For the use only of Registered Medical Practitioners or a Hospital or a Laboratory

Pioglitazone Tablets I.P. 15 mg / Pioglitazone Tablets I.P. 30 mg
Piozone^®15/30

Advice for healthcare professionals

• Pioglitazone should not be used as first line of therapy for diabetes.
• Patients with active bladder cancer or with a history of bladder cancer, and those with
  uninvestigated haematuria, should not receive pioglitazone.
• Prescribers should review the safety and efficacy of pioglitazone in individuals after 3-6 months of treatment to ensure that only patients who are deriving benefit continue to be treated. Pioglitazone should be stopped in patients who do not respond adequately to treatment (eg, reduction in glycosylated haemoglobin HbA1c).
• Before starting pioglitazone, the following known risk factors for development of bladder cancer should be assessed in individuals: age, current or past history of smoking, exposure to some occupational or chemotherapy agents such as cyclophosphamide, or previous irradiation of the pelvic region.
• Use in elderly patients should be considered carefully before and during treatment because the risk of bladder cancer increases with age. Elderly patients should start on the lowest possible dose and be regularly monitored because of the risks of bladder cancer and heart failure associated with pioglitazone.

1. GENERIC NAME
Pioglitazone Tablets I.P. 15 mg / 30 mg

2. Qualitative and Quantitative Composition:
Piozone^®15
Each film coated tablet contains:
Pioglitazone Hydrochloride I.P.
Equivalent to Pioglitazone 15 mg
Colour: Ferric Oxide USP NF (Red)

Piozone^®30
Each film coated tablet contains:
Pioglitazone Hydrochloride I.P.
Equivalent to Pioglitazone 30 mg
Colour: Ferric Oxide USP NF (Yellow)

3.Dosage Form & strength
Refer section 1 & 2

4. Clinical particulars
4.1 Therapeutic indication
As an adjunct to diet and exercise to improve glycemic control in patients with type-II diabetes (NIDDM).

4.2 Posology and method of administration
Posology
Pioglitazone treatment may be initiated at 15 mg or 30 mg once daily. The dose may be increased in increments up to 45mg once daily.
In combination with insulin, the current insulin dose can be continued upon initiation of pioglitazone therapy. If patients report hypoglycaemia, the dose of insulin should be decreased.
Elderly
No dose adjustment is necessary for elderly patients. Physicians should start treatment with the lowest available dose and increase the dose gradually, particularly when pioglitazone is used in combination with insulin.
Renal impairment
No dose adjustment is necessary in patients with impaired renal function (creatinine clearance > 4 ml/min). No information is available from dialysed patients therefore pioglitazone should not be used in such patients.
Hepatic impairment
Pioglitazone should not be used in patients with hepatic impairment.
Paediatric population
The safety and efficacy of pioglitazone in children and adolescents under 18 years of age have not been established
No data are available.

Method of Administration:
For oral use. Pioglitazone tablets are taken orally once daily with or without food. Tablets should be swallowed with a glass of water.

4.3 Contraindications
– Hypersensitivity to the active substance or to any of the Excipients
– Cardiac failure or history of cardiac failure (NYHA stages I to IV)
– Hepatic impairment
– Diabetic ketoacidosis
– Current bladder cancer or a history of bladder cancer
– Uninvestigated macroscopic hematuria

4.4 Special warnings and precautions for use
Congestive Heart Failure
Pioglitazone like other thiazolidinediones, can cause dose-related fluid retention when used alone or in combination with other antidiabetic medications and is most common when Pioglitazone is used in combination with insulin. Fluid retention may lead to or exacerbate congestive heart failure. Patients should be observed for signs and symptoms of congestive heart failure. If congestive heart failure develops, it should be managed according to current standards of care and discontinuation, or dose reduction of Pioglitazone must be considered.

Hypoglycemia
Patients receiving Pioglitazone in combination with insulin or other antidiabetic medications (particularly insulin secretagogues such as sulfonylureas) may be at risk for hypoglycemia. A reduction in the dose of the concomitant antidiabetic medication may be necessary to reduce the risk of hypoglycemia.

Hepatic Effects
There have been post marketing reports of fatal and non-fatal hepatic failure in patients taking Pioglitazone although the reports contain insufficient information necessary to establish the probable cause. There has been no evidence of drug-induced hepatotoxicity in the Pioglitazone controlled clinical trial database to date.
Patients with type 2 diabetes may have fatty liver disease or cardiac disease with episodic congestive heart failure, both of which may cause liver test abnormalities, and they may also have other forms of liver disease, many of which can be treated or managed. Therefore, obtaining a liver test panel (serum alanine aminotransferase [ALT], aspartate aminotransferase [AST], alkaline phosphatase, and total bilirubin) and assessing the patient is recommended before initiating Pioglitazone therapy. In patients with abnormal liver tests, Pioglitazone should be initiated with caution.
Measure liver tests promptly in patients who report symptoms that may indicate liver injury, including fatigue, anorexia, right upper abdominal discomfort, dark urine or jaundice. In this clinical context, if the patient is found to have abnormal liver tests (ALT greater than 3 times the upper limit of the reference range), Pioglitazone treatment should be interrupted, and investigation done to establish the probable cause. Pioglitazone should not be restarted in these patients without another explanation for the liver test abnormalities.
Patients who have serum ALT greater than three times the reference range with serum total bilirubin greater than two times the reference range without alternative etiologies are at risk for severe drug-induced liver injury and should not be restarted on Pioglitazone. For patients with lesser elevations of serum ALT or bilirubin and with an alternate probable cause, treatment with Pioglitazone can be used with caution.

Urinary Bladder Tumors
Tumors were observed in the urinary bladder of male rats in the two-year carcinogenicity study. In addition, during the three-year PROactive clinical trial, 14 patients out of 2605 (0.54%) randomized to Pioglitazone and 5 out of 2633 (0.19%) randomized to placebo were diagnosed with bladder cancer. After excluding patients in whom exposure to study drug was less than one year at the time of diagnosis of bladder cancer, there were 6 (0.23%) cases on Pioglitazone and two (0.08%) cases on placebo. After completion of the trial, a large subset of patients was observed for up to 10 additional years, with little additional exposure to Pioglitazone. During the 13 years of both PROactive and observational follow-up, the occurrence of bladder cancer did not differ between patients randomized to Pioglitazone or placebo (HR =1.00; [95% CI: 0.59−1.72]).
Findings regarding the risk of bladder cancer in patients exposed to Pioglitazone vary among observational studies; some did not find an increased risk of bladder cancer associated with Pioglitazone while others did.
A large prospective10-year observational cohort study conducted in the United States found no statistically significant increase in the risk of bladder cancer in diabetic patients ever exposed to Pioglitazone compared to those never exposed to Pioglitazone (HR =1.06 [95% CI 0.89−1.26]).
A retrospective cohort study conducted with data from the United Kingdom found a statistically significant association between ever exposure to Pioglitazone and bladder cancer (HR: 1.63; [95% CI: 1.22−2.19]).
Associations between cumulative dose or cumulative duration of exposure to Pioglitazone and bladder cancer were not detected in some studies including the 10-year observational study in the U.S. but were in others. Inconsistent findings and limitations inherent in these and other studies preclude conclusive interpretations of the observational data.
Pioglitazone may be associated with an increase in the risk of urinary bladder tumors. There are insufficient data to determine whether pioglitazone is a tumor promoter for urinary bladder tumors.
Consequently, Pioglitazone should not be used in patients with active bladder cancer and the benefits of glycemic control versus unknown risks for cancer recurrence with Pioglitazone should be considered in patients with a prior history of bladder cancer.

Edema
In controlled clinical trials, edema was reported more frequently in patients treated with Pioglitazone than in placebo-treated patients and is dose-related. In post marketing experience, reports of new onset or worsening edema have been received.
Pioglitazone should be used with caution in patients with edema. Because thiazolidinediones, including Pioglitazone can cause fluid retention, which can exacerbate or lead to congestive heart failure, Pioglitazone should be used with caution in patients at risk for congestive heart failure. Patients treated with Pioglitazone should be monitored for signs and symptoms of congestive heart failure.

Fractures
In PROactive (the Prospective Pioglitazone Clinical Trial in Macrovascular Events), 5238 patients with type 2 diabetes and a history of macrovascular disease were randomized to Pioglitazone (N=2605), force-titrated up to 45 mg daily or placebo (N=2633) in addition to standard of care. During a mean follow-up of 34.5 months, the incidence of bone fracture in females was 5.1% (44/870) for Pioglitazone versus 2.5% (23/905) for placebo. This difference was noted after the first year of treatment and persisted during the course of the study. The majority of fractures observed in female patients were nonvertebral fractures including lower limb and distal upper limb. No increase in the incidence of fracture was observed in men treated with Pioglitazone (1.7%) versus placebo (2.1%). The risk of fracture should be considered in the care of patients, especially female patients, treated with Pioglitazone and attention should be given to assessing and maintaining bone health according to current standards of care.

Macular Edema
Macular edema has been reported in post marketing experience in diabetic patients who were taking Pioglitazone or another thiazolidinedione. Some patients presented with blurred vision or decreased visual acuity, but others were diagnosed on routine ophthalmologic examination.
Most patients had peripheral edema at the time macular edema was diagnosed. Some patients had improvement in their macular edema after discontinuation of the thiazolidinedione.
Patients with diabetes should have regular eye exams by an ophthalmologist according to current standards of care. Patients with diabetes who report any visual symptoms should be promptly referred to an ophthalmologist, regardless of the patient’s underlying medications or other physical findings.

4.5 Drug Interactions
Interaction studies have shown that pioglitazone has no relevant effect on either the pharmacokinetics or pharmacodynamics of digoxin, warfarin, phenprocoumon and metformin. Co-administration of pioglitazone with sulfonylureas does not appear to affect the pharmacokinetics of the sulfonylurea. Studies in man suggest no induction of the main inducible cytochrome P450, 1A, 2C8/9 and 3A4. In vitro studies have shown no inhibition of any subtype of cytochrome P450. Interactions with substances metabolised by these enzymes, e.g., oral contraceptives, cyclosporin, calcium channel blockers, and HMG CoA reductase inhibitors are not to be expected.
Co-administration of pioglitazone with gemfibrozil (an inhibitor of cytochrome P450 2C8) is reported to result in a 3-foldincrease in AUC of pioglitazone. Since there is a potential for an increase in dose-related adverse events, a decrease in the dose of pioglitazone may be needed when gemfibrozil is concomitantly administered. Close monitoring of glycemic control should be considered. Co-administration of pioglitazone with rifampicin (an inducer of cytochrome P450 2C8) is reported to result in a 54% decrease in AUC of pioglitazone. The pioglitazone dose may need to be increased when rifampicin is concomitantly administered. Close monitoring of glycaemic control should be considered.

4.6 Use in special populations (Pregnancy, Nursing woman, Pediatric use, Geriatric use)
Pregnancy
Risk Summary
Limited data with Pioglitazone in pregnant women are not sufficient to determine a drug-associated risk for major birth defects or miscarriage. There are risks to the mother and fetus associated with poorly controlled diabetes in pregnancy.
In animal reproduction studies, no adverse developmental effects were observed when pioglitazone was administered to pregnant rats and rabbits during organogenesis at exposures up to 5-and 35-times the 45 mg clinical dose, respectively, based on body surface area.
The estimated background risk of major birth defects is 6-10% in women with pre-gestational diabetes with a HbA1c >7 and has been reported to be as high as 20-25% in women with a HbA1c >10. The estimated background risk of miscarriage for the indicated population is unknown. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2-4% and 15-20%, respectively.
Clinical Considerations
Disease-associated maternal and/or embryo/fetal risk
Poorly controlled diabetes in pregnancy increases the maternal risk for diabetic ketoacidosis, pre-eclampsia, spontaneous abortions, preterm delivery, still birth and delivery complications. Poorly controlled diabetes increases the fetal risk for major birth defects, still birth, and macrosomia related morbidity.
Data
Animal Data
Pioglitazone administered to pregnant rats during organogenesis did not cause adverse developmental effects at a dose of 20 mg/kg (~5-times the 45 mg clinical dose), but delayed parturition and reduced embryofetal viability at 40 and 80 mg/kg, or ≥9-times the 45 mg clinical dose, by body surface area. In pregnant rabbits administered pioglitazone during organogenesis, no adverse developmental effects were observed at 80 mg/kg (~35-times the 45 mg clinical dose), but reduced embryofetal viability at 160 mg/kg, or ~69-times the 45 mg clinical dose, by body surface area. When pregnant rats received pioglitazone during late gestation and lactation, delayed postnatal development, attributed to decreased body weight, occurred in offspring at maternal doses of 10 mg/kg and above or ≥2 times the 45 mg clinical dose, by body surface area.

Lactation
Risk Summary
There is no information regarding the presence of pioglitazone in human milk, the effects on the breastfed infant, or the effects on milk production. Pioglitazone is present in rat milk; however due to species-specific differences in lactation physiology, animal data may not reliably predict drug levels in human milk. The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for Pioglitazone and any potential adverse effects on the breastfed infant from Pioglitazone or from the underlying maternal condition.

Pediatric Use
Safety and effectiveness of Pioglitazone in pediatric patients have not been established.
Pioglitazone is not recommended for use in pediatric patients based on adverse effects observed in adults, including fluid retention and congestive heart failure, fractures, and urinary bladder tumors.

Geriatric Use
A total of 92 patients (15.2%) treated with Pioglitazone in the three pooled 16-to 26-week double-blind, placebo-controlled, monotherapy trials were ≥65 years old and two patients (0.3%) were (18.7%) treated with Pioglitazone were ≥65 years old and 19 (1.8%) were ≥75 years old. In the two pooled 16-to 24-week add-on to metformin trials, 155 patients (15.5%) treated with Pioglitazone were ≥65 years old and 19 (1.9%) were ≥75 years old. In the two pooled 16-to 24-week add-on to insulin trials, 272 patients (25.4%) treated with Pioglitazone were ≥65 years old and 22 (2.1%) were ≥75 years old.
In PROactive, 1068 patients (41.0%) treated with Pioglitazone were ≥65 years old and 42 (1.6%) were ≥75 years old.
In pharmacokinetic studies with pioglitazone, no significant differences were observed in pharmacokinetic parameters between elderly and younger patients [see Clinical Pharmacology (12.3)].
Although clinical experiences have not identified differences in effectiveness and safety between the elderly (≥65 years) and younger patients, these conclusions are limited by small sample sizes for patients ≥75 years old.

4.7 Effects on ability to drive and use machines
Pioglitazone has no or negligible influence on the ability to drive and use machines. However, patients who experience visual disturbance should be cautious when driving or using machines.

4.8 Undesirable effects
Get emergency medical help if you have signs of an allergic reaction: hives; difficult breathing; swelling of your face, lips, tongue, or throat.
Stop using pioglitazone and call your doctor at once if you have symptoms of liver damage: nausea, upper stomach pain, itching, loss of appetite, dark urine, clay-coloured stools, or jaundice (yellowing of the skin or eyes).

Pioglitazone may cause serious side effects.

• shortness of breath (especially when lying down), unusual tiredness, swelling, rapid weight gain;
• Pink or red urine, painful or difficult urination, new or worsening urge to urinate;
• Changes in your vision; or
• Sudden unusual pain in your hand, arm, or foot.

Some people taking pioglitazone have had bladder cancer, but it is not clear if pioglitazone was the actual cause.
Common side effects: Headache; muscle pain; or cold symptoms such as stuffy nose, sinus pain, sneezing, sore throat.

4.9 Overdose
During controlled clinical trials, one case of overdose with Pioglitazone was reported. A male patient took 120 mg per day for four days, then 180 mg per day for seven days. The patient denied any clinical symptoms during this period.
In the event of overdosage, appropriate supportive treatment should be initiated according to the patient’s clinical signs and symptoms.

5. Pharmacological properties
5.1 Mechanism of action
Pioglitazone effects may be mediated by a reduction of insulin resistance. Pioglitazone appears to act via activation of specific nuclear receptors (peroxisome proliferator activated receptor gamma) leading to increased insulin sensitivity of liver, fat and skeletal muscle cells in animals. Treatment with pioglitazone has been shown to reduce hepatic glucose output and to increase peripheral glucose disposal in the case of insulin resistance.

5.2 Pharmacodynamic Properties
Clinical studies demonstrate that Pioglitazone improves insulin sensitivity in insulin-resistant patients. Pioglitazone enhances cellular responsiveness to insulin, increases insulin-dependent glucose disposal and improves hepatic sensitivity to insulin. In patients with type 2 diabetes, the decreased insulin resistance produced by Pioglitazone results in lower plasma glucose concentrations, lower plasma insulin concentrations, and lower HbA1c values. In controlled clinical trials, Pioglitazone had an additive effect on glycemic control when used in combination with a sulfonylurea, metformin, or insulin.
Patients with lipid abnormalities were included in clinical trials with Pioglitazone. Overall, patients treated with Pioglitazone had mean decreases in serum triglycerides, mean increases in HDL cholesterol, and no consistent mean changes in LDL and total cholesterol. There is no conclusive evidence of macrovascular benefit with Pioglitazone.
In a 26-week, placebo-controlled, dose-ranging monotherapy study, mean serum triglycerides decreased in the 15 mg, 30 mg, and 45 mg Pioglitazone dose groups compared to a mean increase in the placebo group. Mean HDL cholesterol increased to a greater extent in patients treated with Pioglitazone than in the placebo-treated patients. There were no consistent differences for LDL and total cholesterol in patients treated with Pioglitazone compared to placebo (see Table).

*Adjusted for baseline, pooled center, and pooled center by treatment interaction †p<0.05 versus placebo
In the two other monotherapy studies (16 weeks and 24 weeks) and in combination therapy studies with sulfonylurea (16 weeks and 24 weeks), metformin (16 weeks and 24 weeks) or insulin (16 weeks and 24 weeks), the results were generally consistent with the data above.

5.3 Pharmacokinetic properties
Following once-daily administration of Pioglitazone, steady-state serum concentrations of both pioglitazone and its major active metabolites, M-III (keto derivative of pioglitazone) and M-IV (hydroxyl derivative of pioglitazone), are achieved within seven days. At steady-state, M-III and M-IV reach serum concentrations equal to or greater than that of pioglitazone. At steady state, in both healthy volunteers and patients with type 2 diabetes, pioglitazone comprises approximately 30% to 50% of the peak total pioglitazone serum concentrations (pioglitazone plus active metabolites) and 20% to 25% of the total AUC.
Cmax, AUC, and trough serum concentrations (Cmin) for pioglitazone and M-III and M-IV, increased proportionally with administered doses of 15 mg and 30 mg per day.

Absorption
Following oral administration of pioglitazone, Tmax of pioglitazone was within two hours. Food delays the Tmax to three to four hours but does not alter the extent of absorption (AUC).

Distribution
The mean apparent volume of distribution (Vd/F) of pioglitazone following single-dose administration is 0.63 ± 0.41 (mean ± SD) L/kg of body weight. Pioglitazone is extensively protein bound (>99%) in human serum, principally to serum albumin. Pioglitazone also binds to other serum proteins, but with lower affinity. M-III and M-IV are also extensively bound (>98%) to serum albumin.
Metabolism
Pioglitazone is extensively metabolized by hydroxylation and oxidation; the metabolites also partly convert to glucuronide or sulfate conjugates. Metabolites M-III and M-IV are the major circulating active metabolites in humans.
In vitro data demonstrate that multiple CYP isoforms are involved in the metabolism of pioglitazone, which include CYP2C8 and, to a lesser degree, CYP3A4 with additional contributions from a variety of other isoforms including the mainly extrahepatic CYP1A1. In vivo study of pioglitazone in combination with gemfibrozil, a strong CYP2C8 inhibitor, showed that pioglitazone is a CYP2C8 substrate [see Dosage and Administration (2.3) and Drug Interactions (7)]. Urinary 6ß-hydroxycortisol/cortisol ratios measured in patients treated with Pioglitazone showed that pioglitazone is not a strong CYP3A4 enzyme inducer.

Excretion and Elimination
Following oral administration, approximately 15% to 30% of the pioglitazone dose is recovered in the urine. Renal elimination of pioglitazone is negligible, and the drug is excreted primarily as metabolites and their conjugates. It is presumed that most of the oral dose is excreted into the bile either unchanged or as metabolites and eliminated in the feces.
The mean serum half-life (t1/2) of pioglitazone and its metabolites (M-III and M-IV) range from three to seven hours and 16 to 24 hours, respectively. Pioglitazone has an apparent clearance, CL/F, calculated to be five to seven L/hr.

Renal Impairment
The serum elimination half-life of pioglitazone, M-III, and M-IV remains unchanged in patients with moderate (creatinine clearance [CLcr] 30 to 50 mL/min) and severe (CLcr <30 mL/min) renal impairment when compared to subjects with normal renal function. Therefore, no dose adjustment in patients with renal impairment is required.

Hepatic Impairment
Compared with healthy controls, subjects with impaired hepatic function (Child-Turcotte-Pugh
Grade B/C) have an approximate 45% reduction in pioglitazone and total pioglitazone (pioglitazone, M-III, and M-IV) mean Cmax but no change in the mean AUC values. Therefore, no dose adjustment in patients with hepatic impairment is required.
There are post marketing reports of liver failure with Pioglitazone and clinical trials have generally excluded patients with serum ALT >2.5 times the upper limit of the reference range. Use caution in patients with liver disease.

Geriatric Patients
In healthy elderly subjects, Cmax of pioglitazone was not significantly different, but AUC values were approximately 21% higher than those achieved in younger subjects. The mean t1/2 of pioglitazone was also prolonged in elderly subjects (about ten hours) as compared to younger subjects (about seven hours). These changes were not of a magnitude that would be considered clinically relevant.

Pediatric Patients
Safety and efficacy of pioglitazone in pediatric patients have not been established. Pioglitazone is not recommended for use in pediatric patients.

Gender
The mean Cmax and AUC values of pioglitazone were increased 20% to 60% in women compared to men. In controlled clinical trials, HbA1c decreases from baseline were generally greater for females than for males (average mean difference in HbA1c 0.5%). Because therapy should be individualized for each patient to achieve glycemic control, no dose adjustment is recommended based on gender alone.

6. Nonclinical properties
6.1 Animal Toxicology or Pharmacology
Carcinogenesis, Mutagenesis, Impairment of Fertility
A two-year carcinogenicity study was conducted in male and female rats at oral doses up to 63 mg/kg (approximately 14 times the maximum recommended human oral dose of 45 mg based on mg/m2). Drug-induced tumors were not observed in any organ except for the urinary bladder of male rats. Benign and/or malignant transitional cell neoplasms were observed in male rats at 4 mg/kg/day and above (approximately equal to the maximum recommended human oral dose based on mg/m2). Urinary calculi with subsequent irritation and hyperplasia were postulated as the mechanism for bladder tumors observed in male rats. A two-year mechanistic study in male rats utilizing dietary acidification to reduce calculi formation was completed in 2009. Dietary acidification decreased but did not abolish the hyperplastic changes in the bladder. The presence of calculi exacerbated the hyperplastic response to pioglitazone but was not considered the primary cause of the hyperplastic changes.
The relevance to humans of the bladder findings in the male rat cannot be excluded.
A two-year carcinogenicity study was also conducted in male and female mice at oral doses up to 100 mg/kg/day (approximately 11 times the maximum recommended human oral dose based on mg/m2). No drug-induced tumors were observed in any organ.
Pioglitazone hydrochloride was not mutagenic in a battery of genetic toxicology studies, including the Ames bacterial assay, a mammalian cell forward gene mutation assay (CHO/HPRT and AS52/XPRT), an in vitro cytogenetics assay using CHL cells, an unscheduled DNA synthesis assay, and an in vivo micronucleus assay.
No adverse effects upon fertility were observed in male and female rats at oral doses up to 40 mg/kg pioglitazone hydrochloride daily prior to and throughout mating and gestation (approximately nine times the maximum recommended human oral dose based on mg/m2).

Animal Toxicology and/or Pharmacology
Heart enlargement has been observed in mice (100 mg/kg), rats (4 mg/kg and above) and dogs (3 mg/kg) treated orally with pioglitazone hydrochloride (approximately 11, 1, and 2 times the maximum recommended human oral dose for mice, rats, and dogs, respectively, based on mg/m2). In a one-year rat study, drug-related early death due to apparent heart dysfunction occurred at an oral dose of 160 mg/kg/day (approximately 35 times the maximum recommended human oral dose based on mg/m2). Heart enlargement was seen in a 13-week study in monkeys at oral doses of 8.9 mg/kg and above (approximately four times the maximum recommended human oral dose based on mg/m2), but not in a 52-week study at oral doses up to 32 mg/kg (approximately 13 times the maximum recommended human oral dose based on mg/m2).

7. Description
Pioglitazone Tablets I.P. 15 mg – Brown colour, circular shaped, slightly biconvex film coated tablet scored in the middle on one side.
Pioglitazone Tablets I.P. 30 mg – Yellow colour, circular shaped, slightly biconvex film coated tablet scored in the middle on one side.

8. Pharmaceutical particulars
8.1 Incompatibilities

8.2 Shelf Life
Refer Pack

8.3 Packaging Information
10 tablets in blister pack.

8.4 Storage and handling instructions
Store at a temperature not exceeding 30ºC.
Medicine: Keep out of reach of children.

9. Patient Counseling Information

• It is important to instruct patients to adhere to dietary instructions and to have blood glucose and glycosylated hemoglobin tested regularly. During periods of stress such as fever, trauma, infection, or surgery, medication requirements may change, and patients should be reminded to seek medical advice promptly.
• Patients who experience an unusually rapid increase in weight or edema or who develop shortness of breath or other symptoms of heart failure while on Pioglitazone should immediately report these symptoms to a physician.
• Tell patients to promptly stop taking Pioglitazone and seek immediate medical advice if there is unexplained nausea, vomiting, abdominal pain, fatigue, anorexia, or dark urine as these symptoms may be due to hepatotoxicity.
• Tell patients to promptly report any sign of macroscopic hematuria or other symptoms such as dysuria or urinary urgency that develop or increase during treatment as these may be due to bladder cancer.
• Tell patients to take Pioglitazone once daily. Pioglitazone can be taken with or without meals. If a dose is missed on one day, the dose should not be doubled the following day.
• When using combination therapy with insulin or other antidiabetic medications, the risks of hypoglycemia, its symptoms and treatment, and conditions that predispose to its development should be explained to patients and their family members.
• Inform female patients that treatment with Pioglitazone, like other thiazolidinediones, may result in an unintended pregnancy in some premenopausal anovulatory females due to its effect on ovulation.

Pioglitazone can cause serious side effects, including new or worse heart failure.

• Pioglitazone can cause your body to keep extra fluid (fluid retention), which leads to swelling (edema) and weight gain. Extra body fluid can make some heart problems worse or lead to heart failure. Heart failure means your heart does not pump blood well enough
• Do not take Pioglitazone if you have severe heart failure
• If you have heart failure with symptoms (such as shortness of breath or swelling), even if these symptoms are not severe, Pioglitazone may not be right for you Call your doctor right away if you have any of the following:
• swelling or fluid retention, especially in the ankles or legs
• shortness of breath or trouble breathing, especially when you lie down
• an unusually fast increase in weight
• unusual tiredness

Pioglitazone can have other serious side effects. See “What are the possible side effects of Pioglitazone?”

What is Pioglitazone?
Pioglitazone is a prescription medicine used with diet and exercise to improve blood sugar (glucose) control in adults with type 2 diabetes. Pioglitazone is a diabetes medicine called pioglitazone that may be taken alone or with other diabetes medicines.
It is not known if Pioglitazone is safe and effective in children under the age of 18. Pioglitazone is not recommended for use in children.
Pioglitazone is not for people with type 1 diabetes.
Pioglitazone is not for people with diabetic ketoacidosis (increased ketones in your blood or urine).

Who should not take Pioglitazone?
Do not take Pioglitazone if you:

• have severe heart failure
• are allergic to any of the ingredients in Pioglitazone. See the end of this Medication Guide for a complete list of ingredients in Pioglitazone

Talk to your doctor before taking Pioglitazone if you have either of these conditions.

What should I tell my doctor before taking Pioglitazone?
Before you take Pioglitazone, tell your doctor if you:

• have heart failure
• have type 1 (“juvenile”) diabetes or had diabetic ketoacidosis
• have a type of diabetic eye disease that causes swelling in the back of the eye (macular edema)
• have liver problems
• have or have had cancer of the bladder
• are pregnant or plan to become pregnant. It is not known if Pioglitazone can harm your unborn baby. Talk to your doctor if you are pregnant or plan to become pregnant about the best way to control your blood glucose levels while pregnant
• are a premenopausal woman (before the “change of life”) who does not have periods regularly or at all. Pioglitazone may increase your chance of becoming pregnant. Talk to your doctor about birth control choices while taking Pioglitazone. Tell your doctor right away if you become pregnant while taking Pioglitazone
• are breastfeeding or plan to breastfeed. It is not known if Pioglitazone passes into your milk and if it can harm your baby. Talk to your doctor about the best way to control your blood glucose levels while breastfeeding

Tell your doctor about all the medicines you take including prescription and over the counter medicines, vitamins, and herbal supplements.
Pioglitazone and some of your other medicines can affect each other. You may need to have your dose of Pioglitazone or certain other medicines changed.
Know the medicines you take. Keep a list of your medicines and show it to your doctor before you start a new medicine. They will tell you if it is okay to take Pioglitazone with other medicines.

How should I take Pioglitazone?

• Take Pioglitazone exactly as your doctor tells you to take it
• Your doctor may change your dose of Pioglitazone. Do not change your Pioglitazone dose unless your doctor tells you to
• Pioglitazone may be prescribed alone or with other diabetes medicines. This will depend on how well your blood sugar is controlled
• Take Pioglitazone one time each day, with or without food
• If you miss a dose of Pioglitazone, take your next dose as prescribed unless your doctor tells you differently. Do not take two doses at one time the next day
• If you take too much Pioglitazone, call your doctor or go to the nearest hospital emergency room right away
• If your body is under stress such as from a fever, infection, accident, or surgery the dose of your diabetes medicines may need to be changed. Call your doctor right away
• Stay on your diet and exercise programs and test your blood sugar regularly while taking Pioglitazone
• Your doctor should do certain blood tests before you start and while you take Pioglitazone
• Your doctor should also do hemoglobin A1C testing to check how well your blood sugar is controlled with Pioglitazone
• Your doctor should check your eyes regularly while you take Pioglitazone

What are the possible side effects of Pioglitazone?
Pioglitazone may cause serious side effects including:

• • See “What is the most important information I should know about Pioglitazone?”
  • low blood sugar (hypoglycemia). This can happen if you skip meals, if you also use another medicine that lowers blood sugar, or if you have certain medical problems. Lightheadedness, dizziness, shakiness, or hunger may happen if your blood sugar is too low. Call your doctor if low blood sugar levels are a problem for you
  • liver problems. Call your doctor right away if you have:
    1. nausea or vomiting
    2. stomach pain
    3. unusual or unexplained tiredness
    4. loss of appetite
    5. dark urine
    6. yellowing of your skin or the whites of your eyes
  • bladder cancer. There may be an increased chance of having bladder cancer when you take Pioglitazone. You should not take Pioglitazone if you are receiving treatment for bladder cancer. Tell your doctor right away if you have any of the following symptoms of bladder cancer:
    1. blood or a red color in your urine
    2. an increased need to urinate
    3. pain while you urinate
  • broken bones (fractures). Usually in the hand, upper arm, or foot in women. Talk to your doctor for advice on how to keep your bones healthy.
  • diabetic eye disease with swelling in the back of the eye (macular edema). Tell your doctor right away if you have any changes in your vision. Your doctor should check your eyes regularly
  • release of an egg from an ovary in a woman (ovulation) leading to pregnancy.

Ovulation may happen when premenopausal women who do not have regular monthly periods take Pioglitazone. This can increase your chance of getting pregnant. The most common side effects of Pioglitazone include:

• cold-like symptoms (upper respiratory tract infection)
• headache
• sinus infection
• muscle pain
• sore throat

Tell your doctor if you have any side effect that bothers you or that does not go away. These are not all the side effects of Pioglitazone. For more information, ask your doctor.
Call your doctor for medical advice about side effects.

10. Details of manufacturer
MANUFACTURED BY
The Madras Pharmaceuticals
No. 137 B, Old Mahabalipuram Road,
Karapakkam, Chennai-600 096,
Tamilnadu.

Marketed by:
Abbott Healthcare Pvt. Ltd.
Angel Space, Bldg. D-4, Gala No. 1 to 6 &
11 to 16 Ground Floor, 101 to 106 &
111 to 116 First Floor, 201 to 206 & 211 to 216
2nd Floor, Pimplas, Dist. Thane, Bhiwandi – 421 302, India.
® Regd. Trade Mark of Abbott Healthcare Pvt. Ltd.

11. Details of permission or licence number with date
Mfg. License No. 247, dated 26.11.2018

12. Date of revision
Version No. 1.0, dated 11th August 2023

For Product Complaints/Adverse events or Queries please write to webmasterindia@abbott.com