Pioglitazone Hydrochloride Dispersible Tablets

Pharmacological action: This product belongs to the class of thiazolidinediones oral antidiabetic drugs, and is a highly selective peroxisome proliferator-activated receptor γ (PPARγ) agonist, which controls blood sugar levels by increasing peripheral and liver insulin sensitivity. Its main mechanism of action is to activate PPARγ nuclear receptors in tissues such as fat, skeletal muscle and liver where insulin acts, thereby regulating the transcription of insulin-responsive genes and controlling the production, transport and utilization of blood sugar.

Chemical name: (±) 5-{4-[2-(5-ethyl-2-pyridyl)ethoxy]benzyl}-2,4-thiazolidinedione hydrochloride. Chemical structure: Molecular formula: C19H20N2O3S·HCl Molecular weight: 392.9

This product is white or off-white tablets

For patients with type 2 diabetes (non-insulin-dependent diabetes mellitus, NIDDM), pioglitazone hydrochloride can be combined with diet control and physical exercise to improve and control blood sugar. Pioglitazone hydrochloride can be used alone, or in combination with sulfonylurea, metformin or insulin when diet control, physical exercise and monotherapy cannot satisfactorily control blood sugar.

This product is a dispersible tablet. When used, add it to an appropriate amount of water, stir it evenly and disperse it before taking it. It can also be taken directly with water. Pioglitazone hydrochloride should be taken once a day, and the medication has nothing to do with eating. Diabetes treatment should be individualized. HbA1C is more ideal for evaluating treatment response. Compared with FB grams alone, it is a better indicator for evaluating long-term blood sugar control. HbA1C reflects the blood sugar situation in the past 2 to 3 months. In clinical application, we recommend that unless blood sugar control deteriorates, the patient's pioglitazone hydrochloride treatment should be long enough (3 months) to evaluate the change in HbA1C. Monotherapy: When diet control and physical exercise alone are not enough to control blood sugar, pioglitazone hydrochloride monotherapy can be used, and the initial dose can be 15 mg 30 mg once a day. If the response to the initial dose is not good, the dose can be increased to 45 mg once a day. If the patient does not respond well to monotherapy, combination therapy should be considered. Combination therapy: Sulfonylurea: When used in combination with sulfonylureas, the initial dose of pioglitazone hydrochloride can be 15 mg or 30 mg once a day. When starting pioglitazone hydrochloride treatment, the sulfonylurea dose can remain unchanged. When patients experience hypoglycemia, the sulfonylurea dose should be reduced. Metformin: When used in combination with metformin, the initial dose of pioglitazone hydrochloride can be 15 mg or 30 mg once a day. When starting pioglitazone hydrochloride treatment, the metformin dose can remain unchanged. Generally speaking, when used in combination with metformin, metformin does not need to be reduced in dose and will not cause hypoglycemia. Insulin: When used in combination with insulin, the initial dose of pioglitazone hydrochloride can be 15 mg or 30 mg once a day. When starting pioglitazone hydrochloride treatment, the insulin dose can remain unchanged. For patients taking pioglitazone hydrochloride and insulin in combination, when hypoglycemia occurs or the plasma glucose concentration drops below 100 mg/dL, the insulin dose can be reduced by 10% to 25%. Further individual adjustments are made based on blood glucose results. The maximum recommended dose of pioglitazone hydrochloride should not exceed 45 mg once a day, because no placebo-controlled clinical studies have been conducted for medications exceeding this dose. No placebo-controlled clinical studies have been conducted for combined medications with doses exceeding 30 mg. For patients with renal insufficiency, no dose adjustment is required (see [Pharmacokinetics], Special Populations, Renal Insufficiency). If patients have clinical manifestations of active liver disease or elevated serum aminotransferase levels (ALT exceeds 2.5 times the upper limit of normal) before treatment begins, pioglitazone hydrochloride treatment should not be started (see [Precautions], General, Effects on the Liver and [Pharmacokinetics], Special Populations, Hepatic Insufficiency). All patients should have liver enzymes monitored before starting pioglitazone hydrochloride treatment and during treatment (see [Precautions], General, Effects on the Liver). There is currently no data on the use of pioglitazone hydrochloride in patients under 18 years of age, so pioglitazone hydrochloride should not be used in pediatric patients. There are currently no data on the combined use of pioglitazone hydrochloride and other thiazolidinediones.

In clinical trials worldwide, more than 3,700 patients with type 2 diabetes were treated with pioglitazone hydrochloride. In clinical trials conducted in the United States, more than 2,500 patients were treated with pioglitazone hydrochloride, more than 1,100 patients were treated for 6 months or more, and more than 450 patients were treated for 1 year or more. Table 1 shows the overall incidence and type of adverse reactions in placebo-controlled clinical trials with pioglitazone hydrochloride monotherapy (doses of 7.5 mg, 15 mg, 30 mg, 45 mg, once a day). Table-1 Placebo-controlled Pioglitazone Hydrochloride Monotherapy Clinical Studies: Adverse Reactions Reported at 5% in Pioglitazone Hydrochloride-Treated Patients (Percentage of Patients) When pioglitazone hydrochloride was co-administered with sulfonylureas (N=373), metformin (N=168), or insulin (N=379), the types of clinical adverse reactions were similar to those of pioglitazone hydrochloride monotherapy, with the only exception of an increased incidence of edema when co-administered with insulin (pioglitazone: 15%, placebo: 7%). The incidence of withdrawal from clinical trials due to adverse reactions (except hyperglycemia) was similar in the placebo group (2.8%) and the pioglitazone hydrochloride group (3.3%). Mild to moderate hypoglycemia has occurred in patients when co-administered with sulfonylureas or insulin. When co-administered with a sulfonylurea, the incidence of hypoglycemia was 1% in the placebo group and 2% in the pioglitazone hydrochloride group. When used with insulin, the incidence of hypoglycemia was 5% in patients treated with placebo, 8% in patients treated with pioglitazone 15 mg, and 15% in patients treated with pioglitazone 30 mg (see Precautions, General, Hypoglycemia). In double-blind studies conducted in the United States, the incidence of anemia was 1.0% in patients treated with pioglitazone HCl as monotherapy and 0.0% in patients treated with placebo. When used with insulin, the incidence of anemia was 1.6% in patients treated with pioglitazone HCl and 1.6% in patients treated with placebo. When used with a sulfonylurea, the incidence of anemia was 0.3% in patients treated with pioglitazone HCl and 1.6% in patients treated with placebo, and when used with metformin, the incidence of anemia was 1.2% in patients treated with pioglitazone HCl and 0.0% in patients treated with placebo. All clinical trials conducted in the United States have shown that the incidence of edema is higher in patients treated with pioglitazone HCl than in patients treated with placebo. When treated as monotherapy, 4.8% of patients treated with pioglitazone HCl had edema compared with 1.2% of patients treated with placebo. The incidence of edema was highest when used in combination with insulin (15.3% in the pioglitazone hydrochloride group and 7.0% in the placebo group). All cases were only mild or moderate (see [Precautions], General, Edema). Laboratory Abnormalities Hematology: Pioglitazone hydrochloride may cause a decrease in hemoglobin and hematocrit. For all clinical studies, the mean hemoglobin level of patients treated with pioglitazone hydrochloride decreased by 2% to 4%. In general, such changes occurred in the first 4 to 12 weeks of treatment and were relatively stable thereafter. These changes may be related to the increase in plasma volume caused by pioglitazone hydrochloride, and no important clinical hematological significance has been found so far. Serum transaminase levels: In placebo-controlled clinical trials conducted in the United States, a total of 4 (0.26%) of 1526 pioglitazone hydrochloride-treated patients and 2 (0.25%) of 793 placebo-treated patients had ALT ≥ 3 times the upper limit of normal. In all clinical studies conducted in the United States, a total of 11 (0.43%) of 2561 patients treated with pioglitazone hydrochloride had ALT ≥ 3 times the upper limit of normal. All patients with follow-up values had reversible increases. In the group treated with pioglitazone hydrochloride, the mean values of bilirubin, AST, ALT, alkaline phosphatase, and GGT at the last visit were lower than the mean values at baseline. In the United States, less than 0.12% of patients withdrew from clinical trials due to abnormal liver function. In informed consent clinical trials, no constitution-specific drug reactions leading to liver failure were observed (see [Precautions], General, Effects on the Liver). CPK level: Sporadic, transient increases in creatine phosphokinase (CPK) levels have been observed during necessary laboratory tests in clinical trials. Seven patients had a single, isolated increase in CPK (more than 10 times the upper limit of normal, values of 2150 to 8610). Of the seven patients, five continued to receive pioglitazone hydrochloride treatment, and two had CPK increases after the end of the trial. These increases were all restored without obvious clinical sequelae. The relationship between this situation and treatment with pioglitazone hydrochloride has not yet been clarified. Macular edema: There have been reports from overseas after the market launch that taking thiazolidinediones, including pioglitazone, has caused or aggravated (diabetic) macular edema and decreased vision, but the frequency of occurrence is very rare. It has not yet been determined whether macular edema is directly related to taking pioglitazone. If a patient experiences decreased vision, the doctor should consider the possibility of macular edema. Diabetic patients should receive regular routine eye examinations by an ophthalmologist. In addition, regardless of whether diabetic patients are receiving treatment or have other physical examination abnormalities, they should be examined by an ophthalmologist promptly if any visual symptom occurs. Fractures: In a randomized clinical trial abroad on patients with type 2 diabetes (average disease duration 9-5 years), researchers noted an increased incidence of fractures in female patients taking pioglitazone. During a mean follow-up of 34.5 months, fractures occurred in 5.1% (44/870) of female patients treated with pioglitazone and only 2.5% (23/905) of patients treated with placebo. This difference was seen one year after the start of treatment and persisted throughout the study. Fractures in female patients were nonvertebral and included both lower extremity and distal upper extremity fractures. The fracture rate in male patients treated with pioglitazone was 1.7% (30/1735), which was not significantly increased compared to 2.1% (37/1728) in the placebo group. When caring for patients treated with pioglitazone, especially female patients, the risk of fracture should be considered and attention should be paid to assessing and maintaining bone health according to current standards of care.

Pioglitazone hydrochloride is contraindicated in patients who are allergic to this product or any of its ingredients.

Precautions for children: It is not yet clear whether pioglitazone hydrochloride is safe and effective for children. Precautions for pregnancy and lactation: 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. Post-term labor and embryotoxicity (manifested as increased post-implantation abortions, delayed development, and decreased birth weight) were observed in rats when they were given oral doses of 30 mg/kg/day and above (based on mg/m2, approximately equivalent to 10 times the maximum recommended oral dose for humans). No functional or behavioral toxicity was observed in the offspring of rats. Embryotoxicity was observed in rabbits when the oral dose reached 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. Pioglitazone hydrochloride should be used during pregnancy only if 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. In lactating mothers, pioglitazone is secreted into breast milk in lactating rats. It is not clear whether humans can secrete pioglitazone hydrochloride into breast milk. Because many drugs can be secreted into breast milk, pioglitazone hydrochloride should not be used in breastfeeding women. Elderly precautions: In placebo-controlled clinical trials of pioglitazone hydrochloride, approximately 500 patients were aged 65 years or older. There were no significant differences in the efficacy and safety of pioglitazone hydrochloride between these patients and younger patients.

Oral contraceptives: When another thiazolidinedione and an oral contraceptive containing ethinyl estradiol or norethindrone are used simultaneously, the plasma concentrations of both will decrease by approximately 30%, which may result in the loss of contraceptive effect. The pharmacokinetic evaluation of the simultaneous use of pioglitazone hydrochloride and oral contraceptives has not been conducted. Therefore, contraception should be more cautious for patients who use pioglitazone hydrochloride and oral contraceptives simultaneously. Glipizide: For healthy subjects, the simultaneous use of pioglitazone hydrochloride (45 mg once a day) and glipizide (5.0 mg once a day) for 7 days did not change the steady-state pharmacokinetic parameters of glipizide. Digoxin: For healthy subjects, the simultaneous use of pioglitazone hydrochloride (45 mg once a day) and digoxin (0.25 mg once a day) for 7 days did not change the steady-state pharmacokinetic parameters of digoxin. Warfarin: For healthy subjects, the simultaneous use of pioglitazone hydrochloride (45 mg once a day) and warfarin did not change the steady-state pharmacokinetic parameters of warfarin. Moreover, in patients receiving long-term warfarin therapy, the use of pioglitazone hydrochloride did not have a clinically significant effect on the prothrombin time. Metformin: For healthy subjects, the simultaneous administration of metformin (1000 mg) and pioglitazone hydrochloride (45 mg) after taking pioglitazone hydrochloride (45 mg) for 7 days did not change the single-dose pharmacokinetic parameters of metformin. The metabolism of pioglitazone requires the CYP3A4 isoform of cytochrome P450. Other drugs that require this enzyme for metabolism include: erythromycin, astemizole, calcium channel blockers, cisapride, adrenocortical hormones, cyclosporine, HMG-CoA reductase inhibitors, tacrolimus, triazolam, trimetrexate, etc. Drugs that inhibit this enzyme include: ketoconazole, itraconazole, etc. The interaction between pioglitazone hydrochloride and the above drugs has not been specifically and formally tested for pioglitazone hydrochloride. In vitro, ketoconazole significantly inhibits the metabolism of pioglitazone (see [Pharmacokinetics], Metabolism). Because more data need to be collected, patients taking ketoconazole and pioglitazone hydrochloride at the same time should have their blood sugar control evaluated more frequently.

Protect from light, store in a cool (not exceeding 20℃) and dry place.

15mg (as pioglitazone)

24 months

Shaanxi Ziguang Chenji Pharmaceutical Co., Ltd.

• Founded in:

  1997-12-23

• Address:

  No. 78, Zhongshan West Road, Jintai District, Baoji City, Shaanxi Province

• Tax NO.:

  916103032213043745

• Registered Funds:

  80.073 million yuan

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