When This Medicine Should Not Be Used:
You should not use this medicine if you have had an allergic reaction to pioglitazone or metformin. You should not use this medicine if you have bladder cancer, severe heart failure, severe liver disease, severe kidney disease, type 1 diabetes, metabolic acidosis (acid in the blood), or diabetic ketoacidosis (ketones in the blood). You should talk with your doctor about temporarily stopping this medicine if you are going to have major surgery or an x-ray procedure with an injection of dyes (contrast agents) into your vein.

How to Use This Medicine:
Tablet, Long Acting Tablet

• Take your medicine as directed. Your dose may need to be changed several times to find what works best for you.
• It is best to take this medicine with food or milk.
• Carefully follow your doctor's instructions about a special diet, exercise, or weight loss. Check your blood sugar on a regular basis at home.
• Swallow the extended-release tablet whole. Do not crush, break, or chew it.
• If you take the extended-release tablet, part of the tablet may pass into your stools. This is normal and is nothing to worry about.
• Drink extra fluids so you will urinate more often and help prevent kidney problems.
• This medicine should come with a Medication Guide. Ask your pharmacist for a copy if you do not have one.

Drugs and Foods to Avoid:
Ask your doctor or pharmacist before using any other medicine, including over-the-counter medicines, vitamins, and herbal products.

• Make sure your doctor knows if you are using other medicines to treat your diabetes, such as insulin. Tell your doctor if you also use digoxin (Lanoxin®), gemfibrozil (Lopid®), isoniazid (Nydrazid®), midazolam (Versed®), morphine, nicotinic acid (Nicobid®, Nicolar®), phenytoin (Dilantin®), procainamide (Procanbid®, Pronestyl®), quinidine (Quinidex®), quinine, ranitidine (Zantac®), rifampin (Rifadin®, Rimactane®), trimethoprim (Bactrim®, Primsol®, Proloprim®, Septra®), or vancomycin (Vancocin®, Vancoled®).
• Make sure your doctor knows if you use asthma medicine, decongestants, diuretics or "water pills" (such as amiloride, furosemide, triamterene, Dyrenium®, or Lasix®), a steroid medicine (such as dexamethasone, prednisolone, prednisone, or Medrol®), a phenothiazine medicine (such as prochlorperazine, Compazine®, Mellaril®, Phenergan®, Thorazine®, or Trilafon®), a thyroid replacement (such as levothyroxine, liothyronine, Cytomel®, or Synthroid®), estrogen hormones (Premarin®), or birth control pills. Tell your doctor if you use heart or blood pressure medicine such as amlodipine, nifedipine, verapamil, Adalat®, Cardizem®, Lotrel®, Norvasc®, Procardia®, or Tiazac®.
• Do not drink alcohol while you are using this medicine.

Warnings While Using This Medicine:

• Make sure your doctor knows if you are pregnant or breastfeeding. Certain women may be at an increased risk for pregnancy while taking this medicine. If you had problems ovulating and had irregular periods in the past, this medicine may cause you to ovulate. This could increase your chance of becoming pregnant. Talk to your doctor about effective birth control while you are using this medicine.
• Make sure your doctor knows if you have kidney disease, liver disease, congestive heart failure, edema (problems with fluid retention or swelling), macular edema (swelling of the back of the eye), adrenal gland problems, pituitary gland problems, or a history of alcoholism or bladder cancer.
• This medicine may not work as well if you have surgery, get hurt, or get sick. Also, avoid getting dehydrated while you are using this medicine, especially if you have a fever, vomiting, or diarrhea. Be sure to drink extra fluids when you exercise or increase your activity level, or if you sweat more than usual.
• Check with your doctor right away if you start having chest pain; shortness of breath; excessive swelling of the hands, wrist, ankles, or feet; or if you are rapidly gaining weight. These may be symptoms of a serious heart problem.
• This medicine may cause a rare, but serious condition called lactic acidosis in some people. Call your doctor right away if you get sick, or if you have unusual tiredness, weakness, muscle pain, stomach pain, trouble breathing, fever, or nausea.
• Tell your doctor right away if you have any of these symptoms: loss of appetite, nausea, vomiting, stomach pain, unusual tiredness or weakness, weight loss, or yellow eyes or skin. These may be symptoms of a serious liver problem.
• This medicine may increase your risk for bladder cancer if you take it for more than 12 months. Tell your doctor right away if you have blood in the urine; a frequent, strong, or increased urge to urinate; painful urination; or pain in the back, lower abdomen, or stomach.
• Check with your doctor if blurred vision, decreased vision, or any other change in vision occurs during your treatment. Your doctor may want you to have your eyes checked by an ophthalmologist (eye doctor).
• This medicine may increase the risk for bone fractures in women. Ask your doctor about ways to keep your bones strong to help prevent fractures.
• Your doctor will do lab tests at regular visits to check on the effects of this medicine. Keep all appointments. You will also need to check your blood sugar on a regular basis at home.
• Some things that can lead to low blood sugar are exercising more than normal or waiting too long to eat. Tell your doctor about any sudden change in your medical condition.

Possible Side Effects While Using This Medicine:
Call your doctor right away if you notice any of these side effects:

• Allergic reaction: Itching or hives, swelling in your face or hands, swelling or tingling in your mouth or throat, chest tightness, trouble breathing
• Blurred vision or other changes in vision.
• Change in how much or how often you urinate, painful urination.
• Cold feeling in your arms or legs.
• Dark-colored urine or pale stools.
• Extreme weakness, tiredness, or confusion.
• Lightheadedness or fainting, slow or uneven heartbeat.
• Nausea, vomiting, loss of appetite, or pain in your upper stomach.
• Pain or swelling in your arms or legs without any injury.
• Rapid breathing, trouble breathing, or stomach pain with nausea and vomiting.
• Rapid weight gain.
• Severe vomiting with fever or diarrhea.
• Shortness of breath with cold sweat and bluish-colored skin.
• Swelling in your hands, ankles, or feet.
• Unusual weakness, bruising, or pale skin.
• Yellowing of your skin or the whites of your eyes.

If you notice these less serious side effects, talk with your doctor:

• Cold or flu symptoms.
• Dizziness.
• Headache.
• Mild nausea, diarrhea, or stomach upset.
• Muscle or joint pain.
• Problems with your teeth.

If you notice other side effects that you think are caused by this medicine, tell your doctor.
Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088