What happens if I overdose Metformin?
Contact 1-800-222-1222 (the American Association of Poison Control Centers), your local poison control center, or emergency room immediately. Symptoms may include dizziness or light-headedness; fast or difficult breathing; feeling of being unusually cold; general feeling of being unwell; muscle pain or tenderness; slow or irregular heartbeat; unusual drowsiness; unusual stomach discomfort; unusual weakness or tiredness.
Proper storage of Metformin extended-release tablets:
Store Metformin extended-release tablets at room temperature, between 68 and 77 degrees F (20 and 25 degrees C). Brief storage at temperatures between 59 and 86 degrees F (15 and 30 degrees C) is permitted. Store away from heat, moisture, and light. Do not store in the bathroom. Keep Metformin extended-release tablets out of the reach of children and away from pets.
Overdose of Metformin in details
Overdose of Metformin has occurred, including ingestion of amounts >50 g. Hypoglycemia was reported in approximately 10% of cases, but no causal association with Metformin has been established. Lactic acidosis has been reported in approximately 32% of Metformin overdose cases. High overdose of Metformin or concomitant risks may lead to lactic acidosis. Lactic acidosis is a medical emergency and must be treated in the hospital. The most effective method to remove lactate and Metformin is haemodialysis. Metformin is dialyzable with a clearance of up to 170 mL/min under good homodynamic conditions. Therefore, hemodialysis may be useful for removal of accumulated drug from patients in whom Metformin overdosage is suspected.
What should I avoid while taking Metformin?
Avoid drinking alcohol. It lowers blood sugar and may increase your risk of lactic acidosis while taking Metformin.
Metformin warnings
Do not use Metformin if you have kidney disease, or if you are in a state of diabetic ketoacidosis (call your doctor for treatment with insulin).
Before taking Metformin, tell your doctor if you have liver disease or a history of heart disease.
Some people have developed a life-threatening condition called lactic acidosis while taking Metformin. Get emergency medical help if you have any of these symptoms of lactic acidosis: weakness, increasing sleepiness, slow heart rate, cold feeling, muscle pain, shortness of breath, stomach pain, feeling light-headed, and fainting.
If you need to have any type of x-ray or CT scan using a dye that is injected into a vein, you may need to temporarily stop taking Metformin. Be sure the doctor knows ahead of time that you are using Metformin.
Know the signs of low blood sugar (hypoglycemia) and how to recognize them, including hunger, headache, confusion, irritability, drowsiness, weakness, dizziness, tremors, sweating, fast heartbeat, seizure (convulsions), fainting, or coma (severe hypoglycemia can be fatal). Always keep a source of sugar available in case you have symptoms of low blood sugar.
Some people have developed a life-threatening condition called lactic acidosis while taking Metformin. Get emergency medical help if you have any of these symptoms of lactic acidosis: weakness, increasing sleepiness, slow heart rate, cold feeling, muscle pain, shortness of breath, stomach pain, feeling light-headed, and fainting.
You may be more likely to develop lactic acidosis if you have congestive heart failure. Older adults may also have a higher risk of developing lactic acidosis. Talk with your doctor about your individual risk.
FDA pregnancy category B. This medication is not expected to be harmful to an unborn baby. Tell your doctor if you are pregnant or plan to become pregnant during treatment. It is not known whether Metformin passes into breast milk or if it could harm a nursing baby. Do not take Metformin without first talking to your doctor if you are breast-feeding a baby. Metformin should not be given to a child younger than 10 years old. Extended-release Metformin (Glucophage XR) should not be given to a child younger than 17 years old.
Avoid drinking alcohol while taking Metformin. Alcohol lowers blood sugar and may increase the risk of lactic acidosis while you are taking this medicine.
What should I discuss with my healthcare provider before taking Metformin?
- If you have an allergy to Metformin or any other part of Metformin (Metformin extended-release suspension).
- If you are allergic to Metformin (Metformin extended-release suspension); any part of Metformin (Metformin extended-release suspension); or any other drugs, foods, or substances. Tell your doctor about the allergy and what signs you had.
- If you have any of these health problems: Acidic blood problem, kidney disease, or liver disease.
- If you have had a recent heart attack or stroke.
- If you are not able to eat or drink like normal, including before certain procedures or surgery.
- If you are having an exam or test with contrast or have had one within the past 48 hours, talk with your doctor.
This is not a list of all drugs or health problems that interact with Metformin (Metformin extended-release suspension).
Tell your doctor and pharmacist about all of your drugs (prescription or OTC, natural products, vitamins) and health problems. You must check to make sure that it is safe for you to take Metformin (Metformin extended-release suspension) with all of your drugs and health problems. Do not start, stop, or change the dose of any drug without checking with your doctor.
Metformin precautions
General
Monitoring of renal function- Metformin is known to be substantially excreted by the kidney, and the risk of Metformin accumulation and lactic acidosis increases with the degree of impairment of renal function. Thus, patients with serum creatinine levels above the upper limit of normal for their age should not receive Metformin®. In patients with advanced age, Metformin® should be carefully titrated to establish the minimum dose for adequate glycemic effect, because aging is associated with reduced renal function. In elderly patients, particularly those ≥80 years of age, renal function should be monitored regularly and, generally, Metformin® should not be titrated to the maximum dose.
Before initiation of Metformin® therapy and at least annually thereafter, renal function should be assessed and verified as normal. In patients in whom development of renal dysfunction is anticipated, renal function should be assessed more frequently and Metformin® discontinued if evidence of renal impairment is present.
Macrovascular Outcomes -
There have been no clinical studies establishing conclusive evidence of macrovascular risk reduction with Metformin® or any other anti-diabetic drug.
Use of concomitant medications that may affect renal function or Metformin disposition- Concomitant medication(s) that may affect renal function or result in significant hemodynamic change or may interfere with the disposition of Metformin, such as cationic drugs that are eliminated by renal tubular secretion, should be used with caution.
Radiologic studies involving the use of intravascular iodinated contrast materials (for example, intravenous urogram, intravenous cholangiography, angiography, and computed tomography (CT) scans with intravascular contrast materials) – Intravascular contrast studies with iodinated materials can lead to acute alteration of renal function and have been associated with lactic acidosis in patients receiving Metformin. Therefore, in patients in whom any such study is planned, Metformin® should be temporarily discontinued at the time of or prior to the procedure, and withheld for 48 hours subsequent to the procedure and reinstituted only after renal function has been re-evaluated and found to be normal.
Hypoxic states – Cardiovascular collapse (shock) from whatever cause, acute congestive heart failure, acute myocardial infarction and other conditions characterized by hypoxemia have been associated with lactic acidosis and may also cause prerenal azotemia. When such events occur in patients on Metformin® therapy, the drug should be promptly discontinued.
Surgical procedures – Metformin® therapy should be temporarily suspended for any surgical procedure (except minor procedures not associated with restricted intake of food and fluids) and should not be restarted until the patient's oral intake has resumed and renal function has been evaluated as normal.
Alcohol intake – Alcohol is known to potentiate the effect of Metformin on lactate metabolism. Patients, therefore, should be warned against excessive alcohol intake, acute or chronic, while receiving Metformin®.
Impaired hepatic function – Since impaired hepatic function has been associated with some cases of lactic acidosis, Metformin® should generally be avoided in patients with clinical or laboratory evidence of hepatic disease.
Vitamin B12 levels – In controlled clinical trials of immediate-release Metformin of 29 weeks duration, a decrease to subnormal levels of previously normal serum Vitamin B12 levels, without clinical manifestations, was observed in approximately 7% of patients. Such decrease, possibly due to interference with B12 absorption from the B12 -intrinsic factor complex, is, however, very rarely associated with anemia and appears to be rapidly reversible with discontinuation of immediate-release Metformin or Vitamin B12 supplementation. Measurement of hematologic parameters on an annual basis is advised in patients on Metformin® and any apparent abnormalities should be appropriately investigated and managed. Certain individuals (those with inadequate Vitamin B12 or calcium intake or absorption) appear to be predisposed to developing subnormal Vitamin B12 levels. In these patients, routine serum Vitamin B12 measurements at two- to three-year intervals may be useful.
Change in clinical status of patients with previously controlled type 2 diabetes – A patient with type 2 diabetes previously well controlled on Metformin® who develops laboratory abnormalities or clinical illness (especially vague and poorly defined illness) should be evaluated promptly for evidence of ketoacidosis or lactic acidosis. Evaluation should include serum electrolytes and ketones, blood glucose and, if indicated, blood pH, lactate, pyruvate, and Metformin levels. If acidosis of either form occurs, Metformin® must be stopped immediately and other appropriate corrective measures initiated.
Hypoglycemia – Hypoglycemia does not occur in patients receiving Metformin® alone under usual circumstances of use, but could occur when caloric intake is deficient, when strenuous exercise is not compensated by caloric supplementation, or during concomitant use with other glucose-lowering agents (such as sulfonylureas and insulin) or ethanol. Elderly, debilitated, or malnourished patients, and those with adrenal or pituitary insufficiency or alcohol intoxication are particularly susceptible to hypoglycemic effects. Hypoglycemia may be difficult to recognize in the elderly, and in people who are taking beta-adrenergic blocking drugs.
Loss of control of blood glucose – When a patient stabilized on any diabetic regimen is exposed to stress such as fever, trauma, infection, or surgery, a temporary loss of glycemic control may occur. At such times, it may be necessary to withhold Metformin® and temporarily administer insulin. Metformin® may be reinstituted after the acute episode is resolved.
The effectiveness of oral antidiabetic drugs in lowering blood glucose to a targeted level decreases in many patients over a period of time. This phenomenon, which may be due to progression of the underlying disease or to diminished responsiveness to the drug, is known as secondary failure, to distinguish it from primary failure in which the drug is ineffective during initial therapy. Should secondary failure occur with Metformin® or sulfonylurea monotherapy, combined therapy with Metformin® and sulfonylurea may result in a response. Should secondary failure occur with combined Metformin®/sulfonylurea therapy, it may be necessary to consider therapeutic alternatives including initiation of insulin therapy.
Information for Patients
Patients should be informed of the potential risks and benefits of Metformin® and of alternative modes of therapy. They should also be informed about the importance of adherence to dietary instructions, of a regular exercise program, and of regular testing of blood glucose, glycosylated hemoglobin, renal function, and hematologic parameters.
The risks of lactic acidosis, its symptoms, and conditions that predispose to its development, as noted in the WARNINGS and PRECAUTIONS sections, should be explained to patients. Patients should be advised to discontinue Metformin® immediately and to promptly notify their health practitioner if unexplained hyperventilation, myalgia, malaise, unusual somnolence, or other nonspecific symptoms occur. Once a patient is stabilized on any dose level of Metformin®, gastrointestinal symptoms, which are common during initiation of Metformin therapy, are unlikely to be drug related. Later occurrence of gastrointestinal symptoms could be due to lactic acidosis or other serious disease.
Patients should be counseled against excessive alcohol intake, either acute or chronic, while receiving Metformin®.
Metformin® alone does not usually cause hypoglycemia, although it may occur when Metformin® is used in conjunction with oral sulfonylureas and insulin. When initiating combination therapy, the risks of hypoglycemia, its symptoms and treatment, and conditions that predispose to its development should be explained to patients and responsible family members.
Patients should be informed that Metformin® must be swallowed whole and not chewed, cut, or crushed, and that the inactive ingredients may occasionally be eliminated in the feces as a soft mass that may resemble the original tablet.
Laboratory Tests
Response to all diabetic therapies should be monitored by periodic measurements of fasting blood glucose and glycosylated hemoglobin levels, with a goal of decreasing these levels toward the normal range. During initial dose titration, fasting glucose can be used to determine the therapeutic response. Thereafter, both glucose and glycosylated hemoglobin should be monitored. Measurements of glycosylated hemoglobin may be especially useful for evaluating long-term control.
Initial and periodic monitoring of hematologic parameters (e.g., hemoglobin/hematocrit and red blood cell indices) and renal function (serum creatinine) should be performed, at least on an annual basis. While megaloblastic anemia has rarely been seen with immediate-release Metformin therapy, if this is suspected, Vitamin B12 deficiency should be excluded.
Drug Interactions (Clinical Evaluation of Drug Interactions Conducted with Immediate-Release Metformin)
Glyburide– In a single-dose interaction study in type 2 diabetes patients, co-administration of Metformin and glyburide did not result in any changes in either Metformin pharmacokinetics or pharmacodynamics. Decreases in glyburide AUC and Cmax were observed, but were highly variable. The single-dose nature of this study and the lack of correlation between glyburide blood levels and pharmacodynamic effects, makes the clinical significance of this interaction uncertain.
Furosemide– A single-dose, Metformin-furosemide drug interaction study in healthy subjects demonstrated that pharmacokinetic parameters of both compounds were affected by co-administration. Furosemide increased the Metformin plasma and blood Cmax by 22% and blood AUC by 15%, without any significant change in Metformin renal clearance. When administered with Metformin, the Cmax and AUC of furosemide were 31% and 12% smaller, respectively, than when administered alone, and the terminal half-life was decreased by 32%, without any significant change in furosemide renal clearance. No information is available about the interaction of Metformin and furosemide when co-administered chronically.
Nifedipine– A single-dose, Metformin-nifedipine drug interaction study in normal healthy volunteers demonstrated that co-administration of nifedipine increased plasma Metformin Cmax and AUC by 20% and 9%, respectively, and increased the amount excreted in the urine. Tmax and half-life were unaffected. Nifedipine appears to enhance the absorption of Metformin. Metformin had minimal effects on nifedipine.
Cationic drugs– Cationic drugs (e.g., amiloride, digoxin, morphine, procainamide, quinidine, quinine, ranitidine, triamterene, trimethoprim, or vancomycin) that are eliminated by renal tubular secretion theoretically have the potential for interaction with Metformin by competing for common renal tubular transport systems. Such interaction between Metformin and oral cimetidine has been observed in normal healthy volunteers in both single- and multiple-dose, Metformin-cimetidine drug interaction studies, with a 60% increase in peak Metformin plasma and whole blood concentrations and a 40% increase in plasma and whole blood Metformin AUC. There was no change in elimination half-life in the single-dose study. Metformin had no effect on cimetidine pharmacokinetics. Although such interactions remain theoretical (except for cimetidine), careful patient monitoring and dose adjustment of Metformin® and/or the interfering drug is recommended in patients who are taking cationic medications that are excreted via the proximal renal tubular secretory system.
Other– Certain drugs tend to produce hyperglycemia and may lead to loss of glycemic control. These drugs include the thiazides and other diuretics, corticosteroids, phenothiazines, thyroid products, estrogens, oral contraceptives, phenytoin, nicotinic acid, sympathomimetics, calcium channel blocking drugs, and isoniazid. When such drugs are administered to a patient receiving Metformin®, the patient should be closely observed for loss of blood glucose control. When such drugs are withdrawn from a patient receiving Metformin®, the patient should be observed closely for hypoglycemia.
In healthy volunteers, the pharmacokinetics of Metformin and propranolol, and Metformin and ibuprofen were not affected when coadministered in single-dose interaction studies.
Metformin is negligibly bound to plasma proteins and is, therefore, less likely to interact with highly protein-bound drugs such as salicylates, sulfonamides, chloramphenicol, and probenecid, as compared to the sulfonylureas, which are extensively bound to serum proteins.
Carcinogenesis, Mutagenesis, Impairment of Fertility
Long-term carcinogenicity studies with Metformin have been performed in rats (dosing duration of 104 weeks) and mice (dosing duration of 91 weeks) at doses up to and including 900 mg/kg/day and 1500 mg/kg/day, respectively. These doses are both approximately four times the maximum recommended human daily dose of 2000 mg based on body surface area comparisons. No evidence of carcinogenicity with Metformin was found in either male or female mice. Similarly, there was no tumorigenic potential observed with Metformin in male rats. There was, however, an increased incidence of benign stromal uterine polyps in female rats treated with 900 mg/kg/day.
There was no evidence of mutagenic potential of Metformin in the following in vitro tests: Ames test (S. typhimurium), gene mutation test (mouse lymphoma cells), or chromosomal aberrations test (human lymphocytes). Results in the in vivo mouse micronucleus test were also negative.
Fertility of male or female rats was unaffected by Metformin when administered at doses as high as 600 mg/kg/day, which is approximately three times the maximum recommended human daily dose based on body surface area comparisons.
Pregnancy
Teratogenic Effects: Pregnancy Category BRecent information strongly suggests that abnormal blood glucose levels during pregnancy are associated with a higher incidence of congenital abnormalities. Most experts recommend that insulin be used during pregnancy to maintain blood glucose levels as close to normal as possible. Because animal reproduction studies are not always predictive of human response, Metformin® should not be used during pregnancy unless clearly needed.
There are no adequate and well-controlled studies in pregnant women with immediate-release Metformin or Metformin®. Metformin was not teratogenic in rats and rabbits at doses up to 600 mg/kg/day. This represents an exposure of about two and six times the maximum recommended human daily dose of 2000 mg based on body surface area comparisons for rats and rabbits, respectively. Determination of fetal concentrations demonstrated a partial placental barrier to Metformin.
Nursing Mothers
Studies in lactating rats show that Metformin is excreted into milk and reaches levels comparable to those in plasma. Similar studies have not been conducted in nursing mothers. Because the potential for hypoglycemia in nursing infants may exist, a decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother. If Metformin® is discontinued, and if diet alone is inadequate for controlling blood glucose, insulin therapy should be considered.
Pediatric Use
No pediatric clinical studies have been conducted with Metformin®. The safety and effectiveness of immediate-release Metformin for the treatment of type 2 diabetes have been established in pediatric patients ages 10 to 16 years (studies have not been conducted in pediatric patients below the age of 10 years). Use of immediate-release Metformin in this age group is supported by evidence from adequate and well-controlled studies of immediate-release Metformin in adults with additional data from a controlled clinical study in pediatric patients ages 10-16 years with type 2 diabetes, which demonstrated a similar response in glycemic control to that seen in adults. In this study, adverse effects were similar to those described in adults. A maximum daily dose of 2000 mg of immediate-release Metformin is recommended.
The safety and efficacy of Metformin® has not been evaluated in pediatric patients.
Geriatric Use
Of the 389 patients who received Metformin® in controlled Phase III clinical studies, 26.5% [103/389] were 65 years and older. No overall differences in effectiveness or safety were observed between these patients and younger patients.
Controlled clinical studies of immediate-release Metformin did not include sufficient numbers of elderly patients to determine whether they respond differently from younger patients, although other reported clinical experience has not identified differences in responses between the elderly and younger patients. Metformin is known to be substantially excreted by the kidney and because of the risk of serious adverse reactions to the drug is greater in patients with impaired renal function, immediate-release Metformin should only be used in patients with normal renal function. Because aging is associated with reduced renal function, immediate-release Metformin should be used with caution as age increases. Care should be taken in dose selection and should be based on careful and regular monitoring of renal function. Generally, elderly patients should not be titrated to the maximum dose of immediate-release Metformin.
What happens if I miss a dose of Metformin?
Take the missed dose as soon as you remember (be sure to take the medicine with food). Skip the missed dose if it is almost time for your next scheduled dose. Do not take extra medicine to make up the missed dose.
References
- DrugBank. "metformin". http://www.drugbank.ca/drugs/DB00331 (accessed September 17, 2018).
- MeSH. "Hypoglycemic Agents". https://www.ncbi.nlm.nih.gov/mesh/68... (accessed September 17, 2018).
Reviews
Consumer reviews
There are no reviews yet. Be the first to write one! |
Information checked by Dr. Sachin Kumar, MD Pharmacology
