Glipizide

G6PD is an enzyme in your body that is responsible for helping red blood cells to work properly. Some patients are born with less of this enzyme in their bodies, leading to the destruction of red blood cells. When glipizide is used in patients with G6PD deficiency, they have a higher chance of experiencing hemolytic anemia (a condition in which the body does not have enough red blood cells to deliver oxygen to your tissues).

G6PD testing may be done to determine whether you are at a higher risk of experiencing hemolytic anemia if you are to be treated with glipizide. 

Before taking glipizide, tell your doctor about all of your medical conditions. Especially tell your doctor if you:

• have kidney, heart, or liver disease
• consume alcohol
• have digestive problems
• have a history of glucose-6-phosphate dehydrogenase (G6PD) deficiency
• have a history of anemia
• are allergic to glipizide (Glucotrol)
• are pregnant or breastfeeding

Tell your doctor about all the medicines you take including prescription and non-prescription medicines, vitamins, and herbal supplements.

Take glipizide exactly as prescribed by your doctor. Follow the directions on your prescription label carefully.

The dosage range for regular glipizide tablets is between 2.5 and 40 mg each day.  The maximum once daily dose is 15 mg.  Amounts above 15 mg per day should be split into different doses throughout the day.  The maximum daily dose is 40 mg.

The dosage range for extended-release glipizide tablets is 5 to 20 mg in one dose each day.  The maximum daily dose is 20 mg.

Contraindications

• Known hypersensitivity to glipizide or any ingredient in the formulation.1

• Diabetes mellitus complicated by acidosis, ketosis, or coma; use of insulin is necessary.1 2

• Monotherapy for type 1 diabetes mellitus.

Warnings/Precautions

Warnings

Possible increased cardiovascular mortality reported with other sulfonylurea antidiabetic agents (i.e., tolbutamide or phenformin).1 75 However, the American Diabetes Association considers the benefits of intensive glycemic control with insulin or sulfonylureas to outweigh the risks overall.97 107 113

General Precautions

Reported infrequently; usually mild;2 27 50 58 59 60 Possible severe hypoglycemia, especially geriatric patients, malnourished patients, and those with adrenal, pituitary, hepatic, or renal insufficiency.1 27 70 71 Strenuous exercise, alcohol ingestion, insufficient caloric intake, or use in combination with other antidiabetic agents may increase risk.1

Appropriate patient selection and careful attention to dosage are important to avoid glipizide-induced hypoglycemia.

Possible loss of glycemic control during periods of stress (e.g., fever of any cause, trauma, infection, surgery).1 2

Temporary discontinuance of glipizide and administration of insulin may be required.1

Use extended-release tablets with caution in patients with severe preexisting GI narrowing, since obstruction may occur.95

When use in fixed combination with metformin hydrochloride, consider the cautions, precautions, and contraindications associated with metformin.

Specific Populations

Category C.1

Many experts recommend that insulin be used during pregnancy.1 95

Not known whether glipizide is distributed into milk;1 discontinue nursing or the drug.1

Safety and efficacy not established.1 However, the ADA states that use may be considered in children with type 2 diabetes mellitus because of greater compliance and convenience and lack of evidence demonstrating better efficacy of insulin for type 2 diabetes mellitus.117

Increased risk of hypoglycemia.1 27 71 Cautious dosing recommended.1 27 71

Increased risk of hypoglycemia.1 27 71 Cautious dosing recommended.1 27 71 (See Hepatic Impairment under Dosage and Administration.)

Generally, not recommended in severe impairment.2 65 72

Increased risk of hypoglycemia.1 27 71 Cautious dosing recommended.1 27 71 (See Renal Impairment under Dosage and Administration.)

Generally, not recommended in severe impairment.2 65 72

Common Adverse Effects

With conventional tablets, nausea,1 50 anorexia,50 vomiting,50 pyrosis,50 gastralgia,1 diarrhea,1 and constipation.1 2 50

With extended-release tablets, asthenia, headache, pain, dizziness, nervousness, tremor, diarrhea, hypoglycemia, and flatulence.95 With glipizide in fixed combination with metformin hydrochloride, upper respiratory tract infection, diarrhea, dizziness, hypertension, nausea/vomiting, musculoskeletal pain, headache, abdominal pain, and urinary tract infection.153

Absorption

Bioavailability

Absorption is essentially complete; 1 30 31 32 33 34 35 36 37 38 80–100% of an oral dose may be absorbed.30 31 95

Onset

15–30 minutes.6 32 33

Duration

In nonfasting diabetic patients, the hypoglycemic action may persist for up to 24 hours.1 39 40 41 42 43 44

Food

Food delays the absorption of conventional tablets but does not affect peak serum concentrations achieved or the extent of absorption of the drug.32 33 Peak serum concentrations following administration of conventional tablets generally are delayed 20–40 minutes in the nonfasting state compared with the fasting state.1 32 33

Peak plasma concentrations of glipizide following adminsitration in fixed combination with metformin hydrochloride with food are delayed by 1 hour.153

Food does not affect the glycemic response or the time to absorption of extended-release tablets.95 Peak blood concentrations following administation of extended-release tablets and food are increased.95

Distribution

Extent

Following IV administration in mice, distributed into the liver and blood, with lower concentrations in the lungs, kidneys, adrenals, myocardium, salivary glands, and retroscapular fat.45 In humans, small amounts of glipizide are apparently distributed into bile30 34 37 and very small amounts are distributed into erythrocytes and saliva.30

Not known if glipizide is distributed into milk.1

Plasma Protein Binding

92–99%.30 34 36 46 95

Elimination

Metabolism

Appears to be almost completely metabolized, 30 34 35 36 37 mainly in the liver.1

Elimination Route

Glipizide and its metabolites are excreted principally in urine30 34 35 36 37 (60–90%) and to a lesser extent in feces (5–20%).30 34 35 37 95

95

Half-life

Terminal elimination half-life of glipizide averages 3–4.7 hours following oral administration in patients with normal renal and hepatic function.9 30 31 32 33 34 35 38 39 48

Terminal elimination half-life of total glipizide metabolites ranges from 2–6 hours.37

Special Populations

Renal or hepatic impairment may increase serum glipizide concentrations and reduce elimination.1 37

Severe renal impairment may decrease the renal excretion of and increase the terminal elimination half-life of glipizide metabolites.37

Glipizide tablets, USP is an oral blood-glucose-lowering drug of the sulfonylurea class.

The Chemical Abstracts name of Glipizide is 1-cyclohexyl-3-[[p-[2-(5-methylpyrazinecarboxamido)ethyl]phenyl]sulfonyl]urea. The molecular formula is C 21H 27N 5O 4S; the molecular weight is 445.55; the structural formula is shown below:

Glipizide, USP is a whitish, odorless powder with a pKa of 5.9. It is insoluble in water and alcohols, but soluble in 0.1 N NaOH; it is freely soluble in dimethylformamide. Glipizide tablets for oral use are available in 5 mg and 10 mg strengths.

Inert ingredients are: colloidal silicon dioxide, lactose (anhydrous), microcrystalline cellulose, pregelatinized starch (corn) and stearic acid.

Glipizide tablets are contraindicated in patients with:

1. Known hypersensitivity to the drug.
2. Type 1 diabetes mellitus, diabetic ketoacidosis, with or without coma. This condition should be treated with insulin.

There is no fixed dosage regimen for the management of diabetes mellitus with Glipizide tablets or any other hypoglycemic agent. In addition to the usual monitoring of urinary glucose, the patient’s blood glucose must also be monitored periodically to determine the minimum effective dose for the patient; to detect primary failure, i.e., inadequate lowering of blood glucose at the maximum recommended dose of medication; and to detect secondary failure, i.e., loss of an adequate blood-glucose-lowering response after an initial period of effectiveness. Glycosylated hemoglobin levels may also be of value in monitoring the patient’s response to therapy.

Short-term administration of Glipizide tablets may be sufficient during periods of transient loss of control in patients usually controlled well on diet.

In general, Glipizide tablets should be given approximately 30 minutes before a meal to achieve the greatest reduction in postprandial hyperglycemia.

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 mg 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 that 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.

In elderly patients, debilitated or malnourished patients, and patients with impaired renal or hepatic function, the initial and maintenance dosing should be conservative to avoid hypoglycemic reactions (see PRECAUTIONS section).

Patients Receiving Insulin

As with other sulfonylurea-class hypoglycemics, many stable non-insulin-dependent diabetic patients receiving insulin may be safely placed on Glipizide tablets. When transferring patients from insulin to Glipizide tablets, the following general guidelines should be considered:

• For patients whose daily insulin requirement is 20 units or less, insulin may be discontinued and Glipizide tablets therapy may begin at usual dosages. Several days should elapse between Glipizide tablets titration steps.
   
• For patients whose daily insulin requirement is greater than 20 units, the insulin dose should be reduced by 50% and Glipizide tablets therapy may begin at usual dosages. Subsequent reductions in insulin dosage should depend on individual patient response. Several days should elapse between Glipizide tablets titration steps.

During the insulin withdrawal period, the patient should test urine samples for sugar and ketone bodies at least three times daily. Patients should be instructed to contact the prescriber immediately if these tests are abnormal. In some cases, especially when patient has been receiving greater than 40 units of insulin daily, it may be advisable to consider hospitalization during the transition period.

Patients Receiving Other Oral Hypoglycemic Agents

As with other sulfonylurea-class hypoglycemics, no transition period is necessary when transferring patients to Glipizide tablets. Patients should be observed carefully (1 to 2 weeks) for hypoglycemia when being transferred from longer half-life sulfonylureas (e.g., chlorpropamide) to Glipizide tablets due to potential overlapping of drug effect.

When colesevelam is coadministered with Glipizide extended-release, maximum plasma concentration and total exposure to Glipizide is reduced. Therefore, Glipizide tablets should be administered at least 4 hours prior to colesevelam.

NDC 51079-810-20

Glipizide
Tablets, USP
5 mg

100 Tablets (10 x 10)

Each tablet contains:
Glipizide, USP . . . . 5 mg

Usual Dosage: See accompanying
prescribing information.

Store at 20° to 25°C (68° to 77°F).
[See USP Controlled Room
Temperature.]

Manufactured by:
Mylan Pharmaceuticals Inc.
Morgantown, WV 26505 U.S.A.

Rx only

S-5441 R9

Packaged and Distributed by:

Mylan Institutional Inc.

Rockford, IL 61103 U.S.A.

This unit dose package is not child resistant.

For institutional use only.

Keep this and all drugs out of the reach of children.

This container provides light-resistance.

See window for lot number and expiration date.

Extended release: Store at 68°F to 77°F (20°C to 25°C); excursions permitted between 59°F to 86°F (15°C to 30°C). Protect from moisture and humidity.

Immediate release: Store below 30°C (86°F).

Glipizide is an oral diabetes medicine that helps control blood sugar levels by helping your pancreas produce insulin.

Glipizide is used together with diet and exercise to treat type 2 diabetes.

Glipizide may also be used for purposes not listed in this medication guide.

Applies to glipizide: oral tablet, oral tablet extended release

Along with its needed effects, glipizide may cause some unwanted effects. Although not all of these side effects may occur, if they do occur they may need medical attention.

Check with your doctor immediately if any of the following side effects occur while taking glipizide:

• Anxiety
• blurred vision
• burning, crawling, itching, numbness, prickling, "pins and needles", or tingling feelings
• chills
• cold sweats
• coma
• confusion
• cool, pale skin
• depression
• difficulty with moving
• dizziness
• fainting
• fast heartbeat
• headache
• increased hunger
• joint pain
• leg cramps
• muscle aching or cramping
• muscle pain or stiffness
• nausea
• nervousness
• nightmares
• pain in the joints
• problems in urination or increase in the amount of urine
• seizures
• shakiness
• slurred speech
• sweating
• swollen joints
• unusual tiredness or weakness

• Abdominal or stomach pain
• bloating
• bloody or black, tarry stools
• body aches or pain
• burning, dry, or itching eyes
• clay-colored stools
• congestion
• constipation
• cough
• dark urine
• decreased vision or other changes in vision
• diarrhea
• difficult or labored breathing
• difficult or painful urination
• dryness or soreness of the throat
• excessive tearing
• fainting
• fast, slow, or irregular heartbeat
• feeling of warmth
• fever
• heartburn
• hoarseness
• indigestion
• itching
• loss of appetite
• pain in the eye
• pounding in the ears
• rash
• redness of the face, neck, arms and occasionally, upper chest
• redness, pain, or swelling of the eye, eyelid, or inner lining of the eyelid
• runny nose
• severe stomach pain
• shortness of breath
• tender, swollen glands in the neck
• tightness in the chest
• trouble in swallowing
• unpleasant breath odor
• voice changes
• vomiting of blood or material that looks like coffee grounds
• wheezing
• yellow eyes or skin

• Agitation
• back or leg pains
• bleeding gums
• blood in the urine or stools
• chest pain
• convulsions
• decreased urine output
• fluid-filled skin blisters
• general body swelling
• general feeling of tiredness or weakness
• high fever
• hostility
• increased thirst
• irritability
• lethargy
• light-colored stools
• lower back or side pain
• muscle twitching
• nosebleeds
• pinpoint red pots on the skin
• rapid weight gain
• sensitivity to the sun
• skin thinness
• sores, ulcers, or white spots on the lips or in the mouth
• stupor
• swelling of the face, ankles, or hands
• unusual bleeding or bruising

Some side effects of glipizide may occur that usually do not need medical attention. These side effects may go away during treatment as your body adjusts to the medicine. Also, your health care professional may be able to tell you about ways to prevent or reduce some of these side effects. Check with your health care professional if any of the following side effects continue or are bothersome or if you have any questions about them:

• Indigestion
• passing of gas

• Acid or sour stomach
• belching
• excess air or gas in the stomach or intestines
• full feeling
• pain
• sleeplessness
• sneezing
• stuffy nose
• trouble sleeping
• unable to sleep

• Decreased interest in sexual intercourse
• dizziness or lightheadedness
• excessive muscle tone
• feeling of constant movement of self or surroundings
• flushing or redness of the skin
• headache, severe and throbbing
• hives or welts
• inability to have or keep an erection
• loss in sexual ability, desire, drive, or performance
• mood or mental changes
• muscle stiffness
• muscle tension or tightness
• sensation of spinning
• skin rash, encrusted, scaly, and oozing
• sleepiness or unusual drowsiness
• unusually warm skin
• walking in unusual manner
• weight loss

• Increased sensitivity of the skin to sunlight
• severe sunburn

Initial dose: 2.5 mg orally once a day 30 minutes before breakfast

Comments:
-Maintenance dosing should be conservative to avoid hypoglycemic reactions.
-Doses can be adjusted with caution taking into account the degree of hepatic, renal, or cardiac function, and the concomitant disease or other drug therapy.

Use: Adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus

Patients with liver disease:
Initial dose: 2.5 mg orally once a day 30 minutes before breakfast

A decision should be made to discontinue breastfeeding or discontinue the drug, taking into account the importance of the drug to the mother. Excreted into human milk: Yes Comments: If diet alone is inadequate for controlling blood glucose, insulin therapy should be considered.

There is limited data which suggests low levels of this drug are present in breast milk. Due to the limited data available and the potential for hypoglycemia in the nursing infant, the manufacturer suggests women who are not able to manage their blood sugar on diet alone consider insulin therapy while breastfeeding.