SITAGLIPTIN

Posology The dose is 100 mg sitagliptin once daily. When used in combination with metformin and/or a PPARγ agonist, the dose of metformin and/or PPARγ agonist should be maintained, and Sitagliptin administered concomitantly. 4). If a dose of Sitagliptin is missed, it should be taken as soon as the patient remembers.

A double dose should not be taken on the same day. Special populations Renal impairment When considering the use of sitagliptin in combination with another anti-diabetic medicinal product, its conditions for use in patients with renal impairment should be checked.

For patients with mild renal impairment (glomerular filtration rate [GFR] ≥ 60 to < 90 mL/min), no dose adjustment is required. For patients with moderate renal impairment (GFR ≥ 45 to < 60 mL/min), no dosage adjustment is required.

For patients with moderate renal impairment (GFR ≥ 30 to < 45 mL/min), the dose of Sitagliptin is 50 mg once daily. For patients with severe renal impairment (GFR ≥ 15 to <30 mL/min) or with end- stage renal disease (ESRD) (GFR < 15 mL/min), including those requiring haemodialysis or peritoneal dialysis, the dose of Sitagliptin is 25 mg once daily Treatment may be administered without regard to the timing of dialysis.

Because there is a dosage adjustment based upon renal function, assessment of renal function is recommended prior to initiation of Sitagliptin and periodically thereafter. Hepatic impairment No dose adjustment is necessary for patients with mild to moderate hepatic impairment.

2). However, because sitagliptin is primarily renally eliminated, severe hepatic impairment is not expected to affect the pharmacokinetics of sitagliptin. Elderly No dose adjustment is necessary based on age. Paediatric population Sitagliptin should not be used in children and adolescents 10 to 17 years of age because of insufficient efficacy.

2. Sitagliptin has not been studied in paediatric patients under 10 years of age. Method of administration Sitagliptin can be taken with or without food.

Summary of the safety profile Serious adverse reactions including pancreatitis and hypersensitivity reactions have been reported. 4) Tabulated list of adverse reactions Adverse reactions are listed below (Table 1) by system organ class and frequency.

Frequencies are defined as: 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.

4. ‡ See TECOS Cardiovascular Safety Study below. Description of selected adverse reactions In addition to the drug-related adverse experiences described above, adverse experiences reported regardless of causal relationship to medication and occurring in at least 5 % and more commonly in patients treated with sitagliptin included upper respiratory tract infection and nasopharyngitis.

5 % higher with sitagliptin than that in the control group) included osteoarthritis and pain in extremity. Some adverse reactions were observed more frequently in studies of combination use of sitagliptin with other anti-diabetic medicinal products than in studies of sitagliptin monotherapy.

These included hypoglycaemia (frequency very common with the combination of sulphonylurea and metformin), influenza (common with insulin (with or without metformin)), nausea and vomiting (common with metformin), flatulence (common with metformin or pioglitazone), constipation (common with the combination of sulphonylurea and metformin), peripheral oedema (common with pioglitazone or the combination of pioglitazone and metformin), somnolence and diarrhoea (uncommon with metformin), and dry mouth (uncommon with insulin (with or without metformin)).

Paediatric population In clinical trials with sitagliptin in paediatric patients with type 2 diabetes mellitus aged 10 to17 years, the profile of adverse reactions was comparable to that observed in adults. 73 m2), and 7,339 patients treated with placebo in the intention-to-treat population.

General Sitagliptin should not be used in patient with type 1 diabetes or the treatment of diabetic ketoacidosis. Acute pancreatitis Use of 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, Sitagliptin and other potentially suspect medicinal products should be discontinued; if acute pancreatitis is confirmed, Sitagliptin should not be restarted.

Caution should be exercised in patients with a history of pancreatitis. e. metformin and/or a PPARγ agonist), rates of hypoglycaemia reported with sitagliptin were similar to rates in patients taking placebo. Hypoglycaemia has been observed when sitagliptin was used in combination with insulin or a sulphonylurea.

2). Renal impairment Sitagliptin is renally excreted. 2). When considering the use of sitagliptin in combination with another anti-diabetic medicinal product, its conditions for use in patients with renal impairment should be checked.

Hypersensitivity reactions Post-marketing reports of serious hypersensitivity reactions in patients treated with sitagliptin have been reported. These reactions include anaphylaxis, angioedema, and exfoliative skin conditions including Stevens-Johnson syndrome.

Onset of these reactions occurred within the first 3 months after initiation of treatment, with some reports occurring after the first dose. If a hypersensitivity reaction is suspected, Sitagliptin should be discontinued. Other potential causes for the event should be assessed, and alternative treatment for diabetes initiated.

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