Pioglitazone
Pioglitazone Uses, Dosage, Side Effects, Food Interaction and all others data.
Pioglitazone is a preparation of Pioglitazone which is a member of the newest class of oral antidiabetic agent called thiazolidinediones. It depends on the presence of Insulin for its mechanism of action. Pioglitazone decreases Insulin resistance in the periphery and in the liver, resulting in increased Insulin dependent glucose disposal and decreased hepatic glucose output. It also improves abnormality in lipid metabolism by activating peroxisome proliferator activated receptor gamma (PPAR-γ).
Pioglitazone enhances cellular responsiveness to insulin, increases insulin-dependent glucose disposal, and improves impaired glucose homeostasis. In patients with type 2 diabetes mellitus, these effects result in lower plasma glucose concentrations, lower plasma insulin concentrations, and lower HbA1c values.
Significant fluid retention leading to the development/exacerbation of congestive heart failure has been reported with pioglitazone - avoid its use in patients in heart failure or at risk of developing heart failure. There is some evidence that pioglitazone may be associated with an increased risk of developing bladder cancer. Pioglitazone should not be used in patients with active bladder cancer and should be used with caution in patients with a history of bladder cancer.
| Trade Name | Pioglitazone |
| Availability | Prescription only |
| Generic | Pioglitazone |
| Pioglitazone Other Names | Pioglitazona, Pioglitazone, Pioglitazonum |
| Related Drugs | Farxiga, metformin, Trulicity, Lantus, Victoza, Tresiba, Levemir |
| Weight | 15mg, 30mg, 45mg, |
| Type | Oral Tablet, Tablet |
| Formula | C19H20N2O3S |
| Weight | Average: 356.439 Monoisotopic: 356.119463206 |
| Protein binding | Pioglitazone is >99% protein-bound in human plasma - binding is primarily to albumin, although pioglitazone has been shown to bind other serum proteins with a lower affinity. The M-III and M-IV metabolites of pioglitazone are >98% protein-bound (also primarily to albumin). |
| Groups | Approved, Investigational |
| Therapeutic Class | Thiazolidinedione Group |
| Manufacturer | Sandoz Limited |
| Available Country | United Kingdom, United States |
| Last Updated: | September 19, 2023 at 7:00 am |
Uses
Pioglitazone is used for an adjunct to diet and exercise to improve glycaemic control in patients with type II diabetes (NIDDM). 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.
Pioglitazone is also used to associated treatment for these conditions: Diabetes, Diabetic Neuropathies, Type 2 Diabetes Mellitus
How Pioglitazone works
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
Pioglitazone dosage
Pioglitazone can be taken once daily without regard to meals. The management of antidiabetic therapy should be individualized. 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 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 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 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
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. 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.
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.
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
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 (Tmax) - food slightly delays the time to peak serum concentration, increasing Tmax 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. Cmax 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. Pioglitazone should be used during pregnancy only if the potential benefit justifies the potential risk to the foetus.
Lactation: It is not known whether Pioglitazone is secreted in human milk. As many drugs are excreted in human milk, it should not be administered to a lactating women.
Contraindication
Pioglitazone is contraindicated in patients with known hypersensitivity to any of its components.
Storage Condition
Store at 25° C.
Innovators Monograph
You find simplified version here Pioglitazone
Pioglitazone contains Pioglitazone see full prescribing information from innovator Pioglitazone Monograph, Pioglitazone MSDS, Pioglitazone FDA label
FAQ
What is Pioglitazone used for?
Pioglitazone is a medicine used to treat type 2 diabetes. Type 2 diabetes is an illness where the body doesn't make enough insulin, or the insulin that it makes doesn't work properly.
How safe is Pioglitazone?
Pioglitazone is usually safe to take for a long time. Your doctor will give you regular tests to check whether it's safe for you to continue taking it.
How long does it take Pioglitazone to work?
Pioglitazone controls type 2 diabetes but does not cure it. It may take 2 weeks for your blood sugar to decrease and 2 to 3 months for you to feel the full effect of Pioglitazone.
What is the mechanism of action of Pioglitazone?
Pioglitazone selectively stimulates the nuclear receptor peroxisome proliferator-activated receptor gamma and to a lesser extent PPAR-α.
What are the common side effects of Pioglitazone?
The common side effects of Pioglitazone are include:
- Blurred vision or other changes in vision.
- flushed, dry skin.
- fruit-like breath odor.
- headache.
- increased thirst.
- increased urination.
- muscle pain or soreness.
- problems with your teeth.
Is Pioglitazone safe during pregnancy?
This drug should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.Pioglitazone is rated "C" by the Food and Drug Administration (FDA). This means that risks to the fetus cannot be ruled out.
Is Pioglitazone safe during breastfeeding?
Pioglitazone is unlikely to pass into breastmilk in clinically important amounts. However, an alternate drug may be preferred, especially while nursing a newborn or preterm infant.
Can I drink alcohol with Pioglitazone?
Yes, you can drink alcohol while taking Pioglitazone. However, it's best to drink no more than 2 units a day. Drinking more than this can increase your risk of low blood sugar.
Can I drive after taking Pioglitazone?
Pioglitazone will not normally affect your ability to drive or use machines but take care if you experience abnormal vision.
What is the best time to take Pioglitazone?
Follow your doctor's instructions when taking this medicine. You'll usually take Pioglitazone once a day. You can take it at any time, for example in the morning or in the evening. Try to take it at the same time every day.
How long does Pioglitazone stay in my system?
The mean serum half-life of Pioglitazone and total Pioglitazone ranges from 3 to 7 hours and 16 to 24 hours, respectively.
Is Pioglitazone bad for kidneys?
The pharmacokinetic properties of Pioglitazone are ideally suited for patients with renal insufficiency.
Does Pioglitazone cause heart failure?
Pioglitazone induced heart failure is known in patients with underlying heart disease, but is not well documented in patients with normal left ventricular function.
When should I stop taking Pioglitazone?
Pioglitazone can cause or worsen congestive heart failure. You should not use this medicine if you have severe or uncontrolled heart failure. Stop using this medicine and call your doctor at once if you have shortness of breath unusual tiredness, swelling, or rapid weight gain.
Is Pioglitazone bad for your liver?
Pioglitazone has been associated with only rare instances of clinically apparent liver injury.
Who should not take Pioglitazone?
This medicine may cause or make heart failure worse. Tell your doctor if you have had heart failure. Do not take Pioglitazone and glimepiride if you have moderate to severe heart failure or any signs of heart failure.
What happen if I overdose of Pioglitazone?
If you think there has been an overdose, call your poison control center or get medical care right away. Be ready to tell or show what was taken, how much, and when it happened.
