Sitazuca MH Adverse Reactions

Summary of the safety profile: There have been no therapeutic clinical trials conducted with Sitagliptin phosphate/Metformin hydrochloride Tablets however bioequivalence of Sitagliptin phosphate/Metformin hydrochloride Tablets with co-administered sitagliptin and metformin has been demonstrated (see Pharmacology: Pharmacokinetics under Actions). Serious adverse reactions including pancreatitis and hypersensitivity reactions have been reported. Hypoglycaemia has been reported in combination with sulphonylurea (13.8%) and insulin (10.9%).
Sitagliptin and metformin: Tabulated list of adverse reactions: Adverse reactions are listed as follows as MedDRA preferred term by system organ class and absolute frequency (Table 4).
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). (See Table 4.)

Click on icon to see table/diagram/image

Description of selected adverse reactions: Some adverse reactions were observed more frequently in studies of combination use of sitagliptin and metformin with other anti-diabetic medicinal products than in studies of sitagliptin and metformin alone. These included hypoglycaemia (frequency very common with sulphonylurea or insulin), constipation (common with sulphonylurea), peripheral oedema (common with pioglitazone), and headache and dry mouth (uncommon with insulin).
Sitagliptin: In monotherapy studies of sitagliptin 100 mg once daily alone compared to placebo, adverse reactions reported were headache, hypoglycaemia, constipation, and dizziness.
Among these patients, adverse events reported regardless of causal relationship to medicinal product occurring in at least 5% included upper respiratory tract infection and nasopharyngitis. In addition, osteoarthritis and pain in extremity were reported with frequency uncommon (>0.5% higher among sitagliptin users than that in the control group).
Metformin: Gastrointestinal symptoms were reported very commonly in clinical studies and post-marketing use of metformin. Gastrointestinal symptoms such as nausea, vomiting, diarrhoea, abdominal pain and loss of appetite occur most frequently during initiation of therapy and resolve spontaneously in most cases. Additional adverse reactions associated with metformin include metallic taste (common); lactic acidosis, liver function disorders, hepatitis, urticaria, erythema, and pruritus (very rare). Long-term treatment with metformin has been associated with a decrease in vitamin B12 absorption which may very rarely result in clinically significant vitamin B12 deficiency (e.g., megaloblastic anaemia).
Frequency categories are based on information available from metformin Summary of Product Characteristics available in the EU.
Paediatric population: In clinical trials with Sitagliptin phosphate/Metformin hydrochloride Tablets in paediatric patients with type 2 diabetes mellitus aged 10 to 17 years, the profile of adverse reactions was generally comparable to that observed in adults. In paediatric patients on or not on background insulin, sitagliptin was associated with an increased risk of hypoglycaemia.
TECOS Cardiovascular Safety Study: The Trial Evaluating Cardiovascular Outcomes with Sitagliptin (TECOS) included 7,332 patients treated with sitagliptin, 100 mg daily (or 50 mg daily if the baseline eGFR was ≥30 and <50 mL/min/1.73 m²), and 7,339 patients treated with placebo in the intention-to-treat population. Both treatments were added to usual care targeting regional standards for HbA1c and CV risk factors. The overall incidence of serious adverse events in patients receiving sitagliptin was similar to that in patients receiving placebo.
In the intention-to-treat population, among patients who were using insulin and/or a sulfonylurea at baseline, the incidence of severe hypoglycaemia was 2.7% in sitagliptin-treated patients and 2.5% in placebo-treated patients; among patients who were not using insulin and/or a sulfonylurea at baseline, the incidence of severe hypoglycaemia was 1.0% in sitagliptin-treated patients and 0.7% in placebo-treated patients. The incidence of adjudication-confirmed pancreatitis events was 0.3% in sitagliptin-treated patients and 0.2% in placebo-treated patients.
Reporting of suspected adverse reactions: Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via the National Reporting System.