Nitazoxanide

Nitazoxanide, also known by the brand name Alinia, is a drug that works against a wide range of parasites and viruses. It is used to treat infections caused by helminths (worms), protozoa, and certain viruses. Specifically, it is approved for treating Cryptosporidium parvum and Giardia lamblia infections in people with healthy immune systems, and it has been repurposed to treat influenza. Chemically, nitazoxanide is the first of the thiazolide class—synthetic compounds built from nitrothiazolyl-salicylamide that have both antiparasitic and antiviral effects.

For treatment, nitazoxanide is a first-line option for Blastocystis species infections and is indicated for Cryptosporidium parvum or Giardia lamblia in both adults and children with normal immune function. It also works against other protozoa and helminths, such as Entamoeba histolytica, Hymenolepis nana, Ascaris lumbricoides, and Cyclospora cayetanensis.

In chronic hepatitis B, early evidence suggests nitazoxanide may be effective over a year of therapy. In one small study, four patients with HBeAg-positive hepatitis B who took 500 mg twice daily all saw their HBV DNA levels drop; two had undetectable DNA, three lost HBeAg, and one lost HBsAg. Among eight HBeAg-negative patients on the same dose, seven had undetectable HBV DNA and two lost HBsAg. In separate cases, nitazoxanide alone or combined with adefovir led to undetectable HBV DNA and loss of both HBeAg and HBsAg. These preliminary results showed a higher rate of HBsAg loss than any currently approved hepatitis B therapy. Because nitazoxanide and interferon share a similar mechanism, using nitazoxanide alone or with nucleos(t)ide analogs may boost HBsAg loss—the ultimate treatment goal. A formal phase 2 study was planned for 2009.

For chronic hepatitis C, Romark initially focused on nitazoxanide. After three phase II trials showed positive results for efficacy and tolerability similar to placebo, with no toxicity, the drug drew interest from hepatologists. However, a 2014 meta-analysis judged those trials to be low-quality and at risk of bias, concluding that more well-designed randomized trials are needed to confirm whether nitazoxanide is effective for chronic hepatitis C.

The only contraindication is a hypersensitivity reaction to nitazoxanide or any inactive ingredient in its formulation.

Side effects do not differ significantly from placebo in giardiasis treatment. They include stomach pain, headache, upset stomach, vomiting, discolored urine, excessive urination, skin rash, itching, fever, flu-like symptoms, and others. In healthy adults, nitazoxanide does not appear to cause serious adverse effects.

Overdose information is limited. Oral doses of 4 grams in healthy adults caused no significant problems. In animals, the oral LD50 exceeds 10 g/kg.

Because nitazoxanide’s active metabolite, tizoxanide, binds to plasma proteins at over 99.9%, taking it with other highly protein-bound drugs that have narrow therapeutic ranges (like warfarin) raises the risk of toxicity. In vitro evidence shows nitazoxanide does not affect the CYP450 system.

Pharmacologically, nitazoxanide’s antiprotozoal action likely comes from interfering with the pyruvate:ferredoxin oxidoreductase (PFOR) enzyme, which is essential for anaerobic energy metabolism. This PFOR inhibition may also help against anaerobic bacteria. Against influenza A virus, it works by blocking the maturation of viral hemagglutinin before it becomes resistant to endoglycosidase H digestion, disrupting hemagglutinin’s transport and insertion into the host cell membrane. In the lab, nitazoxanide also affects glutathione-S-transferase and glutamate-gated chloride channels in nematodes, respiration and other pathways in bacteria and cancer cells, and viral and host transcription factors.

After oral administration, nitazoxanide is quickly broken down into the active metabolite tizoxanide, which is 99% protein-bound. Tizoxanide is then converted into another active form, tizoxanide glucuronide. Peak levels of these metabolites appear in blood plasma 1–4 hours after dosing; nitazoxanide itself is not detected in plasma. About two-thirds of an oral dose is excreted as metabolites in feces, with the rest excreted in urine.