DICHLORPHENAMIDE Drug Interactions: What You Need to Know

INTERACTIONS Aspirin: anorexia, tachypnea, lethargy, and coma have been reported with concomitant use of dichlorphenamide and high-dose aspirin. The concomitant use of dichlorphenamide tablets and high-dose aspirin is contraindicated. Dichlorphenamide tablets should be used with caution in patients receiving lower doses of aspirin ( 4 , 5.2 , 7.1 )

7.1 Aspirin and Other Salicylates Carbonic anhydrase inhibitors, including dichlorphenamide, can cause metabolic acidosis <span class="opacity-50 text-xs">[see Warnings and Precautions ( 5.2 , 5.4 )]</span> , which can increase the risk of salicylate toxicity. Anorexia, tachypnea, lethargy, and coma have been reported with concomitant use of dichlorphenamide and high-dose aspirin. Therefore, concomitant use of dichlorphenamide and high-dose aspirin is contraindicated. Patients with concomitant use of dichlorphenamide and low-dose aspirin should be carefully monitored <span class="opacity-50 text-xs">[see Contraindications ( 4 ) and Warnings and Precautions ( 5.2 )]</span>.

7.2 Drugs that are Substrates of Organic Anion Transporter1 (OAT1) In vitro , dichlorphenamide is an inhibitor of OAT1 transporters. The concomitant administration of dichlorphenamide may increase the plasma exposures of OAT1 substrates. Use of dichlorphenamide with drugs that are sensitive to OAT1 inhibition (e.g., methotrexate, famotidine, oseltamivir) is not recommended <span class="opacity-50 text-xs">[see Clinical Pharmacology ( 12.3 )]</span>.

7.3 Drugs that Cause Hypokalemia The risk of hypokalemia is greater with coadministration of dichlorphenamide and other drugs that can cause hypokalemia (e.g., loop diuretics, thiazide diuretics, laxatives, antifungals, penicillins, and theophylline) <span class="opacity-50 text-xs">[see Warnings and Precautions ( 5.3 )]</span>.

7.4 Drugs that Cause Metabolic Acidosis Coadministration of dichlorphenamide and other drugs that can cause metabolic acidosis may increase the severity of the acidosis <span class="opacity-50 text-xs">[see Warnings and Precautions ( 5.4 )]</span>.

7.5 Drugs that are Inhibitors of OAT1 or OAT3 An in vitro transporter study indicated that dichlorphenamide is a substrate of human transporters OAT1 and OAT3 <span class="opacity-50 text-xs">[see Clinical Pharmacology ( 12.3 )]</span> . Therefore, signs of dichlorphenamide toxicity should be monitored when administered with OAT1 or OAT3 inhibitors.

Dichlorphenamide is contraindicated in the following circumstances: Hypersensitivity to dichlorphenamide or other sulfonamides [see Warnings and Precautions ( 5.1 )] Concomitant use of dichlorphenamide and high dose aspirin [see Warnings and Precautions ( 5.2 ) and Drug Interactions ( 7.1 )] Severe pulmonary disease, limiting compensation to metabolic acidosis caused by dichlorphenamide [see Warnings and Precautions ( 5.4 )] Hepatic insufficiency: dichlorphenamide may aggravate hepatic encephalopathy. Hepatic insufficiency ( 4 ) Severe pulmonary obstruction ( 4 ) Hypersensitivity to dichlorphenamide or other sulfonamides ( 4 ) Concomitant use with high dose aspirin ( 4 )

AND PRECAUTIONS Hypersensitivity and Other Life-Threatening Reactions: discontinue dichlorphenamide at the first appearance of skin rash or any sign of immune- mediated or idiosyncratic adverse reaction ( 5.1 ) Hypokalemia: baseline and periodic measurements of serum potassium are recommended; if hypokalemia develops or persists, consider reducing the dose or discontinuing dichlorphenamide and correcting potassium levels ( 5.3 ) Metabolic acidosis: baseline and periodic measurements of serum bicarbonate are recommended; if metabolic acidosis develops or persists, consider reducing the dose or discontinuing dichlorphenamide ( 5.4 ) Falls: consider reducing the dose or discontinuing dichlorphenamide in patients who experience falls ( 5.5 )

5.1 Hypersensitivity and Other Life-Threatening Reactions Fatalities associated with the administration of sulfonamides have occurred because of adverse reactions including Stevens-Johnson syndrome, toxic epidermal necrolysis, fulminant hepatic necrosis, agranulocytosis, aplastic anemia, and other blood dyscrasias. Pulmonary involvement can occur in isolation or as part of a systemic reaction. Dichlorphenamide should be discontinued at the first appearance of skin rash or any sign of immune- mediated or other life-threatening adverse reaction.

5.2 Concomitant Use of Aspirin or Other Salicylates Carbonic anhydrase inhibitors, including dichlorphenamide, can cause metabolic acidosis <span class="opacity-50 text-xs">[see Warnings and Precautions ( 5.4 )]</span> , which can increase the risk of salicylate toxicity. Anorexia, tachypnea, lethargy, and coma have been reported with concomitant use of dichlorphenamide and high-dose aspirin. Therefore, the concomitant use of dichlorphenamide and high-dose aspirin is contraindicated. Patients with concomitant use of dichlorphenamide and low-dose aspirin should be carefully monitored.

5.3 Hypokalemia Dichlorphenamide increases potassium excretion and can cause hypokalemia. The risk of hypokalemia is greater when dichlorphenamide is used in patients with conditions associated with hypokalemia (e.g., adrenocortical excess, renal tubular acidosis type 1 and 2), and in patients receiving other drugs that may cause hypokalemia <span class="opacity-50 text-xs">[see Drug Interactions ( 7.3 ]</span> . Baseline and periodic measurements of serum potassium during dichlorphenamide treatment is recommended. If hypokalemia develops or persists, consideration should be given to reducing the dose or discontinuing dichlorphenamide and correction of potassium levels.

5.4 Metabolic Acidosis Dichlorphenamide can cause hyperchloremic non-anion gap metabolic acidosis. Concomitant use of dichlorphenamide with other drugs that cause metabolic acidosis may increase the severity of acidosis. Concomitant use of dichlorphenamide in compensated patients with respiratory acidosis, such as in advanced lung diseases, may lead to respiratory decompensation. Baseline and periodic measurements of serum bicarbonate during dichlorphenamide treatment are recommended. If metabolic acidosis develops or persists, consideration should be given to reducing the dose or discontinuing dichlorphenamide <span class="opacity-50 text-xs">[see Drug Interactions ( 7.4) ]</span>.

5.5 Falls Dichlorphenamide increases the risk of falls. The risk of falls is greater in the elderly and with higher doses of dichlorphenamide. Consider dose reduction or discontinuation of dichlorphenamide in patients who experience falls while treated with dichlorphenamide.