Dosing and uses of Glucotrol, Glucotrol XL, Minodiab (glipizide)
Adult dosage forms and strengths
tablet
- 5mg
- 10mg
tablet, extended-release
- 2.5mg
- 5mg
- 10mg
Type 2 Diabetes Mellitus
Immediate-release tablet
- 5 mg PO qDay initially; increase by 2.5-5 mg PRN every several days based on blood glucose
- Maintenance range: 2.5-20 mg PO qDay or q12hr; not to exceed 40 mg/day
Extended-release tablets (Glucotrol XL)
- Initial: 5 mg/day PO given with breakfast; dose adjustment based on blood glucose should not be done more frequently than every 7 days
- Maintenance range: 5-10 mg PO qDay; not to exceed 20 mg/day
Dosing considerations
- Doses >15 mg: PO divided q12hr recommended
Conversion From Immediate Release to Extended Release
Administer the nearest equivalent immediate-release daily dose as extended-release tablet once daily
Alternatively, administer 5 mg PO initially; titrate as necessary
Conversion From Long Half-Life Agents
Observe patients carefully for 1-2 weeks when being converted from long half-life sulfonylureas to glipizide, because of potential for overlapping of hypoglycemic effects
Transferring From Insulin Therapy to Glipizide IR or ER
Current insulin dose <20 units: Discontinue insulin and initiate glipizide therapy at recommended dose
Current insulin dose >20 units: Decrease insulin dose by 50% and initiate glipizide at recommended dose; decrease insulin dose gradually based on patient’s response
Dosing Modifications
Hepatic impairment: 2.5 mg PO qDay initially (immediate release); extended release not studied
Renal impairment: Not studied; if GFR <50 mL/min, may decrease dose by 50% (suggested)
Pediatric dosage forms and strengths
Safety and efficacy not established
Geriatric dosage forms and strengths
Diabetes
2.5 mg PO qDay initially; increase by 2.5-5 mg/day every 1-2 weeks as determined by blood glucose response at intervals of several days
May switch to extended release once daily tablets at the nearest equivalent total daily dose or lower end of recommended range; not to exceed 20 mg/day
Dosing considerations
Because elderly patients are susceptible to the hypoglycemic effects of glucose-lowering drugs, the question of how tightly glucose levels should be controlled in the elderly is controversiaL
Recognizing hypoglycemia in elderly patients may be challenging
Monitoring other parameters associated with cardiovascular disease, such as blood pressure and cholesterol, may be more important than normalized glycemic controL
Initial and maintenance dosing should be conservative
Glucotrol, Glucotrol XL, Minodiab (glipizide) adverse (side) effects
Frequency not defined
Dermatologic reactions
Abdominal pain
Diarrhea
Syncope
Constipation
Flatulence
Dizziness
Nervousness
Headache
Anxiety
Depression
Drowsiness
Erythema
Heartburn
Maculopapular eruptions
Hypoglycemia
Morbilliform eruptions
Nausea/vomiting
Urticaria
Cholestatic jaundice and hepatitis occur rarely but may progress to liver failure
Warnings
Contraindications
Hypersensitivity; sulfa allergy
Type 1 diabetes
Diabetic ketoacidosis with or without coma
Cautions
Patients with risk of severe hypoglycemia include the elderly, debilitated, or malnourished; adrenal or pituitary insufficiency; stress due to infection, fever, trauma, or surgery; concomitant use with beta-blockers or other sympatholytic agents may impair the patient's ability to recognize the signs and symptoms of hypoglycemia; use with caution
If patient is exposed to stress (fever, trauma, infection, surgery), it may be necessary to discontinue glipizide and initiate insulin
Use caution in hepatic/renal impairment
Use with caution in pregnancy and lactation
Increased risk of cardiovascular mortality suggested by product labeling but data is limited
FDA-approved product labeling for many medications have included a broad contraindication in patients with a prior allregic reaction to sulfonamides; however, recent studies have suggested that crossreactivity between antibiotic sulfonamides and nonantibiotic sulfonamides is unlikely to occur; increase in cardiovascular mortality suggested by product labeling but data is limited
Hypoglycemia is more likely to occur when caloric intake is deficient, after severe or prolonged exercise, when alcohol is ingested, or when more than one glucose-lowering drug is used
Hypoglycemia may be difficult to recognize in patients with autonomic neuropathy
Hemolytic anemia may occur with glucose 6-phosphate dehydrogenase (G6PD) deficiency when treated with sulfonylurea agents; consider a nonsulfonylurea alternative
Avoid using the extended-release tablets in patients with severe gastrointestinal narrowing of esophageal dysmotility
Clinical studies have not found conclusive evidence that anti-diabetic drugs reduce macrovascular risk
Loss of efficacy following prolonged use possible; if no contributing factors, to explain loss of efficacy identified, consider discontinuing therapy; additional antidiabetic therapy will be required
Drug interactions overview
- The hypoglycemic action of sulfonylureas may be potentiated by certain drugs including nonsteroidal anti-inflammatory agents, some azoles, and other drugs that are highly protein bound, salicylates, sulfonamides, chloramphenicol, probenecid, coumarins, monoamine oxidase inhibitors, quinolones and beta adrenergic blocking agents; conversely, certain drugs tend to produce hyperglycemia and may lead to loss of control, including thiazides and other diuretics, corticosteroids, phenothiazines, thyroid products, estrogens, oral contraceptives, phenytoin, nicotinic acid, sympathomimetics, calcium channel blocking drugs, and isoniazid; when coadministering glipizide with such drugs, patient should be observed closely for hypoglycemia or hyperglycemia; when such drugs are withdrawn, observe patient closely for loss of control
Pregnancy and lactation
Pregnancy category: C
Lactation: Not known if crosses into breast milk; not recommended
Pregnancy categories
A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.
B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.
C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.
D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.
X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.
NA: Information not available.
Pharmacology of Glucotrol, Glucotrol XL, Minodiab (glipizide)
Mechanism of action
Initial effect to increase insulin secretion from pancreatic beta cells; may also decrease rate of hepatic glucose production and increase insulin receptor sensitivity
Absorption
Bioavailability: 100% (Glucotrol)
Onset: Initial effect (30 min); max effect: (2-3 hr) (Glucotrol)
Duration: 12-24 hr (Glucotrol)
Peak plasma time: 1-3 hr (IR); 6-12 hr (ER)
Distribution
Protein bound: 99% (Glucotrol)
Vd: 10-11 L (Glucotrol)
Metabolism
Extensively metabolized in liver to inactive metabolites
Metabolites: Hydroxycyclohexyl derivatives (inactive)
Elimination
Half-life: 2-5 hr (Glucotrol)
Excretion: Urine (63-90%); feces: (10%)
