Medication
Presentation
Torry A. Hansen
Glyburide
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Generic name: Glyburide
Brand name: Micronase
Other brand names: DiaBeta, Glynase
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Classifications:
Therapeutic: Antidiabetics
Pharmacologic: Sulfonylureas
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Pregnancy Category B
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Description
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Glyburide is an oral blood-glucoselowering drug of the sulfonylurea class.
Glyburide is a white, crystalline
compound. , The chemical name for
glyburide is:
1-[ [p-[2-(5-chloro-o-anisamido)ethyl]phenyl]-sulfonyl]-3-cyclohexylurea
and the molecular weight is 493.99. The
structural formula is represented below.
Glyburide
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Indications (Pharmacia & Upjohn, 2005):
Glyburide tablets are indicated as an adjunct to diet to
lower the blood glucose in patients with non-insulindependent diabetes mellitus (Type II) whose
hyperglycemia cannot be satisfactorily controlled by diet
alone.
Glyburide may be used concomitantly with metformin
when diet and glyburide or diet and metformin alone
do not result in adequate glycemic control.
Actions/Uses

Glyburide appears to lower the blood
glucose acutely by stimulating the release of
insulin from the pancreas, an effect
dependent upon functioning beta cells in
the pancreatic islets. The mechanism by
which glyburide lowers blood glucose
during long-term administration has not
been clearly established.
Extrapancreatic effects may be involved in
the mechanism of action of oral
sulfonylurea hypoglycemic drugs.
Glyburide
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Pharmacokinetics/Pharmacodynamics (Pharmacia &
Upjohn, 2005):
Single dose studies with glyburide in normal subjects demonstrate
significant absorption of glyburide within one hour, peak drug levels at
about four hours, and low but detectable levels at twenty-four hours.
The major metabolite of glyburide is the 4-trans-hydroxy derivative. A
second metabolite, the 3-cis-hydroxy derivative, also occurs. These
metabolites probably contribute no significant hypoglycemic action in
humans since they are only weakly active (1/400th and 1/40th as active,
respectively, as glyburide) in rabbits.
Glyburide is excreted as metabolites in the bile and urine,
approximately 50% by each route. This dual excretory pathway is
qualitatively different from that of other sulfonylureas, which are
excreted primarily in the urine.
Glyburide
Sulfonylurea drugs are extensively bound to
serum proteins. Displacement from protein
binding sites by other drugs may lead to
enhanced hypoglycemic action. In vitro, the
protein binding exhibited by glyburide is
predominantly non-ionic, whereas that
of other sulfonylureas (chlorpropamide,
tolbutamide, tolazamide) is predominantly
ionic.
Acidic drugs such as phenylbutazone,
warfarin, and salicylates displace the ionicbinding sulfonylureas from serum proteins to
a far greater extent than the non-ionic
binding glyburide.
It has not been shown that this difference in
protein binding will result in fewer drugdrug interactions with glyburide.
Contraindications:
Glyburide is contraindicated in patients with:
1. Known hypersensitivity or allergy to the drug.
2. Diabetic ketoacidosis, with or without coma. This
condition should be treated with insulin.
3. Type I diabetes mellitus, as sole therapy.
The administration of oral hypoglycemic drugs
has been reported to be associated with increased
cardiovascular mortality as compared to treatment with diet
alone or diet plus insulin (Herfindal & Gorley, 2003).
Interactions
Glyburide may interact with the following (Deglin & Vallerand, 2005):
Nonsteroidal antiinflammatory agents
Salicylates
Sulfonamides and
Ciprofloxacin
Chloramphenicol,
clofibrate, guanethidine
Probenecid
Coumarins
Monoamine and Oral
miconazole
Oxidase inhibitors
Beta adrenergic
blocking agents
Thiazides and other
diuretics
Corticosteroids
Phenothiazines
Thyroid products
Estrogens, Oral
contraceptives, and
androgens
Alcohol, glucosamine,
fenugreek, chromium,
coenzyme Q-10
Phenytoin
Nictotinic acid
Sympathomimetics
Calcium channel
blocking drugs
Isoniazid
Common Side Effects:
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Hypoglycemia
Gastrointestinal Reactions: Cholestatic
jaundice, hepatitis, liver function abnormalities.
Gastrointestinal disturbances, (eg, nausea,
epigastric fullness, and heartburn are the most
common).
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Dermatologic Reactions: Allergic skin
reactions, (eg, pruritus, erythema, urticaria,
and morbilliform or maculopapular eruptions),
Porphyria cutanea tarda and photosensitivity
reactions have been reported with
sulfonylureas.
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Hematologic Reactions: Leukopenia,
agranulocytosis, thrombocytopenia,
hemolytic anemia, aplastic anemia, and
pancytopenia have been reported with
sulfonylureas.
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Common Side Effects
Metabolic Reactions (Pharmacia & Upjohn, 2005):
Cases of hyponatremia have been reported with
glyburide and all other sulfonylureas, most often in
patients who are on other medications or have medical
conditions known to cause hyponatremia or increase
release of antidiuretic hormone. The syndrome of
inappropriate antidiuretic hormone (SIADH)
secretion has been reported with certain other
sulfonylureas, and it has been suggested that these
sulfonylureas may augment the peripheral
(antidiuretic) action of ADH and/or increase release
of ADH.
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Other Reactions (Pharmacia & Upjohn, 2005):
Changes in accommodation and/or blurred vision
have been reported with glyburide. These are thought
to be related to fluctuation in glucose levels. In
addition to dermatologic reactions, allergic reactions
such as angioedema, arthralgia, myalgia and vasculitis
have been reported.
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Common dosages & frequency
• There is no fixed dosage regimen for the
management of diabetes mellitus with glyburide or
any other hypoglycemic agent.
• The usual starting dose of glyburide is 2.5 to 5
mg daily, administered with breakfast or the first
main meal.
• Those patients who may be more sensitive to
hypoglycemic drugs should be started at 1.25 mg
daily. Failure to follow an appropriate dosage
regimen may precipitate hypoglycemia.
• Transfer of patients from other oral antidiabetic
regimens to glyburide should be done conservatively
and the initial daily dose should be 2.5 to 5 mg
(Pharmacia & Upjohn, 2005).
Common dosages & frequency
Maximum Dose
Daily doses of more than 20 mg are not
recommended.
Dosage Interval
Once-a-day therapy is usually
satisfactory.
Some patients, particularly those
receiving more than 10 mg daily, may
have a more satisfactory response with
twice-a-day dosage.
HOW SUPPLIED
1.25 mg Tablets
2.5 mg Tablets
5 mg Tablets
Specifics of taking/administration
of medication
In diabetic subjects, there is no fixed dosage regimen for management of
blood
glucose levels. Individual determination of the minimum dose that will lower the
blood glucose adequately should be made. If the maximal recommended dose
fails to lower blood glucose adequately in patients on initial trial, glyburide should
be discontinued. During the course of therapy a loss of effectiveness may
occur. It is advisable to ascertain the contribution of the drug in the control of
blood glucose by discontinuing the medication semi-annually or at least annually
with careful monitoring of the patient (Pharmacia & Upjohn, 2005).
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Glyburide is usually administered with breakfast or the first main meal. Do not
administer after the last meal of the day.
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Patients who do not adhere to their prescribed dietary and drug regimen are
more prone to exhibit an unsatisfactory response to therapy.
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Monitoring
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In addition to the usual monitoring of urinary
glucose, the patient’s blood glucose must also
be monitored periodically to determine the
minimum effective dose for the patient; to
detect primary failure, ie, inadequate lowering
of blood glucose at the maximum
recommended dose of medication; and to
detect secondary failure, ie, loss of adequate
blood glucose lowering response after an
initial period of effectiveness.
Glycosylated hemoglobin levels may be of
value in monitoring the patient’s response to
therapy.
The CBC should also be monitored
periodically throughout therapy.
Prescribing Implications
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Glyburide is not recommended for use in
pregnancy or for use in pediatric patients.
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In elderly patients, debilitated or
malnourished patients, and patients with
impaired renal or hepatic function, the
initial and maintenance dosing should be
conservative to avoid hypoglycemic
reactions.
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Adjustment of glyburide dosage should
be considered whenever factors
predisposing the patient to the
development of hypo- or hyperglycemia,
such as weight, life-style changes, stress,
or infection are present.
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Half-life—10 hr.
Glyburide
 Dietary/drug restrictions
(Deglin & Vallerand, 2005):
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Restrict all drugs previously mentioned
that are known to interact with
glyburide.
Ingestion of alcohol may result in a
disulfiram-like reaction.
Glucosamine may worsen blood glucose
control.
Fenugreek, chromium, and coenzyme Q10 may produce additive hypoglycemic
effects.
Suggest a daily intake of no more than
10%-20% protein, 10%-20% from fat (less
than 10% saturated), and 60%-70% from
carbohydrates.
Glyburide
Storage
Store at controlled room temperature 20 degrees to 25 degrees C
(68 degrees to 77 degrees F). Dispense in well closed containers
with safety closures. Keep container tightly closed.
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Glyburide
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Other items specific to this medication
This drug may cause an increase in AST, LDH, BUN, and serum creatinine levels.
Overdose of sulfonylureas can produce hypoglycemia. Mild hypoglycemic symptoms,
without loss of consciousness or neurological findings, should be treated aggressively with
oral glucose and adjustments in drug dosage and/or meal patterns. Close monitoring
should continue until the nurse practitioner is assured that the patient is out of danger.
Severe hypoglycemic reactions with coma, seizure, or other neurological impairment occur
infrequently, but constitute medical emergencies requiring immediate hospitalization. If
hypoglycemic coma is diagnosed or suspected, the patient should be given a rapid
intravenous injection of concentrated (50%) glucose solution. This should be followed by a
continuous infusion of a more dilute (10%) glucose solution at a rate which will maintain
the blood glucose at a level above 100 mg/dL. Patients should be closely monitored for a
minimum of 24 to 48 hours, since hypoglycemia may recur after apparent clinical recovery
(Pharmacia & Upjohn, 2005).
Glyburide—Clinical Research
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Describe and discuss the type of clinical research
conducted using this drug (Pharmacia & Upjohn, 2005):
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In a single dose interaction study with metformin, NIDDM subjects
had decreases in glyburide AUC and Cmax. Results also demonstrated
that coadministration of glyburide and metformin did not result in any
changes in either metformin pharmacokinetics or pharmacodynamics.
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An animal study was undertaken utilizing rats. These rats were given
doses of up to 300 mg/kg/day of glyburide for 18 months. Results
showed that glyburide was nonmutagenic when studied in the
Salmonella microsome test (Ames test) and in the DNA
damage/alkaline elution assay. Researchers concluded that there were
no drug related carcinogenic effects in any of the criteria evaluated in
this oncogenicity study.
Glyburide—Clinical Research
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Reproduction studies have been performed in rabbits and rats at doses up to
500 times the human dose and have revealed no evidence of impaired fertility
or harm to the fetus due to glyburide. There are, however, no adequate and well
controlled studies in pregnant women. Because animal reproduction studies
are not always predictive of human response, glyburide should be used during
pregnancy only if clearly needed.
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The University Group Diabetes Program (UGDP) conducted a randomized,
long-term prospective study. The study was designed to evaluate the
effectiveness of glucose lowering drugs in preventing or delaying vascular
complications in patients with non-insulin-dependent diabetes. UGDP
reported that patients treated for 5 to 8 years with diet plus a fixed dose of
tolbutamide (1.5 grams per day) had a rate of cardiovascular mortality
approximately 2 ½ times that of patients treated with diet alone. It is important
to note that only one drug in the sulfonylurea class (tolbutamide) was included
in this study. However, it is prudent from a safety standpoint to consider that
this warning may also apply to other oral hypoglycemic drugs in this class
(such as glyburide), in view of their close similarities in mode of action and
chemical structure.
Glyburide—Additional Research
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A double-blind, randomized crossover study was conducted using 16 healthy
volunteers. The objective of this study was to investigate the impact of glyburide on
glucose counterregulatory hormones during stepwise hypoglycemic clamp studies.
Researchers concluded that glyburide induces multiple defects in glucose
counterregulatory hormonal responses, notably decreases in both glucagon and GH
release (Van Haeften, 2002).
Langer, et. al. (2000) conducted a randomized, non-blinded, active-controlled study
involving 404 gestational diabetic women with single fetus pregnancies. These
women were randomly assigned to receive either glyburide or human insulin between
11 and 33 weeks of gestation. Achievement of desired glucose control was the
primary endpoint. Maternal and neonatal complications were secondary endpoints.
From their findings researchers concluded that glyburide is a safe and effective
alternative to insulin in women with gestational diabetes.
A randomized, double-blind, placebo-controlled multicenter study was conducted in
152 patients who received either nateglinide (120 mg before three meals daily, n = 51),
glyburide (5 mg q.d. titrated to 10 mg q.d. after 2 weeks, n = 50), or placebo (n = 51)
for 8 weeks. The researchers concluded that nateglinide selectively enhanced early
insulin release and provided better mealtime glucose control with less total insulin
exposure than glyburide (Hollander, et. al., 2001).
Objective data about the patient
that the prescriber needs
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Confirmation that the patient
is diabetic (i.e. blood glucose
levels).
Knowledge concerning
whether the patient has (or
has ever had) kidney or liver
disease.
Assessment data that
excludes adrenal or pituitary
insufficiency.
For females, confirmation
that patient is not pregnant,
planning to become
pregnant, or breastfeeding.
Patient Teaching
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Educate the patient on glyburide,
potential side effects and drug
interactions.
Educate on the pathophysiology of
Type II diabetes.
Educate on the importance of
monitoring blood sugar levels.
If the patient is having surgery,
including dental surgery, instruct
him/her to tell the doctor or dentist
that they are taking glyburide.
Tell the patient that this drug may
make them drowsy. Advise him/her to
not drive a car or operate machinery
until they know how the drug affects
them.
Inform the patient that alcohol can add
to the drowsiness caused by this drug.
Patient Teaching Points
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Cigarette smoking may decrease the
effectiveness of glyburide.
Glyburide may make skin sensitive to sunlight.
Plan to avoid unnecessary or prolonged
exposure to sunlight and to wear protective
clothing, sunglasses, and sunscreen.
Diet should be emphasized as the primary
form of treatment. Caloric restriction and
weight loss are essential in the obese diabetic
patient.
The importance of regular physical activity
should be emphasized.
Emphasize the importance of yearly podiatric
and opthalmologic exams.
Educate on the need for regularly scheduled
lab studies and the importance of keeping all
regularly scheduled follow-up appointments
(American Society of Health-System
Pharmacists, 2004).
Monitoring that should be
implemented with this drug
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Patients need to be monitored closely for adverse
reactions.
Periodic assessment of cardiovascular, ophthalmic,
hematologic, renal and hepatic status is advisable.
Routine laboratory tests that should be performed
include:
CBC
Urinary glucose
Blood glucose
Glycosylated hemoglobin levels
The effectiveness of any hypoglycemic drug including
glyburide, in lowering blood glucose to a desired level
decreases in many patients over a period of time which may
be due to progression of the severity of diabetes or to
diminished responsiveness to the drug. This phenomenon is
known as secondary failure, (to distinguish it from primary
failure in which the drug is ineffective when first given).
Adequate adjustment of dose and adherence to diet should
be assessed before classifying a patient as a secondary
failure (Pharmacia & Upjohn, 2005).
Sample prescription
Quality Health Care
Torry Ann Hansen FNP
1234 Main Street
Hermitage, TN 37076
Patient Name Jane Jacobs
Date 11-05-05
Allergies None
Indication: Type II Diabetes
Rx
Glyburide 2.5 mg PO qd (every day)
Quantity: 32 (thirty-two)
Refill 0 (zero) times
Torry Ann Hansen FNP
References
American Society of Health-System Pharmacists. (2004). Glyburide. Retrieved October 29, 2005 from,
http://www.nlm.nih.gov/medlineplus/druginfo/medmaster/storage-conditions
Deglin, J.H., & Vallerand, A.H. (2005). Davis’s Drug Guide For Nurses. 9th Ed. Philadelphia. F.A. Davis.
Herfindal, E. T., & Gorley, D. R. (2003). Textbook of therapeutics: Drug and disease management (7th
Ed.). Philadelphia: Lippincott Williams & Wilkins.
Hollander, P.A, Schwartz, S.L., Gatlin, M.R., Haas, S.J.,, Zheng, H., Foley, J.E., & Dunning, B.E. (2001).
Comparison of nateglinide and glyburide in previously diet-treated patients with type 2 diabetes. Diabetes
Care 24:983-988.
Langer, O.D, Conway D.L., Berkus, M.D., Xenakis, E.M.J, & Gonzales, O. (2000). A comparison of glyburide and
insulin in women with gestational diabetes. New England Journal of Medicine, 343:1134-38.
Pharmacia & Upjohn. (2005). Micronase. Retrieved October 28, 2005 from,
http://66.218.69.11/search/cache?p=micronase&sm=Yahoo%21+Search&toggle=1&ei=UTF8&u=www.pfizer.com/download/uspi_micronase.pdf&w=micronase&d=TXydx2FULdKb&icp=1&.intl=us
Van Haeften. T.W. (2002). The sulfonylurea glyburide induces impairment of glucagon and growth hormone
responses during mild Insulin-Induced hypoglycemia. Retrieved October 29, 2005 from,
http://www.highbeam.com/library/docfree.asp?DOCID=1G1:82270374&ctrlInfo=Round18%3AMode
c%3ADocG%3AResult&ao=
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