Avandia - instructions for use, dose, side effects, contraindications

Active substanceRosiglitazoneRosiglitazone

Similar drugsTo uncover

pills inwards

Dosage form: & nbspfilm-coated tablets

Composition:

Ingredient		Amount (mg per tablet)
Dosage		4 mg	8 MG
Formula Code		VN	ATJ
Intragranular Ingredients
Rosiglitazone maleate in terms of rosiglitazone		5,30 4,00	10,60 8,00
Carboxymethyl starch sodium		2,00	4,00
Hypromellose-3sR		2,00	4,00
Cellulose microcrystalline		8,00	16,00
Lactose Monohydrate		22,70	45,40
Extragranular Ingredients
Sodium carboxymethyl starch		5,46	10,92
Cellulose microcrystalline		21,85	43,70
Lactose Monohydrate		81,94	163,88
Magnesium stearate		0,75	1.50
Film coating		4,50	9,00
Film coating composition
Ingredient	Content (% w / w)
Dosage	4 mg		8 mg
Gipromellose-6sR	40,00		40,00
Titanium dioxide	16,00		22,50
Macrogol-3000	16,00		46,00
Talc	8,00		-
Lactose	13,00		13,00
Triacetin	6,00		6,00
Iron [II] oxide red	0,40		2,50
Iron [III] oxide yellow	0,60		--

Description:

Tablets 4 mg: orange pentagonal tablets covered with a film sheath, on one side of the "GSK" and "4" on the other.

Tablets 8 mg: red-brown pentagonal pills covered with a film sheath, on one side of the "GSK" and "8" on the other.

Pharmacotherapeutic group:hypoglycemic agent for oral administration.

ATX: & nbsp

A.10.B.G Thiazolidinediones

A.10.B.G.02 Rosiglitazone

Pharmacodynamics:

Rosiglitazone is a selective agonist of the nuclear receptors of PPAR (rex-oisomal proliferator-activated receptor gamma) and a representative of the thiazolidinedione class of hypoglycemic agents. Rosiglitazone, increasing the sensitivity to insulin of adipose tissue, skeletal muscles and liver, improves the course of metabolic processes, reduces the concentration of glucose, insulin and free fatty acids in the blood. In animal models, it has been shown that the drug preserves the function of beta cells, as evidenced by an increase in the mass of pancreatic islets and insulin, and prevents the development of severe hyperglycemia. It is also established that rosiglitazone significantly slows the development of renal dysfunction and systolic arterial hypertension, does not stimulate the secretion of insulin by the pancreas and does not cause hypoglycemia in rats and mice.

In accordance with the mechanism of rosiglitazone, the improvement in glycemic control is accompanied by a clinically significant decrease in serum insulin and its precursors, which are believed to be risk factors for cardiovascular disease.A significant reduction in free fatty acids in the blood is a key feature of rosiglitazone therapy.

Thanks different, but complementary mechanisms of action, combined therapy with rosiglitazone with metformin or derivatives sulfonylureas leads to a synergistic improvement in glycemic control in patients with type 2 diabetes mellitus.

Pharmacokinetics:

Suction: maximum concentration (С_m_Oh) rosiglitazona in the blood serum is achieved within 1 hour, after reception inside. In the range of therapeutic doses, plasma concentrations are directly proportional to the dose. The absolute bioavailability of rosiglitazone after ingestion in doses of 4 mg or 8 mg is about 99%. Admission with food causes a slight decrease in the maximum concentration (approximately 20-28%) and a delay in reaching the maximum concentration (1.75 hours) compared with fasting. These small changes are not clinically significant, and therefore there is no need for any concordance with rosiglitazone over time. The absorption of rosiglitazone is not impaired with an increase in the pH of the gastricsecret.

Distribution: in healthy volunteers, the volume of rosiglitazone is approximately 14 liters. The association of rosiglitazone with plasma proteins is high (approximately 99.8%) and does not depend on the concentration of the drug or the age of the patient. Cumulation rosiglitazona after using the drug 1 or 2 times a day is not noted.

Metabolism: rosiglitazone is subjected to intensive metabolism in the body. The main ways of metabolism are N-demethylation and hydroxylation, followed by binding to sulfate and glucuronic acid. Metabolites rosiglitazona not have clinically significant activity.

Research in vitro show that rosiglitazone basically metabolized with the participation of the isoenzyme СUR2С8 and, to a small extent, with the participation of СУР2С9.

Since rosiglitazone does not significantly inhibit in vitro isoenzymes СUR1А2, 2А6, 2С19, 2D6, 2E1, 3A or 4A, the probability of interaction with drugs metabolized by the indicated P450 isoenzymes is small. In vitro rosiglitazone inhibits СУР2С8 (IC₅₀18 μmol) is moderately, and СУР2С9 (IC₅₀ 50 μmol) is weak. In the study in vivo with warfarin it was shown that rosiglitazone does not interact with substrates СУР2С9.

Excretion: the total plasma clearance of rosiglitazone is about 3 liters / hour, and the half-life is approximately 3-4 hours. The main way of excretion is excretion by the kidneys (approximately 2/3 of the dose). Intestinal excretion is approximately 25% of the dose. In the unchanged form of the drug is not withdrawn. The final half-life is about 130 hours, which indicates a very slow excretion of metabolites. Possible cumulation of metabolites in blood serum is expected with repeated administration of the drug; the main metabolite (parahydroxisulphate) is accumulated to a greater degree, for which a 5-fold increase in the concentration can be expected.

Special patient groups: when фarmakokinetic analysis of the general population, there were no differences in the pharmacokinetics of rosiglitazone between men and women.

Older patients: in the pharmacokinetic analysis of the general population, there were no differences in the pharmacokinetics of rosiglitazone in adult patients and in elderly patients.

Liver failure: in patients with moderate or severe (Child Pugh B/C) degree of liver disease Cmah and AUC were 2 and 3 times higher, respectively, than in patients with impaired liver function due to reduced binding to plasma proteins and reduced clearance of rosiglitazone.

Renal insufficiency: there are no clinically significant differences in the pharmacokinetics of rosiglitazone in patients with impaired renal function or with terminal stage of renal failure on hemodialysis.

Indications:Type 2 diabetes mellitus as a monotherapy in the ineffectiveness of exercise and diet, or in combination with sulfonylureas or metformin derivatives, and as part of triple combination therapy with sulfonylurea derivatives and metformin to improve glycemic control.

Contraindications:

- Hypersensitivity to rosiglitazone or other components of the drug.

- Type 1 diabetes mellitus (in the absence of insulin rosiglitazone ineffective).

- Diabetic ketoacidosis or diabetic precoma.

- Violation of the function of the liver.

- Pregnancy and the period of breastfeeding.

- Age to 18 years (efficacy and safety of the drug are not defined).

- Heart failure, including in anamnesis, functional class I-IV according to the classification of NYHA.

- Acute coronary syndrome (unstable angina, myocardial infarction with elevation and without ST segment elevation).

- Joint application with insulin.

- Hereditary intolerance of galactose, lactase deficiency Lappa, glucose-galactose malabsorption.

Carefully:Severe renal insufficiency, diabetic retinopathy, anemia, osteoporosis, ischemic heart disease (IHD), simultaneous administration of inhibitors (including gemfibrozil) or inducers (incl. rifampicin) isoenzyme CUR2C8.

Pregnancy and lactation:Data on the use of rosiglitazone during pregnancy and during breastfeeding is not enough. Patients with type 2 diabetes mellitus are recommended to use insulin during pregnancy. Thus, the use of rosiglitazone during pregnancy is not shown. If rosiglitazone is needed during breastfeeding, breast-feeding should be discontinued.

Dosing and Administration:

Inside, regardless of food intake. Dose and treatment regimen must be selected individually for each patient. The initial dose is 4 mg / day. After 6-8 weeks, this dose can be increased to 8 mg / day, if there is a need for more careful glycemic control. In patients receiving combined therapy with rosiglitazone and derivatives of sulfonylureas, an increase in the dose of rosiglitazone to 8 mg per day should be carried out with caution, taking into account the clinical state and the risk of adverse reactions associated with fluid retention.

Rosiglitazone can be prescribed 1 or 2 times a day.

Elderly patients

No dosage adjustment is required.

Patients with hepatic impairment

Rosiglitazone is contraindicated for the treatment of patients with impaired liver function.

Patients with impaired renal function

Patients with mild and moderate renal dysfunction do not need to reduce the dose of rosiglitazone. Data obtained by applying rosiglitazona in patients with severe renal dysfunction is limited, therefore, care must be taken in this category of patients.

Side effects:

The undesirable phenomena presented below are listed depending on the anatomical and physiological classification and. frequency of occurrence. Frequency of occurrence is defined as follows: Often (>1/10), often (>1/100 and <1/10), infrequently (>1/1 000 and <1/100), rarely (>1/10 000 and <1/1 000), rarely (<1/10 000, including individual cases). Frequency categories were formed on the basis of clinical studies of the drug and post-registration observations.

In controlled studies, an increase in the concentration ALT is three times higher than the upper limit Norms with the same frequency as the placebo. AT routine practice reported similar undesirable phenomena with Same frequency (rarely).

There are rare spontaneous reports of development of chronic cardiac insufficiency and pulmonary edema. Highly rarely reported development of angioedema and urticaria, rapid and excessive increase in weight body.

Data obtained in clinical research.

From the hematopoiesis and

lymphatic system

Rosiglitazone (compared

Often

with placebo)

Rosiglitazone + metformin

Often

(compared with

metformin)

Rosiglitazone + derivatives

Often

sulfonylureas (by

compared with derivatives

sulfonylureas)

Rosiglitazone + derivatives

Often

sulfonylureas +

metformin (in comparison with

derivatives

sulfonylurea + metto

rmin)

Rosiglitazone + insulin (compared with insulin)

Often

Rosiglitazone + sulfonylurea derivatives +metformin (in comparison with derivatives of sulfonylureas + metformin)

Often

Rosiglitazone + insulin (compared with insulin)

Often

Leukopenia

Rosiglitazone + derivatives of sulfonylureas (in comparison with derivatives of sulfonylurea)

Often

Thrombocytopenia

Rosiglitazone + derivatives of sulfonylureas (in comparison with derivatives of sulfonylurea)

Often

Granulocytopenia

Rosiglitazone + sulfonylurea derivatives + metformin (in comparison with derivatives of sulfonylurea + metformin)

Often

* - often dose-dependent, from mild to moderate severity.

From the side of metabolism

Hypercholesterolemia *

Rosiglitazone (compared with placebo)

Often

Rosiglitazone + metformin (in comparison with metformin)

Rarely

Rosiglitazone + derivatives of sulfonylureas (in comparison with derivatives of sulfonylurea)

Often

Hypertriglyceridemia

Rosiglitazone (compared

Often

with placebo)

Rosiglitazone + derivatives

Often

sulfonylureas (by

compared with derivatives

sulfonylureas)

Hyperlipidemia

Rosiglitazone (compared

Often

with placebo)

Rosiglitazone + metformin

Often

(compared with

metformin)

Rosiglitazone + derivatives

Often

sulfonylureas (by

compared with derivatives

sulfonylureas)

Rosiglitazone + derivatives

Often

sulfonylureas +

metformin (in comparison with

derivatives

sulfonylureas +

metformin)

Weight gain **

Rosiglitazone (compared with placebo)

Often

Rosiglitazone + metformin

(compared with

metformin)

Often

Rosiglitazone + derivatives

sulfonylureas (by

compared with derivatives

sulfonylureas)

Often

Rosiglitazone + derivatives

sulfonylureas +

metformin (in comparison with

derivatives

sulfonylureas +

metformin)

Often

Rosiglitazone + insulin (by

compared with insulin)

Often

Increased appetite

Rosiglitazone (compared

Infrequently

with placebo)

Rosiglitazone + derivatives

Infrequently

sulfonylureas (by

compared with derivatives

sulfonylureas)

Rosiglitazone + insulin (by

Infrequently

compared with insulin)

Hypoglycemia ***

Rosiglitazone + metformin

Often

(compared with

metformin)

Rosiglitazone + derivatives

Often

sulfonylureas (by

compared with derivatives

sulfonylureas)

Rosiglitazone + sulfonylurea derivatives +metformin (in comparison with derivatives of sulfonylurea + metformin)

Often

Rosiglitazone + insulin (compared with insulin)

Often

* - total cholesterol increased along with an increase in the concentration of high-density lipoprotein (HDL) and low-density lipoprotein (LDL), the cholesterol / HDL ratio remained unchanged or improved in long-term studies.

** - weight gain, mainly dose-dependent.

Perhaps due to fluid retention and the accumulation of fatty deposits.

*** - hypoglycemia, mainly dose-dependent, moderate or weak

From the nervous system

Dizziness

Rosiglitazone + metformin (compared with

metformin)

Often

Rosiglitazone + derivatives of sulfonylureas (by

Often

compared with derivatives

sulfonylureas)

Headache

Rosiglitazone + derivatives

Often

sulfonylureas +

metformin (in comparison with

derivatives

sulfonylureas +

metformin)

From the side of cardiovascular

systems

Heart failure

edema

lungs *

Rosiglitazone + derivatives

Often

sulfonylureas (by

compared with metformin +

derivatives

sulfonylureas)

Rosiglitazone + derivatives

Often

sulfonylureas +

metformin (in comparison with

derivatives

sulfonylureas +

metformin)

Rosiglitazone + metformin

Often

(compared with

metformin +

derivatives

sulfonylureas)

Rosiglitazone monotherapy

Infrequently

(compared with

Derivatives of sulfonylureas or metformin)

Rosiglitazone + insulin (compared with insulin)

Often

Myocardial ischemia **

Rosiglitazone (compared with placebo)

Often

Rosiglitazone + metformin (in comparison with metformin)

Often

Rosiglitazone + derivatives of sulfonylureas (in comparison with derivatives of sulfonylurea)

Often

Rosiglitazone + sulfonylurea derivatives + metformin (in comparison with derivatives of sulfonylurea + metformin)

Often

Rosiglitazone + insulin (compared with insulin)

Often

* - Heart failure / pulmonary edema. An increase in the incidence of heart failure was observed with the addition of rosiglitazone to regimens based on the use of insulin or sulfonylurea derivatives. The number of observations does not allow to make an unambiguous conclusion about the connection with the dose of the drug, however, the frequency of cases is higher for a daily dose of rosiglitazone 8 mg compared with a daily dose of 4 mg.

** - data on the possibility of rosiglitazone to increase the risk of myocardial ischemia are inadequate. Retrospective analysis of 42 short-term

clinical studies revealed an increased risk of developing ischemic events with rosiglitazone compared with control groups in general (placebo plus active drugs). In the same analysis, when comparing rosiglitazone with other oral

hypoglycemic drugs, there were no differences in the incidence of ischemic events. The increased risk of myocardial ischemia associated with rosiglitazone has not been confirmed in further long-term randomized controlled clinical trials comparing rosiglitazone with metformin and sulfonylurea derivatives. An increased risk of developing myocardial ischemic damage was observed in patients who received nitrate therapy initially or during a clinical trial for established coronary heart disease. Rosiglitazone is not recommended for patients receiving concomitant nitrate therapy.

From the gastrointestinal side tract

Constipation *

Rosiglitazone (compared

Rarely

with placebo)

Rosiglitazone + metformin

Often

(in comparison with metformin)

Rosiglitazone + derivatives

Rarely

sulfonylureas (by

compared with derivatives

sulfonylureas)

Rosiglitazone + derivatives

Often

sulfonylureas +

metformin (in comparison with

derivatives

sulfonylureas +

metformin) -

Rosiglitazone + insulin (by

Infrequently

compared with insulin)

* - constipation was usually light or

moderate.

From the side of musculoskeletal

systems

Fractures of bones *

Rosiglitazone (compared

Often

with metformin)

From the gastrointestinal side

tract

Constipation *

Rosiglitazone (compared

Rarely

with placebo)

Rosiglitazone + metformin

Often

(in comparison with metformin)

Rosiglitazone + derivatives

Rarely

sulfonylureas (by

compared with derivatives

sulfonylureas)

Rosiglitazone + derivatives

Often

sulfonylureas +

metformin (in comparison with

derivatives

sulfonylureas +

metformin) -

Rosiglitazone + insulin (by

Infrequently

compared with insulin)

* - constipation was usually light or

moderate.

From the side of musculoskeletal

systems

Fractures of bones *

Rosiglitazone (compared

Often

with metformin)

From the gastrointestinal side

tract

Constipation *

Rosiglitazone (compared

Rarely

with placebo)

Rosiglitazone + metformin

Often

(in comparison with metformin)

Rosiglitazone + derivatives

Rarely

sulfonylureas (by

compared with derivatives

sulfonylureas)

Rosiglitazone + derivatives

Often

sulfonylureas +

metformin (in comparison with

derivatives

sulfonylureas +

metformin) -

Rosiglitazone + insulin (by

Infrequently

compared with insulin)

* - constipation was usually light or

moderate.

From the side of musculoskeletal

systems

Fractures of bones *

Rosiglitazone (compared

Often

with metformin)

From the gastrointestinal side

tract

Constipation *

Rosiglitazone (compared

Rarely

with placebo)

Rosiglitazone + metformin

Often

(in comparison with metformin)

Rosiglitazone + derivatives

Rarely

sulfonylureas (by

compared with derivatives

sulfonylureas)

Rosiglitazone + derivatives

Often

sulfonylureas +

metformin (in comparison with

derivatives

sulfonylureas +

metformin) -

Rosiglitazone + insulin (by

Infrequently

compared with insulin)

* - constipation was usually light or

moderate.

From the side of musculoskeletal

systems

Fractures of bones *

Rosiglitazone (compared

Often

with metformin)

Rosiglitazone (compared with glibenclamide)

Often

Rosiglitazone + metformin (in comparison with sulfonylurea +metformin)

Often

Rosiglitazone + sulfonylurea derivatives (compared with metformin + derivatives of sulfonylurea)

Often

Myalgia

Rosiglitazone + sulfonylurea derivatives + metformin (in comparison with derivatives of sulfonylurea + metformin)

Often

* - most of the reports concerned fractures of the upper limbs and distal fractures of the lower extremities.

On the part of the body as a whole:

Peripheral edema *

Rosiglitazone (compared with placebo)

Often

Rosiglitazone + metformin (in comparison with metformin)

Often

Rosiglitazone + derivatives of sulfonylureas (in comparison with derivatives of sulfonylurea)

Often

Rosiglitazone +

derivatives

sulfonylureas +

metformin (in comparison with

derivatives

sulfonylureas +

metformin)

Highly

often

Rosiglitazone + insulin (by

compared with insulin)

Highly

often

* - Often dose-dependent, from mild to

moderate severity.

Data received at post-registration period

Frequency categories of unwanted phenomena are determined on the basis of frequency of adverse events application of rosiglitazone in post-registration period is independent dose or concomitant therapy hypoglycemic drugs.

Occurrence of rare and very rare adverse events were determined by based on post-registration data, and it concerns the frequency of the messages about such phenomena than the true frequency themselves phenomena.

From the immune system

Very Anaphylactic

rarely reaction

From the liver and biliary tract

Seldom were reports of impaired liver function,accompanied by an increase in the activity of "hepatic" enzymes, but the causal relationship between rosiglitazone treatment and the violation of liver function is not established. In patients with diabetes mellitus, there are often violations of the liver.

From the skin and subcutaneous fat

Very angioedema, urticaria, rash, itchy skin

rarely

From the side of the organ of vision:

Very rarely Macular edema

Overdose:Data on overdose of rosiglitazone in humans is very limited. Volunteers who were taken only once inside to 20 mg rosiglitazona, well tolerated this dose. In case of an overdose, it is recommended to start the corresponding symptomatic treatment. The degree of binding of rosiglitazone with plasma proteins is high, so the drug can not be removed from the bloodstream by hemodialysis.

Interaction:

Simultaneous reception of therapeutic doses of rosiglitazone and other oral hypoglycemic drugs, including metformin, glibenclamide and acarbose, does not have a clinically significant effect on the stable pharmacokinetics or pharmacodynamics of these drugs.

As a result of various but complementary mechanisms of action, combined therapy with rosiglitazone and derivatives of sulfonylureas or metformin leads to a synergistic effect on glycemic control in patients with type 2 diabetes mellitus.

Rosiglitazone does not affect the stable pharmacokinetics of digoxin or warfarin and does not affect the anticoagulant activity of warfarin. Rosiglitazone it is metabolized mainly by RMS 2C8 and to a small extent with the participation of RMS 2C9, but it does not have a clinically significant effect on the pharmacokinetics of S (-) - warfarin (substrate for RMS 2S9). Simultaneous reception of rosiglitazone with nifedipine or oral contraceptives (ethinyl estradiol and norethindrone) does not affect the pharmacokinetics of these drugs, which confirms the low probability of its interaction with drugs metabolized via RAS AP4.

Moderate use of alcohol along with rosiglitazone does not have any effect on glycemic control.

Gemfibrozil (inhibitor of the enzyme СUR2С8) at a dose of 600 mg twice a day doubled the concentration of rosiglitazone in the equilibrium state.

Such an increase in rosiglitazone levels is associated with a risk of dose-dependent side effects, therefore, combined with rosiglitazone with inhibitors of COR2C8 may require a reduced dose of rosiglitazone.

Other inhibitors of COR2C8 caused a slight increase in the systemic concentration of rosiglitazone.

Rifampicin (inducer of the enzyme СUR2С8) at a dose of 600 mg per day reduced the systemic concentration of rosiglitazone by 66%.

Therefore, patients who receive concomitantly rosiglitazone and inducers of the enzyme СUR2С8, it is necessary to carry out a thorough control of blood glucose and to change the dose of rosiglitazone, if necessary.

Repeated administration of rosiglitazone increases Cmax and AUC of methotrexate by 18% (90% CI: 11% -26%) and 15% (90% CI: 8% -23%), respectively, compared to the same dose of methotrexate in the absence of rosiglitazone.

Special instructions:

Patients, the in the pre-menopausal period with no ovulation

When using rosiglitazona in women who are in the pre-menopausal period,there is hormonal imbalance, but no significant adverse events associated with menstrual irregularities are observed. In the event of a menstrual cycle, it is necessary to assess the possible risk and the expected benefits of continuing treatment. Due to increased sensitivity to insulin, rosiglitazone therapy in patients with insulin resistance and anovulatory cycle in the premenopause (for example, in patients with polycystic ovary syndrome) may result to the resumption of ovulation and the risk of pregnancy.

Increase in total cholesterol concentration

The increase in the total cholesterol concentration is associated with an increase in both LDL and HDL, and the ratio of total cholesterol to HDL is not changed.

Anemia

Treatment with rosiglitazone was associated with a dose-dependent decrease in hemoglobin concentration. Patients with low hemoglobin content prior to initiation of therapy are at increased risk for developing anemia with rosiglitazone treatment.

Fluid retention and heart failure

Thiazolidinediones can cause fluid retention in the body,which can aggravate or promote the development of symptoms of heart failure. Rosiglitazone can cause a dose-dependent fluid retention in the body. It is necessary to take into account the possible value of fluid retention in weight gain. All patients, especially those receiving combination therapy with insulin or sulfonylureas, and with a risk of developing heart failure, should be observed for the development of adverse events associated with fluid retention, including weight gain and heart failure. Increased attention is required by patients receiving a combination of rosiglitazone with metformin and insulin. Rosiglitazone It is necessary to cancel if there are signs of heart failure. After starting therapy with rosiglitazone and during the titration of the dose, careful medical monitoring of the patient's condition with regard to the following symptoms and signs of heart failure is necessary: rapid and excessive weight gain, dyspnea and / or swelling. With the development of symptoms of heart failure, rosiglitazone should be discontinued and therapy prescribed in accordance with current standards for the treatment of heart failure.

The drug is contraindicated in patients with heart failure of I-IV functional class according to the NYHA classification (New York Heart Association), including in the history.

Patients with acute coronary syndrome (ACS) were not included in the clinical studies. The appointment of rosiglitazone, as well as other oral hypoglycemic drugs, is not recommended for ACS, especially taking into account the increased risk of developing heart failure in ACS. During the acute phase, rosiglitazone should be withdrawn.

The incidence of heart failure was more often reported in patients with a history of heart failure, the incidence of edema and heart failure was also more commonly reported in elderly patients and patients with mild or moderate renal failure. Given the limited experience with rosiglitazone in patients older than 75 years, caution should be exercised in patients of this age group.

Myocardial ischemia

A retrospective analysis of 42, mostly short-term clinical trials, suggests a link between rosiglitazone intake and the risk of developing myocardial ischemia in placebo-controlled studies, but not in comparison with active drugs.In the same analysis, when comparing rosiglitazone with other oral hypoglycemic drugs, there were no differences in the incidence of cardiovascular complications. The relationship between rosiglitazone intake and the risk of ischemia is not established. An increased risk of developing myocardial ischemic damage was observed in patients who received nitrate therapy initially or during a clinical study for established CHD. Rosiglitazone It is not recommended to use in patients receiving concomitant therapy with nitrates.

At present, there is no reliable data on the reduction of the risk of macrovascular complications in patients with type 2 diabetes with oral hypoglycemic drugs, including thiazolidinediones.

Since in patients with type 2 diabetes, the risk of developing coronary artery disease is increased regardless of the choice of an oral hypoglycemic drug, appropriate measures should be taken to reduce the risk of developing cardiovascular complications.

Visual impairment

There are rare reports of the development or deterioration of diabetic macular edema with reduced visual acuity.Such patients often reported the development of peripheral edema. In some cases, such violations were resolved after the abolition of therapy. It should be borne in mind the possibility of developing this complication with complaints of the patient to reduce visual acuity.

Hypoglycaemia

It is possible to develop hypoglycemia associated with the combined use of rosiglitazone and sulfonylurea derivatives, which may require a reduction in the dose of the concomitant drug.

Effect on the condition of bone tissue

In a comparative study of glycemic control lasting 4-6 years ("ADORT" - "Study of outcomes of diabetes progression") with the use of rosiglitazone monotherapy in patients who had not previously received treatment, who was recently diagnosed with type 2 diabetes, there was an increase in the incidence of bone fractures among women. During the 4-6 year period, the incidence of fractures in women taking rosiglitazone, was 9.3% (60/645) compared with 3.5% (21/605) in women taking glibenclamide, and from 5.1% (30/590) in women taking metformin. Most of the reported messages in the rosiglitazone group concerned fractures of the upper limbs and distal fractures of the lower extremities.This localization of fractures differs from that usually observed in postmenopausal osteoporosis (for example, proximal femur or spine). Other studies show that the risk of bone fractures can also exist in men. Nevertheless, the risk of fractures in women is obviously higher than that of men.

In women, an increase in the incidence of fractures was recorded after the first year of use and subsequent application for a long period. When rosiglitazone is prescribed, especially for women, a possible increase in the risk of fractures should be taken into account. It is necessary to monitor bone mineral density (BMD).

In several studies in men and women taking rosiglitazone, cases of a slight decrease in BMD in the spine and femur were recorded. Correlations between changes in BMD and risk of fractures have not been established.

Simultaneous prescribing with other drugs (see also section "Interaction with other drugs" medicinal preparations ")

With simultaneous administration with inhibitors or inductors СUR2С8, careful monitoring of blood glucose and correction of rosiglitazone dose may be required.

Monitoring of liver function

In the course of routine practice, rare reports of liver damage were recorded. Data on the use of rosiglitazone in patients with increased activity of "hepatic" enzymes (ALT 2.5 times higher than the upper limit of the norm) are limited. Thus, before the beginning and periodically during treatment, depending on the clinical picture, all patients should be monitored for activity of "liver" enzymes. Treatment with rosiglitazone does not begin with an increase in the activity of "liver" enzymes, 2.5 times higher than the upper limit of the norm (VGN), or in the presence of any sign of liver disease. At excess of VGN more than 3 times on a background of treatment it is necessary to make a repeated estimation of indicators as soon as possible. In the event that the values remain exceeding the VGN 3 times, treatment with rosiglitazone is stopped. In the case of developing symptoms suggestive of liver dysfunction, such as unexplained nausea, vomiting, abdominal pain, fatigue, anorexia and / or darkening of urine, it is necessary to evaluate the activity of "liver" enzymes. The decision to continue therapy with rosiglitazone should be based on the clinical picture and laboratory data.When jaundice appears, treatment with rosiglitazone should be discontinued.

Patients with impaired renal function

With renal failure of mild to moderate severity, dose adjustment is not required. With regard to the use of the drug in patients with severe renal insufficiency, the data is insufficient, so the drug should be used with caution.

Effect on the ability to drive transp. cf. and fur:Rosiglitazone does not affect the work that requires an increased concentration of attention and speed of psychomotor reactions (including driving).

Form release / dosage:

Tablets, film-coated, 4 mg and 8 mg.

Packaging:

For 14 tablets in PVC / A1 blisters. For 2, 4 or 8 blisters together with instructions for use are placed in a cardboard box.

For 7 tablets in PVC / A1 blisters. One blister, along with instructions for use, is placed in a cardboard box.

Storage conditions:Store at a temperature not exceeding 25 ° C. Keep out of the reach of children.

Shelf life:

2 years.

Do not use after the expiration date printed on the package.

Terms of leave from pharmacies:On prescription

Registration number:П N013617 / 01

Date of registration:14.07.2008

Expiration Date:Unlimited

Date of cancellation:2016-07-21

The owner of the registration certificate:GlaxoSmithKline Trading, ZAO GlaxoSmithKline Trading, ZAO Russia

Manufacturer: & nbsp

GLAXO WELLCOME, S.A. Spain

Representation: & nbspGlaxoSmithKline Trading, ZAOGlaxoSmithKline Trading, ZAO

Information update date: & nbsp21.01.2017

Illustrated instructions

Instructions

Avandia (Avandia)