GLYE-bure-ide, met-FOR-min hye-droe-KLOR-ideOral routeTablet
Lactic acidosis is a rare, but serious, metabolic complication that can occur due to metformin accumulation during treatment with glyburide/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 (greater than 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 greater than 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). In more than 20,000 patient-years exposure to metformin in clinical trials, there were no reports of lactic acidosis. 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/metformin hydrochloride treatment should not be initiated in patients greater than or equal to 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/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/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/metformin hydrochloride, since alcohol potentiates the effects of metformin hydrochloride on lactate metabolism. In addition, glyburide/metformin hydrochloride should be temporarily discontinued prior to any intravascular radiocontrast study and for any surgical procedure.
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. Glyburide/metformin hydrochloride 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/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/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.
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/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 .
Lactic acidosis is a rare, but serious, metabolic complication that can occur due to metformin accumulation during treatment with glyburide/metformin hydrochloride; when it occurs, it is fatal in approximately 50% of cases. The risk of lactic acidosis increases with renal impairment, increased age, diabetes mellitus, congestive heart failure, hepatic insufficiency, and other conditions whenever there is significant tissue hypoperfusion and hypoxemia. Treatment with glyburide/metformin hydrochloride should not be initiated in patients 80 years of age or older unless measurement of creatinine clearance demonstrates that renal function is normal. Therapy should temporarily be discontinued prior to any intravascular radiocontrast study or surgical procedure. Avoid excessive alcohol use since alcohol potentiates the effects of metformin on lactate metabolism. Discontinue therapy immediately and institute supportive measures promptly for suspected lactic acidosis .
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In the U.S.
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Therapeutic Class: Hypoglycemic, Biguanide/Sulfonylurea Combination
Chemical Class: 2nd Generation Sulfonylurea
Glyburide and metformin combination is used to treat high blood sugar levels caused by a type of diabetes mellitus (sugar diabetes) called type 2 diabetes. Normally, after you eat, your pancreas releases insulin to help your body store excess sugar for later use. This process occurs during normal digestion of food. In type 2 diabetes, your body does not work properly to store excess sugar and the sugar remains in your bloodstream. Chronic high blood sugar can lead to serious health problems in the future.
Proper diet is the first step in managing type 2 diabetes, but often medicines are needed to help your body. With two actions, the combination of glyburide and metformin helps your body cope with high blood sugar. Glyburide causes your pancreas to release more insulin into the bloodstream. Metformin reduces the absorption of sugar, reduces the release of stored sugar from the liver, and helps your body's cells use sugar better.
glyburide and metformin is available only with your doctor's prescription.
In deciding to use a medicine, the risks of taking the medicine must be weighed against the good it will do. This is a decision you and your doctor will make. For glyburide and metformin, the following should be considered:
Tell your doctor if you have ever had any unusual or allergic reaction to glyburide and metformin or any other medicines. Also tell your health care professional if you have any other types of allergies, such as to foods, dyes, preservatives, or animals. For non-prescription products, read the label or package ingredients carefully.
Appropriate studies have not been performed on the relationship of age to the effects of glyburide and metformin combination in the pediatric population. Safety and efficacy have not been established.
Appropriate studies performed to date have not demonstrated geriatric-specific problems that would limit the usefulness of glyburide and metformin combination in the elderly. However, elderly patients are more likely to have age-related kidney problems which may require an adjustment of dosage in patients receiving glyburide and metformin combination.
|All Trimesters||B||Animal studies have revealed no evidence of harm to the fetus, however, there are no adequate studies in pregnant women OR animal studies have shown an adverse effect, but adequate studies in pregnant women have failed to demonstrate a risk to the fetus.|
There are no adequate studies in women for determining infant risk when using this medication during breastfeeding. Weigh the potential benefits against the potential risks before taking this medication while breastfeeding.
Using glyburide and metformin with any of the following medicines is not recommended. Your doctor may decide not to treat you with this medication or change some of the other medicines you take.
Using glyburide and metformin with any of the following medicines is usually not recommended, but may be required in some cases. If both medicines are prescribed together, your doctor may change the dose or how often you use one or both of the medicines.
Using glyburide and metformin with any of the following medicines may cause an increased risk of certain side effects, but using both drugs may be the best treatment for you. If both medicines are prescribed together, your doctor may change the dose or how often you use one or both of the medicines.
Certain medicines should not be used at or around the time of eating food or eating certain types of food since interactions may occur. Using alcohol or tobacco with certain medicines may also cause interactions to occur. Discuss with your healthcare professional the use of your medicine with food, alcohol, or tobacco.
Using glyburide and metformin with any of the following is usually not recommended, but may be unavoidable in some cases. If used together, your doctor may change the dose or how often you use glyburide and metformin, or give you special instructions about the use of food, alcohol, or tobacco.
The presence of other medical problems may affect the use of glyburide and metformin. Make sure you tell your doctor if you have any other medical problems, especially:
Follow carefully the special meal plan your doctor gave you. This is the most important part of controlling your condition, and is necessary if the medicine is to work properly. Also, exercise regularly and test for sugar in your blood or urine as directed.
Glyburide and metformin combination should be taken with meals to help reduce the gastrointestinal side effects that may occur during the first few weeks of treatment.
The dose of glyburide and metformin will be different for different patients. Follow your doctor's orders or the directions on the label. The following information includes only the average doses of glyburide and metformin. If your dose is different, do not change it unless your doctor tells you to do so.
The amount of medicine that you take depends on the strength of the medicine. Also, the number of doses you take each day, the time allowed between doses, and the length of time you take the medicine depend on the medical problem for which you are using the medicine.
If you miss a dose of glyburide and metformin, take it as soon as possible. However, if it is almost time for your next dose, skip the missed dose and go back to your regular dosing schedule. Do not double doses.
Store the medicine in a closed container at room temperature, away from heat, moisture, and direct light. Keep from freezing.
Keep out of the reach of children.
Do not keep outdated medicine or medicine no longer needed.
Ask your healthcare professional how you should dispose of any medicine you do not use.
It is very important that your doctor check your progress at regular visits to make sure glyburide and metformin is working properly. Blood tests may be needed to check for unwanted effects.
Under certain conditions, too much metformin can cause lactic acidosis. Symptoms of lactic acidosis are severe and quick to appear and usually occur when other health problems not related to the medicine are present and are very severe, such as a heart attack or kidney failure. Symptoms of lactic acidosis include abdominal or stomach discomfort; decreased appetite; diarrhea; fast, shallow breathing; general feeling of discomfort; muscle pain or cramping; and unusual sleepiness, tiredness, or weakness.
If symptoms of lactic acidosis occur, you should get immediate emergency medical help.
It is very important to follow carefully any instructions from your health care team about:
Check with your doctor right away if you start having chest pain or discomfort; nausea; pain or discomfort in arms, jaw, back, or neck; shortness of breath; sweating; or vomiting while you are using glyburide and metformin. These may be symptoms of a serious heart problem, including a heart attack.
Glyburide and metformin combination can cause low blood sugar. However, it also can occur if you delay or miss a meal or snack, drink alcohol, exercise more than usual, cannot eat because of nausea or vomiting, take certain medicines, or take glyburide and metformin with another type of diabetes medicine. Symptoms of low blood sugar must be treated before they lead to unconsciousness (passing out). Different people feel different symptoms of low blood sugar. It is important that you learn which symptoms of low blood sugar you usually have so that you can treat it quickly and call someone on your healthcare team right away when you need advice.
Symptoms of hypoglycemia (low blood sugar) include anxiety; behavior change similar to being drunk; blurred vision; cold sweats; confusion; cool, pale skin; difficulty in thinking; drowsiness; excessive hunger; fast heartbeat; headache (continuing); nausea; nervousness; nightmares; restless sleep; shakiness; slurred speech; or unusual tiredness or weakness.
If symptoms of low blood sugar occur, eat glucose tablets or gel, corn syrup, honey, or sugar cubes; or drink fruit juice, non-diet soft drink, or sugar dissolved in water. Also, check your blood for low blood sugar. Glucagon is used in emergency situations when severe symptoms such as seizures (convulsions) or unconsciousness occur. Have a glucagon kit available, along with a syringe or needle, and know how to use it. Members of your household also should know how to use it.
Symptoms of hyperglycemia (high blood sugar) include blurred vision; drowsiness; dry mouth; flushed, dry skin; fruit-like breath odor; increased urination (frequency and volume); ketones in urine; loss of appetite; sleepiness; stomachache, nausea, or vomiting; tiredness; troubled breathing (rapid and deep); unconsciousness; or unusual thirst.
High blood sugar may occur if you do not exercise as much as usual, have a fever or infection, do not take enough or skip a dose of your diabetes medicine, or overeat or do not follow your meal plan.
If symptoms of high blood sugar occur, check your blood sugar level and then call your health care professional for instructions.
glyburide and metformin may interact with the dye used for an X-ray or CT scan. Your doctor should advise you to stop taking it before you have any medical exams or diagnostic tests that might cause less urine output than usual. You may be advised to start taking the medicine again 48 hours after the exams or tests if your kidney function is tested and found to be normal.
Do not take glyburide and metformin if you are also using bosentan (Tracleer®). Also, make sure your doctor knows about all other medicines you are using for diabetes, including insulin.
Along with its needed effects, a medicine may cause some unwanted effects. Although not all of these side effects may occur, if they do occur they may need medical attention.
Check with your doctor immediately if any of the following side effects occur:More common
Some side effects may occur that usually do not need medical attention. These side effects may go away during treatment as your body adjusts to the medicine. Also, your health care professional may be able to tell you about ways to prevent or reduce some of these side effects. Check with your health care professional if any of the following side effects continue or are bothersome or if you have any questions about them:More common
Other side effects not listed may also occur in some patients. If you notice any other effects, check with your healthcare professional.
Call your doctor for medical advice about side effects. You may report side effects to the FDA at 1-800-FDA-1088.
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