SITAGLIPTIN ZENTIVA

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.

The frequency of adverse reactions identified from placebo- controlled clinical studies of sitagliptin monotherapy and post-marketing experience Adverse reaction Frequency of adverse reaction Blood and lymphatic system disorders thrombocytopenia Rare Immune system disorders hypersensitivity reactions including anaphylactic responses*,† Not known Metabolism and nutrition disorders hypoglycaemia† Common Nervous system disorders headache Common dizziness Uncommon Respiratory, thoracic and mediastinal disorders interstitial lung disease* Not known Adverse reaction Frequency of adverse reaction Gastrointestinal disorders constipation Uncommon vomiting* Not known acute pancreatitis*,†,‡ Not known fatal and non-fatal haemorrhagic and necrotizing pancreatitis*,† Not known Skin and subcutaneous tissue disorders pruritus* Uncommon angioedema*,† Not known rash*,† Not known urticaria*,† Not known cutaneous vasculitis*,† Not known exfoliative skin conditions including Stevens-Johnson syndrome*,† Not known bullous pemphigoid* Not known Musculoskeletal and connective tissue disorders arthralgia* Not known myalgia* Not known back pain* Not known arthropathy* Not known Renal and urinary disorders impaired renal function* Not known acute renal failure* Not known *Adverse reactions were identified through post-marketing surveillance.

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.

General Sitagliptin should not be used in patients with type 1 diabetes or for 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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