Management of type 2 diabetes mellitus.
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.
Adults : Starting dose of Comet (Metformin Hydrochloride tablet) is 500 mg twice a day or 850 mg once a day, given with meals. Dosage increases should be made in increments of 500 mg weekly or 850 mg every 2 weeks, up to a total of 2000 mg per day, given in divided doses. Starting dose of Comet XR (Metformin Hydrochloride extended release tablet) is 500 mg once daily with the evening meal. Dosage increases should be made in increments of 500 mg weekly, up to a maximum of 2000 mg once daily with the evening meal. If glycemic control is not achieved on Comet XR 2000 mg once daily, a trial of Comet XR 1000 mg twice daily should be considered. Pediatrics : Starting dose of Comet is 500 mg twice a day, given with meals. Dosage increases should be made in increments of 500 mg weekly up to a maximum of 2000 mg per day, given in divided doses.
Cationic Drugs: Cationic drugs (e.g., amiloride, digoxin, morphine, procainamide, quinidine, quinine, ranitidine, triamterene, trimethoprim, or vancomycin) that are eliminated by renal tubular secretion theoretically have the potential for interaction with Metformin by competing for common renal tubular transport systems. Although such interactions remain theoretical (except for cimetidine), careful patient monitoring and dose adjustment of this combination and/or the interfering drug is recommended in patients who are taking cationic medications that are excreted via the proximal renal tubular secretory system.
Carbonic Anhydrase Inhibitors: Topiramate or other carbonic anhydrase inhibitors (e.g., zonisamide, acetazolamide or dichlorphenamide) frequently decrease serum bicarbonate and induce non-anion gap, hyperchloremic metabolic acidosis. Concomitant use of these drugs may induce metabolic acidosis. Use these drugs with caution in patients treated with this combination, as the risk of lactic acidosis may increase.
Inducers of P-glycoprotein and CYP3A4 Enzymes: Rifampin decreased Linagliptin exposure, suggesting that the efficacy of Linagliptin may be reduced when administered in combination with a strong P-gp inducer or CYP 3A4 inducer. As this combination is a fixed-dose combination of Linagliptin and Metformin, use of alternative treatments (not containing Linagliptin) is strongly recommended when concomitant treatment with a strong P-gp or CYP 3A4 inducer is necessary.
Drugs Affecting Glycemic Control: Certain drugs tend to produce hyperglycemia and may lead to loss of glycemic control. These drugs include the thiazides and other diuretics, corticosteroids, phenothiazines, thyroid products, estrogens, oral contraceptives, phenytoin, nicotinic acid, sympathomimetics, calcium channel blocking drugs, and isoniazid. When such drugs are administered to a patient receiving this combination, the patient should be closely observed to maintain adequate glycemic control. When such drugs are withdrawn from a patient receiving this combination, the patient should be observed closely for hypoglycemia.
Renal disease or renal dysfunction (e.g., as suggested by serum creatinine levels > 1.5 mg/ dL [males], > 1.4 mg/dL [females] or abnormal creatinine clearance), Congestive heart failure requiring pharmacologic treatment, Known hypersensitivity to metformin hydrochloride, Acute or chronic metabolic acidosis, including diabetic ketoacidosis, with or without coma. Pregnant mothers: Pregnancy Category B. Metformin should not be used during pregnancy unless clearly needed. Nursing mothers : 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.
Diarrhea, nausea, vomiting, flatulence, asthenia, indigestion, abdominal discomfort, headache etc.
While it does cross the placenta, metformin has not been associated with an increased risk of birth defects or complications. Therefore, if you're already taking metformin before you get pregnant, your doctor may encourage you to continue using the drug throughout your pregnancy. The very limited amounts of metformin observed in breast milk are highly unlikely to lead to substantial exposure in the breastfed baby. Metformin can be considered a safe medication for the treatment of type 2 diabetes in a breastfeeding 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.
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