Nitazoxanide 500 mg: What It Treats, How to Take It and What the Trials Show

Nitazoxanide 500 mg is a three-day tablet treatment for diarrhoea caused by two specific parasites, Giardia and Cryptosporidium. It is sold in the United States as Alinia and as generics, and elsewhere under names such as Nizonide 500. It is a narrow drug with a clear label: it treats two infections, it has to be taken with food, and there is one group of patients in whom it has not been shown to work.

This guide sets out what the US label approves it for, how to take it, and what its trials actually found, including how small some of them were.

The short answer

For adults and children aged 12 and over, the dose is one 500 mg tablet every 12 hours with food for three days. It is approved for diarrhoea caused by Giardia lamblia or Cryptosporidium parvum. In the main adult trials, 85% were well after treatment for Giardia against 44% on placebo, and 96% for Cryptosporidium against 41%. Food almost doubles how much of the drug is absorbed. The most common side effects are abdominal pain, headache, discoloured urine and nausea. It has not been shown to work better than placebo for Cryptosporidium in people with HIV or weakened immunity.

What nitazoxanide is

Nitazoxanide is a synthetic antiprotozoal, meaning it acts against single-celled parasites rather than bacteria or worms. After you swallow it, the parent drug is not detectable in the blood. It is converted to two active metabolites, tizoxanide and tizoxanide glucuronide, which do the work.

Form	Strength	Who it is for
Tablets (Alinia, generics, Nizonide 500)	500 mg	Age 12 and over
Oral suspension (Alinia)	100 mg per 5 mL	Children, dosed by age

What it is approved for, and what it is not

The US label approves nitazoxanide tablets for one thing: diarrhoea caused by Giardia lamblia or Cryptosporidium parvum in patients aged 12 and over. It carries one stated limitation. Nitazoxanide has not been shown to be effective for Cryptosporidium diarrhoea in people with HIV or who are otherwise immunodeficient, and it has not been studied for Giardia in those groups.

That is the whole of the approved use. Everything below is about those two infections.

A note on worms

You will sometimes see nitazoxanide described as a treatment for worm infections. The US label does not include any worm infection. Giardia and Cryptosporidium are protozoa, single-celled organisms, not worms.

This matters because the right drug depends on what is causing the symptoms. Threadworm, roundworm and hookworm are treated with different medicines, which our mebendazole versus albendazole guide covers. Using nitazoxanide on the assumption that it treats worms risks leaving the real infection untreated.

How it works

The label describes the mechanism as interference with an enzyme reaction, pyruvate:ferredoxin oxidoreductase, that these parasites depend on for energy in the low-oxygen conditions of the gut. The label adds, candidly, that this may not be the only way it acts, and that the potential for Giardia or Cryptosporidium to develop resistance has not been examined.

How to take it

Age	Dose	How often	For how long
12 years and over	One 500 mg tablet	Every 12 hours, with food	3 days (6 tablets in total)

The tablets must not be given to children aged 11 or under. The label's reason is simple: one tablet contains more nitazoxanide than the recommended dose for that age group. Younger children are treated with the suspension, dosed by age.

Why you take it with food

Food makes a large difference. Taken with food, the amount of active metabolite reaching the blood (AUC) is almost doubled and the peak concentration rises by almost 50%. The trials gave the tablets with food, which is why the label recommends it.

After a dose with food, the active metabolite tizoxanide peaks at about three hours in adults. Taking a tablet every 12 hours for seven days did not cause it to build up.

Tablets against liquid

The suspension and the tablets are not interchangeable. The label states they are not bioequivalent: the suspension delivers about 70% of what the tablet does. If you are switching between the two, the dose is not simply converted by milligrams, and it should be a prescriber's decision.

How well it works against Giardia

Two double-blind trials in adults and adolescents compared three days of 500 mg twice daily with placebo. Response was judged four to seven days after treatment. "Well" meant no symptoms, no watery stools and no more than two soft stools in the past 24 hours, or no symptoms and no unformed stools in 48 hours.

Trial	Nitazoxanide	Placebo
Study 1, Peru and Egypt	85% (46 of 54)	44% (12 of 27)
Study 2, Egypt	100% (8 of 8)	30% (3 of 10)

Patients who did not complete the studies were counted as failures, which is the stricter way to report it.

How well it works against Cryptosporidium

The same design was used for Cryptosporidium, again in adults and adolescents.

Trial	Nitazoxanide	Placebo
Study 1, Egypt (response 4 to 7 days after treatment)	96% (27 of 28)	41% (11 of 27)
Study 2, Egypt (response 2 to 6 days after treatment)	71% (15 of 21)	43% (9 of 21)

Reading those trials fairly

Three things keep these numbers in proportion.

The trials were small. Giardia Study 2 had eight people on nitazoxanide, so its 100% is eight out of eight. The largest arm across all four trials was 54 people.

Placebo did well too. Between 30% and 44% of people on placebo were well within about a week. Diarrhoea from these infections can settle without treatment in some people, which is part of what the placebo column shows. The drug's contribution is the gap, and that gap was large in the main trials: 41 points for Giardia and 55 for Cryptosporidium.

Feeling well is not the same as clearing the parasite. The label notes that some patients rated well still had Giardia cysts or Cryptosporidium oocysts in their stool afterwards, that the relevance of this is unknown, and that patients should be managed on how they are doing clinically.

Children

The suspension was tested in two trials of children with Cryptosporidium, using age-based doses for three days.

Population	Nitazoxanide	Placebo
Outpatients aged 1 to 11, Egypt	88% (21 of 24)	38% (9 of 24)
Malnourished inpatients aged 12 to 35 months, Zambia	56% (14 of 25)	23% (5 of 22)

The response was clearly lower in hospitalised, malnourished children; 60% of that group were severely underweight. For adolescents aged 12 to 17, the label says tablet safety and efficacy are established from three trials that included 47 young people on 500 mg tablets.

Where it did not work: HIV and weakened immunity

A double-blind, placebo-controlled trial in hospitalised, severely malnourished children with AIDS in Zambia did not produce cure rates significantly different from placebo. This is the basis of the label's limitation: nitazoxanide has not been shown to be superior to placebo for Cryptosporidium diarrhoea in HIV-infected or immunodeficient patients, and it has not been studied for Giardia in them.

If you have HIV, are on immunosuppressive treatment or have another cause of weakened immunity, Cryptosporidium can be prolonged and serious. That needs specialist care rather than a standard three-day course.

Side effects

The label's safety data come from 2,177 people without HIV aged 12 months and over who took nitazoxanide at the recommended dose for at least three days. In pooled controlled trials of 536 people, the most common side effects, each at 2% or more, were:

• Abdominal pain
• Headache
• Chromaturia, meaning a change in urine colour
• Nausea

The label found no differences in side effects by age. Reports received after approval, where no rate can be calculated, add diarrhoea, acid reflux, dizziness, shortness of breath, rash and hives.

The current label does not publish the individual percentages for each side effect, so we do not quote any here. The one contraindication is a known hypersensitivity to nitazoxanide or any ingredient in the tablet.

Drug interactions

The active metabolite tizoxanide is more than 99.9% bound to plasma proteins. The label advises monitoring for side effects when nitazoxanide is taken with other highly protein-bound drugs that have a narrow margin between effective and toxic doses, because they can compete for binding. It names warfarin as the example. If you take warfarin, tell your prescriber before starting nitazoxanide.

Pregnancy and breastfeeding

There are no data on nitazoxanide in pregnant women. In animal studies, no birth defects or fetal toxicity were seen in rats and rabbits at exposures 30 and 2 times, respectively, the maximum human dose. For breastfeeding, the label says there is no information on whether nitazoxanide reaches breast milk or affects the baby. Both situations call for a conversation with your doctor about whether treatment is needed and when.

Older adults, kidney and liver disease

The trials did not include enough people aged 65 and over to show whether they respond differently. The pharmacokinetics of nitazoxanide have not been studied in people with kidney or liver impairment. About two thirds of a dose leaves the body in the faeces and one third in the urine.

Overdose

Information is limited. The label advises symptomatic and supportive treatment, notes that gastric lavage may be appropriate soon after an overdose, and says dialysis is unlikely to help because the drug is so highly protein-bound. There is no specific antidote.

Getting the diagnosis right first

The approval is for diarrhoea caused by Giardia or Cryptosporidium, which normally means a stool test has identified the parasite. Diarrhoea has many other causes, including bacteria, viruses and other parasites, and nitazoxanide is not a general treatment for it. Our intestinal parasites guide covers the common causes and tests, and the metronidazole guide covers another antiprotozoal your doctor may consider.

Buying nitazoxanide

Nitazoxanide is a prescription medicine in the United States. Whatever the source, check that:

• The active ingredient and strength are stated as nitazoxanide 500 mg.
• The manufacturer is named and can be looked up.
• The product is presented for the uses on the label, not as a cure-all.
• The seller does not claim a prescription is unnecessary where one is required.

Our guide to checking whether an online pharmacy is legitimate covers the rest, and our antiparasitic medicine guide explains which drug fits which parasite.

When to see a doctor

See a doctor before treatment to confirm the cause. Seek care promptly if diarrhoea is bloody, if you have a high fever, if you cannot keep fluids down, if you show signs of dehydration such as very little urine or dizziness on standing, or if symptoms have not improved within a few days of finishing the course. Anyone with HIV or weakened immunity should get medical advice rather than self-treating.

Sources

• Nitazoxanide tablets 500 mg, US prescribing information, sections 1, 2, 4, 6, 7, 8, 10, 12 and 14. DailyMed
• ALINIA (nitazoxanide) tablets and oral suspension, US prescribing information, sections 6, 12 and 14, including pediatric Table 7. DailyMed

This article is for information only and is not medical advice. Nitazoxanide is a prescription medicine. Talk to a doctor or pharmacist before starting, stopping or changing any treatment.