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.

Switch to consumer interaction data

CONTRAINDICATED: Use of alcohol or products containing alcohol during nitroimidazole therapy may result in a disulfiram-like reaction in some patients. There have been a few case reports involving metronidazole, although data overall are not convincing. The presumed mechanism is inhibition of aldehyde dehydrogenase (ALDH) by metronidazole in a manner similar to disulfiram. Following ingestion of alcohol, inhibition of ALDH results in increased concentrations of acetaldehyde, the accumulation of which can produce an unpleasant physiologic response referred to as the 'disulfiram reaction'. Symptoms include flushing, throbbing in head and neck, throbbing headache, respiratory difficulty, nausea, vomiting, sweating, thirst, chest pain, palpitation, dyspnea, hyperventilation, tachycardia, hypotension, syncope, weakness, vertigo, blurred vision, and confusion. Severe reactions may result in respiratory depression, cardiovascular collapse, arrhythmia, myocardial infarction, acute congestive heart failure, unconsciousness, convulsions, and death. However, some investigators have questioned the disulfiram-like properties of metronidazole. One study found neither elevations in blood acetaldehyde nor objective or subjective signs of a disulfiram-like reaction to ethanol in six subjects treated with metronidazole (200 mg three times a day for 5 days) compared to six subjects who received placebo.

MANAGEMENT: Because clear evidence is lacking concerning the safety of ethanol use during nitroimidazole therapy, patients should be apprised of the potential for interaction. Consumption of alcoholic beverages and products containing propylene glycol is specifically contraindicated during and for at least 3 days after completion of metronidazole and benznidazole therapy according to their product labeling.

Switch to consumer interaction data

GENERALLY AVOID: Alcohol may potentiate some of the pharmacologic effects of CNS-active agents. Use in combination may result in additive central nervous system depression and/or impairment of judgment, thinking, and psychomotor skills.

MANAGEMENT: Patients receiving CNS-active agents should be warned of this interaction and advised to avoid or limit consumption of alcohol. Ambulatory patients should be counseled to avoid hazardous activities requiring complete mental alertness and motor coordination until they know how these agents affect them, and to notify their physician if they experience excessive or prolonged CNS effects that interfere with their normal activities.

Switch to consumer interaction data

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.

Switch to consumer interaction data

The recommended maximum number of medicines in the 'amebicides' category to be taken concurrently is usually one. Your list includes two medicines belonging to the 'amebicides' category:

• nitazoxanide
• Flagyl (metronidazole)

Note: In certain circumstances, the benefits of taking this combination of drugs may outweigh any risks. Always consult your healthcare provider before making changes to your medications or dosage.