pharmacopeia
GET
/api/v1/drug/pioglitazone

Boxed warning

CONGESTIVE HEART FAILURE Thiazolidinediones, including pioglitazone , cause or exacerbate congestive heart failure in some patients [see Warnings and Precautions (5.1) ] . After initiation of pioglitazone , and after dose increases, monitor patients carefully for signs and symptoms of heart failure (e.g., excessive, rapid weight gain, dyspnea, and/or edema). If heart failure develops, it should be managed according to current standards of care and discontinuation or dose reduction of pioglitazone must be considered. Pioglitazone is not recommended in patients with symptomatic heart failure. Initiation of pioglitazone in patients with established New York Heart Association (NYHA) Class III or IV heart failure is contraindicated [see Contraindications (4) and Warnings and Precautions (5.1) ] . WARNING: CONGESTIVE HEART FAILURE See full prescribing information for complete boxed warning. Thiazolidinediones, including pioglitazone, cause or exacerbate congestive heart failure in some patients. (5.1) After initiation of pioglitazone, and after dose increases, monitor patients carefully for signs and symptoms of heart failure (e.g., excessive, rapid weight gain, dyspnea, and/or edema). If heart failure develops, it should be managed according to current standards of care and discontinuation or dose reduction of pioglitazone must be considered.

2D structure
5-[[4-[2-(5-ethyl-2-pyridinyl)ethoxy]phenyl]methyl]-1,3-thiazolidine-2,4-dione
SMILES CCC1=CN=C(C=C1)CCOC2=CC=C(C=C2)CC3C(=O)NC(=O)S3
InChIKey HYAFETHFCAUJAY-UHFFFAOYSA-N

Mechanism of action

Sourced from openFDA

Pioglitazone is a thiazolidinedione that 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.

Insulin ReceptorPeroxisome Proliferator-activated Receptor alphaPeroxisome Proliferator-activated Receptor gamma

Indications

Sourced from openFDA
  • Monotherapy and Combination Therapy Pioglitazone tablets are indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus in multiple clinical settings [see Clinical Studies (14) ] . Important Limitations of Use Pioglitazone tablets exert its antihyperglycemic effect only in the presence of endogenous insulin.ICD-10: E11.9

Contraindications

Sourced from openFDA
  • Initiation in patients with established NYHA Class III or IV heart failure [see Boxed Warning ]. Use in patients with known hypersensitivity to pioglitazone or any other component of pioglitazone tablets.contraindicated

Dosage & administration

Sourced from openFDA

Initiate pioglitazone tablets at 15 mg or 30 mg once daily. Limit initial dose to 15 mg once daily in patients with NYHA Class I or II heart failure. (2.1) If there is inadequate glycemic control, the dose can be increased in 15 mg increments up to a maximum of 45 mg once daily. (2.1) Obtain liver tests before starting pioglitazone tablets. If abnormal, use caution when treating with pioglitazone tablets, investigate the probable cause, treat (if possible) and follow appropriately. Monitoring liver tests while on pioglitazone tablets are not recommended in patients without liver disease. ( 5.3 ) 2.1 Recommendations for All Patients Pioglitazone tablets should be taken once daily and can be taken without regard to meals. The recommended starting dose for patients without congestive heart failure is 15 mg or 30 mg once daily. The recommended starting dose for patients with congestive heart failure (NYHA Class I or II) is 15 mg once daily. The dose can be titrated in increments of 15 mg up to a maximum of 45 mg once daily based on glycemic response as determined by HbA1c. After initiation of pioglitazone tablets or with dose increase, monitor patients carefully for adverse reactions related to fluid retention such as weight gain, edema, and signs and symptoms of congestive heart failure [see Boxed Warning and Warnings and Precautions (5.5) ] . Liver tests (serum alanine and aspartate aminotransferases, alkaline phosphatase, and total bilirubin) should be obtained prior to initiating pioglitazone tablets.

Warnings & precautions

Sourced from openFDA

Congestive heart failure: Fluid retention may occur and can exacerbate or lead to congestive heart failure. Combination use with insulin and use in congestive heart failure NYHA Class I and II may increase risk. Monitor patients for signs and symptoms. (5.1) Hypoglycemia: When used with insulin or an insulin secretagogue, a lower dose of the insulin or insulin secretagogue may be needed to reduce the risk of hypoglycemia. (5.2) Hepatic effects: Postmarketing reports of hepatic failure, sometimes fatal. Causality cannot be excluded. If liver injury is detected, promptly interrupt pioglitazone and assess patient for probable cause, then treat cause if possible, to resolution or stabilization. Do not restart pioglitazone if liver injury is confirmed and no alternate etiology can be found. (5.3) Bladder cancer: May increase the risk of bladder cancer. Do not use in patients with active bladder cancer. Use caution when using in patients with a prior history of bladder cancer. (5.4) Edema: Dose-related edema may occur. (5.5) Fractures: Increased incidence in female patients. Apply current standards of care for assessing and maintaining bone health. (5.6) Macular edema: Postmarketing reports. Recommend regular eye exams in all patients with diabetes according to current standards of care with prompt evaluation for acute visual changes. (5.7) Macrovascular outcomes: There have been no clinical studies establishing conclusive evidence of macrovascular risk reduction with pioglitazone.

Adverse reactions

Sourced from openFDA

The following serious adverse reactions are discussed elsewhere in the labeling: Congestive heart failure [see Boxed Warning and Warnings and Precautions (5.1) ] Edema [see Warnings and Precautions (5.5) ] Fractures [see Warnings and Precautions (5.6) ] Most common adverse reactions (≥5%) are upper respiratory tract infection, headache, sinusitis, myalgia, and pharyngitis. (6.1) To report SUSPECTED ADVERSE REACTIONS, contact Quallent Pharmaceuticals Health LLC at 1-877-605-7243 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch . 6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. Over 8500 patients with type 2 diabetes have been treated with pioglitazone in randomized, double-blind, controlled clinical trials, including 2605 patients with type 2 diabetes and macrovascular disease treated with pioglitazone in the PROactive clinical trial. In these trials, over 6000 patients have been treated with pioglitazone for six months or longer, over 4500 patients have been treated with pioglitazone for one year or longer, and over 3000 patients have been treated with pioglitazone for at least two years.

Use in specific populations

Sourced from openFDA

Females and Males of Reproductive Potential: Advise premenopausal females of the potential for an unintended pregnancy. (8.3) Pediatrics: Not recommended for use in pediatric patients. (8.4) 8.1 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 [see Clinical Considerations] . 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 [see Data] . The estimated background risk of major birth defects is 6 to 10% in women with pre-gestational diabetes with a HbA1c >7 and has been reported to be as high as 20 to 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 to 4% and 15 to 20%, respectively.

Pharmacokinetics

Sourced from openFDA
Metabolism
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.

Overdosage

Sourced from openFDA

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.

Approval history

Sourced from openFDA
  • Jul 15, 1999NDANDA021073Takeda Pharms Usa
  • Aug 29, 2005NDANDA021842Takeda Pharms Usa
  • Jul 28, 2006NDANDA021925Takeda Pharms Usa
  • Oct 26, 2012ANDAANDA076798Chartwell Rx
  • Jan 25, 2013NDANDA022426Takeda Pharms Usa
  • Feb 6, 2013ANDAANDA202467Macleods Pharms Ltd
  • Feb 13, 2013ANDAANDA200823Aurobindo Pharma Ltd
  • Feb 13, 2013ANDAANDA200268Aurobindo Pharma Ltd

FAERS reports

View JSON
Reference statistics only. FAERS reports are voluntarily submitted and are not incidence rates, safety signals, or causal evidence. Counts reflect reporting volume — how often a reaction was reported, not how often it occurs. For decision-grade use, consult openFDA and the FAERS Public Dashboard directly.
45,220 total reports matchedLatest report Share = reports listing the reaction ÷ total matched reports. Rows can sum to >100% because a single report often lists multiple reactions.
  1. 1Bladder Cancer8,85320%
  2. 2Blood Glucose Increased3,5607.9%
  3. 3Nausea3,1206.9%
  4. 4Weight Decreased2,1984.9%
  5. 5Diarrhoea1,8144.0%
  6. 6Drug Ineffective1,6023.5%
  7. 7Fatigue1,5963.5%
  8. 8Death1,5883.5%
  9. 9Vomiting1,5463.4%
  10. 10Dyspnoea1,5433.4%
  11. 11Dizziness1,5013.3%
  12. 12Decreased Appetite1,4763.3%
  13. 13Weight Increased1,3803.1%
  14. 14Blood Glucose Decreased1,2642.8%
  15. 15Asthenia1,2422.7%

Literature

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Recent PubMed references pinned to Pioglitazone as a MeSH major topic. Citations link to pubmed.ncbi.nlm.nih.gov.

Clinical trials

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The 10 most recently updated of 564 ClinicalTrials.gov registrations naming Pioglitazone as an intervention. Registration is not evidence of efficacy or safety — reference crosswalk only.

Frequently asked questions

How does Pioglitazone work?
Pioglitazone is a thiazolidinedione that 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.
What is Pioglitazone used for?
According to FDA labeling, Pioglitazone carries indications including: Monotherapy and Combination Therapy Pioglitazone tablets are indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus in multiple clinical settings [see Clinical Studies (14) ] . Important Limitations of Use Pioglitazone tablets exert its antihyperglycemic effect only in the presence of endogenous insulin.. This is a reference summary of labeled uses, not medical advice or a treatment recommendation.
What class of drug is Pioglitazone?
Pioglitazone is classified as Thiazolidinediones, Peroxisome Proliferator-activated Receptor alpha Agonist, Peroxisome Proliferator-activated Receptor gamma Agonist, Thiazolidinedione, Insulin Receptor Agonists, Peroxisome Proliferator-activated Receptor alpha Agonists, Peroxisome Proliferator-activated Receptor gamma Agonists, Increased Glucose Transport into Cells, Increased Glycolysis.
What are the brand names for Pioglitazone?
Pioglitazone is marketed under brand names including Actoplus Met, Actos, Duetact, Oseni.
What are the contraindications for Pioglitazone?
Pioglitazone labeling lists contraindications including: Initiation in patients with established NYHA Class III or IV heart failure [see Boxed Warning ]. Use in patients with known hypersensitivity to pioglitazone or any other component of pioglitazone tablets.. Always consult the full prescribing information and a clinician.
Note. Data for pioglitazone is illustrative MVP content compiled from public sources. pharmacopeia is for educational and informational use only and is not a substitute for professional medical advice.

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