Uses of Linaglip-M 5/1000 ER: - Type 2 diabetes mellitus Type 2 Diabetes mellitus Hypersensitivity. Type 1 diabetes, diabetic ketoacidosis or pre-coma, renal failure or dysfunction (CrCl <60 mL/min), hepatic insufficiency, acute alcohol intoxication, alcoholism. Acute conditions w/ the potential to alter renal function eg dehydration, severe infection, shock, IV administration of iodinated contrast agents. Acute or chronic diseases which may cause tissue hypoxia eg cardiac or resp failure, recent MI. Lactation.

Combination Oral hypoglycemic preparations

Linagliptin is indicated to improve glycemic control in patients with type 2 diabetes mellitus. Linagliptin is an inhibitor of DPP-4 (dipeptidyl peptidase-4), an enzyme that degrades the incretin hormones GLP-1 (glucagon like peptide-1) and GIP (glucose dependent insulinotropic polypeptide). Thus, Linagliptin increases the concentrations of active incretin hormones, stimulating the release of insulin from pancreatic beta (β) cells in a glucose-dependent manner and decreasing the secretion of glucagon from pancreatic alpha (α) cells in the circulation.Metformin Hydrochloride is a biguanide type oral antihyperglycemic drug used in the management of type 2 diabetes. It lowers both basal and postprandial plasma glucose. Its mechanism of action is different from those of sulfonylureas and it does not produce hypoglycemia. Metformin Hydrochloride decreases hepatic glucose production, decreases intestinal absorption of glucose and improves insulin sensitivity by an increase in peripheral glucose uptake and utilization.

How to use Linagliptin + Metformin Hydrochloride: Take this medicine in the dose and duration as advised by your doctor. Swallow it as a whole. Do not chew, crush or break it. Linagliptin + Metformin Hydrochloride is to be taken with food. Administration: Should be taken with meals to reduce the gastrointestinal undesirable effects associated with metformin. Adult Dose: Indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus when treatment with both linagliptin and metformin is appropriate. Prompt-release tablets Initial dose (not currently taking metformin): 2.5 mg/500 mg PO BID Initial dose (already taking metformin): Base dose on current metformin dose (eg, if taking metformin 1000 mg BID, initiate with 2.5 mg/1000 mg PO BID) Not to exceed 2.5 mg/1,000 mg BID Extended-release tablets Individualize dose on the basis of both effectiveness and tolerability, while not exceeding the maximum recommended total daily dose of linagliptin/metformin 5 mg/2000 mg Initial dose (not currently taking metformin): 5 mg/1000 mg PO qDay Initial dose (already taking metformin): 5 mg of linagliptin total daily dose and a similar total daily dose of metformin qDay Switch from prompt-release linagliptin/metformin: 5 mg of linagliptin total daily dose and a similar total daily dose of metformin qDay Hepatic impairment: Not recommended because of increased risk of lactic acidosis Child Dose: <18 years: Safety and efficacy not established Renal Dose: Renal impairment Obtain eGFR before starting metformin eGFR <30 mL/min/1.73 m²: Contraindicated eGFR 30-45 mL/min/1.73 m²: Not recommended to initiate treatment Monitor eGFR at least annually or more often for those at risk for renal impairment (eg, elderly) If eGFR falls below 45mL/min/1.73 m² while taking metformin, risks and benefits of continuing therapy should be evaluated If eGFR falls below 30 mL/min/1.73 m²: while taking metformin, discontinue the drug

Linagliptin: Inhibits P-glycoprotein-mediated transport of digoxin (w/ low potency). Increased AUC & Cmax w/ ritonavir. Decreased steady-state AUC & Cmax, & DPP-4 inhibition at trough w/ rifampicin. Weakly inhibits CYP3A4-mediated metabolism (eg simvastatin). Metformin: Increased risk of lactic acidosis in acute alcohol intoxication. Competition on common renal tubular transport systems w/ cationic agents eliminated by renal tubular secretion (eg cimetidine). Risk of renal failure & lactic acidosis w/ intravascular administration of iodinated contrast agents.

Hypersensitivity. Type 1 diabetes, diabetic ketoacidosis or pre-coma, renal failure or dysfunction (CrCl <60 mL/min), hepatic insufficiency, acute alcohol intoxication, alcoholism. Acute conditions w/ the potential to alter renal function eg dehydration, severe infection, shock, IV administration of iodinated contrast agents. Acute or chronic diseases which may cause tissue hypoxia eg cardiac or resp failure, recent MI. Lactation.

Common - Diarrhea - Nausea - Vomiting - Upset stomach - Headache - Nasal congestion (stuffy nose) - Sore throat - Respiratory tract infection - Hypoglycaemia (low blood sugar level) in combination with insulin or sulphonylurea >10% Hypoglycemia (with sulfonylurea) (22.9%) 1-10% Nasopharyngitis (6.3%),Diarrhea (6.3%),Hypoglycemia (without sulfonylurea) (1.4%) Frequency Not Defined Hypersensitivity (eg, urticaria, angioedema, or bronchial hyperactivity),Cough,Decreased appetite,Nausea,Vomiting,Pruritus,Pancreatitis

There are no adequate and well-controlled studies in pregnant women with this combination or its individual component; so it should be used during pregnancy only if clearly needed. Caution should also be excercised when it is administered to a lactating mother.

Precaution: Monitor for pancreatitis, hypoglycaemia, lactic acidosis, renal impairment. Intravascular administration of iodinated contrast agents. Co-administration of insulin. Discontinue treatment 48 hr before elective surgery w/ general, spinal or peridural anaesth. Evaluate serum electrolytes & ketones, blood glucose & if indicated, blood pH, lactate, pyruvate & metformin levels in patients w/ previously well controlled type 2 diabetes on Trajenta Duo who develops laboratory abnormalities or clinical illness. Pregnancy. Childn & adolescents <18 yr. Elderly. Lactation: Metformin excreted in human milk in low concentrations; unknown if linagliptin excreted in human milk No studies in lactating animals have been conducted with the combined components; because the potential for hypoglycemia in nursing infants may exist, a decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother

In the event of an overdose with this combination the usual supportive measures (i.e. remove unabsorbed material from the gastrointestinal tract, perform clinical monitoring, and institute supportive treatment) should be employed. Removal of Linagliptin by hemodialysis or peritoneal dialysis is unlikely but Metformin Hydrochloride is dialyzable. During controlled clinical trials in healthy subjects, with single doses of up to 600 mg of Linagliptin (equivalent to 120 times the recommended daily dose), there were no dose-related clinical adverse drug reactions. Overdose of Metformin Hydrochloride has occurred in case of ingestion of amounts greater than 50 grams. Hypoglycemia was reported in approximately 10% of cases, but no causal association with Metformin Hydrochloride has been established. Lactic acidosis has been reported in approximately 32% of Metformin Hydrochloride overdose cases.

Keep in a cool & dry place (below 30°C), protected from light & moisture. Keep out of the reach of children.

Combination Oral hypoglycemic preparations

Linagliptin: Dipeptidyl peptidase 4 (DPP-4) inhibitor; increases and prolongs incretin hormone activity from glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) which are inactivated by the DPP-4 enzyme; incretins increase insulin release and reduce glucagon secretion Metformin: Decreases hepatic glucose production; decreases GI intestinal glucose absorption; increases target cell insulin sensitivity; lowers both basal and postprandial plasma glucose and unlike sulfonylureas, does not typically produce hypoglycemia or hyperinsulinemia

There are no adequate and well-controlled studies in pregnant women with this combination or its individual component; so it should be used during pregnancy only if clearly needed. Caution should also be excercised when it is administered to a lactating mother.