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Pronunciation |
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(met
FOR
min) |
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U.S. Brand
Names |
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Glucophage® |
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Generic
Available |
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No |
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Canadian Brand
Names |
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Novo-Metformin |
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Synonyms |
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Metformin Hydrochloride |
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Pharmacological Index |
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Antidiabetic Agent (Biguanide) |
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Use |
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Management of noninsulin-dependent diabetes mellitus (type 2) as monotherapy
when hyperglycemia cannot be managed on diet alone. May be used concomitantly
with a sulfonylurea when diet and metformin or sulfonylurea alone do not result
in adequate glycemic control. |
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Pregnancy Risk
Factor |
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B |
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Contraindications |
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Hypersensitivity to metformin or any component; renal disease or renal
dysfunction (serum creatinine greater than or equal to 1.5 mg/dL in males or
greater than or equal to 1.4 mg/dL in females or creatinine clearance <60
mL/minute) which may also result from conditions such as cardiovascular
collapse, acute myocardial infarction, and septicemia; acute or chronic
metabolic acidosis with or without coma (including diabetic ketoacidosis);
should be temporarily withheld (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) in patients
undergoing radiologic studies involving the parenteral administration of
iodinated contrast materials (potential for acute alteration in renal
function) |
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Warnings/Precautions |
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Administration of oral antidiabetic drugs has been reported to be associated
with increased cardiovascular mortality as compared to treatment with diet alone
or diet plus insulin. Metformin is substantially excreted by the kidney - the
risk of accumulation and lactic acidosis increases with the degree of impairment
of renal function. Patients with renal function below the limit of normal for
their age should not receive metformin. In elderly patients, renal function
should be monitored regularly. Use of concomitant medications that may affect
renal function (ie, affect tubular secretion) may affect metformin disposition.
Therapy should be suspended for any surgical procedures. Avoid use in patients
with impaired liver function. Metformin should be discontinued at the time of or
prior to the procedure in patients undergoing radiologic studies in which
intravascular iodinated contrast materials are utilized, and withheld for 48
hours subsequent to the procedure, and reinstituted only after renal function
has been re-evaluated and found to be normal. |
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Adverse
Reactions |
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>10%: Gastrointestinal: Anorexia, nausea, vomiting, diarrhea, epigastric
fullness, constipation, heartburn
1% to 10%:
Dermatologic: Rash, urticaria, photosensitivity
Miscellaneous: Decreased vitamin B12 levels
<1%: Blood dyscrasias, aplastic anemia, hemolytic anemia, bone marrow
suppression, thrombocytopenia, agranulocytosis |
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Overdosage/Toxicology |
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Hypoglycemia has not been observed with ingestions of up to 85 g of
metformin, although lactic acidosis has occurred in such circumstances
Metformin is dialyzable with a clearance of up to 170 mL/minute; hemodialysis
may be useful for removal of accumulated drug from patients in whom metformin
overdosage is suspected |
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Drug
Interactions |
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Decreased effect: Drugs which tend to produce hyperglycemia (eg, diuretics,
corticosteroids, phenothiazines, thyroid products, estrogens, oral
contraceptives, phenytoin, nicotinic acid, sympathomimetics, calcium channel
blocking drugs, isoniazid) may lead to a loss of glycemic control
Increased effect: Furosemide increased the metformin plasma and blood
Cmax without altering metformin renal clearance in a single dose
study
Increased toxicity:
Cationic drugs (eg, amiloride, digoxin, morphine, procainamide, quinidine,
quinine, ranitidine, triamterene, trimethoprim, and vancomycin) which are
eliminated by renal tubular secretion could have the potential for interaction
with metformin by competing for common renal tubular transport systems
Cimetidine increases (by 60%) peak metformin plasma and whole blood
concentrations |
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Mechanism of
Action |
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Decreases hepatic glucose production, decreasing intestinal absorption of
glucose and improves insulin sensitivity (increases peripheral glucose uptake
and utilization) |
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Pharmacodynamics/Kinetics |
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Onset of effect: Within days, maximum effects up to 2 weeks
Distribution: Vd: 654±358 L
Protein binding: 92% to 99%
Protein binding, plasma: negligible
Bioavailability, absolute: 50% to 60% under fasting conditions; food
decreases the extent and slightly delays the absorption; the clinical relevance
is unknown
Half-life, plasma elimination: 6.2 hours
Elimination: Renal; tubular secretion is major route |
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Usual Dosage |
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Oral (allow 1-2 weeks between dose titrations): Generally, clinically
significant responses are not seen at doses <1500 mg daily; however, a lower
recommended starting dose and gradual increased dosage is recommended to
minimize gastrointestinal symptoms
500 mg tablets: Initial: 500 mg twice daily (give with the morning and
evening meals). Dosage increases should be made in increments of 1 tablet every
week, given in divided doses, up to a maximum of 2500 mg/day. Doses of up to
2000 mg/day may be given twice daily. If a dose of 2500 mg/day is required, it
may be better tolerated 3 times/day (with meals).
850 mg tablets: Initial: 850 mg once daily (give with the morning meal).
Dosage increases should be made in increments of 1 tablet every other
week, given in divided doses, up to a maximum of 2550 mg/day. Usual maintenance
dose: 850 mg twice daily (with the morning and evening meals). Some patients may
be given 850 mg 3 times/day (with meals).
Elderly: The initial and maintenance dosing should be conservative, due to
the potential for decreased renal function. Generally, elderly patients should
not be titrated to the maximum dose of metformin.
Transfer from other antidiabetic agents: No transition period is
generally necessary except when transferring from chlorpropamide. When
transferring from chlorpropamide, care should be exercised during the first 2
weeks because of the prolonged retention of chlorpropamide in the body, leading
to overlapping drug effects and possible hypoglycemia.
Concomitant metformin and oral sulfonylurea therapy: If patients have
not responded to 4 weeks of the maximum dose of metformin monotherapy,
consideration to a gradual addition of an oral sulfonylurea while continuing
metformin at the maximum dose, even if prior primary or secondary failure to a
sulfonylurea has occurred.
Dosing adjustment/comments in renal impairment: The plasma and blood
half-life of metformin is prolonged and the renal clearance is decreased in
proportion to the decrease in creatinine clearance. Metformin is contraindicated
in the presence of renal dysfunction defined as a serum creatinine >1.5 mg/dL
in males or >1.4 mg/dL in females or an abnormal creatinine clearance.
Dosing adjustment in hepatic impairment: No studies have been
conducted, however, metformin should be avoided because the presence of liver
disease is a risk factor for the development of lactic acidosis during metformin
therapy. |
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Dietary
Considerations |
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Alcohol: Incidence of lactic acidosis may be increased; avoid or limit use
Food: Food decreases the extent and slightly delays the absorption. Drug may
cause GI upset; take with food to decrease GI upset.
Glucose: Decreases blood glucose concentration. Hypoglycemia does not usually
occur unless a patient is predisposed. Monitor blood glucose concentration.
Exercise caution with administration in patients predisposed to hypoglycemia
(eg, cases of reduced caloric intake, strenuous exercise without repletion of
calories, alcohol ingestion or when metformin is combined with another oral
antidiabetic agent).
Vitamin B12: Decreases absorption of Vitamin B12;
monitor for signs and symptoms of vitamin B12 deficiency
Folic acid: Decreases absorption of folic acid; monitor for signs and
symptoms of folic acid deficiency |
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Monitoring
Parameters |
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Urine for glucose and ketones, fasting blood glucose, hemoglobin
A1c, and fructosamine. Initial and periodic monitoring of hematologic
parameters (eg, hemoglobin/hematocrit and red blood cell indices) and renal
function should be performed, at least annually. While megaloblastic anemia has
been rarely seen with metformin, if suspected, vitamin B12 deficiency
should be excluded. |
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Reference Range |
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Target range: Adults:
Glycosylated hemoglobin: <7% |
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Mental Health: Effects
on Mental Status |
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None reported |
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Mental Health:
Effects on Psychiatric
Treatment |
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May cause leukopenia; use caution with clozapine and carbamazepine;
concurrent use with psychotropics may produce additive
sedation |
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Dental Health: Local
Anesthetic/Vasoconstrictor
Precautions |
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No information available to require special precautions |
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Dental Health:
Effects on Dental Treatment |
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Metformin-dependent diabetics (noninsulin dependent, type 2) should be
appointed for dental treatment in morning in order to minimize chance of
stress-induced hypoglycemia |
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Patient
Information |
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This medication is used to control diabetes; it is not a cure. Other
components of treatment plan are important: follow prescribed diet, medication,
and exercise regimen. Take exactly as directed; with 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. Inform
prescriber of all other prescription or OTC medications you are taking; do not
introduce new medication without consulting prescriber. Do not take other
medication within 2 hours of this medication unless so advised by prescriber.
Maintain regular dietary intake and exercise routine and always carry quick
source of sugar with you. You may experience side effects during first weeks of
therapy (headache, nausea); consult prescriber if these persist. Report severe
or persistent side effects, extended vomiting or flu-like symptoms, skin rash,
easy bruising or bleeding, or change in color of urine or stool.
Breast-feeding precautions: Breast-feeding is not
recommended. |
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Nursing
Implications |
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Patients who are NPO may need to have their dose held to avoid
hypoglycemia |
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Dosage Forms |
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Tablet, as hydrochloride: 500 mg, 625 mg, 750 mg, 850 mg, 1000
mg |
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References |
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Bailey CJ and Turner RC, "Metformin," N Engl J Med, 1996,
334(9):574-9.
Dunn CJ and Peters DH,
"Metformin: A Review of Its Pharmacologic Properties and Therapeutic Use in Diabetes Mellitus,"
Drugs, 1995, 49(5):721-49.
Josephkutty S and Potter JM,
"Comparison of Tolbutamide and Metformin in Elderly Diabetic Patients,"
Diabet Med, 1990, 7(16):510-4.
Lalau JD, Vermersch A, Hary L, et al,
"Type 2 Diabetes in the Elderly: An Assessment of Metformin," Int J Clin
Pharmacol Ther Toxicol, 1990, 28(8):329-32.
"Standards of Medical Care for Patients With Diabetes Mellitus. American Diabetes Association,"
Diabetes Care, 1994, 17(6):616-23. |
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