QTERN

8). Missed dose If a dose is missed and it is ≥ 12 hours until the next dose, the dose should be taken. If a dose is missed and it is < 12 hours until the next dose, the missed dose should be skipped and the next dose taken at the usual time.

Special populations Renal impairment Qtern should not be initiated in patients with a glomerular filtration rate (GFR) < 60 mL/min and should be discontinued at GFR persistently below 45 mL/min. 2). No dose adjustment is recommended based on renal function.

Hepatic impairment This medicinal product can be used in patients with mild or moderate hepatic impairment. Patients with moderate hepatic impairment should be evaluated prior to initiation and during treatment. 4). Elderly (≥ 65 years) No dose adjustment is recommended based on age.

2). Paediatric population The safety and efficacy of this medicinal product in children and adolescents aged 0 to < 18 years have not yet been established. No data are available. Method of administration Qtern is taken orally once daily.

It may be taken at any time of day with or without food. Tablet is to be swallowed whole.

1). The pooled safety analysis comprised 3 treatment groups: saxagliptin plus dapagliflozin plus metformin (492 subjects), saxagliptin plus metformin (336 subjects), and dapagliflozin plus metformin (341 subjects). The safety profile of the combined use of saxagliptin plus dapagliflozin plus metformin was comparable to the adverse reactions identified for the respective mono-components.

The most frequently reported adverse reactions associated with Qtern are upper respiratory tract infections (very common), hypoglycaemia when used with SU (very common), and urinary tract infections (common). 4). Tabulated list of adverse reactions The adverse reactions are presented in table 1.

The safety profile is based on the summarised data from the saxagliptin/dapagliflozin combination clinical trials pooled safety data, and also clinical trials, post-authorisation safety studies and post-marketing experience with the mono-components.

The adverse reactions are listed by system organ class (SOC) and frequency. Frequency categories were defined according to very common (≥ 1/10), common (≥ 1/ 100 to 1/ 10), uncommon (≥ 1/1 000 to 1/100), rare (1/10 000 to < 1/1 000), very rare (< 1/10 000), and not known (cannot be estimated from the available data).

Table 1. Compilation of reported adverse reactions System organ class Very common CommonA Uncommo nB Rare Very Rare Not Known Infections and infestation s Upper respiratory tract infection1 Urinary tract infection2, vulvovaginiti s, balanitis and related genital infection3, gastroenteriti sD Fungal infection Necrotising fasciitis of the perineum (Fournier's gangrene)C,F,7 Immune system disorders Hypersensit ivity reactionsC Anaphylactic reactions including anaphylactic shockC Metabolis m and nutrition disorders Hypoglycae miaD (when used with SU) Dyslipidaemi a4 Volume depletionF, thirst Diabetic KetoacidosisF, G,7 Nervous system disorders Headache, dizziness Gastro- intestinal disorders Abdominal painC, diarrhoea, dyspepsiaD, Constipatio n, dry mouth, pancreatitis System organ class Very common CommonA Uncommo nB Rare Very Rare Not Known gastritisD, nauseaC, vomitingD C Skin and subcutane ous tissue disorders Rash5 DermatitisC , pruritusC, urticariaC AngioedemaC Bullous pemphigoid C,7 Musculo- skeletal and connective tissue disorders Arthralgia, back pain, myalgiaD Renal and urinary disorders Dysuria, polyuriaD,6 Nocturia Reproduct ive system and breast disorders Erectile dysfunction , pruritus genital, vulvovagin al pruritus General disorders and administr ation site conditions FatigueD, oedema peripheralD Investigati ons Creatinine renal clearance decreased during initial treatmentF, haematocrit increasedE Blood creatinine increased during initial treatmentF, blood urea increased, weight decreased A Adverse reactions reported in ≥ 2 % of subjects treated with the combined use of saxagliptin + dapagliflozin in the pooled safety analysis, or if reported in < 2% in the pooled safety analysis, they were based on the individual mono- components data.

Acute pancreatitis Use of DPP-4 inhibitors has been associated with a risk of developing acute pancreatitis. Patients should be informed of the characteristic symptoms of acute pancreatitis; persistent, severe abdominal pain. If pancreatitis is suspected, this medicinal product should be discontinued; if acute pancreatitis is confirmed, it should not be restarted.

Caution should be exercised in patients with a history of pancreatitis. 8). 2). In subjects with moderate renal impairment (GFR < 60 mL/min), a higher proportion of subjects treated with dapagliflozin had adverse reactions of increase in creatinine, phosphorus, parathyroid hormone (PTH) and hypotension, compared with placebo.

This medicinal product should not be initiated in patients with a GFR < 60 mL/min and should be discontinued at GFR persistently below 45 mL/min. The saxagliptin/dapagliflozin fixed dose combination has not been studied in severe renal impairment (GFR < 30 mL/min) or end-stage renal disease (ESRD).

2). • Prior to initiation of concomitant medicinal products 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 persistently falls below GFR < 45 mL/min, treatment with this medicinal product should be discontinued.

1). It may be more pronounced in patients with very high blood glucose concentrations. 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.

g. g. physical examination, blood pressure measurements, laboratory tests including haematocrit and electrolytes) is recommended. 8). Use in patients with hepatic impairment There is limited experience in clinical trials in patients with hepatic impairment.

1).