Drug Interaction Report

MONITOR: Coadministration with nitazoxanide may increase the free plasma concentrations of drugs and/or their active metabolites that are highly bound to plasma proteins. The pharmacologic effects of some drugs may be increased by this interaction. The proposed mechanism is competitive displacement from protein binding sites by tizoxanide, the active metabolite of nitazoxanide that is greater than 99.9% bound to plasma proteins.

MANAGEMENT: Caution is advised when other highly protein-bound drugs are used with nitazoxanide, particularly those with a narrow therapeutic index. Patients should be monitored more closely following the addition or withdrawal of nitazoxanide. When performing therapeutic drug monitoring, total plasma concentrations should be interpreted cautiously due to the possibility of increased free (unbound) drug.

ADJUST DOSING INTERVAL: Food enhances the bioavailability of the pharmacologically active metabolite tizoxanide (desacetyl-nitazoxamide) from nitazoxanide administration. According to the product labeling, administration of nitazoxanide tablets with food increases the area under the plasma concentration-time curve (AUC) of tizoxanide and tizoxanide glucuronide in plasma by almost 2-fold and the peak plasma concentration (Cmax) by almost 50%. Administration of nitazoxanide oral suspension with food increases the AUC of tizoxanide and tizoxandie glucuronide by about 45% to 50% and the Cmax by less than 10%.

MANAGEMENT: Nitazoxanide tablets and oral suspension were administered with food in clinical trials and are recommended to be administered with food to ensure maximal drug levels in plasma.