Actos

Name: Actos

What Is Pioglitazone (Actos)?

Pioglitazone is the generic form of the prescription drug known by the brand name Actos.

It's used along with diet and exercise to help lower blood sugar in people who have type 2 diabetes.

When you have type 2 diabetes, your body doesn't make or use the hormone insulin normally, so it can't control the amount of sugar, or glucose, in the blood.

Pioglitazone is in a class of drugs known as thiazolidinediones.

It lowers blood-sugar levels by making the body's cells more sensitive to insulin, allowing them to take up more glucose from your blood.

Taking pioglitazone, along with adopting a healthy lifestyle, can decrease your risk of developing the serious or life-threatening complications of type 2 diabetes.

These may include cardiovascular diseases, such as heart attack, stroke, and problems related to blood circulation; nerve damage; kidney disease; or eye conditions.

The drug is manufactured by Takeda Pharmaceuticals, and was approved by the Food and Drug Administration (FDA) in 1999.

Pioglitazone Warnings

Pioglitazone carries a black-box warning because it may cause or worsen congestive heart failure.

Before taking pioglitazone, tell your doctor about any conditions you've had that may be related to or affect the heart, such as:

  • Congestive heart failure
  • Heart disease
  • A heart attack
  • A heart defect
  • High cholesterol
  • High blood pressure
  • An irregular heartbeat
  • Sleep apnea

Tell your doctor immediately or get emergency medical attention if you experience symptoms of congestive heart failure, which may include:

  • Shortness of breath
  • Swelling of the arms, hands, feet, ankles, lower back, or lower legs
  • Stomach swelling or pain
  • Waking up during the night feeling short of breath
  • Inability to sleep while laying flat
  • Frequent dry cough or wheezing
  • Fast or racing heartbeat
  • Confusion or difficulty thinking clearly
  • Increased fatigue
  • Difficulty walking or exercising
  • Significant weight gain in a short period of time

Before taking this medication, also tell your doctor if you have or have ever had:

  • Bladder cancer
  • Diabetic eye disease
  • Kidney disease

Pioglitazone may cause liver problems. Tell your doctor if you've ever had liver disease.

Stop taking the medicine and call your healthcare provider right away if you experience:

  • Nausea
  • Vomiting
  • Loss of appetite
  • Pain in the upper right part of your stomach
  • Flu-like symptoms
  • Dark urine
  • Unusual bruising or bleeding
  • Yellowing of the eyes or skin
  • Profound lack of energy

Pioglitazone may also increase a woman's chances of experiencing a broken bone. Tell your doctor right away if you experience any kind of bone pain.

Also, tell your healthcare providers that you're taking pioglitazone before having any type of surgery, including a dental procedure.

You shouldn't take pioglitazone if you have type 1 diabetes (the body doesn't produce any insulin) or diabetic ketoacidosis (a dangerous condition that can occur if high blood sugar is untreated).

Pioglitazone may cause changes in your blood sugar. You should know the symptoms of high (hyperglycemic) or low (hypoglycemic) blood-sugar episodes and be prepared to treat them.

Tell your physician if you experience an illness, fever, injury, or unusual stress while taking pioglitazone, because these can change your blood sugar and the dosage you need.

Pioglitazone controls diabetes, but it doesn't cure it. Continue to take it even if you feel well.

It may take two weeks for your blood sugar to decrease and up to three months to feel the full effects of this drug.

Your physician will probably want to check your glucose levels often while you are taking pioglitazone.

Always wear a diabetic ID bracelet to be sure you get proper treatment in case of an emergency.

Pioglitazone and Bladder Cancer

People who took pioglitazone for more than a year were more likely to develop bladder cancer than those who didn't take the medicine.

The FDA recommends that this drug shouldn't be prescribed to people with bladder cancer or a history of bladder cancer.

Tell your doctor right away if you notice symptoms that could be associated with bladder cancer. These may include:

  • Red or bloody urine
  • Difficult or painful urination
  • An increased need to urinate

Thousands of U.S. patients who took pioglitazone have filed lawsuits against the manufacturer because they believe the risk of bladder cancer wasn't fully disclosed.

Pregnancy and Pioglitazone

Pioglitazone is an FDA Pregnancy Category C drug, which means harm to an unborn baby is possible.

Discuss the risks and benefits of taking this drug during pregnancy with your doctor.

The medicine may also increase the chance that you will become pregnant, even if you don't have regular monthly periods. Talk to your doctor about effective birth-control methods.

It's not known whether pioglitazone passes into breast milk or could harm a breastfeeding baby.

Don't take this medication while breastfeeding without talking to your doctor first.

Pioglitazone Dosage

Pioglitazone comes as a tablet and is typically taken by mouth once a day, with or without meals.

Your dosage will be based on your medical condition, response to treatment, and other drugs you're taking.

Try to take pioglitazone around the same time each day.

Your doctor might start you on a low dose and gradually increase it.

Follow the instructions on your prescription label carefully. Don't take more or less than is prescribed.

Pioglitazone Overdose

If you suspect an overdose, you should contact a poison-control center or emergency room immediately.

You can get reach a poison-control center at (800) 222-1222.

Missed Dose of Pioglitazone

If you miss a dose of pioglitazone, and you remember that same day, take the missed dose as soon as you remember.

If you don't remember until the next day, don't take an extra pill. Just continue on your regular medication schedule.

Don't take more than one dose a day or double up to make up for a missed one.

Which drugs or supplements interact with Actos (pioglitazone)?

  • Gemfibrozil reduces the break down of Actos by certain liver enzymes, increasing blood levels and possibly side effects of Actos. The maximum dose of Actos should not exceed 15 mg daily when combined with gemfibrozil or other drugs that reduce the activity of liver enzymes that break down Actos. Conversely, rifampin increases the breakdown of Actos by the liver, reducing blood levels and possibly the effects of Actos.

What other drugs will affect pioglitazone?

Tell your doctor if you use insulin. Taking pioglitazone while you are using insulin may increase your risk of serious heart problems.

Tell your doctor about all your current medicines and any you start or stop using, especially:

  • gemfibrozil;

  • rifampin; or

  • other oral diabetes medications, such as acetohexamide, chlorpropamide, glimepiride, glipizide, tolbutamide.

This list is not complete and many other medicines may increase or decrease the effects of pioglitazone on lowering your blood sugar. This includes prescription and over-the-counter medicines, vitamins, and herbal products. Not all possible interactions are listed in this medication guide.

Commonly used brand name(s)

In the U.S.

  • Actos

Available Dosage Forms:

  • Tablet

Therapeutic Class: Antidiabetic

Chemical Class: Thiazolidinedione

What do I need to tell my doctor BEFORE I take Actos?

  • If you have an allergy to pioglitazone or any other part of this medicine.
  • If you are allergic to any drugs like this one, any other drugs, foods, or other substances. Tell your doctor about the allergy and what signs you had, like rash; hives; itching; shortness of breath; wheezing; cough; swelling of face, lips, tongue, or throat; or any other signs.
  • If you have any of these health problems: Acidic blood problem, bladder cancer, or type 1 diabetes.
  • If the patient is a child. Do not give this medicine (Actos) to a child.

This is not a list of all drugs or health problems that interact with this medicine.

Tell your doctor and pharmacist about all of your drugs (prescription or OTC, natural products, vitamins) and health problems. You must check to make sure that it is safe for you to take this medicine (Actos) with all of your drugs and health problems. Do not start, stop, or change the dose of any drug without checking with your doctor.

Clinical Studies

Monotherapy

Three randomized, double-blind, placebo-controlled trials with durations from 16 to 26 weeks were conducted to evaluate the use of Actos as monotherapy in patients with type 2 diabetes. These trials examined Actos 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 Actos, 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 Actos 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.

Figure 1. Mean Change from Baseline for HbA1c in a 26-Week Placebo-Controlled Dose-Ranging Study (Observed Values)

Table 17. Glycemic Parameters in a 26-Week Placebo-Controlled Dose-Ranging Monotherapy Trial
Placebo Actos
15 mg
Once
Daily
Actos
30 mg
Once
Daily
Actos
45 mg
Once
Daily
* Adjusted for baseline, pooled center, and pooled center by treatment interaction † p ≤0.05 vs. placebo

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*)

0.7

-0.3

-0.3

-0.9

Difference from placebo (adjusted mean*)
95% Confidence Interval

-1.0†
(-1.6, -0.4)

-1.0†
(-1.6, -0.4)

-1.6†
(-2.2, -1.0)

Fasting Plasma Glucose (mg/dL)

N=79

N=79

N=84

N=77

Baseline (mean)

268

267

269

276

Change from baseline (adjusted mean*)

9

-30

-32

-56

Difference from placebo (adjusted mean*)
95% Confidence Interval

-39†
(-63, -16)

-41†
(-64, -18)

-65†
(-89, -42)

In a 24-week placebo-controlled monotherapy trial, 260 patients with type 2 diabetes were randomized to one of two forced-titration Actos treatment groups or a mock-titration placebo group. Therapy with any previous antidiabetic agent was discontinued six weeks prior to the double-blind period. In one Actos treatment group, patients received an initial dose of 7.5 mg once daily. After four weeks, the dose was increased to 15 mg once daily and after another four weeks, the dose was increased to 30 mg once daily for the remainder of the trial (16 weeks). In the second Actos treatment group, patients received an initial dose of 15 mg once daily and were titrated to 30 mg once daily and 45 mg once daily in a similar manner. Treatment with Actos, as described, produced statistically significant improvements in HbA1c and FPG at endpoint compared to placebo (see Table 18).

Table 18. Glycemic Parameters in a 24-Week Placebo-Controlled Forced-Titration Monotherapy Trial
Placebo Actos
30 mg*
Once
Daily
Actos
45 mg*
Once
Daily
* Final dose in forced titration † Adjusted for baseline, pooled center, and pooled center by treatment interaction ‡ p ≤0.05 vs. placebo

Total Population

HbA1c (%)

N=83

N=85

N=85

Baseline (mean)

10.8

10.3

10.8

Change from baseline (adjusted mean†)

0.9

-0.6

-0.6

Difference from placebo (adjusted mean†)
95% Confidence Interval

-1.5‡
(-2.0, -1.0)

-1.5‡
(-2.0, -1.0)

Fasting Plasma Glucose (mg/dL)

N=78

N=82

N=85

Baseline (mean)

279

268

281

Change from baseline (adjusted mean†)

18

-44

-50

Difference from placebo (adjusted mean†)
95% Confidence Interval

-62‡
(-82, -0.41)

-68‡
(-88, -0.48)

In a 16-week monotherapy trial, 197 patients with type 2 diabetes were randomized to treatment with 30 mg of Actos or placebo once daily. Therapy with any previous antidiabetic agent was discontinued six weeks prior to the double-blind period. Treatment with 30 mg of Actos produced statistically significant improvements in HbA1c and FPG at endpoint compared to placebo (see Table 19).

Table 19. Glycemic Parameters in a 16-Week Placebo-Controlled Monotherapy Trial
Placebo Actos 30 mg
Once Daily
* Adjusted for baseline, pooled center, and pooled center by treatment interaction † p ≤0.050 vs. placebo

Total Population

HbA1c (%)

N=93

N=100

Baseline (mean)

10.3

10.5

Change from baseline (adjusted mean*)

0.8

-0.6

Difference from placebo (adjusted mean*)
95% Confidence Interval

-1.4†
(-1.8, -0.9)

Fasting Plasma Glucose (mg/dL)

N=91

N=99

Baseline (mean)

270

273

Change from baseline (adjusted mean*)

8

-50

Difference from placebo (adjusted mean*)
95% Confidence Interval

-58†
(-77, -38)

Combination Therapy

Three 16-week, randomized, double-blind, placebo-controlled clinical trials were conducted to evaluate the effects of Actos (15 mg and/or 30 mg) on glycemic control in patients with type 2 diabetes who were inadequately controlled (HbA1c ≥8%) despite current therapy with a sulfonylurea, metformin, or insulin. In addition, three 24-week randomized, double-blind clinical trials were conducted to evaluate the effects of Actos 30 mg vs. Actos 45 mg on glycemic control in patients with type 2 diabetes who were inadequately controlled (HbA1c ≥8%) despite current therapy with a sulfonylurea, metformin, or insulin. Previous diabetes treatment may have been monotherapy or combination therapy.

Add-on to Sulfonylurea Trials

Two clinical trials were conducted with Actos in combination with a sulfonylurea. Both studies included patients with type 2 diabetes on any dose of a sulfonylurea, either alone or in combination with another antidiabetic agent. All other antidiabetic agents were withdrawn at least three weeks prior to starting study treatment.

In the first study, 560 patients were randomized to receive 15 mg or 30 mg of Actos or placebo once daily for 16 weeks in addition to their current sulfonylurea regimen. Treatment with Actos as add-on to sulfonylurea produced statistically significant improvements in HbA1c and FPG at endpoint compared to placebo add-on to sulfonylurea (see Table 20).

Table 20. Glycemic Parameters in a 16-Week Placebo-Controlled, Add-on to Sulfonylurea Trial
Placebo
+ Sulfonylurea
Actos 15 mg
+ Sulfonylurea
Actos 30 mg
+ Sulfonylurea
* Adjusted for baseline, pooled center, and pooled center by treatment interaction † p ≤0.05 vs. placebo + sulfonylurea

Total Population

HbA1c (%)

N=181

N=176

N=182

Baseline (mean)

9.9

10.0

9.9

Change from baseline (adjusted mean*)

0.1

-0.8

-1.2

Difference from placebo + sulfonylurea (adjusted mean*)
95% Confidence Interval

-0.9†
(-1.2, -0.6)

-1.3†
(-1.6, -1.0)

Fasting Plasma Glucose (mg/dL)

N=182

N=179

N=186

Baseline (mean)

236

247

239

Change from baseline (adjusted mean*)

6

-34

-52

Difference from placebo + sulfonylurea (adjusted mean*)
95% Confidence Interval

-39†
(-52, -27)

-58†
(-70, -46)

In the second trial, 702 patients were randomized to receive 30 mg or 45 mg of Actos once daily for 24 weeks in addition to their current sulfonylurea regimen. The mean reduction from baseline at Week 24 in HbA1c was 1.6% for the 30 mg dose and 1.7% for the 45 mg dose (see Table 21). The mean reduction from baseline at Week 24 in FPG was 52 mg/dL for the 30 mg dose and 56 mg/dL for the 45 mg dose.

The therapeutic effect of Actos in combination with sulfonylurea was observed in patients regardless of the sulfonylurea dose.

Table 21. Glycemic Parameters in a 24-Week Add-on to Sulfonylurea Trial
Actos 30 mg +
Sulfonylurea
Actos 45 mg +
Sulfonylurea
* Adjusted for baseline, pooled center, and pooled center by treatment interaction

Total Population

HbA1c (%)

N=340

N=332

Baseline (mean)

9.8

9.9

Change from baseline (adjusted mean*)

-1.6

-1.7

Difference from 30 mg daily Actos + sulfonylurea (adjusted mean*) (95% CI)

-0.1
(-0.4, 0.1)

Fasting Plasma Glucose (mg/dL)

N=338

N=329

Baseline (mean)

214

217

Change from baseline (adjusted mean*)

-52

-56

Difference from 30 mg daily Actos + sulfonylurea (adjusted mean*) (95% CI)

-5
(-12, 3)

95% CI = 95% confidence interval

Add-on to Metformin Trials

Two clinical trials were conducted with Actos in combination with metformin. Both trials included patients with type 2 diabetes on any dose of metformin, either alone or in combination with another antidiabetic agent. All other antidiabetic agents were withdrawn at least three weeks prior to starting study treatment.

In the first trial, 328 patients were randomized to receive either 30 mg of Actos or placebo once daily for 16 weeks in addition to their current metformin regimen. Treatment with Actos as add-on to metformin produced statistically significant improvements in HbA1c and FPG at endpoint compared to placebo add-on to metformin (see Table 22).

Table 22. Glycemic Parameters in a 16-Week Placebo-Controlled, Add-on to Metformin Trial
Placebo
+ Metformin
Actos 30 mg
+ Metformin
* Adjusted for baseline, pooled center, and pooled center by treatment interaction † p ≤0.05 vs. placebo + metformin

Total Population

HbA1c (%)

N=153

N=161

Baseline (mean)

9.8

9.9

Change from baseline (adjusted mean*)

0.2

-0.6

Difference from placebo + metformin (adjusted mean*)
95% Confidence Interval

-0.8†
(-1.2, -0.5)

Fasting Plasma Glucose (mg/dL)

N=157

N=165

Baseline (mean)

260

254

Change from baseline (adjusted mean*)

-5

-43

Difference from placebo + metformin (adjusted mean*)
95% Confidence Interval

-38†
(-49, -26)

In the second trial, 827 patients were randomized to receive either 30 mg or 45 mg of Actos once daily for 24 weeks in addition to their current metformin regimen. The mean reduction from baseline at Week 24 in HbA1c was 0.8% for the 30 mg dose and 1.0% for the 45 mg dose (see Table 23). The mean reduction from baseline at Week 24 in FPG was 38 mg/dL for the 30 mg dose and 51 mg/dL for the 45 mg dose.

Table 23. Glycemic Parameters in a 24-Week Add-on to Metformin Study
Actos 30 mg +
Metformin
Actos 45 mg
+ Metformin
* Adjusted for baseline, pooled center, and pooled center by treatment interaction † p ≤0.05 vs. 30 mg daily Actos + metformin

Total Population

HbA1c (%)

N=400

N=398

Baseline (mean)

9.9

9.8

Change from baseline (adjusted mean*)

-0.8

-1.0

Difference from 30 mg daily Actos + Metformin (adjusted mean*) (95% CI)

-0.2
(-0.5, 0.1)

Fasting Plasma Glucose (mg/dL)

N=398

N=399

Baseline (mean)

233

232

Change from baseline (adjusted mean*)

-38

-51

Difference from 30 mg daily Actos + Metformin (adjusted mean*) (95% CI)

-12†
(-21, -4)

95% CI = 95% confidence interval

The therapeutic effect of Actos in combination with metformin was observed in patients regardless of the metformin dose.

Add-on to Insulin Trials

Two clinical trials were conducted with Actos in combination with insulin. Both trials included patients with type 2 diabetes on insulin, either alone or in combination with another antidiabetic agent. All other antidiabetic agents were withdrawn prior to starting study treatment. In the first trial, 566 patients were randomized to receive either 15 mg or 30 mg of Actos or placebo once daily for 16 weeks in addition to their insulin regimen. Treatment with Actos as add-on to insulin produced statistically significant improvements in HbA1c and FPG at endpoint compared to placebo add-on to insulin (see Table 24). The mean daily insulin dose at baseline in each treatment group was approximately 70 units. The majority of patients (75% overall, 86% treated with placebo, 77% treated with Actos 15 mg, and 61% treated with Actos 30 mg) had no change in their daily insulin dose from baseline to the final study visit. The mean change from baseline in daily dose of insulin (including patients with no insulin dose modifications) was -3 units in the patients treated with Actos 15 mg, -8 units in the patients treated with Actos 30 mg, and -1 unit in patients treated with placebo.

Table 24. Glycemic Parameters in a 16-Week Placebo-Controlled, Add-on to Insulin Trial
Placebo
+ Insulin
Actos 15 mg
+ Insulin
Actos 30 mg
+ Insulin
* Adjusted for baseline, pooled center, and pooled center by treatment interaction † p ≤0.05 vs. placebo + insulin

Total Population

HbA1c (%)

N=177

N=177

N=185

Baseline (mean)

9.8

9.8

9.8

Change from baseline (adjusted mean*)

-0.3

-1.0

-1.3

Difference from placebo + Insulin (adjusted mean*)
95% Confidence Interval

-0.7†
(-1.0, -0.5)

-1.0†
(-1.3, -0.7)

Fasting Plasma Glucose (mg/dL)

N=179

N=183

N=184

Baseline (mean)

221

222

229

Change from baseline (adjusted mean*)

1

-35

-48

Difference from placebo + Insulin (adjusted mean*)
95% Confidence Interval

-35†
(-51, -19)

-49†
(-65, -33)

In the second trial, 690 patients receiving a median of 60 units per day of insulin were randomized to receive either 30 mg or 45 mg of Actos once daily for 24 weeks in addition to their current insulin regimen. The mean reduction from baseline at Week 24 in HbA1c was 1.2% for the 30 mg dose and 1.5% for the 45 mg dose. The mean reduction from baseline at Week 24 in FPG was 32 mg/dL for the 30 mg dose and 46 mg/dL for the 45 mg dose (see Table 25). The mean daily insulin dose at baseline in both treatment groups was approximately 70 units. The majority of patients (55% overall, 58% treated with Actos 30 mg, and 52% treated with Actos 45 mg) had no change in their daily insulin dose from baseline to the final study visit. The mean change from baseline in daily dose of insulin (including patients with no insulin dose modifications) was -5 units in the patients treated with Actos 30 mg and -8 units in the patients treated with Actos 45 mg.

The therapeutic effect of Actos in combination with insulin was observed in patients regardless of the insulin dose.

Table 25. Glycemic Parameters in a 24-Week Add-on to Insulin Trial
Actos 30 mg +
Insulin
Actos 45 mg + Insulin
* Adjusted for baseline, pooled center, and pooled center by treatment interaction † p ≤0.05 vs. 30 mg daily Actos + insulin

Total Population

HbA1c (%)

N=328

N=328

Baseline (mean)

9.9

9.7

Change from baseline (adjusted mean*)

-1.2

-1.5

Difference from 30 mg daily Actos + Insulin (adjusted mean*) (95% CI)

-0.3†
(-0.5, -0.1)

Fasting Plasma Glucose (mg/dL)

N=325

N=327

Baseline (mean)

202

199

Change from baseline (adjusted mean*)

-32

-46

Difference from 30 mg daily Actos + Insulin (adjusted mean*) (95% CI)

-14†
(-25, -3)

95% CI = 95% confidence interval

Actos Interactions

Tell your doctor about all the medications you take including prescription and non-prescription medicines, vitamins, and herbal supplements. Especially tell your doctor if you take:

  • atorvastatin (Lipitor)
  • gemfibrozil (Lopid)
  • hormonal contraceptives (birth control pills, patches, rings, implants, and injections)
  • insulin or other medications to treat diabetes
  • ketoconazole (Nizoral)
  • midazolam (Versed)
  • nifedipine (Procardia)
  • rifampin (Rifadin, Rifater, in Rifamate)

This is not a complete list of Actos drug interactions. Ask your doctor or pharmacist for more information.

Actos Precautions

Actos can cause serious side effects, including

  • liver problems. Call your doctor right away if you have:
    • nausea or vomiting
    • stomach pain
    • unusual or unexplained tiredness
    • loss of appetite
    • dark urine
    • yellowing of your skin or the whites of your eyes
  • broken bones (fractures). Usually in the hand, upper arm or foot in women. Talk to your doctor for advice on how to keep your bones healthy.
  • bladder cancer. There may be an increased chance of having bladder cancer when you take Actos. You should not take Actos if you are receiving treatment for bladder cancer. Tell your doctor right away if you have any of the following symptoms of bladder cancer:
    • blood or red color in your urine
    • an increased need to urinate
    • pain while you urinate
  • low blood sugar (hypoglycemia). This can happen if you skip meals, if you also use another medicine that lowers blood sugar or if you have certain medical problems. Lightheadedness, dizziness, shakiness, or hunger may happen if your blood sugar is too low. Call your doctor if low blood sugar levels are a problem for you.
  • diabetic eye disease with swelling in the back of the eye (macular edema). Tell your doctor right away if you have any changes in your vision. Your doctor should check your eyes regularly.
  • release of an egg from an ovary in a woman (ovulation) leading to pregnancy. Ovulation may happen when premenopausal women who do not have regular monthly periods take Actos. This can increase your chance of getting pregnant.
  • new or worse heart failure. Actos 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. Call your doctor right away if you have any of the following:
  • swelling or fluid retention, especially in the ankles or legs
  • shortness of breath or trouble breathing, especially when you lie down
  • an unusually fast increase in weight
  • unusual tiredness

Do not take Actos if you:

  • have severe heart failure
  • are allergic to any of the ingredients in Actos tablets.

Talk to your doctor before taking Actos if you have either of these conditions.

Actos Food Interactions

Medicines can interact with certain foods. In some cases, this may be harmful and your doctor may advise you to avoid certain foods. In the case of Actos there are no specific foods that you must exclude from your diet when receiving this medication.

Inform MD

Before you take starting Actos, tell your doctor if you:

  • have heart failure
  • have type 1 (“juvenile”) diabetes or had diabetic ketoacidosis
  • have a type of diabetic eye disease that causes swelling in the back of the eye (macular edema)
  • have liver problems
  • are pregnant or plan to become pregnant
  • are a premenopausal woman (before the “change of life”) who does not have periods regularly or at all
  • are breastfeeding or plan to breastfeed

Tell your doctor about all the medicines you take including prescription and non-prescription medicines, vitamins, and herbal supplements.

Actos and some of your other medicines can affect each other. You may need to have your dose of Actos or certain other medicines changed.

Adverse Effects

>10%

Edema when used in combination with sulfonylurea or insulin (<27%)

Hypoglycemia (<27%)

Upper respiratory infection (13%)

1-10%

Headache (9%)

Heart failure (up to 8%)

Sinusitis (6%)

Fracture of bone (5%)

Pharyngitis (5%)

Myalgia (5%)

Frequency Not Defined

Aggravated diabetes

Diabetic macular edema

Hepatic failure (rare)

Increased cholesterol

Decreased serum triglycerides

Hematocrit/hemoglobin

Bladder cancer

Decreased visual acuity

Dyspnea

Increased transaminases

Pharyngitis

Sinusitis

Weight gain

Pharmacology

Mechanism of Action

Improves target-cell response to insulin; decreases hepatic gluconeogenesis; depends on the presence of insulin for activity

Absorption

Onset: Initial effect (delayed), max effect (several weeks)

Duration: 24 hr

Peak plasma time: 2-4 hr (delayed by food)

Distribution

Protein bound: >99%

Vd: 0.63 L/kg

Metabolism

Metabolized by hepatic CYP2C8 and CYP3A4 into active metabolites

Active metabolites: Metabolite II (hydroxy derivative), metabolite III (keto derivative), metabolite IV (active hydroxy derivative)

Elimination

Half-life: 3-7 hr

Excretion: Urine (15-30%)

Side effects

The following serious adverse reactions are discussed elsewhere in the labeling:

  • Congestive heart failure [see BOXED WARNING and WARNINGS AND PRECAUTIONS]
  • Edema [see WARNINGS AND PRECAUTIONS]
  • Fractures [see WARNINGS AND PRECAUTIONS]

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
vveighL 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 threeyear 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 (25th/75th percentile) Median (25th/75th percentile) Median (25th/75th percentile) Median (25th/75th 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 (25th/75th percentile) Median (25th/75th 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 addon 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]. 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].

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 comparatortreated 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.

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].
  • Fatal and nonfatal hepatic failure [see WARNINGS AND PRECAUTIONS].

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].

Read the entire FDA prescribing information for Actos (Pioglitazone Hydrochloride)

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Before taking this medicine

You should not use Actos if you are allergic to pioglitazone, or if you have severe or uncontrolled heart failure, active bladder cancer, or diabetic ketoacidosis (call your doctor for treatment with insulin).

To make sure Actos is safe for you, tell your doctor if you have:

  • congestive heart failure or heart disease;

  • fluid retention;

  • a history of bladder cancer;

  • a history of heart attack or stroke; or

  • liver disease.

This medication may increase your risk of developing bladder cancer. Talk with your doctor about your specific risk.

Taking Actos may increase your risk of serious heart problems. However, not treating your diabetes can damage your heart and other organs. Talk to your doctor about the risks and benefits of treating your diabetes with Actos.

Follow your doctor's instructions about using Actos if you are pregnant. Blood sugar control is very important during pregnancy, and your dose needs may be different during each trimester of pregnancy.

Some women using Actos have started having menstrual periods, even after not having a period for a long time due to a medical condition. You may be able to get pregnant if your periods restart. Talk with your doctor about the need for birth control.

Women may be more likely than men to have bone fractures in the upper arm, hand, or foot while taking this medicine. Talk with your doctor if you are concerned about this possibility.

It is not known whether pioglitazone passes into breast milk or if it could harm a nursing baby. You should not breast-feed while using this medicine.

Actos is not approved for use by anyone younger than 18 years old.

What should I avoid while taking Actos?

Avoid drinking alcohol. It lowers blood sugar and may interfere with your diabetes treatment.

Pioglitazone Breastfeeding Warnings

A decision should be made to discontinue breastfeeding or discontinue the drug, taking into account the importance of the drug to the mother. Excreted into human milk: Unknown Excreted into animal milk: Yes Comments: The effects in the nursing infant are unknown.

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