Pioglitazone Hydrochloride Tablets

Actos acts on the intracellular target site of the insulin binding site of the insulin receptor, reduces insulin resistance, inhibits glucose production in the liver, and improves glucose utilization in peripheral tissues to lower blood sugar. It is believed that it works by normalizing the intracellular insulin signaling mechanism that is involved in the main factor of insulin resistance. The improvement of glucose metabolism was confirmed by a double-blind controlled trial in patients with type 2 diabetes who took pioglitazone 30 mg once a day for 12 weeks alone, and confirmed that fasting blood sugar and HbAlc decreased, and 1,5-anhydroglucitol (1,5-AG) increased. In patients with type 2 diabetes who took diet and/or exercise therapy plus sulfonylurea drugs, a double-blind controlled trial was conducted, confirming that fasting blood sugar and HbAlc decreased, 1,5-anhydroglucitol (1,5-AG) increased, and blood insulin decreased. In patients with type 2 diabetes who were taking diet therapy and/or exercise therapy plus voglibose, a double-blind controlled trial was conducted in which Actos 30 mg was taken once a day for 16 consecutive weeks, and fasting blood glucose and HbAlc were confirmed to decrease. Pioglitazone reduced hyperglycemia and hyperinsulinemia in obese type 2 diabetes model animals with insulin resistance (KKAy mice, Wistar obese rats). In addition, pioglitazone had no effect on hyperglycemia in insulin-deficient type 1 diabetic rats (streptozotocin diabetic rats) and normal blood glucose in healthy rats (Sprague-Dawley rats). Improvement of glucose tolerance In Wistar obese rats and Zucker obese rats that have both insulin resistance and abnormal glucose tolerance, pioglitazone was given for 10-12 days. After fasting for 20 hours, it was confirmed by oral glucose that it could inhibit the increase in blood glucose and reduce excessive secretion of insulin. Improvement of insulin resistance In a clinical pharmacology study (glucose clamp method), pioglitazone 30 mg was administered once a day to patients with type 2 diabetes who were treated with diet therapy and/or exercise therapy alone or diet therapy and/or exercise therapy plus sulfonylureas, and it was confirmed that the glucose uptake rate of peripheral tissues and liver increased. Pioglitazone was administered to Wistar obese rats and Zucker obese rats with both insulin resistance and obese diabetes for 14 days, and insulin was administered after 20 hours of fasting. It was confirmed that the administration of insulin had an enhanced hypoglycemic effect. Pioglitazone increased glucose uptake in the glycogen fraction of the diaphragm and the total fat fraction of the peri-epididymal adipose tissue of obese diabetic KKAy mice when stimulated with insulin. In Wistar obese rats with obese diabetes, it inhibited the production of glucose in the liver and improved the utilization of glucose in peripheral tissues. Mechanism of action Increase the effect of insulin in peripheral tissues: Increase the effect of insulin on the soleus muscle of the hind limb of Wistar obese rats (glycogen synthesis and glycolysis promotion effect) (in vitro experiment). In addition, it increases the effect of insulin in free adipocytes in the perididymal adipose tissue of Wistar obese rats (promoting glucose oxidation and total lipid synthesis) (in vitro experiment). Enhances the effect of insulin in the liver: Promotes the activity of glucokinase in the liver of Wistar obese rats, reduces the activity of 6-phosphogluconase, and inhibits the production of sugar (in vivo experiment). Enhances the effect of strong insulin receptors: Restores the phosphorylation of insulin receptors and insulin receptor substrates that have been reduced in the skeletal muscle of Wistar obese rats to normal, and promotes the activity of phosphatidylinositol-3-kinase (in vivo experiment). Inhibitory effect on TNF-alpha; production: Inhibits the production of TNF-alpha; in the skeletal muscle of Wistar obese rats and reduces hyperglycemia (in vivo experiment). Clinical trial results Various clinical trials including double-blind controlled trials were conducted on patients with type 2 diabetes who took pioglitazone 15mg, 30mg or 45mg once a day. Among 821 subjects, the comprehensive blood sugar improvement rate ([moderate improvement] or above moderate) was 50.8% (417/821). In long-term trials (taking for 28-48 weeks or more), blood sugar was stably controlled, fasting blood sugar and HbAlc were maintained, and no weakening of the treatment effect was observed. The following are the results of double-blind controlled trials in patients with type 2 diabetes who had unsatisfactory blood sugar control. Diet therapy and/or exercise therapy alone: In a double-blind controlled trial, pioglitazone was used 30 mg once a day for 12 consecutive weeks, and HbAlc decreased by 1.08 plus mn; 1.47% (mean plus mn; standard deviation of 63 patients). Diet therapy and/or exercise therapy plus sulfonylurea drugs: In a double-blind controlled trial, pioglitazone was used 30 mg once a day for 12 consecutive weeks, and HbAlc decreased by 1.24 plus mn; 1.33% (mean plus mn; standard deviation of 56 patients). Diet therapy and/or exercise therapy plus alpha-glucosidase inhibitors: In a double-blind controlled trial, pioglitazone, 30 mg once a day, for 16 consecutive weeks, reduced HbAlc by 0.91 plus mn; 0.89% (mean plus mn; standard deviation of 55 patients).

The main ingredient of this product is pioglitazone hydrochloride, and its chemical name is (plusmn;) 5-[4-[2-(5-ethyl-2-pyridyl)ethoxy]benzyl]-2,4-thiazolidinedione hydrochloride.

The 15 mg version of Actos is a white or light yellow tablet; the 30 mg version is a white or light yellow tablet with a notch.

Type 2 diabetes. Actos is only used for patients who have not received adequate responses to the following treatments and are presumed to have insulin resistance. Diet therapy and/or exercise therapy alone. Diet therapy and/or exercise therapy plus sulfonylurea drugs. Diet therapy and/or exercise therapy plus beta-glucosidase inhibitors. Note: Actos is only used for patients who have been clearly diagnosed with diabetes. Be careful of diseases other than diabetes such as impaired glucose tolerance, positive urine glucose, and other diabetes-like symptoms (renal diabetes, impaired glucose tolerance in the elderly, thyroid dysfunction, etc.).

Generally, adults take 15-30 mg of pioglitazone orally once a day before or after breakfast. In addition, it can be adjusted appropriately according to the patient's gender, age and symptoms, but the maximum limit is 45 mg. Note: Edema is more common in women. Therefore, when women take the drug, they should pay attention to whether edema occurs. They can start with 15 mg once a day. After increasing from 30 mg once a day to 45 mg, it can be seen that cases of edema are more common, so when increasing to 45 mg, pay attention to whether edema occurs. Elderly people usually have reduced physiological functions, so it is appropriate to start taking the drug with 15 mg once a day.

In clinical trials conducted up to the time of approval in Japan, adverse reactions including abnormal clinical test values occurred in 311 patients (25.4%) out of 1,225 patients who took pioglitazone 15 mg, 30 mg, or 45 mg once daily. The following adverse reactions of Actos have occurred in the above clinical trials and spontaneous reports. Clinically significant adverse reactions should be closely observed during the use of Actos because heart failure may occur or worsen. If edema, sudden weight gain, and symptoms of heart failure occur, the drug should be discontinued and appropriate measures such as loop diuretics should be given. Patients with heart disease may develop heart failure after taking Actos and should be closely monitored. Edema may occur due to an increase in circulating plasma volume (7.6%, 93/1,125 cases)

Patients with heart failure or a history of heart failure (In animal studies, compensatory changes may occur with increased circulating plasma volume, causing increased heart weight. There are clinical cases reported with the onset or worsening of heart failure). Patients with severe ketosis, diabetic coma or pre-coma, or type 1 diabetes. (Hyperglycemia must be corrected rapidly with intravenous fluids and insulin.) Patients with severe liver dysfunction. (Actos is primarily metabolized in the liver and may cause accumulation.) Patients with severe renal dysfunction. Patients with severe infections, before and after surgery, or severe trauma. (Insulin injections are necessary to control blood sugar, so Actos is not suitable.) Patients with a history of allergy to the ingredients of Actos. Pregnant women or women who may become pregnant.

Precautions for children: It is still unclear whether pioglitazone hydrochloride is safe and effective for children. Precautions for pregnancy and lactation: Pregnant women: Pregnancy type C. During organogenesis, rats were given 80 mg/kg orally and rabbits were given 160 mg/kg orally (based on mg/m2, approximately 17 times and 40 times the maximum recommended oral dose for humans, respectively), and no teratogenicity was observed with pioglitazone. When rats were given oral doses of more than 30 mg/kg/day (based on mg/m2, approximately equivalent to 10 times the maximum recommended oral dose for humans), delayed labor and embryotoxicity (manifested as increased post-implantation abortions, delayed development, and decreased birth weight) were observed. No functional or behavioral toxicity was observed in the offspring of rats. Embryotoxicity was observed when rabbits were given oral doses of 160 mg/kg (based on mg/m2, approximately equivalent to 40 times the maximum recommended oral dose for humans). When rats were given oral doses of 10 mg/kg and above (approximately 2 times the maximum recommended oral dose for humans, based on mg/m2) during late pregnancy and lactation, their offspring had reduced body weight and postnatal growth retardation. In women, there are no adequate and well-controlled studies, and pioglitazone hydrochloride should be used during pregnancy only when the potential benefits to the fetus outweigh the potential risks. Because the available data strongly suggest that dysglycemia during pregnancy is associated with increased congenital anomalies and neonatal morbidity and mortality, most experts recommend that insulin be used during pregnancy to try to control blood sugar to normal levels. Lactating mothers: In lactating rats, pioglitazone is secreted into breast milk. It is not clear whether humans can secrete pioglitazone hydrochloride into human milk. Because many drugs are secreted into breast milk, women who are breastfeeding should not use pioglitazone hydrochloride. Elderly precautions: In placebo-controlled clinical trials of pioglitazone hydrochloride, approximately 500 patients were aged 65 years and older. There was no significant difference in the efficacy and safety of pioglitazone hydrochloride between these patients and younger patients.

Be cautious when used in combination with other hypoglycemic drugs: sulfonylureas (glibenclamide, gliclazide, tolbutamide, etc.); sulfonamides (gliptinazole); biguanides (metformin hydrochloride, buformin hydrochloride); nateglinide; alpha-glucosidase inhibitors (voglibose, acarbose); insulin preparations. There are reports of hypoglycemia when Actos is used in combination with sulfonylureas and biguanides. Since there is a possibility of co-use with other hypoglycemic drugs, when used in combination with the above-mentioned drugs, the drug should be administered with caution, for example, the starting dose should be low, and the possibility of hypoglycemia should be considered. When hypoglycemia occurs when it is used in combination with alpha-glucosidase inhibitors, sucrose should not be given but glucose should be given.

Keep away from light and store in sealed container.

15 mg (based on pioglitazone)

36 months.