Steglujan

Posology The recommended starting dose is 5 mg ertugliflozin/100 mg sitagliptin once daily. In patients tolerating the starting dose, the dose may be increased to 15 mg ertugliflozin/100 mg sitagliptin, once daily, if additional glycaemic control is needed.

For patients treated with ertugliflozin who are being switched to Steglujan, the dose of ertugliflozin can be maintained. 8). 4). Missed dose If a dose is missed, it should be taken as soon as the patient remembers. Patients should not take two doses of Steglujan on the same day.

4). 4). 73 m2, Steglujan should be initiated at 5 mg/100 mg and up-titrated to 15 mg/100 mg as needed for glycaemic control. 4). 73 m2 or CrCl is persistently less than 45 mL/min. The fixed-dose combination of ertugliflozin and sitagliptin should not be used in patients with severe renal impairment, with end-stage renal disease (ESRD), or receiving dialysis, as there is no clinical data to support effectiveness in these patients.

Hepatic impairment No dose adjustment of Steglujan is necessary in patients with mild or moderate hepatic impairment. 2). Elderly No dose adjustment of Steglujan is recommended based on age. Elderly patients are more likely to have decreased renal function.

Because renal function abnormalities can occur after initiating ertugliflozin, and sitagliptin is known to be substantially excreted by the kidneys, renal function 4 should be assessed more frequently in elderly patients. 8). Paediatric population The safety and efficacy of Steglujan in children under 18 years of age have not been established.

No data are available. Method of administration Steglujan should be taken orally once daily in the morning, with or without food. In case of swallowing difficulties, the tablet could be broken or crushed as it is an immediate-release dosage form.

1). The incidence and type of adverse reactions in these three studies were similar to the adverse reactions seen with the individual monotherapies ertugliflozin and sitagliptin as described below in Table 1. Ertugliflozin The safety and tolerability of ertugliflozin were assessed in 7 placebo- or active comparator-controlled studies with a total of 3 409 patients with type 2 diabetes mellitus treated with ertugliflozin 5 mg or 15 mg.

9 years. Pool of placebo-controlled trials The primary assessment of safety was conducted in a pool of three 26-week, placebo-controlled trials. 1). These data reflect exposure of 1 029 patients to ertugliflozin with a mean exposure 10 duration of approximately 25 weeks.

Patients received ertugliflozin 5 mg (N=519), ertugliflozin 15 mg (N=510), or placebo (N=515) once daily. The most commonly reported adverse reactions across the clinical program were urinary tract infections, vulvovaginal mycotic infection and other female genital mycotic infections.

4). Sitagliptin Serious adverse reactions including pancreatitis and hypersensitivity reactions have been reported. 4). Tabulated list of adverse reactions Adverse reactions listed below are classified according to frequency and system organ class (SOC), within each frequency grouping, adverse reactions are presented in the order of decreasing seriousness.

Frequency categories are defined according to the following convention: 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), not known (cannot be estimated from the available data).

Table 1:

Adverse reactions from placebo- and active comparator-controlled clinical trials and post-marketing experience System organ class Frequency Adverse reaction Infections and infestations Very common Common Not known Urinary tract infections†,1 Vulvovaginal mycotic infection and other female genital mycotic infections*,†,1 Balanitis candida and other male genital mycotic infections*,†,1 Necrotising fasciitis of the perineum (Fournier’s gangrene)*,a Blood and lymphatic system disorders Rare Thrombocytopenia2 Immune system disorders Not known Hypersensitivity reactions including anaphylactic responses*,a,2 Metabolism and nutrition disorders Common Rare Hypoglycaemia*,†,1,2 DKA*,†,1 Nervous system disorders Common Uncommon Headache2 Dizziness2 Vascular disorders Common Volume depletion*,†,1 Respiratory, thoracic and mediastinal disorders Not known Interstitial lung diseasea,2 11 System organ class Frequency Adverse reaction Gastrointestinal disorders Uncommon Not known Not known Not known Constipation2 Fatal and non-fatal haemorrhagic and necrotising pancreatitis*,a,2 Acute pancreatitisa,*,b,2 Vomitinga,2 Skin and subcutaneous tissue disorders Uncommon Not known Not known Not known Not known Not known Not known Pruritusa,2 Exfoliative skin conditions including Stevens-Johnson syndromea,*,2 Angioedemaa,*,2 Bullous pemphigoida,*,2 Cutaneous vasculitisa,*,2 Rasha,*,1,2 Urticariaa,*,2 Musculoskeletal and connective tissue disorders Not known Not known Not known Not known Arthropathya,2 Back paina,2 Arthralgiaa,2 Myalgiaa,2 Renal and urinary disorders Common Uncommon Not known Not known Increased urination‡,1 Dysuria1, Blood creatinine increased/Glomerular filtration rate decreased†,1 Acute renal failurea,2 Impaired renal functiona,2 Reproductive system and breast disorders Common Vulvovaginal pruritus1 General disorders and administration site conditions Common Thirst§,1 Investigations Common Serum lipids changed¶,1, Haemoglobin increased**,1, BUN increased¶¶,1 1 Adverse reaction with ertugliflozin.

General Steglujan should not be used in patients with type 1 diabetes mellitus. It may increase the risk of diabetic ketoacidosis (DKA) in these patients. Acute pancreatitis Use of dipeptidyl peptidase-4 (DPP-4) inhibitors has been associated with a risk of developing acute pancreatitis.

Patients should be informed of the characteristic symptom of acute pancreatitis: persistent, severe abdominal pain. Resolution of pancreatitis has been observed after discontinuation of sitagliptin (with or without supportive treatment), but very rare cases of necrotising or haemorrhagic pancreatitis and/or death have been reported.

If pancreatitis is suspected, Steglujan and other potentially suspect medicinal products should be discontinued; if acute pancreatitis is confirmed, Steglujan should not be restarted. Caution should be exercised in patients with a history of pancreatitis.

Hypotension/Volume depletion Ertugliflozin causes an osmotic diuresis, which may lead to intravascular volume contraction. 73 m2 or CrCl less than 60 mL/min), elderly patients (≥ 65 years), patients on diuretics, or patients on anti-hypertensive therapy with a history of hypotension.

Before initiating Steglujan, volume status should be assessed and corrected if indicated. Monitor for signs and symptoms after initiating therapy. Due to its mechanism of action, ertugliflozin induces an osmotic diuresis and increases serum creatinine and decreases eGFR.

8). , physical examination, blood pressure measurements, laboratory tests including haematocrit) and electrolytes is recommended for patients receiving Steglujan. Temporary interruption of treatment with Steglujan should be considered until the fluid loss is corrected.

Diabetic ketoacidosis Rare cases of DKA, including life-threatening and fatal cases, have been reported in clinical trials and post-marketing in patients treated with sodium glucose co-transporter-2 (SGLT2) inhibitors, including 5 ertugliflozin.

1.