Alinia

There are no restrictions on food, beverages, or activity during treatment with nitazoxanide unless otherwise directed by your doctor.

Many drugs may affect the way that nitazoxanide is metabolized ("broken down") in the body, leading to higher or lower than expected levels of the medication in the blood. Talk to your doctor before taking any other medicines during treatment with nitazoxanide.

Talk to your doctor before taking other prescription or over-the-counter medications including vitamins, minerals, and herbal products during treatment with nitazoxanide.

Nitazoxanide has not been adequately evaluated in pregnant women.

It is not known whether nitazoxanide is excreted in human milk.

STORAGE: Nitazoxanide should be stored at room temperature, 15 C to 30 C (59 F to 86 F).

Dosage Forms & Strengths

tablet

• 500mg

oral suspension

• 100mg/5mL

Diarrhea Caused by Cryptosporidium Parvum or Giardia Lamblia

500 mg PO q12hr x 3 days

Amebiasis (Orphan)

Treatment for intestinal amebiasis

Orphan indication sponsor

• Romark Laboratories, L.C.; 6200 Courtney Campbell Causeway, Suite 880; Tampa, FL 33607

Dosage Forms & Strengths

tablet

• 500mg

oral suspension

• 100mg/5mL

Diarrhea Caused by Cryptosporidium Parvum or Giardia Lamblia

<1 year: Safety & efficacy not established

1-3 years: 5 mL (100 mg) PO q12hr x 3 days

4-11 years: 10 mL (200 mg) PO q12hr x 3 days

≥12 years: 500 mg PO q12hr x 3 days

You should not use nitazoxanide if you are allergic to it.

To make sure nitazoxanide is safe for you, tell your doctor if you have:

• liver or kidney disease;

• HIV or AIDS; or

• a weak immune system.

The tablet form of this medicine should not be given to a child younger than 12 years old. Children ages 1 to 11 years should use only the oral suspension (liquid) form of nitazoxanide.

Nitazoxanide is not expected to be harmful to an unborn baby. Tell your doctor if you are pregnant.

It is not known whether nitazoxanide passes into breast milk or if it could harm a nursing baby. Tell your doctor if you are breast-feeding a baby.

Follow all directions on your prescription label. Do not take this medicine in larger or smaller amounts or for longer than recommended.

Take nitazoxanide with food.

Nitazoxanide is usually taken once every 12 hours for 3 days. Follow your doctor's dosing instructions very carefully.

Shake the oral suspension (liquid) well just before you measure a dose. Measure liquid medicine with the dosing syringe provided, or with a special dose-measuring spoon or medicine cup. If you do not have a dose-measuring device, ask your pharmacist for one.

Store at room temperature away from moisture and heat. Keep the bottle tightly closed when not in use. Throw away any unused liquid after 7 days.

Absorption

Bioavailability

Rapidly absorbed from GI tract and hydrolyzed to tizoxanide.1 Both nitazoxanide and tizoxanide have antiprotozoal activity.1 10

Peak plasma concentrations of tizoxanide and tizoxanide glucuronide attained within 1–4 hours; nitazoxanide undetectable in plasma.1

The tablets and oral suspension are not bioequivalent.1 Bioavailability of the oral suspension is 70% relative to that of the tablet.1

Food

Food increases extent of absorption.1

Distribution

Plasma Protein Binding

>99%.1

Elimination

Metabolism

Rapidly hydrolyzed to tizoxanide;1 tizoxanide subsequently undergoes conjugation, principally by glucuronidation.1

Elimination Route

Tizoxanide eliminated in urine, bile, and feces;1 tizoxanide glucuronide eliminated in urine and bile.1

Special Populations

Pharmacokinetics not studied in patients with hepatic or renal impairment.1

Storage

Oral

25°C (may be exposed to 15–30°C).1

After reconstitution, store in tight container at 25°C (may be exposed to 15–30°C); discard after 7 days.1

25°C (may be exposed to 15–30°C).1

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

Nitazoxanide is used to treat diarrhea that is caused by certain types of protozoa (tiny, one-celled animals). It belongs to a group of medicines called antiprotozoals.

This medicine is available only with your doctor's prescription.

6.1 Clinical Trials Experience

Because clinical trials are conducted under widely varying conditions, adverse reactions rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.

The safety of Alinia was evaluated in 2177 HIV-uninfected subjects 12 months of age and older who received Alinia Tablets or Alinia for Oral Suspension at the recommended dose for at least three days. In pooled controlled clinical trials involving 536 HIV-uninfected subjects treated with Alinia Tablets or Alinia for Oral Suspension, the most common adverse reactions were abdominal pain, headache, chromaturia and nausea (>2%).

Safety data were analyzed separately for 280 HIV-uninfected subjects ≥12 years of age receiving Alinia at the recommended dose for at least three days in 5 placebo-controlled clinical trials and for 256 HIV-uninfected subjects 1 through 11 years of age in 7 controlled clinical trials. There were no differences between the adverse reactions reported for Alinia-treated subjects based upon age.

6.2 Postmarketing Experience

The following adverse reactions have been identified during post approval use of Alinia. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure. The following is a list of adverse reactions spontaneously reported with Alinia Tablets which were not included in clinical trial listings:

Gastrointestinal disorders: diarrhea, gastroesophageal reflux disease

Nervous System disorders: dizziness

Respiratory, thoracic and mediastinal disorders: dyspnea

Skin and subcutaneous tissue disorders: rash, urticaria

8.1 Pregnancy

Risk Summary

There are no data with Alinia in pregnant women to inform a drug-associated risk. No teratogenicity or fetotoxicity was observed in animal reproduction studies with administration of nitazoxanide to pregnant rats and rabbits during organogenesis at exposure 30 and 2 times, respectively, the exposure at the maximum recommended human dose of 500 mg twice daily based on body surface area (BSA).

In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively.

Data

Animal Data

Nitazoxanide was administered orally to pregnant rats at doses of 0, 200, 800 or 3200 mg/kg/day on gestation days 6 to 15. Nitazoxanide produced no evidence of systemic maternal toxicity when administer once daily via oral gavage to pregnant female rats at levels up to 3200 mg/kg/day during the period of organogenesis .

In rabbits, nitazoxanide administered at doses of 0, 25, 50, or 100 mg/kg/day on gestation days 7 to 20. Oral treatment of pregnant rabbits with nitazoxanide during organogenesis resulted in minimal maternal toxicity and no external fetal anomalies.

8.2 Lactation

Risk Summary

No information regarding the presence of nitazoxanide in human milk, the effects on the breastfed infant, or the effects on milk production is available. The development and health benefits of breastfeeding should be considered along with the mother’s clinical need for Alinia and any potential adverse effects on the breastfed infant from Alinia or from the underlying maternal condition.

8.4 Pediatric Use

The safety and efficacy of Alinia for Oral Suspension for the treatment of diarrhea caused by G. lamblia or C. parvum in pediatric patients 1 to 11 years of age has been established based on three (3) randomized, controlled studies with 104 pediatric subjects treated with Alinia for Oral Suspension 100 mg/5 mL. Furthermore, the safety and efficacy of Alinia for Oral Suspension for the treatment of diarrhea caused by G. lamblia or C. parvum in pediatric patients 12 to 17 years of age has been established based on two (2) randomized controlled studies with 44 pediatric subjects treated with Alinia for Oral Suspension 100 mg/5 mL. [ see Clinical Studies (14.1)]

The safety and efficacy of Alinia Tablets for the treatment of diarrhea caused by G. lamblia or C. parvum in pediatric patients 12 to 17 years of age has been established based on three (3) randomized controlled studies with 47 pediatric subjects treated with Alinia Tablets 500 mg.

A single Alinia Tablet contains a greater amount of nitazoxanide than is recommended for use in pediatric patients 11 years or younger. [ see Dosage and Administration (2.1)].

Safety and efficacy of Alinia for Oral Suspension in pediatric patients less than one year of age has not been studied.

8.5 Geriatric Use

Clinical studies of Alinia Tablets and Alinia for Oral Suspension did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. In general, the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy in elderly patients should be considered when prescribing Alinia Tablets and Alinia for Oral Suspension.

8.6 Renal and Hepatic Impairment

The pharmacokinetics of nitzoxanide in patients with compromised renal or hepatic function has not been studied.

8.7 HIV-Infected or Immunodeficient Patients

Alinia Tablets and Alinia for Oral Suspension have not been studied for the treatment of diarrhea caused by G. lamblia in HIV-infected or immunodeficient patients. Alinia Tablets and Alinia for Oral Suspension have not been shown to be superior to placebo for the treatment of diarrhea caused by C. parvum in HIV-infected or immunodeficient patients [ see Clinical Studies (14)]

Mechanism of Action

The antiprotozoal activity of nitazoxanide is believed to be due to interference with the pyruvate:ferredoxin oxidoreductase (PFOR) enzyme-dependent electron transfer reaction which is essential to anaerobic energy metabolism. Studies have shown that the PFOR enzyme from G. lamblia directly reduces nitazoxanide by transfer of electrons in the absence of ferredoxin. The DNA-derived PFOR protein sequence of C. parvum appears to be similar to that of G. lamblia. Interference with the PFOR enzyme-dependent electron transfer reaction may not be the only pathway by which nitazoxanide exhibits antiprotozoal activity.

Resistance

A potential for development of resistance by C. parvum or G. lamblia to nitazoxanide has not been examined.

Antimicrobial Activity

Nitazoxanide and its metabolite, tizoxanide, are active in vitro in inhibiting the growth of (i) sporozoites and oocysts of C. parvum and (ii) trophozoites of G. lamblia.

Susceptibility Test Methods

For protozoa such as C. parvum and G. lamblia, standardized tests for use in clinical microbiology laboratories are not available.

13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility

Carcinogenesis

Long-term carcinogenicity studies have not been conducted.

Mutagenesis

Nitazoxanide was not genotoxic in the Chinese hamster ovary (CHO) cell chromosomal aberration assay or the mouse micronucleus assay. Nitazoxanide was genotoxic in one tester strain (TA100) in the Ames bacterial mutation assay.

Impairment of Fertility

Nitazoxanide did not adversely affect male or female fertility in the rat at 2400 mg/kg/day (approximately 20 times the clinical adult dose adjusted for body surface area).

Advise patients and parents/caregivers of pediatric patients taking Alinia Tablets or Alinia for Oral Suspension of the following information:

Dosage and Administration:

Alinia Tablets and Alinia for Oral Suspension should be taken with food.

Alinia for Oral Suspension: The container should be kept tightly closed, and the suspension should be shaken well before each administration. The suspension may be stored at room temperature for 7 days, after which any unused portion must be discarded.

Drug-drug Interactions:

Avoid concurrent warfarin use.

Romark, L.C.
3000 Bayport Drive, Suite 200, Tampa, FL 33607
Telephone: 813-282-8544, Fax: 813-282-1162
E-mail: customer.service@romark.com
Web site: www.romark.com

Alinia for Oral Suspension is distributed by Lupin Pharmaceuticals, Inc. under license from Romark.

Lupin Pharma

Baltimore, Maryland 21202 United States

US Patents No. 5,578,621; 6,020,353; 5,968,961; 5,387,598; 6,117,894; 5,965,590.

Alinia is a registered trademark of Romark.

PI-111/106-04 R.07/16

Nitazoxanide is an antiprotozoal agent.

Nitazoxanide is used to treat diarrhea in adults and children caused by the protozoa Giardia lamblia. Nitazoxanide is also used to treat diarrhea caused by the protozoa Cryptosporidium parvum. These conditions are also sometimes referred to as travelers' diarrhea.

Nitazoxanide may also be used for purposes other than those listed in this medication guide.

Talk to your doctor before taking nitazoxanide if you have

• liver disease;
• kidney disease; or
• HIV infection or problems with your immune system.

You may not be able to take nitazoxanide, or you may require a dosage adjustment or special monitoring during treatment if you have any of the conditions listed above.

The nitazoxanide oral suspension contains 1.48 grams of sucrose per 5 mL (teaspoon). Individuals with diabetes may need to monitor their intake of sucrose.

Nitazoxanide is in the FDA pregnancy category B. This means that it is not expected to be harmful to an unborn baby. Do not take nitazoxanide without first talking to your doctor if you are pregnant or could become pregnant during treatment.

It is not known whether nitazoxanide passes into breast milk. Do not take nitazoxanide without first talking to your doctor if you are breast-feeding a baby.

Take the missed dose as soon as you remember. If you do not remember until it is time for the next dose, skip the missed dose and take only the next regularly scheduled dose. Do not take a double dose of the medication.

There are no data on the excretion of nitazoxanide into human milk. The manufacturer recommends that caution be used when administering nitazoxanide to nursing women.