Actos (pioglitazone)

• Actos is used for the treatment of type 2 diabetes in adults. It is used along with a healthy diabetic diet, regular exercise, weight control, smoking reduction, and careful monitoring of blood glucose.
• Actos may be used alone or in combination with metformin (Glucophage, Glucophage XR, Glumetza, Fortamet, Riomet), a drug in a different class of anti-diabetic drugs, that also lowers blood glucose.
• Actos requires naturally-secreted insulin to be effective so it is not recommended in type 1 diabetes where the amount of insulin is very low or absent.
• Nevertheless, Actos is approved for treating type 2 diabetes in combination with insulin as well as another class of diabetes drugs, the sulfonylureas, that increases the amount of insulin produced.

• Pioglitazone is an oral drug that reduces the amount of glucose (sugar) in the blood. It is in a class of anti-diabetic drugs called thiazolidinediones that are used in the treatment of type 2 diabetes. The other member in this class is rosiglitazone (Avandia). (Another member of this class, troglitazone or Rezulin, was removed from the market because of liver toxicity.)

Yes

Yes

ACTOS BLACK BOX WARNING

• Actos and similar drugs can cause or women congestive heart failure in some patients.
• Patients should be monitored for signs and symptoms of heart failure (for example, excessive, rapid weight gain, dyspnea, and/or edema) at the beginning of treatment and after dose increases.
• Actos is not recommended for patients with symptomatic heart failure and patients with established New York Heart Association (NYHA) Class III or IV heart failure should not use Actos.

Other side effects of Actos

The most common side effects of Actos alone or in combination with sulfonylureas, metformin, or insulin are:

• Upper respiratory tract infection
• Headache
• Sinusitis
• Muscle aches
• Tooth disorders
• Hypoglycemia (low blood sugar)
• Sore throat

Possible serious side effects of Actos include:

• Anemia
• Liver injury
• Edema
• Fractures
• Bladder cancer
• Diabetic macular edema

Dose related fluid accumulation (edema) can occur especially when combined with insulin. Fluid accumulation can worsen or lead to heart failure. Actos should not be used in patients with heart disease classified by the New York Heart Association (NYHA) as Class III and IV heart failure or symptomatic heart failure.

Fluid accumulation also may lead to macular edema, resulting in reduced vision. Actos also can reduce red blood cells.

There have been post-marketing reports of liver failure while taking Actos.

Actos has been associated with liver injury. Periodic monitoring of liver-related side effects and liver tests should be conducted in patients taking Actos.

Symptoms of liver injury are:

• Nausea
• Vomiting
• Abdominal pain
• Fatigue
• Anorexia (loss of appetite)
• Dark urine

Actos should be stopped if patients have symptoms of liver injury and liver function test results that are greater than three times the normal level. Liver blood tests are obtained before starting treatment. Monitoring liver tests during treatment is not recommended for patients without liver disease.

Actos may cause ovulation in women who have stopped ovulating if they are premenopausal and insulin resistant. This may lead to pregnancy. For women (but not men) taking Actos, there is an increased risk of bone fractures of the distal bones of the arm and leg. Patients taking Actos should maintain proper bone health.

• Actos is prescribed once daily in doses ranging from 15 to 45 mg.
• The recommended starting dose for patients without heart failure is 15 or 30 mg and for those with heart failure it is 15 mg daily. The dose may be increased in 15 mg intervals to a maximum dose of 45 mg daily if needed.
• Actos may be taken any time of the day, with or without meals.
• If a dose is missed on one day, two doses should not be taken the next day to make up for the missed dose.

• 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.

• There are no adequate studies of Actos in pregnant women. Actos may be used in pregnancy if the physician feels the potential risks are justified.
• It is unknown if Actos is secreted in breast milk. Therefore, the effect of Actos on the nursing infant whose mother is taking Actos is unknown.

What preparations of Actos (pioglitazone) are available?

• Tablets: 15, 30 and 45 mg.

How should I keep Actos (pioglitazone) stored?

• Tablets should be kept at room temperature, 15 C -30 C (59 F -86 F).

How does Actos (pioglitazone) work?

• Patients with type 2 diabetes cannot make enough insulin, and the cells of their body respond less to the insulin that is produced. Since insulin is the hormone that stimulates cells to remove glucose from the blood, the reduced amount of insulin and its reduced effect cause cells to take up less glucose from the blood and the level of glucose in the blood to rise. Pioglitazone often is referred to as an "insulin sensitizer" because it attaches to the insulin receptors on cells throughout the body and causes the cells to become more sensitive (more responsive) to insulin. As a result, more glucose is removed from the blood, and the level of glucose in the blood falls. At least some insulin must be produced by the pancreas in order for pioglitazone to work. Pioglitazone also lowers the level of glucose in the blood by reducing the production and secretion of glucose into the blood by the liver. In addition, pioglitazone may alter the blood concentrations of lipids (fats) in the blood. Specifically, it decreases triglycerides and increases the "good" (HDL) cholesterol.

When was Actos (pioglitazone) approved by the FDA?

• Pioglitazone received FDA approval in July 1999.