Drug Interactions between dichlorphenamide and Metaglip

MONITOR CLOSELY: Coadministration with carbonic anhydrase inhibitors may potentiate the risk of lactic acidosis associated with the use of metformin. Carbonic anhydrase inhibitors can decrease serum bicarbonate and induce non-anion gap, hyperchloremic metabolic acidosis. Use of the carbonic anhydrase inhibitor topiramate in epilepsy and migraine prophylaxis has frequently caused dose-dependent metabolic acidosis in both adult and pediatric patients in controlled trials. Theoretically, metformin-induced lactic acidosis may be more likely in this setting, albeit still rare. In a clinical study of obese patients with type 2 diabetes receiving metformin with topiramate, there were no reported cases of lactic acidosis in over 200 patients who received the combination for 24 weeks. Similarly, acidosis was not observed in a smaller study where 54 patients received the combination for up to 16 weeks.

MANAGEMENT: Caution is advised if metformin is used concomitantly with carbonic anhydrase inhibitors. Close monitoring for the development of lactic acidosis is recommended, particularly in the elderly and patients with other risk factors such as unstable or acute congestive heart failure or other conditions that can lead to hypoperfusion and hypoxemia. Patients should contact their physician immediately if they experience potential signs and symptoms of lactic acidosis such as malaise, myalgia, respiratory distress, increasing somnolence, and nonspecific abdominal distress (especially after stabilization of metformin therapy, when gastrointestinal symptoms are uncommon). With more marked acidosis, there may also be associated hypothermia, hypotension, and resistant bradyarrhythmias. Metformin should be withdrawn promptly if lactic acidosis is suspected. Serum electrolytes, ketones, blood glucose, blood pH, lactate levels, and blood metformin levels may be useful in establishing a diagnosis. Lactic acidosis should be suspected in any diabetic patient with metabolic acidosis lacking evidence of ketoacidosis (ketonuria and ketonemia).

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MONITOR: The efficacy of insulin and other antidiabetic agents may be diminished by certain drugs, including atypical antipsychotics, corticosteroids, diuretics, estrogens, gonadotropin-releasing hormone agonists, human growth hormone, phenothiazines, progestins, protease inhibitors, sympathomimetic amines, thyroid hormones, L-asparaginase, alpelisib, copanlisib, danazol, diazoxide, isoniazid, megestrol, omacetaxine, phenytoin, sirolimus, tagraxofusp, temsirolimus, as well as pharmacologic dosages of nicotinic acid and adrenocorticotropic agents. These drugs may interfere with blood glucose control because they can cause hyperglycemia, glucose intolerance, new-onset diabetes mellitus, and/or exacerbation of preexisting diabetes.

MANAGEMENT: Caution is advised when drugs that can interfere with glucose metabolism are prescribed to patients with diabetes. Close clinical monitoring of glycemic control is recommended following initiation or discontinuation of these drugs, and the dosages of concomitant antidiabetic agents adjusted as necessary. Patients should be advised to notify their physician if their blood glucose is consistently high or if they experience symptoms of severe hyperglycemia such as excessive thirst and increases in the volume or frequency of urination. Likewise, patients should be observed for hypoglycemia when these drugs are withdrawn from their therapeutic regimen.

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MONITOR: Coadministration of metformin with an insulin secretagogue (e.g., sulfonylurea, meglitinide) or insulin may potentiate the risk of hypoglycemia. Although metformin alone generally does not cause hypoglycemia under normal circumstances of use, the added therapeutic effect when combined with other antidiabetic agents may result in hypoglycemia. The risk is further increased when caloric intake is deficient or when strenuous exercise is not compensated by caloric supplementation.

MANAGEMENT: A lower dosage of the insulin secretagogue or insulin may be required when used with metformin. Blood glucose should be closely monitored, and patients should be educated on the potential signs and symptoms of hypoglycemia (e.g., headache, dizziness, drowsiness, nervousness, confusion, tremor, hunger, weakness, perspiration, palpitation, tachycardia) and appropriate remedial actions to take if it occurs. Patients should also be advised to take precautions to avoid hypoglycemia while driving or operating hazardous machinery.

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