Glipizide Er (glipizide)

No dosing information is available for this tab.

Glipizide is administered orally. Conventional (immediate-release) tablets of the drug usually are administered initially as a single daily dose given each morning before breakfast. It is generally recommended that glipizide be administered approximately 30 minutes before a meal to achieve the maximum reduction in postprandial blood glucose concentration. Once-daily dosing of glipizide at dosages up to 15-20 mg daily has been shown to provide adequate control of blood glucose concentration throughout the day in most patients with usual meal patterns; however, some patients may have a more satisfactory response when the drug is administered in 2 or 3 divided doses daily as immediate-release tablets. When glipizide dosage exceeds 15-20 mg daily as immediate-release tablets, the drug usually should be administered in divided doses before meals of sufficient caloric content. When a divided-dosing regimen as immediate-release tablets is employed in patients receiving more than 15 mg of glipizide daily, the doses and schedule of administration should be individualized according to the patient's meal pattern and response. The manufacturer states that dosages greater than 30 mg daily have been given safely in twice-daily dosing regimens for prolonged periods.

Extended-release tablets of glipizide are administered once daily, generally with breakfast or the first main meal of the day. The extended-release tablets should be swallowed whole and should not be divided, chewed, or crushed. Patients receiving the extended-release tablets may occasionally notice a tablet-like substance in their stools; this is normal since the tablet containing the drug is designed to remain intact and slowly release the drug from a nonabsorbable shell during passage through the GI tract.

When given concomitantly with colesevelam, glipizide should be administered at least 4 hours prior to colesevelam.

The fixed combination of glipizide with metformin hydrochloride should be taken once or twice daily with food. See the full prescribing information for additional administration instructions for the combination product.

Store glipizide immediate-release tablets at 20--25degreesC in a tight, light-resistant container. Store glipizide extended-release tablets at 20--25degreesC (excursions permitted to 15--30degreesC) protected from moisture and humidity.

There is no enhanced messaging for this drug.

Contraindicated Drug Combination: This drug combination is contraindicated and generally should not be dispensed or administered to the same patient.

Selected Photosensitizers/Tretinoin-Mequinol

SEVERITY LEVEL: 1-Contraindicated Drug Combination: This drug combination is contraindicated and generally should not be dispensed or administered to the same patient.

MECHANISM OF ACTION: Tretinoin, anthralin, coal tar and derivatives, fluoroquinolones, griseofulvin, organic staining dyes (such as methylene blue, rose bengal, or toluidine blue), phenothiazines, selected NSAIDs (such as diclofenac, ketoprofen, nabumetone, naproxen, piroxicam, and tiaprofenic acid), methotrexate, St. John's wort, sulfonamides, sulfonylureas, tetracyclines, and thiazides are all known photosensitizers.(1)

CLINICAL EFFECTS: Concurrent use of tretinoin in patients taking anthralin, coal tar and derivatives, fluoroquinolones, griseofulvin, organic staining dyes (such as methylene blue, rose bengal, or toluidine blue), phenothiazines, selected NSAIDs (such as diclofenac, ketoprofen, nabumetone, naproxen, piroxicam, and tiaprofenic acid), methotrexate, St. John's wort, sulfonamides, sulfonylureas, tetracyclines, and thiazides may increase the risk of phototoxicity.(1)

PREDISPOSING FACTORS: None determined.

PATIENT MANAGEMENT: The US manufacturer states that tretinoin-mequinol should not be administered to patients receiving photosensitizers including anthralin, coal tar and derivatives, fluoroquinolones, griseofulvin, organic staining dyes (such as methylene blue, rose bengal, or toluidine blue), phenothiazines, selected NSAIDs (such as diclofenac, ketoprofen, nabumetone, naproxen, piroxicam, and tiaprofenic acid), methotrexate, St. John's wort, sulfonamides, sulfonylureas, tetracyclines, and thiazides.(1)

DISCUSSION: Because of the risk of increased photosensitivity, the US manufacturer states that tretinoin-mequinol should not be administered to patients receiving photosensitizers including anthralin, coal tar and derivatives, fluoroquinolones, griseofulvin, organic staining dyes (such as methylene blue, rose bengal, or toluidine blue), methotrexate, phenothiazines, selected NSAIDs (such as diclofenac, ketoprofen, nabumetone, naproxen, piroxicam, and tiaprofenic acid), St. John's wort, sulfonamides, sulfonylureas, tetracyclines, and thiazides.(1)

Severe Interaction: Action is required to reduce the risk of severe adverse interaction.

Antidiabetic Agents/Gatifloxacin

SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction.

MECHANISM OF ACTION: The exact mechanism is unknown.

CLINICAL EFFECTS: Concurrent use of gatifloxacin may result in hypoglycemia and/or hyperglycemia.(1-4) Hypoglycemia is more common during the first three days of concurrent therapy. Hyperglycemia is more common after the first three days of concurrent therapy.(2)

PREDISPOSING FACTORS: Elderly patients, especially those with decreased renal function may be predisposed to this interaction.(2)

PATIENT MANAGEMENT: Patients receiving concurrent gatifloxacin should be closely monitored for hypoglycemia during the first three days of concurrent therapy and for hyperglycemia after the first three days of concurrent therapy. Patients should be instructed to discontinue gatifloxacin if hypoglycemia or hyperglycemia occur.(2)

DISCUSSION: Hypoglycemia has been reported with gatifloxacin and glyburide(1,5,6) or glimepiride.(7) In a study in patients with type 2 diabetes mellitus, concurrent gatifloxacin (400 mg daily for 10 days) had no effect on the pharmacokinetics of glyburide (steady state daily regimen); however, pharmacodynamic interactions have been reported.(2) Health Canada has received 19 reports of hypoglycemia in patients taking gatifloxacin. Seventeen of these involved concurrent hypoglycemic agents. Health Canada has received 2 reports of hyperglycemia in patients taking gatifloxacin and hypoglycemic agents. Health Canada has received 2 reports of patients experiencing hypoglycemia and hyperglycemia during concurrent gatifloxacin and hypoglycemic agents.(3) In a study, 13 reports of dysglycemia were reported in patients taking gatifloxacin. Ten of these patients had diabetes mellitus and were on concurrent hypoglycemic agents. Of these ten patients, nine patients experienced hypoglycemia, while one patient experienced hyperglycemia.(8)

Selected Cyp2c9 Substrates/Asciminib

SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction.

MECHANISM OF ACTION: Asciminib is a moderate inhibitor of CYP2C9.(1) Asciminib may decrease the metabolism of drugs that are CYP2C9 substrates.

CLINICAL EFFECTS: Decreased clearance may increase systemic concentrations of drugs primarily metabolized by CYP2C9, leading to toxicity.(1)

PREDISPOSING FACTORS: None determined.

PATIENT MANAGEMENT: The manufacturer of asciminib states coadministration of the CYP2C9 substrate drug with asciminib should be avoided. Consider an alternative agent that does not depend on CYP2C9 for metabolism. If a patient is taking asciminib 80 mg total daily dose and coadministration of the CYP2C9 substrate is unavoidable, reduce the dosage of the CYP2C9 substrate according to its product labeling.(1) Closely monitor patients stable on CYP2C9 substrates for altered therapeutic effect or toxicity when asciminib therapy is started, adjusted, or stopped.(1)

DISCUSSION: In clinical studies, coadministration of asciminib 40 mg twice daily, 80 mg once daily, and 200 mg twice daily, the area-under-the-curve (AUC) of S-warfarin increased by 41%, 52%, and 314%, respectively. Additionally, the maximum concentration (Cmax) of S-warfarin increased by 8%, 4%, and 7%, respectively.(1) Medications linked to this interaction include fluvastatin, fosphenytoin, glimepiride, glipizide, phenytoin, and tolbutamide. These drugs have a narrow therapeutic range or are designated as CYP2C9 Sensitive Substrates (i.e. moderate 2C9 inhibitors are expected to increase exposure (AUC) to these agents by 2-fold to 5-fold).(2,3)

Selected Photosensitizers/Aminolevulinic Acid

SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction.

MECHANISM OF ACTION: Aminolevulinic acid, anthralin, coal tar and derivatives, fluoroquinolones, griseofulvin, organic staining dyes (such as methylene blue, rose bengal, or toluidine blue), phenothiazines, selected NSAIDs (such as diclofenac, ketoprofen, nabumetone, naproxen, piroxicam, and tiaprofenic acid), methotrexate, St. John's wort, sulfonamides, sulfonylureas, tetracyclines, and thiazides are all known photosensitizers.(1)

CLINICAL EFFECTS: Concurrent use of aminolevulinic acid in patients taking anthralin, coal tar and derivatives, fluoroquinolones, griseofulvin, organic staining dyes (such as methylene blue, rose bengal, or toluidine blue), phenothiazines, selected NSAIDs (such as diclofenac, ketoprofen, nabumetone, naproxen, piroxicam, and tiaprofenic acid), methotrexate, St. John's wort, sulfonamides, sulfonylureas, tetracyclines, and thiazides may increase the risk of phototoxicity.(1)

PREDISPOSING FACTORS: None determined.

PATIENT MANAGEMENT: The US manufacturer states that aminolevulinic acid should be avoided in patients receiving photosensitizers including anthralin, coal tar and derivatives, fluoroquinolones, griseofulvin, organic staining dyes (such as methylene blue, rose bengal, or toluidine blue), phenothiazines, selected NSAIDs (such as diclofenac, ketoprofen, nabumetone, naproxen, piroxicam, and tiaprofenic acid), methotrexate, St. John's wort, sulfonamides, sulfonylureas, tetracyclines, and thiazides for 24 hours before and after administration of aminolevulinic acid.(1)

DISCUSSION: Because of the risk of increased photosensitivity, the US manufacturer states that aminolevulinic acid should be avoided in patients receiving photosensitizers including anthralin, coal tar and derivatives, fluoroquinolones, griseofulvin, organic staining dyes (such as methylene blue, rose bengal, or toluidine blue), phenothiazines, selected NSAIDs (such as diclofenac, ketoprofen, nabumetone, naproxen, piroxicam, and tiaprofenic acid), methotrexate, St. John's wort, sulfonamides, sulfonylureas, tetracyclines, and thiazides for 24 hours before and after administration of aminolevulinic acid.(1)

Selected Photosensitizers/Methoxsalen

SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction.

MECHANISM OF ACTION: Methoxsalen causes photosensitivity due to residual drug which is present in all parts of the skin from photopheresis. Anthralin, coal tar and derivatives, fluoroquinolones, griseofulvin, organic staining dyes (such as methylene blue, rose bengal, or toluidine blue), phenothiazines, selected NSAIDs (such as diclofenac, ketoprofen, nabumetone, naproxen, piroxicam, and tiaprofenic acid), methotrexate, St. John's wort, sulfonamides, sulfonylureas, tetracyclines, and thiazides are other known photosensitizers.(1)

CLINICAL EFFECTS: Concurrent use of methoxsalen in patients taking anthralin, coal tar and derivatives, fluoroquinolones, griseofulvin, organic staining dyes (such as methylene blue, rose bengal, or toluidine blue), phenothiazines, selected NSAIDs (such as diclofenac, ketoprofen, nabumetone, naproxen, piroxicam, and tiaprofenic acid), methotrexate, St. John's wort, sulfonamides, sulfonylureas, tetracyclines, and thiazides may increase the risk of phototoxicity.(1)

PREDISPOSING FACTORS: None determined.

PATIENT MANAGEMENT: The US manufacturer of methoxsalen states that concurrent use of methoxsalen with anthralin, coal tar and derivatives, fluoroquinolones, griseofulvin, organic staining dyes (such as methylene blue, rose bengal, or toluidine blue), phenothiazines, selected NSAIDs (such as diclofenac, ketoprofen, nabumetone, naproxen, piroxicam, and tiaprofenic acid), methotrexate, St. John's wort, sulfonamides, sulfonylureas, tetracyclines, and thiazides should be avoided.(1)

DISCUSSION: All patients who have received methoxsalen become photosensitive. It is unknown what the risk of photosensitivity reactions is when methoxsalen is used concurrently with other photosensitizing agents.(1)

Selected Photosensitizers/Porfimer

SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction.

MECHANISM OF ACTION: Porfimer causes photosensitivity due to residual drug which is present in all parts of the skin. Anthralin, coal tar and derivatives, fluoroquinolones, griseofulvin, organic staining dyes (such as methylene blue, rose bengal, or toluidine blue), phenothiazines, selected NSAIDs (such as diclofenac, ketoprofen, nabumetone, naproxen, piroxicam, and tiaprofenic acid), methotrexate, St. John's wort, sulfonamides, sulfonylureas, tetracyclines, and thiazides are other known photosensitizers.(1)

CLINICAL EFFECTS: Concurrent use of porfimer in patients taking anthralin, coal tar and derivatives, fluoroquinolones, griseofulvin, organic staining dyes (such as methylene blue, rose bengal, or toluidine blue), phenothiazines, selected NSAIDs (such as diclofenac, ketoprofen, nabumetone, naproxen, piroxicam, and tiaprofenic acid), methotrexate, St. John's wort, sulfonamides, sulfonylureas, tetracyclines, and thiazides may increase the risk of phototoxicity.(1)

PREDISPOSING FACTORS: Patients with any hepatic impairment and patients with severe renal impairment have reduced drug elimination and may remain photosensitive for 90 days or longer.(1)

PATIENT MANAGEMENT: The US manufacturer of porfimer states that concurrent use of porfimer with photosensitizers including anthralin, coal tar and derivatives, fluoroquinolones, griseofulvin, organic staining dyes (such as methylene blue, rose bengal, or toluidine blue), phenothiazines, selected NSAIDs (such as diclofenac, ketoprofen, nabumetone, naproxen, piroxicam, and tiaprofenic acid), methotrexate, St. John's wort, sulfonamides, sulfonylureas, tetracyclines, and thiazides should be avoided.(1) Since the photosensitive effect of porfimer may persist for at least 30 days (and for 90 days in some patients), it would be prudent to avoid other photosensitizing agents for at least 30 days after administration of porfimer.

DISCUSSION: All patients who have received porfimer become photosensitive. It is unknown what the risk of photosensitivity reactions is when porfimer is used concurrently with other photosensitizing agents. When porfimer was used in clinical trials, photosensitivity reactions occurred in about 20% of cancer patients and in 69% of high-grade dysplasia in Barretts esophagus patients. Most of the reactions were mild to moderate erythema, but they also included swelling, pruritus, burning sensation, feeling hot, or blisters. The majority of reactions occurred within 90 days of porfimer administration.(1)

Sulfonylureas/Miconazole

SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction.

MECHANISM OF ACTION: Sulfonylureas are sensitive CYP2C9 substrates. Miconazole is a moderate CYP2C9 inhibitor and may inhibit the metabolism of sulfonylureas.(1)

CLINICAL EFFECTS: Concurrent use of miconazole may result in elevated levels and effects of the sulfonylureas, including severe hypoglycemia and coma.(2-4)

PREDISPOSING FACTORS: None determined.

PATIENT MANAGEMENT: The Australian, Canadian, and UK manufacturers of gliclazide and the UK manufacturer of glipizide state that concurrent use with miconazole via systemic routes or oro-mucosal gel is contraindicated.(2-5) The manufacturers of other sulfonylureas and the Australian and UK manufacturers of miconazole advise caution when using the combination of sulfonylureas and miconazole. Monitor blood glucose levels during concurrent therapy. The dose of the sulfonylurea may need to be adjusted.(6-15)

DISCUSSION: A French pharmacovigilance study found that 98 cases of sulfonylurea-induced hypoglycemia were reported between 1985-1990, mostly with gliclazide (46 cases) and glyburide (40 cases). Miconazole was one of the most frequent causes of drug interactions (8 cases).(16) Other cases of severe hypoglycemia after miconazole was started in patients on sulfonylureas have been reported.(17-18)

Moderate Interaction: Assess the risk to the patient and take action as needed.

Antidiabetic Agents/Gymnema

SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed.

MECHANISM OF ACTION: Gymnema has been shown to increase the number of insulin-secreting beta cells in animals. It has also been shown to increase the activity of enzymes responsible for glucose uptake and utilization and inhibit peripheral utilization of glucose.(1)

CLINICAL EFFECTS: Use of gymnema may result in decreased requirements of antidiabetic agents.(2-4)

PREDISPOSING FACTORS: None determined.

PATIENT MANAGEMENT: Diabetic patients should be carefully monitored if gymnema is initiated or discontinued from concurrent therapy. The dosage of the patient's antidiabetic agent(s) may need to be adjusted.(2)

DISCUSSION: In a study in 22 non-insulin-dependent patients, patients had decreased blood glucose, glycosylated hemoglobin, and glycosylated plasma proteins during gymnema therapy. Patients were able to decrease the dosage of their conventional antidiabetic therapy and five patients were able to discontinue their conventional antidiabetic therapy.(3) In a study in 27 insulin-dependent patients, patients had decreased insulin requirements, fasting blood glucose, glycosylated hemoglobin, and glycosylated plasma protein levels.(4)

Antidiabetics, Oral/Aspirin (> 100 Mg); Salicylates

SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed.

MECHANISM OF ACTION: Complex. Salicylates appear to have intrinsic glucose lowering properties via several proposed mechanisms. Also, salicylates may cause protein binding displacement of antidiabetics. Decreased renal clearance may also occur.

CLINICAL EFFECTS: Potentiation of hypoglycemic effects may be observed.

PREDISPOSING FACTORS: None determined.

PATIENT MANAGEMENT: Hypoglycemic signs and blood glucose levels should be monitored. Adjust the antidiabetic dose as needed. Particular caution should be taken when salicylates are started or stopped in patients previously stabilized on antidiabetics.

DISCUSSION: Additional documentation is necessary to confirm this potential interaction.

Antidiabetics, Oral/Clofibrate

SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed.

MECHANISM OF ACTION: Not defined.

CLINICAL EFFECTS: May observe enhanced hypoglycemic effects.

PREDISPOSING FACTORS: Hypoalbuminemia.

PATIENT MANAGEMENT: Monitor blood glucose and watch for signs of hypoglycemia. This is particularly important when clofibrate is started or stopped.

DISCUSSION: Additional documentation is necessary to confirm this potential interaction.

Antidiabetics, Oral/Oxy-Phenylbutazone

SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed.

MECHANISM OF ACTION: Phenylbutazone may displace antidiabetics from plasma protein binding sites. Renal elimination of the active metabolite of acetohexamide may be reduced. Finally, tolbutamide metabolism may be decreased.

CLINICAL EFFECTS: Potentiation of antidiabetic effects.

PREDISPOSING FACTORS: None determined.

PATIENT MANAGEMENT: Hypoglycemic signs and blood glucose levels should be monitored. Adjust the antidiabetic dose as needed.

DISCUSSION: This interaction is well documented.

Antidiabetics, Oral/Sulfonamide Antibacterials

SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed.

MECHANISM OF ACTION: Not fully established. However, it is speculated that sulfonamides may inhibit hepatic metabolism and/or displace oral antidiabetics from plasma protein binding sites.

CLINICAL EFFECTS: Increased serum levels of antidiabetics with potentiation of hypoglycemic effects.

PREDISPOSING FACTORS: None determined.

PATIENT MANAGEMENT: Hypoglycemic signs and blood glucose levels should be monitored. Adjust the antidiabetic dose as needed.

DISCUSSION: Additional documentation is necessary to confirm this interaction.

Antidiabetics/Epinephrine

SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed.

MECHANISM OF ACTION: Gluconeogenesis, glycogenolysis, and lipolysis are increased by epinephrine. Also, insulin secretion and glucose uptake by peripheral tissues are decreased by epinephrine.

CLINICAL EFFECTS: Increased blood glucose resulting in decreased effectiveness of the antidiabetic agent.

PREDISPOSING FACTORS: None determined.

PATIENT MANAGEMENT: Caution when starting or stopping epinephrine in diabetic patients. Adjust the antidiabetic dose as needed based on blood glucose levels.

DISCUSSION: This interaction is likely to occur based upon well documented properties of the interacting drugs. However, there is individual variability in its occurrence.

Antidiabetics/Slt Ophth Non-Cardioselective Beta-Blockers

SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed.

MECHANISM OF ACTION: Not fully established. Probably blockade of a variety of beta-adrenergic responses to hypoglycemia.(1,2)

CLINICAL EFFECTS: Diminished response to sulfonylureas and insulin may occur. Frequency and severity of hypoglycemic episodes may be increased, while warning symptoms of low blood sugar may be masked.(1,2)

PREDISPOSING FACTORS: None determined.

PATIENT MANAGEMENT: Try to avoid beta-blocker therapy, particularly in diabetics prone to hypoglycemic attacks. One of the cardioselective agents may decrease risk of hypertensive attacks and allow more rapid glucose recovery from hypoglycemia. Patients should be counseled not to rely on tachycardia to diagnose hypoglycemia, since it is masked by beta-blocker therapy. Diaphoresis is unaffected by beta-blockade and can be used by the diabetic to recognize hypoglycemia.

DISCUSSION: A double blind, randomized, 12 month study of 39 patients tested the metabolic effects of pindolol (5mg BID) compared to control group on insulin sensitivity. The patient's insulin sensitivity index decreased 17% when on pindolol treatment compared to placebo (p<0.01). Insulin mediated glucose uptake was significantly lower (p<0.05) with propranolol treatment than with placebo.(3) A study of 26 patients with chronic heart failure showed that carvedilol (average daily dose 27.5mg/d) caused a significant decrease in fasting insulin levels (17.09 to 10.77 microU/ml, p <0.05) compared to pre-treatment levels. This trial also showed that patients on carvedilol had significantly (p=0.015) lower fasting insulin levels (10.77 microU/ml) compared to the fasting insulin levels (20.72 microU/ml) of patients on bisoprolol treatment (5.9mg/d).(4) There have been case reports of hypoglycemia following the addition of ophthalmic timolol to a diabetic regimen.(5-7) Studies have shown that ophthalmic beta-blockers, especially the aqueous solution, have significant systemic absorption and do not undergo first-pass metabolism.(8,9)

Glimepiride; Glipizide; Glyburide/Colesevelam

SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed.

MECHANISM OF ACTION: Colesevelam may bind to glimepiride, glipizide, and glyburide in the gastrointestinal track, preventing their absorption.(1,2)

CLINICAL EFFECTS: Simultaneous administration of colesevelam may result in decreased levels and effectiveness of glimepiride,(1) glipizide,(1) or glyburide.(1,2)

PREDISPOSING FACTORS: None determined.

PATIENT MANAGEMENT: Glyburide,(1) glipizide,(3) and glimepiride(4) should be administered four hours before colesevelam.

DISCUSSION: When administered with colesevelam (3.75 g), the area-under-curve (AUC) and maximum concentration (Cmax) of glimepiride (4 mg) decreased by 18% and by 8%, respectively. When administered 4 hours prior to colesevelam, the AUC of glimepiride decreased by 6% and the Cmax increased 3%.(1) When administered with colesevelam (3.75 g), the AUC and Cmax of glipizide (20 mg) decreased by 12% and by 13%, respectively. When administered 4 hours prior to colesevelam, the AUC of glipizide decreased by 4%. There was no effect on glipizide Cmax when glipizide and colesevelam were separated by 4 hours.(1) When administered with colesevelam (3.75 g), AUC and Cmax of glyburide (3 mg) decreased by 32% and by 47%, respectively. When administered 1 hour prior to colesevelam, the AUC and Cmax of glyburide decreased by 20% and 15%, respectively. When administered 4 hours prior to colesevelam, the AUC and Cmax of glyburide decreased by 7% and 4%, respectively.(1,2)

Glinides; Sulfonylureas/Ethyl Alcohol

SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed.

MECHANISM OF ACTION: Alcohol can induce hypoglycemia and interfere with gluconeogenesis in the liver by means of intrinsic hypoglycemic activity.(1-3) Some alcoholic beverages may increase serum glucose levels from their high carbohydrate content.(4) Chronic alcohol intake may decrease half-life of sulfonylureas by increasing liver metabolism.(1, 5-8)

CLINICAL EFFECTS: Alcohol consumption while on a glinide or sulfonylureas may result in a range of reactions, from mild flushing to severe hypoglycemic reactions. Alcohol consumption during chlorpropamide therapy has resulted in a disulfiram-like reaction.

PREDISPOSING FACTORS: None determined.

PATIENT MANAGEMENT: Diabetics should be cautioned about the effects of alcohol consumption on diabetic control, possible flushing with concurrent use, and about unsuspected sources of alcohol such as medications. Patients on chlorpropamide therapy should be counseled about the possibility of a disulfiram-like reaction to alcohol consumption. Alcohol is used to improve docetaxel and paclitaxel solubility. - The quantity of alcohol in paclitaxel injection formulations (0.385-0.396 grams/mL) is similar across manufacturers. A paclitaxel 200 mg dose contains approximately 13 grams of alcohol. - The quantity of alcohol in docetaxel formulations varies approximately 3-fold depending upon the manufacturer. FDA data on alcohol content (21): Product Manufacturer Alcohol/200 mg dose Docetaxel Inj. Pfizer 6.4 grams Docetaxel Inj. Sandoz 5.5 grams Docetaxel Inj. Accord 4.0 grams Taxotere-one vial Sanofi 4.0 grams formulation Docetaxel Inj. Hospira 3.7 grams Docefrez Sun Pharma 2.9 grams Taxotere-two vial Sanofi 2.0 grams formulation

DISCUSSION: Chlorpropamide has been reported to induce facial flushing (5,9-18) and a disulfiram-like reaction(4,9,10,18,19) following alcohol consumption. Tolbutamide has been shown to interact with alcohol in nonalcoholic diabetic patients, alcoholics, and normal subjects.(2,3,6-8,16,17) There is one report of reduced tolerance for alcohol in a patient on tolazamide therapy.(20) In a study in 10 normal subjects, administration of ethanol with glipizide resulted in a delay in return to fasting glucose levels. The time of onset and the extent of hypoglycemia were not altered.(21) Glipizide and glyburide have been reported to have a very low incidence of disulfiram-like reactions with concurrent alcohol; however, in one study, 5 of 11 patients taking glyburide developed flushing after a test dose of alcohol.(18)

Hypoglycemics; Insulin/Bupropion

SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed.

MECHANISM OF ACTION: Bupropion can lower the seizure threshold and when given concurrently with other medications that also lower the threshold there is an increased risk of seizure. Concurrent use of hypoglycemics or insulin increases the risk of hypoglycemia which can result in seizures.(1,2)

CLINICAL EFFECTS: Concurrent use of bupropion and hypoglycemics or insulin may increase the risk of seizure.(1,2)

PREDISPOSING FACTORS: The risk of seizures may be increased in patients with a history of head trauma or prior seizure; CNS tumor; severe hepatic cirrhosis; excessive use of alcohol or sedatives; addiction to opiates, cocaine, or stimulants; use of over-the-counter stimulants an anorectics; a total daily dose of bupropion greater than 450 mg or single doses greater than 150 mg; rapid escalation of bupropion dosage; or with concomitant medications known to lower seizure threshold (antidepressants, antipsychotics, systemic steroids, theophylline).(1,2)

PATIENT MANAGEMENT: The use of bupropion in patients treated with oral hypoglycemic agents or insulin should be undertaken only with extreme caution and with low initial bupropion dosing and small gradual dosage increases.(1,2) Single doses should not exceed 150 mg.(1,2) The maximum daily dose of bupropion should not exceed 300 mg for smoking cessation(2) or 450 mg for depression.(1)

DISCUSSION: Because of the risk of seizure from concurrent bupropion and other agents that lower seizure threshold, the manufacturer of bupropion states that the concurrent use of bupropion and oral hypoglycemic agents or insulin should be undertaken only with extreme caution and with low initial bupropion dosing and small gradual dosage increases.(1,2)

Selected Antidiabetic Agents/Chloroquine; Hydroxychloroquine

SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed.

MECHANISM OF ACTION: The exact mechanism is unknown. Chloroquine and hydroxychloroquine may increase insulin sensitivity by inhibiting insulin metabolism and inflammation and increasing cellular uptake of glucose and glycogen synthesis.(1,2) These effects may result in additive hypoglycemia with anti-diabetic agents.

CLINICAL EFFECTS: Concurrent use of chloroquine or hydroxychloroquine and antidiabetic agents may result in severe hypoglycemia.(3) Hypoglycemia can lead to coma.

PREDISPOSING FACTORS: Elderly patients, especially those with decreased renal function may be predisposed to this interaction.

PATIENT MANAGEMENT: Patients maintained on antidiabetic agents who require concurrent therapy with chloroquine or hydroxychloroquine should be closely monitored for hypoglycemia. A decrease in the dose of insulin or other anti-diabetic medications may be required. Patients should be advised of the risk and symptoms of hypoglycemia and to contact their doctor if hypoglycemia occurs.(3) Signs of hypoglycemia may include confusion, dizziness, feeling shaky, unusual hunger, headaches, irritability, pounding heart or very fast pulse, pale skin, sweating, trembling, weakness, or unusual anxiety.

DISCUSSION: Hydroxychloroquine has been shown to cause severe hypoglycemia including loss of consciousness that could be life threatening.(3) Concomitant hypoglycemic agents may increase the risk and/or severity of this effect. A 77 year old man who was stable on twice daily insulin suffered two episodes of hypoglycemic coma 2 weeks after starting prednisone 5 mg daily and hydroxychloroquine 400 mg daily for rheumatoid arthritis. His insulin dosage required a decrease of 37%.(4) Many studies have investigated the glucose-lowering effect of hydroxychloroquine. In a clinical trial of type II diabetics on maximal doses of sulfonylureas, addition of hydroxychloroquine lowered hemoglobin A1C (HbA1C) up to 1% more than placebo.(5) Another clinical trial of type II diabetics on metformin and glimepiride or gliclazide found that hydroxychloroquine 400 mg daily reduced fasting blood glucose (FBG), post-prandial glucose (PPG), and HbA1C to a similar degree as pioglitazone 15 mg daily at 24 weeks.(6) In a prospective observational study, 250 uncontrolled type II diabetics on metformin, glimepiride, pioglitazone, sitagliptin, and a SGLT-2 inhibitor received hydroxychloroquine 400 mg daily for 48 weeks. HbA1C decreased from 8.83% to 6.44%, FBG decreased by 40.78%, and PPG decreased by 58.95%. The doses of metformin were reduced by 50%, glimepiride and sitagliptin by 75%, and SGLT-2 inhibitors were discontinued in most patients.(7)

Selected Antidiabetic Agents/Clarithromycin; Telithromycin

SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed.

MECHANISM OF ACTION: Clarithromycin and telithromycin may inhibit the metabolism of glipizide(1) and glyburide(1,2) by CYP3A4.

CLINICAL EFFECTS: Concurrent use of glipizide or glyburide and clarithromycin or telithromycin may result in elevated levels of and effects from glipizide and glyburide, including hypoglycemia.

PREDISPOSING FACTORS: None determined.

PATIENT MANAGEMENT: Patients maintained on glipizide or glyburide should be closely monitored if clarithromycin or telithromycin is added to or withdrawn from concurrent therapy. A dosage adjustment of the antidiabetic agent may be required during macrolide therapy.

DISCUSSION: In a study in 12 healthy subjects, clarithromycin (250 mg twice daily) increased the area-under-curve (AUC) and maximum concentration (Cmax) of a single dose of glyburide (0.875 mg) by 1.35-fold and 1.25-fold, respectively.(2) Severe hypoglycemia has been reported in patients following the addition of clarithromycin to glipizide and glyburide therapy.(1)

Selected Antidiabetic Agents/Selected Quinolones

SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed.

MECHANISM OF ACTION: The exact mechanism is unknown.

CLINICAL EFFECTS: Concurrent use of quinolones and antidiabetic agents may result in severe hypoglycemia.(1-7) Hypoglycemia can lead to coma.

PREDISPOSING FACTORS: Elderly patients, especially those with decreased renal function may be predisposed to this interaction.(5)

PATIENT MANAGEMENT: Patients maintained on antidiabetic agents who require concurrent therapy with a quinolone should be closely monitored for hypoglycemia.(1-4) Patients should be instructed to discontinue quinolone use and contact their doctor if hypoglycemia occurs.(2,4) Signs of hypoglycemia may include confusion, dizziness, feeling shaky, unusual hunger, headaches, irritability, pounding heart or very fast pulse, pale skin, sweating, trembling, weakness, or unusual anxiety.

DISCUSSION: Hypoglycemia has been reported with concurrent ciprofloxacin and glyburide,(1,8,9) levofloxacin and glyburide,(2,10,11) norfloxacin and glyburide,(3) levofloxacin and glipizide (12) as well as levofloxacin and metformin-glibenclamide.(14) There has been one report of fatal hypoglycemia with concurrent levofloxacin and glyburide(9) and one of the above reports of hypoglycemia with concurrent levofloxacin and glyburide resulted in hypoxic brain injury.(11) A review of postmarketing adverse event data for the fluoroquinolones and hypoglycemic coma identified 56 reports in FAERS search from October 1987- April 2017 and 11 additional cases in the medical literature. Most patients had risk factors for hypoglycemia. 41 patients were taking one or more hypoglycemic drugs. 13 deaths occurred (some of these patients had renal insufficiency). 9 patients did not fully recover and had resultant disability.(13)

Selected Antidiabetics/Maois

SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed.

MECHANISM OF ACTION: The exact mechanism by which MAO inhibitors affect carbohydrate metabolism and subsequent enhancement of the hypoglycemic action of insulin is not clear. The adrenergic response to hypoglycemia may be blocked by insulin release caused by MAOI's. In vitro studies have shown that MAO inhibitors are capable of both potentiating and inhibiting insulin release, depending on their concentrations. Stimulation of glucose-mediated insulin secretion is believed to be related to the MAO inhibitory effects of the drugs.

CLINICAL EFFECTS: The hypoglycemic response to both insulin and glucose lowering agents including alpha glucosidase inhibitors, meglitinides, and sulfonylurea may be increased.

PREDISPOSING FACTORS: None determined.

PATIENT MANAGEMENT: Concurrent MAO inhibitor therapy for depression in a diabetic patient will often require reduction in dosage of the hypoglycemic agent because of enhanced hypoglycemic effects. Since the extent of the reaction is highly unpredictable, any diabetic patients receiving MAO inhibitors should be monitored for possible excessive hypoglycemia.

DISCUSSION: This interaction is likely to occur. The interaction between MAOIs and insulin is well documented. Additional documentation is necessary to confirm the potential interaction of MAOI's with other glucose lowering agents including alpha glucosidase inhibitors, meglitinides, and sulfonylureas but is expected to occur based on pharmacologic similarity. It may take several weeks for the full hypoglycemic effect of the MAOI to occur. Conversely, it may take several weeks for the effect to dissipate after stopping the MAOI. Furazolidone is known to be a monoamine oxidase inhibitor. Methylene blue, when administered intravenously, has been shown to reach sufficient concentrations to be a potent inhibitor of MAO-A. Metaxalone is a weak inhibitor of MAO.

Selected Antidiabetics/Safinamide

SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed.

MECHANISM OF ACTION: The exact mechanism by which MAO inhibitors such as safinamide affect carbohydrate metabolism and subsequent enhancement of the hypoglycemic action of insulin is not clear. The adrenergic response to hypoglycemia may be blocked by insulin release caused by MAOI's. In vitro studies have shown that MAO inhibitors are capable of both potentiating and inhibiting insulin release, depending on their concentrations. Stimulation of glucose-mediated insulin secretion is believed to be related to the MAO inhibitory effects of the drugs.

CLINICAL EFFECTS: The hypoglycemic response to both insulin and glucose lowering agents including alpha glucosidase inhibitors, meglitinides, and sulfonylurea may be increased.

PREDISPOSING FACTORS: None determined.

PATIENT MANAGEMENT: Concurrent MAO inhibitor therapy for depression in a diabetic patient will often require reduction in dosage of the hypoglycemic agent because of enhanced hypoglycemic effects. Since the extent of the reaction is highly unpredictable, any diabetic patients receiving MAO inhibitors should be monitored for possible excessive hypoglycemia.

DISCUSSION: This interaction is likely to occur. The interaction between MAOIs and insulin is well documented. Additional documentation is necessary to confirm the potential interaction of MAOI's with other glucose lowering agents including alpha glucosidase inhibitors, meglitinides, and sulfonylureas but is expected to occur based on pharmacologic similarity. It may take several weeks for the full hypoglycemic effect of the MAOI to occur. Conversely, it may take several weeks for the effect to dissipate after stopping the MAOI.

Selected Cyp2c9 Substrates/Nitisinone

SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed.

MECHANISM OF ACTION: Nitisinone is a moderate inhibitor of CYP2C9.(1,2)

CLINICAL EFFECTS: Decreased clearance may increase systemic concentrations of drugs primarily metabolized by CYP2C9, leading to toxicity.(1,2)

PREDISPOSING FACTORS: None determined.

PATIENT MANAGEMENT: Decrease the dosage of the CYP2C9 substrate drug by one-half. Additional dose adjustments may be necessary. Closely monitor patients stable on CYP2C9 substrates for altered therapeutic effect or toxicity when nitisinone therapy is started or adjusted.(1)

DISCUSSION: In a study, 16 healthy subjects who were pre-treated with nitisinone (80 mg daily) for 14 days and received a single dose of tolbutamide (500 mg) had an increase in tolbutamide area-under-curve (AUC) and maximum concentration (Cmax) of 131 % and 16 %, respectively, compared to tolbutamide administered alone.(1,2) Medications linked to this interaction include fluvastatin, fosphenytoin, glimepiride, glipizide, phenytoin, tolbutamide, and warfarin. These drugs have a narrow therapeutic range or are designated as CYP2C9 Sensitive Substrates(3,4) (i.e. moderate 2C9 inhibitors are expected to increase exposure (AUC) to these agents by 2-fold to 5-fold).

Sodium Channel Blocker; Potassium Channel Blocker/Lacosamide

SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed.

MECHANISM OF ACTION: Lacosamide may enhance the slow inactivation of voltage-gated sodium channels and may cause dose-dependent bradycardia, prolongation of the PR interval, atrioventricular (AV) block, or ventricular tachyarrhythmia.(1)

CLINICAL EFFECTS: Concurrent use of lacosamide and agents that affect cardiac conduction (sodium channel blockers and potassium channel blockers) may increase the risk of bradycardia, prolongation of the PR interval, atrioventricular (AV) block, or ventricular tachyarrhythmia.(1)

PREDISPOSING FACTORS: None determined.

PATIENT MANAGEMENT: Lacosamide should be used with caution in patients on concomitant medications that affect cardiac conduction, including sodium channel blockers and potassium channel blockers.(1) If concurrent use is needed, obtain an ECG before lacosamide therapy and after lacosamide dose is titrated to steady-state.(1) Patients should be monitored closely when lacosamide is given intravenously.(1)

DISCUSSION: In a clinical trial in patients with partial-onset seizures, asymptomatic first-degree atrioventricular (AV) block occurred in 4/944 (0.4%) of patient who received lacosamide compared to 0/364 (0%) with placebo.(1) In a clinical trial in patients with diabetic neuropathy, asymptomatic first-degree AV block occurred in 5/1023 (0.5%) of patients who received lacosamide compared to 0/291 (0%) with placebo.(1) Second-degree and complete AV block have been reported in patients with seizures.(1) One case of profound bradycardia was observed in a patient during a 15-minute infusion of 150 mg of lacosamide.(1) A case report of a 49 year old male with refractory complex partial and generalized seizures described the development of ventricular tachycardia four months after addition of lacosamide 400 mg/day to the existing regimen of carbamazepine, lamotrigine, clonazepam, and valproate. The patient's ECG showed first-degree AV block, posterior left fascicular block, and severe widening of the QRS complex, all of which resolved upon discontinuation of lacosamide.(2)

Sulfonylureas/Amiodarone

SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed.

MECHANISM OF ACTION: Amiodarone may decrease the metabolism of sulfonylureas by inhibiting CYP2C9. Amiodarone is a moderate CYP2C9 inhibitor.(1-5)

CLINICAL EFFECTS: Increased effectiveness of the sulfonylurea which may result in clinical symptoms of hypoglycemia.

PREDISPOSING FACTORS: This interaction may be more likely in patients using higher doses of amiodarone and who use amiodarone for greater than 180 days.(6)

PATIENT MANAGEMENT: Closely monitor blood glucose levels during concurrent therapy. The dose of the sulfonylurea may need to be adjusted when initiating or discontinuing amiodarone therapy.

DISCUSSION: In a nested case control study, concurrent use of amiodarone and sulfonylureas increased the risk of severe hypoglycemia by 56% (95% CI:0.98-2.46). In patients on sulfonylureas, amiodarone use greater than 180 days and at higher daily doses was associated with a 2.08-fold and a 2.21-fold increase in severe hypoglycemia, respectively, which was statistically significant.(6)

Sulfonylureas/Azole Antifungals

SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed.

MECHANISM OF ACTION: Azole antifungals inhibit the metabolism of sulfonylureas.

CLINICAL EFFECTS: Increased effectiveness of the sulfonylurea which may result in clinical symptoms of hypoglycemia.

PREDISPOSING FACTORS: None determined.

PATIENT MANAGEMENT: Monitor blood glucose levels during concurrent therapy. The dose of the sulfonylurea may need to be adjusted.

DISCUSSION: Prospective and retrospective studies in healthy subjects have documented an interaction between the sulfonylureas and fluconazole and ketoconazole. In vitro studies have shown the metabolism of sulfonylureas to be inhibited by ketoconazole and clotrimazole. In 13 healthy males, fluconazole increased the maximum concentration (Cmax) and area-under-curve (AUC) of a single dose of glipizide (2.5 mg) by 19% and 49%, respectively. In 20 healthy males, fluconazole increased the Cmax and AUC of a single dose of glyburide (5 mg) by 19% and 44%, respectively. In 13 healthy males, fluconazole increased the Cmax and AUC of a single dose of tolbutamide (500 mg) by 11% and 26%, respectively. Although itraconazole was found to have no effect on tolbutamide clearance in a study in rats, additional information is needed to determine if an interaction occurs. In healthy subjects, glucose concentrations decreased during concurrent therapy with glipizide and posaconazole. Voriconazole has been shown to inhibit CYP2C9.

Sulfonylureas/Diazoxide

SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed.

MECHANISM OF ACTION: Unknown.

CLINICAL EFFECTS: In a patient stabilized on a sulfonylurea hypoglycemic agent, hyperglycemia may occur following the addition of diazoxide to the treatment.

PREDISPOSING FACTORS: None determined.

PATIENT MANAGEMENT: Monitor blood glucose and adjust the dose of the sulfonylurea hypoglycemic agent as needed.

DISCUSSION: The concurrent administration of a sulfonylurea hypoglycemic agent and diazoxide has been beneficial in treating chlorpropamide-induced hypoglycemia and diazoxide-induced hyperglycemia. These reports indicate a potential problem if these agents are administered without proper monitoring of the patient's blood glucose.

Sulfonylureas/Systemic Non-Cardioselective Beta-Blockers

SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed.

MECHANISM OF ACTION: Not fully established. Probably blockade of a variety of beta-adrenergic responses to hypoglycemia.

CLINICAL EFFECTS: Diminished response to sulfonylureas and insulin may occur. Frequency and severity of hypoglycemic episodes may be increased, while warning symptoms of low blood sugar may be masked.

PREDISPOSING FACTORS: None determined.

PATIENT MANAGEMENT: Try to avoid beta-blocker therapy, particularly in diabetics prone to hypoglycemic attacks. One of the cardioselective agents may decrease risk of hypertensive attacks and allow more rapid glucose recovery from hypoglycemia. Patients should be counseled not to rely on tachycardia to diagnose hypoglycemia, since it is masked by beta-blocker therapy. Diaphoresis is unaffected by beta-blockade and can be used by the diabetic to recognize hypoglycemia.

DISCUSSION: A class effect of diminished glucose-lowering effects is expected with concurrent use of beta-blockers and sulfonylureas. It is prudent to monitor serum glucose closely in patients receiving beta-blocker therapy because symptoms of hypoglycemia may be masked. A double blind, randomized, 12 month study of 39 patients tested the metabolic effects of pindolol (5 mg BID) compared to control group on insulin sensitivity. The patient's insulin sensitivity index decreased 17% when on pindolol treatment compared to placebo (p<0.01). Insulin mediated glucose uptake was significantly lower (p<0.05) with propranolol treatment than with placebo.(1) A study of 26 patients with chronic heart failure showed that carvedilol (average daily dose 27.5 mg/d) caused a significant decrease in fasting insulin levels (17.09 to 10.77 microU/ml, p <0.05) compared to pre-treatment levels. This trial also showed that patients on carvedilol had significantly (p=0.015) lower fasting insulin levels (10.77 microU/ml) compared to the fasting insulin levels (20.72 microU/ml) of patients on bisoprolol treatment (5.9mg/d).(2)

*Known hypersensitivity to the drug or any ingredients in the formulation

*Known hypersensitivity to sulfonamide derivatives.

*Diabetic ketoacidosis with or without coma. Diabetic ketoacidosis should be treated with insulin.

*Type 1 diabetes mellitus.

There are no contraindication contraindications for this drug.

• Debilitation
• Hepatic porphyria
• High fever >101 degrees fahrenheit
• Hypoglycemic disorder

• Alcohol use disorder
• Disease of liver
• Glucose-6-phosphate dehydrogenase (g6Pd) deficiency
• Hemolytic anemia
• Kidney disease with reduction in glomerular filtration rate (GFr)
• Pituitary insufficiency
• Primary adrenocortical insufficiency

The most common adverse effects of glipizide (>3% of patients) are dizziness, diarrhea, nervousness, tremor, hypoglycemia, and flatulence.

More Frequent

• Hypoglycemic disorder

Rare or Very Rare

• Abnormal hepatic function tests
• Agranulocytosis
• Aplastic anemia
• Blood dyscrasias
• Cholestasis
• Gastrointestinal hemorrhage
• Hemolytic anemia
• Hepatic failure
• Hepatic porphyria
• Hepatitis
• Hepatocellular damage
• Hyponatremia
• Leukopenia
• Maculopapular rash
• Obstructive hyperbilirubinemia
• Pancytopenia
• Porphyria cutanea tarda
• SIADH syndrome
• Thrombocytopenic disorder

More Frequent

• Constipation
• Diarrhea
• Dizziness
• Drowsy
• Flatulence
• Headache disorder
• Nausea
• Nervousness
• Tremor

Less Frequent

• Weight gain

Rare or Very Rare

• Acute abdominal pain
• Eczema
• Erythema
• Gastrointestinal irritation
• Pruritus of skin
• Skin photosensitivity
• Skin rash
• Urticaria

No enhanced messaging available.

Safety and effectiveness of glipizide in pediatric patients have not been established.

The manufacturer states that available data from a small number of published studies and postmarketing experience with use of extended-release glipizide in pregnancy over decades have not identified any drug-associated risks for major birth defects, miscarriage, or adverse maternal outcomes. Glipizide has been shown to be mildly fetotoxic in rats when given at doses of 5-50 mg/kg; the fetotoxic effect is perinatal and similar to that of some other sulfonylureas, and is believed to be directly related to the hypoglycemic effect of the drug. There were no effects on embryofetal development following administration of glipizide to pregnant rats and rabbits during organogenesis at doses 833 and 8 times, respectively, the human dose based on body surface area. No teratogenic effects were observed in reproduction studies in rats or rabbits. However, increased pup mortality was observed in rats given glipizide from gestation day 15 throughout lactation at dosages twice the maximum human dose based on body surface area.

Poorly controlled diabetes mellitus in pregnancy increases the maternal risk for diabetic ketoacidosis, pre-eclampsia, miscarriage, preterm delivery, stillbirth, and delivery complications. In addition, poorly controlled diabetes increases the fetal risk for major birth defects, stillbirth, and macrosomia-related morbidity. Many experts recommend that insulin be used during pregnancy to maintain optimum control of blood glucose concentration. Use of glipizide in pregnant women is generally not recommended, and the drug should be used during pregnancy only when clearly necessary (e.g., when insulin therapy is infeasible).

Neonates born to women with gestational diabetes that were treated with sulfonylureas during pregnancy may be at increased risk for neonatal intensive care admission and may develop respiratory distress, hypoglycemia, or birth injury; they also may be large for gestational age. Sulfonylureas, including glipizide, cross the placenta and have been associated with neonatal adverse reactions such as hypoglycemia. Prolonged, severe hypoglycemia lasting 4-10 days has been reported in some neonates born to women who were receiving sulfonylurea antidiabetic agents up to the time of delivery; this effect has been reported more frequently with the use of those agents having prolonged elimination half-lives. To minimize the risk of neonatal hypoglycemia if glipizide is used during pregnancy, the manufacturer recommends that the drug be discontinued at least 2 weeks before the expected delivery date. Neonates should be observed for symptoms of hypoglycemia and respiratory distress and managed accordingly.

Although it is not known whether glipizide is distributed into milk in humans, some sulfonylurea antidiabetic agents are distributed into human milk. There are no data on the effects of glipizide on milk production. The developmental and health benefits of breast-feeding should be considered along with the mother's clinical need for glipizide and any potential adverse effects on the breast-fed child from glipizide or from the underlying maternal condition. If glipizide is used during breast-feeding, infants should be monitored for signs of hypoglycemia (e.g., jitters, cyanosis, apnea, hypothermia, excessive sleepiness, poor feeding, seizures). If glipizide is discontinued, and if dietary management alone is inadequate for controlling blood glucose concentration, administration of insulin should be considered.

There are no overall differences in safety or effectiveness between younger and older patients receiving glipizide, but greater sensitivity of some individuals cannot be ruled out. Geriatric patients are particularly susceptible to the hypoglycemic action of antidiabetic agents; hypoglycemia may be difficult to recognize in these patients. In general, dosage selection for a geriatric patient should be cautious, usually starting at the low end of the dosage range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy.