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Glipizide/metformin Disease Interactions

There are 11 disease interactions with glipizide / metformin.

Major

Metformin (applies to glipizide/metformin) lactic acidosis

Major Potential Hazard, Moderate plausibility. Applicable conditions: Congestive Heart Failure, Myocardial Infarction, Shock, Anemia, Dehydration, Alcoholism, Renal Dysfunction, Diarrhea, Asphyxia, Vomiting, Diabetic Ketoacidosis

Metformin is contraindicated in patients with acute or chronic metabolic acidosis (including diabetic ketoacidosis) with or without coma. Postmarketing cases of metformin-associated lactic acidosis have resulted in death, hypothermia, hypotension, and resistant bradyarrhythmias. Risk factors include renal dysfunction, age 65 years and older, hypoxic states, excessive alcohol intake, and liver dysfunction. Lactic acidosis has been associated with metformin accumulation in plasma at levels generally exceeding 5 mcg/mL. The risk of metformin-associated lactic acidosis increases with the patient's age because patients 65 years and older have a greater likelihood of having hepatic, renal, or cardiac impairment. Renal function should be assessed more frequently in older adult patients. Several postmarketing cases of metformin-associated lactic acidosis occurred in the setting of acute congestive heart failure, especially when accompanied by hypoperfusion and hypoxemia; cardiovascular collapse (shock), acute myocardial infarction, sepsis, and other conditions associated with hypoxemia (e.g., severe anemia, asphyxia) have been associated with lactic acidosis and may cause prerenal azotemia. When such an event occurs, metformin should be discontinued. Dehydration (e.g., severe diarrhea or vomiting) may increase the risk for volume depletion, hypotension, and renal impairment; such patients may be at increased risk for lactic acidosis. Alcohol potentiates the effect of metformin on lactate metabolism; patients should be advised against excessive alcohol intake while receiving metformin. All patients treated with metformin should have renal function monitored regularly (at least annually or more frequently if necessary). If metformin-associated lactic acidosis is suspected, general supportive measures should be instituted promptly in a hospital setting, as well as immediate discontinuation of metformin. If lactic acidosis is diagnosed or strongly suspected, prompt hemodialysis is recommended to correct the acidosis and remove accumulated metformin. Patients and their families should be educated about the symptoms of lactic acidosis and, if these symptoms occur, they should be instructed to discontinue metformin and contact their health care provider.

References

  1. (2018) "Product Information. Glucophage (metFORMIN)." EMD Serono Inc, SUPPL-34
Major

Metformin (applies to glipizide/metformin) liver disease

Major Potential Hazard, Moderate plausibility.

Metformin decreases the liver uptake of lactate increasing lactate blood levels which may increase the risk of lactic acidosis, especially in at-risk patients. There have been reports of cases of metformin-associated lactic acidosis in patients with liver dysfunction. Metformin should generally be avoided in patients with evidence of hepatic disease.

References

  1. (2018) "Product Information. Glucophage (metFORMIN)." EMD Serono Inc, SUPPL-34
Major

Metformin (applies to glipizide/metformin) renal dysfunction

Major Potential Hazard, Moderate plausibility.

The use of metformin is contraindicated in patients with severe renal dysfunction (estimated GFR [eGFR] less than 30 mL/min/1.73 m2). Metformin is substantially excreted by the kidney; the risk of metformin accumulation and lactic acidosis increases with the degree of renal dysfunction. Before starting metformin, an eGFR should be obtained. Initiation of metformin is not recommended in patients with eGFR between 30 and 45 mL/min/1.73 m2. An eGFR should be obtained at least annually in all patients; in those at risk of developing renal dysfunction (e.g., older adult patients), renal function should be assessed more frequently. In patients whose eGFR falls below 45 mL/min/1.73 m2, the benefit/risk of continuing therapy should be assessed. Postmarketing cases of metformin-associated lactic acidosis primarily occurred with significant renal dysfunction; metformin plasma levels generally exceeded 5 mcg/mL.

References

  1. (2018) "Product Information. Glucophage (metFORMIN)." EMD Serono Inc, SUPPL-34
Major

Oral hypoglycemic agents (applies to glipizide/metformin) cardiovascular risk

Major Potential Hazard, Moderate plausibility. Applicable conditions: Cardiovascular Disease

The use of oral hypoglycemic agents may be associated with an increased risk of cardiovascular mortality compared to treatment with diet alone or diet with insulin. This warning is based on the University Group Diabetes Program (UGDP) study, a long-term prospective clinical trial designed to evaluate the effectiveness of glucose-lowering drugs in preventing or delaying vascular complications in patients with non-insulin-dependent diabetes. Patients treated with diet plus a fixed dosage of either tolbutamide (a sulfonylurea) or phenformin (a biguanide) for 5 to 8 years had a cardiovascular mortality rate approximately 2.5 times that of patients treated with diet alone, resulting in discontinuation of both these treatments in the study. Despite controversy regarding interpretation of these results, clinicians and patients should be aware of the potential risk when making treatment decisions for diabetes, particularly in the presence of underlying cardiovascular disease. Data are not available for other sulfonylureas or biguanides, nor for hypoglycemic agents belonging to other classes. However, given the similarities in chemical structure and/or mode of action, the same caution should be applied.

References

  1. (2002) "Product Information. Diabinese (chlorpropamide)." Pfizer U.S. Pharmaceuticals
  2. (2002) "Product Information. Glucotrol (glipizide)." Pfizer U.S. Pharmaceuticals
  3. "Product Information. Diabeta (glyburide)." Hoechst Marion-Roussel Inc, Kansas City, MO.
  4. (2001) "Product Information. Amaryl (glimepiride)." Hoechst Marion Roussel
  5. (2001) "Product Information. Prandin (repaglinide)." Novo Nordisk Pharmaceuticals Inc
  6. (2001) "Product Information. Tolinase (tolazamide)." Pharmacia and Upjohn
  7. (2001) "Product Information. Orinase (tolbutamide)." Pharmacia and Upjohn
  8. (2001) "Product Information. Dymelor (acetohexamide)." Lilly, Eli and Company
View all 8 references
Major

Sulfonylureas (applies to glipizide/metformin) DKA

Major Potential Hazard, Moderate plausibility. Applicable conditions: Diabetes Type 1, Diabetic Ketoacidosis

The use of some sulfonylurea agents is contraindicated for the treatment of patients with diabetic ketoacidosis, with or without coma. In addition, these agents should not be used as sole therapy in patients with type I diabetes mellitus.

References

  1. (2002) "Product Information. Diabinese (chlorpropamide)." Pfizer U.S. Pharmaceuticals
  2. (2002) "Product Information. Glucotrol (glipizide)." Pfizer U.S. Pharmaceuticals
  3. "Product Information. Diabeta (glyburide)." Hoechst Marion-Roussel Inc, Kansas City, MO.
  4. (2002) "Product Information. Micronase (glyburide)." Pharmacia and Upjohn
  5. (2001) "Product Information. Amaryl (glimepiride)." Hoechst Marion Roussel
  6. (2001) "Product Information. Tolinase (tolazamide)." Pharmacia and Upjohn
  7. (2001) "Product Information. Orinase (tolbutamide)." Pharmacia and Upjohn
View all 7 references
Major

Sulfonylureas (applies to glipizide/metformin) renal/liver disease

Major Potential Hazard, High plausibility. Applicable conditions: Renal Dysfunction

Sulfonylureas are metabolized in the liver, and their metabolites (some with pharmacologic activity) are excreted in the urine and feces. Patients with impaired liver and/or renal function treated with sulfonylureas may be exposed to higher serum drug concentrations, which can increase the potential for severe hypoglycemic episodes induced by these agents. In the presence of hepatic impairment, gluconeogenic capacity may also be diminished, further compounding the risk. Therapy with sulfonylureas should be administered cautiously in patients with liver and/or renal disease. Reduced dosages and longer intervals between dosage adjustments may be required. Hypoglycemia, if it occurs during treatment, may be prolonged in these patients because of slowed metabolism and/or excretion of the drugs.

References

  1. Johnson PC, Hennes AR, Driscoll T, West KM (1959) "Metabolic fate of chlorpropamide in man." Ann N Y Acad Sci, 74, p. 459-72
  2. Brotherton PM, Grieveson P, McMartin C (1970) "A study of the metabolic fate of chlorpropamide in man." Clin Pharmacol Ther, 10, p. 505-14
  3. Petitpierre B, Perrin L, Rudhardt M, et al. (1972) "Behaviour of chlorpropamide in renal insufficiency and under the effect of associated drug therapy." Int J Clin Pharmacol, 6, p. 120-4
  4. Huupponen R, Lammintausta R (1981) "Chlorpropamide bioavailability and pharmacokinetics." Int J Clin Pharmacol Ther Toxicol, 19, p. 331-3
  5. Neuvonen PJ, Karkkainen S, Lehtovaara R (1987) "Pharmacokinetics of chlorpropamide in epileptic patients: effects of enzyme induction and urine pH on chlorpropamide elimination." Eur J Clin Pharmacol, 32, p. 297-301
  6. (1971) "Glibenclamide: a review." Drugs, 1, p. 116-40
  7. Pearson JG, Antal EJ, Raehl CL, Gorsch HK, Craig WA, Albert KS, Welling PG (1986) "Pharmacokinetic disposition of 14C-glyburide in patients with varying renal function." Clin Pharmacol Ther, 39, p. 318-24
  8. Sartor G, Melander A, Schersten B, Wahlin-Boll E (1980) "Comparative single-dose kinetics and effects of four sulfonylureas in healthy volunteers." Acta Med Scand, 208, p. 301-7
  9. Prendergast BD (1984) "Glyburide and glipizide, second-generation oral sulfonylurea hypoglycemic agents." Clin Pharm, 3, p. 473-85
  10. Kobayashi KA, Bauer LA, Horn JR, Opheim K, Wood F, Jr Kradjan WA (1988) "Glipizide pharmacokinetics in young and elderly volunteers." Clin Pharm, 7, p. 224-8
  11. Balant L, Zahnd G, Gorgia A, Schwarz R, Fabre J (1973) "Pharmacokinetics of glipizide in man: influence of renal insufficiency." Diabetologia, Sep, p. 331-8
  12. Pentikainen PJ, Neuvonen PJ, Penttila A (1983) "Pharmacokinetics and pharmacodynamics of glipizide in healthy volunteers." Int J Clin Pharmacol Ther Toxicol, 21, p. 98-107
  13. Lebovitz HE (1985) "Glipizide: a second-generation sulfonylurea hypoglycemic agent. Pharmacology, pharmacokinetics and clinical use." Pharmacotherapy, 5, p. 63-77
  14. (2002) "Product Information. Diabinese (chlorpropamide)." Pfizer U.S. Pharmaceuticals
  15. (2002) "Product Information. Glucotrol (glipizide)." Pfizer U.S. Pharmaceuticals
  16. "Product Information. Diabeta (glyburide)." Hoechst Marion-Roussel Inc, Kansas City, MO.
  17. (2002) "Product Information. Micronase (glyburide)." Pharmacia and Upjohn
  18. Rydberg T, Jonsson A, Roder M, Melander A (1994) "Hypoglycemic activity of glyburide (glibenclamide) metabolites in humans." Diabetes Care, 17, p. 1026-30
  19. Rydberg T, Jonsson A, Melander A (1995) "Comparison of the kinetics of glyburide and its active metabolites in humans." J Clin Pharm Ther, 20, p. 283-95
  20. Badian M, Korn A, Lehr KH, Malerczyk V, Waldhausl W (1992) "Determination of the absolute bioavailability of glimepiride (HOE 490), a new sulphonylurea." Int J Clin Pharmacol Ther Toxicol, 30, p. 481-2
  21. (2001) "Product Information. Amaryl (glimepiride)." Hoechst Marion Roussel
  22. (2001) "Product Information. Tolinase (tolazamide)." Pharmacia and Upjohn
  23. (2001) "Product Information. Dymelor (acetohexamide)." Lilly, Eli and Company
View all 23 references
Moderate

Glipizide XL (applies to glipizide/metformin) GI narrowing

Moderate Potential Hazard, Moderate plausibility. Applicable conditions: Gastrointestinal Obstruction

The extended-release formulation of glipizide (Glucotrol XL) contains a non-deformable material. There have been rare reports of obstructive symptoms in patients with known strictures following the ingestion of similar sustained-release products. Therapy with the extended-release formulation of glipizide should be administered cautiously in patients with preexisting severe gastrointestinal narrowing or obstruction, whether pathologic or iatrogenic.

References

  1. (2002) "Product Information. Glucotrol (glipizide)." Pfizer U.S. Pharmaceuticals
Moderate

Insulin/oral hypoglycemic agents (applies to glipizide/metformin) hypoglycemia

Moderate Potential Hazard, Moderate plausibility. Applicable conditions: Adrenal Insufficiency, Malnourished, Autonomic Neuropathy, Panhypopituitarism, Anorexia/Feeding Problems, Adrenal Insufficiency, Malnourished, Autonomic Neuropathy, Panhypopituitarism, Anorexia/Feeding Problems

Hypoglycemia may commonly occur during treatment with insulin and/or oral hypoglycemic agents. Care should be taken in patients who may be particularly susceptible to the development of hypoglycemic episodes during the use of these drugs, including those who are debilitated or malnourished, those with defective counterregulatory mechanisms (e.g., autonomic neuropathy and adrenal or pituitary insufficiency), and those receiving beta-adrenergic blocking agents.

References

  1. (2002) "Product Information. Diabinese (chlorpropamide)." Pfizer U.S. Pharmaceuticals
  2. (2002) "Product Information. Glucotrol (glipizide)." Pfizer U.S. Pharmaceuticals
  3. "Product Information. Diabeta (glyburide)." Hoechst Marion-Roussel Inc, Kansas City, MO.
  4. (2002) "Product Information. Micronase (glyburide)." Pharmacia and Upjohn
  5. "Product Information. Humulin BR (insulin)." Lilly, Eli and Company, Indianapolis, IN.
  6. (2001) "Product Information. Amaryl (glimepiride)." Hoechst Marion Roussel
  7. (2001) "Product Information. Prandin (repaglinide)." Novo Nordisk Pharmaceuticals Inc
  8. (2001) "Product Information. Tolinase (tolazamide)." Pharmacia and Upjohn
  9. (2001) "Product Information. Dymelor (acetohexamide)." Lilly, Eli and Company
  10. (2001) "Product Information. Lantus (insulin glargine)." Aventis Pharmaceuticals
  11. (2022) "Product Information. NovoLOG (insulin aspart)." Novo Nordisk Pharmaceuticals Inc
  12. (2001) "Product Information. Starlix (nateglinide)." Novartis Pharmaceuticals
  13. (2004) "Product Information. Apidra (insulin glulisine)." Aventis Pharmaceuticals
  14. (2005) "Product Information. Levemir (insulin detemir)." Novo Nordisk Pharmaceuticals Inc
  15. (2015) "Product Information. Tresiba FlexTouch (insulin degludec)." Novo Nordisk Pharmaceuticals Inc
  16. (2018) "Product Information. Glucophage (metFORMIN)." EMD Serono Inc, SUPPL-34
View all 16 references
Moderate

Metformin (applies to glipizide/metformin) B12 deficiency

Moderate Potential Hazard, Moderate plausibility. Applicable conditions: Folic Acid/Cyanocobalamin Deficiency, Anemia Associated with Vitamin B12 Deficiency

Metformin may interfere with vitamin B12 absorption from the B12-intrinsic factor complex. A decrease to subnormal levels of previously normal serum vitamin B12 levels was reported in about 7% of patients treated with metformin during clinical trials. Such decrease may be associated with anemia but appears to be rapidly reversible with metformin discontinuation or vitamin B12 supplementation. Certain patients (those with inadequate vitamin B12 or calcium intake or absorption) appear to be predisposed to developing subnormal levels of vitamin B12; caution may be warranted when metformin is administered to these patients. It is recommended to measure vitamin B12 every 2 to 3 years and hematologic parameters annually in patients on metformin. Any abnormalities should be managed.

References

  1. (2018) "Product Information. Glucophage (metFORMIN)." EMD Serono Inc, SUPPL-34
Moderate

Sulfonylureas (applies to glipizide/metformin) G6PD deficiency

Moderate Potential Hazard, Moderate plausibility. Applicable conditions: G-6-PD Deficiency

Sulfonylureas can cause hemolytic anemia in patients with glucose 6-phosphate dehydrogenase (G6PD) deficiency. Therapy with these agents should be used with caution in patients with G6PD deficiency and consider the use of a non-sulfonylurea alternative. There have been postmarketing reports of hemolytic anemia in patients receiving these drugs who did not have known G6PD deficiency.

References

  1. (2002) "Product Information. Diabinese (chlorpropamide)." Pfizer U.S. Pharmaceuticals
  2. (2002) "Product Information. Glucotrol (glipizide)." Pfizer U.S. Pharmaceuticals
  3. "Product Information. Diabeta (glyburide)." Hoechst Marion-Roussel Inc, Kansas City, MO.
  4. (2002) "Product Information. Micronase (glyburide)." Pharmacia and Upjohn
  5. (2001) "Product Information. Amaryl (glimepiride)." Hoechst Marion Roussel
  6. (2001) "Product Information. Tolinase (tolazamide)." Pharmacia and Upjohn
  7. (2001) "Product Information. Orinase (tolbutamide)." Pharmacia and Upjohn
  8. (2001) "Product Information. Dymelor (acetohexamide)." Lilly, Eli and Company
View all 8 references
Moderate

Sulfonylureas (applies to glipizide/metformin) hyponatremia

Moderate Potential Hazard, Moderate plausibility. Applicable conditions: SIADH, Dehydration

Treatment with sulfonylureas may cause hyponatremia, in patients who are on other medications or have medical conditions known to cause hyponatremia or increase release of antidiuretic hormone. The syndrome of inappropriate antidiuretic hormone (SIADH) secretion has been reported with certain sulfonylureas and these drugs may augment the peripheral (antidiuretic) action of ADH and/or increase release of ADH. Caution should be used when treating patients with hyponatremia or at greater risk of developing hyponatremia such as elderly patients, patients taking diuretics or those who are volume-depleted.

References

  1. (2002) "Product Information. Diabinese (chlorpropamide)." Pfizer U.S. Pharmaceuticals
  2. (2002) "Product Information. Glucotrol (glipizide)." Pfizer U.S. Pharmaceuticals
  3. "Product Information. Diabeta (glyburide)." Hoechst Marion-Roussel Inc, Kansas City, MO.
  4. (2002) "Product Information. Micronase (glyburide)." Pharmacia and Upjohn
  5. (2001) "Product Information. Amaryl (glimepiride)." Hoechst Marion Roussel
  6. (2001) "Product Information. Tolinase (tolazamide)." Pharmacia and Upjohn
  7. (2001) "Product Information. Orinase (tolbutamide)." Pharmacia and Upjohn
  8. (2001) "Product Information. Dymelor (acetohexamide)." Lilly, Eli and Company
View all 8 references

Glipizide/metformin drug interactions

There are 542 drug interactions with glipizide / metformin.

Glipizide/metformin alcohol/food interactions

There are 2 alcohol/food interactions with glipizide / metformin.


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Drug Interaction Classification

These classifications are only a guideline. The relevance of a particular drug interaction to a specific individual is difficult to determine. Always consult your healthcare provider before starting or stopping any medication.
Major Highly clinically significant. Avoid combinations; the risk of the interaction outweighs the benefit.
Moderate Moderately clinically significant. Usually avoid combinations; use it only under special circumstances.
Minor Minimally clinically significant. Minimize risk; assess risk and consider an alternative drug, take steps to circumvent the interaction risk and/or institute a monitoring plan.
Unknown No interaction information available.

Further information

Always consult your healthcare provider to ensure the information displayed on this page applies to your personal circumstances.