{
 "query": "pioglitazone",
 "ingredient": "pioglitazone",
 "slug": "pioglitazone",
 "rxcui": "33738",
 "brands": [
  "Actos"
 ],
 "names": [
  "pioglitazone",
  "pioglitazone hydrochloride"
 ],
 "classes": [
  {
   "id": "A10BG",
   "name": "Thiazolidinediones"
  }
 ],
 "alternatives": [
  "rosiglitazone",
  "troglitazone"
 ],
 "label": {
  "route_mode": "ORAL",
  "route_counts": {
   "ORAL": 52
  },
  "boxed_warning": "WARNING: CONGESTIVE HEART FAILURE \u2022 Thiazolidinediones, including pioglitazone, cause or exacerbate congestive heart failure in some patients [see ] . \u2022 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. \u2022 Pioglitazone is not recommended in patients with symptomatic heart failure. \u2022 Initiation of pioglitazone in patients with established New York Heart Association (NYHA) Class III or IV heart failure is contraindicated [see and ] . \u2022 Thiazolidinediones, including pioglitazone, cause or exacerbate congestive heart failure in some patients. \u2022 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. \u2022 Piog...",
  "indications_and_usage": "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. Pioglitazone tablets should not be used to treat type 1 diabetes or diabetic ketoacidosis, as it would not be effective in these settings. Use caution in patients with liver disease [see ] . Pioglitazone is a thiazolidinedione and an agonist for peroxisome proliferator-activated receptor (PPAR) gamma indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus in multiple clinical settings. ( 14) Important Limitations of Use: \u2022 Not for treatment of type 1 diabetes or diabetic ketoacidosis. ()",
  "contraindications": "\u2022 Initiation in patients with established NYHA Class III or IV heart failure [see ]. \u2022 Use in patients with known hypersensitivity to pioglitazone or any other component of pioglitazone tablets. \u2022 Initiation in patients with established New York Heart Association (NYHA) Class III or IV heart failure [see Boxed Warning] . \u2022 Use in patients with known hypersensitivity to pioglitazone or any other component of pioglitazone tablets.",
  "warnings_and_cautions": "\u2022 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. \u2022 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. \u2022 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. \u2022 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. \u2022 Edema: Dose-related edema may occur. \u2022 Fractures: Increased incidence in female patients. Apply current standards of care for assessing and maintaining bone health. \u2022 Macular edema: Postmarketing reports. Recommend regular...",
  "warnings": "",
  "adverse_reactions": "The following serious adverse reactions are discussed elsewhere in the labeling: \u2022 Congestive heart failure [see and ] \u2022 Edema [see Warnings and Precautions ] \u2022 Fractures [see Warnings and Precautions ] Most common adverse reactions (\u22655%) are upper respiratory tract infection, headache, sinusitis, myalgia, and pharyngitis. To report SUSPECTED ADVERSE REACTIONS, contact Rising Health, LLC at 1-833-395-6928 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 ov...",
  "drug_abuse_and_dependence": "",
  "controlled_substance": "",
  "recent_major_changes": "Warnings and Precautions Urinary bladder tumors () 12/2016",
  "information_for_patients": "See FDA-Approved Patient Labeling (Medication Guide). \u2022 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. \u2022 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. \u2022 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. \u2022 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. \u2022 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....",
  "spl_medguide": "MEDICATION GUIDE Pioglitazone Tablets, USP (pye\" oh gli' ta zone) Read this Medication Guide carefully before you start taking pioglitazone tablets and each time you get a refill. There may be new information. This information does not take the place of talking with your doctor about your medical condition or your treatment. If you have any questions about pioglitazone tablets, ask your doctor or pharmacist. What is the most important information I should know about pioglitazone tablets? Pioglitazone tablets can cause serious side effects, including new or worse heart failure. \u2022 Pioglitazone tablets 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 \u2022 Do not take pioglitazone tablets if you have severe heart failure \u2022 If you have heart failure with symptoms (such as shortness of breath or swelling), even if these symptoms are not severe, pioglitazone tablets may not be right for you Call your doctor right away if you have any of the following: \u2022 swelling or fluid retention, especially in...",
  "clinical_studies": "14.1 Monotherapy Three randomized, double-blind, placebo-controlled trials with durations from 16 to 26 weeks were conducted to evaluate the use of pioglitazone as monotherapy in patients with type 2 diabetes. These trials examined pioglitazone at doses up to 45 mg or placebo once daily in a total of 865 patients. In a 26-week dose-ranging monotherapy trial, 408 patients with type 2 diabetes were randomized to receive 7.5 mg, 15 mg, 30 mg, or 45 mg of pioglitazone, or placebo once daily. Therapy with any previous antidiabetic agent was discontinued eight weeks prior to the double-blind period. Treatment with 15 mg, 30 mg, and 45 mg of pioglitazone produced statistically significant improvements in HbA1c and fasting plasma glucose (FPG) at endpoint compared to placebo (see Figure 1, Table 17). Figure 1 shows the time course for changes in HbA1c in this 26-week study. Table 16. Glycemic Parameters in a 26-Week Placebo-Controlled Dose-Ranging Monotherapy Trial Placebo Pioglitazone 15 mg Once Daily Pioglitazone 30 mg Once Daily Pioglitazone 45 mg Once Daily Total Population HbA1c (%) N = 79 N = 79 N = 85 N = 76 Baseline (mean) 10.4 10.2 10.2 10.3 Change from baseline (adjusted mean) 0....",
  "brand_name": "Pioglitazone",
  "manufacturer": "Preferred Pharmaceuticals, Inc.",
  "application_number": "ANDA200268",
  "pharm_class_epc": [],
  "route": [
   "ORAL"
  ],
  "effective_time": "20260817",
  "set_id": "164c444c-7c56-4482-9cbd-0e0f0ad30c44",
  "has_boxed_warning": true,
  "controlled": false,
  "mentions_rems": false
 },
 "faers": {
  "total": 25065,
  "serious": 19392,
  "death": 3030,
  "hospitalization": 5943,
  "primary_suspect": 25049,
  "top_reactions": [
   [
    "Bladder Cancer",
    7302
   ],
   [
    "Death",
    1383
   ],
   [
    "Nausea",
    1057
   ],
   [
    "Diarrhoea",
    967
   ],
   [
    "Blood Glucose Increased",
    928
   ],
   [
    "Fatigue",
    840
   ],
   [
    "Drug Ineffective",
    804
   ],
   [
    "Acute Kidney Injury",
    799
   ],
   [
    "Chronic Kidney Disease",
    787
   ],
   [
    "Dyspnoea",
    670
   ],
   [
    "Vomiting",
    641
   ],
   [
    "Renal Failure",
    631
   ],
   [
    "Off Label Use",
    630
   ],
   [
    "Weight Decreased",
    565
   ],
   [
    "Dizziness",
    554
   ]
  ],
  "by_year": {
   "2019": 1892,
   "2020": 1586,
   "2021": 1230,
   "2022": 1081,
   "2023": 999,
   "2024": 1037,
   "2025": 975,
   "2026": 469
  },
  "by_year_primary": {
   "2019": 1892,
   "2020": 1585,
   "2021": 1226,
   "2022": 1079,
   "2023": 997,
   "2024": 1033,
   "2025": 974,
   "2026": 468
  }
 },
 "faers_base": {
  "total": 20692304,
  "serious_share": 0.5742697381596559,
  "death_share": 0.09102355155810585
 },
 "recalls": [
  {
   "class": "Class II",
   "date": "20211229",
   "reason": "Superpotent and Failed Tablet/Capsule Specifications",
   "firm": "Aurobindo Pharma USA Inc.",
   "status": "Terminated"
  },
  {
   "class": "Class II",
   "date": "20190923",
   "reason": "Superpotent",
   "firm": "Macleods Pharma Usa Inc",
   "status": "Terminated"
  }
 ],
 "recall_total": 2,
 "drugsfda": {
  "applications": 17,
  "nda": 1,
  "anda": 15,
  "first_approval": "19990715",
  "rems": false,
  "rems_last": "20120517",
  "labeling_supplements": 18,
  "labeling_recent": 0,
  "sponsors": [
   "ACCORD HLTHCARE",
   "AIPING PHARM INC",
   "ALPHAPHARM",
   "ANNORA PHARMA",
   "AUROBINDO PHARMA LTD",
   "CHARTWELL RX",
   "MACLEODS PHARMS LTD",
   "PHARMOBEDIENT"
  ],
  "unapproved": false,
  "first_approval_fmt": "07/15/1999"
 },
 "trials": {
  "total": 566,
  "completed": 386,
  "terminated": 74,
  "with_results": 194,
  "industry": 253,
  "phase3": 127,
  "results_share": 0.5025906735751295,
  "terminated_share": 0.13074204946996468
 },
 "pubmed": {
  "rct": 594,
  "meta": 75,
  "recent_rct": 43,
  "cochrane": [
   {
    "pmid": "33210751",
    "title": "Pioglitazone for prevention or delay of type 2 diabetes mellitus and its associated complications in people at risk for the development of type 2 diabetes mellitus",
    "year": "2020"
   },
   {
    "pmid": "29183107",
    "title": "Insulin-sensitising drugs (metformin, rosiglitazone, pioglitazone, D-chiro-inositol) for women with polycystic ovary syndrome, oligo amenorrhoea and subfertility",
    "year": "2017"
   },
   {
    "pmid": "22592687",
    "title": "Insulin-sensitising drugs (metformin, rosiglitazone, pioglitazone, D-chiro-inositol) for women with polycystic ovary syndrome, oligo amenorrhoea and subfertility",
    "year": "2012"
   },
   {
    "pmid": "20091537",
    "title": "Insulin-sensitising drugs (metformin, rosiglitazone, pioglitazone, D-chiro-inositol) for women with polycystic ovary syndrome, oligo amenorrhoea and subfertility",
    "year": "2010"
   },
   {
    "pmid": "19821299",
    "title": "Insulin-sensitising drugs (metformin, rosiglitazone, pioglitazone, D-chiro-inositol) for women with polycystic ovary syndrome, oligo amenorrhoea and subfertility",
    "year": "2009"
   },
   {
    "pmid": "17054272",
    "title": "Pioglitazone for type 2 diabetes mellitus",
    "year": "2006"
   },
   {
    "pmid": "12917943",
    "title": "Insulin-sensitising drugs (metformin, troglitazone, rosiglitazone, pioglitazone, D-chiro-inositol) for polycystic ovary syndrome",
    "year": "2003"
   }
  ]
 },
 "payments": {
  "year": "2024",
  "usd": 56.8,
  "records": 3,
  "by_name": [
   [
    "Actos",
    56.8
   ]
  ],
  "names_checked": [
   "pioglitazone",
   "Actos"
  ],
  "source": "bulk-index"
 },
 "partd": {
  "year": "2024",
  "claims": 3218582,
  "beneficiaries": 846095,
  "spend": 43025250.2,
  "by_brand": [
   {
    "brand": "Pioglitazone HCl",
    "claims": 3217957,
    "per_claim": 13.168227938,
    "is_generic": true
   },
   {
    "brand": "Actos",
    "claims": 625,
    "per_claim": 1040.734288,
    "is_generic": false
   }
  ],
  "per_claim": 13.367765742802266
 },
 "mdl": [],
 "dsc": [
  {
   "date": "20161212",
   "title": "Updated FDA review concludes that use of type 2 diabetes medicine pioglitazone may be linked to an increased risk of bladder cancer",
   "url": "https://www.fda.gov/Drugs/DrugSafety/ucm519616.htm",
   "kind": "drug",
   "matched": "pioglitazone"
  },
  {
   "date": "20110804",
   "title": "Actos (pioglitazone) - Updated drug labels for pioglitazone-containing medicines",
   "url": "https://www.fda.gov/Drugs/DrugSafety/ucm266555.htm",
   "kind": "drug",
   "matched": "pioglitazone"
  },
  {
   "date": "20110615",
   "title": "Actos - Update to ongoing safety review of Actos (pioglitazone) and increased risk of bladder cancer",
   "url": "https://www.fda.gov/Drugs/DrugSafety/ucm259150.htm",
   "kind": "drug",
   "matched": "pioglitazone"
  },
  {
   "date": "20100917",
   "title": "Actos (pioglitazone) - Ongoing Safety Review of Actos (pioglitazone) and Potential Increased Risk of Bladder Cancer After Two Years Exposure",
   "url": "https://www.fda.gov/Drugs/DrugSafety/ucm226214.htm",
   "kind": "drug",
   "matched": "pioglitazone"
  }
 ],
 "settlements": [],
 "prescrire": {
  "section": "Allergy",
  "names": [
   "pioglitazone"
  ],
  "reason": "Pioglitazone also has a burdensome adverse effect profile, including heart failure, bladder cancer and bone fractures ( Prescrire Int n\u00b0 129, 160). Weight loss. The treatment of excess body weight usually primarily relies on changes to the patient\u2019s physical activity and diet, along with psychological support if necessary.",
  "edition": "2026",
  "qualifier": null,
  "qualified": false,
  "matched": "pioglitazone"
 },
 "eml": {
  "listed": false,
  "status": "",
  "name": "",
  "matched": null,
  "stewardship": []
 },
 "exposure": {
  "years": [
   "2024",
   "2025",
   "2026"
  ],
  "reports_recent": 2475,
  "fills": 3218582,
  "per_million": 768.9721747030214,
  "ratio": 0.27771257808140737,
  "median": 2768.949753790441
 },
 "scores": {
  "safety": {
   "score": 40,
   "letter": "F",
   "why": [
    "Carries an FDA boxed warning, the strongest warning the FDA issues (-30)",
    "FDA issued 4 Drug Safety Communication(s) naming this drug since 2010, most recently 2016 (-20)",
    "Listed by the independent review Prescrire as a drug to avoid (2026 edition) (-10)",
    "769 FDA reports naming it as the suspect drug per million Medicare fills, 0.3x the median drug on this site",
    "Death share in reports is near or below the FAERS average (1.3x)"
   ],
   "weight": 0.35
  },
  "evidence": {
   "score": 76,
   "letter": "B",
   "why": [
    "594 randomized trials and 75 systematic reviews/meta-analyses indexed in PubMed",
    "Prescrire's independent reviewers find its harm-benefit balance unfavourable versus alternatives (-10)",
    "7 independent Cochrane review(s) exist"
   ],
   "weight": 0.25
  },
  "regulatory": {
   "score": 92,
   "letter": "A",
   "why": [
    "Recalls since 2016: 0 Class I, 2 Class II, 0 Class III across 15 generic makers (-3)",
    "Label lists recent major changes to warnings or indications (-5)"
   ],
   "weight": 0.15
  },
  "conflict": {
   "score": 100,
   "letter": "A",
   "why": [
    "Pharma paid doctors $57 tied to this drug last year: negligible",
    "Not named in any pending federal MDL"
   ],
   "weight": 0.15
  },
  "options": {
   "score": 90,
   "letter": "A",
   "why": [
    "Generic versions approved (15 applications)",
    "2 same-class alternative(s) (-10)"
   ],
   "weight": 0.1
  }
 },
 "total": 71,
 "grade": "C",
 "questions": [
  "In 2016 the FDA issued a safety communication about this drug (Updated FDA review concludes that use of type 2 diabetes medicine pioglitazone may be linked to an increased r). Does that risk apply to me?",
  "An independent reviewer (Prescrire) lists this as a drug to avoid because the harms outweigh the benefits versus alternatives. What is your view on that?",
  "This drug carries a boxed warning. Which specific risk does it cover, and does it apply to me?",
  "The most-reported problems in FDA's adverse event data are bladder cancer, death, nausea, diarrhoea. How would we recognize and handle those?",
  "Why this one over rosiglitazone, troglitazone? What would make you pick one of those instead?",
  "What result are we expecting, by when, and what is the plan if it does not happen?",
  "If 100 people like me took this drug, how many would actually get better because of it, and how many would be harmed by it? (Doctors call these the number needed to treat and the number needed to harm.)"
 ]
}