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

Composition:active substance: pioglitazone hydrochloride in terms of 100% substance - 16.53 mg, 33.06 mg or 49.59 mg, equivalent to 15 mg, 30 mg or 45 mg of pioglitazone, respectively;
Excipients: lactose (milk sugar), microcrystalline cellulose, giprolase (hydroxypropyl cellulose), croscarmellose sodium, silicon dioxide colloid, magnesium stearate.

Description:Tablets are white with a creamy or yellowish hue of color, flat-cylindrical, with a bevel. Tablets with a dosage of 45 mg - with a risk.

Pharmacotherapeutic group:Hypoglycemic agent for oral administration.

ATX: & nbsp

A.10.B.G.03 Pioglitazone

Pharmacodynamics:Hypoglycemic agent of thiazolidinedione series for oral administration.Selectively stimulates Υ-receptors, activated by peroxisome proliferator (PPARΥ). PPARΥ 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 PPARΥ 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 found in the blood plasma after 30 minutes. 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 hepatic metabolism - CYP2C8 and CYP3A4, metabolism occurs with the participation of many other isoenzymes, including mainly the extrahepatic isoenzyme CYP1A1. Concentration in plasma of total pioglitazone (pioglitazone with active metabolites) is achieved after 24 hours with daily single use. The equilibrium concentration in plasma and pioglitazone, and total pioglitazone is achieved 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 and total pioglitazone is from 3 to 7 hours and from 16 to 24 hours, respectively.

Indications:Type 2 diabetes mellitus (in monotherapy, in combination with sulfonylureas, mttformin or insulin, when 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; heart failure III-IV class (according to the NYHA classification); severe hepatic insufficiency (increased activity of liver enzymes is 2.5 times higher than the upper limit of normal); 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 performed); bladder cancer at present or in the anamnesis; hematuria of unclear etiology.

Carefully:Edema, anemia, heart failure, impaired liver function (increased activity of "liver" transaminases is 1-2.5 times higher than the upper limit of the norm).
In connection with increased risks of developing bladder cancer, fractures and diseases of the cardiovascular system, it is necessary to carefully evaluate the relationship between benefit and risk before and during the treatment with pioglitazone in elderly patients.

Dosing and Administration:Inside, 1 time per day (regardless of food intake).
Monotherapy: 15-30 mg; the maximum daily dose is 45 mg.
Combination therapy: sulfonylureas, metformin - treatment with pioglitazone begins with the intake of 15 mg or 30 mg (if hypoglycemia occurs, reduce the dose of sulfonylurea or metformin). Treatment in combination with insulin: the initial dose is 15-30 mg / day, the dose of insulin remains the same or decreases by 10-25% (in case the patient reports hypoglycemia, or the plasma glucose concentration drops to less than 100 mg / dL).

Side effects:From the nervous system and sensory organs: dizziness, headache, hypoesthesia, 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 musculoskeletal system: arthralgia, myalgia. Benign and malignant tumors: bladder cancer (infrequently).With long-term 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:Overdose of pioglitazone in monotherapy is not accompanied by the emergence of specific clinical symptoms.
Overdose of pioglitazone in combination with the drug sulfonylureas may be accompanied by the development of symptoms of hypoglycemia.
There is no specific overdose treatment. It requires symptomatic therapy (eg, treatment of hypoglycemia).

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 norethisterone, 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.
Body weight control
In the treatment of type 2 diabetes mellitus, in addition to taking pioglitazone, it is recommended to follow a diet and exercise to maintain the effectiveness of drug therapy, and also in connection with the possible dose-dependent increase in body weight. 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 may be associated with an increase in plasma volume and are not associated with other significant hematologic clinical effects.
Edema
Pioglitazone should be used with caution in patients with edema.
Influence on the cardiovascular system
Against the background of the use of pioglitazone, fluid retention and an increase in the volume of plasma may occur, which may lead to the development or aggravation of the course of heart failure, therefore, if the state of the cardiovascular system worsens, pioglitazone should be discontinued. Patients who have at least 1 risk factor for developing chronic heart failure (CHF) should be treated with a minimal dose and gradually increased. It is necessary to identify early symptoms of CHF, increase in body weight (may indicate the development of CHF), or development of edema, especially in patients with reduced cardiac output. In the case of development of CHF, the drug is immediately withdrawn.
Effects on the liver
It is recommended during the therapy with pioglitazone to regularly monitor the concentration of hepatic enzymes in the blood. The alanine aminotransferase (ALT) content should be determined in all patients prior to the initiation of pioglitazone therapy, every 2 months during the first year of treatment, and periodically during the subsequent years of administration. Also, a determination of liver function in patients with symptoms,Suspected of symptoms of liver failure (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 values more than 2.5 times higher than normal. Patients with a baseline slight increase in ALT (1-2.5 times the norm) at any time during the treatment with pioglitazone should conduct a survey in order to identify the causes of increased activity of "liver" enzymes. The onset or continuation of pioglitazone therapy in patients with a slight increase in the activity of "liver" enzymes can be carried out with caution, and it is necessary to more often check the activity of "liver" transaminases. If there is an increase in the activity of "liver" transaminases (ALT 2.5 times higher than normal), the activity of "liver" enzymes should be determined more often until the indices decrease to normal and initial before therapy.If the ALT level is more than 3 times higher than normal, the definition of laboratory tests should be performed as soon as possible. If ALT values remain more than 3 times higher than normal or if the patient has jaundice, pioglitazone should be discontinued.
Effect on excretory system
A meta-analysis of controlled clinical trials revealed a more frequent development of bladder cancer in the group of patients who received pioglitazone (19 cases per 12506 patients, 0.15%), compared with the control group (7 cases per 10212 patients, 0.07%). Risk factors for developing bladder cancer (old age, smoking, the use of a number of medicinal or chemotherapeutic agents, such as cyclophosphamide, or previous radiation therapy for the pelvic organs) should be evaluated before the use of pioglitazone.
Patients with macrogematria should be examined before applying pioglitazone.
It should be recommended to the patient to immediately consult a doctor if, during the use of pioglitazone, he developed a hematuria, or symptoms such as dysuria, pain in the lumbar region or in the abdominal cavity,or other urgent conditions on the part of the urinary system.
Effect on the organ of vision
Pioglitazone can cause or aggravate edema of the macula, which can lead to a decrease in visual acuity.
Influence on the musculoskeletal system Pioglitazone can increase the incidence of fractures in women.

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

Form release / dosage:Tablets 15 mg, 30 mg and 45 mg.

Packaging:For 10 tablets in a planar cell package.
3 or 6 contour squares with instructions for use in a pack of cardboard.

Storage conditions:In a dry, the dark place at a temperature of no higher than 25 ° C.
Keep out of the reach of children.

Shelf life:2 years. Do not use after the expiration date.

Terms of leave from pharmacies:On prescription

Registration number:LSR-006280/09

Date of registration:10.08.2009

Date of cancellation:2016-10-14

The owner of the registration certificate:AKRIKHIN HFK, JSC AKRIKHIN HFK, JSC Russia

Manufacturer: & nbsp

AKRIKHIN HFK, JSC Russia

Information update date: & nbsp14.10.2016

Illustrated instructions

Instructions

Diaglitazone® (Diaglitazon®)