XR TM is available for oral administration as extended release film-coated tablets containing dapagliflozin and metformin hydrochloride as following quantitative composition: • XIGDUO XR 5/500 mg: Each film-coated tablet contains 5 mg dapagliflozin as dapagliflozin propanediol and 500 mg metformin HCl extended release • XIGDUO XR 5/1000 mg: Each film-coated tablet contains 5 mg dapagliflozin as dapagliflozin propanediol and 1000 mg metformin HCl extended release • XIGDUO XR 10/500 mg: Each film-coated tablet contains 10 mg dapagliflozin as dapagliflozin propanediol and 500 mg metformin HCl extended release • XIGDUO XR 10/1000 mg: Each film-coated tablet contains 10 mg dapagliflozin as dapagliflozin propanediol and 1000 mg metformin HCl extended release See local Prescribing Information for full details prior to prescribing – Prescribing Information may vary from country to country. PRESENTATION: XIGDUO XR tablets are available in the following dosage forms and strengths: • 5 mg/500 mg tablets are orange, capsule shaped, film coated tablets debossed with “1070” and “5/500” on one side and plain on the other side • 5 mg/1000 mg tablets are pink to dark pink, biconvex, oval shaped, film coated tablets debossed with “1071” and “5/1000” on one side and plain on the other side • 10 mg/500 mg tablets are pink, biconvex, capsule shaped, film-coated tablets debossed with “1072” and “10/500” on one side and plain on the other side. • 10 mg/1000 mg tablets are yellow to dark yellow, biconvex, oval-shaped, and film-coated tablets with "1073" and "10/1000" debossed on one side and plain on the reverse side. I NDICATION: XIGDUO XR (dapagliflozin and metformin HCl extended release) is indicated as substitution therapy for treatment of type 2 diabetes mellitus in adjunct to diet and exercise to improve glycemic control in adult patients already controlled with dapagliflozin and metformin XR given concurrently at the same dose level. (see section Clinical trials and Special warning and precautions for use for available data on combination therapy). For study results with respect to combination of therapies, effects on glycaemic control and cardiovascular events, and the populations studied, see sections Special warnings and special precautions for use, Undesirable effects, and Pharmacodynamic properties. DOSAGE: XIGDUO XR should generally be taken orally, once daily with the evening meal. Dosing may be adjusted based on effectiveness and tolerability while not exceeding the maximum recommended daily dose of 10 mg dapagliflozin and 2000 mg metformin HCl. METHOD OF ADMINISTRATION XIGDUO XR tablets must be swallowed whole and never crushed, cut, or chewed. Occasionally, the inactive ingredients of XIGDUO XR will be eliminated in the feces as a soft, hydrated mass that may resemble the original tablet CONTRAINDICATION: XIGDUO XR is contraindicated in: Patients with severe renal impairment (eGFR below 30 mL/min/1.73 m2), end stage renal disease or patients on dialysis Acute or chronic metabolic acidosis, including diabetic ketoacidosis, with or without coma. Diabetic ketoacidosis should be treated with insulin • Patients with a history of any serious hypersensitivity reaction to the active substance or to any of the excipients. Diabetic pre-coma Acute conditions with the potential to alter renal function such as: Dehydration Severe infection Shock Acute or chronic disease which may cause tissue hypoxia such as: Cardiac or respiratory failure Recent myocardial infarction Shock Hepatic impairment Acute alcohol intoxication, alcoholism XIGDUO XR should be temporarily discontinued in patients undergoing radiologic studies involving intravascular administration of iodinated contrast materials because use of such products may result in acute alteration of renal function WARNINGS AND PRECAUTIONS: Xigduo XR is not for people with type 1 diabetes, not for people with diabetic ketoacidosis, not for people with hipersensitivity to dapaglifozin or metformin, and not for people who have moderate to severe kidney problems. No dosage adjustment for XIGDUO XR is indicated in patients with an eGFR greater than or equal to 45 mL/min/1.73m2. XIGDUO XR is not recommended in patients with an eGFR below 45 mL/min/1.73 m2. INTERACTIONS : Co-administration of multiple doses of dapagliflozin and metformin did not meaningfully alter the pharmacokinetics of either dapagliflozin or metformin in healthy subjects. In studies conducted in healthy subjects, dapagliflozin did not alter the pharmacokinetics of pioglitazone, sitagliptin, glimepiride, hydrochlorothiazide, bumetanide, valsartan, simvastatin, digoxin, or warfarin. Certain drugs tend to produce hyperglycemia and may lead to loss of glycemic control. These drugs include the thiazides and other diuretics, corticosteroids, phenothiazines, thyroid products, estrogens , oral contraceptives, phenytoin, nicotinic acid, sympathomimetics, calcium channel blocking drugs, and isoniazid. When such drugs are administered to a patient receiving metformin, the patient should be closely observed for loss of blood glucose control. When such drugs are withdrawn from a patient receiving metformin, the patient should be observed closely for hypoglycemia. In healthy volunteers, the pharmacokinetics of metformin and propranolol, and metformin and ibuprofen were not affected when co-administered in single-dose interaction studies. UNDESIRABLE EFFECTS: dehydration, low blood sugar ( hypoglycemia ), kidney problems, Vitamin B12 deficiency, vaginal yeast infection, balanitis, increased blood cholesterol, bladder cancer, diarrhea, headache, nausea and vomiting, stuffy or runny nose. Pack size XIGDUO XR 5 mg/500 mg: Box of 4 blisters @ 7 film-coated tablets (Reg. No.: DKI1827900217A1) XIGDUO XR 5 mg/1000 mg: Box of 4 blisters @ 7 film-coated tablets (Reg. No.: DKI1827900217B1) XIGDUO XR 10 mg/500 mg: Box of 4 blisters @ 7 film-coated tablets (Reg. No.: DKI1827900217C1) XIGDUO XR 10 mg/1000 mg: Box of 4 blisters @ 7 film-coated tablets (Reg. No.: DKI1827900217D1) HARUS DENGAN RESEP DOKTER Further information is available on request from PT AstraZeneca Indonesia Perkantoran Hijau Arkadia Tower F, 3rd fl , Jl. T.B. Simatupang Kav . 88, Jakarta – 12520 Tel: [phone] FORXIGA is a trade-mark of AstraZeneca group of companies. © AstraZeneca 2022 Promomats ID : ID-5348 Date of preparation : 19 December 2022 Date of Expiry : 19 December 2024 Based on Doc ID : Doc ID-004926708 (5/500); Doc ID-004926665 (5/1000); Doc ID-004926670 (10/500 and 10/1000)

28. ABBREVIATED PRESCRIBING INFORMATION   LOKELMA® (Sodium Zirconium Cyclosilicate), Powder for Oral Suspension 5 g & 10 g. Each sachet contains sodium zirconium cyclosilicate equivalent to sodium.   PRESENTATION: LOKELMA (Sodium Zirconium Cyclosilicate) Powder for oral suspension. White to grey powder.   INDICATION: Lokelma is indicated for the treatment of hyperkalemia in adult patients. Lokelma should not be used as an emergency treatment for life-threatening hyperkalemia because of its delayed onset of action   DOSAGE: Correction phase : The recommended starting dose of Lokelma is 10 g, administered three times a day orally as a suspension in water. When normokalaemia is achieved, the maintenance regimen should be followed. Typically, normokalaemia is achieved within 24 to 48 hours. If patients are still hyperkalaemic after 48 hours of treatment, the same regimen can be continued for an additional 24 hours. If normokalaemia is not achieved after 72 hours of treatment, other treatment approaches should be considered. Maintenance phase : When normokalaemia has been achieved, the minimal effective dose of Lokelma to prevent recurrence of hyperkalaemia should be established. A starting dose of 5 g once daily is recommended, with possible titration up to 10 g once daily, or down to 5 g once every other day, as needed, to maintain a normal potassium level. No more than 10 g once daily should be used for maintenance therapy. Serum potassium levels should be monitored regularly during treatment. Monitoring frequency will depend upon a variety of factors including other medications, progression of chronic kidney disease and dietary potassium intake. If severe hypokalaemia should occur, Lokelma should be discontinued and the patient re-evaluated. Patients on chronic haemodialysis : For patients on dialysis Lokelma should only be dosed on non-dialysis days. The recommended starting dose is 5 g once daily. To establish normokalaemia (4.0-5.0 mmol/L), the dose may be titrated up or down weekly based on the pre-dialysis serum potassium value after the long inter-dialytic interval (LIDI). The dose could be adjusted at intervals of one week in increments of 5 g up to 15 g once daily on non- dialysis days. It is recommended to monitor serum potassium weekly while the dose is adjusted; once normokalaemia is established, potassium should be monitored regularly (e.g., monthly, or more frequently based on clinical judgement including changes in dietary potassium or medication affecting serum potassium).   METHOD OF ADMINISTRATION For oral use. The suspension can be taken with or without food.   CONTRAINDICATION: hypersensitivity to the active substance(s).   WARNINGS AND PRECAUTIONS: Serum potassium levels : Serum potassium should be monitored when clinically indicated, including after changes are made to medicinal products that affect the serum potassium concentration and after the Lokelma dose is titrated. Hypokalaemia : Dose titration as described under maintenance posology may be required in such cases to prevent moderate to severe hypokalaemia . In patients with severe hypokalaemia , Lokelma should be discontinued and the patient re-evaluated QT Prolongation : During correction of hyperkalaemia , a lengthening of the QT interval can be observed as the physiologic result of a decline in serum potassium concentration. The risk of interaction with X-rays : Sodium zirconium cyclosilicate may be opaque to X-rays. If the patient is having abdominal X-rays, radiographers should keep this in mind. Intestinal perforation : The risk for intestinal perforation with the use of Lokelma is currently unknown. Sodium content : Lokelma is considered high in sodium. This should be particularly taken into account for those on a low salt diet     INTERACTIONS : As sodium zirconium cyclosilicate is not absorbed or metabolised by the body, and does not meaningfully bind other medicinal products, there are limited effects on other medicinal products. Sodium zirconium cyclosilicate can transiently increase gastric pH by absorbing hydrogen ions and can lead to changes in solubility and absorption kinetics for co-administered medicinal products with pH- dependent bioavailability   UNDESIRABLE EFFECTS: (≥ 1/100 to < 1/10) : Hypokalaemia , oedema related event.   Pack size Lokelma 5 g, Box, 30 Sachets: Reg. No: DKI2327900623A1 Lokelma 10 g, Box, 30 Sachets: Reg. No: DKI2327900623B1   HARUS DENGAN RESEP DOKTER   Further information is available on request from PT AstraZeneca Indonesia Perkantoran Hijau Arkadia Tower G, 16th fl , Jl. T.B. Simatupang Kav . 88, Jakarta – 12520 Tel: [phone]   LOKELMA is a trademark of AstraZeneca group of companies. © AstraZeneca 2023.   Promomats ID : ID-6161 Date of preparation : 09 September 2023 Date of Expiry : 09 September 2025 Based on Doc ID : Doc ID-005028566 (approval 31 st March 2023)