LINAXA DM For the use of a Registered Medical Practitioner or a Hospital or a Laboratory Only Abbreviated Prescribing information for LINAXA DM [Linagliptin, Dapagliflozin and Metformin Hydrochloride (SR) tablets (5 mg+10 mg +500 mg) (5 mg+10 mg+1000 mg)] [Please refer the complete prescribing information available at www.torrentpharma.com] PHARMACOLOGICAL PROPERTIES: MECHANISM OF ACTION: Linagliptin is an inhibitor of DPP-4, an enzyme that degrades the incretin hormones glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP). Thus, linagliptin increases the concentrations of active incretin hormones, stimulating the release of insulin in a glucose-dependent manner and decreasing the levels of glucagon in the circulation. Both incretin hormones are involved in the physiological regulation of glucose homeostasis. Incretin hormones are secreted at a low basal level throughout the day and levels rise immediately after meal intake. GLP1 and GIP increase insulin biosynthesis and secretion from pancreatic beta cells in the presence of normal and elevated blood glucose levels. Furthermore, GLP-1 also reduces glucagon secretion from pancreatic alpha cells, resulting in a reduction in hepatic glucose output. Dapagliflozin: is an orally active, highly selective SGLT2 inhibitor that improves glycemic control in patients with type 2 diabetes mellitus (T2DM) by reducing renal glucose reabsorption leading to urinary glucose excretion (glucuresis).Metformin: is an antihyperglycemic agent which improves glucose tolerance in patients with type 2 diabetes mellitus, lowering both basal and postprandial plasma glucose. Metformin decreases hepatic glucose production, decreases intestinal absorption of glucose, and improves insulin sensitivity by increasing peripheral glucose uptake and utilization. With metformin therapy, insulin secretion remains unchanged while fasting insulin levels and day-long plasma insulin response may actually decrease. INDICATIONS: It is indicated for the treatment of in patients with type 2 Diabetes Mellitus inadequately controlled on Metformin alone. DOSAGE AND ADMINISTRATION: It should be given orally Dosage: As directed by the Physician. CONTRAINDICATION: Hypersensitivity to any ingredient of the composition. WARNINGS & PRECAUTIONS: Metformin: Lactic acidosis Postmarketing cases of metforminassociated lactic acidosis, including fatal cases, reported Lactic acidosis has a subtle onset and may be accompanied by nonspecific symptoms (eg, malaise, myalgias, abdominal pain, respiratory distress, increased somnolence); however, hypothermia, hypotension, and resistant bradyarrhythmias have occurred with severe acidosis Metformin-associated lactic acidosis characterized by elevated blood lactate concentrations (>5 mmol/L), anion gap acidosis (without evidence of ketonuria or ketonemia), and increased lactate: pyruvate ratio; metformin plasma levels generally >5 mcg/mL. Hypoglycemia with Concomitant Use with Insulin and Insulin Secretagogues Insulin secretagogues and insulin are known to cause hypoglycemia. The use linagliptin in combination with an insulin secretagogue (e.g., sulfonylurea) or insulin was associated with a higher rate of hypoglycemia compared with placebo in reported study Linagliptin.: Hypersensitivity Reactions There have been postmarketing reports of serious hypersensitivity reactions in patients treated with linagliptin. These reactions include anaphylaxis, angioedema, and exfoliative skin conditions. Onset of these reactions occurred predominantly within the first 3 months after initiation of treatment with linagliptin, with some reports occurring after the first dose. If a serious hypersensitivity reaction is suspected, discontinue Linagliptin And Metformin Hydrochloride, assess for other potential causes for the event, and institute alternative treatment for diabetes. Vitamin B Deficiency In metformin, reported study of 29-week duration, a decrease to subnormal levels of previously normal serum vitamin B levels was observed in approximately 7% of metformin-treated patients. Such decrease, possibly due to interference with B absorption from the B -intrinsic factor complex, may be associated with anemia but appears to be rapidly reversible with discontinuation of metformin or vitamin B supplementation. Pancreatitis Acute pancreatitis, including fatal pancreatitis, has been reported in patients treated with linagliptin. In reported clinical trial, acute pancreatitis was reported in 9 (0.3%) patients treated with linagliptin and in 5 (0.1%) patients treated with placebo. Two patients treated with linagliptin in reported clinical trial had acute pancreatitis with a fatal outcome. Dapagliflozin Hypoglycemia Dapagliflozin increases risk of urinary tract infections (UTIs), including life-threatening urosepsis and pyelonephritis that started as UTIs; evaluate for signs and symptoms of urinary tract infections and treat promptly, if indicated. Dapagliflozin can increase the risk of hypoglycemia when combined with insulin or an insulin secretagogue; a lower dose of insulin or insulin secretagogue may be required Dapagliflozin increases risk for genital mycotic infections. DRUG INTERACTIONS: The serum concentration of Linagliptin can be increased when it is combined with Abametapir. The metabolism of Linagliptin can be increased when combined with Abatacept. Aminosalicylic acid may increase the hypoglycemic activities of Dapagliflozin. The metabolism of Dapagliflozin can be decreased when combined with Amiodarone. The risk or severity of lactic acidosis can be increased when Acetazolamide is combined with Metformin. ADVERSE REACTIONS: Excessive thirst and urination, Lactic Acidosis, Pancreatitis, Use with Medications Known to Cause Hypoglycemia, Hypersensitivity Reactions, Vitamin B Deficiency, Severe and Disabling Arthralgia, Bullous Pemphigoid. MARKETED BY: TORRENT PHARMACEUTICALS LTD. IN/ LINAXA DM (5 mg+10 mg +500 mg) (5 mg+10 mg+1000 mg)/Mar-2024/01/ABPI (Additional information is available on request