Applicant/PHRC: Hetero Drugs South Africa (Pty) Ltd.  
Product proprietary name: DEPAGLOZ 5 & 10  
Dosage form and strength: Each film coated tablet contains 5 mg of dapagliflozin  
Each film coated tablet contains 10 mg of dapagliflozin  
Date of Registration Approval: 27 February 2024.  
1.Date of variation submission and approval: Sub: 23 May 2024 & implementable: 25 May 2024. Type IAin: B.II.e.5: addition of 30’s pack size  
PROFESSIONAL INFORMATION FOR DEPAGLOZ 5 & 10  
SCHEDULING STATUS S4  
DEPAGLOZ IS CONTRAINDICATED FOR USE IN TYPE 1 DIABETES. DEPAGLOZ IS NOT  
INDICATED FOR USE IN WEIGHT CONTROL PROGRAMMES AND NOT INDICATED FOR THE  
TREATMENT OF ANY OTHER CONDITIONS EXCEPT TYPE 2 DIABETES.  
There have been reports of metabolic acidosis, including ketoacidosis, which were serious  
life-threatening or fatal, in patients taking DEPAGLOZ.  
Patients who present with signs and symptoms including nausea, vomiting, abdominal pain,  
malaise and shortness of breath, should be assessed for metabolic acidosis, even if blood  
glucose levels are below 11 mmol/L. DEPAGLOZ should be discontinued and the patient  
should be promptly evaluated and managed accordingly.  
Predisposing factors for metabolic acidosis include insulin dose reduction, reduced caloric  
intake, reduced fluid intake or increased insulin requirements due to infections, illness,  
surgery or alcohol abuse. Caution is advised in treating these patients with DEPAGLOZ.  
Predisposing factors for ketoacidosis include low beta-cell function reserve resulting from  
pancreatic disorders, e.g. history of pancreatitis or pancreatic surgery. DEPAGLOZ is  
contraindicated in these patients.  
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Page 1 of 24  
Applicant/PHRC: Hetero Drugs South Africa (Pty) Ltd.  
Product proprietary name: DEPAGLOZ 5 & 10  
Dosage form and strength: Each film coated tablet contains 5 mg of dapagliflozin  
Each film coated tablet contains 10 mg of dapagliflozin  
Date of Registration Approval: 27 February 2024.  
1.Date of variation submission and approval: Sub: 23 May 2024 & implementable: 25 May 2024. Type IAin: B.II.e.5: addition of 30’s pack size  
1 NAME OF THE MEDICINE  
DEPAGLOZ 5 (film coated tablet)  
DEPAGLOZ 10 (film coated tablet)  
2 QUALITATIVE AND QUANTITATIVE COMPOSITION  
DEPAGLOZ 5: Each film coated tablet contains 5 mg of dapagliflozin.  
DEPAGLOZ 10: Each film coated tablet contains 10 mg of dapagliflozin.  
Contains sugar (lactose)  
DEPAGLOZ 5: Contains 25 mg lactose per tablet.  
DEPAGLOZ 10: Contains 50 mg lactose per tablet.  
For a full list of excipients, see section 6.1.  
3 PHARMACEUTICAL FORM  
DEPAGLOZ 5: Pink, round, biconvex, film coated tablets debossed with ‘D32’ on one side and ‘H’ on  
the other side.  
DEPAGLOZ 10: Pink, round, biconvex, film coated tablets debossed with ‘D33’ on one side and ‘H’  
on the other side.  
4 CLINICAL PARTICULARS  
4.1 Therapeutic indications  
DEPAGLOZ is indicated in adults aged 18 years and older with type 2 diabetes mellitus to improve  
glycaemic control as:  
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Applicant/PHRC: Hetero Drugs South Africa (Pty) Ltd.  
Product proprietary name: DEPAGLOZ 5 & 10  
Dosage form and strength: Each film coated tablet contains 5 mg of dapagliflozin  
Each film coated tablet contains 10 mg of dapagliflozin  
Date of Registration Approval: 27 February 2024.  
1.Date of variation submission and approval: Sub: 23 May 2024 & implementable: 25 May 2024. Type IAin: B.II.e.5: addition of 30’s pack size  
Monotherapy  
As an adjunct to diet and exercise to improve glycaemic control in adult patients with type 2 diabetes  
mellitus.  
Add-on combination therapy  
In combination with glucose-lowering medicines, including metformin, a thiazolidinedione, a  
sulfonylurea, a DPP4 inhibitor, or insulin, when these, together with diet and exercise, do not  
provide adequate glycaemic control.  
4.2 Posology and method of administration  
Posology  
Monotherapy and add-on combination therapy  
The recommended dose is 10 mg DEPAGLOZ once daily for monotherapy and add-on combination  
therapy with other glucose-lowering medicines, including metformin, a thiazolidinedione, a  
sulfonylurea, a DPP4 inhibitor, or insulin.  
When DEPAGLOZ is used in combination with insulin or an insulin secretagogue, such as a  
sulphonylurea, a lower dose of insulin or insulin secretagogue may be considered to reduce the  
risk of hypoglycaemia.  
Special populations  
Renal impairment  
No dosage adjustment for DEPAGLOZ is indicated for mild renal impairment. The efficacy of  
DEPAGLOZ is dependent on renal function. DEPAGLOZ should not be used in patients with  
moderate to severe renal impairment (defined as eGFR < 60 mL/min/1,73 m2 by MDRD or CrCl < 60  
mL/min by Cockcroft-Gault) (see sections 4.3, 4.4 and 4.8).  
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Applicant/PHRC: Hetero Drugs South Africa (Pty) Ltd.  
Product proprietary name: DEPAGLOZ 5 & 10  
Dosage form and strength: Each film coated tablet contains 5 mg of dapagliflozin  
Each film coated tablet contains 10 mg of dapagliflozin  
Date of Registration Approval: 27 February 2024.  
1.Date of variation submission and approval: Sub: 23 May 2024 & implementable: 25 May 2024. Type IAin: B.II.e.5: addition of 30’s pack size  
Monitoring of renal function is recommended as follows:  
•
•
Prior to initiation of DEPAGLOZ and at least annually, thereafter.  
Prior to initiation of concomitant medicines that may reduce renal function and periodically  
thereafter.  
•
For renal function approaching moderate renal impairment, at least 2 to 4 times per year. If  
renal function falls below CrCl < 60 mL/min or eGFR < 60 mL/min/1,73 m2, DEPAGLOZ  
treatment should be discontinued.  
Hepatic impairment  
No dosage adjustment for DEPAGLOZ is necessary for patients with mild or moderate hepatic  
impairment. DEPAGLOZ is not recommended for patients with severe hepatic impairment as efficacy  
has not been established (see section 5.2).  
Patients at risk for volume depletion  
For patients at risk for volume depletion due to co-existing conditions or concomitant medications,  
such as loop diuretics, a 5 mg starting dose of DEPAGLOZ may be appropriate (see sections 4.4  
and 4.8).  
Elderly  
No dosage adjustment for DEPAGLOZ is required based on age (see section 4.4).  
Paediatric population  
Safety and effectiveness of DEPAGLOZ in paediatric and adolescent patients have not been  
established.  
Method of administration  
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Applicant/PHRC: Hetero Drugs South Africa (Pty) Ltd.  
Product proprietary name: DEPAGLOZ 5 & 10  
Dosage form and strength: Each film coated tablet contains 5 mg of dapagliflozin  
Each film coated tablet contains 10 mg of dapagliflozin  
Date of Registration Approval: 27 February 2024.  
1.Date of variation submission and approval: Sub: 23 May 2024 & implementable: 25 May 2024. Type IAin: B.II.e.5: addition of 30’s pack size  
DEPAGLOZ is a coated tablet, should not be chewed as it may make them taste very unpleasant.  
DEPAGLOZ should not be broken because the coating is intended to ensure a prolonged release.  
4.3 Contraindications  
•
DEPAGLOZ is contraindicated in patients with hypersensitivity to dapagliflozin or any of the  
excipients listed in section 6.1.  
•
SGLT2 inhibitors such as DEPAGLOZ, are contraindicated in patients with moderate renal  
impairment (creatinine clearance < 60 mL/min, severe renal impairment (creatinine clearance  
< 30 mL/min), end stage renal disease (creatinine clearance < 15 mL/min) and patients on  
dialysis.  
•
•
Diabetes mellitus Type 1.  
Pregnant women or women who are breastfeeding their infants (see section 4.6).  
4.4 Special warnings and precautions for use  
General  
DEPAGLOZ may cause a decrease in systolic blood pressure and diastolic blood pressure.  
DEPAGLOZ should not be used for the treatment of diabetic ketoacidosis.  
Metabolic acidosis including ketoacidosis  
There have been post-marketing reports of ketoacidosis, including diabetic ketoacidosis, in patients  
with type 1 and type 2 diabetes mellitus taking dapagliflozin, as in DEPAGLOZ. DEPAGLOZ is  
contraindicated for the treatment of patients with type 1 diabetes mellitus (see section 4.3).  
Patients treated with DEPAGLOZ 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 11 mmol/L (196 mg/dL). If ketoacidosis is  
suspected, DEPAGLOZ should be discontinued and the patient should be promptly evaluated.  
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Page 5 of 24  
Applicant/PHRC: Hetero Drugs South Africa (Pty) Ltd.  
Product proprietary name: DEPAGLOZ 5 & 10  
Dosage form and strength: Each film coated tablet contains 5 mg of dapagliflozin  
Each film coated tablet contains 10 mg of dapagliflozin  
Date of Registration Approval: 27 February 2024.  
1.Date of variation submission and approval: Sub: 23 May 2024 & implementable: 25 May 2024. Type IAin: B.II.e.5: addition of 30’s pack size  
Predisposing factors for ketoacidosis include low beta-cell function reserve resulting from  
pancreatic disorders, e.g. history of pancreatitis or pancreatic surgery. DEPAGLOZ is not indicated  
in these patients.  
Before initiating dapagliflozin, factors in the patient history that may predispose to ketoacidosis  
should be considered.  
Treatment should be interrupted in patients who are hospitalised for major surgical procedures or  
acute serious medical illnesses. Monitoring of ketones is recommended  
in these patients. Measurement of blood ketone levels is preferred to urine. Treatment  
with dapagliflozin may be restarted when the ketone values are normal and the patient's condition  
has stabilised.  
Patients who may be at higher risk of DKA include patients with a low beta-cell function reserve  
(e.g. type 2 diabetes patients with low C-peptide or latent autoimmune diabetes in adults (LADA) or  
patients with a history of pancreatitis), patients with conditions that lead to restricted food intake or  
severe dehydration, patients for whom insulin doses are reduced and patients with increased  
insulin requirements due to acute medical illness, surgery or alcohol abuse. SGLT2 inhibitors  
should be used with caution in these patients.  
Restarting SGLT2 inhibitor treatment in patients experiencing a DKA while on SGLT2 inhibitor  
treatment is not recommended, unless another clear precipitating factor is identified and resolved.  
Use in patients with renal impairment  
The efficacy of DEPAGLOZ is dependent on renal function (see section 4.3). Therefore, renal  
function should be monitored prior to initiation of DEPAGLOZ and periodically thereafter (see section  
4.2).  
Impairment of renal ruction/acute kidney injury  
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Applicant/PHRC: Hetero Drugs South Africa (Pty) Ltd.  
Product proprietary name: DEPAGLOZ 5 & 10  
Dosage form and strength: Each film coated tablet contains 5 mg of dapagliflozin  
Each film coated tablet contains 10 mg of dapagliflozin  
Date of Registration Approval: 27 February 2024.  
1.Date of variation submission and approval: Sub: 23 May 2024 & implementable: 25 May 2024. Type IAin: B.II.e.5: addition of 30’s pack size  
SGLT2 inhibitors such as DEPAGLOZ may cause a decrease in the glomerular filtration rate (GFR),  
with an increase of serum creatinine and serum urea. Acute kidney injury (AKI) has been reported  
with the use of SGLT2 inhibitors.  
Based on their mode of action, SGLT2 inhibitors cause glycosuria, osmotic diuresis, fluid and  
electrolyte loss with a risk of dehydration/hypovolaemia and hypotension, which may precipitate acute  
kidney injury. Renal function and hydration status should be assessed before treatment is initiated  
with a SGLT2 inhibitor such as DEPAGLOZ and should be frequently monitored during treatment.  
Other factors that may predispose patients to AKI during treatment with SGLT2 inhibitors include  
reduced oral intake of fluids, congestive cardiac failure, gastrointestinal fluid losses, excessive heat  
exposure, and concomitant use of medicines such as diuretics, NSAIDS, ACE inhibitors and ARBs.  
Discontinue treatment with SGLT2 inhibitors in patients with AKI and consider other appropriate  
treatment options for their diabetes mellitus.  
SGLT2 inhibitors such as DEPAGLOZ, are contraindicated in patients with moderate to severe  
renal impairment and in patients on dialysis (see section 4.3).  
Use in patients at risk for volume depletion  
The diuretic effect of DEPAGLOZ is a potential concern for volume depleted patients. There is limited  
experience in patients at increased risk for volume depletion.  
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 at risk for volume depletion due to co-existing conditions or concomitant medicines,  
such as loop diuretics, a 5 mg starting dose of DEPAGLOZ may be appropriate. DEPAGLOZ  
should be permanently discontinued in patients who develop volume depletion (see section 4.8).  
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Page 7 of 24  
Applicant/PHRC: Hetero Drugs South Africa (Pty) Ltd.  
Product proprietary name: DEPAGLOZ 5 & 10  
Dosage form and strength: Each film coated tablet contains 5 mg of dapagliflozin  
Each film coated tablet contains 10 mg of dapagliflozin  
Date of Registration Approval: 27 February 2024.  
1.Date of variation submission and approval: Sub: 23 May 2024 & implementable: 25 May 2024. Type IAin: B.II.e.5: addition of 30’s pack size  
Urinary tract and genital infections  
SGLT2 inhibitors such as DEPAGLOZ have been associated with an increased risk of urinary tract  
infection and/or genital infection in both males and females caused by bacteria and/or fungi. Genital  
and fungal infections appear to be more common in females. Balanoposthitis in males may result in  
phimosis.  
Urinary tract infections were more frequently reported for dapagliflozin, as in DEPAGLOZ  
compared to control in a placebo-pooled analysis up to 24 weeks. Urinary glucose excretion may  
be associated with an increased risk of urinary tract infection; therefore, temporary interruption of  
DEPAGLOZ should be considered when treating pyelonephritis or urosepsis (see section 4.8).  
Treatment with DEPAGLOZ increases the risk for urinary tract infections. There have been  
postmarketing reports of serious urinary tract infections, including pyelonephritis, requiring  
hospitalisation in patients receiving dapagliflozin and other SGLT2 inhibitors. Evaluate patients for  
signs and symptoms of urinary tract infections and treat promptly, if indicated.  
Use with medicines known to cause hypoglycaemia  
Insulin and insulin secretagogues, such as sulfonylureas, cause hypoglycaemia. Therefore, a lower  
dose of insulin or an insulin secretagogue may be required to reduce the risk of hypoglycaemia when  
used in combination with DEPAGLOZ (see section 4.8).  
Other populations  
In general, patients with severe renal impairment (eGFR < 30 mL/min/1,73 m2) or End Stage Renal  
Disease or with recent (< 2 months) cardiovascular event or heart failure New York Heart  
Association class IV or who are breastfeeding or are pregnant, have not been studied.  
Necrotising fasciitis of the perineum (Fournier's gangrene)  
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Applicant/PHRC: Hetero Drugs South Africa (Pty) Ltd.  
Product proprietary name: DEPAGLOZ 5 & 10  
Dosage form and strength: Each film coated tablet contains 5 mg of dapagliflozin  
Each film coated tablet contains 10 mg of dapagliflozin  
Date of Registration Approval: 27 February 2024.  
1.Date of variation submission and approval: Sub: 23 May 2024 & implementable: 25 May 2024. Type IAin: B.II.e.5: addition of 30’s pack size  
Post-marketing cases of necrotising fasciitis of the perineum (also known as Fournier's gangrene)  
have been reported in female and male patients taking SGLT2 inhibitors (see section 4.8). This is a  
rare but serious and potentially life threatening event that requires urgent surgical intervention and  
antibiotic treatment.  
Patients should be advised to seek medical attention if they experience a combination of symptoms  
of pain, tenderness, erythema, or swelling in the genital or perineal area, with fever or malaise. Be  
aware that either uro-genital infection or perineal abscess may precede necrotising fasciitis. If  
Fournier's gangrene is suspected, DEPAGLOZ should be discontinued and prompt treatment  
(including antibiotics and surgical debridement) should be instituted.  
Cardiac failure  
Experience with dapagliflozin in NYHA class IV is limited.  
Lower limb amputations  
An increase in cases of lower limb amputation (primarily of the toe) has been observed in long-term  
studies in type 2 diabetes mellitus with SGLT2 inhibitors. It is unknown whether this constitutes a  
class effect. It is important to counsel patients with diabetes on routine preventative foot care.  
Urine laboratory assessments  
Due to its mechanism of action, patients taking DEPAGLOZ will test positive for glucose in their  
urine.  
Elderly (≥ 65 years)  
Elderly patients may be at a greater risk for volume depletion and are more likely to be treated with  
diuretics.  
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Page 9 of 24  
Applicant/PHRC: Hetero Drugs South Africa (Pty) Ltd.  
Product proprietary name: DEPAGLOZ 5 & 10  
Dosage form and strength: Each film coated tablet contains 5 mg of dapagliflozin  
Each film coated tablet contains 10 mg of dapagliflozin  
Date of Registration Approval: 27 February 2024.  
1.Date of variation submission and approval: Sub: 23 May 2024 & implementable: 25 May 2024. Type IAin: B.II.e.5: addition of 30’s pack size  
Elderly patients are more likely to have impaired renal function, and/or to be treated with anti-  
hypertensive medicines that may cause changes in renal function such as angiotensin-converting  
enzyme inhibitors (ACE-I) and angiotensin II type 1 receptor blockers (ARB). The same  
recommendations for renal function apply to elderly patients as to all patients (see sections 4.2, 4.4,  
4.8 and 5.1).  
Paediatric population  
Safety and efficacy of DEPAGLOZ in paediatric patients has not been established.  
Lactose warning:  
DEPAGLOZ contains lactose. Patients with rare hereditary problems of galactose intolerance, total  
lactase deficiency or glucose-galactose malabsorption should not take this medicine.  
4.5 Interaction with other medicines and other forms of interaction  
Pharmacodynamic interactions  
Diuretics  
Dapagliflozin may add to the diuretic effect of thiazide and loop diuretics and may increase the risk  
of dehydration and hypotension (see section 4.4).  
Insulin and insulin secretagogues  
Insulin and insulin secretagogues, such as sulphonylureas, cause hypoglycaemia. Therefore, a lower  
dose of insulin or an insulin secretagogue may be required to reduce the risk of hypoglycaemia when  
used in combination with dapagliflozin in patients with type 2 diabetes mellitus (see sections 4.2 and  
4.8).  
Pharmacokinetic interactions  
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Page 10 of 24  
Applicant/PHRC: Hetero Drugs South Africa (Pty) Ltd.  
Product proprietary name: DEPAGLOZ 5 & 10  
Dosage form and strength: Each film coated tablet contains 5 mg of dapagliflozin  
Each film coated tablet contains 10 mg of dapagliflozin  
Date of Registration Approval: 27 February 2024.  
1.Date of variation submission and approval: Sub: 23 May 2024 & implementable: 25 May 2024. Type IAin: B.II.e.5: addition of 30’s pack size  
The metabolism of dapagliflozin is primarily mediated by UGT1A9-dependent glucuronide  
conjugation. The major metabolite, dapagliflozin 3-O-glucuronide, is not an SGLT2 inhibitor.  
In invitro studies, dapagliflozin and dapagliflozin 3-O-glucuronide neither inhibited CYP 1A2, 2C9,  
2C19, 2D6, 3A4, nor induced CYP1A2, 2B6 or 3A4. Therefore, dapagliflozin is not expected to alter  
the metabolic clearance of co-administered medicines that are metabolised by these enzymes.  
Dapagliflozin is a weak substrate of the P-glycoprotein (P-gp) active transporter and dapagliflozin 3-  
O-glucuronide is a substrate for the OAT3 active transporter. Dapagliflozin or dapagliflozin 3-O-  
glucuronide did not meaningfully inhibit P-gp, OCT2, OAT1, or OAT3 active transporters.  
The dependence of dapagliflozin elimination on dapagliflozin 3-O-glucuronide formation in humans  
also suggests the possibility of interactions mediated by UGT1A9. Ketoconazole is an in vitro  
inhibitor of dapagliflozin 3-O-glucuronide formation by UGT1A9 (IC50 = 32 μM).  
Effects of other medicines on DEPAGLOZ  
The pharmacokinetics of DEPAGLOZ are not altered by metformin (a human OCT-1 and hOCT-2  
substrate), pioglitazone (a CYP2C8 [major] and CYP3A4 [minor] substrate), sitagliptin (a human  
OAT-3 substrate and P-glycoprotein substrate), glimepiride (a CYP2C9 substrate), voglibose (an  
alpha-glucosidase inhibitor), hydrochlorothiazide, bumetanide, valsartan, or simvastatin (a CYP3A4  
substrate). A 22 % decrease in dapagliflozin systemic exposure following co-administration with  
rifampicin was considered not to be large enough to warrant a dose adjustment.  
Following coadministration of dapagliflozin with mefenamic acid (an inhibitor of UGT1A9), an  
increase in dapagliflozin systemic exposure was seen, but with no clinically meaningful effect on  
24-hour urinary glucose excretion. No dose adjustment is recommended.  
Effect of DEPAGLOZ on other medicines  
DEPAGLOZ did not alter the pharmacokinetics of metformin (an hOCT 1 and hOCT 2 substrate),  
pioglitazone (a CYP2C8 [major] and CYP3A4 [minor] substrate)35, sitagliptin (a hOAT 3 substrate  
and P-glycoprotein substrate), glimepiride (a CYP2C9 substrate), hydrochlorothiazide, bumetanide,  
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Applicant/PHRC: Hetero Drugs South Africa (Pty) Ltd.  
Product proprietary name: DEPAGLOZ 5 & 10  
Dosage form and strength: Each film coated tablet contains 5 mg of dapagliflozin  
Each film coated tablet contains 10 mg of dapagliflozin  
Date of Registration Approval: 27 February 2024.  
1.Date of variation submission and approval: Sub: 23 May 2024 & implementable: 25 May 2024. Type IAin: B.II.e.5: addition of 30’s pack size  
valsartan, simvastatin (a CYP3A4 substrate), digoxin (a P-gp substrate) or warfarin (S warfarin, a  
CYP2C19 substrate, R warfarin or the anticoagulatory effects of warfarin as measured by the  
prothrombin time [International Normalised Ratio (INR)]). Combination of a single dose of  
dapagliflozin and simvastatin resulted in increase in AUC of simvastatin and simvastatin acid but  
these increases in exposure are not considered clinically relevant.  
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.  
Other interactions  
The effects of smoking, diet, herbal products and alcohol use on the pharmacokinetics of DEPAGLOZ  
have not been studied.  
Interference with 1,5-anhydroglucitol (1,5.AG) Assay  
Monitoring glycaemic control with 1,5-AG assay should not be used as measurements of 1,5-AG  
are unreliable in assessing glycaemic control in patients taking SGLT2 inhibitors, including  
DEPAGLOZ. Use alternative methods to monitor glycaemic control.  
Paediatric population  
Interaction studies have only been performed in adults.  
4.6 Fertility, pregnancy and lactation  
Pregnancy  
DEPAGLOZ is contraindicated in pregnancy. Maternal exposure to DEPAGLOZ was associated with  
increased incidence and/or severity of renal pelvic and tubular dilatations in progeny. When  
pregnancy is detected, DEPAGLOZ should be discontinued (see section 4.3).  
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Page 12 of 24  
Applicant/PHRC: Hetero Drugs South Africa (Pty) Ltd.  
Product proprietary name: DEPAGLOZ 5 & 10  
Dosage form and strength: Each film coated tablet contains 5 mg of dapagliflozin  
Each film coated tablet contains 10 mg of dapagliflozin  
Date of Registration Approval: 27 February 2024.  
1.Date of variation submission and approval: Sub: 23 May 2024 & implementable: 25 May 2024. Type IAin: B.II.e.5: addition of 30’s pack size  
Lactation  
Mothers on DEPAGLOZ should not breastfeed their infants.  
DEPAGLOZ must not be used by a nursing woman. DEPAGLOZ is excreted in breast milk. Exposure  
to DEPAGLOZ must be avoided during the first 2 years of life (see section 4.3).  
Fertility  
The effect of dapagliflozin on fertility in humans has not been studied. In male and females,  
dapagliflozin showed no effects on fertility at any dose tested.  
4.7 Effects on ability to drive and use machines  
DEPAGLOZ may cause dizziness which may have an influence on the ability to drive and use  
machines. Patients must bear in mind the possibility of hypoglycaemia and its effects on their motor  
skills.  
4.8 Undesirable effects  
a) Summary of the safety profile  
In type 2 diabetes, the most frequently reported adverse reactions were genital infections.  
b) Tabulated summary of adverse reactions  
Infections and Infestations  
Frequent: Vulvovaginitis, balanitis and related genital infectionsa,b, urinary tract infectiona,d, including  
pyelonephritis, cystitis  
Less frequent: Vulvovaginal pruritus, fungal infection, necrotising fasciitis of the perineum  
(Fournier’s gangrene)  
Immune system disorders  
Less frequent: Angioedema  
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Applicant/PHRC: Hetero Drugs South Africa (Pty) Ltd.  
Product proprietary name: DEPAGLOZ 5 & 10  
Dosage form and strength: Each film coated tablet contains 5 mg of dapagliflozin  
Each film coated tablet contains 10 mg of dapagliflozin  
Date of Registration Approval: 27 February 2024.  
1.Date of variation submission and approval: Sub: 23 May 2024 & implementable: 25 May 2024. Type IAin: B.II.e.5: addition of 30’s pack size  
Metabolism and nutrition disorders  
Frequent: Hypoglycaemia (when used with SU or insulin)a  
Less frequent: Volume depletion, dehydration, hypovolaemia, hypotensiona, thirst, diabetic  
ketoacidosis (when used in type 2 diabetes mellitus)  
Nervous system disorders  
Frequent: Headache, dizziness  
Respiratory, thoracic and mediastinal disorders  
Frequent: Nasopharyngitis  
Gastrointestinal disorders  
Frequent: Diarrhoea  
Less frequent: Constipation, dry mouth  
Skin and subcutaneous tissue disorders  
Frequent: Rash  
Less frequent: Hyperhidrosis  
Musculoskeletal and connective tissue disorders  
Frequent: Back pain, bone fractures  
Renal and urinary disorders  
Frequent: Glucosuria, dysuria, polyuriac  
Less frequent: Nocturia, tubulointerstitial nephritis  
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Page 14 of 24  
Applicant/PHRC: Hetero Drugs South Africa (Pty) Ltd.  
Product proprietary name: DEPAGLOZ 5 & 10  
Dosage form and strength: Each film coated tablet contains 5 mg of dapagliflozin  
Each film coated tablet contains 10 mg of dapagliflozin  
Date of Registration Approval: 27 February 2024.  
1.Date of variation submission and approval: Sub: 23 May 2024 & implementable: 25 May 2024. Type IAin: B.II.e.5: addition of 30’s pack size  
Reproductive system and breast disorders  
Less frequent: pruritus genital  
Investigations  
Frequent: Dyslipidaemia, haematocrit increased, creatinine renal clearance decreased  
during initial treatment  
Less frequent: Blood creatinine increased, blood urea increased, weight decreased  
a See corresponding subsection below for additional information.  
b Genital infection includes the preferred terms: Vulvovaginitis, balanitis and related genital infections  
includes, e.g. the predefined preferred terms: vulvovaginal mycotic infection, vaginal infection,  
balanitis, genital infection fungal, vulvovaginal candidiasis, vulvovaginitis, balanitis candida, genital  
candidiasis, genital infection, genital infection male, penile infection, vulvitis, vaginitis bacterial, vulval  
abscess, balanoposthitis, genitourinary tract infection, penile abscess, posthitis.  
c Polyuria includes the preferred terms: pollakiuria, polyuria, increased urine output, osmotic diuresis.  
d Urinary tract infection includes the preferred terms: Escherichia urinary tract infection, genitourinary  
tract infection, trigonitis, urethritis, kidney infection, and prostatitis.  
c) Description of selected adverse reactions  
Hypoglycaemia  
The frequency of hypoglycaemia depended on the type of background therapy used in each study.  
Studies with add-on sulfonylurea and add-on insulin therapies had higher rates of hypoglycaemia (see  
section 4.4).  
Laboratory findings  
Haematocrit:  
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Page 15 of 24  
Applicant/PHRC: Hetero Drugs South Africa (Pty) Ltd.  
Product proprietary name: DEPAGLOZ 5 & 10  
Dosage form and strength: Each film coated tablet contains 5 mg of dapagliflozin  
Each film coated tablet contains 10 mg of dapagliflozin  
Date of Registration Approval: 27 February 2024.  
1.Date of variation submission and approval: Sub: 23 May 2024 & implementable: 25 May 2024. Type IAin: B.II.e.5: addition of 30’s pack size  
A moderate increase in haematocrit occurs and may be an indication of volume depletion.  
Necrotising fasciitis of the perineum (Fournier's gangrene)  
Cases of Fournier's gangrene have been reported in patients taking SGLT2 inhibitors, including  
dapagliflozin (see section 4.4).  
Increased creatinine  
Adverse reactions related to increased creatinine were grouped (e.g. decreased renal creatinine  
clearance, renal impairment, increased blood creatinine and decreased glomerular filtration rate).  
Evaluation of patients who had renal-related adverse events showed that most had serum creatinine  
changes of ≤ 0,5 mg/dL from baseline. The increases in creatinine were generally transient during  
continuous treatment or reversible after discontinuation of treatment.  
Reporting of suspected adverse reactions  
Reporting suspected adverse reactions after authorisation of the medicine is important. It allows  
continued monitoring of the benefit/risk balance of the medicine. Health care providers are asked to  
report any suspected adverse reactions via “Adverse drug reaction and quality problem reporting  
form”, found online under SAHPRA’s publications: https://www.sahpra.org.za/document/adverse-  
drug-reactions-and-quality-problemreporting-form/ or  
through the mail: pvg.cdma@heterogroups.com.  
to the Holder of certificate of registration  
4.9 Overdose  
In overdose, side effects may be elicited or exacerbated. Appropriate symptomatic and supportive  
treatment should be initiated as dictated by the patient’s clinical status. The removal of  
DEPAGLOZ by haemodialysis has not been studied.  
5 PHARMACEUTICAL PROPERTIES  
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Applicant/PHRC: Hetero Drugs South Africa (Pty) Ltd.  
Product proprietary name: DEPAGLOZ 5 & 10  
Dosage form and strength: Each film coated tablet contains 5 mg of dapagliflozin  
Each film coated tablet contains 10 mg of dapagliflozin  
Date of Registration Approval: 27 February 2024.  
1.Date of variation submission and approval: Sub: 23 May 2024 & implementable: 25 May 2024. Type IAin: B.II.e.5: addition of 30’s pack size  
5.1 Pharmacodynamic properties  
Pharmacological classification: A 21.2 Oral hypoglycaemics  
Pharmacotherapeutic group: Drugs used in diabetes, sodium-glucose co-transporter 2 (SGLT2)  
inhibitors.  
ATC code: A10BK01  
Dapagliflozin is a reversible inhibitor of sodium glucose co-transporter 2 (SGLT2). SGLT2 is  
selectively expressed in the kidney, and is the predominant transporter responsible for reabsorption  
of glucose from the glomerular filtrate back into the circulation. Despite the presence of  
hyperglycaemia in type 2 diabetes mellitus, reabsorption of filtered glucose continues. Dapagliflozin  
reduces both fasting and post-prandial plasma glucose levels by reducing renal glucose  
reabsorption leading to urinary glucose excretion. This glucose excretion (glucuretic effect) is  
observed after the first dose, is continuous over the 24 hour dosing interval, and is sustained for  
the duration of treatment. The amount of glucose removed by the kidney through this mechanism is  
dependent upon the blood glucose concentration and glomerular filtration rate (GFR). Dapagliflozin  
does not impair normal endogenous glucose production in response to hypoglycaemia.  
Dapagliflozin acts independently of insulin secretion and insulin action. Over time, improvement in  
beta cell function (HOMA-2) has been observed with dapagliflozin.  
Urinary glucose excretion (glycosuria) induced by dapagliflozin is associated with caloric loss and  
reduction in weight. The majority of the weight reduction was body fat loss, including visceral fat  
rather than lean tissue or fluid loss as demonstrated by dual energy X-ray absorptiometry (DXA) and  
magnetic resonance imaging. Inhibition of glucose and sodium co-transport by dapagliflozin is also  
associated with mild diuresis and transient natriuresis.  
Dapagliflozin does not inhibit other glucose transporters important for glucose transport into peripheral  
tissues and is 3 000 times more selective for SGLT2 vs. SGLT1, the major transporter in the gut  
responsible for glucose absorption.  
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Applicant/PHRC: Hetero Drugs South Africa (Pty) Ltd.  
Product proprietary name: DEPAGLOZ 5 & 10  
Dosage form and strength: Each film coated tablet contains 5 mg of dapagliflozin  
Each film coated tablet contains 10 mg of dapagliflozin  
Date of Registration Approval: 27 February 2024.  
1.Date of variation submission and approval: Sub: 23 May 2024 & implementable: 25 May 2024. Type IAin: B.II.e.5: addition of 30’s pack size  
The urinary glucose excretion with dapagliflozin results in osmotic diuresis and increases in urinary  
volume. The increase in urinary volume may be associated with a transient increase in urinary sodium  
excretion which may not be associated with changes in serum sodium concentrations.  
Dapagliflozin may cause a decrease in systolic blood pressure and diastolic blood pressure.  
Urinary uric acid excretion was also increased and accompanied by a reduction in serum uric acid  
concentration. At 24 weeks, changes in serum uric acid concentrations from baseline ranged from -  
0,0183 mmol/L to -0,0483 mmol/L.  
5.2 Pharmacokinetic properties  
Absorption  
Dapagliflozin was absorbed after oral administration and can be administered with or without food.  
Maximum dapagliflozin plasma concentrations (Cmax) were usually attained within 2 hours after  
administration in the fasted state. The Cmax and AUC values increased proportional to the  
increment in dapagliflozin dose. The absolute oral bioavailability of dapagliflozin following the  
administration of a 10 mg dose is 78 %. Food had relatively modest effects on the  
pharmacokinetics of dapagliflozin in healthy subjects. Administration with a high-fat meal  
decreased dapagliflozin Cmax by up to 50 % and prolonged Tmax by approximately 1 hour, but did  
not alter AUC as compared with the fasted state. These changes are not considered to be clinically  
meaningful.  
Distribution  
Dapagliflozin is approximately 91 % protein bound. Protein binding was not altered in various disease  
states (e.g. renal or hepatic impairment).  
Biotransformation  
Dapagliflozin is a C-linked glucoside, meaning the aglycone component is attached to glucose by a  
carbon-carbon bond, thereby conferring stability against glucosidase enzymes. The mean plasma  
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Applicant/PHRC: Hetero Drugs South Africa (Pty) Ltd.  
Product proprietary name: DEPAGLOZ 5 & 10  
Dosage form and strength: Each film coated tablet contains 5 mg of dapagliflozin  
Each film coated tablet contains 10 mg of dapagliflozin  
Date of Registration Approval: 27 February 2024.  
1.Date of variation submission and approval: Sub: 23 May 2024 & implementable: 25 May 2024. Type IAin: B.II.e.5: addition of 30’s pack size  
terminal half-life (t1/2) for dapagliflozin was 12,9 hours following a single oral dose of dapagliflozin  
10 mg to healthy subjects. Dapagliflozin is extensively metabolised, primarily to yield dapagliflozin  
3-O-glucuronide, which is an inactive metabolite. Dapagliflozin 3-O-glucuronide accounted for 61 %  
of a 50 mg [14C]-dapagliflozin dose and was the predominant drug-related component in human  
plasma, accounting for 42 % [based on AUC(0-12 h)] of total plasma radioactivity, similar to the 39 %  
contribution by parent compound. No other metabolite accounted for > 5 % of the total plasma  
radioactivity at any time point measured. Dapagliflozin 3-O-glucuronide or other metabolites do not  
contribute to the glucose-lowering effects. The formation of dapagliflozin 3-O-glucuronide is  
mediated by UGT1A9, an enzyme present in the liver and kidney, and CYP mediated metabolism  
was a minor clearance pathway in humans.  
Elimination  
Dapagliflozin and related metabolites are primarily eliminated via urinary excretion with less than 2 %  
as unchanged dapagliflozin. After administration of 50 mg [14C]-dapagliflozin dose, 96 % was  
recovered, 75 % in urine and 21 % in faeces. In faeces, approximately 15 % of the dose was excreted  
as parent compound.  
Linearity/non-linearity  
Dapagliflozin exposure increased in proportion to the increment in dapagliflozin dose over the range  
of 0,1 to 500 mg and its pharmacokinetics did not change with time upon repeated daily dosing for up  
to 24 weeks.  
Pharmacokinetics in special populations  
Renal impairment  
At steady-state (20 mg once daily dapagliflozin for 7 days), patients with type 2 diabetes mellitus  
and mild, moderate or severe renal impairment (as determined by iohexol plasma clearance) had  
mean systemic exposures of dapagliflozin that were 32 %, 60 % and 87 % higher, respectively,  
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Applicant/PHRC: Hetero Drugs South Africa (Pty) Ltd.  
Product proprietary name: DEPAGLOZ 5 & 10  
Dosage form and strength: Each film coated tablet contains 5 mg of dapagliflozin  
Each film coated tablet contains 10 mg of dapagliflozin  
Date of Registration Approval: 27 February 2024.  
1.Date of variation submission and approval: Sub: 23 May 2024 & implementable: 25 May 2024. Type IAin: B.II.e.5: addition of 30’s pack size  
than those of patients with type 2 diabetes mellitus and normal renal function. At dapagliflozin 20  
mg once daily, higher systemic exposure to dapagliflozin in patients with type 2 diabetes mellitus  
and renal impairment did not result in a correspondingly higher renal glucose clearance or 24 hour  
glucose excretion. The renal glucose clearance and 24 hour glucose excretion was lower in  
patients with moderate or severe renal impairment as compared to patients with normal and mild  
renal impairment. The steady-state 24 hour urinary glucose excretion was highly dependent on  
renal function and 85, 52, 18 and 11 g of glucose/day was excreted by patients with type 2  
diabetes mellitus and normal renal function or mild, moderate or severe renal impairment,  
respectively. There were no differences in the protein binding of dapagliflozin between renal  
impairment groups or compared to healthy subjects. The impact of haemodialysis on dapagliflozin  
exposure is not known. Dapagliflozin is contraindicated in patients whose GFR is less than 60  
mL/min (see section 4.3).  
Hepatic impairment  
A single dose (10 mg) dapagliflozin clinical pharmacology study was conducted in patients with mild,  
moderate or severe hepatic impairment (Child-Pugh classes A, B, and C, respectively) and healthy  
matched controls in order to compare the pharmacokinetic characteristics of dapagliflozin between  
these populations. There were no differences in the protein binding of dapagliflozin between hepatic  
impairment groups or compared to healthy subjects. In patients with mild or moderate hepatic  
impairment mean Cmax and AUC of dapagliflozin were up to 12 % and 36 % higher, respectively,  
compared to healthy matched control subjects. These differences were not considered to be clinically  
meaningful and no dose adjustment from the proposed usual dose of 10 mg once daily for  
dapagliflozin is proposed for these populations. In patients with severe hepatic impairment (Child-  
Pugh class C) mean Cmax and AUC of dapagliflozin were up to 40 % and 67 % higher than matched  
healthy controls, respectively. Dapagliflozin is not recommended for use in severe hepatic impairment  
(see section 4.4).  
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Applicant/PHRC: Hetero Drugs South Africa (Pty) Ltd.  
Product proprietary name: DEPAGLOZ 5 & 10  
Dosage form and strength: Each film coated tablet contains 5 mg of dapagliflozin  
Each film coated tablet contains 10 mg of dapagliflozin  
Date of Registration Approval: 27 February 2024.  
1.Date of variation submission and approval: Sub: 23 May 2024 & implementable: 25 May 2024. Type IAin: B.II.e.5: addition of 30’s pack size  
Age  
No dosage adjustment for dapagliflozin from the dose of 10 mg once daily is recommended on the  
basis of age. The effect of age (young: ≥ 18 to < 40 years [n = 105] and elderly: ≥ 65 years [n =  
224]) was evaluated as a covariate in a population pharmacokinetic model and compared to  
patients ≥ 40 to < 65 years using data from healthy subject and patient studies). The mean  
dapagliflozin systemic exposure (AUC) in young patients was estimated to be 10,4 % lower than in  
the reference group [90 % CI: 87,9; 92,2 %] and 25 % higher in elderly patients compared to the  
reference group [90 % CI: 123; 129 %]. These differences in systemic exposure were considered  
not to be clinically meaningful.  
Body Weight  
In a population pharmacokinetic analysis using data from healthy subject and patient studies,  
systemic exposures in high body weight subjects (≥ 120 kg, n = 91) were estimated to be 78,3 % [90  
% CI: 78,2; 83,2 %] of those of reference subjects with body weight between 75 and 100 kg. This  
difference is considered to be small, therefore, no dose adjustment from the proposed dose of 10 mg  
dapagliflozin once daily in type 2 diabetes mellitus patients with high body weight (≥ 120 kg) is  
recommended.  
Subjects with low body weights (< 50 kg) were not well represented in the healthy subject and  
patient studies used in the population pharmacokinetic analysis. Therefore, dapagliflozin systemic  
exposures were simulated with a large number of subjects. The simulated mean dapagliflozin  
systemic exposures in low body weight subjects were estimated to be 29 % higher than subjects  
with the reference group body weight. This difference is considered to be small and based on these  
findings no dose adjustment from the proposed dose of 10 mg dapagliflozin once daily in type 2  
diabetes mellitus patients with low body weight (< 50 kg) is recommended.  
Paediatric population  
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Applicant/PHRC: Hetero Drugs South Africa (Pty) Ltd.  
Product proprietary name: DEPAGLOZ 5 & 10  
Dosage form and strength: Each film coated tablet contains 5 mg of dapagliflozin  
Each film coated tablet contains 10 mg of dapagliflozin  
Date of Registration Approval: 27 February 2024.  
1.Date of variation submission and approval: Sub: 23 May 2024 & implementable: 25 May 2024. Type IAin: B.II.e.5: addition of 30’s pack size  
Pharmacokinetics in the paediatric and adolescent population have not been studied.  
6 PHARMACEUTICAL PARTICULARS  
6.1 List of excipients  
•
•
•
•
•
•
Anhydrous lactose  
Crospovidone  
Magnesium stearate  
Microcrystalline cellulose  
Silicon dioxide  
Opadry II Pink 85F94172 contains polyvinyl alcohol-part hydrolyzed, titanium dioxide,  
macrogol/PEG, talc, iron oxide red, ferrosoferric oxide / Black iron oxide  
6.2 Incompatibilities  
Not applicable.  
6.3 Shelf life  
24 months.  
6.4 Special precautions for storage  
•
•
•
Store at or below 25 °C.  
Keep the tablets in the original container until required for use.  
This medicine does not require any special storage conditions.  
6.5 Nature and contents of container  
HDPE bottles:  
White opaque coloured heavy weight high density polyethylene (HDPE) bottle with 2 g silica gel  
canister enclosed with a white opaque polypropylene, ribbed, child resistant plastic cap with pulp  
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Applicant/PHRC: Hetero Drugs South Africa (Pty) Ltd.  
Product proprietary name: DEPAGLOZ 5 & 10  
Dosage form and strength: Each film coated tablet contains 5 mg of dapagliflozin  
Each film coated tablet contains 10 mg of dapagliflozin  
Date of Registration Approval: 27 February 2024.  
1.Date of variation submission and approval: Sub: 23 May 2024 & implementable: 25 May 2024. Type IAin: B.II.e.5: addition of 30’s pack size  
liners.  
Pack size: 28 or 30 film coated tablets per bottle.  
Blister strips:  
Blister strips of PVC/Aluminium/OPA forming foil and plain Aluminium lidding foil, containing 10 film  
coated tablets per blister.  
Pack size: 10 film coated tablets per blister. 3 or 10 blisters packed in a cardboard outer carton box.  
HDPE bottle and blister strips are enclosed in an outer carton box.  
6.6 Special precautions for disposal and other handling  
No special requirements.  
7 HOLDER OF CERTIFICATE OF REGISTRATION  
Hetero Drugs South Africa (Pty) Ltd.  
Waterfall Corporate Campus  
Building No. 2, First floor  
74 Waterfall Drive  
Midrand  
2066  
8 REGISTRATION NUMBER(S)  
DEPAGLOZ 5: 56/21.2/0305.301.  
DEPAGLOZ 10: 56/21.2/0306.302.  
9 DATE OF FIRST AUTHORISATION/RENEWAL OF AUTHORISATION  
27 February 2024.  
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Page 23 of 24  
Applicant/PHRC: Hetero Drugs South Africa (Pty) Ltd.  
Product proprietary name: DEPAGLOZ 5 & 10  
Dosage form and strength: Each film coated tablet contains 5 mg of dapagliflozin  
Each film coated tablet contains 10 mg of dapagliflozin  
Date of Registration Approval: 27 February 2024.  
1.Date of variation submission and approval: Sub: 23 May 2024 & implementable: 25 May 2024. Type IAin: B.II.e.5: addition of 30’s pack size  
10 DATE OF REVISION OF THE TEXT  
25 May 2024  
23 May 2024  
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