Trajenta medicine 5mg Boehringer controls blood sugar (3 blisters x 10 tablets)

Dosage form Box of 3 blisters x 10 tablets
Specifications Linagliptin

Ingredient

Composition information	Content
Linagliptin	5mg

Uses

indications

Trajenta 5 mg drug is indicated for treatment of type 2 diabetes (T2DM) in adult patients to improve blood sugar control:

Unit of treatment

Patients have not been well controlled by blood sugar by diet and exercise and the patient is not suitable for treatment with metformin due to intolerance or contraindications due to kidney failure .

Coordination therapy

Coordinate with Metformin when diet and exercise along with monochromatic Metformin without good blood sugar control.

Coordinate with pioglitazone or sulfonylurea when the untreated treatment regimen does not control blood sugar.

Coordinate with Metformin + Sulfonylurea or Metformin + Sodium-Glucose 2-to-inhibitors (SGLT2 inhibitors) (Triple Drug treatment regimen) when the two drug regimen does not control blood sugar well.

combine with insulin to use or not with metformin, when this regimen has this insulin combined with a diet and exercise that does not control blood sugar well.

Trajenta is not indicated for patients with type 1 diabetes or diabetes patients with acidic acidosis.

Pharmacology

Pharmacy group

DPP-4 inhibitors

ATC code: A10BH05.

Linagliptin is an enzyme inhibitor DPP-4 (dipeptidyl peptidase 4, EC 3.4.14.5), is an enzyme involved in the inactivated hormone of Incretin GLP-1 and GIP (Peptid-1 like Glucagon, a polypeptide that stimulates insulin dependent on glucose). These hormones are often decomposed quickly by the DPP-4 enzyme. Both invoretin hormones involve physiological regulation for glucose balance.

Incretin is excreted at a low concentration throughout the day and this concentration increases immediately after eating. GLP-1 and GIP increase insulin biosynthesis and excreted from beta cells in the pancreas in normal condition and hyperglycemia. Moreover, GLP-1 also reduces the excretion of glucagon from alpha cells in the pancreas, leading to reducing the excretion of the liver.

Linagliptin (Trajenta) is very effective with DPP-4 and can be separated, thereby increasing the activated and prolonged activated intensein level. Trajenta increases insulin secretion depends on glucose and reduces glucagon secretion, so it generally improves glucose balance. Linagliptin selectively connects with DPP-4 and is selective> 10,000 times compared to the DPP-8 or DPP-9 activity on In vitro.

Clinical trials

Linagliptin single therapy for patients who cannot use metformin

The effectiveness and safety of the single Linagliptin is also evaluated in patients whose treatment with Metformin is inappropriate, due to intolerance or contraindications in an 18 -week part -time blind study study, then expanding safety for up to 34 weeks (patients treated with placebo to Glimepiride).

Linagliptin significantly improves HBA1C, (down 0.60% compared to placebo), from the initial average HBA1C value of 8.09%. The average change of HBA1C compared to the original remains unchanged in the group using linagliptin from week 18 to week 52. Linagliptin also shows significant improvement in the amount of sugar in the plasma (FPG) (down 20.5 mg/dL (equivalent to 1.1 mmol/l) compared to the placebo) and the majority of patients achieve HBA1C target The rate of hypoglycemia is observed in patients treated with linagliptin is similar to placebo and lower in the Glimepiride group during monitoring of expansion safety. The body weight is not significantly different from groups for 18 weeks of control with placebo, and patients treated with Glimepiride have increased body weight during the expansion time to monitor safety.

Linagliptin adds to treatment with Metformin

The effectiveness and safety of Linagliptin in combination with Metformin has been assessed in a mesmerized double blind study of 24 -week placebo. Linagliptin significantly improved HBA1C, (-0.64% compared to placebo), from the initial average value HBA1C 8%. Linagliptin also shows significant improvement in the amount of sugar in hunger (FPG) (down 21.1 mg/dl (equivalent to 1.2 mmol/l), and 2 hours after eating (PPG) decreased by 67.1 mg/dL (equivalent to 3.7 mmol/l) compared to placebo and the proportion of patients achieving HBA1C target The effectiveness and safety of Linagliptin in combination with Metformin from the beginning is assessed in a place where a 24 -week fatal control is redundant. Linagliptin 2.5 mg used twice daily in combination with metformin (500 mg or 1000 mg twice daily) shows significant improvement of blood sugar parameters compared to single -treatment groups (HBA1C initial average 8.65%).

The average HBA1C treatment difference between the group using Linagliptin + Metformin compared to the single Metformin from the beginning of treatment until week 24 (based on the final evaluation results -abbreviated LocF) is a reduction of 0.51% (KTC 95% -0.73, -0,30; p

Moderate HBA1C changes in the placebo group has a place to get a placebo from the beginning of treatment for the Linagliptin group 2.5 mg/metformin 1000 mg twice a day is 1.71% leading to HBA1C control (

affect plasma lipids is generally not available. Reduce body weight when combining linagliptin and metformin similar to the single or placebo Metformin; There is no change from the beginning of treatment for patients with Linagliptin alone. The ratio of hypoglycemia is similar to treatment groups (placebo 1.4%, linagliptin 5 mg 0%, metformin 2.1%, and 2.5 mg linagliptin with metformin twice daily 1.4%).

In addition, this study includes patients (n = 66) with a more severe hyperglycemia (HBA1C at the beginning of treatment ≥11%) and being treated with an open label twice daily Linagliptin 2.5 mg and Metformin 1000 mg. In this patient group, the average HBA1C value at the beginning was 11.8% and the average FPG was 261.8 mg/dl (equivalent to 14.5 mmol/l). The average reduction of HBA1C compared to the original was 3.74% (n = 48) and decreased by 81.2 mg/dL (equivalent to 4.5 mmol/l) for FPG (n = 41) observed in patients who complete clinical tests lasting 24 weeks without risk treatment.

In LOCF analysis, all patients have the main criteria measured at the last tracking (n = 65) without risk treatment, change compared to the original by 3.19% for HBA1C and decreased by 73.6% Mg/DL (equivalent to 4.1 mmol/l) for FPG.

The effectiveness and safety of Linagliptin 2.5 mg twice daily compared to 5 mg once a day in combination with metformin in patients who are not controlled well with blood sugar with mononermin Metfomin, which is assessed in a double blind study, regard to a 12 -week regard. Linagliptin (2.5 mg twice daily and 5 mg once daily) adds to treatment with metformin significantly improving blood sugar parameters compared to placebo. Linagliptin 5 mg once daily and 2.5 mg twice a day decreases significantly to the equivalent level (KTC: -0.07; 0.19), down 0.80%(compared to the original 7.98%), and decreased by 0.74 (compared to the original 7.96%) compared to the placebo. The rate of hypoglycemia observed in patients treated with linagliptin is similar to placebo. Body weight is not significant difference between groups.

Linagliptin adds to treatment with sulphonylurea

The effectiveness and safety of Linagliptin in combination with Sulphonylurea has been assessed in an 18 -week placebo -control blind study. Linagliptin significantly improved HBA1C, (down 0.47% compared to placebo), from the initial average HBA1C value of 8.6%. Linagliptin also showed significant improvement in the proportion of patients achieving HBA1C target

Linagliptin adds to treatment with insulin

The effectiveness and safety of adding 5 mg of linagliptin to single -therapy insulin or combined with Metformin and/or Pioglitazone have been assessed in a double blind study with a placebo lasting for 24 weeks. The average difference is due to the treatment of HBA1C index between Linagliptin compared to the placebo at the beginning until week 24 (analysis based on the final measurement value) is reduced by 0.65% (KTC 95% -0.74, -0.55; p

Linagliptin also shows a significant improvement in thriving blood sugar (FPG) is a decrease of 11.25 mg/dL (equivalent to 0.62 mmol/l) (KTC 95%, -16,14, -6,36; p

Insulin dose daily average at the beginning is 42 units in patients treated with linagliptin and 40 units in patients treated with placebo. The average change of insulin dose per day from the beginning until week 24 is 1.3 units in the placebo group and 0.6 units at Linagliptin treatment group. Body weight is not significant difference between groups. There is no effect on plasma lipids. The ratio of hypoglycemia is similar to treatment groups (22.2% of linagliptin; 21.2% of placebo).

Linagliptin adds to Metformin and Sulphonylurea combining treatment

A 24 -week placebo -control study was conducted to evaluate the effectiveness and safety of Linagliptin 5 mg compared to the placebo, in patients who have not been satisfactorily treated with Metformin combined with sulphonylurea. Linagliptin significantly improves HBA1C (down 0.62% compared to placebo), from the initial average HBA1C value of 8.14%. Linagliptin also shows significant improvement in the proportion of patients achieving HBA1C target

Linagliptin adds to Metformin and Empagliflozin combination treatment

In patients who are not fully controlled with Metformin and Empagliflozin (10 mg (N = 247) or 25 mg (n = 217)), 24 -week treatment with Linagliptin supplementary therapy 5 mg reduces the average calibration compared to HBA1C the original average initial average of 0.53% (significant difference compared to the placebo is 0.32% (95% CI -0.13) 0.58% (significant difference compared to the placebo is 0.47% (95% CI -0.66; -0,28). The proportion of patients with initial average HBA1C ≥7.0% and treatment with Linagliptin 5 mg achieved HBA1C target ( In the subgroups that have been predetermined to have the original HBA1C value ≥8.5% (the number of patients combined with Metformin and Empagliflozin 10 mg or 25 mg respectively n = 66 and n = 42), HBA1C average corrected decreased compared to the original HBA1C after 24 weeks of treatment with Linagliptin supplementary therapy 5 mg, other than 0.0875, other than 0.0875, other than 0.0875 With placebo) and 1.16% (P = 0.0046, different from placebo).

Linagliptin combined from the beginning with pioglitazone

In a 24 -week placebo -control study combined from the beginning of Linagliptin 5 mg with Pioglitazone (30 mg), treatment combined with linagliptin and pioglitazone significantly improved HBA1C compared to Pioglitazone and placebo (down 0.51%), from the original HBA1C value of 8.6%average. Combining from the beginning of Linagliptin and Pioglitazone significantly improves the amount of sugar in the plasma (FPG) (down 14.2 mg/dL (equivalent to 0.8 mmol/l) compared to placebo), and the proportion of patients can achieve HBA1C target ( Linagliptin adds to Metformin and Pioglitazone combination treatment

A 24 -week control study evaluates the safety and effectiveness of Linagliptin 5 mg compared to placebo on untrusted patients with combining treatment for Metformin and Pioglitazone. Linagliptin significantly improves HBA1C (down 0.57% compared to placebo), from the initial average HBA1C value of 8.42%.

Linagliptin also shows significant improvement in patients who achieve HBA1C target

24 -month data for linagliptin to add to metformin and compare with Glimepiride

In a study comparing the effectiveness and safety of the addition of Linagliptin 5 mg or Glimepiride (a sulphonylurea) in patients who have not been well controlled with single -blood sugar with single -treatment Metformin, Linagliptin is similar to Glimepiride in reducing HBA1C, with a different HBA1C average treatment from the initial 104 week with Linagliptin compared to Linaglipin Glimepiride increased by 0.20%. In this study, the ratio of insulin on insulin, indicating the effectiveness of the synthesis and release of insulin, shows significant improvement of statistical significance when taking Linagliptin compared to Glimepiride treatment.

The rate of hypoglycemia in patients with Linagliptin (7.5%) is significantly lower than the Glimepiride group (36.1%). Patients treated with Linagliptin significantly decreased significantly body weight compared to the original, while significantly weight gain in patients using Glimepiride (-1.39 compared to +1.29kg).

Linagliptin adds to treatment in patients with severe renal impairment, 12 -week data with placebo control (stable treatment) and 40 weeks in the phase of fatal expansion (can be adjusted)

The effectiveness and safety of Linagliptin is also evaluated in patients with type 2 diabetes with severe kidney failure in a double study compared to the placebo for 12 weeks, during that time the previous diabetes treatment was kept stable. Patients were previously treated with different therapies including insulin, sulphonylurea, Glinides and Pioglitazone. There is a 40 -week monitoring period, which can adjust the dose of diabetes initially used.

Linagliptin significantly improved HBA1C (down 0.59% changes compared to placebo), from the average initial HBA1C value of 8.2%. A proportion of patients achieving HBA1C goals

Body weight is not significant difference between groups. The rate of hypoglycemia recorded in patients treated with linagliptin is higher than placebo, due to an increase in asymptomatic hypoglycemia events. This can be caused by existing diabetes treatment (insulin and sulphonylurea or Glinides). There is no difference between groups of serious hypoglycemia.

Linagliptin adds to treatment in elderly patients (age ≥70) Type 2 diabetes

The effectiveness and safety of Linagliptin in elderly patients with type 2 diabetes (age ≥70) have been assessed in a double blind study compared to a place of 24 -week placebo. When being researched, the patient is being treated with Metformin and/or sulphonylurea and/or insulin. Dosage of available diabetes medications is kept stable in the first 12 weeks, then the dose is allowed.

Linagliptin significantly improves the HBA1C index, down 0.64% (KTC 95% -0.81, -0.48; P

The proportion of patients with hypoglycemia is also compared to the existing treatment with insulin or not with Metformin (13 out of 35 patients, 37.1% treatment with linagliptin and 6 out of 15 patients, 40% of placebo treatment). However, on the background of sulphonylurea treatment with or not with Metformin, the proportion of patients with hypoglycemia is reported in a group of patients treated with Linaliptin higher (24 out of 82 patients, 29.3%) than placebo (7 out of 42 patients, 16.7%). There is no difference between groups of serious hypoglycemia.

Linagliptin supplements in advance with oral diabetes treatment drugs, lasting more than 52 weeks in Japanese type diabetes patients

The safety and effectiveness of Linagliptin has been assessed in an open label study, parallel group in patients with diabetes type 2 Japanese people are not fully controlled with a oral diabetes treatment (Biguanide, Glinide, Glitazone, Sulphonylurea [Su] or α-glucosidase inhibitors [A-GO]).

Linagliptin significantly improves HBA1C and FPG from the initial value at the 52nd week for all previously treated groups, from the average initial HBA1C value of 7.98%. The range decreased from 0.70% to 0.91%. Improved observations are reduced by 0.88% in Biguanide and Linagliptin; decreased by 0.73% in Glinide and Linagliptin groups; decreased by 0.79% in Glitazone and Linagliptin groups; decreased by 0.70% in Sulphonylurea and Linagliptin groups; and decreased by 0.91% in α-glucosidase and linagliptin inhibitors.

For FPG, the range is reduced from 6.0 mg/dl/0.3 mmol/l and 12.6 mmol/dl/0.7 mmol/l. The reduction level is 12.6 mmol/dl/0.7 mmol/l in Biguanide and Linagliptin; 9.1 mmol/dl/0.5 mmol/l in Glinide and Linagliptin; 9.8 mmol/dl/0.5 mmol/l in Glitazone and Linagliptin groups; 6.7 mmol/dl/0.4 mmol/l in sulphonylurea and linagliptin group; and 6.0 mg/dl/0.3 mmol/l in α-glucosidase and linagliptin inhibitors. The body weight changes is negligible from the beginning until week 52 in all previous treatment groups.

Linagliptin reduces HBA1C similar to Metformin when supplemented with existing treatment with sulphonylurea, with the average HBA1C difference from the beginning until week 52 is 0.18% in Linagliptin group compared to Metformin.

Linagliptin reduced HBA1C similar to Metformin when supplemented with available treatment with α-glucosidase inhibitors, with the average HBA1C difference from the beginning until week 52 is 0.09% in Linagliptin group compared to Metformin.

The hypoglycemic event is reported irregularly and with mild levels in all groups (5.8%) except in patients treated with sulphonylurea. The hypoglycemic rate is mainly observed when using linagliptin with sulphonylurea (81%); However, this frequency is similar when using Metformin on existing patients with sulphonylurea.

Starting treatment with combination of linagliptin and metformin in patients has just been diagnosed with significant hyperglycemia and has not used drugs

The effectiveness and safety of the beginning of treatment with a combination of Linagliptin 5 mg once a day and Metformin twice a day (adjusted for the first 6 weeks to 1500 mg or 2000 mg/day) compared to Linagliptin 5 mg once daily has been studied in a 24 -week test in patients who have just diagnosed with diabetes with TYP 2 diabetes with significant hyperglycemia and without drugs (HBA1C initially original (HBA1C initially initially used. 8.5-12.0%).

After 24 weeks, both monochromatic linagliptin treatment regimes and the beginning of the combination of linagliptin and metformin significantly reduce HBA1C levels, equivalent to 2% and 2.8% compared to the initial average HBA1C value of 9.9% and 9.8%. The treatment difference decreased by 0.8% (95% CI -1.1 to -0.5) showed that the beginning of combined treatment was superior to the single treatment (P

Cardiovascular risk

In a prior rescue advanced analysis for the cardiovascular events independently evaluated from 19 clinical studies (lasting from 18 to 24 months) on 9459 patients with type 2 diabetes, treatment with Linagliptin is not accompanied by an increase in cardiovascular risk.

The main criterion includes a combination of events: appearance or time until the death of the cardiovascular disease, the first appearance of the heart infarction is not fatal, the stroke does not cause death or the hospital is due to an unstable angina, which is not significantly lower than when using Linagliptin compared to both active or placebo drugs. The total has 60 main events in the Linagliptin group and 62 main events in the comparative drug group.

Cardiovascular events are observed with a similar ratio between the group using linagliptin and placebo (dangerous ratio 1.09 (KTC 95%0.68; 1.75)]. In the control studies with placebo, the total number of 43 main events (1.03%) in the Linagliptin group and 29 main events (1.35%) in the placebo group.

Children's subjects

The effectiveness and safety of Linagliptin in children and adolescents have not been established. No data available.

Dynamic pharmacokinetics

Linagliptin pharmacokinetics have been described in healthy people and patients with type 2 diabetes.

Linagliptin concentration in plasma decreases at least 2 stages with long elimination time (Linagliptin's ending time is longer than 100 hours), which is almost completely related to the saturated state, closely linked by Linagliptin with DPP-4 and does not contribute to the accumulation of the drug. Half -life accumulation of Linagliptin is determined after drinking 5 mg of Linagliptin, approximately 12 hours.

After using a single dose every day, plasma concentrations in the stable state of Linagliptin 5 mg achieved after the third dose. Linagliptin's plasma AUC increased by 33% after using 5 mg dose at a stable state compared to the first dose. The variable coefficient in each patient and between patients with AUC Linagliptin is small (equivalent to 12.6% and 28.5%). Linagliptin plasma AUC increases below the proportional level. The pharmacokinetics of Linagliptin are generally equivalent to healthy subjects and in patients with type 2 diabetes.

absorption

The absolute bioavailability of Linagliptin is approximately 30%. Drinking Linagliptin along with a fat -rich meal without a clinical effect on pharmacokinetics, Linagliptin can be used or not with food. In vitro studies show that linagliptin is a substrate of p-glycoprotein and CYP3A4.

Ritonavir, a strong inhibitor of P-Glycoprotein and CYP3A4, leads to an increase in concentration (AUC) 2 times and used many times simultaneously Linagliptin with Rifampicin, a strong induction for P-GP and CYP3A, leading to a decrease of about 40% of the AUC level of Linagliptin in a stable state, probably due to Linagliptin's bioavailability because of the Linagliptin increasing increase P-Glycoprotein.

Distribution

Due to tissue bonds, the average distribution volume is stable after using 5 mg of venous lines of Linagliptin in healthy people at about 1110 liters, showing that Linagliptin is widely distributed to tissues. Linagliptin's plasma protein bonds depend on the concentration, decreasing from about 99% at 1nmol/l concentration to 75 - 89% at a concentration of ≥30 nmol/l, reflecting saturation associated with DPP -4 when increased Linagliptin levels. At high concentrations, when DPP -4 is completely saturated, 70-80% Linagliptin is linked to other plasma proteins other than DPP -4, so 20-30% in non -binding form in plasma.

Metabolism

After taking a dose [14C] Linagliptin oral 10 mg, about 5% of radioactive substances are excreted into the urine. Metabolism plays a secondary role in the elimination of linagliptin. A main metabolites with relatively 13.3% of Linagliptin dose in stable state are detected as non-pharmacological activity and therefore does not contribute to the activity of plasma DPP-4 plasma inhibitors of Linagliptin.

Excretion

After giving healthy people oral orally [14C] Linagliptin, about 85%of the doses of radioactive activity are eliminated by fertilizer (80%) or urine (5%) within 4 days of taking the drug. The renal removal in a stable state is about 70 ml/min.

Special patient group

kidney failure

An open, multi -dose label study conducted to evaluate the pharmacokinetics of Linagliptin (dose of 5 mg) in patients with chronic renal impairment at different degrees compared to healthy evidence. The study includes patients with renal function that is classified based on mild creatinine clearance (50 to

In addition, patients with type 2 diabetes and severe renal failure (

CrCl = [140 - Age (year)] x Body weight (kg) {x 0.85 for female patients}/[72 x Creatinine serum (mg/dl)].

In a stable state, the level of linagliptin in patients with mild renal failure is the same as a healthy person. In the case of medium renal failure, there is a moderate increase in concentration to about 1.7 times compared to the control group. The concentration in patients with type 2 diabetes with severe renal impairment increases about 1.4 times compared to patients with type 2 diabetes with normal kidney function.

Predict the AUC Linagliptin in a stable state in patients with end -stage renal disease ESRD shows the same contact concentration as medium or severe renal impairment patients. In addition, Linagliptin is less likely to be removed significantly through dialysis or peritoneal dialysis. Therefore, it is not necessary to adjust the linagliptin dose in patients at any level of renal failure. In addition, mild kidney failure does not affect the pharmacokinetics of Linagliptin in patients with type 2 diabetes according to the pharmacokinetic analysis evaluation on the research population.

Hepatic failure

In patients with mild average and severe liver failure (according to Child-Pugh classification), the average AUC and CMAX of Linagliptin are like those who are healthy after using 5 mg of Linagliptin. There is no need to adjust the dose of linagliptin for patients with mild, medium or severe liver failure.

Body mass index (BMI)

No need to adjust the dose based on BMI. The non -clinical body mass index affects the pharmacokinetics of Linagliptin based on a pharmacokinetic analysis on the research population from phase I and phase II.

Gender

There is no need to adjust the dose based on gender. Gender does not have clinically related effects on pharmacokinetics of Linagliptin based on a pharmacokinetics analysis on the population of research from phase I and phase II.

Elderly

There is no need to adjust the dose based on age, due to the clinical -related age that affects the pharmacological force of Linagliptin based on a pharmacokinetic analysis on the research population from phase I and phase II. Elderly subjects (65 to 80 years old) have a concentration of blood linagliptin similar to younger subjects.

Children

The studies have not been conducted in the linagliptin pharmacokinetics in patients with children.

Race

There is no need to adjust the dose based on racial factors. The race does not have a significant effect on the concentration of Linagliptin in plasma based on a synthetic analysis from existing pharmacokinetic data, including white skin, Spanish, African -American, Asia. In addition, the pharmacokinetic characteristics of Linagliptin are recorded as in the specialized I studies specially in healthy Japanese, Chinese and white volunteers and whites and African -American 2 -year -old diabetes patients.

Before taking Trajenta medicine 5mg Boehringer controls blood sugar (3 blisters x 10 tablets)

How to use

Take oral use.

Dosage

Adults

The recommended dose is 5 mg once daily. Trajenta can drink with or not with food at any time of the day. When combining linagliptin with a sulphonylurea, the lower doses of sulphonylurea may be considered to reduce the risk of hypoglycemia.

kidney failure

No dose adjustment in patients with renal failure.

Hepatic failure

No dose adjustments in patients with hepatic failure.

Elderly

There is no need to adjust the dose.

Children and teenagers

There is no recommendation to use Trajenta for children under 18 years of age due to lack of data on safety and efficiency.

Note: The above dose is for reference only. Specific dosage depends on the condition and level of progression of the disease. For a suitable dose, you need to consult a doctor or medical specialist.What to do when overdose?

Symptoms

In healthy clinical studies on people, single dose up to 600 mg of linagliptin (equivalent to 120 recommended dose) is well tolerated. There is no experience when using higher doses over 600 mg.

Treatment

In cases of overdose, it is advisable to take common supportive treatments, such as removing not absorbed from the stomach; Clinically monitoring and applying treatments if needed.

What to do when forgetting a dose? However, if the time to relax with the next dose is too short, skip the dose and continue the calendar of the drug. Do not use double dose to compensate for missed dose.

Side Effects

Excessive risk of hypoglycemia when combined with other hypoglycemic drugs.

Warnings

Before using the drug you need to read the instructions carefully and refer to the information below.

Contraindicated

Trajenta Contraindicated in cases of hypersensitivity to active ingredients or any excipients.

Be cautious when using

general

Do not use trajenta in patients with type 1 diabetes or patients with diabetes (ketoacidosis).

Hypoglycemia

Linagliptin single therapy shows that the rate of hypoglycemia is equivalent to the placebo.

In clinical trials using linagliptin as part of the treatment combined with non -hypoglycemic drugs (metformin), the rate of hypoglycemia is reported to Linagliptin is equivalent to placebo.

When using Linagliptin in combination with Suphonylurea (on the foundation of Metformin), the rate of hypoglycemia increases compared to the placebo (see the item of adverse effects).

Sulphonylurea and insulin are known to be the cause of hypoglycemia. Therefore, be careful when using linagliptin in combination with sulphonylurea and/or insulin. Sulphonylurea or insulin can be considered for dosage and user dose).

Acute pancreatitis

Using DPP-4 inhibitors is associated with the risk of progressive pancreatitis. There have been spontaneous reports on side effects of acute pancreatitis from experience used after circulation of Linagliptin. Patients should be notified of the typical symptoms of acute pancreatitis . If pancreatitis is suspected, Trajenta should be stopped; If you have confirmed acute pancreatitis, do not start treating with Trajenta. Be careful with patients with a history of pancreatitis.

Pemphigoid puffer

There have been reports after circulation of pemphigoid puffiness in patients using linagliptin. If there is a suspected pemphigoid bull, it is necessary to stop using trajenta.

The ability to drive and operate machinery

There are no studies conducted on the ability to drive and operate machinery.

Pregnancy

There is very little data on the use of linagliptin in pregnant women. Animal studies do not indicate directly or indirectly the toxicity on fertility. To be cautious, it is better to avoid using Trajenta during pregnancy.

The period of breastfeeding

available data on pharmacological/animal toxicity shows that there is an excretion of linagliptin/metabolic substances in mother milk.

It is not known whether the drug is excreted in breast milk. Therefore, be careful when using Trajenta in breastfeeding women.

Drug interaction

pharmacokinetic interaction

Evaluation of drug interactions on in vitro

Linagliptin is a inhibitor based on weak to medium and weak competition inhibitors for CYP ISOZEMMOME CYP3A4, but does not inhibit other ISOZEMMS. The drug is not an induction substance for CYP isozyme.

Linagliptin is a p-glycoprotein substrate and inhibits digoxin transportation through p-glycoprotein intermediaries with low activity. Based on these results and drug interactive studies on Vivo, Linagliptin is considered to be less likely to interact with other P-GP substrates.

Evaluation of drug interactions on Vivo

Clinical data described below shows the risk of clinical significance interactions due to the low use of the drug. The clinical interactions have not been observed requiring dose adjustments. Linagliptin does not have a significant clinical impact on pharmacokinetics of Metformin, Glibenclamide, Simvastatin, Pioglitazone, Warfarin, Digoxin or oral contraceptives. This provides Vivo evidence that the trend is less likely to interact with the substrates of CYP3A4, CYP2C9, CYP2C8, P-Glycoprotein and organic cation (OCT).

Metformin : In a healthy volunteer, simultaneously use the 850 mg metformin dose three times a day with a dose on the treatment threshold of 10 mg of Linagliptin once daily does not change the clinical significance of linagliptin or metformin. Therefore, Linagliptin is not an inhibitor of OCT intermediaries. However, there are 14% reduction in both AUC and CMAX values of Glibenclamide, which is not significant clinical. Because glibenclamide is metabolized mainly by CYP2C9, these data also supports that Linagliptin is not a CYP2C9 inhibitor. Clinical interactions that are hard to occur with other sulphonylurea (e.g. Glipizide, Tolbutamide and Glimepiride) are excreted mainly by CYP2C9 similar to glibenclamide. Pioglitazone, a CYP2C8 and CYP3A4 substrate, does not have a significant clinical impact on the pharmacokinetics of both Linagliptin or Pioglitazone or the active metabolites of pioglitazone. This shows that Linagliptin is not a metabolic inhibitor through CYP2C8 In Vivo intermediaries and supports the conclusion that Linagliptin's CYP3A4 in Vivo inhibitors are negligible. to the pharmacokinetics of Linagliptin. Simultaneously taken a single dose of 5 mg of Linagliptin and multi -dose 200 mg oral Ritonavir causing AUC and CMAX increase of Linagliptin, respectively and 3 times. The simulation of plasma linagliptin levels in a stable state when available and no use of ritonavir shows an increase in the concentration of drugs that do not accompany accumulation. These changes in the pharmacokinetics of Linagliptin are not considered clinical significance.

Therefore, clinical interactions are difficult to occur with other p-glycoprotein/CYP3A4 inhibitors and do not need to adjust the dose.

Rifampicin : A study conducted a assessment of the effect of rifampicin, a strong induction for P-Glycoprotein and CYP3A4, on the pharmacokinetics of Linagliptin when used at 5 mg dose. Simultaneously using multi-dose Linagliptin along with rifampicin, resulting in 39.6% and 43.8% AUC and CMAX in the stable state of linagliptin and decreased by about 30% of the DPP-4 inhibitors at bottom concentration. Therefore, Linagliptin when combined with a strong P-GP induction substance can be clinically effective, although it may not achieve adequate effect. Therefore, Linagliptin is not an inhibitor of P-Glycoprotein in vivo intermediaries.

Simvastatin: Use daily doses of Linagliptin 10 mg (above the treatment threshold) with minimal effects on pharmacokinetics in the stable state of simvastatin, a sensitive CYP3A4 substrate in healthy volunteers. After using 10 mg of Linagliptin simultaneously with 40 mg of Simvastatin per day for 6 days, Simvastatin's plasma AUC increased by 34% and plasma CMAX increased by 10%. Therefore, Linagliptin is considered as a weak inhibitor metabolized through CYP3A4 intermediaries, and the adjustment of the dose of substances used simultaneously metabolized by CYP3A4 is considered unnecessary. Ethilylestradiol.

The absolute bioavailability of Linagliptin is approximately 30%. Due to the simultaneous use of Linagliptin at a fat -rich meal that has no clinical significance for pharmacokinetics, Linagliptin can be used with or not with food.

Storage

Store in a cool dry place, avoid light, temperature below 30⁰C.

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