What Is Pioglitazone Hydrochloride?

Pioglitazone Hydrochloride Tablets, Type 2 Diabetes This product is only used in patients receiving the following therapies without sufficient results, it is presumed to be insulin resistant patients. 1 1) Use diet therapy and / or exercise therapy only 2) Use diet therapy and / or exercise therapy with sulfonylureas 3) Use diet therapy and / or exercise therapy with alpha-glucosidase inhibitor 4) Use diet therapy and / or Exercise therapy plus biguanides 2 Use diet therapy and / or exercise therapy plus insulin preparations <Notes on indications> This product is only for patients who have been diagnosed with diabetes. In addition to diabetes, there must be diabetic-like symptoms such as impaired glucose tolerance and urine glucose positive (nephrotic diabetes, senile glucose intolerance, and thyroid dysfunction).

Pioglitazone Hydrochloride Tablets, Type 2 Diabetes This product is only used in patients receiving the following therapies without sufficient results, it is presumed to be insulin resistant patients. 1 1) Use diet therapy and / or exercise therapy only 2) Use diet therapy and / or exercise therapy with sulfonylureas 3) Use diet therapy and / or exercise therapy with alpha-glucosidase inhibitor 4) Use diet therapy and / or Exercise therapy plus biguanides 2 Use diet therapy and / or exercise therapy plus insulin preparations <Notes on indications> This product is only for patients who have been diagnosed with diabetes. In addition to diabetes, there must be diabetic-like symptoms such as impaired glucose tolerance and urine glucose positive (nephrotic diabetes, senile glucose intolerance, and thyroid dysfunction).

Drug Name

Pioglitazone hydrochloride tablets

Drug type

Prescription drugs, medicines for medical workers' injuries

Use classification

Hypoglycemic agents

Warnings for pioglitazone hydrochloride tablets

Warning: Congestive heart failure thiazolidinediones, including pioglitazone, are at risk of causing or exacerbating congestive heart failure in some patients (see [Precautions]). When starting this product and increasing the dosage, the symptoms and signs of heart failure (including abnormal rapid weight gain, dyspnea and / or edema) should be closely monitored. If the above symptoms and signs appear, they should be treated according to the standard heart failure treatment plan, and the application of this product must be stopped or the dose should be reduced.
Heart failure patients are prohibited to use this product (see [Contraindications] and [Cautions])

Pioglitazone hydrochloride tablets ingredients

The main ingredient of this product is pioglitazone hydrochloride. Its chemical name is (±) -5- [4- [2- (5-ethyl-2-pyridyl) ethoxy] -benzyl] thiazolidine-2,4. -Dione monohydrochloride structure:

Molecular formula: C ₁₉ H ₂₀ N ₂ 0 ₃ S · HCl
Molecular weight: 392.90

Properties of Pioglitazone Hydrochloride Tablets

This product is a white or light yellow sheet with a score.

Indications of pioglitazone hydrochloride tablets

Type 2 diabetes This product is only used in patients who have received the following treatments without sufficient results and are presumed to be insulin resistant.
1 1) Use diet therapy and / or exercise therapy only 2) Use diet therapy and / or exercise therapy with sulfonylureas 3) Use diet therapy and / or exercise therapy with alpha-glucosidase inhibitor 4) Use diet therapy and / or Exercise therapy with biguanides 2 Use of diet therapy and / or exercise therapy with insulin preparations [Notes on indications]
This product is only used in patients with a clear diagnosis of diabetes. In addition to diabetes, there must be diabetic-like symptoms such as impaired glucose tolerance and urine glucose positive (nephrotic diabetes, senile glucose intolerance, and thyroid dysfunction).

Specifications of pioglitazone hydrochloride tablets

(1) 15mg; (2) 30mg (based on pioglitazone)

Dosage and dosage of pioglitazone hydrochloride tablets

1 The recommended usage for all patients is oral, once a day. The recommended starting dose for patients without congestive heart failure is 15 mg or 30 mg once a day. The recommended starting dose for patients with congestive heart failure (NYHA classification I and II) is 15 mg once a day. According to the change of blood glucose detected by HbAlc, the daily dosage of patients can be gradually increased from 15mg once to the maximum dose of 45mg once.
2 Combined with insulin secretion enhancer or insulin If the patient develops hypoglycemia when this product is combined with insulin secretion enhancer (such as sulfonylureas), the dose of insulin secretion enhancer should be reduced. If the patient has symptoms of hypoglycemia when this product is combined with insulin, the insulin dosage should be reduced by 10% -25%, and the insulin dosage should be further adjusted according to the patient's individual blood glucose response.
[Notes on usage and dosage]
1. It is reported that female patients have a higher chance of edema. Therefore, when female patients take the drug, the initial dose is 15 mg once a day, and it should be observed whether edema occurs.
2. From 30mg to 45mg once a day, patients have been reported to have a higher probability of edema. Therefore, when the amount is increased to 45mg, care should be taken to observe whether edema occurs.
3. When this product is used in combination with insulin preparations, it has been reported that patients are more likely to develop edema, so it is advisable to start taking the drug at 15 mg once a day. Increasing the dose requires caution and careful observation of edema and signs and symptoms of heart failure.
4. Usually elderly patients have reduced physiological function, so it is advisable to start taking medicine at 15 mg once a day.

Adverse reactions of pioglitazone hydrochloride tablets

According to the results of clinical trials conducted in Japan, among 1,368 patients taking pioglitazone 15 mg, 30 mg, or 45 mg once a day, 364 patients (26.6%) had adverse reactions including abnormal laboratory test values. This product has a higher chance of edema in female patients and when combined with insulin [The proportion of edema that occurs when this product is used alone and in combination with other hypoglycemic agents other than insulin: male 3.9% (26/665), 11.2% (72/643) of women, the proportion of edema occurred when combined with insulin: male: 13.6% (3/22), female 28.9% (11/38)]. And compared with patients without diabetic complications, patients with diabetic complications were more likely to develop edema [the proportions of patients with retinopathy, diabetic neuropathy, and diabetic nephropathy were edema: 10.4% (44/422), 11.4% (39/342), 10.6% (30/282)]. In addition, the incidence of hypoglycemia increased when combined with insulin [The proportion of edema that occurred when this product was used alone and when combined with other hypoglycemic agents other than insulin and when combined with insulin was 0.7% (9 / 1308), 33.3% (20/60)] The monitoring results (as of December 2009) after taking the market show that 556 (16.3%) of 3,421 patients had adverse reactions (including abnormal laboratory test values) ). The following adverse reactions of this product appeared in the above clinical trials, post-marketing monitoring results or spontaneous reports.
(1) Clinically significant adverse reactions 1) Because heart failure may occur or worsen, close observation should be performed during taking this product. If there are symptoms / signs such as edema, sudden weight gain, and heart failure (shortness of breath, palpitations, increased heart-to-thoracic ratio, pleural effusion, etc.), the drug should be discontinued and appropriate measures such as myelin diuretics should be given. Patients with concomitant heart disease are more likely to cause heart failure when taking this product or in combination with insulin. Therefore, patients should be closely monitored for signs of heart failure (refer to [careful use of drugs] and [important precautions]).
2) Since the increase in circulating plasma volume may cause edema (8.2%, 112/1368 cases), it should be closely observed. When edema occurs, take appropriate measures such as reducing the dose or stopping medication. If the symptoms do not improve after taking these measures, consider the administration of myelin diuretics (furosemide, etc.) if necessary. Edema is more common in female patients, patients who are coadministered with insulin, or patients with complications of diabetes. In addition, edema has also been reported when the dose was increased from 30 mg to 45 mg once a day. For such patients, special attention should be paid to the occurrence of edema (see [Notes on usage and dosage]).
3) Hepatic dysfunction or jaundice (<0.1%) may be accompanied by significantly increased aspartate aminotransferase (AST), alanine aminotransferase (ALT) and alkaline phosphatase (ALP). Therefore, for patients with potential liver dysfunction, regular liver function tests should be performed if necessary. If abnormalities occur, take appropriate measures such as stopping medication.
4) When combined with other hypoglycemic agents, hypoglycemia symptoms (<0.1 ~ 5%) sometimes occur. When hypoglycemia occurs, the product or a combination of hypoglycemic drugs should be treated with caution such as reducing the dose or suspending medication. When taking this product, symptoms of hypoglycemia are usually given sucrose, but when symptoms of hypoglycemia occur when combined with -glucosidase inhibitors, glucose should be given. When combined with insulin, the incidence of hypoglycemia is higher.
5) Some features of rhabdomyolysis that may occur (with unknown frequency), such as muscle pain, weakness, increased phosphocreatine kinase (CK (CPK)), and increased myoglobin in blood and urine. Once this happens, medication should be stopped and appropriate measures taken.
6) There have been reports of recurrence of gastric ulcers.
(2) Other adverse reactions

In randomized, double-blind, controlled clinical trials of ACTOS conducted abroad, more than 8,500 patients with type 2 diabetes have received this product. Among the prospective clinical studies (the Prospective Pioglitazone Clinical Trialin Macrovascular Events, PROactive), 2605 patients with type 2 diabetes and macrovascular disease received this product. In these clinical trials, more than 6000 patients received this product for 6 months or more, 4500 patients received this product for 1 year or more, and 3,000 patients received This product should be treated for at least 2 years.
In six 16- to 26-week placebo-controlled monotherapy trials and 16- to 24-week combined-drug therapy trials, the incidence rate of patients withdrawing from the trial due to adverse drug events was 4.5%, and the incidence rate in the control group Is 5.8%. The incidence of adverse events that caused patients to withdraw from the trial (1.5%) in the treatment group of this product was lower than that in the placebo group (3.0%), and the most common adverse events that led to withdrawal from the trial were related to poor blood glucose control.
In the PROactive trial, the incidence of patients withdrawing from the trial due to adverse events was 9.0% and 7.7% in this product group and placebo group, respectively. Congestive heart failure is the most common serious adverse event that led patients to withdraw from the trial. The incidence of withdrawal from this trial in patients in this product group was 1.3%, while the incidence in the placebo group was 0.6%.
Common adverse events: 16 to 26 week monotherapy trials. Three 16 to 26 week placebo-controlled monotherapy clinical trials reported the incidence and type of common adverse events in Table 1. The table lists adverse events that occurred> 5% and were more common in this product group than in the placebo group. These adverse events have nothing to do with the dose of this product.

Common adverse events: 16 to 24 weeks of combined treatment trials. In clinical trials of the combination of this product with sulfonylureas, the reported rates and types of common adverse events are shown in Table 2. The table lists adverse events with a incidence of> 5% and more common in the highest dose group of this product.

An uncontrolled double-blind trial at 24 weeks, reporting adverse events with an incidence rate of> 5% and an incidence rate in the product 45mg + sulfonylurea group higher than the product 30mg + sulfonylurea group

Note: The terms peripheral edema, general pancreatic edema, dental edema and fluid retention are all summarized as edema.
In clinical trials of the combination of this product with sulfonylureas, the incidence and types of common adverse events reported are shown in Table 3. The table lists adverse events with a incidence of> 5% and more common in the highest dose group of this product.

Note: The terms peripheral edema, general pancreatic edema, dental edema and fluid retention are all summarized as edema.
In the clinical trials of this product combined with insulin, the incidence and types of common adverse events reported are shown in Table 4. The table lists adverse events that occur at> 5% and are more common at the highest doses of this product.

Note: The terms peripheral edema, general pancreatic edema, dental edema and fluid retention are all summarized as edema.
The common adverse events and types reported in the PROactive trial are shown in Table 5. The table lists adverse events that occurred> 5% and were more common in this product group than in the placebo group.

The average follow-up period was 34.5 months.
Congestive heart failure: Adverse events related to congestive heart failure occurred during clinical trials of 16 to 24 weeks with sulfonylurea drugs, 16 to 24 weeks with insulin clinical trials, and 16 to 24 weeks with metformin clinical trials The rate is shown in Table 6. No fatal adverse events occurred.

Patients with type 2 diabetes complicated by congestive heart failure (NYHA grade or early stage) were randomly divided into groups, taking this product or glibenclamide for 24 weeks according to the double-blind principle, of which the daily dose of this product was 30 mg To 45 mg (n = 262), while the daily dose of glibenclamide is 10 to 15 mg (n = 256). The incidence of adverse events related to congestive heart failure in this trial is summarized in Table 7.

Cardiovascular safety: In the PROactive trial, 5,238 patients with type 2 diabetes with a history of major vascular disease were randomly divided into groups and received standardized products (N = 2605) or placebo (N = 2633) based on standardized care. ) Treatment, where the daily dose in the treatment group of this product can be gradually increased to 45 mg by an incremental method. Almost all patients (95%) were taking cardiovascular drugs at the same time (eg, beta-blockers, ACE inhibitors, angiotensin 2 receptor antagonists, calcium channel blockers, nitrates, diuretics, Aspirin, statins, and clobate). At baseline, patients had an average age of 62 years, an average diabetes duration of 9.5 years, and an average HbAlc of 8.1%. The average follow-up time was 34.5 months.
The main purpose of this study was to investigate the effects of this product on the mortality and incidence of macrovascular events in patients with type 2 diabetes who are at high risk of major vascular events. The primary efficacy variable was the time of first occurrence of any event in the cardiovascular composite endpoint, which included all-cause death, nonfatal myocardial infarction (MI) (including resting myocardial infarction), stroke, acute coronary syndrome, Cardiac intervention (including coronary artery bypass surgery or percutaneous coronary intervention), major lower limb vascular cuts above the ankle, and bypass surgery or vascular reconstruction of the lower limbs. 514 patients (19.7%) in this product group and 572 patients (21.7%) in the placebo group had at least one adverse event (hazard ratio 0.90; 95% confidence interval: 0.80, 1.02: p = 0.10).
When the trial was conducted for 3 years, there was no statistically significant difference in the first occurrence of cardiovascular adverse events between this product group and the placebo group, but at the same time, mortality or overall macrovascular adverse events occurred in this product group. The rate has not increased. The incidence of first adverse events and the total number of adverse events associated with the primary trial endpoints are shown in Table 9.

CABG = Coronary Artery Bypass Grafting: PCI = Percutaneous Interventional Weight Gain: When this product is used alone or in combination with other hypoglycemic drugs, a dose-related weight gain will occur. The mechanism of weight gain is unknown, but it is likely related to the combined effect of fluid retention and fat accumulation.
Tables 10 and 11 summarize the weight changes in the randomized, double-blind, single-drug treatment trials from 16 to 26 weeks and the combination therapy with other drugs from 16 to 24 weeks, as well as the PROactiveivt test.

Note: The median duration of exposure to this product and placebo is 2.7 years.
Edema: Edema that occurs when taking this product will reversibly improve with discontinuation of this product. Edema usually does not require hospitalization unless congestive heart failure occurs at the same time. During the clinical study of this product, the frequency and type of edema are shown in Table 12.

Note: The terms peripheral edema, general pancreatic edema, dental edema and fluid retention are all summarized as edema.

Note: Peripheral edema, generalized edema, depression edema, and fluid retention are collectively summarized as "edema".
Liver function effects: To date, there is no evidence in the controlled clinical trial database of this product that this product induces liver toxicity. A specially designed, randomized, double-blind, three-year trial was used to compare the incidence of ALT elevation of serum ALT to three times the upper limit of normal for ACTOS and glipizide. The basic treatment at this time was metformin and insulin. Checked every 8 weeks for the first 48 weeks of the trial and then every 12 weeks. In this product group and glibenclamide group, 3/1051 (0.3%) patients and 9/1046 (0.9%) patients had ALT values greater than three times the normal reference upper limit, respectively. To date, in this controlled clinical trial data, none of the patients in this product group had serum ALT greater than three times the upper limit of the reference value or total bilirubin greater than twice the upper limit of the reference value, and no patient had severe drug induction Overlay of liver damage.
Hypoglycemia: In the clinical trials of this product, adverse events of hypoglycemia are reported by researchers based on clinical judgment results, and no peripheral blood glucose examination is required to confirm the diagnosis.
In the 16-week clinical trial of sulfonylurea combined with sulfonylureas, the reported incidence of hypoglycemia in the 30 mg group was 3.7% compared to 0.5% in the placebo group. In the 16-week clinical trial with insulin supplementation, the reported incidence of hypoglycemia in the 15 mg group was 7.9%, the 30 mg group was 15.4%, and the placebo group was 4.8%.
In the 24-week clinical trials with sulfonylurea drugs and the 24-week clinical trials with insulin drugs, the incidence of hypoglycemic events was higher in the 45 mg group than in the 30 mg group. In the two trials, (15.7% vs. 13.4%) and (47.8% vs. 43.5%).
Of these four trials, three patients in the 30 mg group of this product in a 24-week clinical trial with insulin combined with insulin were admitted to the hospital due to hypoglycemia (0.9%). An additional 14 patients reported severe hypoglycemia that did not require hospitalization (referring to a hypoglycemic event in which patients' daily activities were significantly affected). These patients received 45mg of this product combined with sulfonylurea drugs (n = 2) or 30mg of this product or 45mg of this product combined with insulin (n = 12).
Bladder tumors: In a two-year carcinogenicity study, tumors were found in the bladder of male rats. In two three-year clinical trials, 16/3656 (0.44%) of patients taking this product developed bladder cancer, and 5/3679 (0.14%) of patients who did not take this product developed bladder cancer. . After excluding bladder cancer patients who were diagnosed with bladder cancer less than one year after exposure to the test drug, 6 (0.16%) and 2 (0.05%) patients were diagnosed with bladder cancer in this product and placebo group, respectively. Because the number of bladder cancer adverse events is too small, it is impossible to determine the causal relationship between bladder cancer and this product.
Macular edema: There have been reports after foreign markets that taking thiazolidinediones including pioglitazone has caused or exacerbated (diabetic) macular edema with decreased vision, but the frequency is very rare. It is not clear whether macular edema is directly related to pioglitazone. If the patient has vision loss, the doctor should consider the possibility of macular edema. Patients with diabetes should receive regular eye examinations by an ophthalmologist. In addition, regardless of whether the diabetic is undergoing treatment or other physical examination abnormalities, as long as any of the visual symptoms appear, they should be promptly examined by an ophthalmologist.
Fractures: In a randomized clinical trial abroad of patients with type 2 diabetes (mean course of 9.5 years), researchers noticed an increase in the incidence of fractures in women taking pioglitazone. During an average follow-up of 34.5 months, the incidence of fractures in female patients in the pioglitazone group was 5.1% (44/870), compared with 2.5% (23/905) in the placebo group. This difference emerged one year after the start of treatment and persisted throughout the study. Fractures in female patients are non-vertebral fractures, including lower extremities and distal upper extremities. The incidence of fractures with pioglitazone in male patients was 1.7% (30/1735), which was not significantly increased compared to 2.1% (37/1728) in the placebo group. Patients treated with pioglitazone, especially female patients, should take into account the risk of fracture and pay attention to assessing and maintaining bone health in accordance with current standards of care.

Contraindications of pioglitazone hydrochloride tablets

(Disabled for patients described below)
Patients with heart failure or a history of heart failure [In animal studies, it is possible that modern compensatory changes with circulating plasma volume may cause cardiac weight gain. There are clinical cases reporting heart failure or worsening heart failure]
Severe ketosis, diabetic coma or pre-coma, or type 1 diabetes.
[Hyperglycemia must be corrected quickly with intravenous infusion and insulin. ]
Patients with severe liver dysfunction [This product is mainly metabolized in the liver and may cause accumulation. ]
Patients with severe renal dysfunction Patients with severe infections, before or after surgery, or patients with severe trauma [It is necessary to inject insulin to control blood sugar, so this product is not suitable for administration. ]
Patients with a history of allergies to the ingredients of this product Pregnant women or women who are likely to become pregnant (refer to [Pregnant women and lactating women] section).

Precautions for pioglitazone hydrochloride tablets

1. Use with caution (use with caution in the following patients)
(1) For the following patients or conditions:
1) Patients with heart disease, such as myocardial infarction, angina pectoris, cardiomyopathy, and hypertensive heart disease, may cause heart failure [with the increase of circulating plasma volume may induce heart failure]. (Reference and [adverse reactions])
2) Liver or kidney dysfunction (refer to [Contraindications])
3) Pituitary insufficiency or adrenal insufficiency [may cause hypoglycemia].
4) Malnutrition, hunger, irregular dietary intake, inadequate or debilitating dietary intake [possibly causing hypoglycemia].
5) Intense muscle movement [may cause hypoglycemia].
6) Excessive drinking [may cause hypoglycemia].
7) Elderly patients (refer to [Medication for elderly patients])
(2) Patients who are using other hypoglycemic drugs. (Refer to [Drug Interactions] and [Adverse Reactions])
2. Important Precautions (1) Because the increase of circulating plasma volume may cause edema, induce heart failure or exacerbation in a short period of time, you should pay attention to the following conditions (refer to [Contraindication] and [Careful Administration]).
(i) This product should not be used in patients with heart failure or a history of heart failure.
(ii) Close observation after taking this product. If symptoms such as edema, sudden weight gain, and heart failure occur, appropriate measures such as discontinuation of the drug should be taken, and diuretics (furosemide, etc.) should be given.
(iii) Patients should be instructed to pay attention to symptoms such as edema, sudden weight gain or change during taking this product. If you have any of the above symptoms, stop taking the medicine immediately and consult your doctor.
(2) It may cause abnormalities in ECG and increase in heart-to-thoracic ratio, so pay close attention to observation; check the ECG regularly, and when you find abnormalities, take careful treatment such as temporarily stopping medicine or reducing the dose. (Refer to [Adverse Reactions].)
(3) When this product is used in combination with other hypoglycemic agents, it may sometimes cause hypoglycemia symptoms. When combined with these drugs, the patient should fully explain the symptoms and treatment of hypoglycemia, and remind patients to pay attention to the symptoms of hypoglycemia. (Refer to [Drug Interactions] and [Adverse Reactions])
(4) This product is only suitable for patients who have not achieved sufficient results through basic therapies such as diet therapy and / or exercise therapy.
(5) This product is limited to patients with inferred insulin resistance. The rough judgment criterion for insulin resistance is body mass index (BMI kg / m2) greater than or equal to 24; or fasting whole blood insulin secretion level is greater than or equal to 5 mU / mL.
(6) Blood sugar and urine sugar should be checked regularly during taking this product to confirm its efficacy. If you have not achieved satisfactory results after taking 3 months, you should switch to other drugs in time.
(7) During the medication period, the following situations may occur: no longer need to continue the medication; the dose needs to be reduced; or the treatment effect is weakened or has no treatment effect due to the patient's incontinence or combined infection. Therefore, attention should be paid to dietary intake, changes in body weight, blood sugar, and presence of infection. Attention should be paid to making regular judgments on whether to continue medication, dosage and medication selection.
(8) It is known that diabetic retinopathy can be exacerbated by a rapid drop in blood glucose. It has been reported in cases using this product, so you should pay attention to this symptom.
(9) Little experience with concomitant use of biguanides.
(10) The safety of 45mg daily dose of this product combined with -glucosidase inhibitor has not been established (the clinical experience of drug use is very little).
(11) The safety of combining this product with an -glucosidase inhibitor and a sulfonylurea drug has not been established (the incidence of adverse reactions has been observed to increase in clinical trials).
3. Precautions during use When the drug is delivered to the patient: The drug in the aluminum-plastic blister package (PTP) should be instructed to take it out of the aluminum-plastic blister (PTP) package. [It has been reported that perforation occurs due to the inadvertent injection of the hard acute corners of the aluminum-plastic blister (PTP) package into the esophageal mucosa, with severe complications such as mediastinitis. ]
4. Other matters needing attention (1) Rats and mice were subjected to gavage oral administration for 24 months, and bladder tumors appeared in male rats 3.6mg / kg / day group.
(2) It has been reported that the number of colon tumors and the volume of colon tumors increased after oral administration of similar drugs troglitazone or rosiglitazone to a familial adenomatous polyposis (FAP) mouse model. Increase.
(3) It has been reported that the use of thiazinidinediones such as pioglitazone causes or exacerbates (diabetes) macular edema. When the patient's vision drops sharply, the possibility of macular edema should be considered.

Pioglitazone hydrochloride tablets for pregnant and lactating women

(1) Not for pregnant women or women who are likely to become pregnant. [The safety of medications during pregnancy has not been established. In the organogenesis period of rats, a drug administration test was performed. In the 40mg / kg group, a high value of embryo and fetal mortality was observed, and a low value of the survival rate of newborn rats. In the kg group, one death or abortion was observed in each of the mother rabbits, and the embryo and fetal mortality rates were high. ]
(2) Breastfeeding women should refrain from taking medications. If they have to take medications, they should stop breastfeeding. [There are reports of drugs appearing in the milk of rats. ]

Pioglitazone hydrochloride tablets for children

The safety of medications for children has not been established (no clinical experience).

Pioglitazone hydrochloride tablets for the elderly

Elderly people usually have physiological decline and should be administered carefully, for example, starting from 15mg once a day, and closely observe whether adverse reactions occur during the course of the disease.
Compared with young subjects, healthy elderly subjects had no significant differences in peak plasma concentrations of pioglitazone, but the AUC value increased by approximately 21%. Compared to young subjects (approximately 7 hours). These changes did not reach the level deemed clinically relevant.

Pioglitazone hydrochloride tablets drug interactions

Table 14 Precautions for combined use (caution should be taken when using this product in combination with the following drugs)

Pioglitazone hydrochloride tablets overdose

Data on overdose in humans are currently lacking. Once overdose occurs, supportive treatment should be given according to the clinical manifestations of the patient.

Clinical trials of pioglitazone hydrochloride tablets

For patients with type 2 diabetes, taking pioglitazone 15 mg, 30 mg, or 45 mg once a day for various clinical trials including double-blind controlled trials. Among 821 subjects, the overall blood glucose improvement rate ([medium Degree of improvement] or above) was 50.8% (417/821).
In the long-term test (taken for 28 to 48 weeks or more), the blood glucose was stably controlled, and the fasting blood glucose and HbAlc remained decreased. No reduction in the therapeutic effect was seen.
The following are the results of a double-blind controlled trial in patients with type 2 diabetes who are unsatisfactory in glycemic control.
1) In a double-blind controlled trial using diet and / or exercise therapy alone, pioglitazone was used once a day at 30 mg for 12 consecutive weeks, and HbAlc decreased by 1.08 ± 1.47% (mean ± SD of 63 patients).
2) In a double-blind controlled trial using diet therapy and / or exercise therapy plus sulfonylurea drugs, pioglitazone was used once a day at 30 mg for 12 consecutive weeks, and HbAlc decreased by 1.24 ± 1.33% (mean ± SD of 56 patients) ).
3) In a double-blind controlled trial using diet therapy and / or exercise therapy plus an -glucosidase inhibitor, pioglitazone was used once a day at 30 mg for 16 consecutive weeks, and HbAlc decreased by 0.91 ± 0.89% (mean of 55 patients ± Standard deviation).
4) Using diet therapy and / or exercise therapy plus biguanide drugs using pioglitazone, 15 mg once a day for 12 weeks, then 30 mg once a day for 16 weeks, HbA1c decreased by 0.67 ± 0.8% (mean ± standard for 83 patients difference).
5) With dietary and / or exercise therapy plus insulin preparations using pioglitazone, 30 mg once a day for 16 weeks, HbA1c decreased by 1.22 ± 1.11% (mean ± SD of 45 patients).

Pharmacology and toxicology of pioglitazone hydrochloride tablets

After acting on the intracellular target site of the insulin binding site of the insulin receptor, this product reduces insulin resistance, inhibits the liver's sugar production, and improves the sugar utilization of peripheral tissues to reduce blood sugar. It is thought to work by normalizing the intracellular insulin information transmission mechanism involved in the main factors that cause insulin resistance.
1. Improving glucose metabolism: By taking pioglitazone 30 mg once a day for 12 weeks for patients with type 2 diabetes who only use diet and / or exercise therapy, a double-blind controlled trial was conducted to confirm the decrease in fasting blood glucose and HbAlc, and 1,5 anhydroglucose Alcohol (1,5-AG) is elevated.
Patients with type 2 diabetes who use diet therapy and / or exercise therapy plus sulfonylurea drugs, take this product once a day for 30 weeks for 12 weeks, and conduct a double-blind controlled trial to confirm the decrease in fasting blood glucose and HbAlc, and 1,5 Anhydroglucitol (1,5-AG) increases and insulin in the blood decreases.
(3) Patients with type 2 diabetes who use diet therapy and / or exercise therapy plus voglibose, take this product once a day for 30 weeks for 16 weeks, and perform a double-blind controlled trial to confirm the decrease in fasting blood glucose and HbAlc.
For insulin-resistant obese type 2 diabetes model animals (KKAy mice, Wistar obese rats), pioglitazone reduces hyperglycemia and hyperinsulinemia. In addition, pioglitazone has no effect on the hyperglycemia of insulin-deficient type 1 diabetic rats (streptomycin diabetic rats) and the normal blood glucose of healthy rats (Sprague-Dawley rats).
2. Improving glucose tolerance In Wistar obese rats and Zucker obese rats that have both insulin resistance and abnormal glucose tolerance, pioglitazone is administered for 10 to 12 days, and after fasting for 20 hours, it is confirmed by oral glucose that it can inhibit blood glucose rise. High and reduced excessive secretion of insulin.
3. Improving effect on insulin resistance For patients with type 2 diabetes who only use diet therapy and / or exercise therapy or diet therapy and / or exercise therapy plus sulfonylurea drugs, a clinical pharmacological test of pioglitazone 30 mg once a day ( Glucose clamp method) to confirm that the glucose uptake rate in peripheral tissues and liver was increased.
For Wistar obese rats and Zucker obese rats that have both insulin resistance and obese diabetes, pioglitazone is administered for 14 days, and insulin is given after a 20-hour fast. It is confirmed that insulin administration has the effect of enhancing hypoglycemia.
(3) Glycogen in the diaphragm and total fat in the surrounding epididymis of obese diabetic KKAy mice were stimulated with insulin, and pioglitazone increased glucose uptake.
In obese diabetic Wistar obese rats, inhibit liver sugar production and increase sugar utilization in peripheral tissues.
4 Mechanism of action Increasing the effect of insulin in peripheral tissues Increasing the effect of insulin on the soleus muscle of hind limbs of Wistar obese rats (glycogen synthesis and glycolysis promotion effect) (in vitro experiments). There is also an effect of increasing insulin (promoting glucose oxidation and total lipid synthesis) in free adipocytes in the adipose tissue around the epididymis of Wistar obese rats (in vitro experiments).
Enhance the effect of insulin in the liver, promote the activity of glucokinase in the liver of Wistar obese rats, reduce the activity of 6-phosphate glucose, and inhibit the production of sugar (in vivo experiments).
(3) The effect of enhancing the insulin receptor restores the reduced phosphorylation of insulin receptor and insulin receptor matrix in skeletal muscle of Wistar obese rats, and promotes the activity of phosphatidylinositol-3-kinase (in vivo experiments).
Inhibition effect on TNF- production inhibits TNF- production in skeletal muscle of Wistar obese rats, while reducing hyperglycemia (in vivo experiment).

Pharmacokinetics of pioglitazone hydrochloride tablets

1. Plasma concentration in healthy adult men When this product was taken orally, the prototype drug and its metabolites I-VI (MI-M-VI) were detected in the blood, of which M-II-M-IV were active metabolites.
In healthy adult men (8), when a single dose of pioglitazone is taken orally 30 mg on an empty stomach, the plasma concentrations of the prototypical and active metabolites are shown in the table below.

Healthy adult men (8 cases) took pioglitazone 30mg at a single dose on an empty stomach or after a meal. There was no significant difference in the pharmacokinetic parameters of the original drug except for the prolongation of the Tmax of the original drug. Therefore, it is believed that eating has a small effect on drug metabolism. . Observing the hypoglycemic effect in Wistar obese rats, the results showed that the activity of M- M- was lower than that of the original drug.
2. Urinary excretion. Healthy adult men (14 patients) took pioglitazone 30mg in a single fasting. The main excretion in the urine was M- M-. The cumulative urine excretion rate was about 30% 48 hours after taking the drug.
3 Healthy adult men (six cases) with blood concentration after repeated administration, taking pioglitazone 30mg once a day for 9 days (withdrawing the drug the next day), the original drug and all active metabolites (the original drug) + M-II M-IV) has reached a stable blood level, so it is considered that there is no drug accumulation after repeated administration.
4 Patients with type 2 diabetes who are using sulfonylurea drugs (glibenzuron, glizide) when taking a combination with sulfonylurea drugs, taking pioglitazone 30mg once a day for 7 days The blood concentrations of the original drug and all active metabolites (the original drug + M-II to M-IV) were similar to those of patients with type 2 diabetes who only used diet therapy. In addition, no effect on the drug-time curve and protein binding rate of sulfonylureas was observed.
5. Patients with type 2 diabetes who are using voglibose in their blood concentration when combined with an -glucosidase inhibitor, taking pioglitazone 30 mg once a day, the original drug and all active metabolites (the original drug + M - M-IV) The blood drug concentration was similar to that of patients with type 2 diabetes who used only diet therapy or combined use of sulfonylureas.
6. Blood Concentrations When Combined with Biguanide Drugs Healthy adult men (14 subjects) who are using metformin multiple times, taking pioglitazone 30mg once a day, the original drug and all active metabolites (the original drug + M -II ~ M-IV) were similar to those obtained by healthy adult males (14 subjects) with pioglitazone alone.
7. Patients with renal insufficiency in special population Compared with subjects with normal renal function, patients with moderate renal impairment (creatinine clearance rate of 30-50ml / min) and severe renal impairment (creatinine clearance rate <30ml / min) The serum clearance half-life of pioglitazone, M-III and M-IV remained unchanged. Therefore, patients with kidney damage do not need to adjust the dose.
Patients with liver dysfunction compared with normal subjects, mean peak concentrations of pioglitazone and total pioglitazone (pioglitazone, M-III and M-IV) in subjects with impaired liver function (CTP grade B / C) It was reduced to 45%, but the average AUC value did not change. Therefore, dose adjustment is not necessary for patients with liver damage.
After marketing, there have been reports of patients with liver failure after taking this product, and subjects with serum ALT values> 2.5 times (reference upper limit) have been excluded in clinical trials, so patients with liver disease should be used with caution.
8. For the metabolism of pioglitazone, a variety of cytochrome P450 isoenzymes 1A1, 1A2, 2C8, 2C9, 2C19, 2D6, and 3A4 are involved. Pioglitazone has little effect on the metabolic activity of human cytochrome P450 isoenzymes 1A1, 1A2, 2A6, 2B6, 2C8, 2C9, 2C19, 2D6, 2E1, and 3A4 expression microsomes (in vitro experiments).

Pioglitazone Hydrochloride Tablets Storage

Store at normal temperature (10-30 )

Packaging of pioglitazone hydrochloride tablets

15mg: 7 tablets / box (aluminum-plastic blister pack, 7 tablets / board, 1 board)
30mg: 7 tablets / box (aluminum-plastic blister pack, 7 tablets / board, 1 board)

Validity of Pioglitazone Hydrochloride Tablets

36 months

Standard for pioglitazone hydrochloride tablets

Import drug registration standard JX20010100 ^[1]