Generic Name: metformin (Oral route)
Lactic acidosis is a rare, but serious, metabolic complication that can occur due to metformin accumulation during treatment with 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 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 hydrochloride and by use of the minimum effective dose of metformin hydrochloride. In particular, treatment of the elderly should be accompanied by careful monitoring of renal function. 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, 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, 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 metformin hydrochloride, since alcohol potentiates the effects of metformin hydrochloride on lactate metabolism. In addition, 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. 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 metformin hydrochloride, gastrointestinal symptoms, which are common during initiation of therapy, 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 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 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 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 metformin 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 .
Commonly used brand name(s):
In the U.S.
Available Dosage Forms:
Therapeutic Class: Hypoglycemic
Chemical Class: Biguanide
Metformin is used to treat a type of diabetes mellitus (sugar diabetes) called type 2 diabetes. With this type of diabetes, insulin produced by the pancreas is not able to get sugar into the cells of the body where it can work properly. Using metformin alone, with a type of oral antidiabetic medicine called a sulfonylurea, or with insulin will help to lower blood sugar when it is too high and help restore the way you use food to make energy.
Many people can control type 2 diabetes with diet alone or diet and exercise. Following a specially planned diet and exercising will always be important when you have diabetes, even when you are taking medicines. To work properly, the amount of metformin you take must be balanced against the amount and type of food you eat and the amount of exercise you do. If you change your diet, your exercise, or both, you will want to test your blood sugar to find out if it is too low. Your doctor will teach you what to do if this happens.
At some point, this medicine may stop working as well and your blood glucose will increase. You will need to know if this happens and what to do. Instead of taking more of this medicine, your doctor may want you to change to another antidiabetic medicine. If that does not lower your blood sugar, your doctor may have you stop taking the medicine and begin receiving insulin injections instead.
Metformin does not help patients who have insulin-dependent or type 1 diabetes because they cannot produce insulin from their pancreas gland. Their blood glucose is best controlled by insulin injections.
Metformin is available only with your doctor's prescription.
Once a medicine has been approved for marketing for a certain use, experience may show that it is also useful for other medical problems. Although this use is not included in product labeling, metformin is used in certain patients with the following medical conditions:
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 this medicine, the following should be considered:
Tell your doctor if you have ever had any unusual or allergic reaction to this medicine 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 performed to date have not demonstrated pediatric-specific problems that would limit the usefulness of metformin tablets in children 10 years old and above. However, safety and efficacy of metformin extended-release tablets in the pediatric population have not been established.
Although appropriate studies on the relationship of age to the effects of metformin have not been performed in the geriatric population, geriatric-specific problems are not expected to limit the usefulness of metformin 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 metformin.
|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.|
Studies in women suggest that this medication poses minimal risk to the infant when used during breastfeeding.
Using this medicine 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 this medicine 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 this medicine 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.
The presence of other medical problems may affect the use of this medicine. Make sure you tell your doctor if you have any other medical problems, especially:
This section provides information on the proper use of a number of products that contain metformin. It may not be specific to Glucophage XR. Please read with care.
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.
Metformin should be taken with meals to help reduce the stomach and intestinal side effects that may occur while you are taking this medicine.
Swallow the extended-release tablet whole. Do not split, crush, or chew it.
If you are taking the extended-release tablet, part of the tablet may pass into your stool after your body has absorbed the medicine. This is normal and nothing to worry about.
The dose of this medicine 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 this medicine. 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 this medicine, 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 that this medicine is working properly. Blood tests may be needed to check for unwanted effects.
It is very important to follow carefully any instructions from your health care team about:
In case of emergency—There may be a time when you need emergency help for a problem caused by your diabetes. You need to be prepared for these emergencies. It is a good idea to wear a medical identification (ID) bracelet or neck chain at all times. Also, carry an ID card in your wallet or purse that says that you have diabetes and a list of all of your medicines.
If you are scheduled to have surgery or medical tests that involve x-rays, you should tell your doctor that you are taking metformin. Your doctor will instruct you to stop taking metformin until at least 2 days after the surgery or medical tests. During this time, if your blood sugar cannot be controlled by diet and exercise, you may be advised to take insulin.
Too much metformin, under certain conditions, 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 include diarrhea, fast and shallow breathing, severe muscle pain or cramping, unusual sleepiness, and unusual tiredness or weakness.
If symptoms of lactic acidosis occur, you should check your blood sugar and get immediate emergency medical help. Also, tell your doctor if severe vomiting occurs.
Metformin can cause low blood sugar (hypoglycemia). 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 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.
Symptoms of 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.
High blood sugar (hyperglycemia) is another problem related to uncontrolled diabetes. Symptoms of mild high blood sugar appear more slowly than those of low blood sugar. These may include blurred vision; drowsiness; dry mouth; flushed, dry skin; fruit-like breath odor; increased urination (frequency and amount); 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 doctor for instructions.
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:Rare
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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