Universal reference book for medicines
Product name: AVANDAGLIM (AVANDAGLIM)

Active substance: glimepiride, rosiglitazone

Type: Oral hypoglycemic drug

Manufacturer: GlaxoSmithKline Trading (Russia) manufactured by SmithKline Beecham Corporation (USA)
Composition, form of production and packaging
The tablets covered with a film cover of
pink color, triangular with rounded edges, with an impression "GSK" on one side and "4/4" on the other side;
on the bend - white.
1 tab.

rosiglitazone * (in the form of maleate) 4 mg

glimepiride 4 mg

Excipients: lactose monohydrate, microcrystalline cellulose, sodium carboxymethyl starch, hypromellose (HPMC) 3cP, magnesium stearate.

Composition of the shell: Opadry ® brown 03B267184 (hypromellose (HPMC) 6cP (E464), titanium dioxide (E171, CI77891), iron dye red oxide (E172, Cl77491), ferric oxide black oxide (E172, Cl77499), macrogol 400).

14 pcs.
- blisters (1) - packs of cardboard.
14 pcs.
- blisters (2) - packs of cardboard.
14 pcs.
- blisters (4) - packs of cardboard.
14 pcs.
- blisters (8) - packs of cardboard.
The tablets covered with a film membrane of red color, biconcave, triangular with rounded edges, with an impression of "GSK" on one side and "8/4" on the other side;
on the bend - white.
1 tab.

rosiglitazone * (in the form of maleate) 8 mg

glimepiride 4 mg

Excipients: lactose monohydrate, microcrystalline cellulose, sodium carboxymethyl starch, hypromellose (HPMC) 3cP, magnesium stearate.

Composition of the shell: Opadry ® red 03B253474 (hypromellose (HPMC) 6cP (E464), titanium dioxide (E171, Cl77891), iron dye red oxide (E172, Cl77491), macrogol 400).

14 pcs.
- blisters (1) - packs of cardboard.
14 pcs.
- blisters (2) - packs of cardboard.
14 pcs.
- blisters (4) - packs of cardboard.
14 pcs.
- blisters (8) - packs of cardboard.
* Nonproprietary international name recommended by WHO - rosiglitazone.

INSTRUCTION FOR THE SPECIALIST.

Description of the drug approved by the manufacturer for the printed edition of 2010.

PHARMACHOLOGIC EFFECT

Oral hypoglycemic drug.
Avandaglium contains two active substances with complementary mechanisms of action that improve glycemic control in patients with type 2 diabetes mellitus: rosiglitazone maleate, a class of thiazolidinediones, and glimepiride, a representative of the class of sulfonylurea derivatives. The mechanism of action of thiazolidinediones consists mainly in enhancing the sensitivity of target tissues to insulin, whereas sulfonylureas derivatives act, in the main, to enhance the release of insulin by functioning β-cells of the pancreas. Due to different but complementary mechanisms of action, combined therapy with rosiglitazone and the sulfonylurea derivative results in a synergistic improvement in glycemic control in patients with type 2 diabetes mellitus.
Rosiglitazone

Selective and potent agonist PPAR -? - receptor nucleus (activated by peroxisome proliferator receptors - gamma), belonging to hypoglycemic drugs of the thiazolidinediones class.
Improves glycemic control by increasing the sensitivity to insulin of key target tissues, such as adipose tissue, skeletal muscles and liver. It is known that insulin resistance plays an important role in the pathogenesis of type 2 diabetes mellitus. Consequently, rosiglitazone improves metabolic control by lowering blood glucose, circulating insulin and free fatty acids.
Hypoglycemic activity of rosiglitazone is demonstrated in experimental models of type 2 diabetes mellitus in animals.
It was shown that rosiglitazone retains the function of β-cells, as evidenced by an increase in the mass of the islets of the pancreas's Langerhans and an increase in the insulin content in them, and also prevents the development of severe hyperglycemia. It has also been established that rosiglitazone significantly slows the development of renal dysfunction and systolic hypertension. Rosiglitazone 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 action rosiglitazona, improving glycemic control is accompanied by a clinically significant decrease in serum insulin concentration.
The concentrations of insulin precursors, which are generally believed to be risk factors for cardiovascular diseases, also decrease. One of the key results of treatment with rosiglitazone is a significant reduction in the concentrations of free fatty acids.
Glimepiride

The main mechanism of hypoglycemic action of glimepiride is to stimulate the release of insulin by functioning β-cells of the pancreas.
In addition, extrapancreatic effects also play a role in the action of sulfonylurea derivatives, such as glimepiride, as confirmed by both preclinical and clinical studies showing that the administration of glimepiride may increase the sensitivity of peripheral tissues to insulin. These findings are consistent with the results of a long-term, randomized, placebo-controlled study in which glimepiride therapy improved postprandial insulin / C-peptide response and glycemic control in general without the development of a clinically significant increase in fasting insulin / C-peptide. However, as in the case of other sulfonylureas, the mechanism of hypoglycemic action of glimepiride for prolonged use is not fully understood.
In healthy volunteers, the minimum effective dose for ingestion is approximately 600 μg.
The effect of glimepiride is dose-dependent and is reproducible. Physiological response to acute physical exertion, i.e. decrease in the secretion of insulin, is maintained by the action of glimepiride.
There was no significant difference in the action of glimepiride when taking the drug 30 minutes before meals or immediately before meals.
A single administration of glimepiride provided good metabolic control in patients with diabetes for more than 24 hours. In addition, in a clinical study, good metabolic control was achieved in 12 of 16 patients with impaired renal function (CC less than 80 mL / min). Although the hydroxylated metabolite of glimepiride causes a small but significant reduction in serum glucose in healthy people, this is only a small part of the overall effect of the drug.
PHARMACOKINETICS

Avandaglim

Repeated administration rosiglitazona (8 mg / day) does not significantly affect the pharmacokinetics of glimepiride with its single administration (4 mg).
A single dose (4 mg) of glimepiride does not have a clinically significant effect on the equilibrium pharmacokinetics of rosiglitazone (8 mg / day).
In a study of the bioequivalence of Avandaglim (4 mg / 4 mg) for such indicators as AUC and Cmax rosiglitazone, it was shown that, with a single admission of the combined Avandaglyme preparation, it was bioequivalent to rosiglitazone at a dose of 4 mg with concomitant administration with glimepiride at a dose of 4 mg on an empty stomach.

AUC of glimepiride with a single admission of fast-acting fasting Vandalemia at a dose of 4 mg / 4 mg was bioequivalent to that with simultaneous administration of glimepiride with rosiglitazone.
The degree of absorption of rosiglitazone and glimepiride with Avandaglym after eating was equivalent to that with simultaneous application as separate preparations.
Further information reflects the pharmacokinetic properties of the individual components of Avandaglium.

Suction

Rosiglitazone

Absolute bioavailability of rosiglitazone after ingestion of 4 mg or 8 mg is about 99%.
With MA rosiglitazona achieved about 1 hour after its intake.
In the range of therapeutic doses, rosiglitazone concentrations in plasma are approximately proportional to its dose.

Taking rosiglitazone with food does not change AUC, but in comparison with fasting, there is a slight decrease in C max (by about 20-28%) and an increase in T max (1.75 h).These small changes are clinically insignificant, and therefore rosiglitazone can be taken regardless of food.
The increase in pH of gastric contents does not affect the absorption of rosiglitazone.
Glimepiride

After ingestion glimepiride completely (100%) is absorbed into the digestive tract.
Studies involving healthy people taking glimepiride orally or patients with type 2 diabetes taking glimepiride orally on a regular basis showed that a large part of it is absorbed within 1 hour after administration, T max is 2-3 hours.
Distribution

Rosiglitazone

V d of rosiglitazone is approximately 14 liters, and the total plasma clearance is about 3 liters / h in healthy volunteers.
High degree of binding to plasma proteins (about 99.8%), does not depend on the concentration of the drug and the age of the patient. Currently there is no data on cumulation rosiglitazona at its reception 1 or 2 times / day.
Glimepiride

With IV introduction of healthy volunteers, V d is 8.8 L (113 ml / kg), the total clearance was 47.8 ml / min.
Protein binding is more than 99.5%.
Metabolism

Rosiglitazone

It is subject to intensive metabolism, it is excreted in the form of metabolites.
The main ways of metabolism are N-demethylation and hydroxylation, followed by conjugation with sulfate and glucuronic acid. Metabolites rosiglitazona not have pharmacological activity.
In vitro studies have shown that rosiglitazone is metabolized predominantly by the isoenzyme CYP2C8 and, to a much lesser extent, by the isoenzyme CYP2C9.

In conditions of in vitro, rosiglitazone does not have a significant inhibitory effect on the isoenzymes CYP1A2, CYP2A6, CYP2C19, CYP2D6, CYP2E1, CYP3A and CYP4A, and therefore it is unlikely that in vivo it will enter into significant metabolic interactions with drugs that are metabolized by these isoenzymes of the cytochrome P450 system .
In vitro rosiglitazone moderately inhibits the CYP2C8 isoenzyme (inhibitory concentration is 18 μmol) and weakly inhibits the CYP2C9 isoenzyme (the inhibitory concentration is 50 μmol). The study of the interaction of rosiglitazone with warfarin in vivo showed that rosiglitazone does not interact with substrates of the isoenzyme CYP2C9.
Glimepiride

Glimepiride is completely metabolized by oxidation with both intravenous administration and oral administration.
Its main metabolites are cyclohexylhydroxymethyl-derivative (M1) and carboxyl derivative (M2). Biotransformation of glimepiride to the M1 derivative occurs with the participation of the CYP2C9 isoenzyme. M1 is further metabolized to M2 by one or more cytosolic enzymes. M1, in contrast to M2, has 1/3 of the pharmacological activity of glimepiride. The clinical significance of the hypoglycemic effect of M1 is not clear.
Excretion

Rosiglitazone

The total plasma clearance of rosiglitazone is about 3 l / h, and the final T 1/2 is approximately 3-4 hours. At present, there is no data on cumulation of rosiglitazone at its intake 1 or 2 times / day.
About 2/3 of the ingested dose of rosiglitazone is excreted by the kidneys, approximately 25% is excreted by the intestine. Unchanged is not found in urine or feces. The final T 1/2 is about 130 hours, which indicates a very slow excretion of metabolites. With repeated ingestion of rosiglitazone, cumulation of its metabolites in plasma, in particular, the main metabolite (parahydroxisulphate), whose concentration, presumably, can increase by 5 times, is possible.
Glimepiride

T 1/2 glimepiride is approximately 5-8 hours. After ingestion of glimepiride labeled with isotope 14 C, about 60% of the administered dose is excreted in the urine on day 7, 80-90% in the form of M1 and M2.
About 40% of the administered dose is excreted with feces, up to 70% - in the form of M1 and M2. Unchanged is not found in urine or feces. With the / in the route of administration, there is no evidence of excretion of glimepiride or its metabolite M1 with bile.
Pharmacokinetics in special clinical cases

There were no significant differences in the pharmacokinetics of rosiglitazone and glimepiride in men and women.

There were no significant differences in the pharmacokinetics of rosiglitazone and glimepiride in elderly and adult patients without impaired renal function.

There were no significant differences in the pharmacokinetics of rosiglitazone in patients with impaired renal function or terminal stage of kidney disease in chronic hemodialysis.

There is no data on the use of glimepiride in patients undergoing hemodialysis.
In patients with renal insufficiency (QC less than 22 ml / min), it was possible to maintain adequate glucose control at a dose of only 1 mg / day.
In patients with moderate and severe hepatic impairment (classes B and C on the Child-Pugh scale), Cmax and AUC were 2-3 times higher, which is the result of increased binding to plasma proteins and reduced rosiglitazone clearance.

Since there is no adequate data on the use of glimepiride in patients with hepatic impairment, Avandaglide is not recommended for use in such patients.

INDICATIONS

- Type 2 diabetes mellitus (for glycemic control when monotherapy with sulfonylureas or thiazolidinedione derivatives is ineffective, as well as patients who have already received combination therapy with thiazolidinedione and sulfonylureas).

Avandaglim can be used in combination with metformin (a three-component combination) for glycemic control.

DOSING MODE

The dosage regimen of Avandaglim is selected and set individually.
It is necessary to take into account the individual current glycemic control in the patient and the risk of developing hypoglycemia.
Avandaglym should be taken 1 time / day during meals.

Adults on transition from rosiglitazone + glimepiride in the form of monopreparations to the combined drug (Avandaglym) the initial dose of the combination should be based on the already taken dosages of rosiglitazone and glimepiride.

With insufficient glycemic control when taking glimepiride monopreparations at a dose of 4 mg / day, the initial dose of Avandaglim is 4 mg rosiglitazone / 4 mg glimepiride.

Patients with insufficient glycemic control who are on treatment with other sulfonylureas (in addition to chloropropramide) at a dosage of at least half of the maximum dose are treated with rosiglitazone at a dosage of 4 mg / day, after adequate glycemic control has been achieved, Avandaglim 4 mg rosiglitazona / 4 mg glimepirid 1 time / day.

The daily dose of Avandaglim can be increased to maintain individual glycemic control in the patient.
The therapeutic effect after dose adjustment may not appear for 6-8 weeks for rosiglitazone and for 1-2 weeks for glimepiride. If necessary, an increase in the dose of rosiglitazone is possible only after 8 weeks of use. The dose is titrated up to a maximum daily dose of 8 mg rosiglitazone / 4 mg glimepiride. Increasing the dose of rosiglitazone to 8 mg per day should be undertaken with caution after evaluating the risk of developing unwanted reactions associated with fluid retention in the body.
The need for glimepiride may decrease during therapy.
In the case of hypoglycemia, it is necessary to reduce the dose of glimepiride or completely to abolish it. Correction of the doses of one of the components of Avandaglium, rosiglitazone or glimepiride, may be required when combined with other drugs.
Currently, there is no data on the use of Avandaglym in children under 18 years of age , so Avandaglima is not recommended for this age group.

The initial and maintenance dose of Avandaglim in elderly patients should be adequately adjusted due to a possible reduction in renal function in this group of patients.
Any dose adjustment should be based on data on kidney function that should be monitored continuously.
In patients with mild to moderate renal insufficiency (QA 30-80 ml / min), when switching from other sulfonylureas to Avandaglim therapy, there is an increased risk of hypoglycemia, therefore appropriate monitoring is recommended in such cases.

Patients with severe renal insufficiency (KC less than 30 ml / min) Avandaglimum is contraindicated.

Data on the use of glimepiride in patients undergoing hemodialysis are not available.

Since there is no adequate data on the use of glimepiride in patients with hepatic impairment , Avandaglide is not recommended for use in such patients.

SIDE EFFECT

The frequency of unwanted reactions is determined as follows: very often (? 1/10), often (? 1/100 and <1/10), sometimes (? 1/1000 and <1/100), rarely (? 1/10 000 and <1/1000) and very rarely (<1/10 000), including individual messages.

Avandaglim

Limited data from recent clinical trials indicate that the safety profile of the combined rosiglitazone and fixed-dose glimepiride is generally similar to that observed with concomitant use of rosiglitazone and other sulfonylurea preparations.

The following data reflect information on the safety profile obtained using rosiglitazone and glimepiride in the form of individual components.

Rosiglitazone

Data from clinical trials

Frequency categories are defined in comparison with the frequency of occurrence of undesirable reactions in the treatment of placebo or the reference preparation, and not absolute values ​​for those undesirable reactions that may be associated with rosiglitazone.
For dose-related adverse reactions the frequency category reflects the maximum dose of rosiglitazone. Frequency categories do not account for other factors, including differences in the duration of studies, the previous state and baseline characteristics of patients. Categories of frequency of adverse reactions identified through clinical trials and may not reflect the frequency of adverse reactions in clinical practice.
P - rosiglitazone, M - metformin, C - sulfonylurea
Side effects F R M + P + C P + C + M
From the hemopoietic system
Anemia Often Often Often Often
Leukopenia Often
Thrombocytopenia Often
granulocytopenia Frequently
Anemia often dose-dependent, ranging from mild to moderate in severity
From the metabolism
Hypercholesterolemia Often Often Often Often
Hypertriglyceridemia Often Often
Hyperlipidemia Often Often Often Often
Weight gain Often Often Often Often
Increased appetite Often Sometimes
Hypoglycemia Often Very often Very often
Total cholesterol was increased concurrently with increased concentration HDL and LDL ratio cholesterol / HDL cholesterol remained unchanged. Increased body weight in a dose-dependent largely, probably due to fluid retention and accumulation of fatty deposits. Hypoglycemia is usually moderate or mild degree, dose-dependent, primarily, with the combined use of insulin and sulfonylureas.
From the nervous system
Dizziness Often Often
Headache is often
the part of the cardiovascular system
Heart failure / pulmonary edema Often Often
Myocardial ischemia Often Often Often Often
Increased incidence of heart failure was observed when attached to rosiglitazone treatment regimes based on sulfonylureas or insulin. The number of observations does not allow an unambiguous conclusion about the connection with the magnitude of the dose, but the incidence of the above daily dose to 8 mg of rosiglitazone, compared with a daily dose of 4 mg. The symptoms of myocardial ischemia were more frequently observed in the appointment of rosiglitazone in patients who are on insulin therapy. Data on the possibility of rosiglitazone increase the risk of myocardial ischemia are insufficient.Retrospective analysis of short-term clinical studies showed an increased risk of ischemic events with rosiglitazone treatment compared with control groups in general (placebo + active agents) in the same assay when compared rosiglitazone with other oral hypoglycemic agents differences in the frequency of ischemic events were observed. An increased risk of myocardial ischemia associated with rosiglitazone, was not confirmed in further long-term randomized controlled clinical trials comparing rosiglitazone with metformin and a sulfonylurea. Association between rosiglitazone and the risk of myocardial ischemia has not been established. Increased risk of ischemic myocardial injury observed in patientstreated with nitrates at baseline or during clinical studies about the established CHD. Rosiglitazone is not recommended in patients receiving concomitant therapy with nitrates.
From the digestive system
Constipation (mild to moderate) Often Often Often Often
on the part of the musculoskeletal system
of bone fractures often
Myalgia Often
Most reports concerned the forearm fractures, hands and feet of women
on the part of the whole body
edema often Often Very often Very often
edema mild to moderate severity, often dose-dependent, more often observed in combination therapy with sulfonylureas or insulin
data obtained during post-marketing
Categories unwanted frequency responses are defined based on the frequency of messages unwanted reactions when applied in post-marketing rosiglitazone period regardless of the dose or concomitant therapy hypoglycemic drugs. Occurrence of rare and very rare side effects were determined on the basis of post-marketing data, and it concerns more the frequency of such effects messages than the true frequency of the effects themselves.
Allergic reactions: very rare - anaphylactic reactions, angioedema, urticaria, rash, pruritus
Cardio-vascular system: seldom - a chronic heart failure / pulmonary edema.
Reports on the development of undesirable reactions data obtained for rosiglitazone, used as a monotherapy or in combination with other hypoglycemic agents. It is known that the risk of developing heart failure is significantly increased in patients with diabetes compared to those who do not have diabetes.
From the digestive system: rarely noted reports of hepatic dysfunction, accompanied by increased levels of liver enzymes, but a causal relationship between treatment with rosiglitazone and liver dysfunction has not been established. Patients with diabetes often have disorders of the liver.
From a sight organ: very rarely - macular edema.
glimepiride
Data from clinical studies and post-marketing period
Undesired reactions are shown below by organ systems and frequency. Occurrence of very frequent, frequent and undesirable reactions, sometimes encountered usually determined based on pooled data controlled clinical studies and reflects the difference between the frequency of occurrence of adverse reactions when receiving glimepiride and reference drug. Occurrence of rare and very rare side effects were determined on the basis of post-marketing data, and it concerns more the frequency of such effects messages than the true frequency of the effects themselves.
From hemopoiesis system: very rarely - thrombocytopenia, leukopenia, hemolytic anemia, erythropenia, granulocytopenia, agranulocytosis, pancytopenia.
From a metabolism: often - hypoglycemia; very rarely - hyponatremia.
From a sight organ: very rarely - visual impairment.
There may be temporary visual disturbances, especially at the beginning of treatment, associated with changes in blood glucose levels. The cause is a temporary change in turgor of tissues, which leads to a change in the refractive index of the lens, this phenomenon depends on the level of glucose in the blood.
From the digestive system:often - nausea; rarely - increased liver enzymes; very rarely - gastrointestinal disorders (vomiting, feeling of pressure and overcrowding epigastric abdominal pain and diarrhea), hepatic dysfunction, manifested by cholestasis, jaundice, hepatitis or liver failure. There are some reports describing liver dysfunction, including cholestasis, jaundice, hepatitis and liver failure in patients treated with sulfonylureas, including glimepiride.
Skin and subcutaneous tissue disorders:sometimes - or pseudo-allergic reactions (pruritus, urticaria or rash); very rare - allergic vasculitis, photosensitivity reactions. Mild reactions may develop into serious, including anaphylactic shock. In the case of hives should be immediately put in the doctor's reputation.
CONTRAINDICATIONS

- heart failure (I-IV NYHA functional class classifying);
- acute coronary syndrome (unstable angina, myocardial infarction without ST segment lift, myocardial infarction with ST segment elevation);
- severe renal failure (creatinine clearance less than 30 mL / min), including patients on hemodialysis;
- impaired liver function;
- type 1 diabetes mellitus;
- diabetic ketoacidosis or diabetic precoma;
- galactose intolerance, lactase deficiency or malabsorption of glucose-galactose;
- the age of 18 years (there are currently no data on the use of Avandaglima in children under 18 years of age, so the use of Avandaglima in this age group is not recommended);
- the combined use of insulin;
- hypersensitivity to rosiglitazone, glimepiride, other sulfonylureas or sulfonamides or to any other component of the drug.
PREGNANCY AND LACTATION

It reported on the ability of rosiglitazone to cross the placenta in humans and is found in fetal tissues. Currently, there is insufficient data on the use of Avandaglima in pregnant women. During pregnancy, women with diabetes are usually recommended to prescribe insulin. Pregnant women appointment Avandaglima not shown.
At present, there is insufficient data on the use Avandaglima in lactating women, therefore Avandaglim should not be used during breastfeeding. It is unknown whether Avandaglim into breast milk. Nursing women with diabetes usually recommended to assign insulin. Appointment Avandaglima lactating women are not shown.
APPLICATION FOR FUNCTIONS OF THE LIVER

In patients with renal insufficiency mild and moderate severity (CC 30-80 ml / min) at the transition from the therapy to other sulfonylureas Avandaglimom therapy have an increased risk of hypoglycemia, however in such cases a corresponding observation.
Patients with severe renal impairment (creatinine clearance less than 30 mL / min) Avandaglim contraindicated.
Data on the use of glimepiride in patients undergoing dialysis, no.
APPLICATION FOR VIOLATIONS OF THE FUNCTION OF KIDNEYS

Since adequate data on the use of glimepiride in patients with impaired liver function are missing, Avandaglim not recommended in such patients.
APPLICATION FOR CHILDREN

There is currently no data on the use of Avandaglima have children under the age of 18 , so the use of Avandaglima not recommended in this age group.
APPLICATION IN ELDERLY PATIENTS

Starting and supporting Avandaglima dose in elderly patients should be adequately adjusted due to possible loss of kidney function in this patient group. Any dose adjustment should be based on evidence of renal function, which should be continuously monitored.
SPECIAL INSTRUCTIONS

Diabetes mellitus type 1
Avandaglim effective only in the presence of insulin and therefore should not be used for the treatment of diabetes mellitus type 1.
Women with premenopausal ages lack of ovulation
due to the ability of rosiglitazone improve insulin sensitivity, treatment Avandaglimom premenopausal women with anovulation and insulin resistance ( for example, patients with polycystic ovarian syndrome) can lead to a resumption of ovulation. Such patients may become pregnant.
Cardiovascular diseases
Rosiglitazone, like other thiazolidinediones, may in some cases cause the development or worsen congestive heart failure. After initiation of therapy Avandaglimom and selection of a desired dosage requires careful monitoring of the patient against the development of heart failure symptoms (rapid and excessive weight gain, dyspnea, edema).
Application Avandaglima contraindicated in heart failure (I-IV NYHA functional class classification). With the development of symptoms of heart failure should consider repealing Avandaglima and prescribe treatment in accordance with the current standards of treatment of heart failure.
Patients with acute coronary syndrome (ACS) were not included in clinical studies. Appointment of rosiglitazone, as well as other oral hypoglycemic agents is contraindicated in patients with ACS, especially taking into account the increased risk of heart failure in ACS. During the acute phase to cancel receiving rosiglitazone.
Currently there is no reliable data on reducing the risk of type 2 diabetes, macrovascular complications with oral hypoglycemic drugs, including thiazolidinediones. Because in patients with type 2 diabetes increases the risk of coronary heart disease, irrespective of the choice of oral hypoglycemic drug, you should take appropriate measures to reduce the risk of cardiovascular complications.
Patients with ocular disorders
in post-marketing period rarely reported cases of primary or worsening cases of diabetic macular edema with decreased visual acuity when using rosiglitazone. Many of these patients had peripheral edema. In some cases, visual disturbances were completely or improved after drug discontinuation. It is necessary to pay special attention to the possibility of macular edema in patients who were impaired visual acuity.
The regulation of blood glucose levels
In stressful situations (e.g., trauma, surgery, infection) regulation of blood glucose levels can be broken, in such a case to maintain a good metabolic control necessary time correction doses of hypoglycemic agents or administration of insulin.
When the risk factors of hypoglycemia, including kidney failure, underweight, malnutrition or simultaneous use of certain medications may require correction or glimepiride dose therapy in general. This also applies to periods of any diseases during therapy, or change the style of life of the patient.
Effect on bone
In a longitudinal study monotherapy of diabetes type 2 patients, not previously treated with oral hypoglycemic agents was an increase in the incidence of fractures in women rosiglitazone group (9.3%; 2.7 per 100 patient-years) compared to metformin groups (5.1%; 1.5 cases per 100 patient-years) and glyburide / glibenclamide (3.5%; 1.3 cases per 100 patient-years). The majority of registered messages in the rosiglitazone group concerned shoulder fracture, hands and feet. Possible increased risk of fractures should be considered in the appointment of rosiglitazone, especially women. Requires monitoring of bone health and maintain her health in accordance with accepted standards of care.
hemolytic anemia
Treatment of patients with deficiency of glucose-6-phosphate dehydrogenase preparations of sulfonylurea derivatives can lead to hemolytic anemia. Because glimepiride belongs to a class of sulfonylurea active drug should be administered with cautious patients with deficiency of glucose-6-phosphate dehydrogenase. As an alternative treatment should be considered products that do not contain a sulphonylurea.
The simultaneous appointment of other drugs
Careful control of blood glucose levels and dose adjustment of rosiglitazone or glimepiride may be necessary while appointing Avandaglima with CYP2C8 and CYP2C9 inhibitors or inducers.
lactose intolerance
Avandaglima tablets contain lactose and should not be administered to patients with the following rare hereditary diseases: galactose intolerance, lactase deficiency, malabsorption of glucose-galactose.
Impact on the ability to drive vehicles and manage mechanisms

Special studies Avandaglima influence on the ability to drive and / or other mechanisms are not conducted. However, assessing the patient's ability to perform tasks that require clear thinking, motor and cognitive skills, it is necessary to consider the possibility of hypoglycemia.
OVERDOSE

There is currently no data on overdose Avandaglima. In clinical studies

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