Side Effects of Glucotrol (glipizide)

Glucotrol (glipizide) is a sulfonylurea used to treat patients with type 2 diabetes. 

Insulin is a hormone that is made in the pancreas that when released into the blood causes cells in the body to remove sugar (glucose) from the blood and reduces the formation of glucose by the liver. 

Patients with type 2 diabetes have high glucose (sugar) levels in their blood because the cells in their bodies are resistant to the glucose-removing effect of the insulin, and the liver produces too much glucose. In addition, in type 2 diabetes the pancreas is unable to produce the increased amounts of insulin that are necessary to overcome the resistance. 

Glucotrol reduces blood glucose by stimulating the pancreas to produce more insulin. Glucotrol is not a cure for diabetes.

Common side effects of Glucotrol include

• headache,
• dizziness,
• nausea,
• vomiting,
• diarrhea,
• heartburn,
• gas, and
• skin rashes (which may cause itching, hives, or a diffuse measles-like rash).

Serious side effects of Glucotrol include

• hepatitis,
• yellowing skin and eyes (jaundice),
• low blood sodium (hyponatremia), and
• low blood sugar (hypoglycemia). 

Drug interactions of Glucotrol include alcohol, which may prolong the action of Glucotrol by delaying its absorption and elimination.

• Cholestyramine may reduce both the absorption and effects of Glucotrol.
• Fluconazole also can increase the absorption and effects of Glucotrol.
• Many drugs can potentially increase or decrease glucose levels thus increasing or decreasing the effects of Glucotrol.
• Drug interactions that cause low blood glucose (hypoglycemia) can occur with
  • nonsteroidal anti-inflammatory drugs (NSAIDs),
  • sulfa drugs,
  • warfarin,
  • miconazole,
  • fluconazole,
  • voriconazole,
  • beta-blockers,
  • androgens,
  • chloramphenicol,
  • cimetidine,
  • ranitidine,
  • clarithromycin,
  • MAO inhibitors,
  • mifepristone,
  • probenecid,
  • quinolone antibiotics, and
  • selective serotonin reuptake inhibitors (SSRIs).
• Drug interactions involving Glucotrol which can result in high blood glucose (hyperglycemia) can occur with
  • thiazide diuretics,
  • loop diuretics,
  • corticosteroids,
  • phenytoin,
  • colesevelam,
  • danazol, and
  • somatropin.
• Rifampin may reduce the blood levels of Glucotrol and this may result in higher levels of sugar in the blood. 

It is not recommended to use Glucotrol for the routine management of diabetes in pregnant women. Insulin is preferred. In the event that Glucotrol is used during pregnancy, the manufacturer recommends that it be stopped at least 1 month before the expected date of delivery. 

Glucotrol is not found in breast milk. However, the risk of developing hypoglycemia in the nursing infant should be weighed against the potential benefit to the mother of taking Glucotrol and a decision should be made to discontinue the drug or to discontinue breastfeeding.

Side effects include:

• headache,
• dizziness,
• nausea,
• vomiting,
• diarrhea,
• heartburn, and
• gas.

Skin rashes can occur and cause itching, hives, or a diffuse measles-like rash.

Rare but serious side effects include:

• hepatitis,
• jaundice, and
• a low blood sodium concentration (hyponatremia).

Glipizide also may cause hypoglycemia. The risk of hypoglycemia increases when glipizide is combined with other glucose reducing agents.

In U.S. and foreign controlled studies, the frequency of serious adverse reactions reported was very low. Of 702 patients, 11.8% reported adverse reactions and in only 1.5% was Glucotrol discontinued.

Hypoglycemia

• See prescribing information.

Gastrointestinal

• Gastrointestinal disturbances are the most common reactions. Gastrointestinal complaints were reported with the following approximate incidence:
  • nausea and diarrhea, one in seventy;
  • constipation and gastralgia, one in one hundred.
  • They appear to be dose-related and may disappear on division or reduction of dosage.
• Cholestatic jaundice may occur rarely with sulfonylureas. Glucotrol should be discontinued if this occurs.

Dermatologic

• Allergic skin reactions including erythema, morbilliform or maculopapular eruptions, urticaria, pruritus, and eczema have been reported in about one in seventy patients.
• These may be transient and may disappear despite continued use of Glucotrol; if skin reactions persist, the drug should be discontinued. Porphyria cutanea tarda and photosensitivity reactions have been reported with sulfonylureas.

Hematologic

• Leukopenia, agranulocytosis, thrombocytopenia, hemolytic anemia, aplastic anemia, and pancytopenia have been reported with sulfonylureas.

Metabolic

• Hepatic porphyria and disulfiram-like reactions have been reported with sulfonylureas.
• In the mouse, Glucotrol pretreatment did not cause an accumulation of acetaldehyde after ethanol administration.
• Clinical experience to date has shown that Glucotrol has an extremely low incidence of disulfiram-like alcohol reactions.

Endocrine Reactions

• Cases of hyponatremia and the syndrome of inappropriate antidiuretic hormone (SIADH) secretion have been reported with this and other sulfonylureas.

Miscellaneous

• Dizziness, drowsiness, and headache have each been reported in about one in fifty patients treated with Glucotrol. They are usually transient and seldom require discontinuance of therapy.

Laboratory Tests

• The pattern of laboratory test abnormalities observed with Glucotrol was similar to that for other sulfonylureas.
• Occasional mild to moderate elevations of SGOT, LDH, alkaline phosphatase, BUN, and creatinine were noted.
• One case of jaundice was reported. The relationship of these abnormalities to Glucotrol is uncertain, and they have rarely been associated with clinical symptoms.

Post-Marketing Experience

The Following Adverse Events Have Been Reported In Post-Marketing Surveillance

Hepatobiliary

• Cholestatic and hepatocellular forms of liver injury accompanied by jaundice have been reported rarely in association with glipizide; Glucotrol should be discontinued if this occurs.

• The hypoglycemic action of sulfonylureas may be potentiated by certain drugs including nonsteroidal anti-inflammatory agents, some azoles, and other drugs that are highly protein bound, salicylates, sulfonamides, chloramphenicol, probenecid, coumarins, monoamine oxidase inhibitors, quinolones and beta adrenergic blocking agents.
• When such drugs are administered to a patient receiving Glucotrol, the patient should be observed closely for hypoglycemia.
• When such drugs are withdrawn from a patient receiving Glucotrol, the patient should be observed closely for loss of control.
• In vitro binding studies with human serum proteins indicate that Glucotrol binds differently than tolbutamide and does not interact with salicylate or dicumarol.
• However, caution must be exercised in extrapolating these findings to the clinical situation and in the use of Glucotrol with these drugs.
• Certain drugs tend to produce hyperglycemia and may lead to loss of control.
• These drugs include the thiazides and other diuretics, corticosteroids, phenothiazines, thyroid products, estrogens, oral contraceptives, phenytoin, nicotinic acid, sympathomimetics, calcium channel blocking drugs, and isoniazid.
• When such drugs are administered to a patient receiving Glucotrol, the patient should be closely observed for loss of control.
• When such drugs are withdrawn from a patient receiving Glucotrol, the patient should be observed closely for hypoglycemia.
• A potential interaction between oral miconazole and oral hypoglycemic agents leading to severe hypoglycemia has been reported. Whether this interaction also occurs with the intravenous, topical, or vaginal preparations of miconazole is not known.
• The effect of concomitant administration of Diflucan (fluconazole) and Glucotrol has been demonstrated in a placebo-controlled crossover study in normal volunteers.
• All subjects received Glucotrol alone and following treatment with 100 mg of DIFLUCAN as a single daily oral dose for 7 days.
• The mean percentage increase in the Glucotrol AUC after fluconazole administration was 56.9% (range: 35 to 81).
• In studies assessing the effect of colesevelam on the pharmacokinetics of glipizide ER in healthy volunteers, reductions in glipizide AUC0-∞ and Cmax of 12% and 13%, respectively were observed when colesevelam was coadministered with glipizide ER.
• When glipizide ER was administered 4 hours prior to colesevelam, there was no significant change in glipizide AUC0-∞ or Cmax, -4% and 0%, respectively.
• Therefore, Glucotrol should be administered at least 4 hours prior to colesevelam to ensure that colesevelam does not reduce the absorption of glipizide.