Side Effects, FDA Warnings and International Recalls

Actos lowers blood sugar by increasing the body’s sensitivity to insulin and reducing the amount of glucose the liver releases. This allows the body to better remove excess blood sugar.

Its manufacturer, Takeda Pharmaceuticals America Inc., makes two additional versions of the drug that combine the active ingredient pioglitazone with metformin: Actoplus Met and Actoplus Met XR (extended release). Two other products combine pioglitazone with other diabetes drugs: glimepiride (Duetact) and alogliptin (Oseni).

The Food and Drug Administration (FDA) approved Actos in 1999, Actoplus Met in 2005, Actoplus Met XR in 2009. Duetact in 2006, and Oseni in 2013.

Eli Lilly partnered with Takeda to market Actos, and it became one of the most successful diabetes medications of all time. In 2007, it ranked as the world’s best-selling diabetes drug after studies linked rival drug Avandia to a higher risk of heart attack. Both come from the same family of drugs: thiazolidinediones or TZDs.

Before the medication’s patent expired in 2011, it had brought in $3.58 billion in United States sales in 2010. The drug’s sales made up 27 percent of Takeda’s revenue.

However, numerous studies and a review by the FDA linked higher dosages and prolonged use of the drug to an increased risk of bladder cancer.

In its 2015 annual report, Takeda said it had set aside $2.7 billion to cover the costs of settling Actos lawsuits that blamed the drug for bladder cancer and other injuries. Despite the lawsuits and FDA review, doctors can still prescribe the drug in the United States.

Meanwhile, health regulators in Germany and France ordered Takeda to pull the drug off the market in 2011 after an analysis of a company-sponsored study showed an increased risk of developing bladder cancer or heart problems. The government in India also banned the drug.

Important Information on Taking Actos

Actos is meant to be used along with diet and exercise to improve blood sugar control in adults with Type 2 diabetes. Depending on how well your body naturally controls blood sugar, your doctor may prescribe pioglitazone by itself or with other diabetes medications.

The medicine comes in a tablet, and you should take it only as directed by your doctor. Instructions in the drug’s label say take it once a day with or without food.

Typically, the dose starts at 15 mg or 30 mg, but some people may require a higher dose. Doctors can increase the dose by 15 mg at a time up to a maximum of 45 mg daily.

One 2022 study noted that for edema, weight gain and heart failure, the risk estimates for pioglitazone were lower for subjects taking less than 45 mg daily. The researchers concluded that lower doses of pioglitazone appear to confer similar benefits with fewer adverse effects than the recommended dose.

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15 mg, 30 mg and 45 mg Actos tablets.

Do not change your dose unless your doctor tells you to. Let your doctor know if you are in an accident, undergo surgery, or develop a fever or an infection. Experiences like these can put added stress on your body, and your doctor may need to alter your dose.

It’s important to continue to follow your diet and exercise regimen and routinely test your blood sugar. Your doctor will likely test your hemoglobin A1C to gauge whether the medication is working. Your doctor should also examine your eyes on a regular basis because the medicine can cause a build-up of fluid in the eyes and affect your vision.

Risks to Discuss with Your Doctor Before Starting Treatment

Before prescribing Actos, your doctor should order certain blood tests, including ones that check for liver problems. They may decide against prescribing the drug to patients with certain conditions, so it’s important to tell your doctor about your medical history.

Let your doctor know if you have heart failure, liver problems, Type 1 diabetes, or diabetic ketoacidosis in the past. Patients with Type 1 diabetes or who have had diabetic ketoacidosis in the past should not take Actos, nor should children younger than 18 years old. Patients with heart failure or liver problems should be watched carefully in case these conditions worsen while taking Actos.

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Source: Actos Medication Guide

Also tell your doctor if you have been diagnosed with bladder cancer or macular edema, which is a diabetic eye disease that causes swelling in the back of the eye.

Pioglitazone can increase the chances of becoming pregnant in some people and can harm your unborn baby. The medicine also passes into breast milk and can affect a nursing baby.

Talk to your doctor about birth control options and let them know if you are pregnant or plan to become pregnant, or are breastfeeding or plan to breastfeed.

Other medicines, vitamins or supplements you take can interact with pioglitazone and cause problems. For example, combining Actos with insulin or other antidiabetic medications can increase your risk of developing very low blood sugar, so a doctor may reduce the dose of the other diabetes drug.

Show your doctor or pharmacist a list of everything you take before you start using a new medication, so they can determine whether to adjust your dose or prescribe a different treatment.

Potential alternatives to Actos include Amaryl (glimepiride), Glucotrol (glipizide) and DiaBeta (glyburide). Prandin (repaglinide), Precose (acarbose) or Symlin (pramlintide) may also be substitutes for pioglitazone. As with Actos, these drugs can either be used alone or with another medication.

Common Side Effects

The most common side effects reported during Actos clinical trials were upper respiratory tract infection, headache, sinus infection, muscle pain and sore throat.

Other reported side effects included swelling, weight gain, back pain, dizziness, gas and diarrhea. The drug’s label says to call your doctor if you experience these side effects and they get worse or don’t go away.

Actoplus Met and Actoplus Met XR can cause the same side effects as Actos, but they can also cause side effects of metformin such as lactic acidosis, a life-threatening condition that occurs when too much lactic acid builds up in the body. Duetact can cause the same side effects as Actos, but it can also cause side effects of glimepiride such as very low blood sugar. Oseni can cause the same side effects as Actos, but it can also cause side effects of alogliptin, such as pancreas or kidney problems.

As of September 2019, the FDA Adverse Events Reporting System (FAERS) Public Dashboard showed 20,135 reports of complications possibly related to Actos since 1999. Of these, 16,404 were flagged as serious, including 2,725 deaths. The FDA points out that the medication may not have been the direct cause of the complications or deaths.

Congestive Heart Failure Black Box Warning

Actos has a black box warning for congestive heart failure. A black box warning is the most serious type of warning the FDA requires on a drug label.

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Source: Actos blackbox warning.

The boxed warning says Actos and other TZDs can cause fluid to buildup in the body when used alone or with other antidiabetic drugs, particularly insulin. This can lead to congestive heart failure or make the condition worse in some patients.

Doctors should carefully monitor patients for signs of heart failure such as rapid weight gain, trouble breathing, or swelling. This is especially the case after a patient first starts treatment or after dose increases.

Combining the drug with insulin may also increase the risk. And so can using the drug if you have New York Heart Association (NYHA) Class III or IV heart failure (more severe forms of heart failure).

Because of the risk, the drug is not recommended for patients with symptoms of heart failure or NYHA Class III or IV heart failure.

The FDA based this warning on clinical trials Takeda had conducted before it released the drug. In one study called the PROactive trial, 5,238 patients with Type 2 diabetes and preexisting heart disease were treated with Actos or a placebo. According to the results, more pioglitazone patients experienced a serious heart failure event than those who had taken the placebo.

In addition, congestive heart failure caused more people to drop out of the trial than any other serious adverse event. About 1.3 percent of pioglitazone patients withdrew from the trial because of the side effect compared to 0.6 percent of patients who had taken a placebo.

FDA Bladder Cancer Review

The FDA alerted the public about a possible risk of bladder cancer in September 2010 and in June 2011 based on results from the first five years of a 10-year study of whether Actos is associated with an increased risk of bladder cancer.

In December 2016, the agency updated the labels of all drugs that contain pioglitazone to warn that an increased risk of bladder cancer has been shown in some studies, but not all. While Takeda’s 10-year study ultimately did not find an increased risk, the PROactive clinical trial and a study using data from the United Kingdom did. The agency also noted early animal studies had shown bladder tumors in rats.

The updated drug labels recommended doctors not prescribe the drugs to patients with active bladder cancer and use caution when prescribing the drugs to patients with a prior history of bladder cancer.

“Overall, we conclude that pioglitazone may be associated with an increased risk in urinary bladder cancer, and we have updated the drug labels to include information about these additional studies.”

“Overall, we conclude that pioglitazone may be associated with an increased risk in urinary bladder cancer, and we have updated the drug labels to include information about these additional studies,” the FDA said.

According to the most recent data from the FDA, bladder cancer is the most frequently reported reaction to Actos. With more than 8,600 reports, it accounts for 46 percent of all adverse events reported to the FAERS database involving the drug.

Recent Bladder Cancer Studies

• 2019

  A review and meta-analysis published in Diabetology International found a “small but statistically significant” increase in the risk of bladder cancer in patients who had ever used pioglitazone compared to patients who had never used the drug. The authors concluded that alternative explanations for this increased risk could not be ruled out.

• 2018

  A review and meta-analysis published in Cancer Medicine found a “slightly but significantly increased risk of bladder cancer.” The authors also found increased risk was tied to higher doses and prolonged use.

• 2017

  A study published in Diabetes, Obesity and Metabolism analyzed Medicare data from nearly a quarter-million beneficiaries. Researchers found a “small absolute increase in risk of bladder cancer” among Actos users compared to people taking other diabetes drugs. They reported the increased risk appeared within the first two years of drug use and continued to increase the longer people took pioglitazone.

• 2016

  A population-based cohort study published in the British Medical Journal found pioglitazone was associated with an increased bladder cancer risk. The researchers looked at medical records of 145,000 people treated with different diabetes drugs in the same class. They found an increased risk and said it was specific to pioglitazone.

Fracture and Liver Failure Risks

The PROactive clinical trial also found an increase in the number of women who took pioglitazone and had bone fractures. Fractures were most likely to happen in the hands, forearms, feet, ankles, and legs, according to information in the drug’s label.

The trial followed participants for nearly three years, and researchers started noticing the difference in female patients after the first year. The trial did not see the same increased risk for men who took the drug.

BONE FRACTURES

5.1 percent of women who took Actos during the PROactive trial had bone fractures compared to 2.5 percent of women who took a placebo.

Source:

Actos Label

A more recent study published in The Journal of Clinical Endocrinology & Metabolism in 2017 also found an increased risk of fractures among people who had taken the drug. The clinical trial followed 3,876 stroke patients for roughly five years.

Researchers found 8.8 percent of those who had taken a placebo had fractures during that time. But those taking pioglitazone had increased relative risks ranging from 47 percent to 60 percent, depending on the type of fracture.

However, a combined analysis of several studies from 2018 did not find an association with pioglitazone and fracture risk.

After Actos became available in the United States, the FDA and Takeda received reports of some fatal and nonfatal cases of liver failure. The drug’s label says there is no way to definitively prove that pioglitazone does not cause liver issues.

It advises doctors to “use caution in patients with liver disease.” It also tells them to test each patient’s liver prior to prescribing the drug and to monitor each patient for signs of liver damage, including fatigue, loss of appetite, right upper abdominal discomfort, dark urine, or yellowed skin (jaundice).

What They Are and How to Manage Them

Actos (pioglitazone) is a prescription drug that’s used to help manage blood sugar levels in people with type 2 diabetes. Actos can cause side effects that range from mild to serious. Examples include heart failure and weight gain.

Actos is used along with diet and exercise to help manage blood sugar in adults with type 2 diabetes. It isn’t approved to treat type 1 diabetes.

The active ingredient in Actos is pioglitazone. (An active ingredient is what makes a drug work.) The drug comes as a tablet that you’ll swallow.

Keep reading to learn about the common, mild, and serious side effects (also called adverse effects) that Actos can cause. For a general overview of the drug, including details about its uses, see this article.

Some people may experience mild or serious side effects during their Actos treatment.

Examples of commonly reported side effects of Actos include:

• infections*
• headache
• sore throat
• muscle aches
• swelling, usually in your feet, ankles, or lower legs

* To learn more about this side effect, see the “Side effects explained” section below.

Keep reading to learn about other possible mild and serious side effects of Actos.

Some people may have mild side effects while taking Actos.

Examples of mild side effects that have been reported with Actos include:

• weight gain*
• infections*
• headache
• sore throat
• muscle aches
• flatulence (gas)
• back pain
• dizziness

* To learn more about this side effect, see the “Side effects explained” section below.

In most cases, these side effects should be temporary. And some may be easily managed, too. But if you have any symptoms that are ongoing or that bother you, talk with your doctor or pharmacist. And don’t stop using Actos unless your doctor recommends it.

Actos may cause mild side effects other than the ones listed above. See the Actos prescribing information for details.

Note: After the Food and Drug Administration (FDA) approves a drug, it tracks side effects of the medication. If you’d like to notify the FDA about a side effect you’ve had with Actos, visit MedWatch.

In rare cases, serious side effects can occur with Actos.

Serious side effects that have been reported with Actos include:

• swelling, usually in your feet, ankles, or lower legs
• bladder cancer
• low blood sugar level
• high blood pressure
• liver problems, such as liver failure
• macular edema (swelling in part of the eye)
• broken bones
• congestive heart failure*
• allergic reaction†

* Actos has a boxed warning for this side effect. This is the most serious warning from the Food and Drug Administration (FDA). To learn more, see the “Side effects explained” section below.
† An allergic reaction is possible after using Actos. But this side effect wasn’t reported in studies. To learn more about this side effect, see the “Side effects explained” section below.

If you develop serious side effects while taking Actos, call your doctor right away. If the side effects seem life threatening or if you think you’re having a medical emergency, immediately call 911 or your local emergency number.

Get answers to some frequently asked questions about the side effects of Actos.

Do side effects of Actos vary depending on whether I take the drug on its own or with metformin?

Yes, it’s possible for side effects to vary depending on whether you take Actos with metformin.

Your doctor may prescribe Actos along with other diabetes drugs to help manage your blood sugar level. In studies, Actos was prescribed in combination with metformin (Fortamet, Glumetza, Riomet), insulin, or sulfonylureas, such as glimepiride (Amaryl) and glipizide (Glucotrol XL).

When Actos is used with metformin,* most side effects of Actos are typically the same as when Actos is used by itself. But metformin commonly causes digestive problems, such as nausea, vomiting, constipation, and diarrhea. So you may experience these side effects if you take Actos with metformin.

For a list of side effects that may occur when Actos is taken with metformin, see the prescribing information for Actos. You can also talk with your doctor or pharmacist.

* Pioglitazone, the active drug in Actos, is available together with metformin as a generic drug and as the brand-name drug ActoPlus MET. For details on this drug combination, including possible side effects, see this article.

Does my risk of side effects from Actos depend on the strength I take (15 mg, 30 mg, or 45 mg)?

Yes. Certain side effects of Actos are dose-dependent, meaning your risk of these side effects is greater at higher doses.

In studies of Actos, weight gain* and swelling were more likely to occur at higher doses of the drug.

If you have other questions about what to expect with Actos based on the strength you’re prescribed, talk with your doctor or pharmacist.

* To learn more about this side effect, see the “Side effects explained” section below.

Will I need to have any lab tests to monitor for side effects of Actos?

Yes, it’s possible you may need lab tests to monitor for side effects of Actos.

In rare cases, taking Actos may lead to liver problems, such as liver failure. If you have liver problems before taking the drug, you may have a higher risk of this side effect.

Before you start treatment with Actos, your doctor will give you liver function tests. If your test results show you have liver disease, your doctor will let you know if it’s safe for you to take Actos.

If your doctor says it’s safe to take Actos, they’ll regularly check your liver function while you’re taking the drug. They may have you stop taking the drug if your liver function worsens over time.

To learn more about getting lab tests to monitor for side effects of Actos, talk with your doctor.

Learn more about some of the side effects Actos may cause.

Weight gain

Weight gain is a common side effect of Actos.

Weight gain can be caused by swelling, which is another possible side effect of Actos. Swelling from Actos usually happens in your feet, ankles, or lower legs.

Keep in mind that swelling and rapid weight gain can be symptoms of congestive heart failure (CHF). Rapid weight gain is defined as gaining more than 2 to 3 pounds in 24 hours or more than 5 pounds in 1 week. CHF is a possible serious side effect of Actos. To learn more, see “Congestive heart failure” right below.

What might help

If you’re concerned about weight gain with Actos, talk with your doctor. They can suggest ways to maintain a weight that’s healthy for you.

If you notice swelling or rapid weight gain while taking the drug, tell your doctor right away. They can check for other symptoms of heart failure and discuss a treatment plan.

Congestive heart failure

Actos has a boxed warning for the risk of new or worsening congestive heart failure (CHF). A boxed warning is the most serious warning from the Food and Drug Administration (FDA).

With CHF, your heart doesn’t pump blood to the rest of your body as effectively as it should.

In studies of Actos, CHF was a rare side effect. CHF can happen when you take the drug by itself or with other diabetes drugs. But your risk of CHF with Actos may be higher if you take the drug together with insulin.

Possible symptoms of CHF include:

• rapid weight gain (defined as gaining more than 2 to 3 pounds in 24 hours or more than 5 pounds in 1 week)
• swelling, especially in your feet, ankles, or lower legs
• shortness of breath
• increased heart rate
• confusion or trouble thinking

What might help

If you have symptoms of CHF, tell your doctor right away. It’s recommended that you avoid taking Actos if you have CHF with symptoms.

You shouldn’t take Actos if you have class 3 or class 4 heart failure. (These are types of serious heart failure.) Based on the type of heart failure you have, your doctor can tell you if Actos is right for you.

Infections

Infections are a common side effect of Actos. Infections that were reported in studies of Actos include sinus infections, upper respiratory infections, and urinary tract infections. The common cold is an example of an upper respiratory infection.

Symptoms will vary based on the specific infection you may have. But possible symptoms include:

• runny or stuffy nose
• headache
• fatigue (low energy)
• cloudy or bloody urine
• urinating more often than usual
• painful urination

What might help

If you have symptoms of an infection while taking Actos, talk with your doctor. They can suggest ways to manage your symptoms. They can also advise if treatments are available for the specific infection you have.

Allergic reaction

Like most drugs, Actos can cause an allergic reaction in some people. But this side effect wasn’t reported in studies.

Symptoms can be mild or serious and can include:

• skin rash
• itchiness
• flushing (temporary warmth, redness, or deepening of skin color)
• swelling under your skin, typically in your eyelids, lips, hands, or feet
• swelling of your mouth, tongue, or throat, which can make it hard to breathe

What might help

If you have mild symptoms of an allergic reaction, such as a mild rash, call your doctor right away. To manage your symptoms, they may suggest an over-the-counter antihistamine you take by mouth, such as Benadryl (diphenhydramine). Or they may recommend a product you apply to skin, such as hydrocortisone cream.

If your doctor confirms you had a mild allergic reaction to Actos, they’ll decide if you should continue using it.

If you have symptoms of a severe allergic reaction, such as swelling or trouble breathing, call 911 or your local emergency number right away. These symptoms could be life threatening and require immediate medical care.

If your doctor confirms you had a serious allergic reaction to Actos, they may have you switch to a different treatment.

Keeping track of side effects

During your Actos treatment, consider keeping notes on any side effects you’re having. Then, you can share this information with your doctor. This is especially helpful to do when you first start taking new drugs or using a combination of treatments.

Your side effect notes can include things such as:

• what dose of drug you were taking when you had the side effect
• how soon after starting that dose you had the side effect
• what your symptoms were from the side effect
• how it affected your daily activities
• what other medications you were also taking
• any other information you feel is important

Keeping notes and sharing them with your doctor will help your doctor learn more about how Actos affects you. And your doctor can use this information to adjust your treatment plan if needed.

In certain situations, it may not be safe to take Actos. Read on to learn more about possible warnings for Actos.

Boxed warning: Risk of congestive heart failure

Actos has a boxed warning for the risk of congestive heart failure (CHF). A boxed warning is the most serious warning from the Food and Drug Administration (FDA).

Taking Actos may lead to new or worsening CHF. It’s recommended that you avoid taking Actos if you have CHF with symptoms. You shouldn’t take Actos if you have class 3 or class 4 heart failure. (These are types of serious heart failure.)

To learn more, see the “Side effects explained” section above.

Other warnings

Actos may not be right for you if you have certain medical conditions or other factors that affect your health. Talk with your doctor about your health history before you take Actos. The list below includes factors to consider.

Bladder cancer. In rare cases, Actos may cause bladder cancer. If you currently have bladder cancer, be sure to tell your doctor before starting Actos treatment. They’ll likely prescribe a drug other than Actos for you.

Liver problems. Rarely, taking Actos may lead to liver problems, such as liver failure. If you have liver problems before taking the drug, you may have a higher risk of this side effect. Your doctor will monitor your liver function closely while you take Actos. Or they may prescribe a treatment other than Actos for your condition.

Osteoporosis. If you have osteoporosis, be sure to tell your doctor before you start taking Actos. Actos may cause broken bones, especially in the arms and legs. You may have a higher risk of this side effect if you have osteoporosis. Your doctor can advise if it’s safe for you to take Actos.

Allergic reaction. If you’ve had an allergic reaction to Actos or any of its ingredients, you shouldn’t take Actos. Ask your doctor what other medications are better options for you.

Irregular periods. Actos can cause ovulation, which raises the likelihood of pregnancy. This effect can occur in females* who don’t usually have ovulation as part of their menstrual cycle. Before you start taking Actos, be sure to tell your doctor if you have irregular periods. They may recommend that you use effective birth control while taking the drug.

* In this article, we use the term “female” to refer to someone’s sex assigned at birth. For information about the difference between sex and gender, see this article.

Alcohol and Actos

There aren’t known safety issues with drinking alcohol while taking Actos.

But keep in mind that alcohol can affect your blood sugar levels. Actos is used to help manage blood sugar levels in people who have type 2 diabetes. So you may need to limit the amount of alcohol you drink while taking the drug.

If you drink alcohol, talk with your doctor about the amount that’s safe for you to consume while taking Actos.

Pregnancy and breastfeeding while taking Actos

It isn’t known if Actos is safe to take during pregnancy or while breastfeeding.

If you’re pregnant or breastfeeding, or planning to become pregnant or breastfeed, talk with your doctor before starting Actos treatment.

Actos is used to treat type 2 diabetes. You may have mild side effects while taking the drug. In rare cases, you may experience serious side effects, such as bladder cancer.

If you have questions about side effects from Actos, talk with your doctor or pharmacist. Below are a few questions you may want to ask:

• How can I maintain a weight that’s healthy for me while taking Actos?
• Do I have a higher risk of any side effects of Actos?
• Will other drugs I’m taking raise my risk of side effects from Actos?

To learn more about Actos, see these articles:

• All About Actos
• Dosage for Actos: What You Need to Know

To get information on different conditions and tips for improving your health, subscribe to any of Healthline’s newsletters. You may also want to check out the online communities at Bezzy. It’s a place where people with certain conditions can find support and connect with others.

Q:

Is there anything I can do to lower my risk of broken bones as a side effect of Actos?

Anonymous

A:

Before you start taking Actos, you should talk with your doctor about your risk of bone fractures. Your doctor will likely perform tests such as a bone mineral density scan to check your bone health. This will help them create a plan for you so that you can take Actos with less risk of fractures.

If you have questions or concerns about bone fractures while taking Actos, talk with your doctor or pharmacist.

The Healthline Pharmacist TeamAnswers represent the opinions of our medical experts. All content is strictly informational and should not be considered medical advice.

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Disclaimer: Healthline has made every effort to make certain that all information is factually correct, comprehensive, and up to date. However, this article should not be used as a substitute for the knowledge and expertise of a licensed healthcare professional. You should always consult your doctor or another healthcare professional before taking any medication. The drug information contained herein is subject to change and is not intended to cover all possible uses, directions, precautions, warnings, drug interactions, allergic reactions, or adverse effects. The absence of warnings or other information for a given drug does not indicate that the drug or drug combination is safe, effective, or appropriate for all patients or all specific uses.

Aktos :: Instructions :: Price :: Description of the drug

Actos (Actos)

1 tablet of Aktos contains:

pioglitazone (as hydrochloride) – 30 mg.

Additional ingredients: lactose monohydrate, carboxymethylcellulose, hydroxypropylcellulose, magnesium stearate.

Aktos is an oral antidiabetic agent containing pioglitazone, an active component of the thiazolidinedione group, which has a pronounced hypoglycemic effect in type 2 diabetes mellitus. The mechanism of action of pioglitazone is dependent on the presence of insulin. Aktos is a highly selective gamma receptor agonist that is activated by PPAR-gamma. PPAR-gamma receptors are found in muscle, adipose, and liver tissues, and activation of these receptors modulates the transcription of a number of genes that are insulin-sensitive and are involved in glucose control and lipid metabolism.

Aktos helps to reduce insulin resistance of peripheral tissues and the liver, resulting in an increase in the consumption of insulin-dependent glucose and a decrease in the release of glucose from the liver.

Unlike sulfonylurea preparations, Actos does not stimulate the production of insulin by the pancreas.

In patients with type 2 diabetes, when taking Actos, a decrease in insulin resistance is recorded, which leads to a decrease in serum glucose and a decrease in plasma insulin levels, as well as a decrease in glycated hemoglobin. There is a significant improvement in glycemic control in people with type 2 diabetes mellitus with combined therapy with Aktos and sulfonylurea derivatives, metformin or insulin.

In patients with type 2 diabetes mellitus with concomitant disorders of lipid metabolism, during therapy with Actos, a decrease in serum triglyceride levels and an increase in high-density lipoprotein levels are recorded without changes in total cholesterol and low-density lipoprotein.

Pharmacokinetics

When taken orally on an empty stomach, peak levels of pioglitazone are recorded after 2 hours, and minimum levels are recorded after 30 minutes from taking the tablet. Eating slightly increases the time to reach peak levels of pioglitazone (up to 3-4 hours), but does not change the degree of absorption.

After a single dose, the apparent volume of distribution reached 0.63±0.41 l/kg. A significant part of the dose of pioglitazone (up to 99%) is bound by serum proteins (most of it is albumin). Individual pioglitazone derivatives also significantly bind to serum proteins. Steady-state levels of pioglitazone are about 30-50% of peak serum levels.

The drug is extensively metabolized in the liver, in particular by hydroxylation and oxidation. The derivatives are further converted into conjugates with sulfuric and glucuronic acid. With multiple doses of the drug Actos, there is a significant level of pioglitazone derivatives M-3 and M-4 in serum. The metabolism of the drug is associated with the main isoenzymes of the P450 system.

After oral administration, about 15-30% of the active ingredient is found in the urine. An insignificant part of unchanged pioglitazone is excreted by the urinary system, excretion by the urinary system occurs mainly in the form of metabolites, as well as their conjugates.

A significant part of pioglitazone is excreted by the liver unchanged and in the form of derivatives.

The mean half-life of total pioglitazone and pioglitazone is 16–24 hours and 3–7 hours, respectively. The clearance rate is 5–7 l / h.

After a single dose, sufficient therapeutic doses of pioglitazone are noted for 24 hours.

Actos is used in the treatment of patients with non-insulin-dependent diabetes mellitus as monotherapy or in combination with insulin stimulating drugs (eg sulfonylurea derivatives) or insulin. The drug should be used only under the condition of diet and sufficient physical activity (in cases where only diet therapy and physical activity do not provide sufficient glycemic control).

Aktos is intended for oral use. Aktos tablets are taken 1 time per day, regardless of food. The dose of tablets should be selected personally, taking into account tolerability, efficacy and concomitant drugs used in complex therapy.

Generally, 15–30 mg/day of pioglitazone monotherapy is recommended in addition to diet and exercise. If necessary, under the supervision of a specialist, the dose can be increased to 45 mg / day. With monotherapy, it is not recommended to prescribe more than 45 mg / day; in case of insufficient glycemic control, additional administration of drugs that stimulate insulin secretion or insulin is recommended.

In combination with other oral antidiabetic drugs, including metformin or sulfonylurea derivatives, Aktos is prescribed at a dose of 15-30 mg / day. The total daily dose of pioglitazone is given as a single dose. At the beginning of therapy with Actos tablets, the dose of sulfonylurea derivatives or other hypoglycemic agents can be left unchanged, however, careful monitoring of glucose levels and a decrease in the dose of hypoglycemic agents with the development of hypoglycemia are necessary. It should be borne in mind that combination therapy with sulfonylurea drugs without changes in their dose is more often accompanied by the development of hypoglycemia (in comparison with combination therapy with metformin and pioglitazone).

In combination with insulin Actos is prescribed at a dose of 15–30 mg/day. The total daily dose of pioglitazone is given as a single dose. At the beginning of therapy with Actos, the dose of insulin can be left unchanged, however, careful monitoring of glucose parameters is necessary and a dose reduction of insulin preparations by 10-25% at glucose values ​​​​less than 100 mg / dl, further changes in the dose of insulin are carried out depending on the indicators of serum glucose levels .

More than 30 mg/day of pioglitazone is not recommended in combination therapy regimens for type 2 diabetes.

The combined use of Aktos with other thiazolidinedione derivatives has not been studied.

Patients with impaired renal filtration do not require dose adjustment of Aktos tablets.

During therapy with Actos tablets, some patients may develop adverse events associated with pioglitazone, including:

• Endocrine system: hypoglycemia (the likelihood of hypoglycemia is higher with combination therapy, while combined use with oral antidiabetic drugs led to the development of hypoglycemia in 2% of cases, and with insulin – in 8-15% of cases).

• Blood system: anemia, decreased levels of hemoglobin and hematocrit (in most cases, it was recorded after 4-12 weeks from the start of therapy).

• Gastrointestinal: increased activity of liver enzymes, hepatitis.

• Other: edema, change in body weight, transient changes in CPK activity.

• The decrease in hemoglobin and hematocrit during therapy with Actos remained constant in most cases and was not associated with clinically significant changes; this effect is likely associated with an increase in plasma volume.

The likelihood of developing edema during therapy with Actos tablets increased with combination therapy with insulin preparations.

In case of undesirable effects, it is recommended to consult a specialist. With the development of hypoglycemia, you should consult a specialist, self-correction of the dose of hypoglycemic drugs and insulin preparations is unacceptable.

Actos is not used in the treatment of patients with intolerance to the active or auxiliary components of the tablets.

Actos is contraindicated in type 1 diabetes mellitus.

Actos tablets are not prescribed for diabetic ketoacidosis.

The use of Aktos tablets is contraindicated in patients with heart failure of the third or fourth degree according to the international classification.

Aktos is not used in pediatrics.

Aktos is contraindicated during pregnancy and lactation. In case of planning or pregnancy during therapy with Actos, it is recommended to contact a specialist who will select the optimal therapy regimen.

Women of reproductive age taking COCs or other estrogen-containing contraceptives should take into account that Actos reduces the effectiveness of oral contraceptives and use additional contraceptives.

Actos, when used in combination, may reduce the effectiveness of contraceptive preparations containing estrogens.

Actos does not affect the pharmacokinetics of digoxin, metformin, indirect anticoagulants and glipizide when used in combination.

The effect of Actos on erythromycin, calcium channel blockers, astemizole, statins, triazolam, itraconazole, tacrolimus and trimetrexate has not been studied.

In vitro, ketoconazole reduces the metabolism of pioglitazone, but the clinical significance of this effect is unknown. Caution should be exercised when using Aktos in combination with ketoconazole.

Overdose of Actos was not accompanied by the development of clinical effects (provided monotherapy with pioglitazone). In case of an overdose of pioglitazone taken in combination with sulfonylurea drugs, hypoglycemia may occur.

No specific antidote. In case of an overdose, which is accompanied by hypoglycemia, the appointment of therapy aimed at normalizing carbohydrate metabolism is indicated.

Aktos tablets, 30 pieces per pack. The tablets are packaged in vials placed in a cardboard box.

Aktos is kept out of reach of children. Specific temperature conditions are not required.

Shelf life – 3 years.

Pioglar, Pioglitazone hydrochloride, Diab-norm, Amalvia, Pioglit, Piouno, Astrozone.

pioglitazone

A10B G03

EliLily&Co (USA)

Country of origin – USA.

Prescribe Actos with caution in patients with edematous syndrome, liver failure (including in the case of an increase in the level of enzymes 1.5-2 times higher than normal), heart failure and anemia.

Therapy with Actos requires the obligatory diet and exercise that are usually recommended for patients with type 2 diabetes.

It is recommended to assess the effectiveness of therapy based on the level of HbA1c, which is the most significant indicator of glycemic control over an extended period (compared to determining the level of serum glucose only on an empty stomach). This indicator allows you to determine the level of glycemia over the past few months. Therapy with Actos tablets should be continued for the entire time required to determine the level of HbA1c, if this therapy is not accompanied by a deterioration in glycemic control.

In patients with an anovulatory cycle and insulin resistance during therapy with Actos tablets, ovulation may resume, which increases the likelihood of pregnancy in the absence of sufficient contraceptive methods.

ALT levels should be checked before initiation of therapy, and periodically during the administration of Actos.

If a liver disorder is suspected, including the development of vomiting, epigastric pain, increased fatigue, loss of appetite and dark urine, it is necessary to conduct an extraordinary determination of liver function parameters. The decision on further therapy is possible only after determining the functional parameters of the liver and taking into account possible risks. The appearance of jaundice while taking Actos tablets requires discontinuation of pioglitazone therapy.

In case of symptoms of liver disease in the acute phase, the start of therapy with Actos tablets is recommended to be postponed. With moderately increased levels of liver enzymes, it is necessary to determine the cause of their increase and make a decision on further therapy based on the results obtained. Patients who have recorded an increase in liver enzymes should conduct more careful monitoring of liver function during therapy with Actos tablets.

The instruction was compiled by a team of authors and editors of the Piluli website. The list of authors of the drug reference book is presented on the site editorial page: Site editors.

References to used sources of information.

Attention!
The description of the preparation “ Aktos ” on this page is a simplified and supplemented version of the official instructions for use. Before purchasing or using the drug, you should consult your doctor and read the annotation approved by the manufacturer.
Information about the drug is provided for informational purposes only and should not be used as a guide to self-medication. Only a doctor can decide on the appointment of the drug, as well as determine the dose and methods of its use.

Actos instructions for use – tablets. Dosage, contraindications and analogues – MedZai.net

In pharmacies France Actos is available in various dosage forms and dosages. Manufacturers and marketing authorization holders also tend to differ. Below are all drugs with the name – Actos, indicating the dosage form of the dosage and method of application. It is also often important to know the manufacturers of each specific drug. Therefore, under each drug listed below, there is information about which factory and in which country all stages of its production took place.

Indications for systemic use

Diabetes mellitus type 2, as monotherapy or in combination with sulfonamide derivatives, metformin or insulin in the absence of effect from diet therapy, exercise and monotherapy with one of the above drugs.

Oral hypoglycemic agent, a derivative of the thiazolidinedione series. A potent, selective peroxisome proliferator-activated receptor gamma (PPAR-gamma) agonist. PPAR-gamma receptors are found in adipose, muscle and liver tissues. Activation of nuclear receptors by PPAR-gamma modulates the transcription of a number of insulin-responsive genes involved in glucose control and lipid metabolism. It reduces insulin resistance in peripheral tissues and in the liver, as a result of which there is an increase in the consumption of insulin-dependent glucose and a decrease in glucose production in the liver. Unlike sulfonylurea derivatives, pioglitazone does not stimulate insulin secretion by pancreatic beta cells.

In type 2 diabetes mellitus (non-insulin dependent), the decrease in insulin resistance under the action of pioglitazone leads to a decrease in blood glucose concentration, a decrease in plasma insulin levels and hemoglobin A1c (glycated hemoglobin, HbA1c).

In type 2 diabetes mellitus (non-insulin dependent) with impaired lipid metabolism, the use of pioglitazone shows a decrease in TG levels and an increase in HDL levels. At the same time, the level of LDL and total cholesterol in such patients does not change.

Pharmacokinetic characteristics of the drug when taken orally

After oral administration on an empty stomach, pioglitazone is detected in the blood plasma after 30 minutes. Cmax in plasma is achieved after 2 hours. When eating, there was a slight increase in the time to reach Cmax up to 3-4 hours, but the degree of absorption did not change.

After taking a single dose, the apparent Vd of pioglitazone averages 0.63±0.41 l/kg. Binding to human serum proteins, mainly albumin, is more than 99%; binding to other serum proteins is less pronounced. Metabolites of pioglitazone M-III and M-IV are also largely associated with serum albumin – more than 98%.

Pioglitazone is extensively metabolized in the liver by hydroxylation and oxidation. Metabolites M-II, M-IV (hydroxy-derivatives of pioglitazone) and M-III (keto-derivatives of pioglitazone) exhibit pharmacological activity in animal models of type 2 diabetes mellitus. Metabolites are also partially converted into conjugates of glucuronic or sulfuric acids.

Metabolism of pioglitazone in the liver occurs with the participation of isoenzymes CYP2C8 and CYP3A4.

T1 / 2 of unchanged pioglitazone is 3-7 hours, total pioglitazone (pioglitazone and active metabolites) – 16-24 hours. Clearance of pioglitazone is 5-7 l / h.

After oral administration, about 15-30% of a dose of pioglitazone is found in the urine. The kidneys excrete a negligible amount of pioglitazone, mainly in the form of metabolites and their conjugates. It is believed that when taken orally, most of the dose is excreted in the bile both unchanged and in the form of metabolites and is excreted from the body with feces.

Serum concentrations of pioglitazone and active metabolites remain at a sufficiently high level 24 hours after a single daily dose.

Side effects when taken orally

Hypoglycemia, headache, sinusitis, myalgia, dental damage, pharyngitis, edema (in 4.8% of cases with monotherapy and in 15.3% – at combinations with insulin), anemia (in 1-1.6% of cases), changes in the level of bilirubin, AST, ALT, alkaline phosphatase and GGT.

Hypersensitivity, type 1 diabetes mellitus, diabetic ketoacidosis, severe heart failure, acute liver disease, 2.5 times normal ALT levels, pregnancy, lactation.

Contraindicated in pregnancy.

FDA Fetal Category C.

Stop breastfeeding during treatment.

Do not use pioglitazone in the presence of clinical manifestations of liver disease in the active phase or with an increase in ALT activity 2. 5 times higher than ULN. With moderately elevated liver enzymes (ALT less than 2.5 times ULN), before or during treatment with pioglitazone, patients should be examined to determine the cause of the increase. With a moderate increase in the activity of liver enzymes, treatment should be started or continued with caution. In this case, more frequent monitoring of the clinical picture and the study of the level of liver enzyme activity are recommended.

In the event of an increase in serum transaminase activity (ALT > 2.5 times ULN), liver function monitoring should be carried out more frequently and until the level returns to normal or to the values ​​observed before treatment. If ALT activity is 3 times the upper limit of the norm, then a second test to determine the activity of ALT should be carried out as soon as possible. If ALT activity remains at 3 times ULN, pioglitazone should be discontinued.

During treatment, if liver dysfunction is suspected (appearance of nausea, vomiting, abdominal pain, fatigue, lack of appetite, dark urine), liver function tests should be determined.