Actos is the brand name of pioglitazone, an oral anti-diabetic used to treat Type II or Non-Insulin Dependent Diaetes Mellitus (NIDDM).
Though it is effective in treating Type II diabetes, especially when used along with dietary and lifestyle medications it has been linked to serious side effects, some of which may be dangerous or life threatening. Concerns about the medication have arisen over adverse events such as kidney disease, bladder cancer and congestive heart failure.
Another member of the same thiazolidinedione (TZD) class of anti-diabetic medications, Avandia (rosiglitazone) has also been the subject of intensive investigation in both the United States and Europe. Because this class of medications has proven to be so dangerous, the FDA placed temporary restrictions on the use of Avandia and has required that a “black-box” warning be placed on Actos.
The black-box warning on Actos warns that people with a history of heart failure should not use the medication. The FDA also required that the “Warnings and Precautions “section of the prescription information for Actos be updated to include notice about the possibility of bladder cancer in those who have used it for over one year.
Takeda is one of the top 20 largest pharmaceutical companies in the world. They partnered with Eli Lilly to market Actos and in 2011, sales reached $3.85 billion in the U.S. alone. Before the drug lost patent protection and became available for generic use, it made up 27 percent of the manufacturer’s yearly revenue and was the best-selling anti-diabetic medication in the U.S.
Takeda has received thousands of lawsuits by patients who have been diagnosed with bladder cancer. These lawsuits state that the manufacturer, Takeda, had knowledge of the dangers of Actos and failed to adequately warn patients and physicians. Takeda has been accused of valuing profits over safety.
What is Actos
Actos is an anti-diabetic medication used to treat Type II diabetes. It is manufactured in tablet form for oral use. It works by increasing the body’s sensitivity to insulin and by decreasing the amount of sugar that is stored in the liver. This makes insulin work better to supply the body’s cells with glucose to use as energy. It is not for Type I (Insulin Dependent Diabetes) or for those with ketoacidosis.
Actos comes in 15 mg, 30 mg and 45 mg tablets and is taken once daily. It can be used alone or with other medications such as Glucophage (metformin) or with insulin as needed.
Side Effects and Drug Interactions of Actos
Actos carries a number of side effects and interactions with other medications, many of which are minor but some are more dangerous and can be life-threatening.
Some of the most common side effects of Actos include:
- Pain in legs or arm
- Back Pain
- Chest Pain
- Cardiac Failure
- Weight Gain
- Myalgia (muscle aches)
- Bladder Cancer
- Macular Edema
- Bone Fractures
- Ovulation in anovulatory women
Actos can also have drug interactions with other prescription medication including:
- Warfarin (blood thinner)
- Digoxin (treats congestive heart failure and arrhythmias)
- Oral Contraceptives
- Fexofenadine (Allegra, anthihistamine)
- Glipizide (oral anti-diabetic)
- Metformin (oral anti-diabetic)
- Midazolam (antianxiety)
- Ranitidine (anti-ulcer)
- Nifedipine, Atorvastatin (calcium channel blockers for blood pressure and cardiac effects)
- Theophylline (asthma)
- Gemfibrozil (cholesterol)
- Ketoconazole (anti-fungal)
- Rifampin (antiviral)
Tell your physician about all of the medication that you are taking and report any side effects to your doctor. Report sudden or bothersome side effects as soon as possible.
Serious Adverse Events of Actos
Bladder Cancer Risk
Studies including pre-clinical (animal) studies performed by Takeda had identified a higher risk of bladder cancer when taking Actos. Animal studies showed that male rats suffered from an increase in bladder tumors after receiving pioglitazone.
Two additional human studies, conducted over a three year period also showed a higher incidence of bladder cancer in those who received Actos vs. other medications. Based on the results of these studies, Takeda was required by the FDA to conduct a 10 year safety study to examine the risk of bladder cancer. The study has not concluded but interim results prompted the FDA to require Takeda to add warnings about bladder cancer to prescribing information.
The latest study results regarding pioglitazone, published in BMJ (formerly British Medical Journal) in May of 2012 revealed that taking Actos for an extended period of time can cause an 83 percent increase in the risk of developing bladder cancer. In addition, a study presented at the May 2012 annual meeting of the American Society of Clinical Oncology suggest that the increased risk may apply to all medications in the same class as Actos and an August 2012 study in the Journal of the National Cancer Institute found that the risk may actually be triple the normal rate when Actos is used for more than five years.
Regulators in France, Germany and other parts of the European Union have suspended the sales of Actos.
Symptoms of Bladder Cancer include:
- Painful urination
- Urinary urgency (increased need to urinate even when bladder is not full)
- Blood in the urine (urine may appear dark or noticeably red)
- Unusual back pain (flank pain, just above hip bones)
If you have any of these symptoms, you should contact your health care provider right away to determine if bladder cancer may be the cause.
Congestive Heart Failure Risk
A black-box warning was required by the FDA to warn users of Actos of the possible risk of developing or worsening Congestive Heart Failure. A “black box” warning is a serious warning that is printed in a black box on the top of the medication’s prescribing information. It is printed in such a way that physicians and other health practitioners will notice the warning right away. Companies are also required to send out notification, warning letters to all practitioners when a change of this type is made by the FDA.
The black box warning states that some patients with known heart failure should not take Actos and that the medication may increase the risk of developing or worsening heart failure.
Symptoms of Congestive Heart Failure include:
- Rapid weight gain
- Edema (fluid retention)
- Dyspnea (difficulty breathing or painful breathing)
- Fatigue (extreme tiredness or lack of energy)
- Swelling of the abdomen or legs
Symptoms of congestive heart failure occur because the heart is unable to supply enough blood to the kidneys to rid the body of water and water collects in the lungs and peripheral spaces of the body. Congestive heart failure can be life threatening in some cases. Patients with a history of heart failure should be closely monitored when taking Actos. Patients with advanced heart failure should not take Actos.
Other Potentially Dangerous Side Effects of Actos
Pioglitazone may increase the risk of bone fractures. Women are more likely to experience this and fractures most often occur in the legs and arms. The PROactive study showed that the incidence of bone fracture in women who were taking Actos was twice that of those taking placebo throughout the course of nearly three years.
Chronic Kidney Disease
A study published in PLoS One by researchers from Taiwan showed that Actos increased the risk of the development of Chronic Kidney Disease by 400 percent. Kidney disease is a known risk of diabetes; however patients who took Actos were four times more likely to develop kidney disease than patients who did not take the medication.
Actos can increase the chance of developing lactic acidosis following the development of heart failure and because Actos can cause hypoglycemia.
Lactic Acidosis can be caused by low blood sugar levels and is increased by kidney damage, heart failure, liver damage and high alcohol intake. The risk of developing lactic acidosis is higher when Actos is taken with metformin or as the combination drug Actoplus met.
Lactic acidosis can be life-threatening but first occurs as symptoms such as:
- Rapid breathing
- Irregular heart rate
- Low blood pressure
- Stomach pain
If you have symptoms of lactic acidosis, it should be considered a medical emergency. You need to seek emergency medical help immediately.
Some reports have been received regarding the occurrence of liver failure in patients who took Actos. The reports included both fatal and non-fatal liver failure cases. Actos has not been proven to cause liver failure but it does affect liver’s metabolism of other medication.
Symptoms of liver failure include:
- Yellowing of the skin or whites of the eyes
- Dark urine
- Light colored feces
- Upper abdominal pain or discomfort
- Anorexia (inability to eat)
If you have symptoms of liver failure you should see your health practitioner right away.
Report your medical history
Always tell your doctor or health practitioner about all of your health conditions and any medication you are taking. For diabetics it is especially important that you let your doctor know about your history and any family history of:
- Type I diabetes
- Liver disease
- Macular edema, macular degeneration or any other eye problems
- Osteoporosis or other fragile bones
- Pregnancy, nurse-feeding or plans to become pregnant
- Kidney disease
- Heart disease
Discuss all of your health conditions, health changes and medications with your physician. This includes over the counter medication as well as nicotine, alcohol and recreational drug use.
Thousands of Actos lawsuits have been filed against both Takeda and Eli Lilly who manufacture and market Actos by patients and family members of patients diagnosed with bladder cancer after taking Actos.
The first federal trial regarding Actos was conducted in Louisiana. The plaintiff (patient) was awarded $1.5 million in actual damages (for medical expenses and work loss) and $9 billion in punitive damages (to punish the company). The lawyers for the plaintiff argued that the drug company was more concerned with making a profit than with patient safety.