GLIPIZIDE
FULL PRESCRIBING INFORMATION: CONTENTS*
- GLIPIZIDE DESCRIPTION
- CLINICAL PHARMACOLOGY
- INDICATIONS & USAGE
- GLIPIZIDE CONTRAINDICATIONS
- WARNINGS
- PRECAUTIONS
- GLIPIZIDE ADVERSE REACTIONS
- OVERDOSAGE
- DOSAGE & ADMINISTRATION
- HOW SUPPLIED
- STORAGE AND HANDLING
- PACKAGE LABEL.PRINCIPAL DISPLAY PANEL SECTION
FULL PRESCRIBING INFORMATION
GLIPIZIDE DESCRIPTION
CLINICAL PHARMACOLOGY
Mechanism of Action:Pharmacokineticsbelow).
Other Effects:
Pharmacokinetics:
INDICATIONS & USAGE
GLIPIZIDE CONTRAINDICATIONS
WARNINGS
SPECIAL WARNING ON INCREASED RISK OF CARDIOVASCULAR MORTALITY: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. This warning is based on the study conducted by the University Group Diabetics Program (UGDP), a long-term prospective clinical trial designed to evaluate the effectiveness of glucose-lowering drugs in preventing or delaying vascular complications in patients with non-insulin-dependent diabetes. The study involved 823 patients who were randomly assigned to one of four treatment groups. (Diabetes, 19, supp. 2:747-830, 1970).
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 2times that of patients treated with diet alone. A significant increase in total mortality was not observed, but the use of tolbutamide was discontinued based on the increase in cardiovascular mortality, thus limiting the opportunity for the study to show an increase in overall mortality. Despite controversy regarding the interpretation of these results, the findings of the UGDP study provide an adequate basis for this warning. The patient should be informed of the potential risks and advantages of glipizide and of alternative modes of therapy.
Although only one drug in the sulfonylurea class (tolbutamide) was included in this study, it is prudent from a safety standpoint to consider that this warning may also apply to other oral hypoglycemic drugs in this class, in view of their close similarities in mode of action and chemical structure.
PRECAUTIONS
GeneralRenal and Hepatic Disease:The metabolism and excretion of glipizide may be slowed in patients with impaired renal and/or hepatic function. If hypoglycemia should occur in such patients, it may be prolonged and appropriate management should be instituted.
Hypoglycemia:All sulfonylurea drugs are capable of producing severe hypoglycemia. Proper patient selection, dosage, and instructions are important to avoid hypoglycemic episodes. Renal or hepatic insufficiency may cause elevated blood levels of glipizide and the latter may also diminish gluconeogenic capacity, both of which increase the risk of serious hypoglycemic reactions. Elderly, debilitated or malnourished patients, and those with adrenal or pituitary insufficiency are particularly susceptible to the hypoglycemic action of glucose-lowering drugs. Hypoglycemia may be difficult to recognize in the elderly, and in people who are taking beta-adrenergic blocking drugs. 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.
Loss of Control of Blood Glucose:When a patient stabilized on any diabetic regimen is exposed to stress such as fever, trauma, infection, or surgery, a loss of control may occur. At such times, it may be necessary to discontinue glipizide and administer insulin.
Laboratory Tests:
Information for Patients:
Drug Interactions:
Carcinogenesis, Mutagenesis, Impairment of Fertility:
Pregnancy:
Nursing Mothers:
Pediatric Use:
Geriatric Use:
GLIPIZIDE ADVERSE REACTIONS
Hypoglycemia:SeePRECAUTIONSandOVERDOSAGEsections.
Gastrointestinal: Gastrointestinal disturbances are the most common reactions. Gastrointestinal complaints were reported with the following approximate incidence: nausea and diarrhea, one in seventy; constipation and gastralgia, one in one hundred. They appear to be dose-related and may disappear on division or reduction of dosage. Cholestatic jaundice may occur rarely with sulfonyluras: Glipizide should be discontinued if this occurs.
Dermatologic:Allergic skin reactions including erythema, morbilliform or maculopoplar eruptions, urticaria, pruritus, and eczema have been reported in about one in sevty patients. These may be transient and may disappear despite continued use of glipizide; it skin reactions persist, the drug should be discontinued. Porphyria cutanea tarda and photosensitivity reactions have been reported with sulonyluras.
Hematologic:Leukopenia, agranulocytosis, thrombocytopenia, hemolytic anemia, aplastic anemia, and pancytopenia have been reported with sulfonylureas.
Metabolic:Hepatic porphyria and disulfiram-like reactions have been reported with sulfonylureas. In the mouse, glipizide pretreatment did not cause an accumulation of acetaldehyde after ethanol administration. Clinical experience to date has shown that glipizide has an extremely low incidence of disulfiram-like alcohol reactions.
Endocrine Reactions:Cases of hyponatremia and the syndrome of inappropriate antidiuretic hormone (SIADH) secretion have been reported with this and other sulfonylureas.
Miscellaneous:Dizziness, drowsiness, and headache have each been reported in about one in fifty patients treated with glipizide. They are usually transient and seldom require discontinuance of therapy.
Laboratory Tests:The pattern of laboratory test abnormalities observed with glipizide was similar to that for other sulfonylureas. Occasional mild to moderate elevations of SGOT, LDH, alkaline phosphatase, BUN and creatinine were noted. One case of jaundice was reported. The relationship of these abnormalities to glipizide is uncertain, and they have rarely been associated with clinical symptoms.
OVERDOSAGE
DOSAGE & ADMINISTRATION
Initial Dose:The recommended starting dose is 5 mg, given before breakfast. Geriatric patients or those with liver disease may be started on 2.5 mg.
Titration:Dosage adjustments should ordinarily be in increments of 2.5 to 5 mg, as determined by blood glucose response. At least several days should elapse between titration steps. If response to a single dose is not satisfactory, dividing the dose may prove effective. The maximum recommended once daily dose is 15 mg. Doses above 15 mg should ordinarily be divided and given before meals of adequate caloric content. The maximum recommended total daily dose is 40 mg.
Maintenance:Some patients may be effectively controlled on a once-a-day regimen, while others show better response with divided dosing. Total daily doses above 15 mg should ordinarily be divided. Total daily doses above 30 mg have been safely given on a b.i.d. basis to long-term patients.
PRECAUTIONSsection).
Patients Receiving Insulin:As with other sulfonylurea-class hypoglycemics, many stable noninsulin- dependent diabetic patients receiving insulin may be safely placed on glipizide. When transferring patients from insulin to glipizide, the following general guidelines should be considered:
Patients Receiving Other Oral Hypoglycemic Agents:As with other sulfonylurea-class hypoglycemics, no transition period is necessary when transferring patients to glipizide. Patients should be observed carefully (1 to 2 weeks) for hypoglycemia when being transferred from longer half-life sulfonylureas (e.g., chlorpropamide) to glipizide due to potential overlapping of drug effect.
HOW SUPPLIED
STORAGE AND HANDLING
PACKAGE LABEL.PRINCIPAL DISPLAY PANEL SECTION
GLIPIZIDEGLIPIZIDE TABLET
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PLEASE, BE CAREFUL!
Be sure to consult your doctor before taking any medication!
