Glyburide (Doanil tablet)

/الحناوى محمد محمد الحناوى/ د محمد محمد د التوليد و النساء التوليد أخصائى و النساء أخصائى

- – مصر دمياط البر رأس مصر – - مستشفى دمياط البر رأس مستشفىwww. Mmhennawy.co.nrwww. Mmhennawy.co.nr

shows promise for women with gestational diabetes and pregnant women with type 2 diabetes

What about women with What about women with type type 2 diabetes, who are taking 2 diabetes, who are taking diabetes pills, or women who diabetes pills, or women who have had gestational diabetes have had gestational diabetes in the past? in the past?

Will they need insulin, or will Will they need insulin, or will diabetes pills be okay to use diabetes pills be okay to use during pregnancyduring pregnancy??

glyburideglyburide Glyburide is a sulfonylurea drug used to Glyburide is a sulfonylurea drug used to

lower blood sugar levels in people with type lower blood sugar levels in people with type 2 diabetes(non-insulin-dependent)2 diabetes(non-insulin-dependent)

Glyburide appears to lower the blood Glyburide appears to lower the blood glucose acutely by stimulating the release glucose acutely by stimulating the release

of insulin from the pancreas, an effect of insulin from the pancreas, an effect dependent upon functioning beta cells in dependent upon functioning beta cells in

the pancreatic isletsthe pancreatic isletsglyburide, a type of sulfonylurea drug, does glyburide, a type of sulfonylurea drug, does

not pass through the placentanot pass through the placenta

PharmacokineticsPharmacokinetics C23H28ClN3O5SC23H28ClN3O5S glyburideglyburide Single dose studies with glyburide Single dose studies with glyburide

tablets in normal subjects demonstrate tablets in normal subjects demonstrate significant absorption of glyburide within significant absorption of glyburide within 1 hour, peak drug levels at about 4 hours 1 hour, peak drug levels at about 4 hours (2-3 hours for micronized glyburide), and (2-3 hours for micronized glyburide), and low but detectable levels at 24 hourslow but detectable levels at 24 hours

GlyburideGlyburideAlso indexed as: DiabetaAlso indexed as: Diabeta®®, ,

Glynase ,PrestabGlynase ,Prestab®®, Micronase, Micronase®®, Pres , Pres TabTab®®

SulfonylureasSulfonylureas First-Generation Agents: First-Generation Agents:

Generic Name: acetohexamideGeneric Name: acetohexamideBrand Name: DymelorBrand Name: Dymelor

Generic Name: chloropropamideGeneric Name: chloropropamideBrand Name: DiabineseBrand Name: Diabinese

Generic Name: tolazamideGeneric Name: tolazamideBrand Name: TolinaseBrand Name: Tolinase

Generic Name: tolbutamideGeneric Name: tolbutamideBrand Name: OrinaseBrand Name: Orinase

Second-Generation AgentsSecond-Generation Agents: : Generic Name: glimepirideGeneric Name: glimepiride

Brand Name: Brand Name: AmarylAmaryl Generic Name: glipizideGeneric Name: glipizide

Brand Names: GlucotrolBrand Names: Glucotrol, , Glucotrol XL Glucotrol XL Generic Name: glyburideGeneric Name: glyburide

Brand Names: DiaBeta, MicronaseBrand Names: DiaBeta, Micronase, , GlynaseGlynase Combination AgentsCombination Agents: : Generic Name: glyburide plus Generic Name: glyburide plus metforminmetformin

Brand Name: Brand Name: GlucoVanceGlucoVance

dosagedosage There is no fixed dosage regimen for the There is no fixed dosage regimen for the

management of diabetes mellitus with management of diabetes mellitus with glyburide or any other hypoglycemic glyburide or any other hypoglycemic agent. In addition to the usual monitoring agent. In addition to the usual monitoring of urinary glucose, the patient's blood of urinary glucose, the patient's blood glucose must also be monitored glucose must also be monitored periodically to determine the minimum periodically to determine the minimum effective dose for the patient effective dose for the patient

Glyburide may be taken with food to avoid Glyburide may be taken with food to avoid gastrointestinal (GI) upsetgastrointestinal (GI) upset

Glyburide is a white, crystalline compound, Glyburide is a white, crystalline compound, formulatedformulated

as Micronase tablets of as Micronase tablets of 1.25, 2.5, and 5 mg strengths for oral 1.25, 2.5, and 5 mg strengths for oral

administration.administration. The usual starting dose of standard glyburide The usual starting dose of standard glyburide

tablets is 2.5-5 mg dailytablets is 2.5-5 mg daily (micronized glyburide tablets: 1.5-3 mg (micronized glyburide tablets: 1.5-3 mg

daily),daily), administered with breakfast or the first main administered with breakfast or the first main

meal. Those patients who may be more meal. Those patients who may be more sensitive to hypoglycemic drugs should be sensitive to hypoglycemic drugs should be started at 1.25 mg of standard glyburide daily started at 1.25 mg of standard glyburide daily (0.75 mg for micronized glyburide daily).(0.75 mg for micronized glyburide daily).

Maximum DoseMaximum DoseStandard Glyburide: Daily doses of Standard Glyburide: Daily doses of

more than 20 mg are not more than 20 mg are not recommendedrecommended..

Micronized Glyburide: Daily doses of Micronized Glyburide: Daily doses of more than 12 mg are not more than 12 mg are not recommendedrecommended

glyburideSU generic Intermediate glyburideSU generic Intermediate acting1.25, 2.5, 5mg5 - 20mgacting1.25, 2.5, 5mg5 - 20mg

Dosage IntervalDosage Interval

Standard Glyburide: Once-a-day therapy Standard Glyburide: Once-a-day therapy is usually satisfactory. Some patients, is usually satisfactory. Some patients, particularly those receiving more than particularly those receiving more than 10 mg daily, may have a more 10 mg daily, may have a more satisfactory response with twice-a-day satisfactory response with twice-a-day dosagedosage..

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

CONTRAINDICATIONSCONTRAINDICATIONSGlyburide Tablets are Glyburide Tablets are

Contraindicated in Patients with:Contraindicated in Patients with:1.1. Known hypersensitivity or allergy Known hypersensitivity or allergy

to the drug. to the drug. 2.2. Diabetic ketoacidosis, with or Diabetic ketoacidosis, with or

without coma. This condition should without coma. This condition should be treated with insulin. be treated with insulin.

3.3. Type I diabetes mellitus, as sole Type I diabetes mellitus, as sole therapy.therapy.

PregnancyPregnancy , Effects , Effects TeratogenicTeratogenic, Pregnancy Category B, Pregnancy Category B Reproduction studies have been performed in rats and Reproduction studies have been performed in rats and

rabbits at doses up to 500 times the human dose and rabbits at doses up to 500 times the human dose and have revealed no evidence of impaired fertility or harm have revealed no evidence of impaired fertility or harm to the fetus due to glyburide. There are, however, no to the fetus due to glyburide. There are, however, no adequate and well-controlled studies in pregnant adequate and well-controlled studies in pregnant women. Because animal reproduction studies are not women. Because animal reproduction studies are not always predictive of human response, this drug should always predictive of human response, this drug should be used during pregnancy only if clearly needed.be used during pregnancy only if clearly needed.

EffectsEffects NonteratogenicNonteratogenic : : 4-10 days  Prolonged severe hypoglycemia (has been 4-10 days  Prolonged severe hypoglycemia (has been

reported in neonates born to mothers who were reported in neonates born to mothers who were receiving a sulfonylurea drug at the time of delivery. receiving a sulfonylurea drug at the time of delivery. This has been reported more frequently with the use of This has been reported more frequently with the use of agents with prolonged half-lives. If glyburide is used agents with prolonged half-lives. If glyburide is used during pregnancy, it should be discontinued at least 2 during pregnancy, it should be discontinued at least 2 weeks before the expected delivery date.weeks before the expected delivery date.

HOW SUPPLIEDHOW SUPPLIEDMicronase Tablets are Supplied as FollowsMicronase Tablets are Supplied as Follows Micronase Tablets 1.25 mg:Micronase Tablets 1.25 mg:  White, round, scored and White, round, scored and

imprinted MICRONASE 1.25. imprinted MICRONASE 1.25. Micronase Tablets 2.5 mg:Micronase Tablets 2.5 mg:  Dark pink, round, scored Dark pink, round, scored

and imprinted MICRONASE 2.5. and imprinted MICRONASE 2.5. Micronase Tablets 5 mg:Micronase Tablets 5 mg:  Blue, round, scored and Blue, round, scored and

imprinted MICRONASE 5.imprinted MICRONASE 5. Storage:Storage:  Store at controlled room temperature 20-25°C Store at controlled room temperature 20-25°C

(68-77°F). Keep container tightly closed. Dispensed in (68-77°F). Keep container tightly closed. Dispensed in well-closed containers with safety closures.well-closed containers with safety closures.

Glynase PresTab Tablets are Supplied as FollowsGlynase PresTab Tablets are Supplied as Follows Glynase PresTab Tablets 1.5 mg:Glynase PresTab Tablets 1.5 mg:  White, ovoid, White, ovoid,

imprinted GLYNASE 1.5/PT Score PT, contour, scored. imprinted GLYNASE 1.5/PT Score PT, contour, scored. Glynase PresTab Tablets 3mg:Glynase PresTab Tablets 3mg:  Blue, ovoid, imprinted Blue, ovoid, imprinted

GLYNASE 3/PT Score Pt, contour, scored. GLYNASE 3/PT Score Pt, contour, scored. Glynase PresTab Tablets 6 mg:Glynase PresTab Tablets 6 mg:  Yellow, ovoid, Yellow, ovoid,

imprinted GLYNASE 6/PT Score PT, contour, imprinted GLYNASE 6/PT Score PT, contour,

insulin is considered the drug of insulin is considered the drug of choice for the treatment of choice for the treatment of gestational diabetes; however, it gestational diabetes; however, it is expensive and its is expensive and its administration is inconvenientadministration is inconvenient

""Women with gestational Women with gestational diabetes mellitus are rarely diabetes mellitus are rarely treated with a sulfonylurea drug, treated with a sulfonylurea drug, because of concern about because of concern about teratogenicity and neonatal teratogenicity and neonatal hypoglycemia hypoglycemia . .

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

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

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

published in The New England published in The New England Journal of Medicine Journal of Medicine

Volume 343Volume 343 October 19, 2000 October 19, 2000 Number 16Number 16

Of the 404 womenwith singleton pregnancies and Of the 404 womenwith singleton pregnancies and gestational diabetes that required treatmen , 201 gestational diabetes that required treatmen , 201 received glyburide and 203 received human received glyburide and 203 received human insulininsulin

between 11 and 33 weeks of gestation between 11 and 33 weeks of gestation The meanThe mean (± (± SD) serum glucose concentration SD) serum glucose concentration

observed during routine visits to the clinic was observed during routine visits to the clinic was 102102± 24 ± 24 mg/dl in the glyburide group and 99mg/dl in the glyburide group and 99± 22 ± 22 mg/dl in the insulin groupmg/dl in the insulin group. .

In addition, 82% of women in the glyburide In addition, 82% of women in the glyburide group and 88% of women in the insulin group and 88% of women in the insulin group had home blood glucose group had home blood glucose measurements that fell into the desired measurements that fell into the desired rangerange

. . No significant differences existed between No significant differences existed between the two groups with regards to perinatal the two groups with regards to perinatal outcome outcome ..

The incidence of macrosomia The incidence of macrosomia between the groups was similar; 11% between the groups was similar; 11% in the glyburide group and 10% in in the glyburide group and 10% in the insulin groupthe insulin group

. . The cord serum of all infants was The cord serum of all infants was measured for the presence of measured for the presence of glyburide; however, the drug was not glyburide; however, the drug was not detected in any of the infants detected in any of the infants ..

There were no significant differences There were no significant differences between the glyburide and insulin groups in between the glyburide and insulin groups in the percentage of infants who were the percentage of infants who were large for large for gestational agegestational age (12 percent and 13 percent, (12 percent and 13 percent, respectivelyrespectively))

who had who had macrosomiamacrosomia, defined as a birth , defined as a birth weight of 4000 g or more (7 percent and 4 weight of 4000 g or more (7 percent and 4 percentpercent

); ); who had who had lung complicationslung complications (8 percent and 6 (8 percent and 6 percentpercent

); ); who had who had hypoglycemiahypoglycemia (9 percent and 6 (9 percent and 6 percentpercent

who were admitted to a who were admitted to a neonatal intensive neonatal intensive care unitcare unit (6 percent and 7 percent (6 percent and 7 percent

who had who had fetal anomaliesfetal anomalies (2 percent and 2 (2 percent and 2 percent )percent )

The The cord-serum insulincord-serum insulin concentrations were concentrations were similar in the two groups)similar in the two groups)

REFERENCESREFERENCES

Langer OD, Conway DL, Berkus MD, Langer OD, Conway DL, Berkus MD, Xenakis EMJ, and Gonzales O. A Xenakis EMJ, and Gonzales O. A comparison of glyburide and insulin in comparison of glyburide and insulin in women with gestational diabetes. N Engl J women with gestational diabetes. N Engl J Med 2000;343:1134-38.Med 2000;343:1134-38.

Greene MF. Oral hypoglycemic drugs for Greene MF. Oral hypoglycemic drugs for gestational diabetes. N Engl J Med gestational diabetes. N Engl J Med 2000;343:1178-79.2000;343:1178-79.

Briggs GK, Freeman RK, Yaffe SJ, editors. Briggs GK, Freeman RK, Yaffe SJ, editors. Drugs in Pregnancy and Lactation. 5th ed. Drugs in Pregnancy and Lactation. 5th ed. Baltimore: Williams & Wilkins. 1998Baltimore: Williams & Wilkins. 1998

CONCLUSIONSCONCLUSIONS::

In women with gestational diabetes, In women with gestational diabetes, glyburide is a clinically effective alternative glyburide is a clinically effective alternative to insulin therapyto insulin therapy

."."The adverse reactions in the newborn are The adverse reactions in the newborn are therefore avoided and control of diabetes in therefore avoided and control of diabetes in the mother is as good as with insulin. Both the mother is as good as with insulin. Both in terms of efficacy and adverse reactions in terms of efficacy and adverse reactions there is no statistical significant differencethere is no statistical significant difference

that glyburide, a type of sulfonylurea drug, that glyburide, a type of sulfonylurea drug, does not pass through the placenta does not pass through the placenta ..

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

ButButWe must still exercise caution We must still exercise caution

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