Actos

Serious warning

The strongest warning the FDA requires. It is printed in a box at the top of the label.

Quoted from the official label, section “Boxed Warning”.

Do not take it if

Quoted from the official label, section “Contraindications”.

How to take it

These directions are for this exact strength and form. Another one is different.

• Initiate ACTOS 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 ACTOS. If abnormal, use caution when treating with ACTOS, investigate the probable cause, treat (if possible) and follow appropriately. Monitoring liver tests while on ACTOS is not recommended in patients without liver disease. ( 5.3 ) 2.1 Recommendations for All Patients ACTOS 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 ACTOS 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 ACTOS. Routine periodic monitoring of liver tests during treatment with ACTOS is not recommended in patients without liver disease. Patients who have liver test abnormalities prior to initiation of ACTOS or who are found to have abnormal liver tests while taking ACTOS should be managed as described under Warnings and Precautions [see Warnings and Precautions (5.3) and Clinical Pharmacology (12.3) ] . 2.2 Concomitant Use with an Insulin Secretagogue or Insulin If hypoglycemia occurs in a patient co-administered ACTOS and an insulin secretagogue (e.g., sulfonylurea), the dose of the insulin secretagogue should be reduced. If hypoglycemia occurs in a patient co-administered ACTOS and insulin, the dose of insulin should be decreased by 10% to 25%. Further adjustments to the insulin dose should be individualized based on glycemic response. 2.3 Concomitant Use with Strong CYP2C8 Inhibitors Coadministration of ACTOS and gemfibrozil, a strong CYP2C8 inhibitor, increases pioglitazone exposure approximately 3-fold. Therefore, the maximum recommended dose of ACTOS is 15 mg daily when used in combination with gemfibrozil or other strong CYP2C8 inhibitors [see Drug Interactions (7.1) and Clinical Pharmacology (12.3) ].

Quoted from the official label, section “Dosage & Administration”.

Other warnings

Quoted from the official label, section “Warnings”.

Pregnancy and breastfeeding

Quoted from the official label, section “OTC — Pregnancy or Breast Feeding”.

Other medicines

Quoted from the official label, section “Drug Interactions”.

If you take too much

In an emergency, call your local emergency number or a poison control centre.

Quoted from the official label, section “Overdosage”.

Use in children

• Safety and effectiveness of ACTOS in pediatric patients have not been established.
• ACTOS is not recommended for use in pediatric patients based on adverse effects observed in
• adults, including fluid retention and congestive heart failure, fractures, and urinary bladder tumors [see Warnings and Precautions (5.1, 5.4, 5.5, and 5.6) ] .

Quoted from the official label, section “Pediatric Use”.

Use in older people

• A total of 92 patients (15.2%) treated with ACTOS in the three pooled 16- to 26-week double-blind, placebo-controlled, monotherapy trials were ≥65 years old and two patients (0.3%) were ≥75 years old.
• In the two pooled 16- to 24-week add-on to sulfonylurea trials, 201 patients (18.7%) treated with ACTOS were ≥65 years old and 19 (1.8%) were ≥75 years old.
• In the two pooled 16- to 24-week add-on to metformin trials, 155 patients (15.5%) treated with ACTOS were ≥65 years old and 19 (1.9%) were ≥75 years old.
• In the two pooled 16- to 24-week add-on to insulin trials, 272 patients (25.4%) treated with ACTOS were ≥65 years old and 22 (2.1%) were ≥75 years old.
• In PROactive, 1068 patients (41.0%) treated with ACTOS were ≥65 years old and 42 (1.6%) were ≥75 years old.
• In pharmacokinetic studies with pioglitazone, no significant differences were observed in pharmacokinetic parameters between elderly and younger patients [see Clinical Pharmacology (12.3) ] .
• Although clinical experiences have not identified differences in effectiveness and safety between the elderly (≥65 years) and younger patients, these conclusions are limited by small sample sizes for patients ≥75 years old.

Quoted from the official label, section “Geriatric Use”.

Side effects

• 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 Takeda Pharmaceuticals America, Inc. at 1-877-TAKEDA-7 (1-877-825-3327) 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 ACTOS in randomized, double-blind, controlled clinical trials, including 2605 patients with type 2 diabetes and macrovascular disease treated with ACTOS in the PROactive clinical trial. In these trials, over 6000 patients have been treated with ACTOS for six months or longer, over 4500 patients have been treated with ACTOS for one year or longer, and over 3000 patients have been treated with ACTOS for at least two years. In six pooled 16- to 26-week placebo-controlled monotherapy and 16- to 24-week add-on combination therapy trials, the incidence of withdrawals due to adverse events was 4.5% for patients treated with ACTOS and 5.8% for comparator-treated patients. The most common adverse events leading to withdrawal were related to inadequate glycemic control, although the incidence of these events was lower (1.5%) with ACTOS than with placebo (3.0%). In the PROactive trial, the incidence of withdrawals due to adverse events was 9.0% for patients treated with ACTOS and 7.7% for placebo-treated patients. Congestive heart failure was the most common serious adverse event leading to withdrawal occurring in 1.3% of patients treated with ACTOS and 0.6% of patients treated with placebo. Common Adverse Events:
• 16- to 26-Week Monotherapy Trials A summary of the incidence and type of common adverse events reported in three pooled 16- to 26-week placebo-controlled monotherapy trials of ACTOS is provided in Table 1. Terms that are reported represent those that occurred at an incidence of >5% and more commonly in patients treated with ACTOS than in patients who received placebo. None of these adverse events were related to ACTOS dose. Table 1. Three Pooled 16- to 26-Week Placebo-Controlled Clinical Trials of ACTOS Monotherapy:
• Adverse Events Reported at an Incidence >5% and More Commonly in Patients Treated with ACTOS than in Patients Treated with Placebo % of Patients Placebo N=259 ACTOS N=606 Upper Respiratory Tract Infection 8.5 13.2 Headache 6.9 9.1 Sinusitis 4.6 6.3 Myalgia 2.7 5.4 Pharyngitis 0.8 5.1 Common Adverse Events:
• 16- to 24-Week Add-on Combination Therapy Trials A summary of the overall incidence and types of common adverse events reported in trials of ACTOS add-on to sulfonylurea is provided in Table 2. Terms that are reported represent those that occurred at an incidence of >5% and more commonly with the highest tested dose of ACTOS. Table 2. 16- to 24-Week Clinical Trials of ACTOS Add-on to Sulfonylurea 16-Week Placebo-Controlled Trial Adverse Events Reported in >5% of Patients and More Commonly in Patients Treated with ACTOS 30 mg + Sulfonylurea than in Patients Treated with Placebo + Sulfonylurea % of Patients Placebo + Sulfonylurea N=187 ACTOS 15 mg + Sulfonylurea N=184 ACTOS 30 mg + Sulfonylurea N=189 Edema 2.1 1.6 12.7 Headache 3.7 4.3 5.3 Flatulence 0.5 2.7 6.3 Weight Increased 0 2.7 5.3 24-Week Non-Controlled Double-Blind Trial Adverse Events Reported in >5% of Patients and More Commonly in Patients Treated with ACTOS 45 mg + Sulfonylurea than in Patients Treated with ACTOS 30 mg + Sulfonylurea % of Patients ACTOS 30 mg + Sulfonylurea N=351 ACTOS 45 mg + Sulfonylurea N=351 Hypoglycemia 13.4 15.7 Edema 10.5 23.1 Upper Respiratory Tract Infection 12.3 14.8 Weight Increased 9.1 13.4 Urinary Tract Infection 5.7 6.8 Note:
• The preferred terms of edema peripheral, generalized edema, pitting edema and fluid retention were combined to form the aggregate term of "edema." A summary of the overall incidence and types of common adverse events reported in trials of ACTOS add-on to metformin is provided in Table 3. Terms that are reported represent those that occurred at an incidence of >5% and more commonly with the highest tested dose of ACTOS. Table 3. 16- to 24-Week Clinical Trials of ACTOS Add-on to Metformin 16-Week Placebo-Controlled Trial Adverse Events Reported in >5% of Patients and More Commonly in Patients Treated with ACTOS + Metformin than in Patients Treated with Placebo + Metformin % of Patients Placebo + Metformin N=160 ACTOS 30 mg + Metformin N=168 Edema 2.5 6.0 Headache 1.9 6.0 24-Week Non-Controlled Double-Blind Trial Adverse Events Reported in >5% of Patients and More Commonly in Patients Treated with ACTOS 45 mg + Metformin than in Patients Treated with ACTOS 30 mg + Metformin % of Patients ACTOS 30 mg + Metformin N=411 ACTOS 45 mg + Metformin N=416 Upper Respiratory Tract Infection 12.4 13.5 Edema 5.8 13.9 Headache 5.4 5.8 Weight Increased 2.9 6.7 Note:
• The preferred terms of edema peripheral, generalized edema, pitting edema and fluid retention were combined to form the aggregate term of "edema." Table 4 summarizes the incidence and types of common adverse events reported in trials of ACTOS add-on to insulin. Terms that are reported represent those that occurred at an incidence of >5% and more commonly with the highest tested dose of ACTOS. Table 4. 16- to 24-Week Clinical Trials of ACTOS Add-on to Insulin 16-Week Placebo-Controlled Trial Adverse Events Reported in >5% of Patients and More Commonly in Patients Treated with ACTOS 30 mg + Insulin than in Patients Treated with Placebo + Insulin % of Patients Placebo + Insulin N=187 ACTOS 15 mg + Insulin N=191 ACTOS 30 mg + Insulin N=188 Hypoglycemia 4.8 7.9 15.4 Edema 7.0 12.6 17.6 Upper Respiratory Tract Infection 9.6 8.4 14.9 Headache 3.2 3.1 6.9 Weight Increased 0.5 5.2 6.4 Back Pain 4.3 2.1 5.3 Dizziness 3.7 2.6 5.3 Flatulence 1.6 3.7 5.3 24-Week Non-Controlled Double-Blind Trial Adverse Events Reported in >5% of Patients and More Commonly in Patients Treated with ACTOS 45 mg + Insulin than in Patients Treated with ACTOS 30 mg + Insulin % of Patients ACTOS 30 mg + Insulin N=345 ACTOS 45 mg + Insulin N=345 Hypoglycemia 43.5 47.8 Edema 22.0 26.1 Weight Increased 7.2 13.9 Urinary Tract Infection 4.9 8.7 Diarrhea 5.5 5.8 Back Pain 3.8 6.4 Blood Creatine Phosphokinase Increased 4.6 5.5 Sinusitis 4.6 5.5 Hypertension 4.1 5.5 Note:
• The preferred terms of edema peripheral, generalized edema, pitting edema and fluid retention were combined to form the aggregate term of "edema." A summary of the overall incidence and types of common adverse events reported in the PROactive trial is provided in Table 5. Terms that are reported represent those that occurred at an incidence of >5% and more commonly in patients treated with ACTOS than in patients who received placebo. Table 5. PROactive Trial:
• Incidence and Types of Adverse Events Reported in >5% of Patients Treated with ACTOS and More Commonly than Placebo % of Patients Placebo N=2633 ACTOS N=2605 Hypoglycemia 18.8 27.3 Edema 15.3 26.7 Cardiac Failure 6.1 8.1 Pain in Extremity 5.7 6.4 Back Pain 5.1 5.5 Chest Pain 5.0 5.1 Mean duration of patient follow-up was 34.5 months. Congestive Heart Failure A summary of the incidence of adverse events related to congestive heart failure is provided in Table 6 for the 16- to 24-week add-on to sulfonylurea trials, for the 16- to 24-week add-on to insulin trials, and for the 16- to 24-week add-on to metformin trials. None of the events were fatal. Table 6. Treatment-Emergent Adverse Events of Congestive Heart Failure (CHF) Patients Treated with ACTOS or Placebo Added on to a Sulfonylurea Number (%) of Patients Placebo-Controlled Trial (16 weeks) Non-Controlled Double-Blind Trial (24 weeks) Placebo + Sulfonylurea N=187 ACTOS 15 mg + Sulfonylurea N=184 ACTOS 30 mg + Sulfonylurea N=189 ACTOS 30 mg + Sulfonylurea N=351 ACTOS 45 mg + Sulfonylurea N=351 At least one congestive heart failure event 2 (1.1%) 0 0 1 (0.3%) 6 (1.7%) Hospitalized 2 (1.1%) 0 0 0 2 (0.6%) Patients Treated with ACTOS or Placebo Added on to Insulin Number (%) of Patients Placebo-Controlled Trial (16 weeks) Non-Controlled Double-Blind Trial (24 weeks) Placebo + Insulin N=187 ACTOS 15 mg + Insulin N=191 ACTOS 30 mg + Insulin N=188 ACTOS 30 mg + Insulin N=345 ACTOS 45 mg + Insulin N=345 At least one congestive heart failure event 0 2 (1.0%) 2 (1.1%) 3 (0.9%) 5 (1.4%) Hospitalized 0 2 (1.0%) 1 (0.5%) 1 (0.3%) 3 (0.9%) Patients Treated with ACTOS or Placebo Added on to Metformin Number (%) of Patients Placebo-Controlled Trial (16 weeks) Non-Controlled Double-Blind Trial (24 weeks) Placebo + Metformin N=160 ACTOS 30 mg + Metformin N=168 ACTOS 30 mg + Metformin N=411 ACTOS 45 mg + Metformin N=416 At least one congestive heart failure event 0 1 (0.6%) 0 1 (0.2%) Hospitalized 0 1 (0.6%) 0 1 (0.2%) Patients with type 2 diabetes and NYHA class II or early class III congestive heart failure were randomized to receive 24 weeks of double-blind treatment with either ACTOS at daily doses of 30 mg to 45 mg (n=262) or glyburide at daily doses of 10 mg to 15 mg (n=256). A summary of the incidence of adverse events related to congestive heart failure reported in this study is provided in Table 7. Table 7. Treatment-Emergent Adverse Events of Congestive Heart Failure (CHF) in Patients with NYHA Class II or III Congestive Heart Failure Treated with ACTOS or Glyburide Number (%) of Subjects ACTOS N=262 Glyburide N=256 Death due to cardiovascular causes (adjudicated) 5 (1.9%) 6 (2.3%) Overnight hospitalization for worsening CHF (adjudicated) 26 (9.9%) 12 (4.7%) Emergency room visit for CHF (adjudicated) 4 (1.5%) 3 (1.2%) Patients experiencing CHF progression during study 35 (13.4%) 21 (8.2%) Congestive heart failure events leading to hospitalization that occurred during the PROactive trial are summarized in Table 8. Table 8. Treatment-Emergent Adverse Events of Congestive Heart Failure (CHF) in PROactive Trial Number (%) of Patients Placebo N=2633 ACTOS N=2605 At least one hospitalized congestive heart failure event 108 (4.1%) 149 (5.7%) Fatal 22 (0.8%) 25 (1.0%) Hospitalized, nonfatal 86 (3.3%) 124 (4.7%) Cardiovascular Safety In the PROactive trial, 5238 patients with type 2 diabetes and a history of macrovascular disease were randomized to ACTOS (N=2605), force-titrated up to 45 mg daily or placebo (N=2633) in addition to standard of care. Almost all patients (95%) were receiving cardiovascular medications (beta blockers, ACE inhibitors, angiotensin II receptor blockers, calcium channel blockers, nitrates, diuretics, aspirin, statins and fibrates). At baseline, patients had a mean age of 62 years, mean duration of diabetes of 9.5 years, and mean HbA1c of 8.1%. Mean duration of follow-up was 34.5 months. The primary objective of this trial was to examine the effect of ACTOS on mortality and macrovascular morbidity in patients with type 2 diabetes mellitus who were at high risk for macrovascular events. The primary efficacy variable was the time to the first occurrence of any event in a cardiovascular composite endpoint that included all-cause mortality, nonfatal myocardial infarction (MI) including silent MI, stroke, acute coronary syndrome, cardiac intervention including coronary artery bypass grafting or percutaneous intervention, major leg amputation above the ankle, and bypass surgery or revascularization in the leg. A total of 514 (19.7%) patients treated with ACTOS and 572 (21.7%) placebo-treated patients experienced at least one event from the primary composite endpoint (hazard ratio 0.90; 95% Confidence Interval:
• 0.80, 1.02; p=0.10). Although there was no statistically significant difference between ACTOS and placebo for the three-year incidence of a first event within this composite, there was no increase in mortality or in total macrovascular events with ACTOS. The number of first occurrences and total individual events contributing to the primary composite endpoint is shown in Table 9. Table 9. PROactive:
• Number of First and Total Events for Each Component within the Cardiovascular Composite Endpoint Cardiovascular Events Placebo N=2633 ACTOS N=2605 First Events n (%) Total events n First Events n (%) Total events n Any event 572 (21.7) 900 514 (19.7) 803 All-cause mortality 122 (4.6) 186 110 (4.2) 177 Nonfatal myocardial infarction (MI) 118 (4.5) 157 105 (4.0) 131 Stroke 96 (3.6) 119 76 (2.9) 92 Acute coronary syndrome 63 (2.4) 78 42 (1.6) 65 Cardiac intervention (CABG/PCI) 101 (3.8) 240 101 (3.9) 195 Major leg amputation 15 (0.6) 28 9 (0.3) 28 Leg revascularization 57 (2.2) 92 71 (2.7) 115 CABG = coronary artery bypass grafting; PCI = percutaneous intervention Weight Gain Dose-related weight gain occurs when ACTOS is used alone or in combination with other antidiabetic medications. The mechanism of weight gain is unclear but probably involves a combination of fluid retention and fat accumulation. Tables 10 and 11 summarize the changes in body weight with ACTOS and placebo in the 16- to 26-week randomized, double-blind monotherapy and 16- to 24-week combination add-on therapy trials and in the PROactive trial. Table 10. Weight Changes (kg) from Baseline During Randomized, Double-Blind Clinical Trials Control Group (Placebo) ACTOS 15 mg ACTOS 30 mg ACTOS 45 mg Median (25 th /75 th percentile) Median (25 th /75 th percentile) Median (25 th /75 th percentile) Median (25 th /75 th percentile) Monotherapy (16 to 26 weeks) -1.4 (-2.7/0.0) N=256 0.9 (-0.5/3.4) N=79 1.0 (-0.9/3.4) N=188 2.6 (0.2/5.4) N=79 Combination Therapy (16 to 24 weeks) Sulfonylurea -0.5 (-1.8/0.7) N=187 2.0 (0.2/3.2) N=183 3.1 (1.1/5.4) N=528 4.1 (1.8/7.3) N=333 Metformin -1.4 (-3.2/0.3) N=160 N/A 0.9 (-1.3/3.2) N=567 1.8 (-0.9/5.0) N=407 Insulin 0.2 (-1.4/1.4) N=182 2.3 (0.5/4.3) N=190 3.3 (0.9/6.3) N=522 4.1 (1.4/6.8) N=338 Table 11. Median Change in Body Weight in Patients Treated with ACTOS Versus Patients Treated with Placebo During the Double-Blind Treatment Period in the PROactive Trial Placebo ACTOS Median (25 th /75 th percentile) Median (25 th /75 th percentile) Change from baseline to final visit (kg) -0.5 (-3.3, 2.0) N=2581 +3.6 (0.0, 7.5) N=2560 Note:
• Median exposure for both ACTOS and Placebo was 2.7 years. Edema Edema induced from taking ACTOS is reversible when ACTOS is discontinued. The edema usually does not require hospitalization unless there is coexisting congestive heart failure. A summary of the frequency and types of edema adverse events occurring in clinical investigations of ACTOS is provided in Table 12. Table 12. Adverse Events of Edema in Patients Treated with ACTOS Number (%) of Patients Placebo ACTOS 15 mg ACTOS 30 mg ACTOS 45 mg Monotherapy (16 to 26 weeks) 3 (1.2%) N=259 2 (2.5%) N= 81 13 (4.7%) N= 275 11 (6.5%) N=169 Combined Therapy (16 to 24 weeks) Sulfonylurea 4 (2.1%) N=187 3 (1.6%) N=184 61 (11.3%) N=540 81 (23.1%) N=351 Metformin 4 (2.5%) N=160 N/A 34 (5.9%) N=579 58 (13.9%) N=416 Insulin 13 (7.0%) N=187 24 (12.6%) N=191 109 (20.5%) N=533 90 (26.1%) N=345 Note:
• The preferred terms of edema peripheral, generalized edema, pitting edema and fluid retention were combined to form the aggregate term of "edema." Table 13. Adverse Events of Edema in Patients in the PROactive Trial Number (%) of Patients Placebo N=2633 ACTOS N=2605 419 (15.9%) 712 (27.3%) Note:
• The preferred terms of edema peripheral, generalized edema, pitting edema and fluid retention were combined to form the aggregate term of "edema." Hepatic Effects There has been no evidence of induced hepatotoxicity with ACTOS in the ACTOS controlled clinical trial database to date. One randomized, double-blind 3-year trial comparing ACTOS to glyburide as add-on to metformin and insulin therapy was specifically designed to evaluate the incidence of serum ALT elevation to greater than three times the upper limit of the reference range, measured every eight weeks for the first 48 weeks of the trial then every 12 weeks thereafter. A total of 3/1051 (0.3%) patients treated with ACTOS and 9/1046 (0.9%) patients treated with glyburide developed ALT values greater than three times the upper limit of the reference range. None of the patients treated with ACTOS in the ACTOS controlled clinical trial database to date have had a serum ALT greater than three times the upper limit of the reference range and a corresponding total bilirubin greater than two times the upper limit of the reference range, a combination predictive of the potential for severe drug-induced liver injury. Hypoglycemia In the ACTOS clinical trials, adverse events of hypoglycemia were reported based on clinical judgment of the investigators and did not require confirmation with fingerstick glucose testing. In the 16-week add-on to sulfonylurea trial, the incidence of reported hypoglycemia was 3.7% with ACTOS 30 mg and 0.5% with placebo. In the 16-week add-on to insulin trial, the incidence of reported hypoglycemia was 7.9% with ACTOS 15 mg, 15.4% with ACTOS 30 mg, and 4.8% with placebo. The incidence of reported hypoglycemia was higher with ACTOS 45 mg compared to ACTOS 30 mg in both the 24-week add-on to sulfonylurea trial (15.7% vs. 13.4%) and in the 24-week add-on to insulin trial (47.8% vs. 43.5%). Three patients in these four trials were hospitalized due to hypoglycemia. All three patients were receiving ACTOS 30 mg (0.9%) in the 24-week add-on to insulin trial. An additional 14 patients reported severe hypoglycemia (defined as causing considerable interference with patient's usual activities) that did not require hospitalization. These patients were receiving ACTOS 45 mg in combination with sulfonylurea (n=2) or ACTOS 30 mg or 45 mg in combination with insulin (n=12). Urinary Bladder Tumors Tumors were observed in the urinary bladder of male rats in the two-year carcinogenicity study [see Nonclinical Toxicology (13.1 )] . During the three year PROactive clinical trial, 14 patients out of 2605 (0.54%) randomized to ACTOS and 5 out of 2633 (0.19%) randomized to placebo were diagnosed with bladder cancer. After excluding patients in whom exposure to study drug was less than one year at the time of diagnosis of bladder cancer, there were 6 (0.23%) cases on ACTOS and two (0.08%) cases on placebo. After completion of the trial, a large subset of patients was observed for up to 10 additional years, with little additional exposure to ACTOS. During the 13 years of both PROactive and observational follow-up, the occurrence of bladder cancer did not differ between patients randomized to ACTOS or placebo (HR =1.00; 95% CI:
• 0.59-1.72) [see Warnings and Precautions (5.4) ] . Laboratory Abnormalities Hematologic Effects ACTOS may cause decreases in hemoglobin and hematocrit. In placebo-controlled monotherapy trials, mean hemoglobin values declined by 2% to 4% in patients treated with ACTOS compared with a mean change in hemoglobin of -1% to +1% in placebo-treated patients. These changes primarily occurred within the first 4 to 12 weeks of therapy and remained relatively constant thereafter. These changes may be related to increased plasma volume associated with ACTOS therapy and are not likely to be associated with any clinically significant hematologic effects. Creatine Phosphokinase During protocol-specified measurement of serum creatine phosphokinase (CPK) in ACTOS clinical trials, an isolated elevation in CPK to greater than 10 times the upper limit of the reference range was noted in nine (0.2%) patients treated with ACTOS (values of 2150 to 11400 IU/L) and in no comparator-treated patients. Six of these nine patients continued to receive ACTOS, two patients were noted to have the CPK elevation on the last day of dosing and one patient discontinued ACTOS due to the elevation. These elevations resolved without any apparent clinical sequelae. The relationship of these events to ACTOS therapy is unknown. 6.2 Postmarketing Experience The following adverse reactions have been identified during post-approval use of ACTOS. Because these reactions are reported voluntarily from a population of uncertain size, it is generally not possible to reliably estimate their frequency or establish a causal relationship to drug exposure.
• New onset or worsening diabetic macular edema with decreased visual acuity [see Warnings and Precautions (5.7) ] .
• Fatal and nonfatal hepatic failure [see Warnings and Precautions (5.3) ] . Postmarketing reports of congestive heart failure have been reported in patients treated with ACTOS, both with and without previously known heart disease and both with and without concomitant insulin administration. In postmarketing experience, there have been reports of unusually rapid increases in weight and increases in excess of that generally observed in clinical trials. Patients who experience such increases should be assessed for fluid accumulation and volume-related events such as excessive edema and congestive heart failure [see Boxed Warning and Warnings and Precautions (5.1) ] .

Quoted from the official label, section “Adverse Reactions”.

What to discuss with your doctor

• See FDA-Approved Patient Labeling (Medication Guide).
• 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.
• 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 ACTOS should immediately report these symptoms to a physician.
• Tell patients to promptly stop taking ACTOS 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.
• 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.
• Tell patients to take ACTOS once daily. ACTOS can be taken with or without meals. If a dose is missed on one day, the dose should not be doubled the following day.
• When using combination therapy with insulin or other antidiabetic medications, the risks of hypoglycemia, its symptoms and treatment, and conditions that predispose to its development should be explained to patients and their family members.
• Inform female patients that treatment with ACTOS, like other thiazolidinediones, may result in an unintended pregnancy in some premenopausal anovulatory females due to its effect on ovulation [see Use in Specific Populations (8.3) ] . Distributed by:
• Takeda Pharmaceuticals America, Inc. Cambridge, MA 02142 ACTOS is a registered trademark of Takeda Pharmaceutical Company Limited. ©2025 Takeda Pharmaceuticals America, Inc. All rights reserved. ACT003 R24

Quoted from the official label, section “Patient Counseling Information”.

Strengths and forms

• FORMS AND STRENGTHS Round tablet contains pioglitazone as follows:
• 15 mg: White to off-white, debossed with "ACTOS" on one side and "15" on the other
• 30 mg: White to off-white, debossed with "ACTOS" on one side and "30" on the other
• 45 mg:
• White to off-white, debossed with "ACTOS" on one side and "45" on the other Tablets:
• 15 mg, 30 mg, and 45 mg ( 3 )

Quoted from the official label, section “Dosage Forms & Strengths”.

What it looks like and how it is packed

• ACTOS is available in 15 mg, 30 mg, and 45 mg tablets as follows:
• 15 mg tablet:
• White to off-white, round, convex, nonscored tablet with "ACTOS" on one side, and "15" on the other, available in:
• NDC 64764-151-04 Bottles of 30 NDC 64764-151-05 Bottles of 90 NDC 64764-151-06 Bottles of 500 30 mg tablet:
• White to off-white, round, flat, nonscored tablet with "ACTOS" on one side, and "30" on the other, available in:
• NDC 64764-301-14 Bottles of 30 NDC 64764-301-15 Bottles of 90 NDC 64764-301-16 Bottles of 500 45 mg tablet:
• White to off-white, round, flat, nonscored tablet with "ACTOS" on one side, and "45" on the other, available in:
• NDC 64764-451-24 Bottles of 30 NDC 64764-451-25 Bottles of 90 NDC 64764-451-26 Bottles of 500 Storage
• Store at 25°C (77°F); excursions permitted to 15-30°C (59-86°F) [see USP Controlled Room Temperature].
• Keep container tightly closed, and protect from light, moisture and humidity.

Quoted from the official label, section “How Supplied”.

What is in it

• ACTOS tablets are a thiazolidinedione and an agonist for peroxisome proliferator-activated receptor (PPAR) gamma that contains an oral antidiabetic medication:
• pioglitazone. Pioglitazone [(±)-5-[[4-[2-(5-ethyl-2-pyridinyl) ethoxy] phenyl] methyl]-2,4-] thiazolidinedione monohydrochloride contains one asymmetric carbon, and the compound is synthesized and used as the racemic mixture. The two enantiomers of pioglitazone interconvert in vivo . No differences were found in the pharmacologic activity between the two enantiomers. The structural formula is as shown:
• Pioglitazone hydrochloride is an odorless white crystalline powder that has a molecular formula of C 19 H 20 N 2 O 3 S
• HCl and a molecular weight of 392.90 daltons. It is soluble in N,N -dimethylformamide, slightly soluble in anhydrous ethanol, very slightly soluble in acetone and acetonitrile, practically insoluble in water, and insoluble in ether. ACTOS is available as a tablet for oral administration containing 15 mg, 30 mg, or 45 mg of pioglitazone (as the base) formulated with the following excipients:
• lactose monohydrate NF, hydroxypropylcellulose NF, carboxymethylcellulose calcium NF, and magnesium stearate NF. Chemical Structure

Quoted from the official label, section “Description”.

Ingredients people check for

Lactose, gluten, dyes, sugars and other ingredients that matter with an allergy, intolerance or diet — as this product’s FDA label lists them.

Same active substance, strength and form in other countries

Matched on active substance, strength and kind of form only. This is not a statement that the products are equivalent or interchangeable: other ingredients, release and approved uses can differ — ask a pharmacist before swapping.

Medicine passport: one printable page to show a pharmacist abroad

Details

Source: NDC Directory · 2026-09-13 · not reviewed by a clinician

Source: US Food and Drug Administration, NDC Directory. Reuse terms: US government work (FDA).

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Other strengths and forms

3 products are sold under this name. Grouped by form; a number on a strength means several companies make it.

Same active substance

These contain the same substance. That does not mean one can replace another — ask a pharmacist.

See every product with Pioglitazone