The authors concluded that more randomized trials with low risk of bias are needed to determine if Nitazoxanide can be used as an effective treatment for chronic hepatitis C patients. Contraindications
Nitazoxanide is contraindicated only in individuals who have experienced a hypersensitivity reaction to nitazoxanide or the inactive ingredients of a nitazoxanide formulation. Adverse effects
The side effects of nitazoxanide do not significantly differ from a placebo treatment for giardiasis; these symptoms include stomach pain, headache, upset stomach, vomiting, discolored urine, excessive urinating, skin rash, itching, fever, flu syndrome, and others. Nitazoxanide does not appear to cause any significant adverse effects when taken by healthy adults. Overdose
Information on nitazoxanide overdose is limited. Oral doses of 4 grams in healthy adults do not appear to cause any significant adverse effects. In various animals, the oral LD50 is higher than 10 g/kg. Interactions
Due to the exceptionally high plasma protein binding (>99.9%) of nitazoxanides metabolite, tizoxanide, the concurrent use of nitazoxanide with other highly plasma protein-bound drugs with narrow therapeutic indices (e.g., warfarin) increases the risk of drug toxicity. In vitro evidence suggests that nitazoxanide does not affect the CYP450 system. Pharmacology
Pharmacodynamics
The anti-protozoal activity of nitazoxanide is believed to be due to interference with the pyruvate:ferredoxin oxidoreductase (PFOR) enzyme-dependent electron-transfer reaction that is essential to anaerobic energy metabolism. PFOR inhibition may also contribute to its activity against anaerobic bacteria.It has also been shown to have activity against influenza A virus in vitro.
This has been met with criticism, both by doctors and members of the airline industry, as sedating young passengers may put them at risk if the flight encounters an emergency and they are unable to react to the situation efficiently, and the drugs side effects, especially the chance of a paradoxical reaction, may result in some individuals becoming hyperactive rather than sedated. The ethics of this use have also been challenged, with the Seattle Childrens hospital arguing in a 2009 article that "Using a medication for your convenience is never an indication for medication in a child. "The American Academy of Sleep Medicines 2017 clinical practice guidelines recommended against the use of diphenhydramine in the treatment of insomnia due to poor effectiveness and low quality of evidence. A major systematic review and network meta-analysis of medications for the treatment of insomnia published in 2022 found little evidence to inform the use of diphenhydramine for insomnia. Nausea
Diphenhydramine also has antiemetic properties, which make it useful in treating the nausea that occurs in vertigo and motion sickness. Special populations
Diphenhydramine is not recommended for people older than 60 or children under the age of six, unless a physician is consulted. These populations should be treated with second-generation antihistamines such as loratadine, desloratadine, fexofenadine, cetirizine, levocetirizine, and azelastine. Due to its strong anticholinergic effects, diphenhydramine is on the Beers list of drugs to avoid in the elderly.Diphenhydramine is category B in the FDA Classification of Drug Safety During Pregnancy. It is also excreted in breast milk.