Pio-LN

Pioglitazone HCl.

Pio-LN 15: each tablet contains Pioglitazone HCl equivalent to Pioglitazone 15 mg.
Pio-LN 30: each tablet contains Pioglitazone HCl equivalent to Pioglitazone 30 mg.

Pharmacology: Pioglitazone lowers insulin resistance by activating nuclear receptors (peroxisome proliferator-activated receptor-gamma), increase insulin sensitivity in the liver, adipose tissue and skeletal muscle cells. In the case of insulin resistance, pioglitazone lowers glucose production in the liver and increasing glucose uptake in peripheral tissues. Fasting plasma glucose and postprandial improved in patients with type 2 diabetes blood sugar control improvements related to plasma insulin concentrations both when fasting and postprandial. Pioglitazone did not affect the function of pancreatic β cells.
Pharmacokinetics: Pioglitazone rapidly adsorbed after oral administration. Peak levels achieved 2 hours after administration. Repeat dosing did not lead to accumulation. Absolute bioavailability >80%.
Pioglitazone and its metabolites bind strongly to plasma protein (>99%).
Pioglitazone is metabolized in the liver by hydroxylation of aliphatic methylene groups, primarily through the cytochrome P-450 2C9 and 3A4. 3 of 6 metabolites are active (M-II, M-III, and M-IV).
Pioglitazone excreted through feces and urine.
Pioglitazone half time 5-6 hours and its metabolites 16-23 hours, but the volume of distribution increases and decreases intrinsic clearance.
Patients with impaired renal function: Pioglitazone and metabolic concentrations were lower in patients with impaired renal function compared with patients with normal kidney function.
Patients with impaired hepatic function: Pioglitazone plasma concentrations did not change but the volume of distribution increases and decreases intrinsic clearance.

Oral combination therapy of type 2 diabetes in patients with poor glycemic control on metformin monotherapy or sulfonylurea.

Adult: Monotherapy: Starting dose 15 or 30 mg, 1 time a day with or without food.
Combinations with metformin or sulfonylurea, pioglitazone 15 mg or 30 mg/day. Metformin or sulfonylurea dose can be continued during administration of pioglitazone therapy. If patients report hypoglycemia, the dose of sulfonylurea should be decreased.
Elderly patients: No dosage adjustment is necessary.
Patients with impaired renal function: No dosage adjustment in patients with impaired renal function (creatinine clearance >4 mL/min). Pioglitazone is not recommended to use in dialysis patients.
Patients with impaired hepatic function: Pioglitazone is not recommended to be used in patients with hepatic impairment.

Hypoglycemia can occur in conjunction with the administration of pioglitazone and insulin sulfonylurea. Symptomatic and supportive therapy should be taken in case of overdose.

Hypersensitivity to pioglitazone.
Heart failure or patients with a history of heart failure.
Liver function abnormalities: Contraindicated in combination with insulin.

There are no clinical studies of the three combinations, between pioglitazone with other oral antidiabetic. Pioglitazone should not be given as monotherapy. Pioglitazone can cause water retention and precipitation may exacerbate heart failure. Patients should be monitored for signs and symptoms of heart failure. Discontinue administration of pioglitazone in case of cardiac dysfunction. Coadministration of pioglitazone with insulin is contraindicated.
NSAIDs and pioglitazone associated with water retention, coadministration may increase the risk of edema. Patients receiving pioglitazone therapy of liver enzymes should be monitored regularly. Perform liver function tests before administration of pioglitazone therapy. Pioglitazone should not be administered to patients with elevated levels of liver enzymes (ALT >2.5 x Upper Limit of Normal/ULN) or the presence of liver disease.
It is recommended that liver function tests be monitor every two months in the first 12 months and periodically thereafter. If ALT levels are increased to > 3 x ULN during pioglitazone therapy, test reassessed, if ALT levels remain >3 x ULN, therapy should be discontinued. If the patient has symptoms suggesting liver dysfunction such as nausea, vomiting, abdominal pain, fatigue, anorexia and dark urine, liver function tests done. Discontinuation decision based on the evaluation of laboratory results. If jaundice is observed, drug therapy should be discontinued.
Pioglitazone can cause weight gain so it is necessary to supervise. Diet is one way to control diabetes. Patients should be advised to adhere strictly to a calorie-controlled diet.
Pioglitazone can cause decreased levels of hemoglobin and heamatocrit, according to haemodilution. Anemia is one of the side effects of administration of pioglitazone. Provision of pioglitazone on polycystic ovary syndrome can lead to stimulation of ovulation so that patients at risk of pregnancy. If the patients is planning become pregnant or if pregnancy occurs, the treatment should be discontinued.
Use in pregnancy and lactation: There are no clinical data on the use of pioglitazone during pregnancy. Pioglitazone should not be used in pregnancy. It is not known whether pioglitazone is secreted in human milk. Pioglitazone should not be administered to breastfeeding women.
Use in children: Pioglitazone is not recommended for children <18 years.

Pioglitazone in combination with metformin: Anemia, weight gain, headaches, visual disturbances, flatulence (rare), arthralgia, haematuria and impotence.
Pioglitazone in combination with a sulfonylurea: Weight gain, glycosuria, hypoglycaemia, increase lactose dehydrogenase, increased appetite, dizziness, headache, vertigo, visual disturbances, sweating, proteinuria, fatigue.

Co-administration pioglitazone with digoxin, warfarin, phenprocoumon and metformin has not relevant effect on either with the pharmacokinetics and pharmacodynamics pioglitazone.
Co-administration of sulfonylurea and pioglitazone does not appear to affect the pharmacokinetics of the sulfonylurea. No induction of the man inducible cytochrome P-450, 1A, 2C8/9 and 3A4.
Interaction with drugs metabolized by enzymes such as oral contraceptives, cyclosporin, calcium-channel blocker and HMG-CoA reductase inhibitors are not to be expected.

Store below 30°C.

Antidiabetic Agents

A10BG03 - pioglitazone ; Belongs to the class of thiazolidinediones. Used in the treatment of diabetes.

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