Glipizide

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Contents 1 Description 2 Mechanism of Action 3 Time Required for Therapeutic Response 4 Pharmacokinetics 5 Special Population Pharmacokinetics 6 Indications and Dosages 6.1 FDA Approved Indications 6.2 Non-FDA Approved Indications 6.3 Dosage Adjustment 6.4 Dosage Limits 7 Administration 8 Monitoring Parameters 9 Contraindications/Precautions 9.1 Contraindications 9.2 Precautions 9.3 Pregnancy indications 9.4 Breast-feeding indications 10 Drug-Drug, -Food, -Herb Interactions 11 Adverse Reactions/Side Effects 12 Overdosage Measures 13 Product Information and Distribution 14 Patient Information 15 References 16 PUBMED References 16.1 Efficacy Trial Articles 16.2 Therapeutic Class Comparison Articles 16.3 Pharmacokinetics Articles 16.4 Drug Interaction Articles 16.5 Adverse Effects Articles 16.6 Compliance Articles 16.7 Pharmacoeconomic Articles 17 External Links	This page is not completed and has not been reviewed for accuracy. You are reading a non-certified PubDrug document. This document is incomplete and not ready for final editing, review, and certification. Until this document is certified, any registered PubDrug user may edit its content. Authored by: author signature (type four tildes) Certified by: frahman Glipizide quick reference Image:Glipizide.png
	Glipizide general drug information
	Pronunciation	GLIP-eh-zide (.wav file)
	Trade Name(s)	Glucotrol
	How Supplied	Tablets:10mg, 5mg, ER 10mg, 5mg and 2.5mg
	Generic Availability	yes
	Patent Expiry Date	type date on which patent expires
	Classification	Sulfonylurea
	Schedule	Rx
	Pregnancy Category	C
	Breast-feeding	Glipizide is not found in breast milk
	Glipizide chemical information
	IUPAC Name	-[2-[4-(cyclohexylcarbamoylsulfamoyl)phenyl]ethyl]- 5-methyl-pyridine-2-
	Empirical Formula	type empirical formula
	Molecular Weight	type molecular weight g/mol
	pharmacokinetic information  |  [enter genomics URL (SEE www.pharmgkb.org) pharmacogenomic information]

Description

GLipizide an oral anti diabetic sulfonylurea used to treat type 2 Diabetes Mellitus. Sulfonylureas were the only oral blood sugar-lowering medications available in the United States until 1995 to treat type 2 diabetes mellitus. Sulfonylureas are classified into 2 generations based on their potency, duration of action and adverse drug effects. First generation sulfonylureas include actohexamide (dymelor), chlorpropamide (diabinese), tolazamide (tolinase) and tolbutmide (orinase). These drugs are not commonly prescribed because the newer second-generation sulfonylureas offer advantages in side effect profiles and have less drug interactions. Some of the second generation sulfonylureas include glimepiride (amaryl), glipizide (glucotrol), Glipizide ER (glucotrol XL), and glyburide (diabeta, glynase, micronase). All of the second generations have a similarl effect in lowering blood glucose level. However, some minor differences do exist between the second generation sufonylureas. For example, glipizide produces a more rapid lowering of blood sugar compared to glyburide but glyburide is slightly more potent than glipizide.^[1] Since all of the drugs in both classes are available generically and have similar effect in lowering blood glucose the choice of which to use will generally depend on the physician. Sulfonylureas are usually used along with diet and exercise to control blood glucose level. Glipizide also has been found to reduce plasma concentrations of very-low-density lipoproteins (VLDL), triglycerides, and plasma low-density lipoproteins (LDL) secondary to an improvement in plasma glucose regulation.^[2]

Mechanism of Action

Glipizide tends to lower blood glucose by stimulating pancreatic beta cells to release insulin. It reduces glucose output from the liver and increases insulin sensitivity at peripheral target sites. .^[2]

Time Required for Therapeutic Response

• Initial: 90 minute
• Maximum: 2-3 hours

Pharmacokinetics

Absorption
Oral absorption of a therapeutic dose produces a peak concentration between 1h to 3 h and absolute bioavailability is estimated to be between 80 to100%. However, the bioavailability of the extended release form is 90% and co administration of food with extended release tablet has no effect on the 2-3 hour lag time in drug absorption. However if glipizide is taken before a high fat breakfast the absorption of this drug is delayed by 40%. .^[2]

Distribution
Approximately 99% of the circulating drug is bound to serum plasma proteins, mainly to albumin. In humans, small amounts of glipizide are distributed into bile and very small amounts are distributed into erythrocytes .^[2]

Metabolism
Glipizide is extensively metabolized in the liver (approximately 90%) to inactive metabolites and both unchanged drug and the metabolites are excreted in the urine .^[2]

Excretion
Following oral administration in healthy individuals or in diabetic patients with normal renal and hepatic function, the terminal elimination half life of glipizide averages between 3- 4.7 hours. Approximately 90 % of the dose is excreted as biotransformation products in urine and feces. The terminal elimination half-life of glipizide metabolites are 2-6 hours in patients with normal renal and hepatic function. .^[2]

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Special Population Pharmacokinetics

• Renal insufficiency: Pharmacokinetics of glipizide are not significantly affected by renal impairment. However, conservative initial and maintenance doses should be given to people with renal impairment to avoid hypoglycemia. ^[3]
• Hepatic insufficiency: Hepatic insufficiency may cause elevated blood levels of glipizide and can also diminish gluconeogenic capacity, both of which increase the risk of hypoglycemia. ^[3]
• Hemodialysis: Type hemodialysis PK.
• Geriatric: Safety and efficacy of glipizide tablets in geriatric patients have not been specifically studied. In clinical studies of the drug, approximately 33% of the patients were 65 years of age or older. In general there were no differences in safety and efficacy of the drug between geriatric and younger patients throughout the clinical studies. However, the possibility that some older patients may exhibit increased sensitivity cannot be ruled out because of decreased hepatic and renal functions seen among the geriatric patients
• Pediatric: Safety and effectiveness in children have not been established
• Gender: No dosage adjustment is needed. .

Indications and Dosages

FDA Approved Indications

Treatment of Type 2 Diabetes Mellitus where hyperglycemia cannot be controlled by diet and exercise alone:

• Starting dose ( In adults).^[3]
  • 5mg by mouth once daily
• Maintenance dose:
  • 10-15mg once a day
  • using bullet points
• Titration schedule: Dose may be adjusted according to the patient’s response and the dosage adjustment should be in increments of 2.5 – 5 mg, depending on the serum glucose value

Add as many indications as necessary

• Starting dose: (In elderly).^[2]
  • 2.5 mg by mouth once daily
  • using bullet points
• Maintenance dose:
  • put maintenance dosing below
  • using bullet points
• Titration schedule: Careful dosage adjustments should be conducted in the elderly and the titration is based on fasting blood glucose

Non-FDA Approved Indications

• Put non-FDA-approved indications here. Use a bullet point for each indication. Dosing for these indications is unnecessary.

^[2]

Dosage Adjustment

Renal insufficiency: type renal insufficiency dosage adjustment here - use bullet points if necessary.
Hepatic insufficiency: Starting dose of glipizide should be 2.5 mg by mouth once daily in patients with hepatic insufficiency.
Hemodialysis: Not known.
Geriatric: Initial dose should be 2.5mg by mouth once daily .

Dosage Limits

• Adults: maximum dosage limit is 40mg/day .^[2]
• Elderly: maximum dosage limit is 40mg/day.^[2]
• Adolescents and children: safety and effective use has not been established
  

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Administration

• Route: Oral
• Method:Regular release glipizide should be given 30 minutes prior to a meal to achieve maxium efficacy.^[2]
  • Swallow the tablet with full (8 oz) glass of water. Do not take it with food, take it 30 minutes before meals..^[2]

• Route:Oral
• Method:Extended release glipizide tablet should be taken with meal and a glass of water to achieve maximum efficacy..^[2]

Monitoring Parameters

• Blood glucose ^[3]
• Urine glucose ^[3]
• HA1c^[3]
• Hepatic laboratory exams^[3]
• Hypoglycemia (fatigue,hunger,profuse sweating) ^[3]

Contraindications/Precautions

Contraindications

• Glipizide is contraindicated in patients with known sulfonylurea hypersensitivity.
• Glipizide is contraindicated as a sole therapy in patients with type 1 diabetes mellitus and in diabetic ketoacidosis. .^[4]

Precautions

• Caution should be exercised in patients with impaired hepatic function.
• Patients with hepatic porphyria should be monitored closely while on glipizide.
• Patients who are exposed to stress (such as fever,trauma, infection or surgery)can loose control of their blood sugar, resulting in discontinuation of glipizide and administration of insulin.

Pregnancy indications

Studies have shown that glipizide crosses the placenta. Abnormal blood glucose levels are associated with a higher incidence of congenital abnormalities. Insulin is the drug of choice for the control of diabetes mellitus during pregnancy. If glipizide is used during pregnancy, discontinue and change to insulin at least 1 month prior to delivery to decrease prolonged hypoglycemia in the neonate.

Breast-feeding indications

Breast-feeding is not recommended.^[3]

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Drug-Drug, -Food, -Herb Interactions

Click the link above to go to the drug interactions page.

Adverse Reactions/Side Effects

TYPE DRUG NAME HERE Adverse Reactions Chart

Incidence	Body System	Adverse Reactions
>10%	All	(Upper Respiratory Infection 10%)
1-10%	CNS	(Dizziness 2%), (Drowsiness 2%),(Headache 2%)
	Cardiovascular	(Arrhythmia 3%), (Flushing 3%)
	Dermatologic	(Erythema 1%),(Eczema 1%),(Urticaria 1%)
	GI	(Nausea 1-2%), (Anorexia 1-2%),(Vomiting 1-2%),(Pyrosis 1-2%),(Gastralgia 1-2) (Diarrhea 1-2%),(Constipation 1-2%)
	Genitourinary	None
	Neuromuscular/skeletal	(Arthralgia 3%),(Leg cramps 3%),(Myalgia 3%)
	Respiratory	(Pharyngitis 1%),(Dyspnea 1%)
	Miscellaneous	(Hypoglycemia 3%)
<1%	All	(Rash),(Anorexia),(Thirst, (Edema)

Overdosage Measures

Symptoms of overdose include low blood sugar, tingling of lips and tongue, nausea, yawning, confusion, agitation, tachycardia, sweating, convulsions, stupor, and coma. Intoxication with sulfonylureas can cause hypoglycemia and are bestway to manage toxicy is by administiring glucose.
Treatment:

• In a suspected overdose,blood sugar should be monitored routinely.
• In the event of hypoglycemia, glucose should be given.

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Product Information and Distribution

Note: appearance only available for brand-name product

Dose/form	Drug color(s)	Drug shape	Markings or odor/flavor
5 mg tablet	White	Circle	Mylan G1/solid line in middle
10 mg tablet	White	Diamond	Pfizer 412
2.5 mg ER tablet	Blue	Round	Logo 871
'		-

• Inactive ingredients for tablets: (5mg tablets)Lactose,Magnesium Stearate,Silicon Dioxide. (10 mg tablets)Corn Starch

Lactose,Microcrystalline Cellulose,Pregelatinized Starch,Silicon Dioxide (Colloidal),Stearic Acid

• Inactive ingredients for solution: add inactive ingredients

Patient Information

• Inform prescriber of all prescriptions, OTC medications, or herbal products you are taking, and any allergies you have.
• Do not take any new medication during therapy unless approved by prescriber.
• This medication is used to control diabetes; it is not a cure.
• Monitor glucose as recommended by prescriber
• Always carry quick source of sugar with you.
• Immediate release tablets should be taken 30 minutes before meals, at the same time each day. Extended release tablets should be taken with breakfast.
• Avoid alcohol while taking this medication; could cause severe reaction (hypoglycemia)
• If you experience hypoglycemic reaction, contact prescriber immediately, and take sugar tablets immediately.
• You may experience more sensitivity to sunlight (use sunscreen, wear protective clothing and eyewear, and avoid direct sunlight.
• Report severe or persistent side effects (eg, hypoglycemia: palpitations, sweaty palms, lightheadedness; extended vomiting; diarrhea or constipation; flu-like symptoms; skin rash; easy bruising or bleeding; or change in color of urine or stool) to the physician immediately.

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References

1. ↑ Cohen.L. Harris.S.Efficacy of glyburide in diabetics poorly contrlled on first generatioin hypoglycemics.Diabetes care 10:555-557 1987.
2. ↑ ^{2.00 2.01 2.02 2.03 2.04 2.05 2.06 2.07 2.08 2.09 2.10 2.11 2.12} Glucotrol.
3. ↑ ^{3.0 3.1 3.2 3.3 3.4 3.5 3.6 3.7 3.8} .
4. ↑ Dipiro JT, Talbert RL, Yee GC, Matzke GR, Wells BG, Posey LM. Pharmacotherapy: A Pathophysiologic Approach. 5th Edition ed. New York, NY: The McGraw-Hill Companies, Inc 2002.

PUBMED References

Efficacy Trial Articles

1. Efficacy, safety, and dose-response characteristics of glipizide gastrointestinal therapeutic system on glycemic control and insulin secretion in NIDDM. Results of two multicenter, randomized, placebo-controlled clinical trials. The Glipizide Gastrointestinal Therapeutic System Study Group.
2. Comparison of efficacy, secondary failure rate, and complications of sulfonylureas.
3. Glipizide versus tolbutamide, an open trial. Effects on insulin secretory patterns and glucose concentrations.
4. Clinical evaluation of a new sulfonylurea in maturity onset diabetes -glipizide.
5. Glipizide: a review of its pharmacological properties and therapeutic use.

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Therapeutic Class Comparison Articles

1. Long-term randomized placebo-controlled double-blind therapeutic comparison of glipizide and glyburide. Glycemic control and insulin secretion during 15 months
2. A one-year study comparing the efficacy and safety of rosiglitazone and glibenclamide in the treatment of type 2 diabetes.
3. Metabolic variations with oral antidiabetic drugs in patients with Type 2 diabetes: comparison between glimepiride and metformin

Pharmacokinetics Articles

1. Bioavailability of immediate- and extended-release formulations of glipizide in healthy male volunteers.
2. Pharmacokinetics and pharmacodynamics of extended-release glipizide GITS compared with immediate-release glipizide in patients with type II diabetes mellitus.
3. http://www.ncbi.nlm.nih.gov/sites/entrez?Db=pubmed&Cmd=ShowDetailView&TermToSearch=8848822&ordinalpos=22&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_RVDocSum The effects of obesity on the pharmacokinetics and pharmacodynamics of glipizide in patients with non-insulin-dependent diabetes mellitus.]
4. Effect of genetic polymorphisms in cytochrome p450 (CYP) 2C9 and CYP2C8 on the pharmacokinetics of oral antidiabetic drugs: clinical relevance.

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Drug Interaction Articles

1. Effect of glipizide treatment on response to an infused glucose load in patients with NIDDM.
2. Structure and intermolecular interactions of glipizide from laboratory X-ray powder diffraction.
3. Potentiation of the hypoglycaemic response to glipizide in diabetic patients by histamine H2-receptor antagonists.
4. Interaction of ethanol and glipizide in humans.

Adverse Effects Articles

1. The sulfonylurea glyburide induces impairment of glucagon and growth hormone responses during mild insulin-induced hypoglycemia
2. Individual sulfonylureas and serious hypoglycemia in older people.

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Compliance Articles

1. type links to articles - use PUBMED links to abstracts
2. add as many as needed

Pharmacoeconomic Articles

1. Economic assessment of troglitazone as an adjunct to sulfonylurea therapy in the treatment of type 2 diabetes
2. A short term cost-effectiveness model for oral antidiabetic medicines in Europe

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External Links

Clinical treatment guidelines

• add clinical treatment guideline external links, if applicable, using bullet points
• do not link to websites that have a bias to a particular drug, such as manufacturer-sponsored information sites

Patient information pages

• add patient information external links, if applicable, using bullet points
• do not link to websites that have a bias to a particular drug, such as manufacturer-sponsored information sites

Other resources

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• do not link to websites that have a bias to a particular drug, such as manufacturer-sponsored information sites

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