DRUGS & SUPPLEMENTS

Inflobid-NXT

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Inflobid-NXT uses

Inflobid-NXT consists of Nitazoxanide, Ofloxacin.

Nitazoxanide:


1 INDICATIONS AND USAGE

Diarrhea caused by Giardia lamblia or Cryptosporidium parvum:

Inflobid-NXT (Nitazoxanide) for Oral Suspension (patients 1 year of age and older) and Inflobid-NXT (Nitazoxanide) Tablets (patients 12 years and older) are indicated for the treatment of diarrhea caused by Giardia lamblia or Cryptosporidium parvum.

Limitations of Use

Inflobid-NXT (Nitazoxanide) for Oral Suspension and Inflobid-NXT (Nitazoxanide) Tablets have not been shown to be effective for the treatment of diarrhea caused by Cryptosporidium parvum in HIV-infected or immunodeficient patients [ see Clinical Studies (14.2)]

Inflobid-NXT (Nitazoxanide) is an antiprotozoal indicated for the treatment of diarrhea caused by Giardia lamblia or Cryptosporidium parvum (1).

Limitations of Use:

Inflobid-NXT (Nitazoxanide) has not been shown to be effective for the treatment of diarrhea caused by C. parvum in HIV-infected or immunodeficient patients (1).

2 DOSAGE & ADMINISTRATION

  • Inflobid-NXT Tablets should not be administered to pediatric patient 11 years of age or younger ( 2.1)
  • Dosage for treatment of diarrhea caused by G. lamblia or C. parvum ( 2.1):
Age Dosage Duration
1-3 years 5 mL of Inflobid-NXT (Nitazoxanide) for Oral Suspension (100 mg Inflobid-NXT (Nitazoxanide)) every 12 hours with food
4-11 years 10 mL of Inflobid-NXT (Nitazoxanide) for Oral Suspension (200 mg Inflobid-NXT (Nitazoxanide)) every 12 hours with food 3 days
12 years and older One Inflobid-NXT (Nitazoxanide) Tablet (500 mg Inflobid-NXT (Nitazoxanide)) every 12 hours with food or 25 mL of Inflobid-NXT (Nitazoxanide) for Oral Suspension (500 mg Inflobid-NXT (Nitazoxanide)) every 12 hours with food

2.1 Recommended Dosage and Important Administration Instructions

Important Administration Instructions for Pediatric Patients 11 years of Age or Younger:

Inflobid-NXT (Nitazoxanide) tablets should not be administered to pediatric patients 11 years of age or younger because a single tablet contains a greater amount of Inflobid-NXT (Nitazoxanide) than the recommended dosing in this pediatric age group.

Table 1. Recommended Dosage

Age Dosage Duration
1-3 years

5 mL of Inflobid-NXT (Nitazoxanide) for Oral suspension

(100 mg Inflobid-NXT (Nitazoxanide)) taken orally every 12 hours with food

4-11 years

10 mL of Inflobid-NXT (Nitazoxanide) for Oral Suspension

(200 mg Inflobid-NXT (Nitazoxanide)) taken orally every 12 hours with food

3 Days
12 years and older One Inflobid-NXT (Nitazoxanide) Tablet (500 mg Inflobid-NXT (Nitazoxanide)) taken orally every 12 hours with food or 25 mL of Inflobid-NXT (Nitazoxanide) for Oral Suspension (500 mg Inflobid-NXT (Nitazoxanide)) taken orally every 12 hours with food

2.2 Directions for Mixing Inflobid-NXT for Oral Suspension

Reconstitute Inflobid-NXT (Nitazoxanide) for Oral Suspension as follows:

  • Measure 48 mL of water for preparation of the 100 mg/5 mL suspension
  • Tap bottle until all powder flows freely.
  • Add approximately one-half of the 48 mL of water required for reconstitution and shake vigorously to suspend powder.
  • Add remainder of water and again shake vigorously

Keep container tightly closed, and shake the suspension well before each administration. The reconstituted suspension may be stored for 7 days at room temperature, after which any unused portion must be discarded.

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3 DOSAGE FORMS AND STRENGTHS

  • Inflobid-NXT Tablets: 500 mg ( 3.1)
  • Inflobid-NXT (Nitazoxanide) for Oral Suspension: 100 mg/5 mL ( 3.2)

3.1 Inflobid-NXT (Nitazoxanide) Tablets (500 mg)

Round, yellow, film-coated tablets debossed with Inflobid-NXT (Nitazoxanide) on one side and 500 on the other side. Each tablet contains 500 mg of Inflobid-NXT (Nitazoxanide).

3.2 Inflobid-NXT for Oral Suspension (100 mg/5 mL)

Pink-colored powder formulation that, when reconstituted as directed, contains 100 mg nitazoxanide/5 mL. The reconstituted suspension has a pink color and strawberry flavor.

4 CONTRAINDICATIONS

Hypersensitivity

4.1 Hypersensitivity

Inflobid-NXT (Nitazoxanide) Tablets and Inflobid-NXT (Nitazoxanide) for Oral Suspension are contraindicated in patients with a prior hypersensitivity to Inflobid-NXT (Nitazoxanide) or any other ingredient in the formulations.

6 ADVERSE REACTIONS

The most common adverse reactions in ≥2% of patients were abdominal pain, headache, chromaturia, and nausea.

To report SUSPECTED ADVERSE REACTIONS, contact Romark at 813-282-8544 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

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 Inflobid-NXT (Nitazoxanide) was evaluated in 2177 HIV-uninfected subjects 12 months of age and older who received Inflobid-NXT (Nitazoxanide) Tablets or Inflobid-NXT (Nitazoxanide) for Oral Suspension at the recommended dose for at least three days. In pooled controlled clinical trials involving 536 HIV-uninfected subjects treated with Inflobid-NXT (Nitazoxanide) Tablets or Inflobid-NXT (Nitazoxanide) 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 Inflobid-NXT (Nitazoxanide) 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 Inflobid-NXT (Nitazoxanide). 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 Inflobid-NXT (Nitazoxanide) 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

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7 DRUG INTERACTIONS

Competition for binding sites may occur when administered concurrently with other highly plasma protein-bound drugs with narrow therapeutic indices. Monitor for adverse reactions.

7.1 Highly Protein Bound Drugs with Narrow Therapeutic Indices

Tizoxanide (the active metabolite of Inflobid-NXT (Nitazoxanide)) is highly bound to plasma protein (>99.9%). Therefore, monitor for adverse reactions when administering Inflobid-NXT (Nitazoxanide) concurrently with other highly plasma protein-bound drugs with narrow therapeutic indices, as competition for binding sites may occur (e.g., warfarin).

8 USE IN SPECIFIC POPULATIONS

Pediatric Patients: Safety and efficacy of Inflobid-NXT for Oral Suspension in pediatric patients less than one year of age has not been studied ( 8.4).

8.1 Pregnancy

Risk Summary

There are no data with Inflobid-NXT (Nitazoxanide) in pregnant women to inform a drug-associated risk. No teratogenicity or fetotoxicity was observed in animal reproduction studies with administration of Inflobid-NXT (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

Inflobid-NXT (Nitazoxanide) was administered orally to pregnant rats at doses of 0, 200, 800 or 3200 mg/kg/day on gestation days 6 to 15. Inflobid-NXT (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, Inflobid-NXT (Nitazoxanide) was administered at doses of 0, 25, 50, or 100 mg/kg/day on gestation days 7 to 20. Oral treatment of pregnant rabbits with Inflobid-NXT (Nitazoxanide) during organogenesis resulted in minimal maternal toxicity and no external fetal anomalies.

8.2 Lactation

Risk Summary

No information regarding the presence of Inflobid-NXT 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 Inflobid-NXT (Nitazoxanide) and any potential adverse effects on the breastfed infant from Inflobid-NXT (Nitazoxanide) or from the underlying maternal condition.

8.4 Pediatric Use

The safety and efficacy of Inflobid-NXT (Nitazoxanide) 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 Inflobid-NXT (Nitazoxanide) for Oral Suspension 100 mg/5 mL. Furthermore, the safety and efficacy of Inflobid-NXT (Nitazoxanide) 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 Inflobid-NXT (Nitazoxanide) for Oral Suspension 100 mg/5 mL. [ see Clinical Studies (14.1)]

The safety and efficacy of Inflobid-NXT (Nitazoxanide) 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 Inflobid-NXT (Nitazoxanide) Tablets 500 mg.

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

Safety and efficacy of Inflobid-NXT (Nitazoxanide) for Oral Suspension in pediatric patients less than one year of age has not been studied.

8.5 Geriatric Use

Clinical studies of Inflobid-NXT Tablets and Inflobid-NXT (Nitazoxanide) 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 Inflobid-NXT (Nitazoxanide) Tablets and Inflobid-NXT (Nitazoxanide) 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

Inflobid-NXT (Nitazoxanide) Tablets and Inflobid-NXT (Nitazoxanide) for Oral Suspension have not been studied for the treatment of diarrhea caused by G. lamblia in HIV-infected or immunodeficient patients. Inflobid-NXT (Nitazoxanide) Tablets and Inflobid-NXT (Nitazoxanide) 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)]

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10 OVERDOSAGE

Limited information on Inflobid-NXT (Nitazoxanide) overdosage is available. Single oral doses of up to 4000 mg Inflobid-NXT (Nitazoxanide) have been administered to healthy adult volunteers without significant adverse effects. In the event of overdose, gastric lavage may be appropriate soon after oral administration. Patients should be observed and given symptomatic and supportive treatment. There is no specific antidote for overdose with Inflobid-NXT (Nitazoxanide). Because tizoxanide is highly protein bound (>99.9%), dialysis is unlikely to significantly reduce plasma concentrations of the drug.

11 DESCRIPTION

Inflobid-NXT (Nitazoxanide) Tablets and Inflobid-NXT (Nitazoxanide) for Oral Suspension contain the active ingredient, Inflobid-NXT (Nitazoxanide), a synthetic antiprotozoal for oral administration. Inflobid-NXT (Nitazoxanide) is a light yellow crystalline powder. It is poorly soluble in ethanol and practically insoluble in water. Chemically, Inflobid-NXT (Nitazoxanide) is 2-acetyloxy- N-(5-nitro-2-thiazolyl)benzamide. The molecular formula is C 12H 9N 3O 5S and the molecular weight is 307.3. The structural formula is:

Inflobid-NXT (Nitazoxanide) Tablets contain 500 mg of Inflobid-NXT (Nitazoxanide) and the following inactive ingredients: maize starch, pregelatinized corn starch, hydroxypropyl methylcellulose, sucrose, sodium starch glycollate, talc, magnesium stearate, soy lecithin, polyvinyl alcohol, xanthan gum, titanium dioxide, FD&C Yellow No. 10 Aluminum Lake, FD&C Yellow No. 6 Aluminum Lake, and FD&C Blue No. 2 Aluminum Lake.

Inflobid-NXT (Nitazoxanide) for Oral Suspension, when reconstituted with 48 mL of water, produces 60 mL of a homogeneous suspension with a pink color that contains 100 mg Inflobid-NXT (Nitazoxanide) per 5 mL and the following inactive ingredients: sodium benzoate, sucrose, xanthan gum, microcrystalline cellulose and carboxymethylcellulose sodium, anhydrous citric acid, sodium citrate dihydrate, maltodextrin, modified food starch, triacetin, FD&C Red No. 40 and artificial strawberry flavoring.

structure

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12 CLINICAL PHARMACOLOGY

12.1 Mechanism of Action

Inflobid-NXT is an antiprotozoal [ see Microbiology (12.4))].

12.3 Pharmacokinetics

Absorption

Single Dosing:

Following oral administration of Inflobid-NXT (Nitazoxanide) Tablets or Oral Suspension, the parent drug, Inflobid-NXT (Nitazoxanide), is not detected in plasma. The pharmacokinetic parameners 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 Inflobid-NXT (Nitazoxanide) Tablet with food to subjects ≥12 years of age

Tizoxanide Tizoxanide Glucuronide
Age C max (µg/mL) T max (hr) AUC t (µg-hr/mL) C max (µg/mL) T max (hr) AUC t (µg-hr/mL)
12 - 17 years 9.1 (6.1) 4.0 (1-4) 39.5 (24.2) 7.3 (1.9) 4.0 (2-8) 46.5 (18.2)
>18 years 10.6 (2.0) 3.0 (2-4) 41.9 (6.0) 10.5 (1.4) 4.5 (4-6) 63.0 (12.3)

*T max is given as a Mean (Range)

Table 3. Mean (+/-SD) plasma pharmacokinetic of tizoxanide and tizoxanide glucuronide parameter values following administration of single dose of Inflobid-NXT (Nitazoxanide) for Oral Suspension with food to subjects ≥1year of age

Tizoxanide Tizoxanide Glucuronide
Age Dose C max (µg/mL) *T max (hr) AUC t (µg-hr/mL) C max (µg/mL) *T max (hr) AUC inf (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)

*T max is given as a Mean (Range)

Multiple dosing:

Following oral administration of a single Inflobid-NXT (Nitazoxanide) Tablet every 12 hours for 7 consecutive days, there was no significant accumulation of Inflobid-NXT (Nitazoxanide) metabolites tizoxanide or tizoxanide glucuronide detected in plasma.

Bioavailability:

Inflobid-NXT (Nitazoxanide) for Oral Suspension is not bioequivalent to Inflobid-NXT (Nitazoxanide) Tablets. The relative bioavailability of the suspension compared to the tablet was 70%.

When Inflobid-NXT (Nitazoxanide) Tablets are administered with food, the AUC t of tizoxanide and tizoxanide glucuronide in plasma is increased almost two-fold and the C max is increased by almost 50%.

When Inflobid-NXT (Nitazoxanide) for Oral Suspension was administered with food, the AUC t of tizoxanide and tizoxanide glucuronide increased by about 45-50% and the C max increased by ≤10%.

Inflobid-NXT (Nitazoxanide) Tablets and Inflobid-NXT (Nitazoxanide) for Oral Suspension were administered with food in clinical trials and hence they are recomended to be administered with food

Distribution

In plasma, more than 99% of tizoxanide is bound to proteins.

Elimination

Metabolism

Following oral administration in humans, Inflobid-NXT (Nitazoxanide) is rapidly hydrolyzed to an active metabolite, tizoxanide (desacetyl-nitazoxanide). 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 Inflobid-NXT (Nitazoxanide) 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 Inflobid-NXT (Nitazoxanide) 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 Inflobid-NXT (Nitazoxanide) for Oral Suspension in pediatric patients 1-11 years of age are provided above in Table 3.

Drug Interaction Studies

In vitro studies have demonstrated that tizoxanide has no significant inhibitory effect on cytochrome P450 enzymes.

12.4 MICROBIOLOGY

Mechanism of Action

The antiprotozoal activity of Inflobid-NXT (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 Inflobid-NXT (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 Inflobid-NXT (Nitazoxanide) exhibits antiprotozoal activity.

Resistance

A potential for development of resistance by C. parvum or G. lamblia to Inflobid-NXT (Nitazoxanide) has not been examined.

Antimicrobial Activity

Inflobid-NXT (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 NONCLINICAL TOXICOLOGY

13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility

Carcinogenesis

Long-term carcinogenicity studies have not been conducted.

Mutagenesis

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

Impairment of Fertility

Inflobid-NXT (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).

14 CLINICAL STUDIES

14.1 Diarrhea Caused by G. lamblia

Diarrhea caused by G. lamblia in adults and adolescents 12 years of age or older:

In a double-blind, controlled trial conducted in Peru and Egypt in adults and adolescents with diarrhea and with one or more enteric symptoms (e.g., abdominal pain, nausea, vomiting, fever, abdominal distention, loss of appetite, flatulence) caused by G. lamblia, a three-day course of treatment with Inflobid-NXT (Nitazoxanide) Tablets administered 500 mg BID was compared with a placebo tablet for 3 days. A third group of patients received open-label Inflobid-NXT (Nitazoxanide) for Oral Suspension administered 500 mg/25 mL of suspension BID for 3 days. A second double-blind, controlled trial (Study 2) conducted in Egypt in adults and adolescents with diarrhea and with or without enteric symptoms (e.g., abdominal colic, abdominal tenderness, abdominal cramps, abdominal distention, fever, bloody stool) caused by G. lamblia compared Inflobid-NXT (Nitazoxanide) Tablets administered 500 mg BID for 3 days to a placebo tablet. For both of these studies, clinical response was evaluated 4 to 7 days following the end of treatment. A clinical response of ‘well’ was defined as ‘no symptoms, no watery stools and no more than 2 soft stools with no hematochezia within the past 24 hours’ or ‘no symptoms and no unformed stools within the past 48 hours.’ The following clinical response rates were obtained:

Table 4. Adult and Adolescent Patients with Diarrhea Caused by G. lamblia

Clinical Response Rates* 4 to 7 Days Post-therapy

% (Number of Successes/Total)


Inflobid-NXT (Nitazoxanide) Tablets


Inflobid-NXT (Nitazoxanide) for Oral Suspension


Placebo Tablets


Study 1


85% (46/54) ¶ §


83% (45/54) ¶ §


44% (12/27)


Study 2


100% (8/8)


-


30% (3/10)


* Includes all patients randomized with G. lamblia as the sole pathogen. Patients failing to complete the studies were treated as failures.

Clinical response rates statistically significantly higher when compared to placebo.

§ The 95% confidence interval of the difference in response rates for the tablet and suspension is (-14%, 17%).

Some patients with ‘well’ clinical responses had G. lamblia cysts in their stool samples 4 to 7 days following the end of treatment. The relevance of stool examination results in these patients is unknown. Patients should be managed based upon clinical response to treatment.

Diarrhea caused by G. lamblia in pediatric patients 1 through 11 years of age:

In a randomized, controlled trial conducted in Peru in 110 pediatric patients with diarrhea and with or without enteric symptoms (e.g., abdominal distention, right iliac fossa tenderness) caused by G. lamblia, a three-day course of treatment with Inflobid-NXT (Nitazoxanide) (100 mg BID in pediatric patients ages 24-47 months, 200 mg BID in pediatric patients ages 4 through 11 years) was compared to a five-day course of treatment with metronidazole (125 mg BID in pediatric patients ages 2 through 5 years, 250 mg BID in pediatric patients ages 6 through 11 years). Clinical response was evaluated 7 to 10 days following initiation of treatment with a ‘well’ response defined as ‘no symptoms, no watery stools and no more than 2 soft stools with no hematochezia within the past 24 hours’ or ‘no symptoms and no unformed stools within the past 48 hours.’ The following clinical cure rates were obtained:

Table 5. Clinical Response Rates in Pediatric Patients 7 to 10 Days Following Initiation of Therapy

Intent-to-Treat and Per Protocol Analyses

% (Number of Successes/Total), [95% Confidence Interval]


Population


Inflobid-NXT (Nitazoxanide) (3 days)


Metronidazole (5 days)


95% CI Diff §


Intent-to-treat analysis


85% (47/55)


80% (44/55 )


[-9%, 20%]


Per protocol analysis


90% (43/48)


83% (39/47 )


[-8%, 21%]


Intent-to-treat analysis includes all patients randomized with patients not completing the study treated as failures.

Per protocol analysis includes only patients who took all of their medication and completed the study. Seven patients in each treatment group missed at least one dose of medication and one in the metronidazole treatment group was lost to follow-up.

§ 95% Confidence Interval on the difference in response rates (nitazoxanide-metronidazole).

Some patients with ‘well’ clinical responses had G. lamblia cysts in their stool samples 4 to 7 days following the end of treatment. The relevance of stool examination results in these patients is unknown. Patients should be managed based upon clinical response to treatment.

14.2 Diarrhea Caused by C. parvum

Diarrhea caused by C. parvum in adults and adolescents 12 years of age or older:

In a double-blind, controlled trial conducted in Egypt in adults and adolescents with diarrhea and with or without enteric symptoms (e.g., abdominal pain/cramps, nausea, vomiting) caused by C. parvum, a three-day course of treatment with Inflobid-NXT (Nitazoxanide) Tablets administered 500 mg BID was compared with a placebo tablet for 3 days. A third group of patients received open-label Inflobid-NXT (Nitazoxanide) for Oral Suspension administered 500 mg/25 mL of suspension BID for 3 days. Clinical response was evaluated 4 to 7 days following the end of treatment. A clinical response of ‘well’ was defined as ‘no symptoms, no watery stools and no more than 2 soft stools within the past 24 hours’ or ‘no symptoms and no unformed stools within the past 48 hours.’ The following clinical response rates were obtained:

Table 6. Clinical Response Rates in Adult and Adolescent Patients 4 to 7 Days Post-therapy

% (Number of Successes/Total)


Inflobid-NXT (Nitazoxanide) Tablets


Inflobid-NXT (Nitazoxanide) Suspension


Placebo Tablets


Intent-to-treat analysis*


96% (27/28) ¶ §


87% (27/31) ¶ §


41% (11/27)


* Includes all patients randomized with C. parvum as the sole pathogen. Patients failing to complete the study were treated as failures.

Clinical response rates statistically significantly higher when compared to placebo.

§ The 95% confidence interval of the difference in response rates for the tablet and suspension is (-10%, 28%).

In a second double-blind, placebo-controlled study of Inflobid-NXT (Nitazoxanide) tablets conducted in Egypt in adults and adolescents with diarrhea and with or without enteric symptoms (e.g., abdominal colic, abdominal cramps, epigastric pain) caused by C. parvum as the sole pathogen, clinical and parasitological response rates showed a similar trend to the first study. Clinical response rates, evaluated 2 to 6 days following the end of treatment, were 71% (15/21) in the Inflobid-NXT (Nitazoxanide) group and 42.9% (9/21) in the placebo group.

Some patients with ‘well’ clinical responses had C. parvum oocysts in their stool samples 4 to 7 days following the end of treatment. The relevance of stool examination results in these patients is unknown. Patients should be managed based upon clinical response to treatment.

Diarrhea caused by C. parvum in pediatric patients 1 through 11 years of age :

In two double-blind, controlled trials in pediatric patients with diarrhea and with or without enteric symptoms (e.g., abdominal distention, colic, left iliac fossa tenderness) caused by C. parvum, a three-day course of treatment with Inflobid-NXT (Nitazoxanide) (100 mg BID in pediatric patients ages 12-47 months, 200 mg BID in pediatric patients ages 4 through 11 years) was compared with a placebo. One study was conducted in Egypt in outpatients ages 1 through 11 years with diarrhea caused by C. parvum. Another study was conducted in Zambia in malnourished pediatric patients admitted to the hospital with diarrhea caused by C. parvum. Clinical response was evaluated 3 to 7 days post-therapy with a ‘well’ response defined as ‘no symptoms, no watery stools and no more than 2 soft stools within the past 24 hours’ or ‘no symptoms and no unformed stools within the past 48 hours.’ The following clinical response rates were obtained:

Table 7. Clinical Response Rates in Pediatric Patients 3 to 7 Days Post-therapy Intent-to-Treat Analyses

% (Number of Successes/Total)


Population


Nitazoxanide*


Placebo


Outpatient Study, age 1 - 11 years


88% (21/24)


38% (9/24)


Inpatient Study, Malnourished , age 12-35 months


56% (14/25)


23% (5/22 )


* Clinical response rates statistically significantly higher compared to placebo.

60% considered severely underweight, 19% moderately underweight, 17% mild underweight.

Some patients with ‘well’ clinical responses had C. parvum oocysts in their stool samples 3 to 7 days following the end of treatment. The relevance of stool examination results in these patients is unknown. Patients should be managed based upon clinical response to treatment.

Diarrhea caused by C. parvum in Acquired Immune Deficiency Syndrome (AIDS) patients :

A double-blind, placebo-controlled trial did not produce clinical cure rates that were significantly different from the placebo control when conducted in hospitalized, severely malnourished pediatric patients with acquired immune deficiency syndrome (AIDS) in Zambia. In this study, the pediatric patients received a three day course of Inflobid-NXT (Nitazoxanide) suspension (100 mg BID in pediatric patients ages 12-47 months, 200 mg BID in pediatric patients ages 4 through 11 years) and were evaluated for response four days after the end of treatment.

16 HOW SUPPLIED

16.1 Inflobid-NXT Tablets (500 mg)

Inflobid-NXT (Nitazoxanide) tablets are round, yellow, film-coated tablets debossed with Inflobid-NXT (Nitazoxanide) on one side and 500 on the other side. Each tablet contains 500 mg of Inflobid-NXT (Nitazoxanide). The tablets are packaged in HDPE bottles of 12 and 30 tablets.

Bottles of 12 tablets NDC 67546-111-14

Bottles of 30 tablets NDC 67546-111-12

Store the tablets at 25 oC (77 oF); excursions permitted to 15 oC-30 oC (59 oF-86 oF).

16.2 Inflobid-NXT for Oral Suspension (100 mg/5 mL)

Inflobid-NXT (Nitazoxanide) for oral suspension is a pink-colored powder formulation that, when reconstituted as directed, contains 100 mg nitazoxanide/5 mL. The reconstituted suspension has a pink color and strawberry flavor. Inflobid-NXT (Nitazoxanide) for oral suspension is available as:

Bottles of 60 mL NDC 27437-106-01

Store the unsuspended powder at 25 oC (77 oF); excursions permitted to 15 oC-30 oC (59 oF-86 oF).

The reconstituted suspension may be stored for 7 days at room temperature, after which any unused portion must be discarded

17 PATIENT COUNSELING INFORMATION

Advise patients and parents/caregivers of pediatric patients taking Inflobid-NXT (Nitazoxanide) Tablets or Inflobid-NXT (Nitazoxanide) for Oral Suspension of the following information:

Dosage and Administration:

Inflobid-NXT (Nitazoxanide) Tablets and Inflobid-NXT (Nitazoxanide) for Oral Suspension should be taken with food.

Inflobid-NXT (Nitazoxanide) 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.

MANUFACTURER INFORMATION

Romark, L.C.

3000 Bayport Drive, Suite 200, Tampa, FL 33607

Telephone: 813-282-8544, Fax: 813-282-1162

E-mail: customer.serviceInflobid-NXT (Nitazoxanide)romark.com

Web site: www.romark.com

Inflobid-NXT (Nitazoxanide) 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.

Inflobid-NXT (Nitazoxanide) is a registered trademark of Romark.

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

Romark Logo Lupin Logo

Ofloxacin:


Pharmacological action

Inflobid-NXT is an antimicrobial agents of broad-spectrum action type from fluoroquinolone group. Bactericidal action of Inflobid-NXT (Ofloxacin) is due to blockage of the enzyme DNA gyrase in bacterial cells. This medication is highly active against most of gram-negative bacteria: Escherichia coli, Salmonella spp., Shigella spp., Proteus spp., Morganella morganii, Klebsiella spp. (including Klebsiella pneumoniae), Enterobacter spp., Serratia spp., Citrobacter spp., Yersinia spp., Providencia spp., Haemophilus influenzae, Neisseria gonorrhoeae, Neisseria meningitidis, Mycoplasma spp., Legionella pneumophila, Acinetobacter spp., and Chlamydia spp.

Inflobid-NXT (Ofloxacin) is active against some gram-positive bacteria (including Staphylococcus spp., Streptococcus spp., especially beta-hemolytic streptococci).

Enterococcus faecalis, Streptococcus pneumoniae, Pseudomonas spp. are moderately susceptible to Inflobid-NXT (Ofloxacin).

Anaerobic bacteria (except Bacteroides ureolyticus) are insensitive to Inflobid-NXT (Ofloxacin).

This drug is resistant to beta-lactamases.

Pharmacokinetics

After oral administration Inflobid-NXT (Ofloxacin) is rapidly and completely absorbed from the gastrointestinal tract. Ingestion has a little effect on the extent of absorption but may slow its speed. Cmax plasma levels reached in 2 hours.

The protein binding is 25%. Inflobid-NXT (Ofloxacin) is widely distributed in tissues and body fluids (organs of urinary system, reproductive organs, prostate, lung, ENT organs, gall bladder, bone, skin).This medicine is excreted in the urine in unchanged form (about 80% in 24 h). A small portion of the active substance (4%) is excreted in the feces. T1/2 is 6 h.

Why is Inflobid-NXT prescribed?

Infectious-inflammatory diseases caused by microorganisms sensitive to Inflobid-NXT (Ofloxacin), including: diseases of the lower respiratory tract, ear, nose, throat, skin, soft tissues, bones, joints, infectious and inflammatory diseases of the abdominal organs (except bacterial enteritis) and pelvic infection, kidney and urinary tract, prostatitis, gonorrhea.

Dosage and administration

Dosing regimen of Inflobid-NXT is individual. Daily dose of 200-800 mg, the multiplicity of application 2 times / day. For patients with impaired renal function (creatinine clearance 20-50 ml / min), the first dose is 200 mg, then 100 mg every 24 hours. When CC is less than 20 ml / min, the first dose is 200 mg, then 100 mg every 48 hours.

Inflobid-NXT (Ofloxacin) side effects, adverse reactions

Digestive system: nausea, vomiting, diarrhea, abdominal pain and cramps, appetite loss, dry mouth, flatulence, gastrointestinal dysfunction, constipation; rarely - liver damage, liver necrosis, jaundice, hepatitis, intestinal perforation, pseudomembranous colitis, bleeding from the gastrointestinal tract, disorders of the oral mucosa, heartburn, elevated liver enzymes, including GGT and LDH, increased serum bilirubin.

CNS and peripheral nervous system: insomnia, dizziness, fatigue, drowsiness, nervousness; rarely - convulsions, anxiety, cognitive changes, depression, abnormal dreams, euphoria, hallucinations, paresthesia, syncope, tremor, confusion, nystagmus, suicidal thoughts or attempts, disorientation, psychotic reactions, paranoia, phobia, agitation, aggressiveness, emotional instability, peripheral neuropathy, ataxia, incoordination, exacerbation of extrapyramidal disorders, speech disorder.

Allergic reactions: skin rash, itching, rarely - angioedema, urticaria, vasculitis, allergic pneumonitis, anaphylactic shock, erythema multiforme, Stevens-Johnson syndrome, erythema nodosum, exfoliative dermatitis, toxic epidermal necrolysis, conjunctivitis.

Sexual system: an itch on the external genitalia in women, vaginitis, vaginal discharge; rare - burning, irritation, pain and rash in the genital area of women, dysmenorrhea, menorrhagia, metrorrhagia, vaginal candidiasis.

Cardiovascular system: rarely - heart failure, edema, hypertension, hypotension, palpitation, vasodilatation, cerebral thrombosis, pulmonary edema, and tachycardia.

Urinary system: rarely - dysuria, urinary frequency, urinary retention, anuria, polyuria formation of kidney stones, kidney failure, nephritis, hematuria, albuminuria, candiduria.

Musculoskeletal system: rarely - arthralgia, myalgia, tendonitis, muscle weakness, exacerbation of myasthenia gravis.

Metabolism: rarely - thirst, weight loss, hyper- or hypoglycemia (especially in patients with diabetes mellitus receiving insulin or oral hypoglycemic agents), acidosis, increase in serum triglycerides, cholesterol, potassium.

Respiratory system: rarely - cough, runny nose, respiratory failure, dyspnea, bronchospasm, stridor.

Sensory organs: rarely - hearing loss, tinnit, diplopia, nystagmus, impaired clarity of vision, disturbances of taste, smell, photophobia.

Dermatological reactions: rarely - photosensitivity, hyperpigmentation, vesicle-bullous eruption.

Hematopoietic system: rarely - anemia, hemorrhage, pancytopenia, agranulocytosis, leukopenia, reversible suppression of bone marrow hematopoiesis, thrombocytopenia, thrombocytopenic purpura, petechiae, ecchymosis, increased prothrombin time.

Other: chest pain, sore throat, fever, body aches, rarely - fatigue, chills, malaise, epistaxis, increased sweating.

Inflobid-NXT contraindications

Pregnancy, lactation, childhood and adolescence to 18 years, increased sensitivity to Inflobid-NXT (Ofloxacin) or other quinolone derivatives.

Using during pregnancy and breastfeeding

Inflobid-NXT is contraindicated during pregnancy and lactation.

Category effects on the fetus by FDA - C.

Special instructions

Use with caution in patients with impaired renal function and liver.

During the period of treatment required to conduct monitoring of blood glucose. Long-term therapy is necessary to periodically monitor the kidney function, liver and peripheral blood picture.

When using Inflobid-NXT (Ofloxacin) it should be ensure adequate hydration of the body, the patient should be subjected to ultraviolet irradiation.

In experimental studies the mutagenic potential was not been identified. Long-term studies to determine the carcinogenicity of Inflobid-NXT (Ofloxacin) were not conducted.

Safety and efficacy in children and adolescents under the age of 18 is not defined.

Use with caution in patients whose activities are connected with the necessity of high concentration of attention and quickness of psychomotor reactions.

Inflobid-NXT drug interactions

Simultaneous administration of Inflobid-NXT (Ofloxacin) with:

  • antacids containing calcium, magnesium or aluminum, with sucralfate, with preparations containing two-and trivalent cations, such as iron, or multivitamins containing zinc it may be in breach absorption of quinolones, resulting in a decrease in their concentration in the body. These medications should not be used for 2 hours before or within 2 hours after taking Inflobid-NXT (Ofloxacin).
  • NSAIDs increases the risk of stimulating effect on the central nervous system and seizures.
  • theophylline may increase its concentration in blood plasma (including the equilibrium state), increasing half-life. This increases the risk of adverse reactions associated with the action of theophylline.
  • beta-lactam antibiotics, aminoglycosides and metronidazole there were observed additive interaction.

    Inflobid-NXT in case of emergency / overdose

    Symptoms: drowsiness, nausea, vomiting, dizziness, disorientation, lethargy, confusion.

    Treatment: gastric lavage, maintenance of vital functions.

  • Inflobid-NXT pharmaceutical active ingredients containing related brand and generic drugs:

    infoActive ingredient is the part of the drug or medicine which is biologically active. This portion of the drug is responsible for the main action of the drug which is intended to cure or reduce the symptom or disease. The other portions of the drug which are inactive are called excipients; there role is to act as vehicle or binder. In contrast to active ingredient, the inactive ingredient's role is not significant in the cure or treatment of the disease. There can be one or more active ingredients in a drug.


    Inflobid-NXT available forms, composition, doses:

    infoForm of the medicine is the form in which the medicine is marketed in the market, for example, a medicine X can be in the form of capsule or the form of chewable tablet or the form of tablet. Sometimes same medicine can be available as injection form. Each medicine cannot be in all forms but can be marketed in 1, 2, or 3 forms which the pharmaceutical company decided based on various background research results.
    Composition is the list of ingredients which combinedly form a medicine. Both active ingredients and inactive ingredients form the composition. The active ingredient gives the desired therapeutic effect whereas the inactive ingredient helps in making the medicine stable.
    Doses are various strengths of the medicine like 10mg, 20mg, 30mg and so on. Each medicine comes in various doses which is decided by the manufacturer, that is, pharmaceutical company. The dose is decided on the severity of the symptom or disease.


    Inflobid-NXT destination | category:

    infoDestination is defined as the organism to which the drug or medicine is targeted. For most of the drugs what we discuss, human is the drug destination.
    Drug category can be defined as major classification of the drug. For example, an antihistaminic or an antipyretic or anti anginal or pain killer, anti-inflammatory or so.


    Inflobid-NXT Anatomical Therapeutic Chemical codes:

    infoA medicine is classified depending on the organ or system it acts [Anatomical], based on what result it gives on what disease, symptom [Therapeutical], based on chemical composition [Chemical]. It is called as ATC code. The code is based on Active ingredients of the medicine. A medicine can have different codes as sometimes it acts on different organs for different indications. Same way, different brands with same active ingredients and same indications can have same ATC code.


    Inflobid-NXT pharmaceutical companies:

    infoPharmaceutical companies are drug manufacturing companies that help in complete development of the drug from the background research to formation, clinical trials, release of the drug into the market and marketing of the drug.
    Researchers are the persons who are responsible for the scientific research and is responsible for all the background clinical trials that resulted in the development of the drug.


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    References

    1. Dailymed."ALINIA (NITAZOXANIDE) TABLET [AVERA MCKENNAN HOSPITAL]". https://dailymed.nlm.nih.gov/dailym... (accessed August 28, 2018).
    2. Dailymed."OFLOXACIN SOLUTION [BAUSCH & LOMB INCORPORATED]". https://dailymed.nlm.nih.gov/dailym... (accessed August 28, 2018).
    3. Dailymed."OFLOXACIN: 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/dailym... (accessed August 28, 2018).

    Frequently asked Questions

    Can i drive or operate heavy machine after consuming Inflobid-NXT?

    Depending on the reaction of the Inflobid-NXT after taken, if you are feeling dizziness, drowsiness or any weakness as a reaction on your body, Then consider Inflobid-NXT not safe to drive or operate heavy machine after consumption. Meaning that, do not drive or operate heavy duty machines after taking the capsule if the capsule has a strange reaction on your body like dizziness, drowsiness. As prescribed by a pharmacist, it is dangerous to take alcohol while taking medicines as it exposed patients to drowsiness and health risk. Please take note of such effect most especially when taking Primosa capsule. It's advisable to consult your doctor on time for a proper recommendation and medical consultations.

    Is Inflobid-NXT addictive or habit forming?

    Medicines are not designed with the mind of creating an addiction or abuse on the health of the users. Addictive Medicine is categorically called Controlled substances by the government. For instance, Schedule H or X in India and schedule II-V in the US are controlled substances.

    Please consult the medicine instruction manual on how to use and ensure it is not a controlled substance.In conclusion, self medication is a killer to your health. Consult your doctor for a proper prescription, recommendation, and guidiance.

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    Review

    sDrugs.com conducted a study on Inflobid-NXT, and the result of the survey is set out below. It is noteworthy that the product of the survey is based on the perception and impressions of the visitors of the website as well as the views of Inflobid-NXT consumers. We, as a result of this, advice that you do not base your therapeutic or medical decisions on this result, but rather consult your certified medical experts for their recommendations.

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    The information was verified by Dr. Arunabha Ray, MD Pharmacology

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