Actoplus Met contains a combination of metformin and pioglitazone, two oral diabetes medicines that help control blood sugar levels.

Actoplus Met is used together with diet and exercise to improve blood sugar control in adults with type 2 diabetes mellitus who do not use daily insulin injections.

Actoplus Met is not for treating type 1 diabetes.

You should not use Actoplus Met if you have severe heart failure, severe kidney disease, active bladder cancer, metabolic acidosis, or ketoacidosis (call your doctor for treatment).

Actoplus Met can cause or worsen congestive heart failure. Call your doctor at once if you have shortness of breath (even with mild exertion), swelling, or rapid weight gain.

If you need to have any type of x-ray or CT scan using a dye that is injected into your veins, you may need to temporarily stop taking Actoplus Met.

You may develop lactic acidosis, a dangerous build-up of lactic acid in your blood. Call your doctor or get emergency medical help if you have unusual muscle pain, trouble breathing, stomach pain, dizziness, feeling cold, or feeling very weak or tired.

Before taking this medicine

You should not use Actoplus Met if you are allergic to metformin or pioglitazone, or if you have:

• severe heart failure;

• severe kidney disease;

• active bladder cancer; or

• metabolic acidosis or ketoacidosis (call your doctor for treatment).

If you need to have surgery or any type of x-ray or CT scan using a dye that is injected into your veins, you may need to temporarily stop taking this medicine. Be sure your caregivers know ahead of time that you are using this medicine.

To make sure Actoplus Met is safe for you, tell your doctor if you have ever had:

• kidney problems;

• congestive heart failure or other heart problems;

• fluid retention;

• eye problems caused by diabetes;

• bladder cancer;

• a heart attack or stroke;

• liver disease; or

• if you are 80 years or older.

This medication may increase your risk of developing bladder cancer. Talk with your doctor about your specific risk.

You may develop lactic acidosis, a dangerous build-up of lactic acid in your blood. This may be more likely if you have other medical conditions, a severe infection, chronic alcoholism, or if you are 65 or older. Ask your doctor about your risk.

Actoplus Met may increase your risk of serious heart problems, but not treating your diabetes can also damage your heart and other organs. Talk to your doctor about the risks and benefits of this medicine.

Follow your doctor's instructions about using this medicine if you are pregnant or you become pregnant. Controlling diabetes is very important during pregnancy, and having high blood sugar may cause complications in both the mother and the baby.

Metformin may stimulate ovulation in a premenopausal woman and may increase the risk of unintended pregnancy. Talk to your doctor about your risk.

Women may be more likely to have a broken bone while using Actoplus Met. Talk with your doctor about ways to keep your bones healthy.

It may not be safe to breastfeed while using this medicine. Ask your doctor about any risk.

Actoplus Met is not approved for use by anyone younger than 18 years old.

Take Actoplus Met exactly as prescribed by your doctor. Follow all directions on your prescription label and read all medication guides or instruction sheets. Use the medicine exactly as directed.

Take Actoplus Met with meals. Take the extended-release tablet once daily with your evening meal.

Swallow the tablet whole and do not crush, chew, or break it.

You may have low blood sugar (hypoglycemia) and feel very hungry, dizzy, irritable, confused, anxious, or shaky. To quickly treat hypoglycemia, eat or drink a fast-acting source of sugar (fruit juice, hard candy, crackers, raisins, or non-diet soda).

Your doctor may prescribe a glucagon injection kit in case you have severe hypoglycemia. Be sure your family or close friends know how to give you this injection in an emergency.

Blood sugar levels can be affected by stress, illness, surgery, exercise, alcohol use, or skipping meals. Ask your doctor before changing your dose or medication schedule.

Actoplus Met is only part of a complete treatment program that may also include diet, exercise, weight control, blood sugar testing, and special medical care. Follow your doctor's instructions very closely.

If you take extra vitamin B12 while you are taking Actoplus Met, take only the amount of vitamin B12 that your doctor has prescribed.

Store at room temperature away from moisture, heat, and light. Keep the bottle tightly closed when not in use.

Usual Adult Dose of Actoplus Met for Diabetes Type 2:

Individualize dose based on safety, efficacy, and prior therapy
-All doses provided as pioglitazone/metformin

Immediate-release (IR):
Initial dose: 15 mg/500 mg IR orally twice a day or 15 mg/850 mg IR orally once a day
-For patients inadequately control on metformin monotherapy: May initiate with 15 mg/850 mg IR orally twice a day (depending on previous metformin dose)
-For patients with NYHA Class I or Class II CHF: Initial dose: 15 mg/500 mg IR or 15 mg/850 mg IR orally once a day
Maintenance dose: Gradually titrate dose based on safety and efficacy
Maximum dose: Pioglitazone 45 mg/Metformin 2550 mg per day

Extended-release (XR):
Initial dose: 15 mg/1000 mg XR or 30 mg/1000 mg XR orally once a day
-For patients inadequately control on pioglitazone or metformin monotherapy: 15 mg/1000 mg XR twice a day (depending on previous metformin dose) or 30 mg/1000 mg XR orally once a day
Maintenance dose: Gradually titrate dose based on safety and efficacy
Maximum dose: Pioglitazone 45 mg/Metformin 2000 mg per day

Comments:
-Initial doses for patients receiving combination therapy as separate tablets should be as close as possible to current regimen.
-Take with meals and gradually titrate metformin doses to reduce gastrointestinal side effects; metformin doses above 2000 mg may be better tolerated given 3 times a day.
-After initiation of therapy, and with each dose increase, carefully monitor for adverse reactions related to fluid retention.
-If hypoglycemia occurs with concomitant use of insulin or insulin secretagogue, the insulin or insulin secretagogue dose should be reduced.

Use: As an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus when treatment with both pioglitazone and metformin is appropriate.

You should not use Actoplus Met if you are allergic to metformin or pioglitazone, or if you have:

• severe heart failure;

• severe kidney disease;

• active bladder cancer; or

• metabolic acidosis or ketoacidosis (call your doctor for treatment).

If you need to have surgery or any type of x-ray or CT scan using a dye that is injected into your veins, you may need to temporarily stop taking this medicine. Be sure your caregivers know ahead of time that you are using this medicine.

To make sure Actoplus Met is safe for you, tell your doctor if you have ever had:

• kidney problems;

• congestive heart failure or other heart problems;

• fluid retention;

• eye problems caused by diabetes;

• bladder cancer;

• a heart attack or stroke;

• liver disease; or

• if you are 80 years or older.

This medication may increase your risk of developing bladder cancer. Talk with your doctor about your specific risk.

You may develop lactic acidosis, a dangerous build-up of lactic acid in your blood. This may be more likely if you have other medical conditions, a severe infection, chronic alcoholism, or if you are 65 or older. Ask your doctor about your risk.

Actoplus Met may increase your risk of serious heart problems, but not treating your diabetes can also damage your heart and other organs. Talk to your doctor about the risks and benefits of this medicine.

Follow your doctor's instructions about using this medicine if you are pregnant or you become pregnant. Controlling diabetes is very important during pregnancy, and having high blood sugar may cause complications in both the mother and the baby.

Metformin may stimulate ovulation in a premenopausal woman and may increase the risk of unintended pregnancy. Talk to your doctor about your risk.

Women may be more likely to have a broken bone while using Actoplus Met. Talk with your doctor about ways to keep your bones healthy.

It may not be safe to breastfeed while using this medicine. Ask your doctor about any risk.

Actoplus Met is not approved for use by anyone younger than 18 years old.

Take the medicine as soon as you can, but skip the missed dose if it is almost time for your next dose. Do not take two doses at one time.

Get your prescription refilled before you run out of medicine completely.

Seek emergency medical attention or call the Poison Help line at 1-800-222-1222. An overdose of metformin can cause lactic acidosis, which can be fatal.

Avoid drinking alcohol. It can lower your blood sugar and may increase your risk of lactic acidosis.

Get emergency medical help if you have signs of an allergic reaction to Actoplus Met: hives; difficult breathing; swelling of your face, lips, tongue, or throat.

Some people using Actoplus Met develop lactic acidosis, which can be fatal. Get emergency medical help if you have even mild symptoms such as:

• unusual muscle pain;

• feeling cold;

• trouble breathing;

• feeling dizzy, light-headed, tired, or very weak;

• stomach pain, vomiting; or

• slow or irregular heart rate.

Call your doctor at once if you have:

• pink or red urine, painful or difficult urination, new or worsening urge to urinate;

• changes in your vision;

• heart problems - swelling, rapid weight gain, feeling short of breath;

• liver problems - loss of appetite, nausea, vomiting, stomach pain, tiredness, dark urine, jaundice (yellowing of the skin or eyes); or

• low red blood cells (anemia) - pale skin, unusual tiredness, feeling light-headed or short of breath, cold hands and feet.

Common Actoplus Met side effects may include:

• headache;

• weight gain;

• diarrhea; or

• cold symptoms such as stuffy nose, sinus pain, sneezing, sore throat.

This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

Many drugs can interact with metformin and pioglitazone, making this medicine less effective or increasing your risk of lactic acidosis. This includes prescription and over-the-counter medicines, vitamins, and herbal products. Not all possible interactions are listed here. Tell your doctor about all your current medicines and any medicine you start or stop using.