Glyburide

(micronase, glynase, DiaBeta)

shows promise for women with gestational diabetes and pregnant women with type 2 diabetes
BY ABHISHEK JAGUESSAR

 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?

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

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

Sulfonylureas First-Generation Agents:

Generic Name: acetohexamide Brand Name: Dymelor Generic Name: chloropropamide Brand Name: Diabinese Generic Name: tolazamide Brand Name: Tolinase Generic Name: tolbutamide Brand Name: Orinase Second-Generation Agents: Generic Name: glimepiride Brand Name: Amaryl Generic Name: glipizide Brand Names: Glucotrol ,Glucotrol XL Generic Name: glyburide Brand Names: DiaBeta, Micronase ,Glynase Combination Agents: Generic Name: glyburide plus metformin Brand Name: GlucoVance

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

 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).

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

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

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.

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.

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,

 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 .

 . 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 secondgeneration sulfonylureas for the treatment of gestational diabetes, more studies need to be conducted before these medications can be considered safe in pregnancy.

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

The new sulphonylurea called glyburide does not cross the placental barrier

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 24mg/dl in the glyburide group and 99 22 mg/dl in the insulin group .

 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 .

 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 .

 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)

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 2000;343:1134-38. Greene MF. Oral hypoglycemic drugs for gestational diabetes. N Engl J Med 2000;343:1178-79. Briggs GK, Freeman RK, Yaffe SJ, editors. Drugs in Pregnancy and Lactation. 5th ed. Baltimore: Williams & Wilkins. 1998

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 .

 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.

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."