Glyburide

1

• Glyburide
• (micronase, glynase, DiaBeta)
• shows promise for women with gestational diabetes
  and pregnant women with type 2 diabetes
• ?/ ???? ???? ???????
• ?????? ?????? ? ???????
• ?????? ??? ???? ????? - ???
• www.geocities.com/mmhennawy

2

• What about women with type 2 diabetes, who are
  taking diabetes pills, or women who have had
  gestational diabetes in the past?
• Will they need insulin, or will diabetes pills be
  okay to use during pregnancy?

3
glyburide

• Glyburide is a sulfonylurea drug used to lower
  blood sugar levels in people with type 2
  diabetes(non-insulin-dependent)
• 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
• glyburide, a type of sulfonylurea drug, does not
  pass through the placenta

4
Pharmacokinetics

• C23H28ClN3O5S glyburide
• Single dose studies with glyburide tablets in
  normal subjects demonstrate significant
  absorption of glyburide within 1 hour, peak drug
  levels at about 4 hours (2-3 hours for micronized
  glyburide), and low but detectable levels at 24
  hours
• Glyburide
• Also indexed as Diabeta, Glynase ,Prestab,
  Micronase, Pres Tab

5
Sulfonylureas

• First-Generation Agents
• Generic Name acetohexamideBrand Name Dymelor
• Generic Name chloropropamideBrand Name
  Diabinese
• Generic Name tolazamideBrand Name Tolinase
• Generic Name tolbutamideBrand Name Orinase
• Second-Generation Agents
• Generic Name glimepirideBrand Name Amaryl
• Generic Name glipizideBrand Names Glucotrol,
  Glucotrol XL
• Generic Name glyburideBrand Names DiaBeta,
  Micronase, Glynase
• Combination Agents
• Generic Name glyburide plus metformin Brand
  Name GlucoVance

6
dosage

• There is no fixed dosage regimen for the
  management of diabetes mellitus with glyburide or
  any other hypoglycemic agent. 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
• Glyburide may be taken with food to avoid
  gastrointestinal (GI) upset

7

• Glyburide is a white, crystalline compound,
  formulated
• as Micronase tablets of
• 1.25, 2.5, and 5 mg strengths for oral
  administration.
• The usual starting dose of standard glyburide
  tablets is 2.5-5 mg daily
• (micronized glyburide tablets 1.5-3 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
  of standard glyburide daily (0.75 mg for
  micronized glyburide daily).

8
Maximum Dose

• Standard Glyburide Daily doses of more than 20
  mg are not recommended.
• Micronized Glyburide Daily doses of more than 12
  mg are not recommended
• glyburideSU generic Intermediate acting1.25, 2.5,
  5mg5 - 20mg

9
Dosage Interval

• Standard Glyburide 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.
• Micronized Glyburide Once-a-day therapy is
  usually satisfactory. Some patients, particularly
  those receiving more than 6 mg daily, may have a
  more satisfactory response with twice-a-day dosag

10
CONTRAINDICATIONS

• Glyburide Tablets are 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.

11
Pregnancy

• , Effects Teratogenic, Pregnancy Category B
• Reproduction studies have been performed in rats
  and rabbits 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, this drug
  should be used during pregnancy only if clearly
  needed.
• Effects Nonteratogenic
• 4-10 days  Prolonged severe hypoglycemia (has
  been reported in neonates born to mothers who
  were receiving a sulfonylurea drug at the time of
  delivery. This has been reported more frequently
  with the use of agents with prolonged half-lives.
  If glyburide is used during pregnancy, it should
  be discontinued at least 2 weeks before the
  expected delivery date.

12
HOW SUPPLIED

• Micronase Tablets are Supplied as Follows
• Micronase Tablets 1.25 mg White, round, scored
  and imprinted MICRONASE 1.25.
• Micronase Tablets 2.5 mg Dark pink, round,
  scored and imprinted MICRONASE 2.5.
• Micronase Tablets 5 mg Blue, round, scored and
  imprinted MICRONASE 5.
• Storage Store at controlled room temperature
  20-25C (68-77F). Keep container tightly closed.
  Dispensed in well-closed containers with safety
  closures.
• Glynase PresTab Tablets are Supplied as Follows
• Glynase PresTab Tablets 1.5 mg White, ovoid,
  imprinted GLYNASE 1.5/PT Score PT, contour,
  scored.
• Glynase PresTab Tablets 3mg Blue, ovoid,
  imprinted GLYNASE 3/PT Score Pt, contour, scored.
  
• Glynase PresTab Tablets 6 mg Yellow, ovoid,
  imprinted GLYNASE 6/PT Score PT, contour,

13

• insulin is considered the drug of choice for the
  treatment of gestational diabetes however, it is
  expensive and its administration is inconvenient
• "Women with gestational diabetes mellitus are
  rarely treated with a sulfonylurea drug, because
  of concern about teratogenicity and neonatal
  hypoglycemia .

14

• . Gestational diabetes is rarely diagnosed during
  the first trimester of pregnancy, the period when
  organogenesis and more severe malformations
  occur. Therefore it seems unlikely that a
  pregnant female would receive treatment for
  gestational diabetes during this time period.
  Even though the results of this study show
  promise with regards to the use of
  second-generation sulfonylureas for the treatment
  of gestational diabetes, more studies need to be
  conducted before these medications can be
  considered safe in pregnancy.

15
A Comparison of Glyburide and Insulin in Women
with Gestational Diabetes Mellitus.

• The new sulphonylurea called glyburide does not
  cross the placental barrier

16
published in The New England Journal of Medicine
Volume 343 October 19, 2000 Number 16

• Of the 404 womenwith singleton pregnancies and
  gestational diabetes that required treatmen , 201
  received glyburide and 203 received human insulin
• between 11 and 33 weeks of gestation
• The mean ( SD) serum glucose concentration
  observed during routine visits to the clinic was
  102 24 mg/dl in the glyburide group and 99 22
  mg/dl in the insulin group.

17

• In addition, 82 of women in the glyburide group
  and 88 of women in the insulin group had home
  blood glucose measurements that fell into the
  desired range
• . No significant differences existed between the
  two groups with regards to perinatal outcome .

18

• The incidence of macrosomia between the groups
  was similar 11 in the glyburide group and 10
  in the insulin group
• . The cord serum of all infants was measured for
  the presence of glyburide however, the drug was
  not detected in any of the infants .

19

• There were no significant differences between the
  glyburide and insulin groups in the percentage of
  infants who were large for gestational age (12
  percent and 13 percent, respectively)
• who had macrosomia, defined as a birth weight of
  4000 g or more (7 percent and 4 percent
• ) who had lung complications (8 percent and 6
  percent
• ) who had hypoglycemia (9 percent and 6 percent
• who were admitted to a neonatal intensive care
  unit (6 percent and 7 percent
• who had fetal anomalies (2 percent and 2 percent
  )
• The cord-serum insulin concentrations were
  similar in the two groups)

20
REFERENCES

• Langer OD, Conway DL, Berkus MD, Xenakis EMJ, and
  Gonzales O. A comparison of glyburide and insulin
  in women with gestational diabetes. N Engl J Med
  20003431134-38.
• Greene MF. Oral hypoglycemic drugs for
  gestational diabetes. N Engl J Med
  20003431178-79.
• Briggs GK, Freeman RK, Yaffe SJ, editors. Drugs
  in Pregnancy and Lactation. 5th ed. Baltimore
  Williams Wilkins. 1998

21
CONCLUSIONS

• In women with gestational diabetes, glyburide is
  a clinically effective alternative to insulin
  therapy
• ."The adverse reactions in the newborn are
  therefore avoided and control of diabetes in the
  mother is as good as with insulin. Both in terms
  of efficacy and adverse reactions there is no
  statistical significant difference
• that glyburide, a type of sulfonylurea drug, does
  not pass through the placenta .

22

• The percentage of newborns who were large for
  their gestational age was similar in both groups
  of women. In addition, there were no
  statistically significant differences in the
  infants' rates of birth defects, lung
  complications or low blood sugar.

23
But

• We must still exercise caution in applying these
  findings to clinical practice. Results need to be
  duplicated and the risk for fetal malformations
  with the use of these agents during pregnancy
  remains a concern."