Sulfonylurea

Glipizide

Approved 29 Dec 2016OralTablet, extended release

The FDA lists this product in 49 strengths and forms.

Indications

Glipizide extended-release tablets are indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus. Glipizide extended-release tablet is a sulfonylurea indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus Limitations of Use: Not for treatment of type 1 diabetes or diabetic ketoacidosis

1.1Limitations of Use

Glipizide extended-release tablets are not recommended for the treatment of type 1 diabetes mellitus or diabetic ketoacidosis.

Contraindications

Glipizide is contraindicated in patients with: Known hypersensitivity to glipizide or any of the product’s ingredients. Hypersensitivity to sulfonamide derivatives. Known hypersensitivity to glipizide or any of the product’s ingredients ( 4 ). Hypersensitivity to sulfonamide derivatives ( 4 ).

Warnings and precautions

Hypoglycemia: May be severe. Ensure proper patient selection, dosing, and instructions, particularly in at-risk populations (e.g., elderly, renally impaired) and when used with other anti-diabetic medications ( 5.1 ). Hemolytic Anemia: Can occur if glucose 6-phosphate dehydrogenase (G6PD) deficient.Consider a non-sulfonylurea alternative ( 5.2 ). Potential Increased Risk of Cardiovascular Mortality with Sulfonylureas: Inform patient of risks, benefits and treatment alternatives ( 5.3 ).

Macrovascular Outcomes: No clinical studies have established conclusive evidence of macrovascular risk reduction with glipizide extended-release tablets or any other antidiabetic drug ( 5.4 ).

5.1Hypoglycemia

All sulfonylurea drugs, including glipizide, are capable of producing severe hypoglycemia [see Adverse Reactions (6) ] . Concomitant use of glipizide extended-release tablets with other anti-diabetic medication can increase the risk of hypoglycemia. A lower dose of glipizide extended-release tablets may be required to minimize the risk of hypoglycemia when combining it with other anti-diabetic medications. Educate patients to recognize and manage hypoglycemia.

Interactions

Certain medications may affect glucose metabolism, requiring glipizide extended-release tablets dose adjustment and close monitoring of blood glucose (7.1).
Miconazole: Monitor patients closely. Severe hypoglycemia can occur when glipizide tablets and oral miconazole are used concomitantly ( 7.2 , 12.3 ).
Fluconazole: Monitor patients closely. An increase in glipizide tablets AUC was seen after fluconazole administration ( 7.3 , 12.3 ).
Colesevelam: Glipizide extended-release tablets should be administered at least 4 hours prior to colesevelam (7.4 , 12.3 ).

7.1Drugs Affecting Glucose Metabolism

A number of medications affect glucose metabolism and may require glipizide extended-release tablets dose adjustment and close monitoring for hypoglycemia or worsening glycemic control. The following are examples of medication that may increase the glucose lowering effect of glipizide extended-release tablets, increase the susceptibility to and/or intensity of hypoglycemia: antidiabetic agents, ACE inhibitors, angiotensin II receptor blocking agents, disopyramide, fibrates, fluoxetine, monoamine oxidase inhibitors, pentoxifylline, pramlintide, propoxyphene, salicylates, somatostatin analogs (e.g., octreotide), sulfonamide antibiotics, nonsteroidal anti-inflammatory agents, chloramphenicol, probenecid, coumarins, voriconazole, H2 receptor antagonists, and quinolones.

When these medications are administered to a patient receiving glipizide extended-release tablets, monitor the patient closely for hypoglycemia. When these medications are discontinued from a patient receiving glipizide extended-release tablets, monitor the patient closely for worsening glycemic control. The following are examples of medication that may reduce the glucose-lowering effect of glipizide extended-release tablets, leading to worsening glycemic control: atypical antipsychotics (e.g., olanzapine and clozapine), corticosteroids, danazol, diuretics, estrogens, glucagon, isoniazid, niacin, oral contraceptives, phenothiazines, progestogens (e.g., in oral contraceptives), protease inhibitors, somatropin, sympathomimetic agents (e.g., albuterol, epinephrine, terbutaline), thyroid hormones, phenytoin, nicotinic acid, and calcium channel blocking drugs.

When such drugs are administered to patients receiving glipizide extended-release tablets, monitor the patients closely for worsening glycemic control. When these medications are discontinued from patients receiving glipizide extended-release tablets, monitor the patients closely for hypoglycemia. Alcohol, beta-blockers, clonidine, and reserpine may lead to either potentiation or weakening of the glucose-lowering effect.

Increased frequency of monitoring may be required when glipizide extended-release tablet is co-administered with these drugs. The signs of hypoglycemia may be reduced or absent in patients taking sympatholytic drugs such as beta-blockers, clonidine, guanethidine, and reserpine. Increased frequency of monitoring may be required when glipizide extended-release tablet is co-administered with these drugs.

7.2Miconazole

Monitor patients closely for hypoglycemia when glipizide extended-release tablet is co-administered with miconazole. A potential interaction between oral miconazole and oral hypoglycemic agents leading to severe hypoglycemia has been reported [see Clinical Phamacology (12.3 )].

7.3Fluconazole

Monitor patients closely for hypoglycemia when glipizide extended-release tablet is co-administered with fluconazole. Concomitant treatment with fluconazole increases plasma concentrations of glipizide, which may lead to hypoglycemia [ see Clinical Pharmacology (12.3 )].

7.4Colesevelam

Glipizide extended-release tablets should be administered at least 4 hours prior to the administration of colesevelam. Colesevelam can reduce the maximum plasma concentration and total exposure of glipizide when the two are coadministered [ see Clinical Pharmacology (12.3)].

Adverse reactions

The following serious adverse reactions are discussed in more detail below and elsewhere in the labeling: Hypoglycemia [see Warnings and Precautions (5.1) ] Hemolytic anemia [see Warnings and Precautions (5.2) ] Most common adverse reactions (incidence > 3%) are dizziness, diarrhea, nervousness,tremor, hypoglycemia and flatulence ( 6.1 ). To report SUSPECTED ADVERSE REACTIONS, contact Rising Pharmaceuticals, Inc. at1-866-562-4597 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

6.1Clinical Trials Experience

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. In clinical trials, 580 patients from 31 to 87 years of age received glipizide extended-release tablets in doses from 5 mg to 60 mg in both controlled and open trials.

The dosages above 20 mg are not recommended dosages. In these trials, approximately 180 patients were treated with glipizide extended-release tablets for at least 6 months. Table 1 summarizes the incidence of adverse reactions, other than hypoglycemia, that were reported in pooled double-blind, placebo-controlled trials in ≥3% of glipizide extended-release tablets-treated patients and more commonly than in patients who received placebo.

Table 1: Incidence (%) of Adverse Reactions Reported in ≥3% of Patients Treated in Placebo-Controlled Clinical Trials and More Commonly in Patients Treated with glipizide extended-release tablets (Excluding Hypoglycemia) Adverse Effect Glipizide Extended-Release Tablets (%) (N=278) Placebo (%) (N=69) Dizziness 6.8

5.8 Diarrhea 5.4

0.0 Nervousness 3.6

2.9 Tremor 3.6

0.0 Flatulence 3.2

1.4 Hypoglycemia Of the 580 patients that received glipizide extended-release tablets in clinical trials, 3.4% had hypoglycemia documented by a blood-glucose measurement <60 mg/dL and/or symptoms believed to be associated with hypoglycemia and 2.6% of patients discontinued for this reason. Hypoglycemia was not reported for any placebo patients. Gastrointestinal Reactions In clinical trials, the incidence of gastrointestinal (GI) side effects (nausea, vomiting, constipation, dyspepsia), occurred in less than 3% of glipizide extended-release tablets -treated patients and were more common in glipizide extended-release tablets -treated patients than those receiving placebo.

Dermatologic Reactions In clinical trials, allergic skin reactions, i.e., urticaria occurred in less than 1.5% of treated patients and were more common in glipizide extended-release tablets treated patients than those receiving placebo. These may be transient and may disappear despite continued use of glipizide extended-release tablets; if skin reactions persist, the drug should be discontinued. Laboratory Tests Mild to moderate elevations of ALT, LDH, alkaline phosphatase, BUN and creatinine have been noted.

The relationship of these abnormalities to glipizide is uncertain.

6.2Postmarketing Experience

The following adverse reactions have been identified during post approval use of glipizide extended-release tablets. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure. Abdominal pain Cholestatic and hepatocellular forms of liver injury accompanied by jaundice Leukopenia, agranulocytosis, thrombocytopenia, hemolytic anemia [see Warnings and Precautions (5.2) ] , aplastic anemia, pancytopenia Hepatic porphyria and disulfiram-like reactions Hyponatremia and the syndrome of inappropriate antidiuretic hormone (SIADH) secretion Rash There have been reports of gastrointestinal irritation and gastrointestinal bleeding with use of another drug with this non-dissolvable extended release formulation.

Glipizide

Indications

1.1Limitations of Use

Contraindications

Warnings and precautions

5.1Hypoglycemia

Two medicines in one question?

5.2Hemolytic Anemia Treatment

5.3Increased Risk of Cardiovascular Mortality with Sulfonylureas

5.4Macrovascular Outcomes

5.5Gastrointestinal Obstruction

Interactions

7.1Drugs Affecting Glucose Metabolism

7.2Miconazole

7.3Fluconazole

7.4Colesevelam

Adverse reactions

6.1Clinical Trials Experience

6.2Postmarketing Experience

Composition

Strengths and forms

Official product information

At a glance

Guidelines