Drug Interactions between metformin and Qsymia

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 topiramate, a carbonic anhydrase inhibitor, 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.

Pharmacokinetically, topiramate may increase the plasma concentrations of metformin. In study subjects receiving topiramate 100 mg and metformin 500 mg every 12 hours, the average steady-state metformin peak plasma concentration (Cmax) and systemic exposure (AUC) increased by 17% and 25%, respectively, while plasma clearance decreased by 20%. The clinical significance of these changes is unknown. Topiramate pharmacokinetics were not affected.

MANAGEMENT: Caution is advised if metformin is used concomitantly with carbonic anhydrase inhibitors including topiramate. 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 Metformin should be withdrawn promptly if lactic acidosis is suspected.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: Since weight loss may affect glycemic control and increase the risk of hypoglycemia in type 2 diabetes mellitus, patients receiving anorectic drugs may require periodic adjustments of their antidiabetic medications.

MANAGEMENT: Blood glucose should be closely monitored during weight loss treatment, and appropriate changes made to the antidiabetic drug regimen as needed. Patients should be apprised of the risk of hypoglycemia and be alert to potential signs and symptoms such as headache, dizziness, drowsiness, nervousness, confusion, tremor, hunger, weakness, perspiration, palpitation, and tachycardia. For antidiabetic medications that are not glucose-dependent, reduction in the dosage should be considered to mitigate the risk of hypoglycemia.

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MONITOR: Coadministration with topiramate may increase the plasma concentrations of phentermine. The exact mechanism of interaction has not been established. When a single 15 mg dose of phentermine was administered with a 92 mg dose of topiramate, phentermine peak plasma concentration (Cmax) and systemic exposure (AUC) increased by 13% and 42%, respectively, compared to phentermine administered alone. No significant changes were observed in the pharmacokinetics of topiramate.

MANAGEMENT: Caution is advised when phentermine is used in combination with topiramate. Patients should be monitored for potentially increased adverse effects of phentermine such as dizziness, restlessness, insomnia, tremor, headache, euphoria, dysphoria, palpitation, tachycardia, and blood pressure elevation.

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