11. There is no experience with doses above 600 mg in humans.In the event of an overdose, it is reasonable to employ the usual supportive measures, e.g., remove unabsorbed material from the gastrointestinal tract, employ clinical monitoring and institute clinical measures if required.Pharmacotherapeutic group: Drugs used in diabetes, dipeptidyl peptidase 4 (DPP-4) inhibitors, ATC code: A10BH05Linagliptin is an inhibitor of the enzyme DPP-4 (dipeptidyl peptidase 4, EC 3.4.14.5) an enzyme which is involved in the inactivation of the incretin hormones GLP-1 and GIP (glucagon-like peptide1, glucose-dependent insulinotropic polypeptide). Poster presented at: 70th American Diabetes Association Scientific Sessions. Evaluation of the pharmacokinetic interaction between the dipeptidyl peptidase-4 inhibitor linagliptin and pioglitazone in healthy volunteers. Linagliptin improves glycemic control in type 2 diabetes patients inadequately controlled by metformin and sulfonylurea without weight gain or hypoglycemia. Due to the concentration dependent binding of linagliptin to DPP-4, the pharmacokinetics of linagliptin based on total exposure is not linear; indeed total plasma AUC of linagliptin increased in a less than dose-proportional manner while unbound AUC increases in a roughly dose-proportional manner. It allows continued monitoring of the benefit/risk balance of the medicinal product. Barnett AH, Harper R, Toorawa R, Patel S, Woerle HJ. Rodbard HW, Jellinger PS, Davidson JA et al. Zannad F, Cannon CP, Cushman WC et al. These hormones are rapidly degraded by the enzyme DPP-4.
Food and Drug Administration. Therefore, caution is advised when linagliptin is used in combination with a sulphonylurea and/or insulin. In addition, linagliptin is not expected to be eliminated to a therapeutically significant degree by hemodialysis or peritoneal dialysis. Drugs.com provides accurate and independent information on more than 24,000 prescription drugs, over-the-counter medicines and natural products. Linagliptin binds very effectively to DPP-4 in a reversible manner and thus leads to a sustained increase and a prolongation of active incretin levels. Healthcare professionals are asked to report any suspected adverse reactions via:Website: www.mhra.gov.uk/yellowcard or search for MHRA Yellow Card in the Google Play or Apple App StoreDuring controlled clinical trials in healthy subjects, single doses of up to 600 mg linagliptin (equivalent to 120 times the recommended dose) were generally well tolerated. Del Prato S, Barnett AH, Huisman H et al. In a cardiovascular and renal safety study (CARMELINA) with median observation period of 2.2 years, adjudicated acute pancreatitis was reported in 0.3% of patients treated with linagliptin and in 0.1% of patients treated with placebo.
23. The clinical trials before marketing authorisation have been performed up to a BMI equal to 40 kg/mNo dosage adjustment is necessary based on gender. Effect of linagliptin on the pharmacokinetics and pharmacodynamics of warfarin in healthy volunteers.
3. Poster presented at: European Association for the Study of Diabetes 46th Annual Meeting.
Linagliptin monotherapy improves glycaemic control in type 2 diabetes patients for whom metformin therapy is inappropriate. 22. When linagliptin is added to metformin, the dose of metformin should be maintained, and linagliptin administered concomitantly.When linagliptin is used in combination with a sulphonylurea or with insulin, a lower dose of the sulphonylurea or insulin, may be considered to reduce the risk of hypoglycaemia (see section 4.4)For patients with renal impairment, no dose adjustment for linagliptin is required. Results were consistent for patients treated with or without metformin.Table 3 Major adverse cardiovascular events (MACE) and mortality by treatment group in the CAROLINA studyPrimary CV composite (Cardiovascular death, non-fatal MI, non-fatal stroke)** Test on non-inferiority to demonstrate that the upper bound of the 95% CI for the hazard ratio is less than 1.3For the entire treatment period (median time on treatment 5.9 years) the rate of patients with moderate or severe hypoglycaemia was 6.5% on linagliptin versus 30.9% on glimepiride, severe hypoglycaemia occurred in 0.3% of patients on linagliptin versus 2.2% on glimepiride.The European Medicines Agency has deferred the obligation to submit the results of studies with linagliptin in one or more subsets of the paediatric population in Type 2 diabetes (see section 4.2 for information on paediatric use).The pharmacokinetics of linagliptin has been extensively characterised in healthy subjects and patients with type 2 diabetes.
Food and Drug Administration. Therefore, caution is advised when linagliptin is used in combination with a sulphonylurea and/or insulin. In addition, linagliptin is not expected to be eliminated to a therapeutically significant degree by hemodialysis or peritoneal dialysis. Drugs.com provides accurate and independent information on more than 24,000 prescription drugs, over-the-counter medicines and natural products. Linagliptin binds very effectively to DPP-4 in a reversible manner and thus leads to a sustained increase and a prolongation of active incretin levels. Healthcare professionals are asked to report any suspected adverse reactions via:Website: www.mhra.gov.uk/yellowcard or search for MHRA Yellow Card in the Google Play or Apple App StoreDuring controlled clinical trials in healthy subjects, single doses of up to 600 mg linagliptin (equivalent to 120 times the recommended dose) were generally well tolerated. Del Prato S, Barnett AH, Huisman H et al. In a cardiovascular and renal safety study (CARMELINA) with median observation period of 2.2 years, adjudicated acute pancreatitis was reported in 0.3% of patients treated with linagliptin and in 0.1% of patients treated with placebo.
23. The clinical trials before marketing authorisation have been performed up to a BMI equal to 40 kg/mNo dosage adjustment is necessary based on gender. Effect of linagliptin on the pharmacokinetics and pharmacodynamics of warfarin in healthy volunteers.
3. Poster presented at: European Association for the Study of Diabetes 46th Annual Meeting.
Linagliptin monotherapy improves glycaemic control in type 2 diabetes patients for whom metformin therapy is inappropriate. 22. When linagliptin is added to metformin, the dose of metformin should be maintained, and linagliptin administered concomitantly.When linagliptin is used in combination with a sulphonylurea or with insulin, a lower dose of the sulphonylurea or insulin, may be considered to reduce the risk of hypoglycaemia (see section 4.4)For patients with renal impairment, no dose adjustment for linagliptin is required. Results were consistent for patients treated with or without metformin.Table 3 Major adverse cardiovascular events (MACE) and mortality by treatment group in the CAROLINA studyPrimary CV composite (Cardiovascular death, non-fatal MI, non-fatal stroke)** Test on non-inferiority to demonstrate that the upper bound of the 95% CI for the hazard ratio is less than 1.3For the entire treatment period (median time on treatment 5.9 years) the rate of patients with moderate or severe hypoglycaemia was 6.5% on linagliptin versus 30.9% on glimepiride, severe hypoglycaemia occurred in 0.3% of patients on linagliptin versus 2.2% on glimepiride.The European Medicines Agency has deferred the obligation to submit the results of studies with linagliptin in one or more subsets of the paediatric population in Type 2 diabetes (see section 4.2 for information on paediatric use).The pharmacokinetics of linagliptin has been extensively characterised in healthy subjects and patients with type 2 diabetes.