Piouno

General characteristics. Structure:

Active ingredient: 16,54 mg, 33,07 mg or 49,61 mgpioglitazon of a hydrochloride that 15 mg, 30 mg or 45 mg of a pioglitazon are equivalent.

Excipients: lactoses monohydrate, a hypro rod, a karmelloza, silicon dioxide colloid, magnesium stearate, the water purified.

Pharmacological properties:

Pharmacodynamics. Hypoglycemic means of a tiazolidindionovy row for oral administration.

Pioglitazon stimulates the specific gamma receptors of a kernel activated by a peroksisomny proliferator (PPARg). Modulates a transcription of the genes sensitive to insulin and participating in control of concentration of glucose in blood and metabolism of lipids in fatty, muscular fabrics and a liver.

Unlike the drugs derivative of sulphonylurea, пиоглитазон does not stimulate insulin secretion, however shows activity only at kept insulin - synthetic function of a pancreas.

Pioglitazon reduces insulin resistance of peripheral fabrics and a liver, increases a consumption of insulin-dependent glucose and reduces emission of glucose from a liver; reduces concentration of glucose, insulin and glikozilirovanny hemoglobin. Against the background of therapy pioglitazony concentration of triglycerides and free fatty acids in a blood plasma decreases, and also concentration of lipoproteins of high density increases.

For patients with a diabetes mellitus 2 types improve control of concentration of glucose in blood as on an empty stomach, and after meal.

Pharmacokinetics. Absorption. Pioglitazon is quickly soaked up, the maximum concentration of a pioglitazon in a blood plasma is reached usually in 2 hours after intake. In the range of therapeutic doses of concentration in a blood plasma in proportion increase with increase in a dose. Equilibrium concentration is reached in 4-7 days after the beginning of therapy. At multiple dose of cumulation of a pioglitazon and its metabolites does not occur. Meal does not influence absorption. Bioavailability makes over 80%.

Distribution. The volume of distribution makes 0,25 l/kg of body weight. Communication with proteins of plasma of a pioglitazon makes more than 99%, its metabolites – more than 98%.

Metabolism. Pioglitazon is exposed to metabolism by a hydroxylation and oxidation. Preferential this process happens with the participation of isoenzymes of P450 cytochrome (CYP2C8 and CYP3A4), and also, in a little smaller degree, other isoenzymes. 3 of 6 identified metabolites (M) show pharmacological activity (M-II, M-III, M-IV). Taking into account pharmacological activity, concentration and extent of linkng with proteins of plasma, пиоглитазон and a metabolite of M-III equally cause the general activity, the contribution of a metabolite of M-IV to the general activity of drug approximately by 3 times exceeds a contribution of a pioglitazon, and relative activity of a metabolite of M-II is minimum.

Results of the researches In vitro showed what пиоглитазон does not inhibit isoenzymes of CYP1A, CYP2C8/9, CYP3A4.

Removal. It is removed preferential through intestines, and also kidneys (15-30%) in the form of metabolites and their conjugates. The elimination half-life of not changed pioglitazon from a blood plasma averages 3-7 hours, and for all active metabolites 16–24 hours.

Concentration of a pioglitazon and active metabolites in a blood plasma remains at rather high level within 24 hours after single introduction of a daily dose.

And/or at a renal failure of correction of doses it is not required to patients of advanced age.

Against the background of an abnormal liver function the fraction of a free pioglitazon is higher.

Indications to use:

Diabetes mellitus 2 types. In monotherapy:

• at patients with excess body weight at inefficiency is a diet and physical exercises at intolerance of Metforminum or existence of contraindications to its use.

 As a part of a combination therapy:

• with Metforminum at patients with excess body weight in the absence of adequate glycemic control against the background of monotherapy by Metforminum;
• with sulphonylurea derivatives only at patients to whom Metforminum, in the absence of adequate glycemic control against the background of monotherapy by sulphonylurea derivatives is contraindicated.
• with insulin in the absence of adequate glycemic control against the background of therapy by insulin at patients to whom Metforminum is contraindicated.

Route of administration and doses:

In 1 times a day irrespective of meal. The recommended initial doses make 15 or 30 mg of 1 times a day. The maximum daily dose at monotherapy – 45 mg, at a combination therapy – 30 mg.

At purpose of a pioglitazon in a combination with Metforminum, reception of Metforminum can be continued in the same dose.

In a combination with sulphonylurea derivatives: in an initiation of treatment their reception can be continued in the same dose. In case of development of a hypoglycemia, the dose derivative sulphonylurea is recommended to be reduced.

In a combination with insulin: the initial dose of a pioglitazon – 15-30 mg/days, a dose of insulin remains former or decreases by 10-25% at emergence of a hypoglycemia.

For elderly patients of dose adjustment it is not required.

Patients with a renal failure. For patients with a renal failure (clearance of creatinine more than 4 ml/min.) dose adjustment is not required. About use of a pioglitazon for the patients receiving treatment by a hemodialysis this is not present. Therefore, it is not necessary to apply пиоглитазон at this group of patients.

Patients with an abnormal liver function. It is not necessary to apply пиоглитазон at patients with an abnormal liver function.

Children and teenagers. There are no data on use of a pioglitazon for patients aged up to 18 years therefore use of a pioglitazon for the specified age group is not recommended.

Features of use:

Use at pregnancy and during breastfeeding. Efficiency and safety of a pioglitazon at pregnant women was not studied therefore it is contraindicated to use drug during pregnancy. It was proved what пиоглитазон slows down growth of a fruit. It is unknown whether it is removed пиоглитазон with breast milk therefore drug should not be accepted to women during breastfeeding. In need of purpose of drug during breastfeeding, breastfeeding should be stopped.

When performing therapy of a diabetes mellitus 2 types in addition to reception of a pioglitazon are recommended to adhere to a diet and to carry out physical exercises for maintenance of efficiency of medicinal therapy, and also in connection with possible increase in body weight.

Against the background of use of a pioglitazon the delay of liquid and increase in volume of plasma is possible that it can lead to development or aggravation of a course of heart failure, therefore, at an aggravation of symptoms of cardiovascular system it is necessary to stop reception of a pioglitazon.

Patients who have at least 1 risk factor of development of the chronic heart failure (CHF) should begin treatment with the minimum dose and gradually to raise it. It is necessary to reveal timely initial symptoms of HSN, increase in body weight (can confirm development of HSN) or development of hypostases, especially at patients with reduced cordial emission. In case of development of HSN drug is immediately cancelled.

Pioglitazon can cause an abnormal liver function. Prior to treatment and periodically during therapy it is necessary to investigate activity of "hepatic" enzymes. If activity of an alaninaminotrasferaza (ALT) exceeds by 2.5 times the upper bound of norm, or in the presence of other symptoms of a liver failure, use of a pioglitazon is contraindicated. If at 2 consecutive researches activity of ALT exceeds the upper bound of norm by 3 times or at the patient jaundice, treatment pioglitazony immediately develops stop. If the patient has symptoms assuming an abnormal liver function (inexplicable nausea, vomiting, abdominal pain, weakness, anorexia, urine darkening) it is necessary to investigate activity of "pechenochna" of enzymes immediately.

Pioglitazon can cause decrease in hemoglobin or a hematocrit by 4% and 4.1% respectively that can be a consequence of hemodilution (because of a liquid delay).

Pioglitazon increases sensitivity of fabrics to insulin that increases risk of development of a hypoglycemia in the patients receiving the combination therapy containing derivatives of sulphonylurea or insulin. The dose decline of the last can demand.

Pioglitazon can cause or aggravate makula hypostasis that can lead to decrease in visual acuity.

Pioglitazon can increase the frequency of changes at women.

At patients with a syndrome of polycystic ovaries increase in sensitivity to insulin can lead to resuming of an ovulation and possible pregnancy. To patients with a syndrome of polycystic ovaries, not persons interested to become pregnant, it is necessary to use reliable methods of contraception. At pregnancy emergence treatment should be stopped immediately.

Influence on ability to manage motor transport and mechanisms. Considering side effects of drug it is necessary to be careful during the driving of motor transport and work with the mechanisms demanding concentration of attention.

Side effects:

Frequency: very often - more than 1/10, it is frequent - more than 1/100 and less than 1/10, infrequently - more than 1/1000 and less than 1/100, is rare - more than 1/10000 and less than 1/1000, is very rare - less than 1/10000, including separate messages.

Monotherapy pioglitazony:

From sense bodys: often - a vision disorder.

From respiratory system: often - upper respiratory tract infections; infrequently - sinusitis.

From a metabolism: often - increase in body weight.

From a nervous system: often - a hypesthesia; infrequently - sleeplessness.

Combination of a pioglitazon with Metforminum:

From bodies of a hemopoiesis: often - anemia.

From sense bodys: often - a vision disorder.

From the alimentary system: infrequently - a meteorism.

From a metabolism: often - increase in body weight.

From a musculoskeletal system: often - an arthralgia.

From a nervous system: often - a headache.

From urinogenital system: often - a hamaturia, erectile dysfunction.

Combination of a pioglitazon with sulphonylurea derivatives:

From sense bodys: infrequently - вертиго, a vision disorder.

From the alimentary system: often - a meteorism.

Others: infrequently - fatigue.

From a metabolism: often - increase in body weight; infrequently - increase in activity of a lactate dehydrogenase (LDG), increase in appetite, a hypoglycemia.

From a nervous system: often - dizziness; infrequently - a headache.

From urinogenital system: infrequently - a glucosuria, a proteinuria.

From integuments: infrequently - the increased sweating.

Combination of a pioglitazon with Metforminum and derivatives of sulphonylurea:

From a metabolism: very often - a hypoglycemia; often - increase in body weight, increase in activity of a kreatinfosfokinaza (KFK).

From a musculoskeletal system: often - an arthralgia.

Combination of a pioglitazon with insulin:

From a metabolism: often - a hypoglycemia.

From a musculoskeletal system: often - a dorsodynia, an arthralgia.

From respiratory system: often - short wind, bronchitis.

From cardiovascular system: often – heart failure.

Others: very often - hypostases.

Post-marketing experience:

From sense bodys: frequency is unknown - makula hypostasis, a fracture of bones.

At prolonged use of a pioglitazon over 1 year in 6-9% cases at patients hypostases, poorly or moderately expressed and usually not demanding therapy cancellations are observed.

Visual disturbances are shown preferential at the beginning of therapy and are connected with change of concentration of glucose in a blood plasma, as well as at reception of other hypoglycemic means.

Interaction with other medicines:

At use of a pioglitazon in a combination with other peroral hypoglycemic drugs development of a hypoglycemia is possible. In this case the dose decline of other peroral hypoglycemic drug can be required.

Against the background of the combined use of a pioglitazon with insulin development of heart failure is possible.

Pioglitazon does not influence pharmacokinetics and a pharmacodynamics of a glipizid, digoxin, warfarin, Metforminum.

Gemfibrozil increases AUC value (the areas under a curve "concentration time") a pioglitazona by 3 times. Rifampicin accelerates metabolism of a pioglitazon for 54%.

In vitro кетоконазол inhibits metabolism of a pioglitazon.

Contraindications:

• hypersensitivity to a pioglitazon or to other components of drug;
• diabetes mellitus of 1 type;
• diabetic ketoacidosis;
• heart failure, including in the anamnesis (the I-IV class on NYHA classification);
• a liver failure (increase in activity of "hepatic" enzymes is 2,5 times higher than the upper bound of norm);
• chronic renal failure (clearance of creatinine (CC) less than 4 ml/min.);
• deficit of lactase, lactose intolerance, glyukozo-galaktozny malabsorption;
• pregnancy, breastfeeding period;
• children's age up to 18 years (clinical trials of safety and efficiency of use of a pioglitazon for children were not carried out).

With care – an edematous syndrome, anemia.

Overdose:

The hypoglycemia at reception of a pioglitazon in a combination with derivatives of sulphonylurea and insulin is possible.

Treatment: symptomatic therapy.

Storage conditions:

To store in the dry, protected from light place at a temperature not above 25 °C. To store in the place, unavailable to children. A period of validity - 3 years. Not to use after expiry date.

Issue conditions:

According to the recipe

Packaging:

Tablets of 15 mg, 30 mg, 45 mg. On 15 tablets in the blister from PVC / aluminum foil. 2 blisters (on 15 tablets) together with the application instruction in a cardboard pack.