4. Drug-Drug Interactions

Patient profiles will be assessed to identify those drug regimens that may result in clinically significant drug-drug interactions. The following drug-drug interactions are considered clinically relevant for nitazoxanide. Only those drug-drug interactions classified as clinical significance level 1/contraindicated or those considered life-threatening which have not yet been classified will be reviewed.

Highly Plasma Protein-Bound Medications

(e.g., hydantoins, salicylates, warfarin) [clinical significance level – 3- moderate (CP)]

Nitazoxanide is rapidly metabolized to tizoxanide following oral administration. Because tizoxanide is highly bound to plasma proteins (>99.9%), caution should be exercised when dosing nitazoxanide concurrently with other drugs highly protein bound possessing narrow therapeutic indices as competition for binding sites may occur with potential for toxicity. However, in an open-label, randomized, crossover study, investigators assessed nitazoxanide effects on warfarin pharmacokinetics and pharmacodynamics after a single warfarin 25 mg dose in 14 adult male volunteers and found that warfarin pharmacokinetic/pharmacodynamic parameters did not change significantly following nitazoxanide administration. Until further confirmatory data are available, it may be prudent to monitor patients for signs of warfarin toxicity and changes in INR when warfarin and nitazoxanide are administered concurrently. Similarly, until contrasting data are available, monitor patients for signs and symptoms of hydantoin or salicylate toxicity when nitazoxanide is administered adjunctively.