Rosiglitazone & Metformin

Metformin/rosiglitazone is a prescription medication used to treat type 2 diabetes in adults. It is a single tablet containing two different prescription medications, metformin and rosiglitazone. Metformin belongs to a group of drugs called biguanides, which cause the liver to make less glucose. Rosiglitazone belongs to a group of drugs called thiazolidinediones, which increase the body's sensitivity to insulin to help control blood glucose levels. 

Metformin/rosiglitazone is available in 4 tablet strengths. It is taken by mouth, with meals, as directed by your doctor.

Common side effects of metformin/rosiglitazone include diarrhea, nausea, upset stomach, cold-like symptoms. Do not drink alcohol while taking this medication.

Metformin/rosiglitazone is a prescription medication used to treat type 2 diabetes (non-insulin dependent diabetes). Metformin/rosiglitazone may be used alone or with other diabetes medicines.

This medication may be prescribed for other uses. Ask your doctor or pharmacist for more information.

Rosiglitazone & Metformin may be found in some form under the following brand names:

• Avandamet

Metformin/rosiglitazone may cause serious side effects. See "Drug Precautions". Some serious side effects include:

• new or worse heart failure
• heart attack
• swelling (edema)
• weight gain
• liver problems. Call your doctor right away if you have unexplained symptoms such as:
  • nausea or vomiting
  • stomach pain
  • unusual or unexplained tiredness
  • loss of appetite
  • dark urine
  • yellowing of your skin or the whites of your eyes.
• macular edema (a diabetic eye disease with swelling in the back of the eye)
• fractures (broken bones), usually in the hand, upper arm or foot
• low red blood cell count (anemia)
• low blood sugar(hypoglycemia)
• ovulation (release of egg from an ovary in a woman) leading to pregnancy

Common side effects of metformin/rosiglitazone include:

• diarrhea, nausea, and upset stomach
• cold-like symptoms
• headache
• joint aches
• dizziness

This is not a complete list of metformin/rosiglitazone side effects. Ask your doctor or pharmacist for more information.

Tell your doctor about all the medicines you take including prescription and non-prescription medicines, vitamins or herbal supplements. Especially tell your doctor if you take:

• insulin
• any medicines for high blood pressure, high cholesterol or heart failure, or for prevention of heart disease or stroke

This is not a complete list of metformin/rosiglitazone drug interactions. Ask your doctor or pharmacist for more information.

In 2010 the FDA severely restricted the use of metformin/rosiglitazone, due to the risk of "cardiovascular events" such as heart attacks and strokes. After thorough review and analysis of the research, the FDA announced, in 2013, that there is not an increased risk of cardiovascular events, compared to treatment with standard diabetes medications. Use of this medication is no longer restricted.

Metformin/rosiglitazone may cause serious side effects, including:

New or worse heart failure

• Rosiglitazone, one of the medicines in metformin/rosiglitazone, can cause your body to keep extra fluid (fluid retention), which leads to swelling (edema) and weight gain. Extra body fluid can make some heart problems worse or lead to heart failure. Heart failure means your heart does not pump blood well enough.
• If you have severe heart failure, you cannot start metformin/rosiglitazone.
• If you have heart failure with symptoms (such as shortness of breath or swelling), even if these symptoms are not severe, metformin/rosiglitazone may not be right for you.

Call your doctor right away if you have any of the following:

• swelling or fluid retention, especially in the ankles or legs
• shortness of breath or trouble breathing, especially when you lie down
• an unusually fast increase in weight
• unusual tiredness

Myocardial Infarction (“Heart Attack”)

Rosiglitazone, one of the medicines in metformin/rosiglitazone, may raise the risk of heart attack. The risk of having a heart attack may be higher in people who take metformin/rosiglitazone with insulin. Most people who take insulin should not also take metformin/rosiglitazone.

Symptoms of a heart attack can include the following:

• chest discomfort in the center of your chest that lasts for more than a few minutes, or that goes away or comes back
• chest discomfort that feels like uncomfortable pressure, squeezing, fullness or pain
• pain or discomfort in your arms, back, neck, jaw or stomach
• shortness of breath with or without chest discomfort
• breaking out in a cold sweat
• nausea or vomiting
• feeling lightheaded

Call your doctor or go to the nearest hospital emergency room right away if you think you are having a heart attack.

People with diabetes have a greater risk for heart problems. It is important to work with your doctor to manage other conditions, such as high blood pressure or high cholesterol.

Metformin, one of the medicines in metformin/rosiglitazone, can cause a rare but serious condition called lactic acidosis (a build-up of an acid in the blood) that can cause death. Lactic acidosis is a medical emergency and must be treated in the hospital.

Most people who have had lactic acidosis with metformin have other things that, combined with the metformin, led to the lactic acidosis. Tell your doctor if you have any of the following, because you have a higher chance for getting lactic acidosis with metformin/rosiglitazone if you:

• have kidney problems or your kidneys are affected by certain X-ray tests that use injectable dye. People with kidney problems should not take metformin/rosiglitazone.
• have liver problems
• drink alcohol very often, or drink a lot of alcohol in short-term "binge" drinking
• get dehydrated (lose a large amount of body fluids). This can happen if you are sick with a fever, vomiting or diarrhea. Dehydration can also happen when you sweat a lot with activity or exercise and do not drink enough fluids.
• have surgery
• have a heart attack, severe infection, or stroke
• are 80 years of age or older, and your kidneys are not working properly

The best way to keep from having a problem with lactic acidosis from metformin is to tell your doctor if you have any of the problems in the list above. Your doctor may decide to stop your metformin/rosiglitazone for a while if you have any of these things.

Lactic acidosis can be hard to diagnose early, because the early symptoms could seem like the symptoms of many other health problems besides lactic acidosis. You should call your doctor right away if you get the following symptoms, which could be signs of lactic acidosis:

• you feel very weak or tired
• you have unusual (not normal) muscle pain
• you have stomach pains
• you have trouble breathing
• you feel dizzy or lightheaded
• you have a slow or irregular heartbeat

Metformin/rosiglitazone can have other serious side effects. Be sure to read "Side Effects".

Do not take metformin/rosiglitazone if you:

• have kidney problems. Before you take metformin/rosiglitazone and while you take it, your doctor should test your blood to check for signs of kidney problems.
• have a condition known as metabolic acidosis, including diabetic ketoacidosis.
• are going to have an x-ray procedure with an injection of dyes (contrast agents) in your vein with a needle. Talk to your doctor about when to stop metformin/rosiglitazone and when to start it again.

Do not drink a lot of alcohol while taking metformin/rosiglitazone. This means you should not “binge drink”, and you should not drink a lot of alcohol on a regular basis. Drinking a lot of alcohol can increase the chance of getting lactic acidosis.

Follow dietary (food) recommendations made by your doctor and dietitian which should include a healthy diet. Skipping meals should be avoided as this can cause problems maintaining blood sugar control. There are no specific foods to avoid while using metformin/rosiglitazone.

Before receiving metformin/rosiglitazone, tell your doctor about all your medical conditions, including if you:

• have heart problems or heart failure
• have kidney problems
• have type 1 (“juvenile”) diabetes or had diabetic ketoacidosis. These conditions should be treated with insulin.
• are going to have dye injected into a vein for an X-ray, CAT scan, heart study, or other type of scanning
• drink a lot of alcohol (all the time or short binge drinking).
• develop a serious condition such as a heart attack, severe infection, or a stroke.
• are 80 years old or older. People who are over 80 years old should not take metformin/rosiglitazone unless their kidney function is checked and it is normal.
• have a type of diabetic eye disease called macular edema (swelling of the back of the eye).
• have liver problems. Your doctor should do blood tests to check your liver before you start taking metformin/rosiglitazone and during treatment as needed.
• had liver problems while taking Rezulin (troglitazone), another medicine for diabetes.

Tell your doctor if you are pregnant or breastfeeding.

Tell your doctor about all the medicines you take including prescription and non-prescription medicines, vitamins or herbal supplements. 

Tell your doctor if you are pregnant or plan to become pregnant.

The FDA categorizes medications based on safety for use during pregnancy. Five categories - A, B, C, D, and X, are used to classify the possible risks to an unborn baby when a medication is taken during pregnancy.

This medication falls into category C. No studies have been done in animals, and no well-controlled studies have been done in pregnant women. Metformin/rosiglitazone should be given to a pregnant woman only if clearly needed.

You and your doctor should talk about the best way to control your diabetes during pregnancy. If you are a premenopausal woman (before the “change of life”) who does not have regular monthly periods, metformin/rosiglitazone may increase your chances of becoming pregnant. Talk to your doctor about birth control choices while taking metformin/rosiglitazone. Tell your doctor right away if you become pregnant while taking metformin/rosiglitazone.

Tell your doctor if you are breastfeeding or planning to breastfeed. It is not known if metformin/rosiglitazone passes into breast milk. You should not use metformin/rosiglitazone while breastfeeding.

Metformin/rosiglitazone comes as a tablet to be taken by mouth with meals. This medicine should be taken at the same time(s) each day. If you miss a dose of metformin/rosiglitazone, take it as soon as you remember, unless it is time to take your next dose. Take your next dose at the usual time. Do not take double doses to make up for a missed dose.

• It can take 2 weeks for metformin/rosiglitazone to start lowering your blood sugar. It may take 2 to 3 months to see the full effect on your blood sugar level.
• Test your blood sugar regularly as your doctor tells you.

Take metformin/rosiglitazone exactly as prescribed. Follow the directions on your prescription label carefully. Your doctor will probably start you on a low dose and gradually increase your dose as necessary. Do not adjust your dose unless your doctor tells you to.

If you take too much this medication, call your healthcare provider or local Poison Control Center, or seek emergency medical attention right away.

• Store metformin/rosiglitazone at room temperature.
• Keep metformin/rosiglitazone in the container it comes in. Keep the container closed tightly.
• Safely, throw away metformin/rosiglitazone that is out of date or no longer needed.
• Keep metformin/rosiglitazone and all medicines out of the reach of children.

WARNINGS

Rosiglitazone maleate: CONGESTIVE HEART FAILURE

Thiazolidinediones, including rosiglitazone, cause or exacerbate congestive heart failure in some patients. After initiation of AVANDAMET®, and after dose increases, observe patients carefully for signs and symptoms of heart failure (including excessive, rapid weight gain, dyspnea, and/or edema). If these signs and symptoms develop, the heart failure should be managed according to current standards of care. Furthermore, discontinuation or dose reduction of AVANDAMET must be considered.

AVANDAMET is not recommended in patients with symptomatic heart failure. Initiation of AVANDAMET in patients with established NYHA Class III or IV heart failure is contraindicated.

Metformin hydrochloride: LACTIC ACIDOSIS

Lactic acidosis is a rare, but serious complication that can occur due to metformin accumulation. The risk increases with conditions such as sepsis, dehydration, excess alcohol intake, hepatic insufficiency, renal impairment, and acute congestive heart failure. 

Symptoms include malaise, myalgias, respiratory distress, increasing somnolence, and nonspecific abdominal distress. Laboratory abnormalities include low pH, increased anion gap and elevated blood lactate.

If acidosis is suspected, discontinue AVANDAMET and hospitalize the patient immediately.