Topiramate and Zonisamide interaction

Kidney stones: avoid use with other carbonic anhydrase inhibitors, other drugs causing metabolic acidosis, or in patients on a ketogenic diet ( 5.16 )

Caution should be used when TROKENDI XR is given with other drugs that predispose patients to heat-related disorders; these drugs include, but are not limited to, other carbonic anhydrase inhibitors and drugs with anticholinergic activity .

Carbonic anhydrase inhibitors can promote stone formation by reducing urinary citrate excretion and by increasing urinary pH [see Warnings and Precautions (5.4) ] .

Other Carbonic Anhydrase Inhibitors Concomitant use of topiramate, a carbonic anhydrase inhibitor, with any other carbonic anhydrase inhibitor (e.g., zonisamide or acetazolamide) may increase the severity of metabolic acidosis and may also increase the risk of kidney stone formation.

Patients should be monitored for the appearance or worsening of metabolic acidosis when TROKENDI XR is given concomitantly with another carbonic anhydrase inhibitor [see Clinical Pharmacology (12.3) ].

The risks of hyperammonemia and various manifestations of encephalopathy may be increased in patients treated with zonisamide and concomitantly taking other medications that can cause hyperammonemia, including valproic acid or topiramate [see Warnings and Precautions ( 5 )].

Patients should be carefully observed for signs of central nervous system (CNS) depression, such as somnolence and sedation, when ZONISADE is used with other drugs with sedative properties because of potential additive effects.

• ZONISADE should be used with caution if used in combination with alcohol or other CNS depressants ( 7.1 ).

CYP3A4 Inducers If co-administration with a potent CYP3A4 inducer is necessary, the patient should be closely monitored and the dose of ZONISAMIDE and other drugs that CYP3A4 substrates may need to be adjusted [see Clinical Pharmacology ( 12.3 )] .