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Canagliflozin / metformin Disease Interactions

There are 8 disease interactions with canagliflozin / metformin:

Major

Metformin (applies to canagliflozin/metformin) lactic acidosis

Major Potential Hazard, High plausibility. Applicable conditions: Renal Dysfunction, Liver Disease, Congestive Heart Failure, Dehydration, Shock, Myocardial Infarction, Asphyxia, Diarrhea, Vomiting, Anemia, Alcoholism

The use of metformin is contraindicated in patients with renal dysfunction (serum creatinine >= 1.5 mg/dL in males and 1.4 mg/dL in females, or above the upper limit of normal for age); congestive heart failure requiring pharmacologic treatment (especially unstable or acute CHF where there is risk of hypoperfusion and hypoxemia); and any condition associated with hypoxemia (e.g., severe anemia, myocardial infarction, asphyxia, shock), dehydration (e.g., severe diarrhea or vomiting), or sepsis. Patients with these conditions may be at increased risk for the development of lactic acidosis, which is a rare but serious metabolic complication associated with metformin accumulation in plasma usually at levels exceeding 5 mcg/mL. Metformin should also not be administered to patients with acute or chronic metabolic acidosis. In addition, metformin should generally be avoided in alcoholics and patients with clinical or laboratory evidence of hepatic disease, since alcohol potentiates the effects of metformin on lactate metabolism and impaired hepatic function may significantly limit the ability to clear lactate. All patients treated with metformin should have renal function monitored regularly (at least annually or more frequently if necessary) and be advised of the significance of nonspecific symptoms such as malaise, myalgias, respiratory distress, increasing somnolence, and gastrointestinal disturbances that arise after stabilization of metformin dosage. More marked acidosis may be associated with hypothermia, hypotension, and resistant bradyarrhythmias. Immediate medical attention is necessary if these symptoms occur, and metformin therapy withheld until the situation can be clarified. If lactic acidosis is diagnosed, prompt supportive measures and hemodialysis are recommended.

References

  1. DeFronzo RA, Goodman AM, and the Multicenter Metformin Study Group "Efficacy of metformin in patients with non-insulin-dependent diabetes mellitus." N Engl J Med 333 (1995): 541-9
  2. Lalau JD, Mourlhon C, Bergeret A, Lacroix C "Consequences of metformin intoxication." Diabetes Care 21 (1998): 2036-7
  3. Luft D, Schmulling RM, Eggstein M "Lactic acidosis in biguanide-treated diabetics: a review of 330 cases." Diabetologia 14 (1978): 75-87
  4. Chalopin JM, Tanter Y, Besancenot JF, Cabanne JF, Rifle G "Treatment of metformin-associated lactic acidosis with closed recirculation bicarbonate-buffered hemodialysis." Arch Intern Med 144 (1984): 203-5
  5. Lalau JD, Andrejak M, Moriniere P, Coevoet B, Debussche X, Westeel PF, Fournier A, Quichaud J "Hemodialysis in the treatment of lactic acidosis in diabetics treated by metformin: a study of metformin elimination." Int J Clin Pharmacol Ther Toxicol 27 (1989): 285-8
  6. Misbin RI, Green L, Stadel BV, Gueriguian JL, Gubbi A, Fleming GA "Lactic acidosis in patients with diabetes treated with metformin." N Engl J Med 338 (1998): 265-6
  7. Stumvoll M, Nurjhan N, Perriello G, Dailey G, Gerich JE "Metabolic effects of metformin in non-insulin-dependent diabetes mellitus." N Engl J Med 333 (1995): 550-4
  8. Pearlman BL, Fenves AZ, Emmett M "Metformin-associated lactic acidosis." Am J Med 101 (1996): 109-10
  9. Ryder RE "Lactic acidotic coma with multiple medication including metformin in a patient with normal renal function." Br J Clin Pract 38 (1984): 229-30,232
  10. De Fronzo RA, Goodman AM "Efficacy of metformin in non-insulin dependent diabetes mellitus." N Engl J Med 334 (1996): 269-70
  11. Wiholm BE, Myrhed M "Metformin-associated lactic acidosis in Sweden 1977-1991." Eur J Clin Pharmacol 44 (1993): 589-91
  12. Biron P "Metformin monitoring." Can Med Assoc J 123 (1980): 11-2
  13. Bailey CJ, Path MR, Turner RC "Metformin." N Engl J Med 334 (1996): 574-9
  14. "Product Information. Glucophage (metformin)." Bristol-Myers Squibb, Princeton, NJ.
  15. Deutsch JC, Santhoshkumar CR, Kolhouse JF "Efficacy of metformin in non-insulin-dependent diabetes mellitus." N Engl J Med 334 (1996): 269
  16. Stang M, Wysowski DK, ButlerJones D "Incidence of lactic acidosis in metformin users." Diabetes Care 22 (1999): 925-7
  17. Lustik SJ, Vogt A, Chhibber AK "Postoperative lactic acidosis in patients receiving metformin." Anesthesiology 89 (1998): 266-7
  18. Assan R, Heuclin C, Ganeval D, Bismuth C, George J, Girard JR "Metformin-induced lactic acidosis in the presence of acute renal failure." Diabetologia 13 (1977): 211-7
  19. Sambol NC, Chiang J, Lin ET, Goodman AM, Liu CY, Benet LZ, Cogan MG "Kidney function and age are both predictors of pharmacokinetics of metformin." J Clin Pharmacol 35 (1995): 1094-102
  20. Gueriguian J, Green L, Misbin RI, Stadel B, Fleming GA "Efficacy of metformin in non-insulin dependent diabetes mellitus." N Engl J Med 334 (1996): 269
  21. Lalau JD, Westeel PF, Debussche X, Dkissi H, Tolani M, Coevoet B, Temperville B, Fournier A, Quichaud J "Bicarbonate haemodialysis: an adequate treatment for lactic acidosis in diabetics treated by metformin." Intensive Care Med 13 (1987): 383-7
View all 21 references
Major

Oral hypoglycemic agents (applies to canagliflozin/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. "Product Information. Glucotrol (glipizide)." Pfizer US Pharmaceuticals, New York, NY.
  2. "Product Information. Prandin (repaglinide)." Novo Nordisk Pharmaceuticals Inc, Princeton, NJ.
  3. "Product Information. Diabeta (glyburide)." Hoechst Marion-Roussel Inc, Kansas City, MO.
  4. "Product Information. Amaryl (glimepiride)." Hoechst Marion-Roussel Inc, Kansas City, MO.
  5. "Product Information. Dymelor (acetohexamide)" Lilly, Eli and Company, Indianapolis, IN.
  6. "Product Information. Tolinase (tolazamide)" Pharmacia and Upjohn, Kalamazoo, MI.
  7. "Product Information. Glucophage (metformin)." Bristol-Myers Squibb, Princeton, NJ.
  8. "Product Information. Diabinese (chlorpropamide)." Pfizer US Pharmaceuticals, New York, NY.
View all 8 references
Major

SGLT-2 inhibitors (applies to canagliflozin/metformin) liver dysfunction

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

Sodium-glucose cotransporter 2 (SGLT2) inhibitors ertugliflozin and canagliflozin are not recommended for use in patients with severe hepatic impairment due to lack of clinical data. Dapagliflozin has not been studied in patients with severe hepatic impairment and caution is recommended. Dosage adjustments are not necessary in patients with mild or moderate hepatic impairment.

Major

SGLT-2 inhibitors (applies to canagliflozin/metformin) renal dysfunction

Major Potential Hazard, Moderate plausibility.

The glucose lowering effects of sodium-glucose cotransporter 2 (SGLT2) inhibitors is decreased in patients with worsening renal function. Additionally, patients with renal impairment function (eGFR less than 60 mL/min/1.73 m2) the elderly, and patients on loop diuretics may be more likely to experience adverse reactions related to volume depletion such as hypotension and acute kidney injury during therapy. Renal function should be evaluated prior to treatment initiation and monitored regularly in at-risk patients. Assess volume status and correct volume depletion before initiating therapy. The use of SGLT-2 inhibitors in patients undergoing dialysis is contraindicated. In both patients with and without type 2 diabetes, beneficial effects in chronic kidney disease and heart failure have been observed with SGLT2 inhibitor therapy. The manufacturer's product labeling should be consulted for indication specific renal dosing for SGLT2 inhibitors.

Moderate

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

Moderate Potential Hazard, Moderate plausibility. Applicable conditions: 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. Fauci AS, Braunwald E, Isselbacher KJ, Wilson JD, Martin JB, Kasper DL, Hauser SL, Longo DL, eds. "Harrison's Principles of Internal Medicine. 14th ed." New York, NY: McGraw-Hill Health Professionals Division (1998):
  2. "Product Information. Glucotrol (glipizide)." Pfizer US Pharmaceuticals, New York, NY.
  3. "Product Information. Novolog (insulin aspart)" Novo Nordisk Pharmaceuticals Inc, Princeton, NJ.
  4. "Product Information. Glucophage (metformin)." Bristol-Myers Squibb, Princeton, NJ.
  5. "Product Information. Prandin (repaglinide)." Novo Nordisk Pharmaceuticals Inc, Princeton, NJ.
  6. "Product Information. Humulin BR (insulin)." Lilly, Eli and Company, Indianapolis, IN.
  7. "Product Information. Diabeta (glyburide)." Hoechst Marion-Roussel Inc, Kansas City, MO.
  8. "Product Information. Starlix (nateglinide)" Novartis Pharmaceuticals, East Hanover, NJ.
  9. "Product Information. Dymelor (acetohexamide)" Lilly, Eli and Company, Indianapolis, IN.
  10. "Product Information. Amaryl (glimepiride)." Hoechst Marion-Roussel Inc, Kansas City, MO.
  11. "Multum Information Services, Inc. Expert Review Panel"
  12. "Product Information. Diabinese (chlorpropamide)." Pfizer US Pharmaceuticals, New York, NY.
  13. "Product Information. Lantus (insulin glargine)" Aventis Pharmaceuticals, Swiftwater, PA.
  14. "Product Information. Tolinase (tolazamide)" Pharmacia and Upjohn, Kalamazoo, MI.
  15. "Product Information. Micronase (glyburide)." Pharmacia and Upjohn, Kalamazoo, MI.
View all 15 references
Moderate

Metformin (applies to canagliflozin/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 (cyanocobalamin) absorption from the B12-intrinsic factor complex. A decrease to subnormal levels of previously normal serum B12 levels has been reported in approximately 7% of patients treated with metformin during controlled clinical trials. Although the decrease is generally well-tolerated and rarely associated with clinical manifestations such as megaloblastic anemia, caution may be warranted when metformin therapy is administered in patients with preexisting B12 deficiency. Vitamin B12 supplementation as well as annual measurements of hematologic parameters may be appropriate.

References

  1. Deutsch JC, Santhosh-Kumar CR, Kolhouse JF "Efficacy of metformin in non-insulin-dependent diabetes mellitus." N Engl J Med 334 (1996): 269
  2. Callaghan TS, Hadden DR, Tomkin GH "Megaloblastic anaemia due to vitamin B12 malabsorption associated with long-term metformin treatment." Br Med J 280 (1980): 1214-5
  3. Stowers JM, Smith OA "Vitamin B 12 and metformin." Br Med J 3 (1971): 246-7
  4. "Product Information. Glucophage (metformin)." Bristol-Myers Squibb, Princeton, NJ.
  5. Tomkin GH "Metformin and B 12 malabsorption." Ann Intern Med 76 (1972): 668
  6. Tomkin GH, Hadden DR, Weaver JA, Montgomery DA "Vitamin-B12 status of patients on long-term metformin therapy." Br Med J 2 (1971): 685-7
View all 6 references
Moderate

SGLT-2 inhibitors (applies to canagliflozin/metformin) hypotension

Moderate Potential Hazard, Moderate plausibility. Applicable conditions: Renal Dysfunction

Sodium-glucose cotransporter 2 (SGLT-2) inhibitors cause intravascular volume contraction which may lead to symptomatic hypotension after treatment initiation especially in the elderly, in patients with impaired renal function, patients with low systolic blood pressure, or those using diuretics . Volume status should be assessed and corrected before starting treatment and patients should be monitored during therapy.

Moderate

SGLT-2 inhibitors (applies to canagliflozin/metformin) infections

Moderate Potential Hazard, Moderate plausibility. Applicable conditions: Infection - Bacterial/Fungal/Protozoal/Viral

An increase in the risk of genital mycotic infections has been reported with the use of a sodium-glucose cotransporter 2 (SGLT-2) inhibitors. Care should be exercised when using this agent in patients who have a history of genital mycotic infections or who are uncircumcised as these patients are more likely to develop genital mycotic infections. Monitor and treat appropriately.

Canagliflozin / metformin drug interactions

There are 448 drug interactions with canagliflozin / metformin

Canagliflozin / metformin alcohol/food interactions

There are 2 alcohol/food interactions with canagliflozin / metformin

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.