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

Pharmacodynamics:Hypoglycemic agent of thiazolidinedione series for oral administration. Selectively stimulates γ-receptors activated by peroxisome proliferator (PPARγ). PPARγ receptors are found in tissues that play an important role in the mechanism of action of insulin (fat, skeletal muscle tissue and in the liver).Activation of nuclear receptors PPARγ modulates the transcription of a number of genes sensitive to insulin, involved in controlling the concentration of glucose in the blood and in the metabolism of lipids. Reducing insulin resistance, increases the consumption of insulin-dependent glucose and reduces the release of glucose from the liver. Reduces the level of triglycerides, increases the concentration of high-density lipoproteins and cholesterol. Unlike derivatives of sulfonylureas, it does not stimulate insulin secretion.

Pharmacokinetics:

After ingestion, absorption is high; pioglitazone is detected in the blood plasma after 30 minutes, bioavailability does not depend on food intake. The maximum concentration is achieved after 2 hours, after meals - after 3-4 hours. The volume of distribution is 0.22-1.04 l / kg. The connection with plasma proteins is 99%. Intensively metabolized by hydroxylation and oxidation; metabolites are also partially converted to glucuronide or sulfate conjugates. Metabolites M-II and M-IV (pioglitazone hydroxide derivatives) and M-III (keto derivatives of pioglitazone) exhibit pharmacological activity. The main isoenzymes of cytochrome P450, involved in the hepatic metabolism of pioglitazone - CYP2C8 and CYP3A4, are metabolized with the participation of many others.isoenzymes (mainly extrahepatic isoenzyme CYP1A1). The equilibrium concentration in the plasma of pioglitazone and its active metabolites is reached after 7 days.

It is excreted mainly with bile in unchanged form or in the form of metabolites and is removed with feces; kidneys - 15-30% in the form of metabolites and their conjugates. The half-life of pioglitazone is from 3 to 7 hours of active metabolites - from 16 to 24 hours.

Indications:Type 2 diabetes mellitus (in monotherapy, in combination with sulfonylurea derivatives, metformin or insulin in those cases where diet, exercise and monotherapy with one of the hypoglycemic agents mentioned above do not allow adequate glycemic control).

Contraindications:

Hypersensitivity to the drug;

diabetes mellitus type 1;

diabetic ketoacidosis;

severe heart failure (NYHA class III-IV);

severe hepatic insufficiency (increased activity of liver enzymes is 2.5 times higher than the upper limit of the norm);

pregnancy, the period of breastfeeding;

Children under 18 years of age (no clinical studies of the safety and efficacy of pioglitazone in children have been conducted).

Carefully:Edema syndrome, anemia, heart failure, impaired liver function.

Dosing and Administration:

Inside, squeezed enough water, 1 time per day (regardless of food intake).

Monotherapy:

15-30 mg per day; the maximum daily dose is 45 mg.

Combination therapy:

In combination with sulfonylureas or metformin, treatment with Astrosone is started with 15 mg or 30 mg (hypoglycemia is decreased by the dose of sulfonylurea or metformin).

In combination with insulin: the initial dose of Astrozone is 15-30 mg / day, the dose of insulin remains the same or decreases by 10-25% when hypoglycemia occurs.

Side effects:

From the nervous system and sense organs: dizziness, headache, hyposthenia, insomnia, vision disorders.

From the respiratory system: pharyngitis; sinusitis.

From the side of metabolism: weight gain, hypoglycemia.

On the part of the hematopoiesis system: anemia.

From the gastrointestinal tract: Flatulence.

From the laboratory indicators: increased activity of alanine aminotransferase and creatinine phosphokinase; decrease in hematocrit and hemoglobin.

From the side of the musculoskeletal system: arthralgia, myalgia.

With prolonged use of pioglitazone over 1 year in 6-9% of cases, patients experience edema, mild or moderate, and usually do not require discontinuation of therapy.

Visual disorders are manifested primarily at the beginning of therapy and are associated with changes in plasma glucose levels, as with other hypoglycemic agents.

In rare cases, on the background of taking pioglitazone, heart failure may develop.

On the background of pioglitazone therapy, a clinically insignificant decrease in hemoglobin level and a decrease in hematocrit may be possible.

Overdose:In case of an overdose, appropriate measures should be taken, based on clinical symptoms and laboratory test scores.

Interaction:

Pharmacokinetic studies on the combined use of pioglitazone and oral contraceptives have not been conducted. The use of other thiazolidinediones together with oral contraceptives containing ethinyl estradiol or norethindrone, was accompanied by a 30% decrease in the concentration of both hormones in the plasma, which can lead to a significant reduction in the contraceptive effect.Therefore, care should be taken when using pioglitazone and oral contraceptives together.

There are no changes in pharmacokinetics with simultaneous administration with glipizide, digoxin, warfarin, metformin.

In vitro studies it was found that ketoconazole significantly inhibits the metabolism of pioglitazone. Better blood glucose control should be performed in patients receiving concomitantly pioglitazone and ketoconazole.

There is no data on the use of pioglitazone in triple combination with other oral hypoglycemic drugs.

Special instructions:

Hypoglycemic conditions

Patients receiving pioglitazone in combination with insulin or oral hypoglycemic agents, have the risk of developing hypoglycemic conditions. In this case, it may be necessary to reduce the dose of jointly used hypoglycemic drugs.

Ovulation

In patients with insulin resistance and anovulatory cycle in the pre-menopausal period, treatment with thiazolidinediones, including pioglitazone, can cause the onset of ovulation.A consequence of improving the sensitivity of these patients to insulin is the risk of pregnancy if adequate contraceptive methods are not used. When the offensive or planning of pregnancy should stop therapy with pioglitazone.

Hematologic changes

The use of pioglitazone can cause a decrease in hemoglobin and hematocrit. These changes can be associated with an increase in the volume of plasma.

Edema

Pioglitazone should be used with caution in patients with edema.

Influence on the cardiovascular system

In preclinical studies, thiazolidinediones, including pioglitazone, caused an increase in the volume of plasma and the development of cardiac muscle hypertrophy (due to an increase in preload). In clinical studies, of which patients with grade III and IV heart failure (NYHA classification) were excluded, there was no increase in the incidence of serious side effects from the cardiovascular system potentially associated with an increase in plasma volume (eg, chronic heart failure).

Effects on the liver

During therapy with pioglitazone, it is recommended to regularly monitor liver function.In all patients, it is necessary to determine the alanine aminotransferase (ALT) content prior to the initiation of pioglitazone therapy, every 2 months during the first year of treatment and periodically during the subsequent years of taking the drug. Determination of liver function should also be carried out in patients with symptoms of liver damage (nausea, vomiting, abdominal pain, weakness, anorexia, dark urine). The decision on the possibility of further use of pioglitazone should be based on the indicators of laboratory tests. When jaundice develops, discontinue use of the drug.

Therapy with pioglitazone should not be started in patients with active liver disease, or with an increase in ALT rates more than 2.5 times higher than normal. In patients with a slight increase in ALT (1-2.5 times the norm) in the treatment with pioglitazone, a check should be conducted to identify the causes of increased activity of liver enzymes. The onset or continuation of pioglitazone therapy in patients with a slight increase in liver transaminase activity may be performed with caution, with the need for more frequent monitoring of liver function.If the ALT level is 3 times higher than normal, a second study should be carried out as soon as possible. If ALT values remain 3 or more times normal, or if the patient has jaundice, pioglitazone should be discontinued.

Effect on the ability to drive transp. cf. and fur:There is no evidence of the effect of pioglitazone on the ability to drive and other mechanisms.

Form release / dosage:Tablets 30 mg.

Packaging:For 30 tablets in cans of polymer or polymer bottles. For 10 tablets in a contour mesh box made of polyvinylchloride film and aluminum foil printed lacquered. 1 bank or 1 bottle, 3 or 6 contour packs with instructions for use in a pack of cardboard box.

Storage conditions:

Store at a temperature of 15 ° C to 30 ° C in a dry, dark place.

Keep out of the reach of children.

Shelf life:2 years. Do not use after expiry date.

Terms of leave from pharmacies:On prescription

Registration number:LSR-010488/08

Date of registration:24.12.2008

Expiration Date:Unlimited

The owner of the registration certificate:PHARMSTANDART-FORESTRY, OJSC PHARMSTANDART-FORESTRY, OJSC Russia

Manufacturer: & nbsp

PHARMSTANDART-FORESTRY, OJSC Russia

Information update date: & nbsp27.09.2017

Illustrated instructions

Instructions

Astroson® (Astrozone®)