phl-Pioglitazone

Uses

phl-Pioglitazone is used for an adjunct to diet and exercise to improve glycaemic control in patients with type II diabetes (NIDDM). phl-Pioglitazone is used for monotherapy and also used for use in combination with sulphonylurea, Metformin or Insulin when diet and exercise plus the single agent does not result in adequate glycaemic control.

phl-Pioglitazone is also used to associated treatment for these conditions: Diabetes, Diabetic Neuropathies, Type 2 Diabetes Mellitus

How phl-Pioglitazone works

phl-Pioglitazone is a selective agonist at peroxisome proliferator-activated receptor-gamma (PPARγ) in target tissues for insulin action such as adipose tissue, skeletal muscle, and liver. Activation of PPARγ increases the transcription of insulin-responsive genes involved in the control of glucose and lipid production, transport, and utilization. Through this mechanism, pioglitazone both enhances tissue sensitivity to insulin and reduces the hepatic production of glucose (i.e. gluconeogenesis) - insulin resistance associated with type 2 diabetes mellitus is therefore improved without an increase in insulin secretion by pancreatic beta cells.

Dosage

phl-Pioglitazone dosage

phl-Pioglitazone can be taken once daily without regard to meals. The management of antidiabetic therapy should be individualized. phl-Pioglitazone monotherapy may be initiated at 15 mg or 30 mg once daily dosages in patients not adequately controlled with diet and exercise alone. For patients who respond inadequately to the initial dose of phl-Pioglitazone, the dose can be increased up to 45 mg once daily. For patients not responding adequately to monotherapy, combination therapy should be considered.

Maximum recommended daily dose of phl-Pioglitazone should not exceed 45 mg since doses higher than 45 mg have not been studied in placebo controlled clinical studies. Besides, no placebo controlled clinical studies of more than 30 mg once daily have been conducted in combination therapy.

Side Effects

The overall incidence and types of adverse events reported in placebo controlled clinical trials of phl-Pioglitazone monotherapy at doses of 7.5 mg, 15 mg, 30 mg or 45 mg once daily are upper respiratory tract infection (13.2%), headache (9.1%), sinusitis (6.3%), myalgia (5.4%), tooth disorder (5.3%), and pharyngitis (5.1%).

Toxicity

The oral TDLo observed in mice is 24 mg/kg for 4 days and for rats is 3 mg/kg for 6 days.

One instance of overdose was reported during clinical trials with pioglitazone in which a patient took an oral dose of 120mg daily for four days, followed by 180mg daily for seven days - this patient did not report any adverse clinical symptoms during this time. In the event of overdosage, employ symptomatic and supportive measures according to the patient's clinical status.

Precaution

phl-Pioglitazone exerts its antihyperglycaemic effect only in the presence of Insulin. Therefore, it should not be used in Type 1 diabetes or for the treatment of diabetic ketoacidosis. phl-Pioglitazone should be used with caution in case of combination antidiabetic therapy and hepatic insufficiency. Liver enzyme should be monitored regularly.

Interaction

Administration of thiazolidinediones with an oral contraceptive containing ethinyl oestradiol and norethindrone reduces the plasma concentration of both hormones by approximately 30% which could result in loss of contraception.

Food Interaction

• Take with or without food. Food delays drug absorption, but not to a clinically significant extent.

[Moderate] GENERALLY AVOID: Alcohol may cause hypoglycemia or hyperglycemia in patients with diabetes.

Hypoglycemia most frequently occurs during acute consumption of alcohol.

Even modest amounts can lower blood sugar significantly, especially when the alcohol is ingested on an empty stomach or following exercise.

The mechanism involves inhibition of both gluconeogenesis as well as the counter-regulatory response to hypoglycemia.

Episodes of hypoglycemia may last for 8 to 12 hours after ethanol ingestion.

By contrast, chronic alcohol abuse can cause impaired glucose tolerance and hyperglycemia.

Moderate alcohol consumption generally does not affect blood glucose levels in patients with well controlled diabetes.

A disulfiram-like reaction (e.g., flushing, headache, and nausea) to alcohol has been reported frequently with the use of chlorpropamide and very rarely with other sulfonylureas.

MANAGEMENT: Patients with diabetes should avoid consuming alcohol if their blood glucose is not well controlled, or if they have hypertriglyceridemia, neuropathy, or pancreatitis.

Patients with well controlled diabetes should limit their alcohol intake to one drink daily for women and two drinks daily for men (1 drink = 5 oz wine, 12 oz beer, or 1.5 oz distilled spirits) in conjunction with their normal meal plan.

Alcohol should not be consumed on an empty stomach or following exercise.

phl-Pioglitazone Hypertension interaction

[Moderate] Thiazolidinediones can cause dose-related edema.

Therapy with thiazolidinediones should be administered cautiously in patients at risk for congestive heart failure as well as those with fluid overload or other conditions that may be adversely affected by excess fluid such as hypertension.

Patients should be monitored for signs and symptoms of heart failure such as dyspnea, swelling of legs or ankles, and weight gain.

phl-Pioglitazone Drug Interaction

Moderate: insulin glargine, insulin glargine, pregabalinUnknown: aspirin, aspirin, ubiquinone, dapagliflozin, omega-3 polyunsaturated fatty acids, canagliflozin, sitagliptin, empagliflozin, metoprolol, metoprolol, semaglutide, dulaglutide, liraglutide, cyanocobalamin, ascorbic acid, ergocalciferol, cholecalciferol

phl-Pioglitazone Disease Interaction

Major: CHF, type I diabetesModerate: bladder cancer, edema, liver disease, macular edema, premenopausal anovulation, weight gainMinor: anemia

Volume of Distribution

The average apparent volume of distribution of pioglitazone is 0.63 ± 0.41 L/kg.

Elimination Route

Following oral administration of pioglitazone, peak serum concentrations are observed within 2 hours (T_max) - food slightly delays the time to peak serum concentration, increasing T_max to approximately 3-4 hours, but does not alter the extent of absorption. Steady-state concentrations of both parent drug and its primary active metabolites are achieved after 7 days of once-daily administration of pioglitazone. C_max and AUC increase proportionately to administered doses.

Half Life

The mean serum half-life of pioglitazone and its metabolites (M-III and M-IV) range from 3-7 hours and 16-24 hours, respectively.

Clearance

The apparent clearance of orally administered pioglitazone is 5-7 L/h.

Elimination Route

Approximately 15-30% of orally administered pioglitazone is recovered in the urine. The bulk of its elimination, then, is presumed to be through the excretion of unchanged drug in the bile or as metabolites in the feces.

Pregnancy & Breastfeeding use

Pregnancy: There are no adequate and well controlled studies in pregnant women. phl-Pioglitazone should be used during pregnancy only if the potential benefit justifies the potential risk to the foetus.

Lactation: It is not known whether phl-Pioglitazone is secreted in human milk. As many drugs are excreted in human milk, it should not be administered to a lactating women.

Contraindication

phl-Pioglitazone is contraindicated in patients with known hypersensitivity to any of its components.

Storage Condition

Store at 25° C.

Innovators Monograph

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