Avandaryl

AVANDARYL®
(ah-VAN-duh-ril)
(rosiglitazone maleate and glimepiride) Tablets

Read this Medication Guide carefully before you start taking AVANDARYL and each time you get a refill. There may be new information. This information does not take the place of talking with your doctor about your medical condition or your treatment. If you have any questions about AVANDARYL, ask your doctor or pharmacist.

What is the most important information I should know about AVANDARYL?

AVANDARYL may cause serious side effects, including:

New or worse heart failure

• The risk of heart failure may be higher in people who take AVANDARYL with insulin. Most people who take insulin should not also take AVANDARYL.
• Rosiglitazone, one of the two drugs that make up AVANDARYL, 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 AVANDARYL.
• If you have heart failure with symptoms (such as shortness of breath or swelling), even if these symptoms are not severe, AVANDARYL 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

AVANDARYL can have other serious side effects. Be sure to read the section “What are possible side effects of AVANDARYL?”

What is AVANDARYL?

AVANDARYL contains 2 prescription medicines to treat diabetes, rosiglitazone maleate (AVANDIA®) and glimepiride. AVANDARYL is used with diet and exercise to treat adults with type 2 (“adult-onset” or “non-insulin dependent”) diabetes mellitus (“high blood sugar”).

Glimepiride can help your body release more of its own insulin. Rosiglitazone can help your body respond better to the insulin made in your body and does not cause your body to make more insulin. These medicines can work together to help control your blood sugar.

AVANDARYL is not for people with type 1 diabetes mellitus or to treat a condition called diabetic ketoacidosis.

It is not known if AVANDARYL is safe and effective in children younger than 18 years old.

Who should not take AVANDARYL?

Many people with heart failure should not start taking AVANDARYL. See “What should I tell my doctor before taking AVANDARYL?”

Do not take AVANDARYL if you are allergic to rosiglitazone or glimepiride or any of the ingredients in AVANDARYL. See the end of this leaflet for a complete list of ingredients in AVANDARYL.

Symptoms of a severe allergic reaction with AVANDARYL may include:

• swelling of your face, lips, tongue, or throat
• problems with breathing or swallowing
• skin rash or itching
• raised red areas on your skin (hives)
• blisters on your skin or in your mouth, nose, or eyes
• peeling of your skin
• fainting or feeling dizzy
• very rapid heartbeat

What should I tell my doctor before taking AVANDARYL?

Before starting AVANDARYL, ask your doctor about what the choices are for diabetes medicines and what the expected benefits and possible risks are for you in particular.

Before taking AVANDARYL, tell your doctor about all of your medical conditions, including if you:

• have heart problems or heart failure.
• have type 1 (“juvenile”) diabetes or had diabetic ketoacidosis. These conditions should be treated with insulin and should not be treated with AVANDARYL.
• 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 AVANDARYL and during treatment as needed.
• had liver problems while taking REZULIN™ (troglitazone), another medicine for diabetes.
• have kidney problems. If people with kidney problems use AVANDARYL, they may need a lower dose of the medication.
• have glucose 6-phosphate dehydrogenase (G6PD) deficiency. This condition runs in families. People with G6PD deficiency who take glimepiride (one of the medicines in AVANDARYL) may develop hemolytic anemia (fast breakdown of red blood cells).
• are pregnant or plan to become pregnant. It is not known if AVANDARYL can harm your unborn baby. 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, AVANDARYL may increase your chances of becoming pregnant. Talk to your doctor about birth control choices while taking AVANDARYL. Tell your doctor right away if you become pregnant while taking AVANDARYL.
• are breastfeeding or planning to breastfeed. It is not known if AVANDARYL passes into breast milk. You and your doctor should decide if you will take AVANDARYL or breastfeed. You should not do both.

Tell your doctor about all of the medicines you take including prescription and non-prescription medicines, vitamins or herbal supplements. AVANDARYL and certain other medicines can affect each other and may lead to serious side effects including high or low blood sugar, or heart problems. 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.

Know the medicines you take. Keep a list of all your medicines and show it to your doctor and pharmacist before you start a new medicine. They will tell you if it is alright to take AVANDARYL with other medicines.

How should I take AVANDARYL?

• Take AVANDARYL exactly as prescribed. Your doctor may need to change your dose until your blood sugar is better controlled.
• Take AVANDARYL by mouth one time each day with your first main meal.
• It usually takes a few days for AVANDARYL to start lowering your blood sugar. It may take 2 to 3 months to see the full effect on your blood sugar level.
• AVANDARYL should be taken at least 4 hours before taking colesevelam (WELCHOL).
• If you miss a dose of AVANDARYL, 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.
• If you take too much AVANDARYL, call your doctor or poison control center right away.
• Test your blood sugar regularly as your doctor tells you.
• Your doctor should do blood tests to check your liver before you start AVANDARYL and during treatment as needed. Your doctor should also do regular blood sugar tests (for example, “A1c”) to monitor your response to AVANDARYL.
• Call your doctor if you get sick, get injured, get an infection, or have surgery. AVANDARYL may not control your blood sugar levels during these times. Your doctor may need to stop AVANDARYL for a short time and give you insulin to control your blood sugar level.
• Diet and exercise can help your body use its blood sugar better. It is important to stay on your recommended diet, lose extra weight, and get regular exercise while taking AVANDARYL.

What are possible side effects of AVANDARYL?

AVANDARYL may cause serious side effects, including:

• New or worse heart failure. See “What is the most important information I should know about AVANDARYL?”
• Heart attack. AVANDARYL may increase the risk of a heart attack. Talk to your doctor about what this means to you.

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.

• Swelling (edema). AVANDARYL can cause swelling due to fluid retention. See “What is the most important information I should know about AVANDARYL?”
• Low blood sugar (hypoglycemia). Lightheadedness, dizziness, shakiness, 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 low blood sugar levels are a problem for you.
• Weight gain. Rosiglitazone, one of the medicines in AVANDARYL, can cause weight gain that may be due to fluid retention or extra body fat. Weight gain can be a serious problem for people with certain conditions including heart problems. See “What is the most important information I should know about AVANDARYL?”
• Liver problems. It is important for your liver to be working normally when you take AVANDARYL. Your doctor should do blood tests to check your liver before you start taking AVANDARYL and during treatment as needed. 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). Tell your doctor right away if you have any changes in your vision. Your doctor should check your eyes regularly. Very rarely, some people have had vision changes due to swelling in the back of the eye while taking rosiglitazone, one of the medicines in AVANDARYL.
• Fractures (broken bones), usually in the hand, upper arm, or foot. Talk to your doctor for advice on how to keep your bones healthy.
• Low red blood cell count (anemia).
• Ovulation (release of egg from an ovary in women) leading to pregnancy. Ovulation may happen in premenopausal women who do not have regular monthly periods. This can increase the chance of pregnancy. See “What should I tell my doctor before taking AVANDARYL?”

The most common side effects with AVANDARYL include cold-like symptoms and headache.

Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

How should I store AVANDARYL?

• Store AVANDARYL at room temperature, 59°F to 86°F (15°C to 30°C). Keep AVANDARYL in the container it comes in. Keep the container closed tightly.
• Safely, throw away AVANDARYL that is out of date or no longer needed.

Keep AVANDARYL and all medicines out of the reach of children.

General information about AVANDARYL

Medicines are sometimes prescribed for purposes other than those listed in a Medication Guide. Do not use AVANDARYL for a condition for which it was not prescribed. Do not give AVANDARYL to other people, even if they have the same symptoms you have. It may harm them.

This Medication Guide summarizes important information about AVANDARYL. If you would like more information, talk with your doctor. You can ask your doctor or pharmacist for information about AVANDARYL that is written for healthcare professionals. You can also find out more about AVANDARYL by calling 1-888-825-5249.

What are the ingredients in AVANDARYL?

Active Ingredients: rosiglitazone maleate and glimepiride.

Inactive Ingredients: hypromellose 2910, lactose monohydrate, macrogol (polyethylene glycol), magnesium stearate, microcrystalline cellulose, sodium starch glycolate, titanium dioxide, triacetin, and 1 or more of the following: yellow, red, or black iron oxides.

Always check to make sure that the medicine you are taking is the correct one. AVANDARYL tablets are triangles with rounded corners and look like this:

4 mg/1 mg - yellow with “gsk” on one side and “4/1” on the other.

4 mg/2 mg - orange with “gsk” on one side and “4/2” on the other.

4 mg/4 mg - pink with “gsk” on one side and “4/4” on the other.

8 mg/2 mg - pale pink with “gsk” on one side and “8/2” on the other.

8 mg/4 mg - red with “gsk” on one side and “8/4” on the other.

This Medication Guide has been approved by the U.S. Food and Drug Administration.

Tell your doctor about all the medicines you take including prescription and non-prescription medicines, vitamins or herbal supplements. Avandaryl and certain other medicines can affect each other and may lead to serious side effects including high or low blood sugar, or heart problems. 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.

Know the medicines you take. Keep a list of all your medicines and show it to your doctor and pharmacist before you start a new medicine. They will tell you if it is alright to take Avandaryl with other medicines.

Before starting Avandaryl, ask your doctor about what the choices are for diabetes medicines and what the expected benefits and possible risks are for you in particular.

Before taking Avandaryl, tell your doctor about all your medical conditions, including if you:

• have heart problems or heart failure.
• have type 1 (“juvenile”) diabetes or had diabetic ketoacidosis. These conditions should be treated with insulin and should not be treated with Avandaryl.
• 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 Avandaryl and during treatment as needed.
• had liver problems while taking Rezulin (troglitazone), another medicine for diabetes.
• have kidney problems. If people with kidney problems use Avandaryl, they may need a lower dose of the medication.
• have glucose 6-phosphate dehydrogenase (G6PD) deficiency. This condition runs in families. People with G6PD deficiency who take glimepiride (one of the medicines in this combination product) may develop hemolytic anemia (fast breakdown of red blood cells).
• are pregnant or plan to become pregnant. Avandaryl should not be used during pregnancy. It is not known if Avandaryl can harm your unborn baby. 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, Avandaryl may increase your chances of becoming pregnant. Talk to your doctor about birth control choices while taking Avandaryl. Tell your doctor right away if you become pregnant while taking Avandaryl.
• are breastfeeding or planning to breastfeed. It is not known if Avandaryl passes into breast milk. You should not use Avandaryl while breast-feeding.

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

In the U.S.

• Avandaryl

Available Dosage Forms:

• Tablet

Therapeutic Class: Antidiabetic

Chemical Class: 2nd Generation Sulfonylurea

• Tell all of your health care providers that you take Avandaryl. This includes your doctors, nurses, pharmacists, and dentists.
• Do not drive if your blood sugar has been low. There is a greater chance of you having a crash.
• Be careful if you have G6PD deficiency. Anemia may happen.
• Check your blood sugar as you have been told by your doctor.
• Have blood work checked as you have been told by the doctor. Talk with the doctor.
• Have an eye exam as you have been told by your doctor.
• Talk with your doctor before you drink alcohol.
• Follow the diet and workout plan that your doctor told you about.
• If you also take colesevelam, take it at least 4 hours after you take this medicine.
• This medicine may raise the chance of death from heart disease. Talk with your doctor.
• It may be harder to control your blood sugar during times of stress like when you have a fever, an infection, an injury, or surgery. A change in level of physical activity or exercise and a change in diet may also affect your blood sugar. Talk with your doctor.
• This medicine may raise the chance of broken bones. The chance may be higher in women. Broken bones were seen after people took Avandaryl for 1 year. Most of the broken bones happened in the upper arm, hand, or foot. Talk with your doctor about how to keep your bones healthy or if you have any questions.
• If you are 65 or older, use this medicine with care. You could have more side effects.
• Do not give to a child. Talk with your doctor.
• There is a chance of pregnancy in women of childbearing age who have not been ovulating. If you want to avoid pregnancy, use birth control that you can trust while taking Avandaryl.
• Tell your doctor if you are pregnant or plan on getting pregnant. You will need to talk about the benefits and risks of using this medicine while you are pregnant.
• Tell your doctor if you are breast-feeding. You will need to talk about any risks to your baby.

• If your symptoms or health problems do not get better or if they become worse, call your doctor.
• Do not share your drugs with others and do not take anyone else's drugs.
• Keep a list of all your drugs (prescription, natural products, vitamins, OTC) with you. Give this list to your doctor.
• Talk with the doctor before starting any new drug, including prescription or OTC, natural products, or vitamins.
• This medicine comes with an extra patient fact sheet called a Medication Guide. Read it with care. Read it again each time this medicine is refilled. If you have any questions about Avandaryl (rosiglitazone and glimepiride), please talk with the doctor, pharmacist, or other health care provider.
• If you think there has been an overdose, call your poison control center or get medical care right away. Be ready to tell or show what was taken, how much, and when it happened.

This information should not be used to decide whether or not to take this medicine or any other medicine. Only the healthcare provider has the knowledge and training to decide which medicines are right for a specific patient. This information does not endorse any medicine as safe, effective, or approved for treating any patient or health condition. This is only a brief summary of general information about Avandaryl. It does NOT include all information about the possible uses, directions, warnings, precautions, interactions, adverse effects, or risks that may apply to this medicine. This information is not specific medical advice and does not replace information you receive from the healthcare provider. You must talk with the healthcare provider for complete information about the risks and benefits of using Avandaryl.

Review Date: October 4, 2017

Therapy with Avandaryl should be individualized for each patient. The risk-benefit of initiating monotherapy versus dual therapy with Avandaryl should be considered.

No studies have been performed specifically examining the safety and efficacy of Avandaryl in patients previously treated with other oral hypoglycemic agents and switched to Avandaryl. Any change in therapy of type 2 diabetes should be undertaken with care and appropriate monitoring as changes in glycemic control can occur. [See Indications and Usage (1).]

Starting Dose

The recommended starting dose is 4 mg/1 mg administered once daily with the first meal of the day. For adults already treated with a sulfonylurea or rosiglitazone, a starting dose of 4 mg/2 mg may be considered.

All patients should start the rosiglitazone component of Avandaryl at the lowest recommended dose. Further increases in the dose of rosiglitazone should be accompanied by careful monitoring for adverse events related to fluid retention [see Boxed Warning, Warnings and Precautions (5.1)].

When switching from combination therapy of rosiglitazone plus glimepiride as separate tablets, the usual starting dose of Avandaryl is the dose of rosiglitazone and glimepiride already being taken.

When colesevelam is coadministered with glimepiride, maximum plasma concentration and total exposure to glimepiride is reduced. Therefore, Avandaryl should be administered at least 4 hours prior to colesevelam.

Dose Titration

Dose increases should be individualized according to the glycemic response of the patient. Patients who may be more sensitive to glimepiride [see Warnings and Precautions (5.3)], including the elderly, debilitated, or malnourished, and those with renal, hepatic, or adrenal insufficiency, should be carefully titrated to avoid hypoglycemia. If hypoglycemia occurs during up-titration of the dose or while maintained on therapy, a dosage reduction of the glimepiride component of Avandaryl may be considered. Increases in the dose of rosiglitazone should be accompanied by careful monitoring for adverse events related to fluid retention [see Boxed Warning, Warnings and Precautions (5.1)].

To switch to Avandaryl for adults currently treated with rosiglitazone, dose titration of the glimepiride component of Avandaryl is recommended if patients are not adequately controlled after 1 to 2 weeks. The glimepiride component may be increased in no more than 2 mg increments. After an increase in the dosage of the glimepiride component, dose titration of Avandaryl is recommended if patients are not adequately controlled after 1 to 2 weeks.

To switch to Avandaryl for adults currently treated with sulfonylurea, it may take 2 weeks to see a reduction in blood glucose and 2 to 3 months to see the full effect of the rosiglitazone component. Therefore, dose titration of the rosiglitazone component of Avandaryl is recommended if patients are not adequately controlled after 8 to 12 weeks. Patients should be observed carefully (1 to 2 weeks) for hypoglycemia when being transferred from longer half-life sulfonylureas (e.g., chlorpropamide) to Avandaryl due to potential overlapping of drug effect. After an increase in the dosage of the rosiglitazone component, dose titration of Avandaryl is recommended if patients are not adequately controlled after 2 to 3 months.

Maximum Dose

The maximum recommended daily dose is 8 mg rosiglitazone and 4 mg glimepiride.

Specific Patient Populations

Elderly and Malnourished Patients and Those With Renal, Hepatic, or Adrenal Insufficiency: In elderly, debilitated, or malnourished patients, or in patients with renal, hepatic, or adrenal insufficiency, the starting dose, dose increments, and maintenance dosage of Avandaryl should be conservative to avoid hypoglycemic reactions. [See Warnings and Precautions (5.3), Clinical Pharmacology (12.3).]

Hepatic Impairment: Liver enzymes should be measured prior to initiating treatment with Avandaryl. Therapy with Avandaryl should not be initiated if the patient exhibits clinical evidence of active liver disease or increased serum transaminase levels (ALT >2.5X upper limit of normal at start of therapy). After initiation of Avandaryl, liver enzymes should be monitored periodically per the clinical judgment of the healthcare professional. [See Warnings and Precautions (5.6), Clinical Pharmacology (12.3).]

Pregnancy and Lactation: Avandaryl should not be used during pregnancy or in nursing mothers.

Pediatric Use: Safety and effectiveness of Avandaryl in pediatric patients have not been established. Avandaryl and its components, rosiglitazone and glimepiride, are not recommended for use in pediatric patients.

Drugs Metabolized by Cytochrome P450

Rosiglitazone: An inhibitor of CYP2C8 (e.g., gemfibrozil) may increase the AUC of rosiglitazone and an inducer of CYP2C8 (e.g., rifampin) may decrease the AUC of rosiglitazone. Therefore, if an inhibitor or an inducer of CYP2C8 is started or stopped during treatment with rosiglitazone, changes in diabetes treatment may be needed based upon clinical response. [See Clinical Pharmacology (12.4).]

A potential interaction between oral miconazole and oral hypoglycemic agents leading to severe hypoglycemia has been reported. Whether this interaction also occurs with the IV, topical, or vaginal preparations of miconazole is not known. Potential interactions of glimepiride with other drugs metabolized by cytochrome P450 2C9 also include phenytoin, diclofenac, ibuprofen, naproxen, and mefenamic acid. [See Clinical Pharmacology (12.4).]

Glimepiride: There may be an interaction between glimepiride and inhibitors (e.g., fluconazole) and inducers (e.g., rifampin) of CYP 2C9. Fluconazole may inhibit the metabolism of glimepiride, causing increased plasma concentrations of glimepiride which may lead to hypoglycemia. Rifampin may induce the metabolism of glimepiride, causing decreased plasma concentrations of glimepiride which may lead to worsening glycemic control.

Drugs Affecting Glucose Metabolism

A number of medications affect glucose metabolism and may require glimepiride dose adjustment and particularly close monitoring for hypoglycemia or worsening glycemic control.

The following are examples of medications that may increase the glucose-lowering effect of sulfonylureas including glimepiride, increasing the susceptibility to and/or intensity of hypoglycemia: oral anti-diabetic medications, pramlintide acetate, insulin, angiotensin converting enzyme (ACE) inhibitors, H2 receptor antagonists, fibrates, propoxyphene, pentoxifylline, somatostatin analogs, anabolic steroids and androgens, cyclophosphamide, phenyramidol, guanethidine, fluconazole, sulfinpyrazone, tetracyclines, clarithromycin, disopyramide, quinolones, and those drugs that are highly protein-bound, such as fluoxetine, nonsteroidal anti-inflammatory drugs, salicylates, sulfonamides, chloramphenicol, coumarins, probenecid, and monoamine oxidase inhibitors. When these medications are administered to a patient receiving Avandaryl, monitor the patient closely for hypoglycemia. When these medications are withdrawn from a patient receiving Avandaryl, monitor the patient closely for worsening glycemic control.

The following are examples of medications that may reduce the glucose-lowering effect of sulfonylureas including glimepiride, leading to worsening glycemic control: danazol, glucagon, somatropin, protease inhibitors, atypical antipsychotic medications (e.g., olanzapine and clozapine), barbiturates, diazoxide, laxatives, rifampin, thiazides and other diuretics, corticosteroids, phenothiazines, thyroid hormones, estrogens, oral contraceptives, phenytoin, nicotinic acid, sympathomimetics (e.g., epinephrine, albuterol, and terbutaline), and isoniazid. When these medications are administered to a patient receiving Avandaryl, monitor the patient closely for worsening glycemic control. When these medications are withdrawn from a patient receiving Avandaryl, monitor the patient closely for hypoglycemia.

Beta-blockers, clonidine, and reserpine may lead to either potentiation or weakening of glimepiride’s glucose-lowering effect.

Both acute and chronic alcohol intake may potentiate or weaken the glucose-lowering action of glimepiride in an unpredictable fashion.

The signs of hypoglycemia may be reduced or absent in patients taking sympatholytic drugs such as beta-blockers, clonidine, guanethidine, and reserpine.

Miconazole

A potential interaction between oral miconazole and sulfonylureas leading to severe hypoglycemia has been reported. Whether this interaction also occurs with other dosage forms of miconazole is not known.

Concomitant Administration of Colesevelam

Colesevelam can reduce the maximum plasma concentration and total exposure of glimepiride when the two are coadministered. However, absorption is not reduced when glimepiride is administered 4 hours prior to colesevelam. Therefore, Avandaryl should be administered at least 4 hours prior to colesevelam.

• Diabetes (Type 1 and Type 2)
• Oral Diabetes Prescription Medications

Usual Adult Dose of Avandaryl for Diabetes Type 2:

Individualize dose based on safety, efficacy, and prior therapy; asses the risk versus benefit of initiating with combination therapy versus monotherapy

Initial dose: rosiglitazone 4 mg/glimepiride 1 mg orally once a day
-Patients receiving a sulfonylurea or rosiglitazone: May consider a starting dose of rosiglitazone 4 mg/glimepiride 2 mg orally once a day
-Patients receiving rosiglitazone and glimepiride as individual components: Initial dose is the combination product containing the same dose of each component

Dose Titration: Individualize based on glycemic response and safety concerns for each component.
-Patients switching from rosiglitazone: Titrate glimepiride after 1 to 2 weeks in increments of no more than 2 mg; following increase, rosiglitazone may be titrated after 1 to 2 weeks
-Patients switching from sulfonylurea: Titrate rosiglitazone after 8 to 12 weeks; allow 2 to 3 months to see full effect of increase before further titration

Maximum dose: rosiglitazone 8 mg/glimepiride 4 mg

Comments: Take with first meal of the day.
-Monitor closely for fluid related adverse events, particularly with rosiglitazone initiation and titration.
-If hypoglycemia occurs, dose reduction of the glimepiride component may be necessary.

Use: To improve glycemic control in adult patients with type 2 diabetes mellitus as an adjunct to diet and exercise.

Seek emergency medical attention or call the Poison Help line at 1-800-222-1222. An Avandaryl overdose can cause life-threatening hypoglycemia.

Symptoms of severe hypoglycemia include extreme weakness, blurred vision, sweating, trouble speaking, tremors, stomach pain, confusion, and seizure (convulsions).

Applies to glimepiride / rosiglitazone: oral tablet

Along with its needed effects, glimepiride / rosiglitazone may cause some unwanted effects. Although not all of these side effects may occur, if they do occur they may need medical attention.

Check with your doctor immediately if any of the following side effects occur while taking glimepiride / rosiglitazone:

• Body aches or pain
• chills
• cough
• difficulty with breathing
• ear congestion
• fever
• headache
• injury
• loss of voice
• nasal congestion
• runny nose
• sneezing
• sore throat
• unusual tiredness or weakness

• Anxiety
• blurred vision
• chest pain or discomfort
• cold sweats
• coma
• confusion
• cool, pale skin
• decreased urine output
• depression
• dilated neck veins
• dizziness
• extreme fatigue
• fast heartbeat
• increased hunger
• irregular breathing
• irregular heartbeat
• nausea
• nightmares
• seizures
• shakiness
• slurred speech
• swelling of the face, fingers, feet, or lower legs
• tightness in the chest
• troubled breathing with exertion
• unusual bleeding or bruising
• weight gain

• Abdominal or stomach pain or tenderness
• agitation
• back, leg, or stomach pains
• bleeding gums
• bloody, black, or tarry stools
• blue lips and fingernails
• coughing that sometimes produces a pink frothy sputum
• dark urine
• decreased appetite
• difficult, fast, or noisy breathing
• fluid-filled skin blisters
• general body swelling
• hostility
• increased sweating
• increased thirst
• irritability
• itching or skin rash
• large, hive-like swelling on the face, eyelids, lips, tongue, throat, hands, legs, feet, or sex organs
• light-colored stools
• loss of appetite
• muscle pain or cramps
• muscle twitching
• nosebleeds
• pain or discomfort in the arms, jaw, back, or neck
• redness of the skin
• seizures
• sensitivity to the sun
• skin thinness
• sores, ulcers, or white spots on the lips or in the mouth
• stupor
• sweating
• swollen glands
• vomiting
• yellow eyes or skin

Some side effects of glimepiride / rosiglitazone may occur that usually do not need medical attention. These side effects may go away during treatment as your body adjusts to the medicine. Also, your health care professional may be able to tell you about ways to prevent or reduce some of these side effects. Check with your health care professional if any of the following side effects continue or are bothersome or if you have any questions about them:

• Lack or loss of strength

• Burning, stinging, itching, or redness of the skin not present before treatment

• Diarrhea