Avandaryl: Uses, Side Effects and Dosage

ABOUT THIS MEDICATION

What the medication is used for:

AVANDARYL^® (ah-VAN-duh-ril) is a medicine used in addition to diet and exercise to lower blood sugar in patients with type 2 diabetes (non-insulin dependent) when all other diabetes medicines taken orally (by mouth) have not lowered blood sugar enough or are not appropriate.

Before starting AVANDARYL^®, your doctor will discuss the possible benefits and possible side effects of AVANDARYL^® to decide if AVANDARYL^® is right for you. Your doctor will ask you to read and sign a form indicating you understand the cardiovascular risks of AVANDARYL^®.

In order for AVANDARYL^® to be effective, you should continue to exercise and follow the diet recommended for your diabetes while taking AVANDARYL^®.

People who have diabetes have problems with insulin. Insulin is produced by an organ called the pancreas (PAN-kree-us). Inside the pancreas are special cells called beta-cells that actually make insulin. Insulin is a hormone (body’s own natural chemical) that allows the body's tissues to absorb glucose (known as "sugar") from the bloodstream to provide the body energy.

People with Type 2 diabetes do not make enough insulin, or the body tissues become less sensitive to insulin. When the tissues do not respond normally to insulin, it is as if they cannot “hear” the signals insulin sends out – this is called "insulin resistance."

With diabetes, sugar (glucose) builds up in the blood. This can lead to serious medical problems including kidney damage, heart disease, loss of limbs, and blindness. The main goal of treating diabetes is to lower your blood sugar to a normal level. Lowering and controlling blood sugar may help prevent or delay complications of diabetes such as heart disease, kidney disease or blindness.

What it does:

AVANDARYL^® combines two glucose-lowering medicines, rosiglitazone maleate (AVANDIA^®) and glimepiride (Amaryl^®), together in one tablet. These two medicines work together to help you achieve better blood sugar control. Rosiglitazone helps your body use its own insulin better by making the tissues more sensitive to insulin. The tissues are better able to "hear" the signals insulin sends out. That means the tissues will absorb sugar more easily. Glimepiride helps your body to release more of its own insulin. Together, these medicines keep the amount of sugar in your blood at a more normal level.

When it should not be used:

• If you have or have had heart problems or heart failure (the heart cannot pump enough blood to the body’s or other organs), talk to your doctor. AVANDARYL^® can cause your body to keep extra fluid (fluid retention), which can make some heart problems worse, lead to heart failure, swelling and weight gain.
• If you have Type 1 diabetes – this needs different treatment.
• If you are allergic to AVANDARYL^®, any of its components, or other sulfonylurea or sulfonamide drugs.
• If you have serious liver problems.
• If you have diabetic ketoacidosis (dangerously high levels of ketones, which signals the body doesn't have enough insulin).

• If you are pregnant or breastfeeding. Other medicines are used to control your diabetes while you are pregnant or breastfeeding.

What the medicinal ingredient is:

AVANDARYL^® tablets contain two active ingredients, rosiglitazone maleate (AVANDIA^®) and glimepiride (Amaryl^®), in one tablet.

What the nonmedicinal ingredients are:

lactose monohydrate, microcrystalline cellulose, sodium starch glycolate, hypromellose 2910, magnesium stearate, titanium dioxide, macrogol (polyethylene glycol), and one or more of the following: yellow, red, or black iron oxides

What dosage forms it comes in:

rosiglitazone maleate/glimepiride tablets

4mg/1mg, 4mg/2mg, 4mg/4mg

WARNINGS AND PRECAUTIONS

Serious Warnings and Precautions

• AVANDARYL^®, which contains rosiglitazone, may

  increase the risk of serious heart problems, including:

  • heart failure
  • angina (chest pain)
  • heart attack (myocardial infarction)
  • fluid retention (with or without rapid weight gain)

• AVANDARYL^® should not be used if you have or have

  had heart problems.

Before you use AVANDARYL^®, talk to your doctor about other options to treat your diabetes.

Before you use AVANDARYL^®, talk to your doctor or pharmacist about all your medical conditions, including if:

• you have experienced edema (swelling in the wrists,

  hands, feet or ankles).

• you have been diagnosed with angina (chest pain) or have

  had a heart attack.

• you have heart-related risks, including cigarette smoking,

  high blood pressure, high cholesterol, or a family history of heart attack.

• you have kidney problems.

• you are taking nitrate medicines (such as nitroglycerin or

  isosorbide dinitrate).

• you have a type of diabetic eye disease called macular

  edema (swelling in the back of the eye).

• you have liver problems.
• you are breastfeeding.
• you are pregnant or planning to become pregnant.

• you are not near menopause but not ovulating (e.g., you

  are a patient with polycystic ovary syndrome), AVANDARYL^® could make you ovulate again, which means you could get pregnant. Talk to your doctor about effective methods of birth control (e.g., hormonal contraceptive pills).

• you have a blood disease called G6PD-deficiency anemia.

AVANDARYL^® may cause low blood sugar (hypoglycemia). Make sure you know what to do if your blood sugar gets too low (ask your doctor, pharmacist or diabetes educator). Teach your friends, co-workers, or family members what they can do to help you if you have low blood sugar.

Broken bones, usually in the hand, upper arm or foot, have been seen in people taking rosiglitazone, one of the active ingredients of AVANDARYL^®. Talk to your doctor about the risk of fracture.

The safety and effectiveness of AVANDARYL^® have not been established in children under 18 years of age, therefore

AVANDARYL^® is not recommended for use in these patients.

AVANDARYL^® is not approved for use with insulin therapy, therefore AVANDARYL^® is not recommended for use with insulin.

AVANDARYL^® is not approved for use with metformin, therefore AVANDARYL^® is not recommended for use with metformin.

INTERACTIONS WITH THIS MEDICATION

AVANDARYL^® may affect how other medicines work, and some medicines may affect how AVANDARYL^® works. Drugs that may interact with the two active ingredients in AVANDARYL^® (rosiglitazone maleate and glimepiride) include acetylsalicylic acid (ASA), corticosteroids, diuretics (water pills), gemfibrozil (used to lower cholesterol and triglyceride levels in your blood), methotrexate (used to treat psoriasis and rheumatoid arthritis), non-steroidal anti-inflammatory drugs (NSAID), rifampin (used to treat tuberculosis), “sulfa drugs” (e.g. sulphonamides), warfarin, some antibiotics (e.g. clarithromycin, tetracycline) or beta-blockers (heart drug).

Tell your doctor and pharmacist about every medication you take. This means both prescription medications (the ones your doctor writes for you) and over-the-counter medications (the ones you buy in the drugstore, like cold or allergy medicines), or natural health products (herbal medicines).

PROPER USE OF THIS MEDICATION

Usual dose:

The usual starting dose of AVANDARYL^® may be 4 mg/1 mg, 4 mg/2 mg, or 4 mg/4 mg, depending on your previous treatment with rosiglitazone (AVANDIA^®) and/or glimepiride (AMARYL^®). Your doctor will decide on the dose of AVANDARYL^® that is suitable for you.

AVANDARYL^® should be taken by mouth once a day with a meal.

Your doctor may need to adjust your dose until your blood sugar is better controlled. AVANDARYL^® can begin to work 1 or 2 weeks after you start taking it. It may take 2-3 months to see the optimal effects.

Test your blood sugar regularly as your doctor tells you.

Remember: this medicine has been prescribed only for you. Do not give it to anybody else.

Take your AVANDARYL^® each day, as instructed by your doctor. AVANDARYL^® can help control your blood sugar levels only if you take it regularly.

Overdose:

Taking too much of any medicine can be dangerous.

Missed Dose:

Take the missed dose as soon as possible, unless it is almost time for your next dose. Do not take two doses at the same time.

Recommended clinical and laboratory tests while taking AVANDARYL^®:

Your doctor may do additional blood sugar tests to see how well AVANDARYL^® is working.

Your doctor may also recommend a blood test to monitor your liver before you start AVANDARYL^® and repeat the test periodically while you are on AVANDARYL^®.

Your doctor should check your eyes regularly. Rarely, some patients have experienced vision changes due to swelling in the back of the eye while taking AVANDARYL^®.

SIDE EFFECTS AND WHAT TO DO ABOUT THEM

Very common side effects (could affect more than one in 10 people):

• Edema (fluid retention or swelling) which could lead to or

  worsen heart failure. If you notice swelling in your extremities (arms and legs, hands and feet), an unusually rapid increase in weight, or if you experience unusual tiredness, trouble breathing or shortness of breath, call your doctor. These symptoms, although not specific, may signal heart problems or heart failure. Pay closer attention to these symptoms as fluid retention is common if you are using AVANDARYL^®.

Common side effects (could affect up to one in 10 people):

• Anemia (low red blood cell count) which may make you

  feel very weak or tired.

  • Chest pain (angina)
  • Heart failure or pulmonary edema (fluid accumulation in the lungs). Symptoms of heart failure include shortness of breath, getting tired easily after light physical activity such as walking, unusual tiredness, waking up short of breath at night, swollen ankles or feet, and an unusually rapid increase in weight. Symptoms of fluid in the lungs are breathlessness, which may be very severe and usually worsens on lying down. Stop taking AVANDARYL^® and call your doctor right away if you experience these symptoms.
  • Stomach (gastrointestinal) symptoms such as nausea.
  • Broken bones usually in the hand, upper arm or foot. Talk to your doctor about the risk of fracture.

  • A small increase in total cholesterol levels. Total

    cholesterol is made up of "good cholesterol" (HDLc) and "bad cholesterol" (LDLc) and it is the balance of these that is more important than the total level. AVANDARYL^®, does not affect the balance of good and bad cholesterol. If you have any concerns about your cholesterol levels, you should speak to your doctor.

  • Low blood sugar (hypoglycemia). Dizziness, lack of energy, drowsiness, headache, trembling, sweating. or hunger may mean that your blood sugar is too low. This can happen if you skip meals, drink alcohol, use another medicine that lowers blood sugar, exercise (particularly hard or long), or if you have certain medical problems. Call your doctor if you feel that your symptoms of low blood sugar are uncomfortable.
  • Increased weight. Tell your doctor if you gain a lot of weight in a short period of time.

Uncommon side effects (could affect up to one in 100 people):

• Mild allergic reactions may develop into more severe reactions with shortness of breath, chest tightness and in some cases low blood pressure which may present as lightheadedness. Therefore, if rash or hives, or any of the more serious symptoms occur, stop taking

  AVANDARYL^® and call your doctor right away.

• Constipation
• Increased hunger

Rare side effects (could affect up to one in 1,000 people):

• Liver problems. If you experience nausea, vomiting, stomach pain, lack of appetite, tiredness, dark urine, light-coloured bowel movements, or yellowing of the skin, stop taking AVANDARYL^® and call your doctor right away. Additionally, liver problems may result in the build-up of bile in the liver (cholestasis). Irritation or inflammation of the liver (hepatitis) may also occur and may lead to liver failure (failure of the liver to carry out its normal function).
• Blurred vision due to swelling (or fluid) in the back of the eye.

In case of drug overdose, contact a health care practitioner, hospital emergency department or regional Poison Control Centre immediately, even if there are no symptoms.

Very rare side effects (could affect up to one in 10,000 people):

• Allergic reactions, which may include hives or rash

  (which may be itchy), or more serious symptoms which may occur suddenly, such as swelling of the face, lips, mouth, tongue or throat (which may cause difficulty in swallowing or breathing). Stop taking AVANDARYL^® and contact your doctor or other healthcare professional immediately if any of these occur.

• Stomach or intestinal (gastrointestinal) symptoms such as nausea, vomiting, pressure or pain in the stomach (or upper abdomen) and diarrhea.
• Decreases in certain types of blood cells (white blood cells and platelets), which may increase your risk of infection or bleeding.
• Decrease in the amount of sodium (salt) in your blood, which may present as weakness, fatigue or confusion if mild and as seizures (convulsions) if severe. If you have these symptoms, stop taking AVANDARYL^® and call your doctor right away.
• Breakthrough bleeding (unexpected vaginal bleeding or spotting) while using oral contraceptives, or generally, if you experience any symptoms that persist or become troublesome, these should be discussed with your doctor.
• Skin reactions caused by sensitivity of the skin to light.

You may experience swelling of the parotid gland (salivary glands located over the jaw, in front of the ears).

This is not a complete list of side effects. If you experience any unexpected effects while taking AVANDARYL^®, contact your doctor or pharmacist.

HOW TO STORE IT

Store AVANDARYL^® at room temperature (15°C to 30°C), out of the reach of children.

REPORTING SUSPECTED SIDE EFFECTS

You can report any suspected adverse reactions associated with the use of health products to the Canada Vigilance Program by one of the following 3 ways:

• Report online at www.healthcanada.gc.ca/medeffect
• Call toll-free at 1-866-234-2345

• Complete a Canada Vigilance Reporting Form and:

  • Fax toll-free to 1-866-678-6789, or

  • Mail to: Canada Vigilance Program Health Canada

    Postal Locator 0701C

    Ottawa, ON K1A 0K9

Postage paid labels, Canada Vigilance Reporting Form and the adverse reaction reporting guidelines are available on the MedEffect™ Canada Web site at www.healthcanada.gc.ca/medeffect.

NOTE: Should you require information related to the management of side effects, contact your health professional. The Canada Vigilance Program does not provide medical advice.

MORE INFORMATION

This document plus the full product monograph, prepared for health professionals can be found at:

http://www.gsk.ca or by contacting the sponsor, GlaxoSmithKline Inc.,

7333 Mississauga Road

Mississauga, Ontario

Canada L5N 6L4

1-800-387-7374

Last revised: March 1, 2011

^© 2011 GlaxoSmithKline, All Rights Reserved

^®AVANDARYL is a registered trademark, used under license by GlaxoSmithKline Inc.

^®AVANDIA is a registered trademark, used under license by GlaxoSmithKline Inc.

Amaryl^® is a registered trademark of the group sanofi-aventis.