Janumet pills 850mg + 50mg, 56pcs

Composition

One film coated tablet contains:

Sitagliptin Phosphate monohydrate 50 mg;

Metformin hydrochloride 850 mg.

Auxiliary substances:

Microcrystalline cellulose 59.30 mg;

Povidone 48.23 mg;

Sodium stearyl fumarate 13.78 mg;

Sodium Lauryl sulfate 3,445 mg.

The shell of the Opadray II Pink tablet,85 F 94203 (17.23 mg) contains:

Polyvinyl alcohol 47,800%;

Titanium dioxide (E 171) 6,000%;

Macrogol – 3350 23,500%;

Talc 22.590%;

Iron oxide black (E 172) 0.005%;

Iron oxide red (E 172) 0.105%.

Pharmacological action

Yanumet is a combination of two hypoglycemic drugs with a complementary mechanism of action designed to improve glycemic control in patients with type 2 diabetes: sitagliptin, an inhibitor of the enzyme dipeptidyl peptidase-4 (DPP-4), and metformin, a representative of the biguanide class.

Sitagliptin is an orally active, highly selective DPP-4 inhibitor intended for the treatment of type 2 diabetes mellitus. The pharmacological effects of a class of DPP-4 inhibitors are mediated by incretin activation.

By inhibiting DPP-4, sitagliptin increases the concentration of two known active hormones of the incretin family: glucagon-like peptide 1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP). Incretins are part of the internal physiological system for regulating glucose homeostasis. At normal or elevated blood glucose concentrations, GLP-1 and GIP promote increased insulin synthesis and secretion by pancreatic beta cells. GLP-1 also suppresses glucagon secretion by pancreatic alpha cells, thus reducing glucose synthesis in the liver.

This mechanism of action differs from the mechanism of action of sulfonylurea derivatives, which stimulate the release of insulin even at low blood glucose concentrations, which is fraught with the development of sulfonyl-induced hypoglycemia not only in patients with type 2 diabetes, but also in healthy individuals.

Being a highly selective and effective inhibitor of the DPP-4 enzyme, sitagliptin at therapeutic concentrations does not inhibit the activity of related DPP-8 or DPP-9 enzymes.

Sitagliptin differs in chemical structure and pharmacological action from analogues of GLP-1, insulin, sulfonylurea derivatives or meglitinides, biguanides, agonists of gamma-receptors activated by the peroxisome proliferator (PPARy), alpha-glycosidase inhibitors and amylin analogues.

Metformin is a hypoglycemic drug that increases glucose tolerance in patients with type 2 diabetes mellitus, reducing basal and postprandial blood glucose concentrations. Its pharmacological mechanisms of action differ from those of oral hypoglycemic drugs of other classes. Metformin reduces glucose synthesis in the liver, reduces glucose absorption in the intestine, and increases insulin sensitivity by capturing and disposing of glucose.

Indications

• Yanumet is indicated as an adjunct to diet and exercise regimen to improve glycemic control in patients with type II diabetes mellitus who have not achieved adequate control during metformin or sitagliptin monotherapy, or after unsuccessful combined treatment with the two drugs.

• Yanumet is indicated in combination with sulfonylurea derivatives (a combination of three drugs) as an adjunct to diet and exercise regimen to improve glycemic control in patients with type II diabetes who have not achieved adequate control after treatment with two of the following three medications: metformin, sitagliptin, or sulfonylurea derivatives.

• Yanumet is indicated in combination with PPAR-α agonists (e. g. thiazolidinediones) as an adjunct to diet and exercise regimen to improve glycemic control in patients with type II diabetes who have not achieved adequate control after treatment with two of the following three medications: metformin, sitagliptin, or a PPAR-A agonist.

• Yanumet is indicated for patients with type II diabetes mellitus (a combination of three drugs) as an adjunct to diet and exercise regimen to improve glycemic control in combination with insulin.

Use during pregnancy and lactation

There have been no adequately controlled studies of the drug Yanumet or its components in pregnant women, therefore, there are no data on the safety of its use in pregnant women.

The drug Yanumet, like other oral hypoglycemic drugs, is not recommended for use during pregnancy.

No experimental studies of the combined drug Yanumet have been conducted to assess its effect on reproductive function.

Only available data from sitagliptin and metformin studies are provided.

Contraindications

• Hypersensitivity to sitagliptin phosphate, metformin hydrochloride or any other component of the drug;wbr>Acute conditions that may affect kidney function: dehydration, severe infections, shock;

• Acute or chronic diseases that can lead to tissue hypoxia, such as heart or respiratory failure, a recent myocardial infarction, or shock.

• Moderate or severe renal impairment (creatinine clearance

• Impaired liver function;

• Acute alcohol intoxication, alcoholism;

• Breast-feeding period;

• Type I diabetes mellitus;

• Acute or chronic metabolic acidosis, including diabetic ketoacidosis (with or without coma);

• Radiological studies (intravascular use of iodine-containing contrast agents).

• Side effects

From the digestive tract: at the beginning of the course of treatment — anorexia, diarrhea, nausea, vomiting, flatulence, abdominal pain (reduced when taken with food); metallic taste in the mouth (3%).

From the cardiovascular system and blood (hematopoiesis, hemostasis): in isolated cases — megaloblastic anemia (the result of impaired absorption of vitamin B12 and folic acid).

From the side of metabolism: hypoglycemia; in rare cases-lactate acidosis (weakness, drowsiness, hypotension, resistant bradyarrhythmia, respiratory disorders, abdominal pain, myalgia, hypothermia).

Skin disorders: rash, dermatitis.

Interaction

Sitagliptin and metformin

Simultaneous use of multiple doses of sitagliptin (50 mg twice daily) and metformin (1000 mg twice daily) was not accompanied by significant changes in the pharmacokinetic parameters of sitagliptin or metformin in patients with type 2 diabetes mellitus.

Studies of the inter-drug effect on the pharmacokinetic parameters of the drug Yanumet have not been conducted, but a sufficient number of similar studies have been conducted for each of the components of the drug, sitagliptin and metformin.

Sitagliptin

In drug interaction studies, sitagliptin did not have a clinically significant effect on the pharmacokinetics of the following drugs: metformin, rosiglitazone, glibenclamide, simvastatin, warfarin, oral contraceptives. Based on these data, sitagliptin does not inhibit the CYP isoenzymes of the cytochrome CYP3A4,2C8 or 2C9 system. In vitro data indicate that sitagliptin also does not inhibit the isoenzymes CYP2D6,1A2C19 and 2B6 and does not induce CYP3A4. According to a population pharmacokinetic analysis of patients with type 2 diabetes mellitus, concomitant therapy did not have a clinically significant effect on the pharmacokinetics of sitagliptin.

The study evaluated a number of drugs most commonly used in patients with type 2 diabetes, including: hypocholesterolemic drugs (statins, fibrates, ezetimibe), antiplatelet agents (clopidogrel), antihypertensive drugs (ACE inhibitors, angiotensin II receptor antagonists, beta-blockers, slow calcium channel blockers, hydrochlorothiazide, analgesics, and nonsteroidal anti-inflammatory drugs (naproxen, diclofenac, celecoxib), antidepressants (bupropion, fluoxetine, sertraline), antihistamines (cetirizine), proton pump inhibitors (omeprazole, lansoprazole) and drugs for the treatment of erectile dysfunction (sildenafil).

There was an increase in the AUC (11%), as well as the average cmax (18%) of digoxin when co-administered with sitagliptin. This increase is not considered clinically significant, but patient monitoring is recommended when digoxin is co-administered. The AUC and cmax of sitagliptin increased by 29% and 68%, respectively, with a single oral dose of 100 mg of JANUVIA and 600 mg of cyclosporine (a potent p-glycoprotein inhibitor). These changes in the pharmacokinetic parameters of sitagliptin are not clinically significant.

Metformin

Glyburide – in the study of drug-to-drug interactions between single doses of metformin and glyburide in patients with type 2 diabetes mellitus, no changes in the pharmacokinetic and pharmacodynamic parameters of metformin were observed. Changes in glyburide AUC and Cmax values were highly variable. Insufficient information (single dose) and the discrepancy between the plasma concentration of glyburide and the observed pharmacodynamic effects call into question the clinical significance of this interaction.

Furosemide-in a study of drug-to-drug interactions between single doses of metformin and furosemide in healthy volunteers, changes in the pharmacokinetic parameters of both drugs were observed.

Furosemide increased the C max concentration of metformin in plasma and whole blood by 22%, the AUC value of metformin in whole blood by 15%, without changing the renal clearance of the drug. The C max and AUC values of furosemide, in turn, decreased by 31% and 12%, respectively, and the elimination half-life decreased by 32%, without significant changes in the renal clearance of furosemide. There is no information about the inter-drug interaction of the two drugs during long-term joint use.

Nifedipine – a study of the drug-drug interaction between nifedipine and metformin after a single dose of drugs in healthy volunteers revealed an increase in plasma cmax and AUC of metformin by 20% and 9%, respectively, as well as an increase in the amount of metformin excreted by the kidneys. The tmax and half-life of metformin did not change. It is based on increased absorption of metformin in the presence of nifedipine. The effect of metformin on the pharmacokinetics of nifedipine is minimal.

Cationic drugs – cationic drugs (i. e., amiloride, digoxin, morphine, procainamide, quinidine, quinine, ranitidine, triamterene, trimethoprim, or vancomycin) released by tubular secretion can theoretically interact with metformin, competing for a shared renal tubular transport system. Similar competition was observed when metformin and cimetidine were co-administered to healthy volunteers in single-and multiple-dose studies, with a 60% increase in the C max concentration of metformin in plasma and whole blood and a 40% increase in the AUC value of metformin in plasma and whole blood. In the single-dose study, the half-life of metformin did not change. Metformin did not affect the pharmacokinetics of cimetidine. Although these drug-drug interactions are mainly of theoretical significance (with the exception of cimetidine), careful monitoring of the patient and dose adjustment of Yanumet and/or the above-mentioned cationic drugs excreted by the proximal renal tubules are recommended in cases of simultaneous use.

Some medications have hyperglycemic potential and may interfere with established glycemic control. These include thiazide and other diuretics, glucocorticosteroids, phenothiazines, thyroid medications, estrogens, oral contraceptives, phenytoin, nicotinic acid, sympathomimetics, slow calcium channel blockers, and isoniazid. When prescribing these drugs to a patient receiving Yanumet, careful monitoring of the parameters of glycemic control is recommended. No changes in the pharmacokinetic parameters of these drugs were observed when metformin and propranolol or metformin and ibuprofen were administered simultaneously to healthy volunteers.

Only a small proportion of metformin binds to plasma proteins, therefore, inter-drug interactions of metformin with drugs that actively bind to plasma proteins (salicylates, sulfonamides, chloramphenicol and probenecid) are unlikely, unlike sulfonylurea derivatives, which also actively bind to plasma proteins.

How to take, course of use and dosage

The dosage regimen of Yanumet should be selected individually, based on current therapy, efficacy and tolerability, but not exceeding the maximum recommended daily dose of sitagliptin 100 mg.

The drug Yanumet is usually prescribed 2 times a day with meals, with a gradual increase in the dose, in order to minimize possible side effects from the gastrointestinal tract (GIT), characteristic of metformin. The initial dose of Yanumet depends on the current hypoglycemic therapy.

Overdose

Sitagliptin: in healthy volunteers, single doses of up to 800 mg were generally well tolerated. When using a dose of 800 mg in a clinical study, a slight prolongation of the Q–Tc interval was detected, which was not considered clinically significant. There is no experience of using the drug in doses exceeding 800 mg.

No dose-related adverse reactions were observed in studies with 600 mg/day for 10 days and 400 mg for 28 days. Sitagliptin is poorly dialyzed: according to clinical studies, only 13.5% of the dose was eliminated during a 3-4-hour hemodialysis session. If clinically necessary, prolonged hemodialysis is prescribed. There are no data on the effectiveness of sitagliptin peritoneal dialysis.

Metformin: Cases of metformin overdose have been reported, including ingestion in amounts exceeding 50 g. Hypoglycemia was detected in approximately 10% of all overdose cases, but no causal relationship with metformin overdose was established. Lactic acidosis was reported in approximately 32% of all metformin overdose cases.

Emergency hemodialysis is necessary (metformin is dialyzed at a rate of up to 170 ml / min in conditions of good hemodynamics) to accelerate the elimination of excess metformin in case of suspected overdose. In case of an overdose of Yanumet, it is necessary to start standard maintenance measures: removal of the remaining drug from the gastrointestinal tract that has not yet been absorbed, monitoring of vital signs, including ECG, hemodialysis, and the appointment of maintenance therapy if necessary.

Special instructions

Use in the elderly of Yanumet: since the main route of elimination of sitagliptin and metformin is the kidneys, and since the excretory function of the kidneys decreases with age, precautions for prescribing Yanumet increase in proportion to age.

Elderly patients should be carefully selected for the dose and regularly monitored for renal function.

Form of production

Pills.

Storage conditions

At a temperature not exceeding 25 °C.

Shelf

life is 2 years.

Active ingredient

Metformin, Sitagliptin

Conditions of release from pharmacies

By prescription

Dosage form

Tablets

Purpose

For adults as directed by your doctor

Indications

Type 2 Diabetes