Vipdomet - Instructions For Use, Analogues, Reviews, 12.5 + 1000 Mg

2024 Author: Rachel Wainwright | [email protected]. Last modified: 2023-12-15 07:39

Vipdomet

Vipdomet: instructions for use and reviews

1. 1. Release form and composition
2. 2. Pharmacological properties
3. 3. Indications for use
4. 4. Contraindications
5. 5. Method of application and dosage
6. 6. Side effects
7. 7. Overdose
8. 8. Special instructions
9. 9. Application during pregnancy and lactation
10. 10. Use in childhood
11. 11. In case of impaired renal function
12. 12. For violations of liver function
13. 13. Use in the elderly
14. 14. Drug interactions
15. 15. Analogs
16. 16. Terms and conditions of storage
17. 17. Terms of dispensing from pharmacies
18. 18. Reviews
19. 19. Price in pharmacies

Latin name: Vipdomet

ATX code: A10BD13

Active ingredient: metformin (Metformin), alogliptin (Alogliptin)

Producer: Takeda, GmbH (Germany)

Description and photo update: 2018-27-11

Prices in pharmacies: from 1389 rubles.

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Vipdomet is a combined oral hypoglycemic agent.

Release form and composition

Dosage form - film-coated tablets: oblong, biconvex, light yellow, engraved on one side "12.5 / 500" (dosage 12.5 mg + 500 mg) or "12.5 / 1000" (dosage 12, 5 mg + 1000 mg), on the other - "322M" (7 pcs. In blisters, in a cardboard box 2, 4 or 8 blisters and instructions for using Vipdomet).

Composition of 1 tablet:

• active substances: metformin hydrochloride - 500 or 1000 mg; alogliptin (as alogliptin benzoate) - 12.5 mg;
• auxiliary components: microcrystalline cellulose, crospovidone, magnesium stearate, povidone K30, mannitol;
• composition of the film shell: hypromellose 2910, titanium dioxide, talc, iron dye yellow oxide.

Pharmacological properties

Pharmacodynamics

Vipdomet contains two hypoglycemic substances as active substances that have different mechanisms of action and mutually complement each other's effects: metformin is a representative of the biguanide class, alogliptin is an inhibitor of the enzyme dipeptidyl peptidase-4 (DPP-4).

Metformin

Metformin is a hypoglycemic biguanide that reduces both basal and postprandial (postprandial) plasma glucose levels. It does not stimulate insulin secretion and therefore does not cause hypoglycemia.

Metformin increases the sensitivity of peripheral receptors to insulin, enhances the utilization of glucose by cells. By inhibiting gluconeogenesis and glycogenolysis, it reduces the production of glucose by the liver. It also delays the absorption of glucose in the intestine.

Acting on glycogen synthase, metformin activates the synthesis of intracellular glycogen. Increases the transport capacity of specific types of membrane glucose transporters (GLUT-1 and GLUT-4). Has a beneficial effect on lipid metabolism: it reduces the level of total cholesterol, triglycerides and low density lipoproteins.

Alogliptin

Alogliptin is a potent highly selective DPP-4 inhibitor. The selectivity of the substance against DPP-4 is more than 10,000 times higher than against other related enzymes, including DPP-8 and DPP-9. Dipeptidyl peptidase-4 is the main enzyme involved in the rapid destruction of hormones of the incretin family, such as glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1), which are secreted in the intestine, and their concentration increases with food intake. They increase the synthesis of insulin and its secretion by the beta cells of the pancreas. GLP-1 also suppresses glucagon secretion and decreases hepatic glucose production. Thus, at an increased concentration of glucose in the blood, alogliptin, by increasing the concentration of incretins, increases the glucose-dependent secretion of insulin and decreases the secretion of glucagon. In patients with type 2 diabetes mellitus, accompanied by hyperglycemia, as a result of these changes, the concentration of glycosylated hemoglobin (HbA1c) decreases and the plasma glucose concentration decreases both on an empty stomach and after a meal.

Pharmacokinetics

Metformin

After oral administration, the maximum concentration (Cmax) is noted after 2.5 hours.

The absolute bioavailability in healthy volunteers is 50-60%.

Absorption of metformin hydrochloride is saturable and incomplete. The pharmacokinetics of absorption are not considered to be linear. The unabsorbed fraction of the substance in the amount of 20–30% is excreted through the intestines.

The connection of metformin with plasma proteins is negligible. The drug is distributed in erythrocytes. The volume of distribution (Vd) can range from 63 to 276 liters.

Metformin is not metabolized. It is excreted by the kidneys unchanged.

Renal clearance of metformin more than 400 ml / min. This indicates the elimination of the drug by glomerular filtration and tubular secretion.

The half-life (T _1/2) is approximately 6.5 hours.

In case of impaired renal function, the clearance of metformin decreases in proportion to creatinine clearance (CC) and T _1/2 increases, as a result of which an increase in the concentration of the drug in plasma is possible.

Alogliptin

The parameters of the pharmacokinetics of the drug in healthy volunteers and patients with type 2 diabetes mellitus are similar.

After its single oral administration in a dose of up to 800 mg, rapid absorption is noted. The time to reach Cmax is 1–2 hours.

Absolute bioavailability is about 100%.

Signs of clinically significant cumulation of alogliptin after repeated administration were not observed in either healthy volunteers or patients with type 2 diabetes mellitus.

The area under the concentration-time curve (AUC) of a drug substance at a single dose in the dose range from 6.25 to 100 mg increases proportionally. The coefficient of individual differences in AUC among patients is approximately 17%.

The AUC _{(0-inf) of} alogliptin after a single dose is similar to the AUC _(0-24) after taking the same dose once a day for 6 days, which shows that there is no time dependence in the kinetics of alogliptin due to repeated administration.

After a single intravenous administration of the drug at a dose of 12.5 mg to healthy volunteers, Vd in the terminal phase was 417 L. This indicates a good tissue distribution of alogliptin.

The drug binds to plasma proteins by about 20-30%.

Alogliptin is metabolized slightly, 60–70% of the dose is excreted by the kidneys unchanged.

With oral administration of ¹⁴ C-labeled alogliptin, two major metabolites have been identified: N-demethylated alogliptin (MI, <1% starting material) and N-acetylated alogliptin (M-II, <6% starting material). The active metabolite is MI, a highly selective DPP-4 inhibitor, similar in effect to alogliptin. M-II has no inhibitory activity against DPP-4 and other DPP-enzymes.

According to data obtained in vitro, the isoenzymes CYP2D6 and CYP3A4 take a limited role in the metabolism of alogliptin. Also, studies have found that alogliptin at concentrations achieved with a dose of 25 mg does not inhibit CYP2C9, CYP2C8, CYP2CIQ, CYP2B6, CYP2D6, CYP1A2 and CYP3M, does not induce CYP2B6, CYP1A2 and CYP2C9.

In vitro, alogliptin induces CYP3A4 to a small extent, but in vivo such a response has not been detected.

In vitro studies have shown that the drug does not inhibit type 2 human organic cation renal transporters (OCT2), human renal human organic anion transporters of the first (OAT1) and third (OAT3) types.

When the drug is taken in therapeutic doses, the (S) -enantiomer is not detected. More than 99% of alogliptin is present in the body as the (R) -enantiomer.

With oral administration of ¹⁴ C-labeled alogliptin, 76% of the total radioactivity was excreted by the kidneys, 13% through the intestines.

The average renal clearance (170 ml / min) is greater than the average glomerular filtration rate (about 120 ml / min). This suggests that alogliptin is partially cleared by elimination.

Terminal T _1/2 is 21 hours on average.

Race, gender, advanced age (65–81 years) and body weight of patients do not have a clinically significant effect on the pharmacokinetics of alogliptin. Pharmacokinetic parameters have not been studied in children under 18 years of age.

In patients with mild renal impairment (CC 50-80 ml / min), the AUC of alogliptin increases by about 1.7 times, but this deviation is within the permissible range, so there is no need to adjust the dose of the drug.

With renal failure of moderate severity (CC 30-50 ml / min) AUC increases approximately 2 times. In patients with severe renal failure (CC <30 ml / min) and patients with end-stage chronic renal failure, there is an increase in AUC by about 4 times. In end-stage renal disease, patients underwent hemodialysis immediately after taking alogliptin. Within a three-hour session, about 7% of the dose was removed from the body.

Indications for use

Vipdomet is prescribed in addition to diet therapy and physical activity in

patients over 18 years of age with type 2 diabetes mellitus (to improve glycemic control).

As monotherapy, the drug is recommended in the following cases:

• monotherapy with metformin does not allow achieving adequate glycemic control;
• the patient is already receiving combined treatment with metformin and alogliptin separately (to replace two drugs with one).

In combination therapy, Vipdomet is used in combination with the following agents:

• pioglitazone - in cases where glycemia cannot be adequately controlled with a combination of metformin + pioglitazone;
• insulin - in cases where glycemia cannot be adequately controlled by a combination of insulin + metformin.

Contraindications

Absolute:

• type 1 diabetes mellitus;
• diabetic ketoacidosis, diabetic precoma, coma;
• current or history of lactic acidosis;
• renal failure with CC <60 ml / min;
• acute conditions that threaten the development of impaired renal function, such as fever, severe infectious diseases, dehydration (diarrhea, repeated vomiting), hypoxia (bronchopulmonary diseases, kidney infections, sepsis, shock);
• impaired liver function, liver failure;
• chronic alcoholism or acute alcohol intoxication;
• clinically significant manifestations of acute and chronic conditions / diseases that can lead to tissue hypoxia (for example, respiratory failure, acute / chronic heart failure with unstable hemodynamic parameters, acute myocardial infarction);
• massive trauma or extensive surgery, if insulin therapy is necessary;
• adherence to a low-calorie diet (less than 1000 kcal / day);
• the period of X-ray or radioisotope studies with intravascular administration of an iodine-containing contrast agent (48 hours before and 48 hours after);
• simultaneous use of sulfonylurea derivatives;
• age under 18;
• pregnancy and the period of breastfeeding;
• a history of serious hypersensitivity reactions to any DPP-4 inhibitor;
• hypersensitivity to metformin, alogliptin or any excipient of Vipdomet.

Relative:

• history of pancreatitis;
• the need to perform heavy physical work in patients over the age of 60;
• simultaneous use of pioglitazone.

Vipdomet, instructions for use: method and dosage

Vipdomet is taken orally 1 tablet 2 times a day with meals, swallowing whole and washed down with water.

If the next appointment is missed, the patient should take the missed pill as soon as possible, unless this means taking a double dose. Otherwise, you do not need to take the missed pill.

The optimal dose is selected individually.

Patients who have not achieved adequate glycemic control with metformin monotherapy are prescribed at the beginning of treatment 2 times a day, 1 tablet Vipdomet 12.5 + 1000 mg or 12.5 + 500 mg, which depends on the dose of metformin already taken.

When Vipdomet replaces the combination of metformin + alogliptin in the form of separate drugs, the daily doses of alogliptin and metformin taken earlier should be retained in the drug. Since Vipdomet is taken 1 tablet 2 times a day, a single dose of metformin is left unchanged (500 or 1000 mg), and a single dose of alogliptin in the composition of the drug is reduced by 2 times (12.5 mg).

When Vipdomet is prescribed to patients who received a combination of metformin + pioglitazone, metformin is canceled, and the dose of pioglitazone is retained. In this case, 2 times a day, 1 tablet of Vipdomet 12.5 + 1000 mg or 12.5 + 500 mg is prescribed, which depends on the dose of metformin prescribed before. Patients receiving such a combination should be closely monitored, as there is a risk of hypoglycemia.

For patients who failed to achieve adequate glycemic control with combination therapy with metformin at the maximum tolerated dose and insulin, the dosage of Vipdomet is determined as follows: the dose of metformin should be maintained, the dose of alogliptin should be 12.5 mg 2 times a day. The insulin dose may be reduced to prevent hypoglycemia.

Side effects

The frequency of side effects is divided into groups as follows: very often -> 1/10, often - from> 1/100 to <1/10, very rarely - <1/10 000, the frequency has not been established - adverse reactions recorded in the post-marketing period …

Possible violations from various organs and body systems:

• gastrointestinal tract: very often (due to the action of metformin) - loss of appetite, diarrhea, abdominal pain, nausea, vomiting (usually occur at the beginning of treatment, in most cases go away on their own); often - gastritis, gastroenteritis, gastroesophageal reflux disease; frequency not established (under the influence of alogliptin) - acute pancreatitis;
• hepatobiliary system: very rarely (under the influence of metformin) - impaired liver function indicators, hepatitis; the frequency has not been established (under the influence of alogliptin) - impaired liver function, including liver failure;
• immune system: the frequency has not been established (under the influence of alogliptin) - signs of hypersensitivity, including anaphylactic reactions;
• nervous system: often - headache, metallic taste in the mouth;
• metabolism: very rarely (due to metformin) - vitamin B ₁₂ deficiency, lactic acidosis;
• infections: often - nasopharyngitis, upper respiratory tract infections;
• skin and subcutaneous tissues: very often (due to metformin) - urticaria, erythema; often - itching, rash; the frequency has not been established (under the influence of alogliptin) - angioedema, polymorphic erythema, exfoliative diseases, including Stevens-Johnson syndrome.

Overdose

There is no information on cases of overdose of Vipdomet.

In clinical studies, a daily dose of 400 mg alogliptin was used in patients with type 2 diabetes mellitus for 14 days, and 800 mg in healthy volunteers. These doses are 16 and 32 times, respectively, higher than the recommended dose of alogliptin - 25 mg / day. The development of any serious reactions was not noted. During hemodialysis (within a 3-hour session), 7% of the drug dose is removed. There are no data on the effectiveness of peritoneal dialysis.

With a significant overdose of metformin, lactic acidosis may develop. In this case, the reception of Vipdomet is canceled, the patient is urgently hospitalized. Lactate and metformin are well removed from the body by hemodialysis.

When taking Vipdomet in a dose that is significantly higher than the recommended one, you should wash the stomach and call a doctor. Further treatment is symptomatic.

special instructions

A rare but serious complication of metformin cumulation (fatal in the absence of emergency care) is lactic acidosis. Cases of the development of this condition are mainly observed in patients with diabetes mellitus and severe renal failure. However, other factors such as liver failure, decompensated diabetes mellitus, ketosis, alcoholism, prolonged fasting, or any condition associated with severe hypoxia can also be affected. By considering these risks, the incidence of lactic acidosis can be reduced.

The development of lactic acidosis should be assumed when a nonspecific symptom such as muscle cramps appears, accompanied by severe asthenia and / or abdominal pain and / or dyspeptic disorders. Lactic acidosis is characterized by acidotic shortness of breath and hypothermia, which subsequently leads to coma. When conducting diagnostic laboratory tests, it is revealed: an increase in the concentration of lactate in the blood plasma above 5 mmol / l, a decrease in blood pH below 7.25, an increase in the anion gap and the ratio of lactate / pyruvate.

If you suspect lactic acidosis, you should stop taking Vipdomet and immediately consult a doctor.

The risk of lactic acidosis increases with the degree of impaired renal function. For this reason, before taking a hypoglycemic agent and regularly during the period of therapy, it is required to determine creatinine clearance: in patients with normal renal function - at least once a year, in patients with CC at the lower limit of the norm and in the elderly - 2-4 times a year …

Given the possible impairment of renal function, care must be taken in elderly patients with the simultaneous use of diuretics, non-steroidal anti-inflammatory or antihypertensive drugs.

When prescribing a planned operation, Vipdomet must be canceled 48 hours before it is carried out. It is allowed to resume taking at least 48 hours after surgery, provided that the kidney function is normal.

There are isolated cases of acute pancreatitis in the setting of hypoglycemic therapy. The doctor should warn patients about the characteristic symptom of this disease - severe persistent abdominal pain, sometimes radiating to the back. If you suspect the development of acute pancreatitis, Vipdomet is canceled, if the diagnosis is confirmed, the reception is not resumed. There is no evidence of an increased risk for patients with a history of pancreatitis, but care must be taken.

In the course of post-marketing studies, reports of liver dysfunction (up to liver failure) were received when taking alogliptin. The causal relationship with the drug has not been reliably established, however, during the period of treatment, patients should be periodically examined for possible deviations in liver function tests. If abnormalities are found, and another reason for their occurrence has not been established, the doctor should consider stopping the use of Vipdomet.

It is not recommended to concomitantly prescribe sulfonylurea derivatives if Vipdomet is required as part of a combination therapy, since the safety and efficacy of such a combination has not been studied. With the additional appointment of pioglitazone or insulin, it is recommended to reduce their doses, this will reduce the risk of hypoglycemia.

If in patients in whom the disease was previously adequately controlled by Vipdomet, clinical symptoms of type 2 diabetes mellitus or laboratory abnormalities appear, first of all, ketoacidosis or lactic acidosis should be excluded. For this, tests are carried out for plasma concentrations of glucose and metformin, lactate and pyruvate, for blood pH, electrolytes and ketones. With the development of acidosis of any etiology, the drug is canceled and appropriate corrective measures are taken.

Influence on the ability to drive vehicles and complex mechanisms

Vipdomet does not affect or slightly affects the psychomotor functions of a person. However, given the risk of hypoglycemia, while the use of other hypoglycemic agents (insulin or pioglitazone), care should be taken when performing potentially hazardous work.

Application during pregnancy and lactation

Animal studies of alogliptin have not shown direct or indirect adverse effects on the reproductive system. Similarly, studies of metformin did not reveal a negative effect. The study of combination therapy with alogliptin and metformin in pregnant rats using doses approximately 5–20 times higher than those recommended for humans revealed toxic effects on the reproductive system. Vipdomet is contraindicated in pregnancy.

Whether alogliptin penetrates into breast milk is unknown. Metformin in some quantities passes into the mother's milk, therefore, the risk of side effects in infants cannot be excluded. In this regard, Vipdomet is contraindicated during lactation.

Pediatric use

Pharmacokinetic parameters of the drug in patients under 18 years of age have not been studied, therefore Vipdomet is not used in pediatrics.

With impaired renal function

In patients with mild renal impairment (CC> 60 ml / min), dosage adjustment is not required. However, kidney function should be monitored during treatment.

In case of moderate and severe renal failure, as well as in patients with end-stage renal failure, the use of Vipdom is contraindicated.

For violations of liver function

Vipdomet is contraindicated in liver failure.

Use in the elderly

Elderly patients (≥ 65 years) do not need dose adjustment, but treatment should be carried out with caution because of the possible age-related decline in renal function.

Drug interactions

Studies of the pharmacokinetic interaction of Vipdomet with other drugs have not been conducted, therefore, the data on the interaction of each of the active substances of the drug separately are given below.

Alogliptin

Clinically significant pharmacokinetic interactions have not been established when using alogliptin in combination with the following hypoglycemic agents: metformin, pioglitazone (thiazolidinedione), glibenclamide (a sulfonylurea derivative), α-glycosidase inhibitors.

In vitro studies have shown that alogliptin at the recommended dose (25 mg / day) does not induce or inhibit CYP 450 isoforms, so interaction with substrates of this isoform is not expected.

In vitro studies have shown that alogliptin is neither an inhibitor nor a substrate for OCT2, OATZ and OAT1. Also, interaction with inhibitors and substrates of p-glycoprotein has not been established.

In clinical trials, alogliptin did not significantly affect the pharmacokinetics of the following drugs: metformin, digoxin, cimetidine, fexofenadine, midazolam, atorvastatin, glibenclamide, (R) - and (S) -warfarin, tolbutamide, pioglitazone contraceptives, caffeine, dextrastore norethindrone and ethinyl estradiol).

Given the interactions described above, it is assumed that alogliptin does not inhibit the isoenzymes of the cytochrome system CYP2D6, CYP3A4, CYP2C9 and CYPIA2, p-glycoprotein and OCT2.

The following drugs did not have a significant effect on the pharmacokinetic parameters of alogliptin in studies: cyclosporin (an inhibitor of p-glycoprotein), fluconazole (an inhibitor of CYP2C9), gemfibrozil (an inhibitor of CYP2C8 / 9), voglibose (an inhibitor of α-glycosidase), ketoconazole, digoxin, atorvastatin, cimetidine, metformin.

When taken simultaneously with warfarin in healthy volunteers, alogliptin had no effect on either the International Normalized Ratio (MHO) or the prothrombin index.

Alogliptin is only slightly metabolized by the cytochrome P450 (CYP) enzyme system, so interactions with CYP inhibitors are not expected.

Metformin

Metformin is contraindicated to use simultaneously with iodine-containing X-ray contrast agents, since the risk of lactic acidosis is high. Reception of Vipdomet should be discontinued at least 48 hours before the study. It is allowed to resume therapy no earlier than 48 hours after it, but on condition that during the examination, renal function was recognized as normal.

During the period of treatment with metformin, it is not recommended to consume alcohol (as well as to take ethanol-containing drugs), since with acute alcohol intoxication, lactic acidosis may develop, especially in patients with hepatic insufficiency and patients who follow a low-calorie diet or receive insufficient nutrition.

In functional renal failure, loop diuretics can lead to the development of lactic acidosis. If the CC is below 60 ml / min, Vipdomet is contraindicated.

Sulfonylurea derivatives, salicylates, acarbose and insulin, when used simultaneously with metformin, increase the risk of hypoglycemia.

More frequent monitoring of blood glucose concentration, especially at the beginning of treatment, is required with the simultaneous use of drugs with indirect hyperglycemic action, for example, danazol, diuretics, chlorpromazine (in daily doses ≥ 100 mg), β2-adrenergic agonists, tetracosactide, glucocorticosteroids (as systemic and local action). If necessary, taking into account the level of glucose in the blood, it is necessary to adjust the dose of Vipdomet.

Nifedipine, when combined with metformin, increases its absorption and maximum concentration.

Cationic drugs secreted in the renal tubules (quinine, quinidine, morphine, amiloride, vancomycin, triamterene, ranitidine, procainamide, trimethoprim, digoxin, cimetidine) compete with metformin for tubular transport systems, which can increase its maximum concentration. In this regard, when using such combinations, it is recommended to carefully monitor glycemia, if necessary, adjust the dose of Vipdomet and / or cationic drugs.

Angiotensin-converting enzyme (ACE) inhibitors can reduce the concentration of glucose in the blood, which requires a dose adjustment of Vipdomet.

Analogs

Vipdomet's analogues are Avandamet, Bagomet Plus, Velmetia, Galvus Met, Glibomet, Glybenfazh, Glykambi, Glukovans, Gluconorm, Metglib, Glimecomb, Sinjardi, Reduxin Met, Yanumet and others.

Terms and conditions of storage

Keep out of the reach of children at a temperature not exceeding 25 ° C.

The shelf life is 3 years.

Terms of dispensing from pharmacies

Dispensed by prescription.

Reviews about Vipomet

On the forums and medical sites there are no reviews about Vipomet, which would allow us to evaluate its effectiveness and degree of safety.

Price for Vipdomet in pharmacies

The price of Vipdomet for a pack of 56 tablets 12.5 mg + 500 mg or 12.5 mg + 1000 mg is approximately 1157-1760 rubles.

Vipdomet: prices in online pharmacies

Drug name Price Pharmacy

Vipdomet 12.5 mg + 1000 mg film-coated tablets 56 pcs. 1389 RUB Buy

Vipdomet 12.5 mg + 500 mg film-coated tablets 56 pcs. 1459 RUB Buy

Vipdomet tablets p.o. 12.5mg + 1000mg 56 pcs. RUB 1503 Buy

Vipdomet tablets p.o. 12.5mg + 500mg 56 pcs. 1523 RUB Buy

Anna Kozlova Medical journalist About the author

Education: Rostov State Medical University, specialty "General Medicine".

Information about the drug is generalized, provided for informational purposes only and does not replace the official instructions. Self-medication is hazardous to health!