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

Composition:1 tablet contains:
Tablets 15 mg
Active substance: pioglitazone hydrochloride 16.53 mg, equivalent to pioglitazone 15 mg.
Excipients: lactose - 96.27 mg, hydroxypropylcellulose
(low viscosity) - 2.4 mg, calcium carboxymethylcellulose - 3.6 mg, magnesium stearate - 1.2 mg, purified water - q.s.
Tablets 30 mg
Active substance: pioglitazone hydrochloride 33.07 mg, equivalent to pioglitazone 30 mg.
Excipients: lactose 79.73 mg, hydroxypropylcellulose
(low viscosity) - 2.4 mg, calcium carboxymethylcellulose - 3.6 mg, magnesium stearate - 1.2 mg, purified water - q.s.

Description:Tablets 15 mg: white to almost white, round biconvex tablets with engraving "15" on one side.

Tablets 30 mg: white to almost white color round flat tablets with a facet and an engraving "30" on one side.

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 into 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 liver metabolism - CYP2C8 and CYP3A4, are metabolized 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 derivatives of sulfonylureas, metformin or insulin in those cases,when diet, exercise and the appointment of monotherapy with one of the above-mentioned hypoglycemic agents do not allow to achieve adequate glycemic control).

Contraindications:- Hypersensitivity to the drug;
- Type 1 diabetes mellitus, diabetic ketoacidosis;
- Cardiac insufficiency 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 the norm);
- bladder cancer (at present or in the anamnesis);
- macrogematuria of unclear etiology;
- pregnancy, the period of breastfeeding;
- Children under 18 years of age (clinical safety studies and
effectiveness of pioglitazone in children was not performed);
- Galactose intolerance, lactase deficiency or glucose-galactose malabsorption.

Carefully:Edema syndrome, anemia, heart failure, impaired liver function. 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, hypostension, 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 ALA and creatine phosphokinase; decrease in hemoglobin concentration, decrease in hematocrit.
From the musculoskeletal system: arthralgia, myalgia. Benign or malignant tumors: bladder cancer.
With long-term use of pioglitazone, more than 1 year, in 6-9% of cases, patients may develop edema, mild to moderate and
usually not requiring withdrawal of therapy.
Visual disturbances appear primarily at the beginning of therapy and are associated with a change in the concentration of glucose in the blood plasma, as well as when taking 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 concentration, a decrease in hematocrit, is possible.
* Signs of the development of bladder cancer, which, if they occur, the patient should immediately notify the attending physician - hematuria, frequent urination, pain when urinating, pain in the lumbar region or in the abdominal cavity.

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 a risk of developing hypoglycemic conditions. In this case, it may be necessary to reduce the dose of jointly used hypoglycemic drugs.
Elderly
Depending on the age, elderly patients at risk of developing bladder cancer, fractures, or heart failure should evaluate the need for pioglitazone therapy (before or during treatment).
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 means are not used
contraception. 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
In preclinical studies, thiazolidinediones, including pioglitazone, caused an increase in the volume of plasma and the development of cardiac muscle hypertrophy (due to preload). In clinical studies, of which patients with grade 3 and 4 heart failure (NYHA) were excluded, there was no increase in the incidence of serious cardiovascular side effects potentially associated with increased plasma volume (eg, chronic heart failure).
Effects on the liver
It is recommended during the therapy with pioglitazone to regularly monitor the concentration of hepatic enzymes in the blood. The content of alanine transferase (ALT) 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 taking the drug. Liver function in patients with symptoms suspected of liver failure (nausea, vomiting, abdominal pain, weakness, anorexia, dark urine) should also be performed.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 baseline slight increase in ALT (1-2.5 times the norm) or at any time during 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 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 has been an increase in 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.
Risk of developing bladder cancer
In controlled clinical trials, bladder cancer cases were more often reported in the test group of patients (19 cases per 12506 patients, 0.15%) than in the control group of patients (7 cases per 10212 patients, 0.07%).
After patients who participated in the study for less than one year from the diagnosis of bladder cancer were excluded from the study, 7 cases (0.06%) in the test group of patients and 2 cases (0.02%) in the control group group of patients. There are also epidemiological data suggesting an increased risk of developing bladder cancer in diabetic patients taking high daily doses of pioglitazone over a long period of time. However, these data do not exclude the risk of developing bladder cancer in the short-term treatment with pioglitazone.
The risk of developing bladder cancer includes such factors as old age, smoking (in the present or in the past of the patient),influence of some professional factors, chemotherapy (including cyclophosphamide), radiotherapy of pelvic organs. Macroscopic studies should be conducted to identify any macrohematuria before starting therapy with pioglitazone. The patient should immediately notify the treating physician of any symptoms of dysuria, in particular such as urination, pain during urination, back or abdominal pain, or any acute development of symptoms from the bladder and / or the urinary tract.

Effect on the ability to drive transp. cf. and fur:Given the side effects of pioglitazone, care must be taken when driving vehicles and working with other mechanisms that require increased concentration and speed
psychomotor reactions.

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

Packaging:10 tablets in a blister of aluminum foil and PVC / PVDH film.

1, 3 or 5 blisters together with instructions for use in a cardboard bundle.

Storage conditions:In a dry 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 printed on the package.

Terms of leave from pharmacies:On prescription

Registration number:LS-001671

Date of registration:16.07.2011

The owner of the registration certificate:Ranbaxy Laboratories LimitedRanbaxy Laboratories Limited India

Manufacturer: & nbsp

RANBAXY LABORATORIES, Ltd. India

Representation: & nbspRABBAYS LABORATORY LIMITEDRABBAYS LABORATORY LIMITED

Information update date: & nbsp26.11.2013

Illustrated instructions

Instructions

Pioglar (Pyoglar)