Expiration date: 04/2025
Composition
One tablet film-coated contains: sitagliptin phosphate monohydrate 64,25 mg (equivalent to 50 mg sitagliptin), Metformin hydrochloride 1000 mg.
Excipients: cellulose microcrystalline of 59.30 mg, povidone 48,23 mg, sodium fumarate of 13.78 mg, sodium lauryl 3,445 mg.
Coated tablet Pink Opadry II, 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) of 0.005 %, iron oxide red (E 172) 0,105 %.
One tablet film-coated contains: Sitagliptin phosphate monohydrate 50 mg, Metformin hydrochloride 850 mg.
Excipients: cellulose microcrystalline of 59.30 mg, povidone 48,23 mg, sodium fumarate of 13.78 mg, sodium lauryl 3,445 mg.
Coated tablet Pink Opadry II, 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) of 0.005 %, iron oxide red (E 172) 0,105 %.
Packaging
56 pieces.
Pharmacological action
Drug Janumet is a combination of two hypoglycemic agents with complementary (complementary) mechanism of action designed to improve glycemic control in patients with diabetes type 2 diabetes: sitagliptin, an inhibitor of the enzyme dipeptidyl peptidase-4 (DPP-4), and Metformin, representative of the class of biguanides.
Sitagliptin is active in oral administration, a highly selective DPP-4 inhibitor intended for the treatment of diabetes mellitus type 2. Pharmacological effects class of drugs-inhibitors of DPP-4-mediated activation of incretin. By inhibiting DPP-4, sitagliptin increases the concentration of two known active hormone of the incretin family: glucagon-like peptide 1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP). Incretins are part of the internal physiological regulation of glucose homeostasis. At normal or elevated concentrations of blood glucose GLP-1 and GIP contribute to increased synthesis and secretion of insulin from the beta cells of the pancreas. GLP-1 also suppresses glucagon secretion alpha cells of the pancreas, reducing, thus, the synthesis of glucose in the liver. This mechanism of action differs from mechanism of action of sulfonylureas, which stimulate insulin release at low concentrations of blood glucose, which can lead to the development sulfonyl-induced hypoglycemia not only in patients with diabetes type 2 diabetes but also in healthy individuals. Being highly selective and effective inhibitor of the enzyme DPP-4, sitagliptin, in therapeutic concentrations does not inhibit activity of the related enzymes DPP-8 or DPP-9. Sitagliptin differs in chemical structure and pharmacological action from analogues of GLP-1, insulin, derived sulfonylureas or meglitinide, biguanide, agonist receptor gamma, peroxisome proliferator-activated (PPARy), inhibitors of alpha-glycosidase and analogues Amelina.
Metformin is a hypoglycemic drug that improves glucose tolerance in patients with diabetes type 2 diabetes, lowering both basal and postprandial concentration of glucose in the blood. Its pharmacological mechanisms of action are different from the mechanisms of action of oral hypoglycemic drugs of other classes. Metformin reduces glucose synthesis in the liver, reduces the absorption of glucose in the intestine, and improves insulin sensitivity by capturing and utilization of glucose
Testimony
Janumet shown as addition to diet regime and physical exercise to improve glycemic control in patients with diabetes mellitus type II, have not attained adequate control on monotherapy with Metformin or sitagliptin, or after failure of combined treatment with two drugs. Janumet shown in combination with sulfonylureas (combination of three drugs) as a Supplement to diet regime and physical exercise to improve the control of glycemia in patients with diabetes mellitus type II, have not reached adequate control after treatment two of the following three drugs: Metformin, sitagliptin or sulfonylurea derivatives. Janumet shown in combination with agonists of PPAR-? (e.g. thiazolidinediones) as an adjunct to diet and regime of physical activity to improve the control of glycemia in patients with diabetes mellitus type II, have not reached adequate control after treatment two of the following three drugs: Metformin, sitagliptin, or an agonist of PPAR-?. Janumet shown in patients with diabetes mellitus type II (combination of three drugs) as a Supplement to diet regime and physical exercise to improve control of blood glucose in combination with insulin.
Contraindications
- hypersensitivity to sitagliptin phosphate, Metformin hydrochloride or to any component of the drug,
- acute conditions that can affect kidney function: dehydration, severe infection, shock,
- acute or chronic disease which may cause tissue hypoxia such as cardiac or respiratory failure, recent myocardial - infarction, shock,
- moderate or severe renal dysfunction (creatinine clearance
- abnormal liver function,
- acute alcohol intoxication, alcoholism,
- lactation,
- diabetes mellitus type I,
- acute or chronic metabolic acidosis, including diabetic ketoacidosis (with or without coma),
- radiological studies (intravascular administration of iodinated contrast materials).
Application of pregnancy and breastfeeding
Was not carried out adequately controlled studies of the drug Janumet or its components in pregnant women, therefore, data on the safety of its use in pregnant women no. Drug Janumet as other oral hypoglycemic drugs not recommended for use during pregnancy. Was not carried out experimental studies of combined drug Janumet to assess its impact on reproductive function. Given only the available data from studies of sitagliptin and Metformin.
Method of application and doses
The dosage regimen of the drug Janumet should be individualized based on current therapy, efficacy and tolerability, but not exceeding the maximum recommended daily dose of sitagliptin 100 mg. the Drug is usually prescribed Janumet in mode 2 times a day during meals, with a gradual increase in dose to minimize potential side effects from the gastrointestinal tract (GIT), characteristic for Metformin. The initial dose of the drug Janumet depends on the current hypoglycemic therapy.
Special instructions
Use in the elderly Janumet: since the main route of elimination of sitagliptin and Metformin are the kidneys, and as with age, the excretory function of the kidneys is reduced, the precautions in the appointment of Janumet increasing in proportion to age. Older patients are conduct a thorough selection of doses and regular monitoring of renal function.
Drug interactions
Sitagliptin and Metformin
Simultaneous reception of multiple doses of sitagliptin (50 mg 2 times per night) and Metformin (1000 mg 2 times a day) was not accompanied by significant changes of pharmacokinetic parameters of sitagliptin or Metformin in patients with diabetes type 2 diabetes.
Studies because of drug influence on the pharmacokinetic parameters of the drug Janumet not carried out, but carried out a sufficient number of such studies for each component of the drug, sitagliptin and Metformin.
Sitagliptin
In interaction studies with other drugs, sitagliptin had no clinically significant effect on the pharmacokinetics of the following drugs: Metformin, rosiglitazona, glibenclamide, simvastatin, warfarin, oral contraceptives. Based on these data, sitagliptin does not inhibit CYP isozymes of cytochrome CYP3A4,2C9, or 2C8. In vitro data suggest that sitagliptin is not also inhibits the isoenzymes CYP2D6,1A2,2C19 and 2B6 and does not induce CYP3A4. According to the population pharmacokinetic analysis of patients with diabetes type 2 diabetes and related therapy had no clinically significant effect on the pharmacokinetics of sitagliptin. The study evaluated several drugs most commonly used by patients with diabetes mellitus type 2, including: cholesterol-lowering drugs (statins, fibrates, ezetimibe), antiplatelet agents (clopidogrel), antihypertensive drugs (ACE inhibitors, receptor antagonists of angiotensin II, beta-blockers, blockers slow calcium channels, hydrochlorothiazide, analgesics and non-steroidal 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).
The increase in AUC (11 %) and the average C max (18 %) of digoxin when used together with sitagliptin. This increase is not considered clinically significant, however, while receiving digoxin, it is recommended to monitor the patient. The increase in AUC and C max of sitagliptin on 29% and 68 %, respectively, when sharing a single oral dose of the drug of JANUVIA at a dose of 100 mg and cyclosporine (a potent inhibitor of p-glycoprotein) in a dose of 600 mg. These changes of pharmacokinetic parameters of sitagliptin are not clinically significant.
Metformin
Glyburide - in a study of drug-drug interactions single doses of Metformin and glyburide in patients with diabetes mellitus type 2 did not observe any changes in pharmacokinetic and pharmacodynamic parameters of Metformin. Change the values of AUC and Cmax glyburide was vysokoperedelnyh. Insufficient information (single reception) and the discrepancy between plasma concentrations of glyburide the observed pharmacodynamic effects call into question the clinical significance of this interaction.
Furosemide - drug-drug interaction study, single doses of Metformin and furosemide in healthy volunteers observed the changes of pharmacokinetic parameters of both drugs. Furosemide increased the concentration value C max of Metformin in plasma and whole blood by 22 %, the AUC of Metformin in the blood by 15 %, while not modifying the renal clearance of the drug. Values of C max and AUC of furosemide, in turn, decreased by 31% and 12 %, respectively, and the elimination half-life was decreased by 32 %, without significant changes in renal clearance of furosemide. Information on drug-drug interaction of two drugs with long-term joint application no.
Nifedipine - the study of drug-drug interaction between nifedipine and Metformin after a single dose of drugs in healthy volunteers showed an increase in plasma C max and AUC of Metformin by 20% and 9 %, respectively, as well as increasing the amount secreted by the kidneys Metformin. T max and half-life of Metformin is not changed. The basis - increase the 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) secreted by tubular secretion, theoretically may interact with Metformin by competing for shared renal tubular transport system. Similar competition was observed by the simultaneous administration of Metformin and cimetidine in healthy volunteers in studies of single and multiple doses, with 60% increase in the concentration of C max of Metformin in plasma and whole blood and 40% increase in AUC values of Metformin in plasma and whole blood. In the study, single doses, the half-life of Metformin were not changed. Metformin did not affect the pharmacokinetics of cimetidine. And although these drug-drug interactions are mostly theoretical (except for cimetidine), it is recommended to carefully monitor the patient and adjust the dose of the drug Janumet and/or the above cationic medications excreted by proximal renal tubules divisions, in cases of their simultaneous reception.
Some drugs have hyperglycemic potential and can intervene in established control of glycemia. These include thiazide and other diuretics, corticosteroids, phenothiazines, thyroid medications, estrogens, oral contraceptives, phenytoin , nicotinic acid , sympathomimetics, blockers "slow" calcium channels and isoniazid . In the appointment of the listed drugs are the patient receiving the drug Janumet, it is recommended that careful observation of the parameters of glycemic control. While receiving healthy volunteers Metformin or propranolol and Metformin and ibuprofen were not observed changes of pharmacokinetic parameters of these drugs.
Only a small proportion of Metformin is associated with plasma proteins, therefore drug-drug interaction of Metformin with drugs, actively binds to plasma proteins (salicylates, sulfonamides, chloramphenicol and probenecid), it is unlikely, in contrast to sulfonylureas derivatives that are actively bound to plasma proteins.
Overdose
Sitagliptin: in healthy volunteers single doses up to 800 mg, as a rule, well tolerated. When used in clinical study dose of 800 mg showed insignificant prolongation of the interval Q–Tc, which were not considered as clinically significant. There is no experience with the drug in doses exceeding 800 mg per the studies have not reported adverse reactions associated with the dose, the application of 600 mg/day for 10 days and 400 mg for 28 days. Sitagliptin poorly cialisinuaecy: according to clinical studies, over a 3-4 hour hemodialysis session was displayed only 13.5% of the dose. In the case of clinical need prescribe prolonged hemodialysis. Data about the effectiveness of peritoneal dialysis sitagliptin no. Metformin: there are cases of Metformin overdose, including ingestion in amounts greater than 50 g. Hypoglycemia was detected in approximately 10% of all cases of overdose, however, a causal relationship with overdose of Metformin have not been established. On the development of lactic acidosis has been reported in approximately 32% of all cases of overdosage of Metformin. Need emergency hemodialysis (Metformin cialisinuaecy speeds of up to 170 ml/min under good hemodynamic conditions) to accelerate the excretion of excess of Metformin if you suspect an overdose of it. In case of drug overdose Janumet should start standard support activities including: removal from the blood residue of the drug, which has not yet been absorbirovanija, monitoring of vital signs, including ECG, hemodialysis, and the appointment of maintenance therapy if necessary.
Storage conditions
Keep at temperature not exceeding 25 °C.
Shelf life
2 years.