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Nitazoxanide


General


Pronunciation

(nye ta ZOX a nide)


Brand Names: U.S.

  • Alinia

Indications


Use: Labeled Indications

Treatment of diarrhea caused by Cryptosporidium parvum or Giardia lamblia


Contraindications


Hypersensitivity to nitazoxanide or any component of the formulation


Dosing and Administration


Dosing: Adult

Diarrhea caused by Cryptosporidium parvum or Giardia lamblia: Oral suspension or tablets: 500 mg every 12 hours for 3 days

Clostridium difficile-associated diarrhea (off-label use): Oral suspension or tablets: 500 mg every 12 hours for 7 to 10 days (Musher 2006; Musher 2009)

Cryptosporidiosis-associated diarrhea in HIV-infected patients (off-label use): Oral: 500 to 1,000 mg twice daily for 14 days (must be used in conjunction with optimized ART, electrolyte replacement, and symptomatic treatment and rehydration) (HHS [OI adult 2015])


Dosing: Geriatric

Refer to adult dosing.


Dosing: Pediatric

Diarrhea caused by Cryptosporidium parvum or Giardia lamblia: Oral: Note: May consider increasing duration up to 14 days in HIV-exposed/-infected patients with cryptosporidiosis (CDC 2009):

Children 1 to 3 years: Oral suspension: 100 mg every 12 hours for 3 days; may consider increasing duration up to 14 days in HIV-exposed/-infected pediatric patients with cryptosporidiosis (CDC 2009)

Children 4 to 11 years: Oral suspension: 200 mg every 12 hours for 3 days; may consider increasing duration up to 14 days in HIV-exposed/-infected pediatric patients with cryptosporidiosis (CDC 2009)

Children ≥12 years: Refer to adult dosing.

Cryptosporidiosis-associated diarrhea in HIV-infected patients (off-label use): Adolescents: Refer to adult dosing.


Dosing: Renal Impairment

There are no dosage adjustments provided in the manufacturer 's labeling (has not been studied); use with caution.


Dosing: Hepatic Impairment

There are no dosage adjustments provided in the manufacturer 's labeling (has not been studied); use with caution.


Reconstitution

For preparation at time of dispensing, add 48 mL incrementally to 60 mL bottle; shake vigorously. Resulting suspension is 20 mg/mL (100 mg per 5 mL).


Administration

Administer with food. Shake suspension well prior to administration.


Dietary Considerations

Should be taken with food.


Storage

Suspension: Prior to and following reconstitution, store at 25 � �C (77 � �F); excursions permitted to 15 � �C to 30 � �C (59 � �F to 86 � �F). For preparation at time of dispensing, add 48 mL incrementally to 60 mL bottle; shake vigorously. Resulting suspension is 20 mg/mL (100 mg per 5 mL). Following reconstitution, discard unused portion of suspension after 7 days.

Tablet: Store at 25 � �C (77 � �F); excursions permitted to 15 � �C to 30 � �C (59 � �F to 86 � �F).


Dosage Forms/Strengths


Dosage Forms

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Suspension Reconstituted, Oral:

Alinia: 100 mg/5 mL (60 mL) [contains fd&c red #40, sodium benzoate; strawberry flavor]

Tablet, Oral:

Alinia: 500 mg [contains fd&c blue #2 aluminum lake, fd&c yellow #10 aluminum lake, fd&c yellow #6 aluminum lake, soybean lecithin]


Drug Interactions

There are no known significant interactions.


Adverse Reactions


Rates of adverse effects were similar to those reported with placebo.

1% to 10%:

Central nervous system: Headache (1% to 3%)

Gastrointestinal: Abdominal pain (7% to 8%), diarrhea (2% to 4%), nausea (3%), vomiting (1%)

<1% (Limited to important or life-threatening): Allergic reaction, ALT increased, anemia, anorexia, appetite increased, creatinine increased, diaphoresis, dizziness, eye discoloration (pale yellow), fever, flatulence, hypertension, infection, malaise, pruritus, rhinitis, salivary glands enlarged, tachycardia, urine discoloration


Warnings/Precautions


Disease-related concerns:

- Hepatic impairment: Use with caution in patients with hepatic impairment.

- HIV: Safety and efficacy have not been established in patients with HIV infection.

- Renal impairment: Use with caution in patients with renal impairment.

Special populations:

- Immunocompromised patients: Safety and efficacy have not been established in patients with immunodeficiency.

Dosage form specific issues:

- Benzyl alcohol and derivatives: Some dosage forms may contain sodium benzoate/benzoic acid; benzoic acid (benzoate) is a metabolite of benzyl alcohol; large amounts of benzyl alcohol ( ≥99 mg/kg/day) have been associated with a potentially fatal toxicity ( "gasping syndrome " �) in neonates; the "gasping syndrome " � consists of metabolic acidosis, respiratory distress, gasping respirations, CNS dysfunction (including convulsions, intracranial hemorrhage), hypotension, and cardiovascular collapse (AAP [Inactive" 1997]; CDC, 1982); some data suggests that benzoate displaces bilirubin from protein binding sites (Ahlfors, 2001); avoid or use dosage forms containing benzyl alcohol derivative with caution in neonates. See manufacturer 's labeling.

- Sucrose: Oral suspension contains sucrose; use caution in patients with diabetes mellitus.


Pregnancy Risk Factor

B


Pregnancy Considerations

Adverse events have not been observed in animal reproduction studies. Human data is not available, however nitazoxanide may be used in during pregnancy after the first trimester in women with severe symptoms of cryptosporidiosis (HHS [opportunistic; adult] 2015).


Actions


Pharmacology

Nitazoxanide is rapidly metabolized to the active metabolite tizoxanide in vivo. Activity may be due to interference with the pyruvate:ferredoxin oxidoreductase (PFOR) enzyme-dependent electron transfer reaction which is essential to anaerobic metabolism. In vitro, nitazoxanide and tizoxanide inhibit the growth of sporozoites and oocysts of Cryptosporidium parvum and trophozoites of Giardia lamblia.


Metabolism

Hepatic, to an active metabolite, tizoxanide. Tizoxanide undergoes conjugation to form tizoxanide glucuronide. Nitazoxanide is not detectable in the serum following oral administration.


Excretion

Tizoxanide: Urine (<10%), bile, and feces (60%); Tizoxanide glucuronide: Urine and bile


Time to Peak

Plasma: Tizoxanide and tizoxanide glucuronide: 1-4 hours


Half-Life Elimination

Tizoxanide: 1 to 1.6 hours


Protein Binding

Tizoxanide: >99%


Patient and Family Education


Patient Education

- Discuss specific use of drug and side effects with patient as it relates to treatment. (HCAHPS: During this hospital stay, were you given any medicine that you had not taken before? Before giving you any new medicine, how often did hospital staff tell you what the medicine was for? How often did hospital staff describe possible side effects in a way you could understand?)

- Patient may experience headache, abdominal pain, or diarrhea. Have patient report immediately to prescriber severe nausea or severe vomiting (HCAHPS).

- Educate patient about signs of a significant reaction (eg, wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat). Note: This is not a comprehensive list of all side effects. Patient should consult prescriber for additional questions.

Intended Use and Disclaimer: Should not be printed and given to patients. This information is intended to serve as a concise initial reference for healthcare professionals to use when discussing medications with a patient. You must ultimately rely on your own discretion, experience and judgment in diagnosing, treating and advising patients.

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