Detailed Drug Information:

DRUG CLASS AND MECHANISM: Pioglitazone is a 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 II 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.) Patients with type II diabetes cannot make enough insulin, and the cells of their body do not respond normally to the reduced amounts of insulin that are present. (Insulin is the hormone produced by the pancreas that stimulates cells to remove glucose from the blood.) 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. 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. Pioglitazone received FDA approval on July 16, 1999.

PREPARATIONS: Tablets: 15, 30 and 45 mg.

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

PRESCRIBED FOR: Pioglitazone is used for the treatment of type II diabetes along with a healthy diabetic diet, regular exercise, weight control, smoking reduction, and careful monitoring of blood glucose. Pioglitazone may be used alone or in combination with metformin, a drug in a different class of anti-diabetic drugs, that also lowers blood glucose. Since it requires naturally-secreted insulin to be effective, pioglitazone is not recommended in type I diabetes where the amount of insulin is very low or absent. Nevertheless, pioglitazone is approved for treating type II diabetes in combination with insulin as well as another class of anti-diabetic drugs, the sulfonylureas.

DOSING: Pioglitazone is prescribed once daily in doses ranging from 15 to 45 mg. Pioglitazone 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.

DRUG INTERACTIONS: To date, no formal studies to evaluate drug interactions of pioglitazone with other drugs have been conducted. However, since another thiazolidinedione that is similar to pioglitazone may reduce the effectiveness of oral contraceptives (potentially leading to pregnancy), caution should be used when using pioglitazone with an oral contraceptive.

Clinical studies using pioglitazone 15-45mg did not reveal changes in blood levels for the following drugs: glipizide, digoxin, warfarin or metformin. In addition, the clotting of blood did not appear to be changed enough by pioglitazone to require alterations in the doses of the blood thinner, warfarin.

PREGNANCY: There are no adequate studies of pioglitazone in pregnant women. Pioglitazone may be used in pregnancy if the physician feels the potential risks are justified.

NURSING MOTHERS: It is unknown if pioglitazone is secreted in breast milk. Therefore, the safety to a nursing infant when the mother is taking pioglitazone is unknown.

SIDE EFFECTS AND PRECAUTIONS: The most common side effects seen in clinical trials with pioglitazone alone or in combination with sulfonylureas, metformin, or insulin were upper respiratory tract infection, headache, sinusitis, muscle aches, tooth disorders, hypoglycemia, and sore throat. In addition, fluid accumulation (edema) occurred in less than 5% of patients taking pioglitazone alone but 15% of patients taking pioglitazone and insulin (as compared with 2% and 7% of patients receiving placebo, respectively). Fluid accumulation can lead to heart failure.

To date, no formal studies to evaluate drug interactions of pioglitazone with other drugs have been conducted. Nevertheless, because it interacts with the liver enzymes that eliminate some other drugs, there is the potential for pioglitazone to increase the elimination of such drugs as erythromycin, calcium channel blockers (e.g.,Cardizem), cisapride (Propulsid), corticosteroids, cyclosporine, tacrolimus, triazolam (e.g.,Halcion), trimetrexate, and HMG-CoA reductase inhibitors (e.g., Lipitor). This would reduce their effectiveness.

Since another thiazolidinedione antidiabetic drug has been associated with liver injury, it is recommended that periodic monitoring of liver-related side effects and liver function be done in patients taking pioglitazone. Side effects while taking pioglitazone which may be due to liver injury include nausea, vomiting, abdominal pain, fatigue, anorexia (loss of appetite), or dark urine. Blood liver tests also are recommended during pioglitazone therapy.

Studies in the laboratory have shown that an anti-fungal drug, ketoconazole (Nizoral), prevents the elimination of pioglitazone. This could lead to increased levels of pioglitazone and hypoglycemia (seriously reduced level of sugar in the blood). Therefore, the manufacturer of pioglitazone recommends more frequent monitoring of blood sugar among patients taking both pioglitazone and ketoconazole or the drugs related to ketoconazole, fluconazole (Diflucan) and itraconazole (Sporanox).

Pioglitazone may cause ovulation in women who have stopped ovulating if they are pre-menopausal and insulin resistant. This may lead to pregnancy.

Since studies of pioglitazone excluded patients with heart disease classified by the New York Heart Association (NYHA) as Class III and IV (more serious disease), it is not known how diabetics with serious heart disease will respond to pioglitazone, particularly since it may lead to fluid accumulation and heart failure.