Actos (pioglitazone) can cause a number of side effects, some of which may be serious or even life-threatening. The most dangerous side effects include bladder cancer, macular edema, bone fractures and the possibility of liver failure.
Actos was temporarily discontinued in the United States due to side effects discovered after the drug was approved. The FDA required the manufacturer of Actos to include more stringent warnings and allowed the medication back onto the market; however Actos has been discontinued or severely restricted in other countries because of the dangers.
Other medications of this class have exhibited similar dangerous toxicities and have been recalled. Actos and medications like it have been listed as drugs to “avoid” by the well-known magazine and non-profit organization Consumer Reports along with multiple health organizations.
Multiple lawsuits have been filed against Takeda, the manufacturer of Actos claiming that Takeda knew about risks to patients using Actos but valued profits above patient safety. The first federal trial regarding damage caused by Actos was tried in Louisiana and resulted in $9 million in punitive damages along with $1.5 million in actual damages.
Other patients who experience serious side effects after taking Actos may be able to pursue legal options.
Life threatening Side Effects of Actos
Though Actos is often effective at treating Type II diabetes, it can cause a number of side effects, including bladder cancer and heart failure.
Increased risk of bladder cancer
Studies conducted by the pharmaceutical manufacturer identified the risk of bladder cancer long before the drug was approved for human use. Pre-clinical, animal studies showed that male rats experienced a higher rate of bladder tumor formation after receiving pioglitazone.
Takeda, the manufacturer of Actos also conducted two human studies which showed a higher incidence of bladder cancer over a three year period when compared to other drugs. After the results of these studies were available, the FDA required Takeda to undertake a 10-year safety study examining the increased risk of bladder cancer. The results of that study have not been fully tabulated but interim reports caused the FDA to require that Takeda add warnings regarding bladder cancer risk to Actos prescribing information.
Results of several studies published in 2012 indicate that the risk of increased bladder cancer may be worse if the drug is taken for an extended period of time. A study published in BMJ (British Medical Journal) showed an 83% increase when Actos is taken for over a year, while a study published in the Journal of the National Cancer Institute showed that the risk of bladder cancer may be triple that of patients not taking Actos when the medication is used for more than five years.
You should contact your health care provider immediately if you have any symptoms of bladder cancer such as:
- Painful urination
- Increased urge to urinate
- Blood in the urine
- Sudden or unusual back pain
Increased risk of heart failure
Actos has been shown to cause or increase the risk of heart failure, particularly in those who have a pre-existing cardiac condition.
In June of 2007, the FDA required the manufacturer of Actos to include a black-box warning about the increased risk of heart failure worsening or development. A black-box is a severe warning printed at the top of prescribing information meant to call attention to the serious side effects that may be posed by a medication. Manufacturers who are required to issue black box warnings must also send out warning notices to all prescribers regarding the danger.
The black box warning on prescribing information for Actos warns practitioners that the medication may cause or worsen heart failure and that some patients with certain cardiac conditions should not take the medication.
The increased risk of heart failure after taking Actos may be worsened by other effects of the medication such as water retention and sudden weight gain related to edema. When the body is unable to rid itself of excess water, a greater burden is placed on the heart and kidneys. Water may collect in the lungs and peripheral body cavity spaces. Congestive heart failure can become a medical emergency.
You should contact your health care provider immediately if you have any symptoms of heart failure such as:
- Fluid retention (edema)
- Sudden weight gain
- Painful or difficulty breathing (dyspnea)
- Extreme tiredness or lack of energy (fatigue)
- Unusual swelling of the abdomen or legs
Severe Side Effects of Actos
Severe side effects are those side effects which can be medically significant and may cause physical harm. In most cases, severe side effects will not be life-threatening but may result in permanent injury. Severe side effects of Actos include: increased number of bone fractures, macular edema, risk of kidney disease and risk of liver disease.
Prescribing information for pioglitazone shows an increased risk of bone loss and fractures in women. Long term studies of the drug class have shown a risk that is twice or three times greater than patients who did not receive the medication. The risk may also be increased in men as well and most commonly includes the extremities but also the hips as well. Patients who are taking the medication should have regular physical exams, including a check for bone density and other measures that show an increased risk for fractures.
The medication class that Actos (pioglitazone) belongs to, thiazolidinedione anti-diabetics can cause macular edema. Macular edema is a swelling or fluid gathering in the back of the eye or retinal. Patients with macular edema often experience blurry vision and may not see as well. Macular edema can cause permanent changes to visual acuity. Patients with diabetes should have regular eye exams because diabetes may also cause retinal damage. Patients taking Actos should report the medication use to their ophthalmologist and see a physician immediately if sudden vision changes occur.
Actos and similar medications may also pose a particular risk to kidney health. A direct link between a worsened risk of kidney disease has not been fully established but a study conducted in Taiwan, published in the medical journal PLoS One showed that eight percent of study patients using Actos developed chronic kidney disease, even when the drug was given at low doses and used for less than one year. As Actos can also cause edema and heart failure, it may put an additional burden on the kidney, contributing to kidney disease.
Several cases of liver failure have been reported in patients receiving Actos. Reports include incidents of both non-fatal and fatal hepatic impairment in those using Actos. A direct cause has not been established but it is known that Actos can affect the liver’s metabolism of other medications which demonstrates a possible link. Liver symptoms such as jaundice or yellowing of the skin and whites of the eyes, dark urine, light colored feces or unusual abdominal pain should be reported to a physician. Actos should only be used with caution in those who have existing mild liver impairment and is not recommended in those with more advanced liver disease.
The use of pioglitazone and other similar medications may result in ovulation of women who have a condition known as premenopausal anovulation. These women may be at an increased risk for becoming pregnant while taking Actos. The frequency of this side effect has not been well studied and adequate contraception in all women of child-bearing age is recommended.
Common Side Effects of Actos
In addition to life-threatening and severe side effects of Actos, the medication may cause a number of well-known or common side effects. Side effects of medication, including Actos can occur at any time while taking it. Side effects are often most bothersome when beginning medication or increasing the dosage amounts.
Common adverse events of Actos include:
- Leg, Arm, Back or Chest Pain
- Muscle Aches
- Sinusitis and Pharyngitis
- Weight Gain
- Flatulence or Gassiness
- Low Blood Sugar
Side effect rates tend to be worse when the medication is taken at higher doses. Be sure to discuss any side effects with your physician or provider. Most of these common side effects will not be dangerous but if side effects occur suddenly or become particularly bothersome or debilitating, contact your health care provider right away.
Actos, like many other medications can cause interactions with other drugs. These interactions can include medications that are taken over-the-counter. Drug interactions can sometimes be serious or even life-threatening. . You should discuss all of your medical conditions and medications that you are taking with your doctor and pharmacist
Drugs that are known to interact with Actos include:
- Warfarin (blood thinner) – may decrease blood thinning effect
- Digoxin (treats congestive heart failure and arrhythmias) – may increase toxicity of digoxin
- Oral Contraceptives – may increase pregnancy risk
- Fexofenadine (Allegra, anthihistamine) – may increase side effects of fexofenadine and increase the risk of hypoglycemia
- Midazolam (antianxiety) – may decrease anti-anxiety effects
- Ranitidine (anti-ulcer) – may decrease the effectiveness of Actos
- Nifedipine, Atorvastatin (calcium channel blockers for blood pressure and cardiac effects) – may increase the risk of hypertension and arrhythmia, may decrease the effectiveness of Actos
- Theophylline (asthma) – may increase the toxicity of theophylline, may decrease the effectiveness of Actos
- Gemfibrozil (cholesterol) – may increase the effemay increase the risk of hypoglycemia
- Ketoconazole (anti-fungal) –may increase the risk of hypoglycemia
- Rifampin (antiviral) – decrease the effectiveness of Actos
- Glipizide (oral anti-diabetic) – changes in blood sugar should be closely monitored
- Metformin (oral anti-diabetic) – changes in blood sugar should be closely monitored
- Other anti-diabetic medications– changes in blood sugar should be closely monitored
In addition to known drug interactions, pioglitazone can cause allergic reactions to the medication itself or any of the inactive ingredients. Symptoms allergic reaction can include rash, itching, gastrointestinal intolerance and more severe reactions such as swelling of the face, lips or throat and difficulty breathing. Any allergic reaction should be reported to a practitioner, allergic reactions that involve swelling or difficulty breathing should be treated as a medical emergency.
Do not take Actos if you are allergic to any of the following:
- Pioglitazone or relatives such as rosiglitazone
- Carboxymethylcellulose Calcium
- Lactose Monohydrate
- Magnesium Stearate
If you or a loved one has suffered severe injury or death related to the use of Actos, you may be entitled to damages from the manufacturer.