Actions of Antidiazox in details
The antiprotozoal activity of Antidiazox 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 Giardia lamblia directly reduces Antidiazox by transfer of electrons in the absence of ferredoxin. The DNA-derived PFOR protein sequence of Cryptosporidium parvum appears to be similar to that of Giardia lamblia. Interference with the PFOR enzyme-dependent electron transfer reaction may not be the only pathway by which Antidiazox exhibits antiprotozoal activity.
How should I take Antidiazox?
Dosing
The dose of Antidiazox will be different for different patients. Follow your doctor's orders or the directions on the label. The following information includes only the average doses of Antidiazox. If your dose is different, do not change it unless your doctor tells you to do so.
The amount of medicine that you take depends on the strength of the medicine. Also, the number of doses you take each day, the time allowed between doses, and the length of time you take the medicine depend on the medical problem for which you are using the medicine.
It is important to take Antidiazox with food.
It is very important to shake the oral suspension for of the medicine well before measuring each dose.
For the oral suspension dosage form: Use a specially marked measuring syringe or spoon to measure each dose accurately. The average household teaspoon may not hold the right amount of liquid.
- For oral dosage form (oral suspension):
- For treatment of diarrhea caused by protozoal infections
- Adults and adolescents—Ages 12 years or older: 25 milliliters (mL) every 12 hours for 3 days.
- Children—Ages 12 to 47 months: 5 milliliters (mL) every 12 hours for 3 days.
- Children—Ages 4 to 11 years: 10 milliliters (mL) every 12 hours for 3 days.
- For treatment of diarrhea caused by protozoal infections
- For oral dosage form (tablets):
- For treatment of diarrhea caused by protozoal infections
- Adults and adolescents—Ages 12 years or older: 500 milligrams (mg) every 12 hours for 3 days.
- Children—Ages 11 months or younger: Tablet dosage form is not for use in children.
- For treatment of diarrhea caused by protozoal infections
Missed Dose
If you miss a dose of Antidiazox, take it as soon as possible. However, if it is almost time for your next dose, skip the missed dose and go back to your regular dosing schedule. Do not double doses.
Storage
Store the medicine in a closed container at room temperature, away from heat, moisture, and direct light. Keep from freezing.
Keep out of the reach of children.
Do not keep outdated medicine or medicine no longer needed.
Ask your healthcare professional how you should dispose of any medicine you do not use.
The suspension may be stored for 7 days. Any unused suspension must be disposed of after 7 days.
Antidiazox administration
Take Antidiazox exactly as directed by your doctor. If you do not understand these instructions, ask your pharmacist, nurse, or doctor to explain them to you.
Take Antidiazox with food.
Shake the suspension well before measuring a dose. To ensure that you get the correct dose, measure the suspension with a dose-measuring spoon, dropper, or cup, not with a regular table spoon. If you do not have a dose-measuring device, ask your pharmacist where you can get one.
Store the suspension at room temperature. The suspension may be stored for 7 days, after which any unused portion must be discarded.
Antidiazox pharmacology
Mechanism of Action
Antidiazox is an antiprotozoal.
Pharmacokinetics
Absorption
Single Dosing:
Following oral administration of Antidiazox tablets or oral suspension, the parent drug, Antidiazox, is not detected in plasma. The pharmacokinetic parameters of the metabolites, tizoxanide and tizoxanide glucuronide are shown in Tables 2 and 3 below.
Table 2. Mean (+/- SD) plasma pharmacokinetic parameters of tizoxanide and tizoxanide glucuronide following administration of a single dose of one 500 mg Antidiazox tablets with food to subjects ≥12 years of age
| Tizoxanide | Tizoxanide Glucuronide | |||||
| Age | Cmax (μg/mL) | *Tmax (hr) | AUCԏ (μg•hr/mL) | Cmax (μg/mL) | *Tmax (hr) | AUCԏ (μg•hr/mL) |
| 12-17 years ≥18 years | 9.1 (6.1) 10.6 (2.0) | 4.0 (1-4) 3.0 (2-4) | 39.5 (24.2) 41.9 (6.0) | 7.3 (1.9) 10.5 (1.4) | 4.0 (2-8) 4.5 (4-6) | 46.5 (18.2) 63.0 (12.3) |
* Tmax is given as a Mean (Range)
Table 3. Mean (+/- SD) plasma pharmacokinetic of tizoxanide and tizoxanide glucuronide parameter values following administration of a single dose of Antidiazox for oral suspension with food to subjects ≥1 year of age
| Tizoxanide | Tizoxanide Glucuronide | ||||||
| Age | Dose | Cmax (μg/mL) | *Tmax (hr) | AUCinf (μg•hr/mL) | Cmax (μg/mL) | *Tmax (hr) | AUCinf (μg•hr/mL) |
| 1-3 years | 100 mg | 3.11 (2.0) | 3.5 (2-4) | 11.7 (4.46) | 3.64 (1.16) | 4.0 (3-4) | 19.0 (5.03) |
| 4-11 years | 200 mg | 3.00 (0.99) | 2.0 (1-4) | 13.5 (3.3) | 2.84 (0.97) | 4.0 (2-4) | 16.9 (5.00) |
| ≥18 years | 500 mg | 5.49 (2.06) | 2.5 (1-5) | 30.2 (12.3) | 3.21 (1.05) | 4.0 (2.5-6) | 22.8 (6.49) |
* Tmax is given as a Mean (Range)
Multiple dosing:
Following oral administration of a single Antidiazox tablet every 12 hours for 7 consecutive days, there was no significant accumulation of Antidiazox metabolites tizoxanide or tizoxanide glucuronide detected in plasma.
Bioavailability:
Antidiazox for oral suspension is not bioequivalent to Antidiazox tablets. The relative bioavailability of the suspension compared to the tablet was 70%.
When Antidiazox tablets are administered with food, the AUCԏ of tizoxanide and tizoxanide glucuronide in plasma is increased almost two-fold and the Cmax is increased by almost 50%.
When Antidiazox for oral suspension was administered with food, the AUCԏ of tizoxanide and tizoxanide glucuronide increased by about 45-50% and the Cmax increased by ≤10%.
Antidiazox tablets and Antidiazox for oral suspension were administered with food in clinical trials and hence they are recommended to be administered with food.
Distribution
In plasma, more than 99% of tizoxanide is bound to proteins.
Elimination
Metabolism
Following oral administration in humans, Antidiazox is rapidly hydrolyzed to an active metabolite, tizoxanide (desacetyl-Antidiazox). Tizoxanide then undergoes conjugation, primarily by glucuronidation.
Excretion
Tizoxanide is excreted in the urine, bile and feces, and tizoxanide glucuronide is excreted in urine and bile. Approximately two-thirds of the oral dose of Antidiazox is excreted in the feces and one-third in the urine.
Specific Populations
Pediatric Patients
The pharmacokinetics of tizoxanide and tizoxanide glucuronide following administration of Antidiazox tablets in pediatric patients 12-17 years of age are provided above in Table 2. The pharmacokinetics of tizoxanide and tizoxanide glucuronide following administration of Antidiazox for oral suspension in pediatric patients 1-11 years of age are provided above in Table 3.
Drug Interaction Studies
In vitro studies demonstrated that tizoxanide has no significant inhibitory effect on cytochrome P450 enzymes.
Microbiology
Mechanism of Action
The antiprotozoal activity of Antidiazox 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 Antidiazox 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 Antidiazox exhibits antiprotozoal activity.
Resistance
A potential for development of resistance by C. parvum or G. lamblia to Antidiazox has not been examined.
Antimicrobial Activity
Antidiazox 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.
References
- DailyMed. "NITAZOXANIDE: DailyMed provides trustworthy information about marketed drugs in the United States. DailyMed is the official provider of FDA label information (package inserts).". https://dailymed.nlm.nih.gov/dailyme... (accessed September 17, 2018).
- NCIt. "Nitazoxanide: NCI Thesaurus (NCIt) provides reference terminology for many systems. It covers vocabulary for clinical care, translational and basic research, and public information and administrative activities.". https://ncit.nci.nih.gov/ncitbrowser... (accessed September 17, 2018).
- EPA DSStox. "Nitazoxanide: DSSTox provides a high quality public chemistry resource for supporting improved predictive toxicology.". https://comptox.epa.gov/dashboard/ds... (accessed September 17, 2018).
Reviews
The results of a survey conducted on ndrugs.com for Antidiazox are given in detail below. The results of the survey conducted are based on the impressions and views of the website users and consumers taking Antidiazox. We implore you to kindly base your medical condition or therapeutic choices on the result or test conducted by a physician or licensed medical practitioners.User reports
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Information checked by Dr. Sachin Kumar, MD Pharmacology
