ADULTS
Your doctor will start therapy at a low dose and increase it until your blood sugar levels are under control.
For patients not previously treated with diabetes medications
The recommended starting dose is 1.25 milligrams of glyburide with 250 milligrams of metformin once or twice daily with meals. The dosage can be increased every two weeks until blood sugar levels are controlled. The maximum recommended daily dosage of Glucovance for previously untreated patients is 10 milligrams of glyburide with 2,000 milligrams of metformin.
For patients previously treated with glyburide (or a similar drug) or metformin:
The recommended starting dose of Glucovance is either 2.5 or 5 milligrams of glyburide with 500 milligrams of metformin twice daily with meals. The maximum recommended daily dosage of Glucovance for previously treated patients is 20 milligrams of glyburide with 2,000 milligrams of metformin.
CHILDREN
Glucovance is not for use in children.
OLDER ADULTS
Since kidney function declines with age, it should be closely monitored in people taking Glucovance after age 65. Older patients are usually not prescribed the maximum recommended dose of Glucovance.
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Sunday, August 31, 2008
Glucovance Drug Interactions Explained
Beta Blockers
Taking Glucovance with beta blockers can increase your risk of low blood sugar (hypoglycemia). If you are taking Glucovance along with a beta blocker, you may need to be monitored more closely, and your healthcare provider may need to adjust your Glucovance dose -- especially when you are starting or stopping a beta blocker.
Calcium Channel Blockers
Taking Glucovance with calcium channel blockers can make Glucovance less effective, increasing your chance of high blood sugar (hyperglycemia). If you are taking these medicines together, you may need to be monitored more closely, and your healthcare provider may need to adjust your Glucovance dose -- especially when you are starting or stopping a calcium channel blocker.
Certain Decongestants
Taking Glucovance with certain decongestants can make Glucovance less effective, increasing your chance of high blood sugar (hyperglycemia). Decongestants are in many cough and cold products, so be sure to talk with your healthcare provider before taking any of these products.
Cimetidine (Tagamet)
Taking Glucovance with cimetidine can increase the level of Glucovance in your blood, increasing your risk of side effects. Your healthcare provider may need to adjust your dose of these medications or may suggest an alternative to cimetidine.
Corticosteroids
Taking Glucovance with corticosteroids can make Glucovance less effective, increasing your chance of high blood sugar (hyperglycemia). If you are taking these drugs together, you may need to be monitored more closely, and your healthcare provider may need to adjust your Glucovance dose -- especially when you are starting or stopping a corticosteroid.
Taking Glucovance with beta blockers can increase your risk of low blood sugar (hypoglycemia). If you are taking Glucovance along with a beta blocker, you may need to be monitored more closely, and your healthcare provider may need to adjust your Glucovance dose -- especially when you are starting or stopping a beta blocker.
Calcium Channel Blockers
Taking Glucovance with calcium channel blockers can make Glucovance less effective, increasing your chance of high blood sugar (hyperglycemia). If you are taking these medicines together, you may need to be monitored more closely, and your healthcare provider may need to adjust your Glucovance dose -- especially when you are starting or stopping a calcium channel blocker.
Certain Decongestants
Taking Glucovance with certain decongestants can make Glucovance less effective, increasing your chance of high blood sugar (hyperglycemia). Decongestants are in many cough and cold products, so be sure to talk with your healthcare provider before taking any of these products.
Cimetidine (Tagamet)
Taking Glucovance with cimetidine can increase the level of Glucovance in your blood, increasing your risk of side effects. Your healthcare provider may need to adjust your dose of these medications or may suggest an alternative to cimetidine.
Corticosteroids
Taking Glucovance with corticosteroids can make Glucovance less effective, increasing your chance of high blood sugar (hyperglycemia). If you are taking these drugs together, you may need to be monitored more closely, and your healthcare provider may need to adjust your Glucovance dose -- especially when you are starting or stopping a corticosteroid.
Symptoms of a Glucovance Overdose
The effects of a Glucovance overdose may include:
* Low blood sugar (hypoglycemia)
* Lactic acidosis, due to the metformin component of Glucovance (see Metformin and Lactic Acidosis).
Possible symptoms of low blood sugar include:
* Sweating
* Shakiness
* Extreme hunger
* Dizziness
* Cold sweats
* Blurry vision.
More severe low blood sugar symptoms include:
* Changes in behavior, such as irritability
* Loss of coordination
* Difficulty speaking
* Confusion
* Seizures
* Loss of consciousness
* Coma
* Loss of life.
Lactic acidosis symptoms include:
* Feeling tired or weak
* Muscle pain
* Trouble breathing
* Abdominal pain (or stomach pain)
* Feeling cold
* Dizziness or lightheadedness
* A slow or irregular heartbeat
* Loss of life.
* Low blood sugar (hypoglycemia)
* Lactic acidosis, due to the metformin component of Glucovance (see Metformin and Lactic Acidosis).
Possible symptoms of low blood sugar include:
* Sweating
* Shakiness
* Extreme hunger
* Dizziness
* Cold sweats
* Blurry vision.
More severe low blood sugar symptoms include:
* Changes in behavior, such as irritability
* Loss of coordination
* Difficulty speaking
* Confusion
* Seizures
* Loss of consciousness
* Coma
* Loss of life.
Lactic acidosis symptoms include:
* Feeling tired or weak
* Muscle pain
* Trouble breathing
* Abdominal pain (or stomach pain)
* Feeling cold
* Dizziness or lightheadedness
* A slow or irregular heartbeat
* Loss of life.
On-line Medication Resources
* Drugs.com is a new Internet drug information resource. You have to register, but it's free. Drugs.com gets its main database and Care Guide information from Micromedex, a part of the global Thomson Health Care Information group. The Drug Interactions information comes from Multum Information Services, a company that specializes in solutions to the growing problem of adverse drug events. A pharmacist at Drugs.com tells me that the site contains about 24,000 drug names. It unfortunately has an interface that makes entering more than a few items tedious. The URL is
http://www.drugs.com/
* Drugstore.com has an excellent and easy-to-use drug interaction tool, albeit one that is hard to find. The URL is Drug Interactions
* The Express Scripts “Check Interactions” site is http://www.drugdigest.org/DD/Interaction/ChooseDrugs/1,4109,,00.html.
* Another drug interaction site is Discovery Health’s “Drug Interaction Checker.” The URL of this tool is http://health.discovery.com/encyclopedias/checker/checker.jsp.
* The Diabetes Monitor: Medications has many links to Web sites about diabetes medications. The URL is
http://www.diabetesmonitor.com/other-05.htm
* RxList - The Internet Drug Index is a free, searchable database of more than 4,500 prescription and over-the-counter medications. The search engine uses fuzzy logic, so you can often find a drug even when you misspell its name. The URL is
http://www.rxlist.com/
* Healthtouch® Drug Information enables you to find information about more than 10,000 prescription and over-the-counter medications. You can enter either the generic or brand name of the drug, but you have to spell it correctly. While it includes more drugs than RxList, the information it provides is less detailed. The URL is
http://www.healthtouch.com/level1/p_dri.htm
* Johns Hopkins IntelliHealth lets you search its U. S. Pharmacopeia database for drug information. The URL is
http://www.intelihealth.com/email/drugs
http://www.drugs.com/
* Drugstore.com has an excellent and easy-to-use drug interaction tool, albeit one that is hard to find. The URL is Drug Interactions
* The Express Scripts “Check Interactions” site is http://www.drugdigest.org/DD/Interaction/ChooseDrugs/1,4109,,00.html.
* Another drug interaction site is Discovery Health’s “Drug Interaction Checker.” The URL of this tool is http://health.discovery.com/encyclopedias/checker/checker.jsp.
* The Diabetes Monitor: Medications has many links to Web sites about diabetes medications. The URL is
http://www.diabetesmonitor.com/other-05.htm
* RxList - The Internet Drug Index is a free, searchable database of more than 4,500 prescription and over-the-counter medications. The search engine uses fuzzy logic, so you can often find a drug even when you misspell its name. The URL is
http://www.rxlist.com/
* Healthtouch® Drug Information enables you to find information about more than 10,000 prescription and over-the-counter medications. You can enter either the generic or brand name of the drug, but you have to spell it correctly. While it includes more drugs than RxList, the information it provides is less detailed. The URL is
http://www.healthtouch.com/level1/p_dri.htm
* Johns Hopkins IntelliHealth lets you search its U. S. Pharmacopeia database for drug information. The URL is
http://www.intelihealth.com/email/drugs
Possible food and drug interactions
If Glucovance is taken with certain other drugs, the effects of either drug could be increased, decreased, or altered. It is especially important to check with your doctor before combining Glucovance with the following:
Airway-opening drugs such as Proventil and Ventolin
Beta-blockers (heart and blood-pressure drugs such as Inderal and Tenormin)
Birth control pills
Calcium channel blockers (heart medications) such as Calan, Isoptin, and Procardia
Chloramphenicol (Chloromycetin)
Ciprofloxacin (Cipro)
Estrogens such as Premarin
HydroDiuril, Lasix, and other diuretics
Isoniazid (Rifamate)
Major tranquilizers such as Compazine, Stelazine, and Thorazine
MAO inhibitors such as the antidepressants Nardil and Parnate
Nonsteroidal anti-inflammatory drugs such as Advil, Motrin, Naprosyn, and Voltaren
Niacin (Niacor, Niaspan)
Phenytoin (Dilantin)
Probenecid
Steroids such as prednisone (Deltasone)
Sulfa drugs such as Bactrim
Thyroid medications such as Synthroid
Warfarin (Coumadin)
Airway-opening drugs such as Proventil and Ventolin
Beta-blockers (heart and blood-pressure drugs such as Inderal and Tenormin)
Birth control pills
Calcium channel blockers (heart medications) such as Calan, Isoptin, and Procardia
Chloramphenicol (Chloromycetin)
Ciprofloxacin (Cipro)
Estrogens such as Premarin
HydroDiuril, Lasix, and other diuretics
Isoniazid (Rifamate)
Major tranquilizers such as Compazine, Stelazine, and Thorazine
MAO inhibitors such as the antidepressants Nardil and Parnate
Nonsteroidal anti-inflammatory drugs such as Advil, Motrin, Naprosyn, and Voltaren
Niacin (Niacor, Niaspan)
Phenytoin (Dilantin)
Probenecid
Steroids such as prednisone (Deltasone)
Sulfa drugs such as Bactrim
Thyroid medications such as Synthroid
Warfarin (Coumadin)
Special warnings
About Glucovance
Avoid excessive alcohol intake while taking Glucovance. Heavy drinking increases the danger of lactic acidosis and can also trigger an attack of low blood sugar (hypoglycemia).
Missed meals, malnutrition, general debility, liver or kidney problems, other medications, and over-exertion also increase the risk of hypoglycemia. Symptoms of a mild case include cold sweats, dizziness, shakiness, and hunger. Severe hypoglycemia can lead to seizures and coma. If you notice any of the warning signs, check with your doctor immediately.
Lactic acidosis also becomes more likely when you become dehydrated. If you experience severe vomiting, diarrhea, fever, or if your fluid intake is significantly reduced, tell your doctor.
Taking Glucovance with certain diabetes drugs, such as Avandia, can increase the risk of hypoglycemia, weight gain, and liver problems. Your doctor will periodically test your liver function to guard against any problems.
Glucovance occasionally causes a mild deficiency of vitamin B12. Your doctor will check annually and may prescribe a supplement if necessary.
Some experts suspect that the glyburide component of Glucovance may lead to more heart problems than treatment with diet alone. In a long-term trial of a similar drug, researchers noted an increase in heart-related deaths (though the overall mortality rate remained unchanged). If you have a heart condition, you may want to discuss this potential risk with your doctor.
Avoid excessive alcohol intake while taking Glucovance. Heavy drinking increases the danger of lactic acidosis and can also trigger an attack of low blood sugar (hypoglycemia).
Missed meals, malnutrition, general debility, liver or kidney problems, other medications, and over-exertion also increase the risk of hypoglycemia. Symptoms of a mild case include cold sweats, dizziness, shakiness, and hunger. Severe hypoglycemia can lead to seizures and coma. If you notice any of the warning signs, check with your doctor immediately.
Lactic acidosis also becomes more likely when you become dehydrated. If you experience severe vomiting, diarrhea, fever, or if your fluid intake is significantly reduced, tell your doctor.
Taking Glucovance with certain diabetes drugs, such as Avandia, can increase the risk of hypoglycemia, weight gain, and liver problems. Your doctor will periodically test your liver function to guard against any problems.
Glucovance occasionally causes a mild deficiency of vitamin B12. Your doctor will check annually and may prescribe a supplement if necessary.
Some experts suspect that the glyburide component of Glucovance may lead to more heart problems than treatment with diet alone. In a long-term trial of a similar drug, researchers noted an increase in heart-related deaths (though the overall mortality rate remained unchanged). If you have a heart condition, you may want to discuss this potential risk with your doctor.
Saturday, August 23, 2008
Note It
Every effort has been made to ensure that the information provided by Cerner Multum, Inc. ('Multum') is accurate, up-to-date, and complete, but no guarantee is made to that effect. Drug information contained herein may be time sensitive. Multum information has been compiled for use by healthcare practitioners and consumers in the United States and therefore Multum does not warrant that uses outside of the United States are appropriate, unless specifically indicated otherwise. Multum's drug information does not endorse drugs, diagnose patients or recommend therapy. Multum's drug information is an informational resource designed to assist licensed healthcare practitioners in caring for their patients and/or to serve consumers viewing this service as a supplement to, and not a substitute for, the expertise, skill, knowledge and judgment of healthcare practitioners. The absence of a warning for a given drug or drug combination in no way should be construed to indicate that the drug or drug combination is safe, effective or appropriate for any given patient. Multum does not assume any responsibility for any aspect of healthcare administered with the aid of information Multum provides. The information contained herein is not intended to cover all possible uses, directions, precautions, warnings, drug interactions, allergic reactions, or adverse effects. If you have questions about the drugs you are taking, check with your doctor, nurse or pharmacist.
Medication Look Like
Glyburide and metformin is available with a prescription under the brand name Glucovance. Other brand or generic formulations may also be available. Ask your pharmacist any questions you have about this medication, especially if it is new to you.
* Glucovance 1.25 mg glyburide/250 mg metformin--pale yellow, capsule-shaped, film-coated tablets
* Glucovance 2.5 mg glyburide/500 mg metformin--pale orange, capsule-shaped, film-coated tablets
* Glucovance 5 mg glyburide/500mg metformin-- yellow, capsule-shaped, film-coated tablets
* Glucovance 1.25 mg glyburide/250 mg metformin--pale yellow, capsule-shaped, film-coated tablets
* Glucovance 2.5 mg glyburide/500 mg metformin--pale orange, capsule-shaped, film-coated tablets
* Glucovance 5 mg glyburide/500mg metformin-- yellow, capsule-shaped, film-coated tablets
Thursday, August 21, 2008
Sulfonylureas for type 2 diabetes
Examples
Generic Name Brand Name
glimepiride Amaryl
glipizide Glucotrol
glipizide and metformin Metaglip
glyburide DiaBeta, Glynase, Micronase
glyburide and metformin hydrochloride Glucovance
Most sulfonylurea medications for type 2 diabetes can be taken once a day. Some need to be taken twice a day.
These medications work for a long time and can cause low blood sugar. It is very important not to skip or delay meals when taking these medications.
Glucovance is a combination medication that contains glyburide and metformin hydrochloride, a biguanide.
Metaglip is a combination medication that contains glipizide and metformin.
How It Works
Sulfonylurea medications:
* Increase the amount of insulin produced by the pancreas. This is the primary action of these medications.
Because Glucovance and Metaglip are combination medications that contain metformin, they decrease the amount of sugar your liver makes and may increase your body's ability to respond to insulin.
Why It Is Used
Sulfonylurea medications are prescribed when changes in diet, weight loss, and exercise do not keep the blood sugar level within a safe range. When taking one of these medications, it is still important to eat a balanced diet, exercise, and lose weight if needed.
These medications can help control blood sugar levels in children and young adults who have type 2 diabetes and are overweight.
Sulfonylurea medications are not safe if you:
* Are pregnant or trying to become pregnant. They may harm the fetus.
* Have liver or kidney problems. Sulfonylurea medications are broken down by the liver and pass out of the body through urine produced in the kidneys.
Tell your doctor if you have had a serious allergic reaction to a sulfa antibiotic, such as Bactrim or Septra. You may not be able to use a sulfonylurea.
How Well It Works
Sulfonylurea medications work rapidly to control elevated blood sugar levels; they often are the first medication selected to treat people newly diagnosed with type 2 diabetes. Metformin is preferred for initial treatment because it doesn't cause low blood sugar or weight gain. The great majority of people have better control of their blood sugar by using a sulfonylurea medication along with diet and exercise than by using diet and exercise alone.
However, the medication may become less effective after several years of use. Some people who no longer respond to one sulfonylurea may respond to a different one.
Results of the United Kingdom Prospective Diabetes Study (UKPDS) showed that sulfonylurea medications:
* Were as effective as metformin and insulin in reducing blood sugar levels of people with type 2 diabetes.1
* Decreased the risk for complications of the eyes (retinopathy), kidneys (nephropathy), and nerves (neuropathy).2
Sulfonylurea medications do not decrease fat (triglycerides) in the blood as does metformin.
Side Effects
Side effects are uncommon when sulfonylureas are taken as prescribed. Low blood sugar is the most common side effect. The risk of very low blood sugar is greater with medications that work longer in the body.
Drinking alcohol increases the risk of a low blood sugar level if you take a sulfonylurea medication. If you drink alcohol, limit yourself to only 1 to 2 drinks per day and eat something before you drink alcohol.
Sulfonylurea medications can cause weight gain. They also tend to keep insulin levels in the body high for long periods of time. Over time, high levels of insulin (hyperinsulinemia) may increase your chances of getting heart disease.
Blood levels of vitamin B12 can decrease in some people who take metformin.
See Drug Reference for a full list of side effects. (Drug Reference is not available in all systems.)
What To Think About
Sulfonylurea medications are an effective treatment for many people with type 2 diabetes. If one of these medications keeps your blood sugar within a safe range, your risks of long-term complications of diabetes can be reduced. Other important factors that contribute to complications include high blood pressure, being overweight, high cholesterol levels, and smoking.
Few studies have been done on the use of oral medications for type 2 diabetes in children, and they have not been approved by the U.S. Food and Drug Administration (FDA) for use in children. But because these oral medications are safe for adults, most health professionals use them to treat children with type 2 diabetes.
Generic Name Brand Name
glimepiride Amaryl
glipizide Glucotrol
glipizide and metformin Metaglip
glyburide DiaBeta, Glynase, Micronase
glyburide and metformin hydrochloride Glucovance
Most sulfonylurea medications for type 2 diabetes can be taken once a day. Some need to be taken twice a day.
These medications work for a long time and can cause low blood sugar. It is very important not to skip or delay meals when taking these medications.
Glucovance is a combination medication that contains glyburide and metformin hydrochloride, a biguanide.
Metaglip is a combination medication that contains glipizide and metformin.
How It Works
Sulfonylurea medications:
* Increase the amount of insulin produced by the pancreas. This is the primary action of these medications.
Because Glucovance and Metaglip are combination medications that contain metformin, they decrease the amount of sugar your liver makes and may increase your body's ability to respond to insulin.
Why It Is Used
Sulfonylurea medications are prescribed when changes in diet, weight loss, and exercise do not keep the blood sugar level within a safe range. When taking one of these medications, it is still important to eat a balanced diet, exercise, and lose weight if needed.
These medications can help control blood sugar levels in children and young adults who have type 2 diabetes and are overweight.
Sulfonylurea medications are not safe if you:
* Are pregnant or trying to become pregnant. They may harm the fetus.
* Have liver or kidney problems. Sulfonylurea medications are broken down by the liver and pass out of the body through urine produced in the kidneys.
Tell your doctor if you have had a serious allergic reaction to a sulfa antibiotic, such as Bactrim or Septra. You may not be able to use a sulfonylurea.
How Well It Works
Sulfonylurea medications work rapidly to control elevated blood sugar levels; they often are the first medication selected to treat people newly diagnosed with type 2 diabetes. Metformin is preferred for initial treatment because it doesn't cause low blood sugar or weight gain. The great majority of people have better control of their blood sugar by using a sulfonylurea medication along with diet and exercise than by using diet and exercise alone.
However, the medication may become less effective after several years of use. Some people who no longer respond to one sulfonylurea may respond to a different one.
Results of the United Kingdom Prospective Diabetes Study (UKPDS) showed that sulfonylurea medications:
* Were as effective as metformin and insulin in reducing blood sugar levels of people with type 2 diabetes.1
* Decreased the risk for complications of the eyes (retinopathy), kidneys (nephropathy), and nerves (neuropathy).2
Sulfonylurea medications do not decrease fat (triglycerides) in the blood as does metformin.
Side Effects
Side effects are uncommon when sulfonylureas are taken as prescribed. Low blood sugar is the most common side effect. The risk of very low blood sugar is greater with medications that work longer in the body.
Drinking alcohol increases the risk of a low blood sugar level if you take a sulfonylurea medication. If you drink alcohol, limit yourself to only 1 to 2 drinks per day and eat something before you drink alcohol.
Sulfonylurea medications can cause weight gain. They also tend to keep insulin levels in the body high for long periods of time. Over time, high levels of insulin (hyperinsulinemia) may increase your chances of getting heart disease.
Blood levels of vitamin B12 can decrease in some people who take metformin.
See Drug Reference for a full list of side effects. (Drug Reference is not available in all systems.)
What To Think About
Sulfonylurea medications are an effective treatment for many people with type 2 diabetes. If one of these medications keeps your blood sugar within a safe range, your risks of long-term complications of diabetes can be reduced. Other important factors that contribute to complications include high blood pressure, being overweight, high cholesterol levels, and smoking.
Few studies have been done on the use of oral medications for type 2 diabetes in children, and they have not been approved by the U.S. Food and Drug Administration (FDA) for use in children. But because these oral medications are safe for adults, most health professionals use them to treat children with type 2 diabetes.
Dosage
Adults: Oral:
Initial therapy (no prior treatment with sulfonylurea or metformin): 1.25 mg/250 mg once daily with a meal; patients with Hb A1c >9% or fasting plasma glucose (FPG) >200 mg/dL may start with 1.25 mg/250 mg twice daily
Dosage may be increased in increments of 1.25 mg/250 mg, at intervals of not less than 2 weeks; maximum daily dose: 10 mg/2000 mg (limited experience with higher doses)
Previously treated with a sulfonylurea or metformin alone: Initial: 2.5 mg/500 mg or 5 mg/500 mg twice daily; increase in increments no greater than 5 mg/500 mg; maximum daily dose: 20 mg/2000 mg
When switching patients previously on a sulfonylurea and metformin together, do not exceed the daily dose of glyburide (or glyburide equivalent) or metformin.
Note: May combine with a thiazolidinedione in patients with an inadequate response to glyburide/metformin therapy (risk of hypoglycemia may be increased).
Elderly: Oral: Conservative doses are recommended in the elderly due to potentially decreased renal function; do not titrate to maximum dose; should not be used in patients 80 years of age unless renal function is verified as normal
Dosage adjustment in renal impairment: Risk of lactic acidosis increases with degree of renal impairment; contraindicated in renal disease or renal dysfunction (see Contraindications)
Dosage adjustment in hepatic impairment: Use conservative initial and maintenance doses and avoid use in severe hepatic disease
Note: Dose must be individualized. Dosages expressed as glyburide/metformin components.
Initial therapy (no prior treatment with sulfonylurea or metformin): 1.25 mg/250 mg once daily with a meal; patients with Hb A1c >9% or fasting plasma glucose (FPG) >200 mg/dL may start with 1.25 mg/250 mg twice daily
Dosage may be increased in increments of 1.25 mg/250 mg, at intervals of not less than 2 weeks; maximum daily dose: 10 mg/2000 mg (limited experience with higher doses)
Previously treated with a sulfonylurea or metformin alone: Initial: 2.5 mg/500 mg or 5 mg/500 mg twice daily; increase in increments no greater than 5 mg/500 mg; maximum daily dose: 20 mg/2000 mg
When switching patients previously on a sulfonylurea and metformin together, do not exceed the daily dose of glyburide (or glyburide equivalent) or metformin.
Note: May combine with a thiazolidinedione in patients with an inadequate response to glyburide/metformin therapy (risk of hypoglycemia may be increased).
Elderly: Oral: Conservative doses are recommended in the elderly due to potentially decreased renal function; do not titrate to maximum dose; should not be used in patients 80 years of age unless renal function is verified as normal
Dosage adjustment in renal impairment: Risk of lactic acidosis increases with degree of renal impairment; contraindicated in renal disease or renal dysfunction (see Contraindications)
Dosage adjustment in hepatic impairment: Use conservative initial and maintenance doses and avoid use in severe hepatic disease
Note: Dose must be individualized. Dosages expressed as glyburide/metformin components.
Dietary Considerations
May cause GI upset; take with food to decrease GI upset. Dietary modification based on ADA recommendations is a part of therapy. Decreases blood glucose concentration. Hypoglycemia may occur. Must be able to recognize symptoms of hypoglycemia (palpitations, sweaty palms, lightheadedness). Monitor for signs and symptoms of vitamin B12 deficiency. Monitor for signs and symptoms of folic acid deficiency.
Glucovance FDA approval
The first combination oral antihyperglycemic agent was recently approved by the Food and Drug Administration (FDA). Glucovance™, a combination of glyburide and metformin, is manufactured by Bristol-Myers Squibb. It is FDA-approved as first-line therapy for patients with Type 2 diabetes mellitus (DM) whose glucose is not controlled with diet and exercise. It can also be used as second-line therapy for patients whose blood glucose levels are not controlled with either a sulfonylurea or metformin alone.
Each individual component of Glucovance™ has its own unique mechanism of action. Glyburide, a sulfonylurea, lowers blood glucose by stimulating the pancreas to secrete insulin. Metformin, a biguanide, works by decreasing gluconeogenesis and intestinal glucose absorption, as well as enhancing insulin sensitivity.
Some common adverse effects associated with Glucovance™ include diarrhea, upper respiratory infection, lightheadedness, dizziness, shaking, hunger, and headache. Additionally, due to the metformin component, Glucovance™ may cause lactic acidosis, a rare but serious adverse effect. The risk of lactic acidosis increases with patient age and degree of renal insufficiency. To avoid lactic acidosis, it is recommended to 1) monitor renal function, 2) use the lowest dose possible of the metformin component, and 3) do not initiate its use in patients 80 years of age or older. Glucovance™ also has the potential to cause hypoglycemia because it stimulates insulin secretion. The risk is greatest in patients with decreased caloric intake, those taking concurrent glucose-lowering medications, or those ingesting alcohol.
Caution should be exercised when initiating or discontinuing agents that may cause hypoglycemia (e.g., nonsteroidal anti-inflammatory agents, warfarin, beta blockers) or hyperglycemia (e.g., diuretics, steroids, phenytoin, estrogens, calcium channel blockers) while patients are receiving Glucovance™. Drug interactions may also occur between metformin and agents that are excreted by renal tubular secretion (e.g., digoxin, procainamide, amiloride, quinidine, vancomycin).
Glucovance™ is contraindicated when serum creatinine levels are 1.5 mg/dL or higher in males or 1.4 mg/dL or higher in females, hypersensitivity to either component, kidney dysfunction, congestive heart failure, and acute or chronic metabolic acidosis.
If the patient's current combination therapy (e.g., glyburide [or another sulfonylurea] plus metformin) is changed to Glucovance™, the dose should not exceed the daily dose of sulfonylurea and metformin already being taken. See Table 1 for specific dosing recommendations of Glucovance™.
There are three tablet strengths of Glucovance™ available: 1.25 mg/250 mg (glyburide/metformin), 2.5 mg/500 mg, and 5 mg/500 mg. Based on the average wholesale price (AWP), the costs are approximately $0.66, $0.78, and $0.78 per tablet, respectively.
There are advantages for combining glyburide and metformin: 1) lower doses are required for glucose control, 2) fewer adverse effects may occur, and 3) increase in patient acceptance and compliance. In addition, patients should maintain a good diet and exercise program, as well as regular blood glucose monitoring.
Each individual component of Glucovance™ has its own unique mechanism of action. Glyburide, a sulfonylurea, lowers blood glucose by stimulating the pancreas to secrete insulin. Metformin, a biguanide, works by decreasing gluconeogenesis and intestinal glucose absorption, as well as enhancing insulin sensitivity.
Some common adverse effects associated with Glucovance™ include diarrhea, upper respiratory infection, lightheadedness, dizziness, shaking, hunger, and headache. Additionally, due to the metformin component, Glucovance™ may cause lactic acidosis, a rare but serious adverse effect. The risk of lactic acidosis increases with patient age and degree of renal insufficiency. To avoid lactic acidosis, it is recommended to 1) monitor renal function, 2) use the lowest dose possible of the metformin component, and 3) do not initiate its use in patients 80 years of age or older. Glucovance™ also has the potential to cause hypoglycemia because it stimulates insulin secretion. The risk is greatest in patients with decreased caloric intake, those taking concurrent glucose-lowering medications, or those ingesting alcohol.
Caution should be exercised when initiating or discontinuing agents that may cause hypoglycemia (e.g., nonsteroidal anti-inflammatory agents, warfarin, beta blockers) or hyperglycemia (e.g., diuretics, steroids, phenytoin, estrogens, calcium channel blockers) while patients are receiving Glucovance™. Drug interactions may also occur between metformin and agents that are excreted by renal tubular secretion (e.g., digoxin, procainamide, amiloride, quinidine, vancomycin).
Glucovance™ is contraindicated when serum creatinine levels are 1.5 mg/dL or higher in males or 1.4 mg/dL or higher in females, hypersensitivity to either component, kidney dysfunction, congestive heart failure, and acute or chronic metabolic acidosis.
If the patient's current combination therapy (e.g., glyburide [or another sulfonylurea] plus metformin) is changed to Glucovance™, the dose should not exceed the daily dose of sulfonylurea and metformin already being taken. See Table 1 for specific dosing recommendations of Glucovance™.
There are three tablet strengths of Glucovance™ available: 1.25 mg/250 mg (glyburide/metformin), 2.5 mg/500 mg, and 5 mg/500 mg. Based on the average wholesale price (AWP), the costs are approximately $0.66, $0.78, and $0.78 per tablet, respectively.
There are advantages for combining glyburide and metformin: 1) lower doses are required for glucose control, 2) fewer adverse effects may occur, and 3) increase in patient acceptance and compliance. In addition, patients should maintain a good diet and exercise program, as well as regular blood glucose monitoring.
Thursday, August 14, 2008
GlyBURIDE
Drug Information Provided by Lexi-Comp
This information has been developed and provided by an independent third-party source. Merck & Co., Inc. does not endorse and is not responsible for the accuracy of the content, or for practices or standards of non-Merck sources.
Medication Safety Issues
Sound-alike/look-alike issues:
GlyBURIDE may be confused with glipiZIDE, Glucotrol®
Dia?eta® may be confused with Diabinese®, Zebeta®
Micronase® may be confused with microK®, miconazole, Micronor®, Microzide™
High alert medication: The Institute for Safe Medication Practices (ISMP) includes this medication among its list of drugs which have a heightened risk of causing significant patient harm when used in error.
Pronunciation
(GLYE byoor ide)
U.S. Brand Names
* Dia?eta®
* Glynase® PresTab®
* Micronase®
Index Terms
* Diabeta
* Glibenclamide
* Glybenclamide
* Glybenzcyclamide
Generic Available
Yes
Canadian Brand Names
* Albert® Glyburide
* Apo-Glyburide®
* Dia?eta®
* Euglucon®
* Gen-Glybe
* Novo-Glyburide
* Nu-Glyburide
* PMS-Glyburide
* ratio-Glyburide
* Sandoz-Glyburide
Pharmacologic Category
*
Antidiabetic Agent, Sulfonylurea
Pharmacologic Category Synonyms
* Oral Hypoglycemic Agent, Sulfonylurea
* Sulfonylurea
Use
Management of type 2 diabetes mellitus (noninsulin dependent, NIDDM)
Use: Unlabeled/Investigational
Alternative to insulin in women for the treatment of gestational diabetes (11-33 weeks gestation)
Pregnancy Risk Factor
B/C (manufacturer dependent)
Pregnancy Implications
Glyburide was not found to significantly cross the placenta in vitro and was not found in the cord serum infants of mothers taking glyburide for gestational diabetes mellitus (GDM). Reported teratogenic effects may be due to poorly controlled maternal diabetes; abnormal blood glucose levels in the mother are associated with a higher incidence of congenital abnormalities. Nonteratogenic effects such as hypoglycemia in the neonate have been associated with maternal glyburide use. The manufacturer recommends that if glyburide is used during pregnancy, it should be discontinued at least 2 weeks before the expected delivery date. Although studies have shown positive outcomes using glyburide for the treatment of GDM, use may not be appropriate for all women. When compared to insulin for the treatment of GDM, as the severity of GDM increased, the success rate of treatment decreased. It should be noted that studies using glyburide for the treatment of GDM have initiated treatment after the period of organogenesis. Insulin is considered the drug of choice for the control of diabetes mellitus during pregnancy.Reproduction studies differ by manufacturer labeling. Because adverse events were not observed in animal reproduction studies, one manufacturer classifies glyburide as pregnancy category B. Because adverse events were noted in animal studies during the period of lactation, another manufacturer classifies glyburide as pregnancy category C.
Lactation
Does not enter breast milk/ use caution
Breast-Feeding Considerations
Data from initial studies note that glyburide was not detected in breast milk. Breast-feeding is not recommended by the manufacturer. Potentially, hypoglycemia may occur in a nursing infant exposed to a sulfonylurea via breast milk.
Contraindications
Hypersensitivity to glyburide, any component of the formulation, or other sulfonamides; type 1 diabetes mellitus (insulin dependent, IDDM), diabetic ketoacidosis; concurrent use with bosentan
Warnings/Precautions
Concerns related to adverse reactions:
• Cardiovascular mortality: Product labeling states oral hypoglycemic drugs may be associated with an increased cardiovascular mortality as compared to treatment with diet alone or diet plus insulin. Data to support this association are limited, and several studies, including a large prospective trial (UKPDS) have not supported an association.
• Hypoglycemia: All sulfonylurea drugs are capable of producing severe hypoglycemia. Hypoglycemia is more likely to occur when caloric intake is deficient, after severe or prolonged exercise, when ethanol is ingested, or when more than one glucose-lowering drug is used. It is also more likely in elderly patients, malnourished patients and in patients with impaired renal, hepatic, adrenal and/or pituitary function; use with caution.
• Sulfonamide allergy: Chemical similarities are present among sulfonamides, sulfonylureas, carbonic anhydrase inhibitors, thiazides, and loop diuretics (except ethacrynic acid). Use in patients with sulfonamide allergy is specifically contraindicated in product labeling, however, a risk of cross-reaction exists in patients with allergy to any of these compounds; avoid use when previous reaction has been severe.
Disease-related concerns:
• Stress-related states: It may be necessary to discontinue therapy and administer insulin if the patient is exposed to stress (fever, trauma, infection, surgery).
Special populations:
• Elderly: Rapid and prolonged hypoglycemia (>12 hours) despite hypertonic glucose injections have been reported; age and hepatic and renal impairment are independent risk factors for hypoglycemia; dosage titration should be made at weekly intervals.
• Pediatrics: Safety and efficacy have not been established in children.
Adverse Reactions
Frequency not defined.
Cardiovascular: Vasculitis
Central nervous system: Headache, dizziness
Dermatologic: Erythema, maculopapular eruptions, morbilliform eruptions, pruritus, purpura, rash, urticaria, photosensitivity reaction
Endocrine & metabolic: Disulfiram-like reaction, hypoglycemia, hyponatremia (SIADH reported with other sulfonylureas)
Gastrointestinal: Nausea, epigastric fullness, heartburn, constipation, diarrhea, anorexia
Genitourinary: Nocturia
Hematologic: Leukopenia, thrombocytopenia, hemolytic anemia, agranulocytosis, aplastic anemia, pancytopenia, porphyria cutanea tarda
Hepatic: Cholestatic jaundice, hepatitis, transaminase increased
Neuromuscular & skeletal: Arthralgia, myalgia, paresthesia
Ocular: Blurred vision
Renal: Diuretic effect (minor)
Miscellaneous: Allergic reaction
Drug Interactions
Inhibits CYP2C8 (weak), 3A4 (weak)
Beta-blockers: Beta-blockers may enhance the hypoglycemic effect of glyburide and mask tachycardia as an initial symptom of hypoglycemia.
Bosentan: Glyburide may enhance the hepatotoxic effect and increase the metabolism of bosentan. Bosentan may increase the metabolism of glyburide. Concomitant use is contraindicated
Chloramphenicol: Chloramphenicol may decrease the metabolism of glyburide.
Cimetidine: Cimetidine may decrease the metabolism, via CYP isoenzymes, of glyburide.
Cyclic antidepressants: Cyclic antidepressants may enhance the hypoglycemic effect of glyburide.
Cyclosporine: Glyburide may increase the serum concentration of cyclosporine.
Fibric acid derivatives: Fibric acid derivatives may enhance the hypoglycemic effect of glyburide.
Fluconazole: Fluconazole may increase the serum concentration of glyburide.
Pegvisomant: Pegvisomant may enhance the hypoglycemic effect of glyburide.
Quinolone antibiotics: Quinolone antibiotics may enhance the hypoglycemic effect of glyburide.
Rifampin: Rifampin may increase the metabolism, via CYP isoenzymes, of glyburide.
Salicylates: Salicylates may enhance the hypoglycemic effect of glyburide. Of concern with regular, higher doses of salicylates, not sporadic, low doses.
Sulfonamide derivatives (sulfadiazine, sulfadoxine, sulfamethoxazole, sulfisoxazole): Sulfonamide derivatives (except sulfacetamide) may enhance the hypoglycemic effect of glyburide.
Ethanol/Nutrition/Herb Interactions
Ethanol: Caution with ethanol (may cause hypoglycemia).
Herb/Nutraceutical: Herbs with hypoglycemic properties may enhance the hypoglycemic effect of glyburide. This includes alfalfa, aloe, bilberry, bitter melon, burdock, celery, damiana, fenugreek, garcinia, garlic, ginger, ginseng (American), gymnema, marshmallow, stinging nettle
Mechanism of Action
Stimulates insulin release from the pancreatic beta cells; reduces glucose output from the liver; insulin sensitivity is increased at peripheral target sites
Pharmacodynamics/Kinetics
Onset of action: Serum insulin levels begin to increase 15-60 minutes after a single dose
Duration: ?24 hours
Absorption: Significant within 1 hour
Distribution: 9-10 L
Protein binding, plasma: >99% primarily to albumin
Metabolism: Hepatic; forms metabolites (weakly active)
Half-life elimination: Diabeta®, Micronase®: 10 hours; Glynase® PresTab®: ?4 hours; may be prolonged with renal or hepatic impairment
Time to peak, serum: Adults: 2-4 hours
Excretion: Feces (50%) and urine (50%) as metabolites
Dosage
Oral: Adults:
Dia?eta®, Micronase®:
Initial: 2.5-5 mg/day, administered with breakfast or the first main meal of the day. In patients who are more sensitive to hypoglycemic drugs, start at 1.25 mg/day.
Increase in increments of no more than 2.5 mg/day at weekly intervals based on the patient's blood glucose response
Maintenance: 1.25-20 mg/day given as single or divided doses; maximum: 20 mg/day
Elderly: Initial: 1.25-2.5 mg/day, increase by 1.25-2.5 mg/day every 1-3 weeks
Micronized tablets (Glynase® PresTab®): Adults:
Initial: 1.5-3 mg/day, administered with breakfast or the first main meal of the day in patients who are more sensitive to hypoglycemic drugs, start at 0.75 mg/day. Increase in increments of no more than 1.5 mg/day in weekly intervals based on the patient's blood glucose response.
Maintenance: 0.75-12 mg/day given as a single dose or in divided doses. Some patients (especially those receiving >6 mg/day) may have a more satisfactory response with twice-daily dosing. Maximum: 12 mg/day
Dosing adjustment/comments in renal impairment: Clcr <50 mL/minute: Not recommended
Dosing adjustment in hepatic impairment: Use conservative initial and maintenance doses and avoid use in severe disease
Administration: Oral
Administer with meals at the same time each day. Patients who are anorexic or NPO may need to have their dose held to avoid hypoglycemia.
Monitoring Parameters
Signs and symptoms of hypoglycemia, fasting blood glucose, hemoglobin A1c
Reference Range
Recommendations for glycemic control in adults with diabetes:
Hb A1c: <7%
Preprandial capillary plasma glucose: 70-130 mg/dL
Peak postprandial capillary blood glucose: <180 mg/dL
Blood pressure: <130/80 mm Hg
Dietary Considerations
Should be taken with meals at the same time each day. Dietary modification based on ADA recommendations is a part of therapy. Decreases blood glucose concentration. Hypoglycemia may occur. Must be able to recognize symptoms of hypoglycemia (palpitations, sweaty palms, lightheadedness).
Patient Education
Do not take any new medication during therapy unless approved by prescriber. This medication is used to control diabetes; it is not a cure. Monitor glucose as recommended by prescriber. Other important components of treatment plan may include prescribed diet and exercise regimen (consult prescriber or diabetic educator). If you experience hypoglycemic reaction, contact prescriber immediately. Always carry quick source of sugar with you. Take exactly as directed, 30 minutes before meal(s) at the same time each day. Do not change dose or discontinue without consulting prescriber. Avoid alcohol while taking this medication; could cause severe reaction. Do not take other medication within 2 hours of this medication unless advised by prescriber. You may experience more sensitivity to sunlight (use sunscreen, wear protective clothing and eyewear, and avoid direct sunlight); headache; or nausea (consult prescriber if these persist). Report severe or persistent side effects; hypoglycemia (palpitations, sweaty palms, lightheadedness); extended vomiting, diarrhea, or constipation; flu-like symptoms; skin rash; easy bruising or bleeding; or change in color of urine or stool. Pregnancy/breast-feeding precautions: Inform prescriber if you are or intend to become pregnant. Do not breast-feed.
Geriatric Considerations
Rapid and prolonged hypoglycemia (>12 hours) despite hypertonic glucose injections has been reported; age, hepatic, and renal impairment are independent risk factors for hypoglycemia; dosage titration should be made at weekly intervals. How “tightly” a geriatric patient's blood glucose should be controlled is controversial; however, a fasting blood sugar <150 mg/dL is now an acceptable endpoint. Such a decision should be based on the patient's functional and cognitive status, how well they recognize hypoglycemic or hyperglycemic symptoms, and how to respond to them and their other disease states. Use with caution in the elderly with renal insufficiency.
Anesthesia and Critical Care Concerns/Other Considerations
The possibility of higher doses of sulfonylureas eliciting an increase in cardiovascular events, because of their effects on blocking potassium sensitive ATP channels, has been raised. Longer-term prospective trials of sulfonylurea therapy, such as the UKPDS, do not reveal any increased cardiovascular mortality.
Cardiovascular Considerations
The possibility of higher doses of sulfonylureas eliciting an increase in cardiovascular events, because of their effects on blocking potassium sensitive ATP channels, has been raised. However, there are presently only limited data to support this premise, particularly with newer generation agents. An early study suggested poor cardiovascular outcomes in patients with diabetes treated with tolbutamide. Retrospective studies evaluating cardiovascular outcomes following angioplasty and acute myocardial infarction in patients with diabetes receiving newer sulfonylureas are inconsistent. Longer-term prospective trials of sulfonylurea therapy, such as the UKPDS, do not reveal any increased cardiovascular mortality.
Dental Health: Effects on Dental Treatment
Glyburide-dependent patients with diabetes (noninsulin dependent, type 2) should be appointed for dental treatment in morning in order to minimize chance of stress-induced hypoglycemia.
Dental Health: Vasoconstrictor/Local Anesthetic Precautions
No information available to require special precautions
Mental Health: Effects on Mental Status
Dizziness is common
Mental Health: Effects on Psychiatric Treatment
May rarely cause agranulocytosis; use caution with clozapine and carbamazepine; phenothiazines and TCAs may antagonize glimepiride hypoglycemic effects; MAO inhibitors and TCAs may enhance hypoglycemic effects
Nursing: Physical Assessment/Monitoring
Assess allergy history prior to beginning therapy. Assess potential for interactions with other prescriptions, OTC medications, or herbal products patient may be taking. Assess results of laboratory tests, therapeutic effectiveness, and adverse response (eg, hypoglycemia) at regular intervals during therapy. Teach patient proper use (or refer patient to diabetic educator) for instruction, possible side effects/appropriate interventions, and adverse symptoms to report.
Dosage Forms
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Tablet: 1.25 mg, 2.5 mg, 5 mg
Dia?eta®, Micronase®: 1.25 mg, 2.5 mg, 5 mg
Tablet, micronized: 1.5 mg, 3 mg, 6 mg
Glynase® PresTab®: 3 mg, 6 mg
Pricing: U.S. (www.drugstore.com)
Tablets (Diabeta)
1.25 mg (50): $27.11
2.5 mg (30): $28.20
5 mg (30): $35.99
Tablets (GlyBURIDE)
1.25 mg (30): $12.99
2.5 mg (30): $12.99
5 mg (30): $11.99
Tablets (GlyBURIDE Micronized)
1.5 mg (60): $16.00
3 mg (60): $20.99
6 mg (60): $33.99
Tablets (Glynase)
1.5 mg (60): $47.69
3 mg (60): $70.13
6 mg (60): $109.42
Tablets (Micronase)
1.25 mg (30): $17.39
2.5 mg (30): $28.10
5 mg (30): $44.99
References
ACOG Practice Bulletin, Clinical Management Guidelines for Obstetrician-Gynecologists, Number 60, March 2005, "Pregestational Diabetes Mellitus," Obstet Gynecol , 2005, 105(3):675-85.
American Diabetes Association, “Standards of Medical Care in Diabetes Mellitus - 2008,” Diabetes Care, 2008, 30(Suppl 1):12-54.
“A Study of the Effects of Hypoglycemia Agents on Vascular Complications in Patients With Adult-onset Diabetes. VI. Supplementary Report on Nonfatal Events in Patients Treated With Tolbutamide. The University Group Diabetes Program,” Diabetes, 1976, 25(12):1129-53.
Brodows RG, “Benefits and Risks With Glyburide and Glipizide in Elderly NIDDM Patients,” Diabetes Care, 1992, 15(1):75-80.
“Effect of Intensive Blood-Glucose Control With Metformin on Complications in Overweight Patients With Type 2 Diabetes (UKPDS 34). UK Prospective Diabetes Study (UKPDS) Group,” Lancet, 1998, 352(9131):854-65.
Elliott BD, Schenker S, Langer O, et al, "Comparative Placental Transport of Oral Hypoglycemic Agents in Humans: A Model of Human Placental Drug Transfer," Am J Obstet Gynecol, 1994, 171(3):653-60.
Feig DS, Briggs GG, Kraemer JM, et al, "Transfer of Glyburide and Glipizide Into Breast Milk," Diabetes Care, 2005, 28(8):1851-5.
Gabbe SG and Graves CR, "Management of Diabetes Mellitus Complicating Pregnancy," Obstet Gynecol, 2003, 102(4):857-68.
Garratt KN, Brady PA, Hassinger NL, et al, “Sulfonylurea Drugs Increase Early Mortality in Patients With Diabetes Mellitus After Direct Angioplasty for Acute Myocardial Infarction,” J Am Coll Cardiol, 1999, 33(1):119-24.
Gavin JR 3d, “Glyburide: New Insights Into Its Effects on the Beta Cell and Beyond - Introduction,” Am J Med, 1990, 89(2A):1S-2S.
“Intensive Blood-Glucose Control With Sulphonylureas or Insulin Compared With Conventional Treatment and Risk of Complications in Patients With Type 2 Diabetes (UKPDS 33) UK Prospective Diabetes Study (UKPDS) Group,” Lancet, 1998, 352(9131):837-53.
Jacobson GF, Ramos GA, Ching JY, et al, "Comparison of Glyburide and Insulin for the Management of Gestational Diabetes in a Large Managed Care Organization," Am J Obstet Gynecol, 2005, 193(1):118-24.
Klamann A, Sarfert P, Launhardt V, et al, “Myocardial Infarction in Diabetic vs Nondiabetic Subjects. Survival and Infarct Size Following Therapy With Sulfonylureas (Glibenclamide),” Eur Heart J, 2000, 21(3):220-9.
Langer O, Conway D, Berkus M, et al, “A Comparison of Glyburide and Insulin in Women With Gestational Diabetes Mellitus,” N Engl J Med, 2000, 343(16):1134-8.
Langer O, Yogev Y, Xenakis EM, et al, "Insulin and Glyburide Therapy: Dosage, Severity Level of Gestational Diabetes, and Pregnancy Outcome," Am J Obstet Gynecol , 2005, 192(1):134-9.
Meinert CL, Knatterud GL, Prout TE, et al, “A Study of the Effects of Hypoglycemic Agents on Vascular Complications in Patients With Adult-Onset Diabetes. II. Mortality Results,” Diabetes, 1970, 19:789-830.
Nadel HL, “Formulary Conversion From Glipizide to Glyburide: A Cost-Minimization Analysis,” Hosp Pharm, 1995, 30:472-74.
Nataas OB and Nesthus I, “Immune Haemolytic Anaemia Induced by Glibenclamide in Selective IgA Deficiency,” Br Med J (Clin Res Ed), 1987, 295(6594):366-7.
O'Keefe JH, Blackstone EH, Sergeant P, et al, “The Optimal Mode of Coronary Revascularization for Diabetics. A Risk-Adjusted Long-Term Study Comparing Coronary Angioplasty and Coronary Bypass Surgery,” Eur Heart J, 1998, 19(11):1696-703.
Pearson JG, “Pharmacokinetics of Glyburide,” Am J Med, 1985, 79(3B):67-71.
Rosenstock J, Corrao PJ, Goldberg RB, et al, “Diabetes Control in the Elderly: A Randomized, Comparative Study of Glyburide Versus Glipizide in Noninsulin-Dependent Diabetes Mellitus,” Clin Ther, 1993, 15(6):1031-40.
Schwinghammer TL, Antal EJ, Kubacka RT, et al, “Pharmacokinetics and Pharmacodynamics of Glyburide in Young and Elderly Nondiabetic Adults,” Clin Pharm, 1991, 10(7):532-8.
Sillence DO and Court JM, “Glibenclamide-Induced Hypoglycemia,” Br Med J, 1975, 3(5981):490-1.
Sonnenblick M and Shilo S, “Glibenclamide Induced Prolonged Hypoglycaemia,” Age Ageing, 1986, 15(3):185-9.
International Brand Names
* Amecladin (PH)
* Apo-Glibenclamide (NZ)
* Benclamin (TH)
* Betanase (AE, BH, CY, EG, IL, IQ, IR, JO, KW, LB, LY, OM, QA, SA, SY, YE)
* Betanese 5 (BF, BJ, CI, ET, GH, GM, GN, KE, LR, MA, ML, MR, MU, MW, NE, NG, SC, SD, SL, SN, TN, TZ, UG, ZA, ZM, ZW)
* Bevoren (LU)
* Calabren (CZ)
* Clamide (HK)
* Daonil (AE, AR, AU, BB, BD, BE, BF, BH, BJ, BM, BO, BR, BS, BZ, CH, CI, CL, CN, CO, CR, CY, DK, DO, EC, EG, ET, FR, GB, GH, GM, GN, GR, GT, GY, HK, HN, HR, ID, IE, IL, IN, IQ, IR, IT, JM, JO, JP, KE, KP, KW, LB, LR, LU, LY, MA, ML, MR, MU, MW, MX, MY, NE, NG, NI, NL, NO, NZ, OM, PA, PE, PH, PK, PR, PT, PY, QA, RU, SA, SC, SD, SG, SL, SN, SR, SV, SY, TH, TN, TT, TW, TZ, UG, UY, VE, YE, ZA, ZM, ZW)
* Daono (TH)
* Debtan (TH)
* Diaben (AE, BH, CY, EG, IL, IQ, IR, JO, KW, LB, LY, OM, QA, SA, SY, YE)
* Diabitor (PH)
* Dibelet (MY, TH)
* Euclamin (PL)
* Euglucan (FR)
* Euglucon (AE, AR, AT, AU, BB, BD, BE, BF, BH, BJ, BM, BO, BR, BS, BZ, CH, CI, CL, CN, CO, CR, CY, CZ, DE, DO, EC, EG, ES, ET, FI, GH, GM, GN, GR, GT, GY, HK, HN, HR, ID, IL, IN, IQ, IR, IT, JM, JO, JP, KE, KP, KW, LB, LR, LU, LY, MA, ML, MR, MU, MW, MX, MY, NE, NG, NI, NL, OM, PA, PE, PH, PK, PR, PT, PY, QA, RU, SA, SC, SD, SE, SG, SL, SN, SR, SV, SY, TH, TN, TT, TW, TZ, UG, UY, VE, YE, ZA, ZM, ZW)
* Euglusid (CN)
* Gilemal (AT, BG, HN, HU)
* Gliban (AE, BH, CY, EG, IL, IQ, IR, JO, KW, LB, LY, OM, QA, SA, SY, YE)
* Glibedal (HR)
* Gliben (IT, NZ)
* Glibenclamid (HR)
* Glibenclamid Pharmavit (HU)
* Glibenclamid-ratiopharm (LU)
* Glibenhexal (LU)
* Glibens (CO)
* Glibesyn (MY, SG)
* Glibet (IN)
* Glibetic (IL)
* Glibil (AE, BH, CY, EG, IL, IQ, IR, JO, KW, LB, LY, OM, QA, SA, SY, YE)
* Gliboral (BF, BJ, CI, ET, GH, GM, GN, KE, LR, MA, ML, MR, MU, MW, NE, NG, SC, SD, SL, SN, TN, TZ, UG, ZA, ZM, ZW)
* Glidiabet (PE)
* Glimel (AU, HK, SG)
* Glimide (MY)
* Glisulin (KP)
* Glitisol (BB, BM, BS, BZ, GY, HK, JM, NL, SR, TT)
* Gluben (IL)
* Glucal (MX)
* Glucobene (HU)
* Glucomid (BF, BJ, CI, ET, GH, GM, GN, KE, LR, MA, ML, MR, MU, MW, NE, NG, SC, SD, SL, SN, TN, TZ, UG, ZA, ZM, ZW)
* Gluconic (ID)
* Glulo (ID)
* Glyamid (ID)
* Glycomin (ZA)
* Glynase (BB, BM, BS, BZ, GY, JM, NL, SR, TT)
* Hemi-Daonil (AR, FR, MA, NL)
* Insol (PH)
* Lodulce (PH)
* Maninil (EE, PL)
* Manoglucon (TH)
* Melix (AE, BB, BF, BH, BJ, BM, BS, BZ, CI, CY, EG, ET, GH, GM, GN, GY, IL, IQ, IR, JM, JO, KE, KW, LB, LR, LY, MA, ML, MR, MU, MW, NE, NG, NL, OM, QA, SA, SC, SD, SL, SN, SR, SY, TN, TT, TZ, UG, YE, ZA, ZM, ZW)
* Miglucan (FR)
* Norboral (MX)
* Norglicem (ES)
* Orabetic (PH)
* Pira (AR)
* Renabetic (ID)
* Semi-Daonil (AE, AR, AU, BH, CH, CY, EG, GB, HK, ID, IE, IL, IQ, IR, JO, KW, LB, LY, MA, NZ, OM, PT, QA, SA, SY, YE)
* Semi-Euglucon (AR, AT, AU, NL, PH, TH)
* Sugril (TH)
* Tiabet (ID)
* Trodeb (ID)
* Unil-5 (TH)
* Xeltic (HK)
This information has been developed and provided by an independent third-party source. Merck & Co., Inc. does not endorse and is not responsible for the accuracy of the content, or for practices or standards of non-Merck sources.
Medication Safety Issues
Sound-alike/look-alike issues:
GlyBURIDE may be confused with glipiZIDE, Glucotrol®
Dia?eta® may be confused with Diabinese®, Zebeta®
Micronase® may be confused with microK®, miconazole, Micronor®, Microzide™
High alert medication: The Institute for Safe Medication Practices (ISMP) includes this medication among its list of drugs which have a heightened risk of causing significant patient harm when used in error.
Pronunciation
(GLYE byoor ide)
U.S. Brand Names
* Dia?eta®
* Glynase® PresTab®
* Micronase®
Index Terms
* Diabeta
* Glibenclamide
* Glybenclamide
* Glybenzcyclamide
Generic Available
Yes
Canadian Brand Names
* Albert® Glyburide
* Apo-Glyburide®
* Dia?eta®
* Euglucon®
* Gen-Glybe
* Novo-Glyburide
* Nu-Glyburide
* PMS-Glyburide
* ratio-Glyburide
* Sandoz-Glyburide
Pharmacologic Category
*
Antidiabetic Agent, Sulfonylurea
Pharmacologic Category Synonyms
* Oral Hypoglycemic Agent, Sulfonylurea
* Sulfonylurea
Use
Management of type 2 diabetes mellitus (noninsulin dependent, NIDDM)
Use: Unlabeled/Investigational
Alternative to insulin in women for the treatment of gestational diabetes (11-33 weeks gestation)
Pregnancy Risk Factor
B/C (manufacturer dependent)
Pregnancy Implications
Glyburide was not found to significantly cross the placenta in vitro and was not found in the cord serum infants of mothers taking glyburide for gestational diabetes mellitus (GDM). Reported teratogenic effects may be due to poorly controlled maternal diabetes; abnormal blood glucose levels in the mother are associated with a higher incidence of congenital abnormalities. Nonteratogenic effects such as hypoglycemia in the neonate have been associated with maternal glyburide use. The manufacturer recommends that if glyburide is used during pregnancy, it should be discontinued at least 2 weeks before the expected delivery date. Although studies have shown positive outcomes using glyburide for the treatment of GDM, use may not be appropriate for all women. When compared to insulin for the treatment of GDM, as the severity of GDM increased, the success rate of treatment decreased. It should be noted that studies using glyburide for the treatment of GDM have initiated treatment after the period of organogenesis. Insulin is considered the drug of choice for the control of diabetes mellitus during pregnancy.Reproduction studies differ by manufacturer labeling. Because adverse events were not observed in animal reproduction studies, one manufacturer classifies glyburide as pregnancy category B. Because adverse events were noted in animal studies during the period of lactation, another manufacturer classifies glyburide as pregnancy category C.
Lactation
Does not enter breast milk/ use caution
Breast-Feeding Considerations
Data from initial studies note that glyburide was not detected in breast milk. Breast-feeding is not recommended by the manufacturer. Potentially, hypoglycemia may occur in a nursing infant exposed to a sulfonylurea via breast milk.
Contraindications
Hypersensitivity to glyburide, any component of the formulation, or other sulfonamides; type 1 diabetes mellitus (insulin dependent, IDDM), diabetic ketoacidosis; concurrent use with bosentan
Warnings/Precautions
Concerns related to adverse reactions:
• Cardiovascular mortality: Product labeling states oral hypoglycemic drugs may be associated with an increased cardiovascular mortality as compared to treatment with diet alone or diet plus insulin. Data to support this association are limited, and several studies, including a large prospective trial (UKPDS) have not supported an association.
• Hypoglycemia: All sulfonylurea drugs are capable of producing severe hypoglycemia. Hypoglycemia is more likely to occur when caloric intake is deficient, after severe or prolonged exercise, when ethanol is ingested, or when more than one glucose-lowering drug is used. It is also more likely in elderly patients, malnourished patients and in patients with impaired renal, hepatic, adrenal and/or pituitary function; use with caution.
• Sulfonamide allergy: Chemical similarities are present among sulfonamides, sulfonylureas, carbonic anhydrase inhibitors, thiazides, and loop diuretics (except ethacrynic acid). Use in patients with sulfonamide allergy is specifically contraindicated in product labeling, however, a risk of cross-reaction exists in patients with allergy to any of these compounds; avoid use when previous reaction has been severe.
Disease-related concerns:
• Stress-related states: It may be necessary to discontinue therapy and administer insulin if the patient is exposed to stress (fever, trauma, infection, surgery).
Special populations:
• Elderly: Rapid and prolonged hypoglycemia (>12 hours) despite hypertonic glucose injections have been reported; age and hepatic and renal impairment are independent risk factors for hypoglycemia; dosage titration should be made at weekly intervals.
• Pediatrics: Safety and efficacy have not been established in children.
Adverse Reactions
Frequency not defined.
Cardiovascular: Vasculitis
Central nervous system: Headache, dizziness
Dermatologic: Erythema, maculopapular eruptions, morbilliform eruptions, pruritus, purpura, rash, urticaria, photosensitivity reaction
Endocrine & metabolic: Disulfiram-like reaction, hypoglycemia, hyponatremia (SIADH reported with other sulfonylureas)
Gastrointestinal: Nausea, epigastric fullness, heartburn, constipation, diarrhea, anorexia
Genitourinary: Nocturia
Hematologic: Leukopenia, thrombocytopenia, hemolytic anemia, agranulocytosis, aplastic anemia, pancytopenia, porphyria cutanea tarda
Hepatic: Cholestatic jaundice, hepatitis, transaminase increased
Neuromuscular & skeletal: Arthralgia, myalgia, paresthesia
Ocular: Blurred vision
Renal: Diuretic effect (minor)
Miscellaneous: Allergic reaction
Drug Interactions
Inhibits CYP2C8 (weak), 3A4 (weak)
Beta-blockers: Beta-blockers may enhance the hypoglycemic effect of glyburide and mask tachycardia as an initial symptom of hypoglycemia.
Bosentan: Glyburide may enhance the hepatotoxic effect and increase the metabolism of bosentan. Bosentan may increase the metabolism of glyburide. Concomitant use is contraindicated
Chloramphenicol: Chloramphenicol may decrease the metabolism of glyburide.
Cimetidine: Cimetidine may decrease the metabolism, via CYP isoenzymes, of glyburide.
Cyclic antidepressants: Cyclic antidepressants may enhance the hypoglycemic effect of glyburide.
Cyclosporine: Glyburide may increase the serum concentration of cyclosporine.
Fibric acid derivatives: Fibric acid derivatives may enhance the hypoglycemic effect of glyburide.
Fluconazole: Fluconazole may increase the serum concentration of glyburide.
Pegvisomant: Pegvisomant may enhance the hypoglycemic effect of glyburide.
Quinolone antibiotics: Quinolone antibiotics may enhance the hypoglycemic effect of glyburide.
Rifampin: Rifampin may increase the metabolism, via CYP isoenzymes, of glyburide.
Salicylates: Salicylates may enhance the hypoglycemic effect of glyburide. Of concern with regular, higher doses of salicylates, not sporadic, low doses.
Sulfonamide derivatives (sulfadiazine, sulfadoxine, sulfamethoxazole, sulfisoxazole): Sulfonamide derivatives (except sulfacetamide) may enhance the hypoglycemic effect of glyburide.
Ethanol/Nutrition/Herb Interactions
Ethanol: Caution with ethanol (may cause hypoglycemia).
Herb/Nutraceutical: Herbs with hypoglycemic properties may enhance the hypoglycemic effect of glyburide. This includes alfalfa, aloe, bilberry, bitter melon, burdock, celery, damiana, fenugreek, garcinia, garlic, ginger, ginseng (American), gymnema, marshmallow, stinging nettle
Mechanism of Action
Stimulates insulin release from the pancreatic beta cells; reduces glucose output from the liver; insulin sensitivity is increased at peripheral target sites
Pharmacodynamics/Kinetics
Onset of action: Serum insulin levels begin to increase 15-60 minutes after a single dose
Duration: ?24 hours
Absorption: Significant within 1 hour
Distribution: 9-10 L
Protein binding, plasma: >99% primarily to albumin
Metabolism: Hepatic; forms metabolites (weakly active)
Half-life elimination: Diabeta®, Micronase®: 10 hours; Glynase® PresTab®: ?4 hours; may be prolonged with renal or hepatic impairment
Time to peak, serum: Adults: 2-4 hours
Excretion: Feces (50%) and urine (50%) as metabolites
Dosage
Oral: Adults:
Dia?eta®, Micronase®:
Initial: 2.5-5 mg/day, administered with breakfast or the first main meal of the day. In patients who are more sensitive to hypoglycemic drugs, start at 1.25 mg/day.
Increase in increments of no more than 2.5 mg/day at weekly intervals based on the patient's blood glucose response
Maintenance: 1.25-20 mg/day given as single or divided doses; maximum: 20 mg/day
Elderly: Initial: 1.25-2.5 mg/day, increase by 1.25-2.5 mg/day every 1-3 weeks
Micronized tablets (Glynase® PresTab®): Adults:
Initial: 1.5-3 mg/day, administered with breakfast or the first main meal of the day in patients who are more sensitive to hypoglycemic drugs, start at 0.75 mg/day. Increase in increments of no more than 1.5 mg/day in weekly intervals based on the patient's blood glucose response.
Maintenance: 0.75-12 mg/day given as a single dose or in divided doses. Some patients (especially those receiving >6 mg/day) may have a more satisfactory response with twice-daily dosing. Maximum: 12 mg/day
Dosing adjustment/comments in renal impairment: Clcr <50 mL/minute: Not recommended
Dosing adjustment in hepatic impairment: Use conservative initial and maintenance doses and avoid use in severe disease
Administration: Oral
Administer with meals at the same time each day. Patients who are anorexic or NPO may need to have their dose held to avoid hypoglycemia.
Monitoring Parameters
Signs and symptoms of hypoglycemia, fasting blood glucose, hemoglobin A1c
Reference Range
Recommendations for glycemic control in adults with diabetes:
Hb A1c: <7%
Preprandial capillary plasma glucose: 70-130 mg/dL
Peak postprandial capillary blood glucose: <180 mg/dL
Blood pressure: <130/80 mm Hg
Dietary Considerations
Should be taken with meals at the same time each day. Dietary modification based on ADA recommendations is a part of therapy. Decreases blood glucose concentration. Hypoglycemia may occur. Must be able to recognize symptoms of hypoglycemia (palpitations, sweaty palms, lightheadedness).
Patient Education
Do not take any new medication during therapy unless approved by prescriber. This medication is used to control diabetes; it is not a cure. Monitor glucose as recommended by prescriber. Other important components of treatment plan may include prescribed diet and exercise regimen (consult prescriber or diabetic educator). If you experience hypoglycemic reaction, contact prescriber immediately. Always carry quick source of sugar with you. Take exactly as directed, 30 minutes before meal(s) at the same time each day. Do not change dose or discontinue without consulting prescriber. Avoid alcohol while taking this medication; could cause severe reaction. Do not take other medication within 2 hours of this medication unless advised by prescriber. You may experience more sensitivity to sunlight (use sunscreen, wear protective clothing and eyewear, and avoid direct sunlight); headache; or nausea (consult prescriber if these persist). Report severe or persistent side effects; hypoglycemia (palpitations, sweaty palms, lightheadedness); extended vomiting, diarrhea, or constipation; flu-like symptoms; skin rash; easy bruising or bleeding; or change in color of urine or stool. Pregnancy/breast-feeding precautions: Inform prescriber if you are or intend to become pregnant. Do not breast-feed.
Geriatric Considerations
Rapid and prolonged hypoglycemia (>12 hours) despite hypertonic glucose injections has been reported; age, hepatic, and renal impairment are independent risk factors for hypoglycemia; dosage titration should be made at weekly intervals. How “tightly” a geriatric patient's blood glucose should be controlled is controversial; however, a fasting blood sugar <150 mg/dL is now an acceptable endpoint. Such a decision should be based on the patient's functional and cognitive status, how well they recognize hypoglycemic or hyperglycemic symptoms, and how to respond to them and their other disease states. Use with caution in the elderly with renal insufficiency.
Anesthesia and Critical Care Concerns/Other Considerations
The possibility of higher doses of sulfonylureas eliciting an increase in cardiovascular events, because of their effects on blocking potassium sensitive ATP channels, has been raised. Longer-term prospective trials of sulfonylurea therapy, such as the UKPDS, do not reveal any increased cardiovascular mortality.
Cardiovascular Considerations
The possibility of higher doses of sulfonylureas eliciting an increase in cardiovascular events, because of their effects on blocking potassium sensitive ATP channels, has been raised. However, there are presently only limited data to support this premise, particularly with newer generation agents. An early study suggested poor cardiovascular outcomes in patients with diabetes treated with tolbutamide. Retrospective studies evaluating cardiovascular outcomes following angioplasty and acute myocardial infarction in patients with diabetes receiving newer sulfonylureas are inconsistent. Longer-term prospective trials of sulfonylurea therapy, such as the UKPDS, do not reveal any increased cardiovascular mortality.
Dental Health: Effects on Dental Treatment
Glyburide-dependent patients with diabetes (noninsulin dependent, type 2) should be appointed for dental treatment in morning in order to minimize chance of stress-induced hypoglycemia.
Dental Health: Vasoconstrictor/Local Anesthetic Precautions
No information available to require special precautions
Mental Health: Effects on Mental Status
Dizziness is common
Mental Health: Effects on Psychiatric Treatment
May rarely cause agranulocytosis; use caution with clozapine and carbamazepine; phenothiazines and TCAs may antagonize glimepiride hypoglycemic effects; MAO inhibitors and TCAs may enhance hypoglycemic effects
Nursing: Physical Assessment/Monitoring
Assess allergy history prior to beginning therapy. Assess potential for interactions with other prescriptions, OTC medications, or herbal products patient may be taking. Assess results of laboratory tests, therapeutic effectiveness, and adverse response (eg, hypoglycemia) at regular intervals during therapy. Teach patient proper use (or refer patient to diabetic educator) for instruction, possible side effects/appropriate interventions, and adverse symptoms to report.
Dosage Forms
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Tablet: 1.25 mg, 2.5 mg, 5 mg
Dia?eta®, Micronase®: 1.25 mg, 2.5 mg, 5 mg
Tablet, micronized: 1.5 mg, 3 mg, 6 mg
Glynase® PresTab®: 3 mg, 6 mg
Pricing: U.S. (www.drugstore.com)
Tablets (Diabeta)
1.25 mg (50): $27.11
2.5 mg (30): $28.20
5 mg (30): $35.99
Tablets (GlyBURIDE)
1.25 mg (30): $12.99
2.5 mg (30): $12.99
5 mg (30): $11.99
Tablets (GlyBURIDE Micronized)
1.5 mg (60): $16.00
3 mg (60): $20.99
6 mg (60): $33.99
Tablets (Glynase)
1.5 mg (60): $47.69
3 mg (60): $70.13
6 mg (60): $109.42
Tablets (Micronase)
1.25 mg (30): $17.39
2.5 mg (30): $28.10
5 mg (30): $44.99
References
ACOG Practice Bulletin, Clinical Management Guidelines for Obstetrician-Gynecologists, Number 60, March 2005, "Pregestational Diabetes Mellitus," Obstet Gynecol , 2005, 105(3):675-85.
American Diabetes Association, “Standards of Medical Care in Diabetes Mellitus - 2008,” Diabetes Care, 2008, 30(Suppl 1):12-54.
“A Study of the Effects of Hypoglycemia Agents on Vascular Complications in Patients With Adult-onset Diabetes. VI. Supplementary Report on Nonfatal Events in Patients Treated With Tolbutamide. The University Group Diabetes Program,” Diabetes, 1976, 25(12):1129-53.
Brodows RG, “Benefits and Risks With Glyburide and Glipizide in Elderly NIDDM Patients,” Diabetes Care, 1992, 15(1):75-80.
“Effect of Intensive Blood-Glucose Control With Metformin on Complications in Overweight Patients With Type 2 Diabetes (UKPDS 34). UK Prospective Diabetes Study (UKPDS) Group,” Lancet, 1998, 352(9131):854-65.
Elliott BD, Schenker S, Langer O, et al, "Comparative Placental Transport of Oral Hypoglycemic Agents in Humans: A Model of Human Placental Drug Transfer," Am J Obstet Gynecol, 1994, 171(3):653-60.
Feig DS, Briggs GG, Kraemer JM, et al, "Transfer of Glyburide and Glipizide Into Breast Milk," Diabetes Care, 2005, 28(8):1851-5.
Gabbe SG and Graves CR, "Management of Diabetes Mellitus Complicating Pregnancy," Obstet Gynecol, 2003, 102(4):857-68.
Garratt KN, Brady PA, Hassinger NL, et al, “Sulfonylurea Drugs Increase Early Mortality in Patients With Diabetes Mellitus After Direct Angioplasty for Acute Myocardial Infarction,” J Am Coll Cardiol, 1999, 33(1):119-24.
Gavin JR 3d, “Glyburide: New Insights Into Its Effects on the Beta Cell and Beyond - Introduction,” Am J Med, 1990, 89(2A):1S-2S.
“Intensive Blood-Glucose Control With Sulphonylureas or Insulin Compared With Conventional Treatment and Risk of Complications in Patients With Type 2 Diabetes (UKPDS 33) UK Prospective Diabetes Study (UKPDS) Group,” Lancet, 1998, 352(9131):837-53.
Jacobson GF, Ramos GA, Ching JY, et al, "Comparison of Glyburide and Insulin for the Management of Gestational Diabetes in a Large Managed Care Organization," Am J Obstet Gynecol, 2005, 193(1):118-24.
Klamann A, Sarfert P, Launhardt V, et al, “Myocardial Infarction in Diabetic vs Nondiabetic Subjects. Survival and Infarct Size Following Therapy With Sulfonylureas (Glibenclamide),” Eur Heart J, 2000, 21(3):220-9.
Langer O, Conway D, Berkus M, et al, “A Comparison of Glyburide and Insulin in Women With Gestational Diabetes Mellitus,” N Engl J Med, 2000, 343(16):1134-8.
Langer O, Yogev Y, Xenakis EM, et al, "Insulin and Glyburide Therapy: Dosage, Severity Level of Gestational Diabetes, and Pregnancy Outcome," Am J Obstet Gynecol , 2005, 192(1):134-9.
Meinert CL, Knatterud GL, Prout TE, et al, “A Study of the Effects of Hypoglycemic Agents on Vascular Complications in Patients With Adult-Onset Diabetes. II. Mortality Results,” Diabetes, 1970, 19:789-830.
Nadel HL, “Formulary Conversion From Glipizide to Glyburide: A Cost-Minimization Analysis,” Hosp Pharm, 1995, 30:472-74.
Nataas OB and Nesthus I, “Immune Haemolytic Anaemia Induced by Glibenclamide in Selective IgA Deficiency,” Br Med J (Clin Res Ed), 1987, 295(6594):366-7.
O'Keefe JH, Blackstone EH, Sergeant P, et al, “The Optimal Mode of Coronary Revascularization for Diabetics. A Risk-Adjusted Long-Term Study Comparing Coronary Angioplasty and Coronary Bypass Surgery,” Eur Heart J, 1998, 19(11):1696-703.
Pearson JG, “Pharmacokinetics of Glyburide,” Am J Med, 1985, 79(3B):67-71.
Rosenstock J, Corrao PJ, Goldberg RB, et al, “Diabetes Control in the Elderly: A Randomized, Comparative Study of Glyburide Versus Glipizide in Noninsulin-Dependent Diabetes Mellitus,” Clin Ther, 1993, 15(6):1031-40.
Schwinghammer TL, Antal EJ, Kubacka RT, et al, “Pharmacokinetics and Pharmacodynamics of Glyburide in Young and Elderly Nondiabetic Adults,” Clin Pharm, 1991, 10(7):532-8.
Sillence DO and Court JM, “Glibenclamide-Induced Hypoglycemia,” Br Med J, 1975, 3(5981):490-1.
Sonnenblick M and Shilo S, “Glibenclamide Induced Prolonged Hypoglycaemia,” Age Ageing, 1986, 15(3):185-9.
International Brand Names
* Amecladin (PH)
* Apo-Glibenclamide (NZ)
* Benclamin (TH)
* Betanase (AE, BH, CY, EG, IL, IQ, IR, JO, KW, LB, LY, OM, QA, SA, SY, YE)
* Betanese 5 (BF, BJ, CI, ET, GH, GM, GN, KE, LR, MA, ML, MR, MU, MW, NE, NG, SC, SD, SL, SN, TN, TZ, UG, ZA, ZM, ZW)
* Bevoren (LU)
* Calabren (CZ)
* Clamide (HK)
* Daonil (AE, AR, AU, BB, BD, BE, BF, BH, BJ, BM, BO, BR, BS, BZ, CH, CI, CL, CN, CO, CR, CY, DK, DO, EC, EG, ET, FR, GB, GH, GM, GN, GR, GT, GY, HK, HN, HR, ID, IE, IL, IN, IQ, IR, IT, JM, JO, JP, KE, KP, KW, LB, LR, LU, LY, MA, ML, MR, MU, MW, MX, MY, NE, NG, NI, NL, NO, NZ, OM, PA, PE, PH, PK, PR, PT, PY, QA, RU, SA, SC, SD, SG, SL, SN, SR, SV, SY, TH, TN, TT, TW, TZ, UG, UY, VE, YE, ZA, ZM, ZW)
* Daono (TH)
* Debtan (TH)
* Diaben (AE, BH, CY, EG, IL, IQ, IR, JO, KW, LB, LY, OM, QA, SA, SY, YE)
* Diabitor (PH)
* Dibelet (MY, TH)
* Euclamin (PL)
* Euglucan (FR)
* Euglucon (AE, AR, AT, AU, BB, BD, BE, BF, BH, BJ, BM, BO, BR, BS, BZ, CH, CI, CL, CN, CO, CR, CY, CZ, DE, DO, EC, EG, ES, ET, FI, GH, GM, GN, GR, GT, GY, HK, HN, HR, ID, IL, IN, IQ, IR, IT, JM, JO, JP, KE, KP, KW, LB, LR, LU, LY, MA, ML, MR, MU, MW, MX, MY, NE, NG, NI, NL, OM, PA, PE, PH, PK, PR, PT, PY, QA, RU, SA, SC, SD, SE, SG, SL, SN, SR, SV, SY, TH, TN, TT, TW, TZ, UG, UY, VE, YE, ZA, ZM, ZW)
* Euglusid (CN)
* Gilemal (AT, BG, HN, HU)
* Gliban (AE, BH, CY, EG, IL, IQ, IR, JO, KW, LB, LY, OM, QA, SA, SY, YE)
* Glibedal (HR)
* Gliben (IT, NZ)
* Glibenclamid (HR)
* Glibenclamid Pharmavit (HU)
* Glibenclamid-ratiopharm (LU)
* Glibenhexal (LU)
* Glibens (CO)
* Glibesyn (MY, SG)
* Glibet (IN)
* Glibetic (IL)
* Glibil (AE, BH, CY, EG, IL, IQ, IR, JO, KW, LB, LY, OM, QA, SA, SY, YE)
* Gliboral (BF, BJ, CI, ET, GH, GM, GN, KE, LR, MA, ML, MR, MU, MW, NE, NG, SC, SD, SL, SN, TN, TZ, UG, ZA, ZM, ZW)
* Glidiabet (PE)
* Glimel (AU, HK, SG)
* Glimide (MY)
* Glisulin (KP)
* Glitisol (BB, BM, BS, BZ, GY, HK, JM, NL, SR, TT)
* Gluben (IL)
* Glucal (MX)
* Glucobene (HU)
* Glucomid (BF, BJ, CI, ET, GH, GM, GN, KE, LR, MA, ML, MR, MU, MW, NE, NG, SC, SD, SL, SN, TN, TZ, UG, ZA, ZM, ZW)
* Gluconic (ID)
* Glulo (ID)
* Glyamid (ID)
* Glycomin (ZA)
* Glynase (BB, BM, BS, BZ, GY, JM, NL, SR, TT)
* Hemi-Daonil (AR, FR, MA, NL)
* Insol (PH)
* Lodulce (PH)
* Maninil (EE, PL)
* Manoglucon (TH)
* Melix (AE, BB, BF, BH, BJ, BM, BS, BZ, CI, CY, EG, ET, GH, GM, GN, GY, IL, IQ, IR, JM, JO, KE, KW, LB, LR, LY, MA, ML, MR, MU, MW, NE, NG, NL, OM, QA, SA, SC, SD, SL, SN, SR, SY, TN, TT, TZ, UG, YE, ZA, ZM, ZW)
* Miglucan (FR)
* Norboral (MX)
* Norglicem (ES)
* Orabetic (PH)
* Pira (AR)
* Renabetic (ID)
* Semi-Daonil (AE, AR, AU, BH, CH, CY, EG, GB, HK, ID, IE, IL, IQ, IR, JO, KW, LB, LY, MA, NZ, OM, PT, QA, SA, SY, YE)
* Semi-Euglucon (AR, AT, AU, NL, PH, TH)
* Sugril (TH)
* Tiabet (ID)
* Trodeb (ID)
* Unil-5 (TH)
* Xeltic (HK)
Glucovance Oral Uses
Glyburide is an anti-diabetic drug (sulfonylurea-type) used along with a proper diet and exercise program to control high blood sugar. It is used in patients with type 2 diabetes (non-insulin-dependent diabetes). It works by stimulating the release of your body's natural insulin. Effectively controlling high blood sugar helps prevent heart disease, strokes, kidney disease, blindness, and circulation problems, as well as sexual function problems (impotence).
How to use Glyburide Oral
Take this medication by mouth with breakfast or the first main meal, usually once daily; or use as directed by your doctor. Some patients, especially those taking higher doses, may be directed to take this drug twice a day. The dosage is based on your medical condition and response to therapy.
Use this medication regularly in order to get the most benefit from it. To help you remember, use it at the same time(s) each day. Monitor blood glucose levels on a regular basis. Inform your doctor if your blood glucose measurements are too high or too low.
How to use Glyburide Oral
Take this medication by mouth with breakfast or the first main meal, usually once daily; or use as directed by your doctor. Some patients, especially those taking higher doses, may be directed to take this drug twice a day. The dosage is based on your medical condition and response to therapy.
Use this medication regularly in order to get the most benefit from it. To help you remember, use it at the same time(s) each day. Monitor blood glucose levels on a regular basis. Inform your doctor if your blood glucose measurements are too high or too low.
GLUCOVANCE - Drug Description
GLUCOVANCE® (Glyburide and Metformin HCl Tablets) contains two oral antihyper-glycemic drugs used in the management of type 2 diabetes, glyburide and metformin hydrochloride.
Glyburide is an oral antihyperglycemic drug of the sulfonylurea class. The chemical name for glyburide is 1-[[p-[2-(5-chloro-o-anisamido)ethyl]phenyl]sulfonyl]-3-cyclo-hexylurea. Glyburide is a white to off-white crystalline compound with a molecular formula of C23H28ClN3O5S and a molecular weight of 494.01. The glyburide used in GLUCOVANCE has a particle size distribution of 25% undersize value not more than 6 µm, 50% undersize value not more than 7-10 µm, and 75% undersize value not more than 21 µm. The structural formula is represented below.
GLUCOVANCE® (Glyburide and Metformin HCl Tablets) Structural Formula Illustration
Metformin hydrochloride is an oral antihyperglycemic drug used in the management of type 2 diabetes. Metformin hydrochloride (N,N-dimethylimidodicarbonimidic diamide monohydrochloride) is not chemically or pharmacologically related to sulfonylureas, thiazolidinediones, or α-glucosidase inhibitors. It is a white to off-white crystalline compound with a molecular formula of C4H12ClN5 (monohydrochloride) and a molecular weight of 165.63. Metformin hydrochloride is freely soluble in water and is practically insoluble in acetone, ether, and chloroform. The pKa of metformin is 12.4. The pH of a 1% aqueous solution of metformin hydrochloride is 6.68. The structural formula is as shown:
GLUCOVANCE® (Glyburide and Metformin HCl Tablets) Structural Formula Illustration
GLUCOVANCE is available for oral administration in tablets containing 1.25 mg glyburide with 250 mg metformin hydrochloride, 2.5 mg glyburide with 500 mg metformin hydrochloride, and 5 mg glyburide with 500 mg metformin hydrochloride. In addition, each tablet contains the following inactive ingredients: microcrystalline cellulose, povidone, croscarmellose sodium, and magnesium stearate. The tablets are film coated, which provides color differentiation.
Glyburide is an oral antihyperglycemic drug of the sulfonylurea class. The chemical name for glyburide is 1-[[p-[2-(5-chloro-o-anisamido)ethyl]phenyl]sulfonyl]-3-cyclo-hexylurea. Glyburide is a white to off-white crystalline compound with a molecular formula of C23H28ClN3O5S and a molecular weight of 494.01. The glyburide used in GLUCOVANCE has a particle size distribution of 25% undersize value not more than 6 µm, 50% undersize value not more than 7-10 µm, and 75% undersize value not more than 21 µm. The structural formula is represented below.
GLUCOVANCE® (Glyburide and Metformin HCl Tablets) Structural Formula Illustration
Metformin hydrochloride is an oral antihyperglycemic drug used in the management of type 2 diabetes. Metformin hydrochloride (N,N-dimethylimidodicarbonimidic diamide monohydrochloride) is not chemically or pharmacologically related to sulfonylureas, thiazolidinediones, or α-glucosidase inhibitors. It is a white to off-white crystalline compound with a molecular formula of C4H12ClN5 (monohydrochloride) and a molecular weight of 165.63. Metformin hydrochloride is freely soluble in water and is practically insoluble in acetone, ether, and chloroform. The pKa of metformin is 12.4. The pH of a 1% aqueous solution of metformin hydrochloride is 6.68. The structural formula is as shown:
GLUCOVANCE® (Glyburide and Metformin HCl Tablets) Structural Formula Illustration
GLUCOVANCE is available for oral administration in tablets containing 1.25 mg glyburide with 250 mg metformin hydrochloride, 2.5 mg glyburide with 500 mg metformin hydrochloride, and 5 mg glyburide with 500 mg metformin hydrochloride. In addition, each tablet contains the following inactive ingredients: microcrystalline cellulose, povidone, croscarmellose sodium, and magnesium stearate. The tablets are film coated, which provides color differentiation.
What side effects may occur?
Side effects cannot be anticipated. If any develop or change in intensity, inform your doctor as soon as possible. Only your doctor can determine if it is safe for you to continue taking Glucovance.
* More common side effects may include:
Cold sweats, diarrhea, dizziness, headache, hunger, nausea, shakiness, stomach pain, upper respiratory infections, vomiting
* More common side effects may include:
Cold sweats, diarrhea, dizziness, headache, hunger, nausea, shakiness, stomach pain, upper respiratory infections, vomiting
Most important fact about Glucovance
Very rarely, Glucovance has been known to cause a dangerous condition called lactic acidosis, a buildup of lactic acid in the blood. Lactic acidosis is a medical emergency that requires immediate treatment in the hospital. Notify your doctor without delay if you experience any of the following symptoms:
A slow or irregular heartbeat; a cold, dizzy, or light-headed feeling; a weak, tired, or uncomfortable feeling; stomach discomfort; trouble breathing; unusual muscle pain
How should you take Glucovance?
Glucovance is taken once or twice a day with meals.
--If you miss a dose...
Take it as soon as you remember. If it is almost time for your next dose, skip the one you missed and go back to your regular schedule. Never take 2 doses at the same time.
--Storage instructions...
Store at room temperature and protect from light.
A slow or irregular heartbeat; a cold, dizzy, or light-headed feeling; a weak, tired, or uncomfortable feeling; stomach discomfort; trouble breathing; unusual muscle pain
How should you take Glucovance?
Glucovance is taken once or twice a day with meals.
--If you miss a dose...
Take it as soon as you remember. If it is almost time for your next dose, skip the one you missed and go back to your regular schedule. Never take 2 doses at the same time.
--Storage instructions...
Store at room temperature and protect from light.
Why Glucovance Prescribed?
Glucovance is used in the treatment of type 2 (noninsulin dependent) diabetes. Diabetes develops when the body's ability to burn sugar declines and the unused sugar builds up in the bloodstream. Ordinarily, sugar is moved out of the blood and into the body's cells by the hormone insulin. A buildup occurs when the body either fails to make enough insulin or doesn't respond to it properly.
Glucovance is a combination of 2 drugs--glyburide (DiaBeta, Micronase) and metformin (Glucophage)--that attack high blood sugar levels in several ways. The glyburide component stimulates the pancreas to produce more insulin and helps the body use it properly. The metformin component also encourages proper insulin utilization, and in addition works to decrease sugar production and absorption.
Glucovance is prescribed when diet and exercise prove insufficient to keep blood sugar levels under control. Glucovance can also be combined with other diabetes drugs such as Avandia.
Glucovance is a combination of 2 drugs--glyburide (DiaBeta, Micronase) and metformin (Glucophage)--that attack high blood sugar levels in several ways. The glyburide component stimulates the pancreas to produce more insulin and helps the body use it properly. The metformin component also encourages proper insulin utilization, and in addition works to decrease sugar production and absorption.
Glucovance is prescribed when diet and exercise prove insufficient to keep blood sugar levels under control. Glucovance can also be combined with other diabetes drugs such as Avandia.
Saturday, August 9, 2008
Your Lipid Profile
When doctors order a lab test called a lipid profile (sometimes called a lipid panel), they are looking for information about the amounts of four types of fats in the blood. You will be asked to give a small sample of blood from your arm. The results can help your doctor evaluate your risk for heart disease.
* Cholesterol helps the body form hormones, vitamin D and other important substances, but too much of it in the blood can clog and damage the blood vessels. Because it is a fat-like substance that doesn't mix with blood, cholesterol has to combine with proteins to form lipoproteins. Lipoproteins can travel in the blood to all the organs and tissues of the body.
* Low-density lipoproteins (LDLs, or "bad" cholesterol) build up in the blood and increase your risk of heart disease.
* High-density lipoproteins (HDLs, or "good" cholesterol) carry cholesterol to the liver, where it is removed from the body.
* Triglycerides store energy for your body to use when it is needed. If there is too much, it can block blood vessels and cause other health problems such as abdominal pain and pancreatitis.
It's important to know that the ranges listed below are the most common results, and apply mainly to people without existing medical problems. The ideal range for each person depends on individual risk factors, including conditions such as diabetes or heart disease. Your doctor will help you determine the levels that are healthiest for you.
Mg/dl means milligrams per deciliter. This is a way to measure tiny amounts of substances (a milligram is one-thousandth of a gram) in one deciliter (one-tenth of a liter) of your blood.
The symbol < means "less than."
The symbol > means "more than."
Total Cholesterol (lower is better)
Best = <200 mg/dL
Borderline high = 200-239 mg/dL
High = 240 mg/dL or higher
Triglycerides (lower is better)
Best = <150 mg/dL
Borderline high = 150-199 mg/dL
High = 200-499 mg/dL
Very high = 500 mg/dl or higher
LDL Cholesterol (lower is better)
Best = <100 mg/dL
Good = 100-129 mg/dL
Borderline high = 130-159 mg/dL
High = 160-189 mg/dL
Very high = 190 mg/dL or higher
HDL Cholesterol (higher is better)
Low = <40 mg/dL
Best = 60 mg/dL or higher
Risk Factors
Certain conditions or behaviors will increase your risk for heart disease. The major risk factors include:
* Smoking
* High blood pressure or on blood pressure medication
* Low HDL cholesterol
* Family history of early heart disease (heart disease in father or brother before age 55; heart disease in mother or sister before age 65)
* Age (men 45 years or older; women 55 years or older)
Some of these can be changed (like smoking or diet) and some cannot (like age or family history). You can ask your doctor for advice on how to change what you can.
If you already have some risk factors, your doctor might ask you to make changes to your lifestyle - like losing weight and exercising more - and/or recommend medications to lower your cholesterol.
Your doctor will most likely recommend lifestyle changes and consider drug therapy when:
* You are considered high risk because you already have heart disease.
* You are considered at moderately high risk of heart disease because you have 2 or more major risk factors in addition to other health conditions, and you have an LDL of 100 or more.
* You are considered at moderate risk of heart disease because you have two or more major risk factors and your LDL is 160 or more.
(If your LDL is 130 - 159, only lifestyle changes - not drug therapy - might be recommended.)
* You are considered at lower risk of heart disease because you have 0 or 1 risk factors and your LDL is 190 or more.
(If your LDL is 160 - 189, lifestyle changes will be recommended and drug therapy might be considered.)
* Cholesterol helps the body form hormones, vitamin D and other important substances, but too much of it in the blood can clog and damage the blood vessels. Because it is a fat-like substance that doesn't mix with blood, cholesterol has to combine with proteins to form lipoproteins. Lipoproteins can travel in the blood to all the organs and tissues of the body.
* Low-density lipoproteins (LDLs, or "bad" cholesterol) build up in the blood and increase your risk of heart disease.
* High-density lipoproteins (HDLs, or "good" cholesterol) carry cholesterol to the liver, where it is removed from the body.
* Triglycerides store energy for your body to use when it is needed. If there is too much, it can block blood vessels and cause other health problems such as abdominal pain and pancreatitis.
It's important to know that the ranges listed below are the most common results, and apply mainly to people without existing medical problems. The ideal range for each person depends on individual risk factors, including conditions such as diabetes or heart disease. Your doctor will help you determine the levels that are healthiest for you.
Mg/dl means milligrams per deciliter. This is a way to measure tiny amounts of substances (a milligram is one-thousandth of a gram) in one deciliter (one-tenth of a liter) of your blood.
The symbol < means "less than."
The symbol > means "more than."
Total Cholesterol (lower is better)
Best = <200 mg/dL
Borderline high = 200-239 mg/dL
High = 240 mg/dL or higher
Triglycerides (lower is better)
Best = <150 mg/dL
Borderline high = 150-199 mg/dL
High = 200-499 mg/dL
Very high = 500 mg/dl or higher
LDL Cholesterol (lower is better)
Best = <100 mg/dL
Good = 100-129 mg/dL
Borderline high = 130-159 mg/dL
High = 160-189 mg/dL
Very high = 190 mg/dL or higher
HDL Cholesterol (higher is better)
Low = <40 mg/dL
Best = 60 mg/dL or higher
Risk Factors
Certain conditions or behaviors will increase your risk for heart disease. The major risk factors include:
* Smoking
* High blood pressure or on blood pressure medication
* Low HDL cholesterol
* Family history of early heart disease (heart disease in father or brother before age 55; heart disease in mother or sister before age 65)
* Age (men 45 years or older; women 55 years or older)
Some of these can be changed (like smoking or diet) and some cannot (like age or family history). You can ask your doctor for advice on how to change what you can.
If you already have some risk factors, your doctor might ask you to make changes to your lifestyle - like losing weight and exercising more - and/or recommend medications to lower your cholesterol.
Your doctor will most likely recommend lifestyle changes and consider drug therapy when:
* You are considered high risk because you already have heart disease.
* You are considered at moderately high risk of heart disease because you have 2 or more major risk factors in addition to other health conditions, and you have an LDL of 100 or more.
* You are considered at moderate risk of heart disease because you have two or more major risk factors and your LDL is 160 or more.
(If your LDL is 130 - 159, only lifestyle changes - not drug therapy - might be recommended.)
* You are considered at lower risk of heart disease because you have 0 or 1 risk factors and your LDL is 190 or more.
(If your LDL is 160 - 189, lifestyle changes will be recommended and drug therapy might be considered.)
Lipid Profile
A blood test, or the results of a blood test, that measures levels of lipids, or fats, including cholesterol and triglycerides. Factors such as your age, sex, and genetics influence your lipid profile. Certain aspects of your lifestyle, including your diet, level of physical activity, level of diabetes control, and smoking status, also affect your lipid profile. And some medical conditions can raise or lower cholesterol and triglyceride levels.
A lipid profile is a direct measure of three blood components: cholesterol, triglycerides, and high-density lipoproteins (HDLs). Cholesterol is a vital substance that your body uses to produce such things as digestion-aiding material, hormones, and cell membranes. It is both produced by the body and absorbed from some of the foods you eat. Cholesterol and triglycerides are transported in the blood by combinations of lipids and proteins called lipoproteins. HDLs, the so-called "good" or "healthy" cholesterol, are lipoproteins made mostly of protein and little cholesterol. HDLs can help to clear cholesterol deposits in blood vessels left by another blood component called low-density lipoproteins, or LDLs.
LDL levels may be calculated from the three directly measured lipids or may be more accurately measured by a direct test. LDLs and very-low-density lipoproteins (VLDLs) are the so-called "bad" cholesterols. Unlike HDLs, LDLs and VLDLs are high-cholesterol particles. While cholesterol is necessary for various bodily functions, too much cholesterol is harmful, since excess cholesterol can be deposited in blood vessel walls. These fat deposits can lead to atherosclerosis, or hardening of the arteries, and cardiovascular disease, the number one killer in the United States. High levels of triglycerides are also associated with an increased risk of heart disease.
People with Type 1 diabetes whose blood glucose levels are controlled tend to have lipid levels similar to people who don't have diabetes and may even have higher levels of HDL, possibly because of the effects of insulin. People who have Type 2 diabetes, however, tend to have high levels of triglycerides and low HDL levels. And while people with Type 2 diabetes tend to have similar LDL levels as people who don't have diabetes, their LDL particles seem to be smaller and more prone to causing damage. Premenopausal women who do not have diabetes tend to have better cholesterol levels than men, but this protective effect seems to be negated in women with diabetes. Both sexes show an increase in lipoprotein levels as they age.
The American Diabetes Association (ADA) recommends that people with diabetes who have lipid levels that need correction have a lipid profile taken at least annually. Because alcohol and food intake before the test can cause temporary elevations of cholesterol and triglycerides, it is necessary to fast for 9-12 hours before the test and to abstain from alcohol for 24 hours before.
According to the ADA, low-risk cholesterol levels in adults with diabetes are LDL levels below 100 mg/dl, HDL levels above 40 mg/dl (above 50 mg/dl for women), and triglycerides below 150 mg/dl. If all your levels fall in these low-risk categories, you and your doctor may decide that you only need to have a lipid profile done every two years. People with diabetes who have cholesterol levels out of the low-risk ranges may be given a repeat test to verify the results.
A child with diabetes older than two years should be tested at the time of diagnosis if there is a family history of high cholesterol or heart disease or if family history is unknown. If there is no family history of high cholesterol or heart disease, the child should be tested at puberty. Children 12 and older who are diagnosed with diabetes should have a lipid profile done at the time of diagnosis and again after blood sugar levels have been brought under control. Subsequent checks of children need only be done every five years if levels are acceptable.
A lipid profile is a direct measure of three blood components: cholesterol, triglycerides, and high-density lipoproteins (HDLs). Cholesterol is a vital substance that your body uses to produce such things as digestion-aiding material, hormones, and cell membranes. It is both produced by the body and absorbed from some of the foods you eat. Cholesterol and triglycerides are transported in the blood by combinations of lipids and proteins called lipoproteins. HDLs, the so-called "good" or "healthy" cholesterol, are lipoproteins made mostly of protein and little cholesterol. HDLs can help to clear cholesterol deposits in blood vessels left by another blood component called low-density lipoproteins, or LDLs.
LDL levels may be calculated from the three directly measured lipids or may be more accurately measured by a direct test. LDLs and very-low-density lipoproteins (VLDLs) are the so-called "bad" cholesterols. Unlike HDLs, LDLs and VLDLs are high-cholesterol particles. While cholesterol is necessary for various bodily functions, too much cholesterol is harmful, since excess cholesterol can be deposited in blood vessel walls. These fat deposits can lead to atherosclerosis, or hardening of the arteries, and cardiovascular disease, the number one killer in the United States. High levels of triglycerides are also associated with an increased risk of heart disease.
People with Type 1 diabetes whose blood glucose levels are controlled tend to have lipid levels similar to people who don't have diabetes and may even have higher levels of HDL, possibly because of the effects of insulin. People who have Type 2 diabetes, however, tend to have high levels of triglycerides and low HDL levels. And while people with Type 2 diabetes tend to have similar LDL levels as people who don't have diabetes, their LDL particles seem to be smaller and more prone to causing damage. Premenopausal women who do not have diabetes tend to have better cholesterol levels than men, but this protective effect seems to be negated in women with diabetes. Both sexes show an increase in lipoprotein levels as they age.
The American Diabetes Association (ADA) recommends that people with diabetes who have lipid levels that need correction have a lipid profile taken at least annually. Because alcohol and food intake before the test can cause temporary elevations of cholesterol and triglycerides, it is necessary to fast for 9-12 hours before the test and to abstain from alcohol for 24 hours before.
According to the ADA, low-risk cholesterol levels in adults with diabetes are LDL levels below 100 mg/dl, HDL levels above 40 mg/dl (above 50 mg/dl for women), and triglycerides below 150 mg/dl. If all your levels fall in these low-risk categories, you and your doctor may decide that you only need to have a lipid profile done every two years. People with diabetes who have cholesterol levels out of the low-risk ranges may be given a repeat test to verify the results.
A child with diabetes older than two years should be tested at the time of diagnosis if there is a family history of high cholesterol or heart disease or if family history is unknown. If there is no family history of high cholesterol or heart disease, the child should be tested at puberty. Children 12 and older who are diagnosed with diabetes should have a lipid profile done at the time of diagnosis and again after blood sugar levels have been brought under control. Subsequent checks of children need only be done every five years if levels are acceptable.
Saturday, August 2, 2008
Comparison of Glyburide
A direct comparison of glyburide and pioglitazone monotherapy among patients with recently diagnosed type 2 diabetes mellitus demonstrated that pioglitazone is a safe and effective first-line treatment for long-term use. The overall tolerability, adverse-effect profile, and improved level of glycemic control with glyburide and pioglitazone in this trial are consistent with those of previous reports that compared sulfonylureas and thiazolidinediones.[14-16]
After 56 weeks of treatment, glycemic control based on A1C was comparable between the glyburide and pioglitazone groups. However, the profile of A1C measurements from 16-56 weeks suggests a trend of deteriorating glycemic control in the glyburide group and sustained glycemic control in the pioglitazone group. Although these trends are subtle, this observation is consistent with that of reports comparing pioglitazone and gliclazide[14,15] as well as reports on sulfonylurea therapy in the United Kingdom Prospective Diabetes Study (UKPDS).[16] Because these trials enrolled only patients with recently diagnosed type 2 diabetes mellitus, one possibility for deteriorating glycemic control with sulfonylurea monotherapy may have been declining β-cell function with disease progression. The A1C profile from the current study suggests that pioglitazone sustains its efficacy over a longer time than do sulfonylureas and indicates possible β-cell-sparing effects with pioglitazone.[17] Consistent with this possibility, early discontinuation of treatment was greater with glyburide than pioglitazone monotherapy, which in part was attributable to lack of therapeutic efficacy.
The frequency of adverse events leading to study drug discontinuation was also higher with glyburide than pioglitazone. Not unexpectedly, hypoglycemia was the most common adverse event leading to glyburide treatment discontinuation. Adverse events typically attributed to thiazolidinedione therapy, such as edema and weight gain, were observed with both treatments during this trial. Although edema affecting the extremities was reported by more patients treated with pioglitazone than with glyburide, each event was classified as mild or moderate, except one case of severe edema in a pioglitazone-treated patient. The weight increase observed with either treatment is also consistent with results reported in other controlled clinical trials and is a known adverse effect of both drugs.[13] Several interrelated factors, including decreased glycosuria and caloric retention with improved glycemic control, expansion of the subcutaneous fat depot, and fluid retention have been suggested explanations for weight gain with thiazolidinediones.[18]
Overall, a greater mean decrease in ALT was noted with pioglitazone than with glyburide. In addition, a higher proportion of patients treated with glyburide exceeded the upper limit of normal for ALT at the final visit compared with patients treated with pioglitazone. Together these findings support previous reports that pioglitazone reduces hepatic fat content and is not associated with hepatotoxic adverse effects.19
Although this study was not powered to evaluate cardiac outcomes, the frequency of cardiac disorders was 2-fold greater in glyburide than pioglitazone treated patients. Of note, congestive heart failure was reported in only two patients in the trial, one in each treatment group. However, patients with New York Heart Association class III or IV cardiac disorders were not included in this trial.
Interpretation of the study results is limited by the high rate of patient withdrawal. However, the rate of attrition likely did not introduce a selection bias, as an equivalent number of subjects in each treatment group (glyburide 49.0%, pioglitazone 46.6%) withdrew from the study before week 56. Another limitation of this study is that patients were not treated with exactly comparable doses of pioglitazone and glyburide. Patients in the pioglitazone group were taking a mean daily dose of approximately 36 mg (maximum recommended dose 45 mg), whereas patients in the glyburide group were taking a mean daily dose of approximately 10 mg (maximum recommended dose 20 mg). However, since this study was designed as a treat-to-target study, investigators were instructed to adjust the study drug dosage as necessary to achieve and maintain a fasting plasma glucose level between 69 and 141 mg/dl. The observation that glycemic control was equivalent between groups indicates that the investigators complied with this objective.
After 56 weeks of treatment, glycemic control based on A1C was comparable between the glyburide and pioglitazone groups. However, the profile of A1C measurements from 16-56 weeks suggests a trend of deteriorating glycemic control in the glyburide group and sustained glycemic control in the pioglitazone group. Although these trends are subtle, this observation is consistent with that of reports comparing pioglitazone and gliclazide[14,15] as well as reports on sulfonylurea therapy in the United Kingdom Prospective Diabetes Study (UKPDS).[16] Because these trials enrolled only patients with recently diagnosed type 2 diabetes mellitus, one possibility for deteriorating glycemic control with sulfonylurea monotherapy may have been declining β-cell function with disease progression. The A1C profile from the current study suggests that pioglitazone sustains its efficacy over a longer time than do sulfonylureas and indicates possible β-cell-sparing effects with pioglitazone.[17] Consistent with this possibility, early discontinuation of treatment was greater with glyburide than pioglitazone monotherapy, which in part was attributable to lack of therapeutic efficacy.
The frequency of adverse events leading to study drug discontinuation was also higher with glyburide than pioglitazone. Not unexpectedly, hypoglycemia was the most common adverse event leading to glyburide treatment discontinuation. Adverse events typically attributed to thiazolidinedione therapy, such as edema and weight gain, were observed with both treatments during this trial. Although edema affecting the extremities was reported by more patients treated with pioglitazone than with glyburide, each event was classified as mild or moderate, except one case of severe edema in a pioglitazone-treated patient. The weight increase observed with either treatment is also consistent with results reported in other controlled clinical trials and is a known adverse effect of both drugs.[13] Several interrelated factors, including decreased glycosuria and caloric retention with improved glycemic control, expansion of the subcutaneous fat depot, and fluid retention have been suggested explanations for weight gain with thiazolidinediones.[18]
Overall, a greater mean decrease in ALT was noted with pioglitazone than with glyburide. In addition, a higher proportion of patients treated with glyburide exceeded the upper limit of normal for ALT at the final visit compared with patients treated with pioglitazone. Together these findings support previous reports that pioglitazone reduces hepatic fat content and is not associated with hepatotoxic adverse effects.19
Although this study was not powered to evaluate cardiac outcomes, the frequency of cardiac disorders was 2-fold greater in glyburide than pioglitazone treated patients. Of note, congestive heart failure was reported in only two patients in the trial, one in each treatment group. However, patients with New York Heart Association class III or IV cardiac disorders were not included in this trial.
Interpretation of the study results is limited by the high rate of patient withdrawal. However, the rate of attrition likely did not introduce a selection bias, as an equivalent number of subjects in each treatment group (glyburide 49.0%, pioglitazone 46.6%) withdrew from the study before week 56. Another limitation of this study is that patients were not treated with exactly comparable doses of pioglitazone and glyburide. Patients in the pioglitazone group were taking a mean daily dose of approximately 36 mg (maximum recommended dose 45 mg), whereas patients in the glyburide group were taking a mean daily dose of approximately 10 mg (maximum recommended dose 20 mg). However, since this study was designed as a treat-to-target study, investigators were instructed to adjust the study drug dosage as necessary to achieve and maintain a fasting plasma glucose level between 69 and 141 mg/dl. The observation that glycemic control was equivalent between groups indicates that the investigators complied with this objective.
Metformin Hydrochloride
Lactic acidosis
Lactic acidosis is a rare, but serious, metabolic complication that can occur due to metformin accumulation during treatment with glyburide and metformin hydrochloride; when it occurs, it is fatal in approximately 50% of cases. Lactic acidosis may also occur in association with a number of pathophysiologic conditions, including diabetes mellitus, and whenever there is significant tissue hypoperfusion and hypoxemia. Lactic acidosis is characterized by elevated blood lactate levels (> 5 mmol/L), decreased blood pH, electrolyte disturbances with an increased anion gap, and an increased lactate/pyruvate ratio. When metformin is implicated as the cause of lactic acidosis, metformin plasma levels > 5 mcg/mL are generally found.
The reported incidence of lactic acidosis in patients receiving metformin hydrochloride is very low (approximately 0.03 cases/1000 patient-years, with approximately 0.015 fatal cases/1000 patient-years). Reported cases have occurred primarily in diabetic patients with significant renal insufficiency, including both intrinsic renal disease and renal hypoperfusion, often in the setting of multiple concomitant medical/surgical problems and multiple concomitant medications. Patients with congestive heart failure requiring pharmacologic management, in particular those with unstable or acute congestive heart failure who are at risk of hypoperfusion and hypoxemia, are at increased risk of lactic acidosis. The risk of lactic acidosis increases with the degree of renal dysfunction and the patient’s age. The risk of lactic acidosis may, therefore, be significantly decreased by regular monitoring of renal function in patients taking metformin and by use of the minimum effective dose of metformin. In particular, treatment of the elderly should be accompanied by careful monitoring of renal function. Glyburide and metformin hydrochloride treatment should not be initiated in patients ≥ 80 years of age unless measurement of creatinine clearance demonstrates that renal function is not reduced, as these patients are more susceptible to developing lactic acidosis. In addition, glyburide and metformin hydrochloride should be promptly withheld in the presence of any condition associated with hypoxemia, dehydration, or sepsis. Because impaired hepatic function may significantly limit the ability to clear lactate, glyburide and metformin hydrochloride should generally be avoided in patients with clinical or laboratory evidence of hepatic disease. Patients should be cautioned against excessive alcohol intake, either acute or chronic, when taking glyburide and metformin hydrochloride, since alcohol potentiates the effects of metformin hydrochloride on lactate metabolism. In addition, glyburide and metformin hydrochloride should be temporarily discontinued prior to any intravascular radiocontrast study and for any surgical procedure (see also PRECAUTIONS).
The onset of lactic acidosis often is subtle, and accompanied only by nonspecific symptoms such as malaise, myalgias, respiratory distress, increasing somnolence and nonspecific abdominal distress. There may be associated hypothermia, hypotension, and resistant bradyarrhythmias with more marked acidosis. The patient and the patient’s physician must be aware of the possible importance of such symptoms and the patient should be instructed to notify the physician immediately if they occur (see also PRECAUTIONS). Glyburide and metformin hydrochloride tablets should be withdrawn until the situation is clarified. Serum electrolytes, ketones, blood glucose, and, if indicated, blood pH, lactate levels, and even blood metformin levels may be useful. Once a patient is stabilized on any dose level of glyburide and metformin hydrochloride, gastrointestinal symptoms, which are common during initiation of therapy with metformin, are unlikely to be drug related. Later occurrence of gastrointestinal symptoms could be due to lactic acidosis or other serious disease.
Levels of fasting venous plasma lactate above the upper limit of normal but less than 5 mmol/L in patients taking glyburide and metformin hydrochloride do not necessarily indicate impending lactic acidosis and may be explainable by other mechanisms, such as poorly controlled diabetes or obesity, vigorous physical activity, or technical problems in sample handling. (See also PRECAUTIONS.)
Lactic acidosis should be suspected in any diabetic patient with metabolic acidosis lacking evidence of ketoacidosis (ketonuria and ketonemia).
Lactic acidosis is a medical emergency that must be treated in a hospital setting. In a patient with lactic acidosis who is taking glyburide and metformin hydrochloride, the drug should be discontinued immediately and general supportive measures promptly instituted. Because metformin hydrochloride is dialyzable (with a clearance of up to 170 mL/min under good hemodynamic conditions), prompt hemodialysis is recommended to correct the acidosis and remove the accumulated metformin. Such management often results in prompt reversal of symptoms and recovery. (See also CONTRAINDICATIONS and PRECAUTIONS).
Lactic acidosis is a rare, but serious, metabolic complication that can occur due to metformin accumulation during treatment with glyburide and metformin hydrochloride; when it occurs, it is fatal in approximately 50% of cases. Lactic acidosis may also occur in association with a number of pathophysiologic conditions, including diabetes mellitus, and whenever there is significant tissue hypoperfusion and hypoxemia. Lactic acidosis is characterized by elevated blood lactate levels (> 5 mmol/L), decreased blood pH, electrolyte disturbances with an increased anion gap, and an increased lactate/pyruvate ratio. When metformin is implicated as the cause of lactic acidosis, metformin plasma levels > 5 mcg/mL are generally found.
The reported incidence of lactic acidosis in patients receiving metformin hydrochloride is very low (approximately 0.03 cases/1000 patient-years, with approximately 0.015 fatal cases/1000 patient-years). Reported cases have occurred primarily in diabetic patients with significant renal insufficiency, including both intrinsic renal disease and renal hypoperfusion, often in the setting of multiple concomitant medical/surgical problems and multiple concomitant medications. Patients with congestive heart failure requiring pharmacologic management, in particular those with unstable or acute congestive heart failure who are at risk of hypoperfusion and hypoxemia, are at increased risk of lactic acidosis. The risk of lactic acidosis increases with the degree of renal dysfunction and the patient’s age. The risk of lactic acidosis may, therefore, be significantly decreased by regular monitoring of renal function in patients taking metformin and by use of the minimum effective dose of metformin. In particular, treatment of the elderly should be accompanied by careful monitoring of renal function. Glyburide and metformin hydrochloride treatment should not be initiated in patients ≥ 80 years of age unless measurement of creatinine clearance demonstrates that renal function is not reduced, as these patients are more susceptible to developing lactic acidosis. In addition, glyburide and metformin hydrochloride should be promptly withheld in the presence of any condition associated with hypoxemia, dehydration, or sepsis. Because impaired hepatic function may significantly limit the ability to clear lactate, glyburide and metformin hydrochloride should generally be avoided in patients with clinical or laboratory evidence of hepatic disease. Patients should be cautioned against excessive alcohol intake, either acute or chronic, when taking glyburide and metformin hydrochloride, since alcohol potentiates the effects of metformin hydrochloride on lactate metabolism. In addition, glyburide and metformin hydrochloride should be temporarily discontinued prior to any intravascular radiocontrast study and for any surgical procedure (see also PRECAUTIONS).
The onset of lactic acidosis often is subtle, and accompanied only by nonspecific symptoms such as malaise, myalgias, respiratory distress, increasing somnolence and nonspecific abdominal distress. There may be associated hypothermia, hypotension, and resistant bradyarrhythmias with more marked acidosis. The patient and the patient’s physician must be aware of the possible importance of such symptoms and the patient should be instructed to notify the physician immediately if they occur (see also PRECAUTIONS). Glyburide and metformin hydrochloride tablets should be withdrawn until the situation is clarified. Serum electrolytes, ketones, blood glucose, and, if indicated, blood pH, lactate levels, and even blood metformin levels may be useful. Once a patient is stabilized on any dose level of glyburide and metformin hydrochloride, gastrointestinal symptoms, which are common during initiation of therapy with metformin, are unlikely to be drug related. Later occurrence of gastrointestinal symptoms could be due to lactic acidosis or other serious disease.
Levels of fasting venous plasma lactate above the upper limit of normal but less than 5 mmol/L in patients taking glyburide and metformin hydrochloride do not necessarily indicate impending lactic acidosis and may be explainable by other mechanisms, such as poorly controlled diabetes or obesity, vigorous physical activity, or technical problems in sample handling. (See also PRECAUTIONS.)
Lactic acidosis should be suspected in any diabetic patient with metabolic acidosis lacking evidence of ketoacidosis (ketonuria and ketonemia).
Lactic acidosis is a medical emergency that must be treated in a hospital setting. In a patient with lactic acidosis who is taking glyburide and metformin hydrochloride, the drug should be discontinued immediately and general supportive measures promptly instituted. Because metformin hydrochloride is dialyzable (with a clearance of up to 170 mL/min under good hemodynamic conditions), prompt hemodialysis is recommended to correct the acidosis and remove the accumulated metformin. Such management often results in prompt reversal of symptoms and recovery. (See also CONTRAINDICATIONS and PRECAUTIONS).
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