Trajenta duo 2.5mg/500mg Boehringerer treatment of type 2 diabetes (60 tablets)

metformin hydrochloride increases the transport ability of all glucose transportation through the cell membrane (GLUT) to date.

In humans, metformin hydrochloride also has a favorable effect on lipid metabolism, independent of the effect on blood sugar. This effect is recorded in the dose of treatment in clinical studies with a long and long -term research time: Metformin hydrochloride reduces total cholesterol, LDL cholesterol and triglycerides.

pharmacokinetic

linagliptin

absorption

Absolutely bioavailability of Linagliptin is about 30%. Drinking Linagliptin along with a fat -rich meal that does not affect 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 P - Glycoprotein and CYP3A4 increases the concentration of drugs (AUC) 2 times and used many times simultaneously Linagliptin with Rifampicin, a powerful induction for P - GP and CYP3A, leading to a decrease of about 40% of the AUC level of Linagliptin in a stable state, maybe due to Linagliptin's increased rise Application P - Glycoprotein.

Distribution

Due to tissue bonds, the average appsed distribution volume is in a stable state after using a single -dose of 5 mg of vein line of Linagliptin in healthy people at about 1110 liters, showing that Linagliptin is widely distributed to tissues. Linagliptin's plasma protein bonds depend on concentration, reduced from about 99% at a concentration of 1 nmol/l to 75 - 89% at a concentration of ≥ 30 nmol/l, reflecting the saturation associated with DPP - 4 when increasing the concentration of linagliptin. At high concentrations, when DPP - 4 is completely saturated, 70 - 80% of Linagliptin is linked to other plasma proteins other than DPP - 4, so 30-20% 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 metabolite with a relatively 13.3% linagliptin dose in a stable state is detected as a substance without pharmacological activity and therefore does not contribute to the inhibition of DPP - 4 plasma inhibitors of Linagliptin.

Elimination

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.

Renal failure: There is no need to adjust the linagliptin dose in patients with renal impairment at any level. In addition, mild kidney failure does not affect the pharmacokinetics of Linagliptin in patients with diabetes type 2 according to the pharmacokinetic analysis assessment of the research population.

Hepatic failure: There is no need to adjust the linagliptin dose for patients with mild, medium or severe liver failure.

metformin

absorption

After taking 1 oral metformin dose, TMAX is achieved after 2.5 hours. Absolute bioavailability of Metformin Hydrochloride 500 mg or 850 mg in healthy volunteers is about 50 - 60%.

After an oral dose, the non -absorbing drug is found in feces of 20 - 30%.

After oral use, Metformin Hydrochloride is absorbed in incomplete and saturated. Pharmacoderminium absorption of Metformin Hydrochloride is thought to be non -linear.

Distribution

drugs are negligible with plasma proteins. Metformin Hydrochloride is distributed into red blood cells. The peak concentration in the blood is lower than the peak concentration in plasma and appears at the same time. Many possibilities are a secondary distribution compartment. The average distribution volume (VD) is in the range of 63 - 276L.

Metabolism

metformin hydrochloride eliminates urine in a constant form. No metabolites in humans.

Elimination

The renal waste of the metformin hydrochloride> 400 ml/min shows that metformin hydrochloride is eliminated by glomerular filtration and excreted through the renal tubules. After an oral dose, the apparent sale time is about 6.5 hours. When renal function decreases, the removal of drugs through the kidneys decreases proportional to the clearing of creatinine, so the sale time also lasts, resulting in an increase in plasma metformin hydrochloride levels in plasma.

When encountering side effects of the drug, it is necessary to notify the doctor for timely treatment.

Be cautious when using

should not use Trajenta Duo 2.5 mg/500 mg for patients with type 1 diabetes or patients with diabetes.

Use with known drugs that cause hypoglycemia

Higher hypoglycemia ratio when using linagliptin combined with insulin in patients with severe renal impairment. Therefore, to reduce the risk of hypoglycemia when used in conjunction with Trajenta Duo 2.5 mg/500 mg, it may be required to take a lower dose than insulin or insulin secretion.

Elderly, weak, or malnutrition patients, and patients with pituitary or adrenal impairment or alcohol poisoning are especially sensitive to hypoglycemic effects. Hypoglycemia may be difficult to identify in the elderly, and in patients taking β - adrenergic inhibitors.

Lactic acidic acidosis

Risk factors of lactic acidic acidosis related to Metformin include renal failure, simultaneous use with certain drugs (eg anhydrase carbonic inhibitors such as Topiramate), aged 65 and older, performing screens using contrast drugs, surgery and performing other tricks, reducing inhaled oxygen (eg acute congestion), drinking a lot of alcohol and liver failure.

kidney failure

Lactic acidosis related to Metformin during after -sales drug monitoring occurs mainly in patients with severe renal failure. The risk of metformin accumulation and lactic acidosis associated with metformin increases with the severity of renal failure because Metformin is excreted mainly through the kidneys.

Before the beginning of treatment with Metformin, it is estimated that the level of glomerular filtration (EGFR) of the patient.

Contraindicated Metformin in patients with EGFR is less than 30 ml/min/1.73m2.

It is not recommended to start treatment with Metformin in patients with EGFR in the range of 30 - 45 ml/min/1.73m2.

Collect data on EGFR at least once a year in all patients using Metformin. In patients who are likely to increase the risk of renal failure (such as the elderly) the kidney function should be evaluated more often.

In patients using Metformin and there is an EGFR drop below 45 ml/min/1.73m2.

Medicine interaction: Concomitant use of metformin with some drugs may increase the risk of lactic acidosis related to metformin.

Patients aged 65 and over

The risk of lactic acidosis is related to the patient's age because the elderly patients are likely to have liver failure, kidney failure, heart failure than younger patients. Need to evaluate kidney function more often for older patients.

Perform diagnostic tests using contrast drug

Injecting of the intravascular contrast in patients who are being treated for metformin can lead to impairment of renal function and cause lactic acidosis.

Stop using Metformin before or at the time of performing a scan using iodine -containing contrast drug in patients with EGFR in the range of 30-60 ml/min/1.73m2, patients with a history of liver failure, alcoholism, heart failure or patients will use contrast drugs containing iodine by artery. Reassess EGFR 48 hours after screening and reuse Metformin if the kidney function is stable.

Surgery or other procedures

Food and fluid storage during surgery or performing other procedures may increase the risk of decreased volume, hypotension and kidney failure. Metformin should be temporarily stopped temporarily when the patient has a limited amount of food and deposits.

Metformin hydrochloride must be stopped 48 hours before surgery under the program with systemic anesthesia, spinal anesthesia or external epidural. It is possible to reuse the drug after 48 hours from the surgery or after the patient is raised again by oral and only when the kidney function is determined to be normal.

Inhalation oxygen reduction

The after -sales monitoring process has recorded a number of lactic acidosis related to metformin occurring in acute congestive heart failure (especially when accompanied by reduced perfusion and hypoxemia). Cardiovascular collapse (shock), acute myocardial infarction, bacterial infection and other diseases related to hypoxemia are associated with lactic acidosis and may also cause nitrogen nitrogen before the kidneys. When these events occur, stop Metformin.

Drinking alcohol

Hepatic failure

Patients with hepatic impairment can progress to lactic acidosis related to metformin due to lactate elimination decrease, leading to increased lactate levels in the blood. Therefore, avoid using Metformin in patients who have been diagnosed with liver disease through tested or clinical evidence assessing risks - the benefits of continuing the regimen.

Pancreatitis

There have been after -sales reports of acute pancreatitis, including dead pancreatitis in patients using linagliptin. Read carefully about the possible signs and symptoms of pancreatitis. If suspected of pancreatitis, immediately stop using Trajenta Duo 2.5 mg/500 mg and start appropriate treatment. It is unknown whether the patient has a history of pancreas, which increases or does not risk pancreatic inflammation while using Trajenta Duo 2.5 mg/500 mg.

Heart function

Heart failure is at higher risk of oxygen and renal failure. In patients with stable chronic heart failure, Trajenta Duo can be used for 2.5 mg/500 mg provided with regular monitoring of heart and kidney function.

Contraindicated Trajenta Duo 2.5 mg/500 mg for patients with acute heart failure and heart failure because the drug contains Metformin.

Pemphigoid puffer

There have been reports after circulation of pemphigoid puffiness in patients using linagliptin. If there is suspicion of pemphigoid bullous, it is necessary to stop using Trajenta duo 2.5 mg/500 mg.

The ability to drive and operate machinery

There has been no research on the effect of the drug on the ability to drive and operate machinery.

Pregnancy

There is no appropriate study and strict control conducted on pregnant women using Trajenta Duo 2.5 mg/500 mg or its individual active ingredients. Reproductive non -clinical studies conducted on mice using drugs combined with Trajenta Duo 2.5 mg/500 mg does not show the teratogenic effect of simultaneous use of linagliptin and metformin.

To be cautious, better to avoid using Trajenta Duo 2.5 mg/500 mg during pregnancy.

When a patient plans to get pregnant and during pregnancy, he should not treat diabetes with Trajenta Duo 2.5 mg/500 mg, but should use insulin to maintain as close as normal as possible to reduce the risk of pregnancy deformities related to abnormal blood sugar levels.

The period of breastfeeding

In humans, metformin has excreted in breast milk. It is still unclear whether Linagliptin is excreted in breast milk or not. Dojenta duo should not be used 2.5 mg/500 mg in breastfeeding women.

Drug interaction

linagliptin

Assessment of In vitro interaction:

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

Linagliptin is a p - glycoprotein substrate and inhibits the transport of digoxin through p - glycoprotein intermediaries with low activity. Based on these results and studies on Vivo, Linagliptin interactive drugs are considered to be less likely to cause interaction with other P -GP substrates.

Interaction assessment in vivo:

Linagliptin has no clinical impact related to the pharmacokinetics of Metformin, Glibenclamide, Simvastatin, Pioglitazone, Warfarin, Digoxin or oral contraceptives, which provides in vivo evidence that the trend is less likely to cause drug interactions with substrates of CYP3A4, CYP2C9, CYP2C8, P - Glycoprotein Organic Cationic Transporter (OCT).

Oral contraceptive pills: Concomitant use with 5 mg of linagliptin does not change the pharmacokinetics in the stable state of levonorgestrel or ethinylelestradiol.

Absolutely bioavailability of Linagliptin is about 30%. Due to the simultaneous use of Linagliptin at a fat -rich meal that does not cause clinical effects on pharmacokinetics, Linagliptin can be used or not with food.

metformin

The risk of lactic acidic acidosis increases in acute alcoholic poisoning patients (especially in the case of fasting, malnutrition or liver failure) due to the active ingredient Metformin of Trajenta Duo 2.5 mg/500 mg (see the cautious part when used). Alcohol and alcohol should be avoided.

Cation original drugs are excreted mainly through the renal tubules (for example, cimetidine) can interact with metformin due to competition to be transported by the renal tubules. Therefore, it is advisable to consider monitoring the blood sugar closely, adjust the dose in the recommended dose and change the treatment of diabetes when used simultaneously with cation removal drugs through the renal tubules.

ANHYDRASE CARBONS: Topiramate or carbon dioxide inhibitors (Zonisamide, Acetazolamide or Dichlorphenamide) regularly cause hype of serum bicarbonate and cause hypertension metabolism, without changing anion space. Concomitant use of these drugs can cause metabolic acidosis. Be careful to use these medications in patients treated with Trajenta Duo 2.5 mg/500 mg due to an increased risk of lactic acidic acidosis.

Injecting of the intravascular contrast in patients who are being treated for metformin can lead to impairment of renal function and cause lactic acidosis.

Stop using Metformin before or at the time of performing a scan using iodine -containing contrast drug in patients with EGFR in the range of 30-60 ml/min/1.73m2, patients with a history of liver failure, alcoholism, heart failure or patients will use contrast drugs containing iodine by artery. Reassess EGFR 48 hours after screening and reuse Metformin if the kidney function is stable.