Summary of Product Characteristics Updated 23-Aug-2016 | Pfizer Limited
PosologyAs for any hypoglycaemic agent, dosage must be adapted for each individual case.Short term administration of glipizide may be sufficient during periods of transient loss of control in patients usually controlled well on diet.In general, glipizide should be given shortly before a meal to achieve the greatest reduction in post-prandial hyperglycaemia.
Initial DoseThe recommended starting dose is 5 mg, given before breakfast or the midday meal. Mild diabetics, geriatric patients or those with liver disease may be started on 2.5 mg.
TitrationDosage adjustments should ordinarily be in increments of 2.5 mg or 5 mg, as determined by blood glucose response. At least several days should elapse between titration steps. The maximum recommended single dose is 15 mg. If this is not sufficient, splitting the daily dosage may prove effective. Doses above 15 mg should ordinarily be divided.
MaintenanceSome patients may be effectively controlled on a once-a-day regimen. Total daily dosage above 15 mg should ordinarily be divided.The maximum recommended daily dosage is 20 mg.
Paediatric populationSafety and effectiveness in children have not been established.
Use in Elderly and High-Risk PatientsIn elderly, debilitated and malnourished patients or patients with an impaired renal or hepatic function, the initial and maintenance dosing should be conservative to avoid hypoglycaemic reactions (see Initial Dose and section 4.4).
Patients Receiving Other Oral Hypoglycaemic AgentsAs with other sulfonylurea class hypoglycaemics, no transition period is necessary when transferring patients to glipizide. Patients should be observed carefully (1-2 weeks) for hypoglycaemia when being transferred from longer half-life sulfonylureas (e.g. chlorpropamide) to glipizide due to potential overlapping of drug effect.
Method of administrationFor oral use only.
Glucose-6-phosphate dehydrogenase deficiencySince glipizide belongs to the class of sulfonylurea agents, caution should be used in patients with G6PD deficiency. Treatment of patients with G6PD deficiency with sulfonylurea agents can lead to haemolytic anaemia and a non-sulfonylurea alternative should be considered.
HypoglycaemiaAll sulfonylurea agents are capable of producing severe hypoglycaemia. 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 hypoglycaemic reactions. Elderly, debilitated or malnourished patients and those with adrenal or pituitary insufficiency are particularly susceptible to the hypoglycaemic action of glucose-lowering drugs.Hypoglycaemia may be difficult to recognise in the elderly, and in people who are taking beta-adrenergic blocking drugs (see section 4.5). Hypoglycaemia 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 glucoseWhen a patient stabilised on a 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.The effectiveness of any oral hypoglycaemic drug, including glipizide, in lowering blood glucose to a desired level decreases in many patients over a period of time, which may be due to progression of the severity of diabetes or due to diminished responsiveness to the drug. This phenomenon is known as secondary failure, to distinguish it from primary failure in which the drug is ineffective in an individual patient when first given. Adequate adjustment of dose and adherence to diet should be assessed before classifying a patient as a secondary failure.
Renal and Hepatic DiseaseThe pharmacokinetics and/or pharmacodynamics of glipizide may be affected in patients with impaired renal or hepatic function. If hypoglycaemia should occur in such patients, it may be prolonged and appropriate management should be instituted.
Information for PatientsPatients should be informed of the potential risks and advantages of glipizide and of alternative modes of therapy. They should also be informed about the importance of adherence to dietary instructions, of a regular exercise program, and of regular testing of urine and/or blood glucose.The risks of hypoglycaemia, its symptoms and treatment, and conditions that predispose to its development should be explained to patients and responsible family members. Primary and secondary failure should also be explained.
Laboratory TestsBlood and urine glucose should be monitored periodically. Measurement of glycosylated haemoglobin may be useful.This product contains lactose. Patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency, glucose-galactose malabsorption should not take this medicine.
The following products are likely to increase the hypoglycaemic effect:- Contraindicated combinations
MiconazoleIncrease in hypoglycaemic effect, possibly leading to symptoms of hypoglycaemia or even coma.- Inadvisable combinations
Nonsteroidal Anti-inflammatory Drugs (e.g. phenylbutazone)Increase in hypoglycaemic effect of sulfonylureas (displacement of sulfonylurea binding to plasma proteins and/or decrease in sulfonylurea elimination).
AlcoholIncrease in hypoglycaemic reaction, which can lead to hypoglycaemic coma.- Combinations requiring precaution
FluconazoleIncrease in the half-life of the sulfonylurea, possibly giving rise to symptoms of hypoglycaemia.
VoriconazoleAlthough not studied, voriconazole may increase the plasma levels of sulfonylureas, (e.g. tolbutamide, glipizide and glyburide) and therefore cause hypoglycaemia. Careful monitoring of blood glucose is recommended during co-administration.
Salicylates (acetylsalicylic acid)Increase in hypoglycaemic effect by high doses of acetylsalicylic acid (hypoglycaemic action of the acetylsalicylic acid).
Beta-blockersAll beta-blockers mask some of the symptoms of hypoglycaemia (i.e. palpitations and tachycardia). Most non cardio selective beta-blockers increase the incidence and severity of hypoglycaemia.
Angiotensin-converting Enzyme InhibitorsThe use of angiotensin-converting enzyme inhibitors may lead to an increased hypoglycaemic effect in diabetic patients treated with sulfonylureas.
CimetidineThe use of cimetidine may be associated with a reduction in post prandial blood glucose in patients treated with glipizide.The hypoglycaemic action of sulfonylureas, in general may also be potentiated by monoamine oxidase inhibitors, quinolones and drugs that are highly protein bound, such as sulfonamides, chloramphenicol, probenecid, coumarins and fibrates.When such drugs are administered to (or withdrawn from) a patient receiving glipizide, the patient should be observed closely for hypoglycaemia (or loss of control).The following products could lead to hyperglycaemia:- Inadvisable combinations
DanazolDiabetogenic effect of danazol. If it cannot be avoided, warn the patient and step up self monitoring of blood glucose and urine. Possibly adjust the dosage of antidiabetic agent during treatment with danazol and after its discontinuation.- Combinations requiring precaution
Phenothiazines (e.g. chlorpromazine) at High Doses (> 100 mg/day of chlorpromazine)Elevation in blood glucose (reduction in insulin release).
CorticosteroidsElevation in blood glucose.
Sympathomimetics (e.g. ritodrine, salbutamol, terbutaline)Elevation in blood glucose due to beta-2-adrenoceptor stimulation.
ProgestogensDiabetogenic effects of high-dose progestogens. Warn the patient and step up self-monitoring of blood glucose and urine. Possibly adjust the dosage of antidiabetic agent during treatment with the neuroleptics, corticoids or progestogen and after discontinuation.Other drugs that may produce hyperglycaemia and lead to a loss of control include the thiazides and other diuretics, thyroid products, oestrogens, oral contraceptives, phenytoin, nicotinic acid, calcium channel blocking drugs, and isoniazid.When such drugs are administered to (or withdrawn from) a patient receiving glipizide, the patient should be observed closely for hypoglycaemia.
PregnancyGlipizide is contraindicated in pregnancy.Glipizide was found to be mildly fetotoxic in rat reproductive studies. No teratogenic effects were found in rat or rabbit studies.Prolonged severe hypoglycaemia (4- 10 days) has been reported in neonates born to mothers who were receiving a sulfonylurea drug at the time of delivery.Because recent information suggests that abnormal blood glucose levels during pregnancy are associated with a higher incidence of congenital abnormalities, many experts recommend that insulin be used during pregnancy to maintain blood glucose levels as close to normal as possible.
Breast-feedingNo data are available on secretion into breast milk. Therefore glipizide is contraindicated in lactation.
Reporting of suspected adverse reactionsReporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via the Yellow Card Scheme at: www.mhra.gov.uk/yellowcard.
AbsorptionGastrointestinal absorption of glipizide in humans is uniform, rapid and essentially complete. Peak plasma concentrations occur 1 to 3 hours after a single oral dose. The half-life of elimination ranges from 2 to 4 hours in normal subjects, whether given intravenously or orally. The metabolic and excretory patterns are similar with the two routes of administration, indicating that first-pass metabolism is not significant. Glipizide does not accumulate in plasma on repeated oral administration. Total absorption and disposition of an oral dose were unaffected by food in normal volunteers, but absorption was delayed by about 40 minutes. Thus, glipizide was more effective when administered about 30 minutes before, rather than with, a test meal in diabetic patients.
DistributionProtein binding was studied in serum from volunteers who received either oral or intravenous glipizide and found to be 98 % to 99 % one hour after either route of administration. The apparent volume of distribution of glipizide after intravenous administration was 11 L, indicative of localisation within the extracellular fluid compartment. In mice, no glipizide or metabolites were detectable autoradiographically in the brain or spinal cord of males or females, nor in the foetuses of pregnant females. In another study, however, very small amounts of radioactivity were detected in the foetuses of rats given labelled drug.
BiotransformationThe metabolism of glipizide is extensive and occurs mainly in the liver.
EliminationThe primary metabolites are inactive hydroxylation products and polar conjugates and are excreted mainly in the urine. Less than 10 % unchanged glipizide is found in urine.
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