ONDANSETRON HYDROCHLORIDE- ondansetron hydrochloride tablet, film coated

United States - English - NLM (National Library of Medicine)

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Active ingredient:
ONDANSETRON HYDROCHLORIDE (UNII: NMH84OZK2B) (ONDANSETRON - UNII:4AF302ESOS)
Available from:
NuCare Pharmaceuticals,Inc.
Administration route:
ORAL
Prescription type:
PRESCRIPTION DRUG
Therapeutic indications:
Ondansetron tablets are indicated for the prevention of nausea and vomiting associated with: - highly emetogenic cancer chemotherapy, including cisplatin greater than or equal to 50 mg/m 2 - initial and repeat courses of moderately emetogenic cancer chemotherapy - radiotherapy in patients receiving either total body irradiation, single high-dose fraction to the abdomen, or daily fractions to the abdomen Ondansetron tablets are also indicated for the prevention of postoperative nausea and/or vomiting. Ondansetron tablets are contraindicated in patients: - known to have hypersensitivity (e.g., anaphylaxis) to ondansetron or any of the components of the formulation [see Adverse Reactions (6.2)] - receiving concomitant apomorphine due to the risk of profound hypotension and loss of consciousness Risk Summary Available data do not reliably inform the association of ondansetron and adverse fetal outcomes. Published epidemiological studies on the association between ondansetron and fetal outcomes have report
Product summary:
Ondansetron Tablets USP, 4 mg are white to off-white, oval shaped, film-coated tablets debossed with F on one side and 91 on the other side. NDC 68071-5047-3 BOTTLES OF 30 Store at 20° to 25°C (68° to 77°F); excursions permitted to 15° to 30°C (59° to 86°F) [see USP Controlled Room Temperature]. Protect from light.
Authorization status:
Abbreviated New Drug Application
Authorization number:
68071-5047-3

ONDANSETRON HYDROCHLORIDE- ondansetron hydrochloride tablet, film coated

NuCare Pharmaceuticals,Inc.

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HIGHLIGHTS OF PRESCRIBING INFORMATION

These highlights do not include all the information needed to use ONDANSETRON TABLETS safely and

effectively. See full prescribing information for ONDANSETRON TABLETS.

ONDANSETRON tablets, for oral use

Initial U.S. Approval: 1991

INDICATIONS AND USAGE

Ondansetron tablets are a 5-HT

receptor antagonist indicated for the prevention of:

nausea and vomiting associated with highly emetogenic cancer chemotherapy, including cisplatin greater than or equal

to 50 mg/m

nausea and vomiting associated with initial and repeat courses of moderately emetogenic cancer chemotherapy (1)

nausea and vomiting associated with radiotherapy in patients receiving either total body irradiation, single high-dose

fraction to the abdomen, or daily fractions to the abdomen (1)

postoperative nausea and/or vomiting (1)

DOSAGE AND ADMINISTRATION

See full prescribing information for the recommended dosage in adults and pediatrics. (2)

Patients with severe hepatic impairment: do not exceed a total daily dose of 8 mg. (2.2, 8.6)

DOSAGE FORMS AND STRENGTHS

Tablets: 4 mg, 8 mg, and 24 mg ( 3)

CONTRAINDICATIONS

Patients known to have hypersensitivity (e.g., anaphylaxis) to ondansetron or any components of the formulation. (4)

Concomitant use of apomorphine (4)

WARNINGS AND PRECAUTIONS

Hypersensitivity reactions including anaphylaxis and bronchospasm: Discontinue ondansetron if suspected. Monitor

and treat promptly per standard of care until signs and symptoms resolve. (5.1)

QT interval prolongation and Torsade de Pointes: Avoid in patients with congenital long QT syndrome; monitor with

electrocardiograms (ECGs) if concomitant electrolyte abnormalities, cardiac failure or arrhythmias, or use of other QT

prolonging drugs. (5.2)

Serotonin syndrome: Reported with 5-HT

receptor antagonists alone but particularly with concomitant use of

serotonergic drugs. If such symptoms occur, discontinue ondansetron and initiate supportive treatment. If concomitant

use of ondansetron with other serotonergic drugs is clinically warranted, patients should be made aware of a potential

increased risk for serotonin syndrome. (5.3)

Masking of progressive ileus and/or gastric distention following abdominal surgery or chemotherapy-induced nausea

and vomiting: Monitor for decreased bowel activity, particularly in patients with risk factors for gastrointestinal

obstruction. (5.4)

ADVERSE REACTIONS

The most common adverse reactions in adults for the:

prevention of chemotherapy-induced (greater than or equal to 5%) are: headache, malaise/fatigue, constipation,

diarrhea (6.1)

prevention of radiation-induced nausea and vomiting (greater than or equal to 2%) are: headache, constipation, and

diarrhea (6.1)

prevention of postoperative nausea and vomiting (greater than or equal to 9%) are: headache and hypoxia (6.1)

To report SUSPECTED ADVERSE REACTIONS, contact Aurobindo Pharma USA, Inc. at 1-866-850-2876 or

FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

See 17 for PATIENT COUNSELING INFORMATION.

Revised: 6/2018

FULL PRESCRIBING INFORMATION: CONTENTS*

1 INDICATIONS AND USAGE

2 DOSAGE AND ADMINISTRATION

2.1 Dosage

2.2 Dosage in Hepatic Impairment

3 DOSAGE FORMS AND STRENGTHS

4 CONTRAINDICATIONS

5 WARNINGS AND PRECAUTIONS

5.1 Hypersensitivity Reactions

5.2 QT Prolongation

5.3 Serotonin Syndrome

5.4 Masking of Progressive Ileus and Gastric Distension

6 ADVERSE REACTIONS

6.1 Clinical Trials Experience

6.2 Postmarketing Experience

7 DRUG INTERACTIONS

7.1 Serotonergic Drugs

7.2 Drugs Affecting Cytochrome P-450 Enzymes

7.3 Tramadol

7.4 Chemotherapy

7.5 Alfentanil and Atracurium

8 USE IN SPECIFIC POPULATIONS

8.1 Pregnancy

8.2 Lactation

8.4 Pediatric Use

8.5 Geriatric Use

8.6 Hepatic Impairment

8.7 Renal Impairment

9 DRUG ABUSE AND DEPENDENCE

10 OVERDOSAGE

11 DESCRIPTION

12 CLINICAL PHARMACOLOGY

12.1 Mechanism of Action

12.2 Pharmacodynamics

12.3 Pharmacokinetics

13 NONCLINICAL TOXICOLOGY

13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility

14 CLINICAL STUDIES

14.1 Prevention of Chemotherapy-Induced Nausea and Vomiting

14.2 Radiation-Induced Nausea and Vomiting

14.3 Postoperative Nausea and Vomiting

16 HOW SUPPLIED/STORAGE AND HANDLING

17 PATIENT COUNSELING INFORMATION

FULL PRESCRIBING INFORMATION

Sections or subsections omitted from the full prescribing information are not listed.

1 INDICATIONS AND USAGE

Ondansetron tablets are indicated for the prevention of nausea and vomiting associated with:

highly emetogenic cancer chemotherapy, including cisplatin greater than or equal to 50 mg/m

initial and repeat courses of moderately emetogenic cancer chemotherapy

radiotherapy in patients receiving either total body irradiation, single high-dose fraction to the

abdomen, or daily fractions to the abdomen

Ondansetron tablets are also indicated for the prevention of postoperative nausea and/or vomiting.

2 DOSAGE AND ADMINISTRATION

2.1 Dosage

The recommended dosage regimens for adult and pediatric patients are described in Table 1 and Table

2, respectively.

Corresponding doses of ondansetron tablets, ondansetron orally disintegrating tablets and ondansetron

oral solution may be used interchangeably.

Table 1: Adult Recommended Dosage Regimen for Prevention of Nausea and Vomiting

Indication

Dosage Regimen

Highly Emetogenic

Cancer Chemotherapy

A single 24 mg dose administered 30 minutes before the start of single-day

highly emetogenic chemotherapy, including cisplatin greater than or equal to

50 mg/m

Moderately

Emetogenic Cancer

Chemotherapy

administered

minutes

before

start

chemotherapy,

with

subsequent 8 mg dose 8 hours after the first dose.

Then administer 8 mg twice a day (every 12 hours) for 1 to 2 days after

completion of chemotherapy.

Radiotherapy

For total body irradiation: 8 mg administered 1 to 2 hours before each fraction

of radiotherapy each day.

For single high-dose fraction radiotherapy to the abdomen: 8 mg administered

1 to 2 hours before radiotherapy, with subsequent 8 mg doses every 8 hours

after the first dose for 1 to 2 days after completion of radiotherapy.

For daily fractionated radiotherapy to the abdomen: 8 mg administered 1 to 2

hours before radiotherapy, with subsequent 8 mg doses every 8 hours after the

first dose for each day radiotherapy is given.

Postoperative

16 mg administered 1 hour before induction of anesthesia.

Table 2: Pediatric Recommended Dosage Regimen for Prevention of Nausea and Vomiting

Indication

Dosage Regimen

Moderately

Emetogenic

Cancer

Chemotherapy

12 to 17 years of age: 8 mg administered 30 minutes before the start of chemotherapy,

with a subsequent 8 mg dose 8 hours after the first dose.

Then administer 8 mg twice a day (every 12 hours) for 1 to 2 days after completion of

chemotherapy.

4 to 11 years of age: 4 mg administered 30 minutes before the start of chemotherapy,

with a subsequent 4 mg dose 4 and 8 hours after the first dose.

Then

administer

three

times

days

after

completion

chemotherapy.

2.2 Dosage in Hepatic Impairment

In patients with severe hepatic impairment (Child-Pugh score of 10 or greater), do not exceed a total

daily dose of 8 mg [see Use in Specific Populations (8.6), Clinical Pharmacology (12.3)] .

3 DOSAGE FORMS AND STRENGTHS

Ondansetron tablets USP, 4 mg are white to off-white, oval shaped, film-coated tablets debossed

with ‘F’ on one side and ‘91’ on the other side.

Ondansetron tablets USP, 8 mg are yellow colored, oval shaped, film-coated tablets debossed with

‘F’ on one side and ‘92’ on the other side.

Ondansetron tablets USP, 24 mg are pink colored, oval shaped, film-coated tablets debossed with

‘C’ on one side and ‘71’ on the other side.

4 CONTRAINDICATIONS

Ondansetron tablets are contraindicated in patients:

known to have hypersensitivity (e.g., anaphylaxis) to ondansetron or any of the components of the

formulation [see Adverse Reactions (6.2)]

receiving concomitant apomorphine due to the risk of profound hypotension and loss of

consciousness

5 WARNINGS AND PRECAUTIONS

5.1 Hypersensitivity Reactions

Hypersensitivity reactions, including anaphylaxis and bronchospasm, have been reported in patients who

have exhibited hypersensitivity to other selective 5-HT

receptor antagonists. If hypersensitivity

reactions occur, discontinue use of ondansetron; treat promptly per standard of care and monitor until

signs and symptoms resolve [see Contraindications (4)].

5.2 QT Prolongation

Electrocardiogram (ECG) changes including QT interval prolongation have been seen in patients

receiving ondansetron. In addition, postmarketing cases of Torsade de Pointes have been reported in

patients using ondansetron. Avoid ondansetron in patients with congenital long QT syndrome. ECG

monitoring is recommended in patients with electrolyte abnormalities (e.g., hypokalemia or

hypomagnesemia), congestive heart failure, bradyarrhythmias, or patients taking other medicinal

products that lead to QT prolongation [see Clinical Pharmacology (12.2)] .

5.3 Serotonin Syndrome

The development of serotonin syndrome has been reported with 5-HT

receptor antagonists alone.

Most reports have been associated with concomitant use of serotonergic drugs (e.g., selective

serotonin reuptake inhibitors (SSRIs), serotonin and norepinephrine reuptake inhibitors (SNRIs),

monoamine oxidase inhibitors, mirtazapine, fentanyl, lithium, tramadol, and intravenous methylene blue).

Some of the reported cases were fatal. Serotonin syndrome occurring with overdose of ondansetron

alone has also been reported. The majority of reports of serotonin syndrome related to 5-HT

receptor

antagonist use occurred in a post-anesthesia care unit or an infusion center.

Symptoms associated with serotonin syndrome may include the following combination of signs and

symptoms: mental status changes (e.g., agitation, hallucinations, delirium, and coma), autonomic

instability (e.g., tachycardia, labile blood pressure, dizziness, diaphoresis, flushing, hyperthermia),

neuromuscular symptoms (e.g., tremor, rigidity, myoclonus, hyperreflexia, incoordination), seizures,

with or without gastrointestinal symptoms (e.g., nausea, vomiting, diarrhea). Patients should be

monitored for the emergence of serotonin syndrome, especially with concomitant use of ondansetron

and other serotonergic drugs. If symptoms of serotonin syndrome occur, discontinue ondansetron and

initiate supportive treatment. Patients should be informed of the increased risk of serotonin syndrome,

especially if ondansetron is used concomitantly with other serotonergic drugs [see Drug Interactions

(7.1), Overdosage (10)] .

5.4 Masking of Progressive Ileus and Gastric Distension

The use of ondansetron in patients following abdominal surgery or in patients with chemotherapy-

induced nausea and vomiting may mask a progressive ileus and/or gastric distension. Monitor for

decreased bowel activity, particularly in patients with risk factors for gastrointestinal obstruction.

Ondansetron is not a drug that stimulates gastric or intestinal peristalsis. It should not be used instead of

nasogastric suction.

6 ADVERSE REACTIONS

6.1 Clinical Trials Experience

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed

in the clinical trials of a drug cannot be directly compared with rates in the clinical trials of another

drug and may not reflect the rates observed in practice.

The following adverse reactions have been reported in clinical trials of patients treated with

ondansetron, the active ingredient of ondansetron tablets. A causal relationship to therapy with

ondansetron was unclear in many cases.

Prevention of Chemotherapy-Induced Nausea and Vomiting

The most common adverse reactions reported in greater than or equal to 4% of 300 adults receiving a

single 24 mg dose of ondansetron orally in 2 trials for the prevention of nausea and vomiting associated

with highly emetogenic chemotherapy (cisplatin greater than or equal to 50 mg/m

) were: headache

(11%) and diarrhea (4%).

The most common adverse reactions reported in 4 trials in adults for the prevention of nausea and

vomiting associated with moderately emetogenic chemotherapy (primarily cyclophosphamide-based

regimens) are shown in Table 3.

Table 3: Most Common Adverse Reactions in Adults

for the Prevention of Nausea and

Vomiting Associated with Moderately Emetogenic Chemotherapy [Primarily Cyclophosphamide-

based Regimens]

a

Reported in greater than or equal to 5% of patients treated with ondansetron and at a rate that exceeded

placebo.

Adverse Reaction

Ondansetron 8 mg Twice Daily

(n = 242)

Placebo

(n = 262)

Headache

58 (24%)

34 (13%)

Malaise/fatigue

32 (13%)

6 (2%)

Constipation

22 (9%)

1 (<1%)

Diarrhea

15 (6%)

10 (4%)

Less Common Adverse Reactions

Central Nervous System: Extrapyramidal reactions (less than 1% of patients).

Hepatic: Aspartate transaminase (AST) and/or alanine transaminase (ALT) values exceeded twice the

upper limit of normal in approximately 1% to 2% of 723 patients receiving ondansetron and

cyclophosphamide-based chemotherapy in U.S. clinical trials. The increases were transient and did not

appear to be related to dose or duration of therapy. On repeat exposure, similar transient elevations in

transaminase values occurred in some courses, but symptomatic hepatic disease did not occur. The role

of cancer chemotherapy in these biochemical changes is unclear.

Liver failure and death has been reported in cancer patients receiving concurrent medications, including

potentially hepatotoxic cytotoxic chemotherapy and antibiotics. The etiology of the liver failure is

unclear.

Integumentary: Rash (approximately 1% of patients).

Other (less than 2%): Anaphylaxis, bronchospasm, tachycardia, angina, hypokalemia,

electrocardiographic alterations, vascular occlusive events, and grand mal seizures. Except for

bronchospasm and anaphylaxis, the relationship to ondansetron is unclear.

Prevention of Radiation-Induced Nausea and Vomiting

The most common adverse reactions (greater than or equal to 2%) reported in patients receiving

ondansetron and concurrent radiotherapy were similar to those reported in patients receiving

ondansetron and concurrent chemotherapy and were headache, constipation, and diarrhea.

Prevention of Postoperative Nausea and Vomiting

The most common adverse reactions reported in adults in trial(s) of prevention of postoperative nausea

and vomiting are shown in Table 4. In these trial(s), patients were receiving multiple concomitant

perioperative and postoperative medications in both treatment groups.

Table 4: Most Common Adverse Reactions in Adults

for the Prevention of Postoperative

Nausea and Vomiting

Adverse Reaction

Ondansetron 16 mg

as a Single Dose

(n = 550)

Placebo

(n = 531)

Headache

49 (9%)

27 (5%)

Hypoxia

49 (9%)

35 (7%)

Pyrexia

45 (8%)

34 (6%)

Dizziness

36 (7%)

34 (6%)

Gynecological disorder

36 (7%)

33 (6%)

a

Reported in greater than or equal to 5% of patients treated with ondansetron and at a rate that exceeded

placebo.

Anxiety/agitation

33 (6%)

29 (5%)

Urinary retention

28 (5%)

18 (3%)

Pruritus

27 (5%)

20 (4%)

6.2 Postmarketing Experience

The following adverse reactions have been identified during post-approval use of ondansetron.

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.

Cardiovascular

Arrhythmias (including ventricular and supraventricular tachycardia, premature ventricular contractions,

and atrial fibrillation), bradycardia, electrocardiographic alterations (including second-degree heart

block, QT/QTc interval prolongation, and ST segment depression), palpitations, and syncope. Rarely

and predominantly with intravenous ondansetron, transient ECG changes including QT interval

prolongation have been reported.

General

Flushing. Rare cases of hypersensitivity reactions, sometimes severe (e.g., anaphylactic reactions,

angioedema, bronchospasm, shortness of breath, hypotension, laryngeal edema, stridor) have also been

reported.

Laryngospasm, shock, and cardiopulmonary arrest have occurred during allergic reactions in patients

receiving injectable ondansetron.

Hepatobiliary

Liver enzyme abnormalities.

Lower Respiratory

Hiccups.

Neurology

Oculogyric crisis, appearing alone, as well as with other dystonic reactions.

Skin

Urticaria, Stevens-Johnson syndrome, and toxic epidermal necrolysis.

Eye Disorders

Cases of transient blindness, predominantly during intravenous administration, have been reported.

These cases of transient blindness were reported to resolve within a few minutes up to 48 hours.

7 DRUG INTERACTIONS

7.1 Serotonergic Drugs

Serotonin syndrome (including altered mental status, autonomic instability, and neuromuscular symptoms)

has been described following the concomitant use of 5-HT

receptor antagonists and other

serotonergic drugs, including selective serotonin reuptake inhibitors (SSRIs) and serotonin and

noradrenaline reuptake inhibitors (SNRIs). Monitor for the emergence of serotonin syndrome. If

symptoms occur, discontinue ondansetron and initiate supportive treatment [see Warnings and Precautions

(5.3)] .

7.2 Drugs Affecting Cytochrome P-450 Enzymes

Ondansetron does not itself appear to induce or inhibit the cytochrome P-450 drug-metabolizing enzyme

system of the liver [see Clinical Pharmacology (12.3)] . Because ondansetron is metabolized by hepatic

cytochrome P-450 drug-metabolizing enzymes (CYP3A4, CYP2D6, CYP1A2), inducers or inhibitors of

these enzymes may change the clearance and, hence, the half-life of ondansetron. In patients treated with

potent inducers of CYP3A4 (i.e., phenytoin, carbamazepine, and rifampin), the clearance of ondansetron

was significantly increased and ondansetron blood concentrations were decreased. However, on the

basis of available data, no dosage adjustment for ondansetron is recommended for patients on these

drugs [see Clinical Pharmacology (12.3)] .

7.3 Tramadol

Although no pharmacokinetic drug interaction between ondansetron and tramadol has been observed,

data from 2 small trials indicate that when used together, ondansetron may increase patient-controlled

administration of tramadol. Monitor patients to ensure adequate pain control when ondansetron is

administered with tramadol.

7.4 Chemotherapy

Carmustine, etoposide, and cisplatin do not affect the pharmacokinetics of ondansetron.

In a crossover trial in 76 pediatric patients, intravenous ondansetron did not increase systemic

concentrations of high-dose methotrexate.

7.5 Alfentanil and Atracurium

Ondansetron does not alter the respiratory depressant effects produced by alfentanil or the degree of

neuromuscular blockade produced by atracurium. Interactions with general or local anesthetics have not

been studied.

8 USE IN SPECIFIC POPULATIONS

8.1 Pregnancy

Risk Summary

Available data do not reliably inform the association of ondansetron and adverse fetal outcomes.

Published epidemiological studies on the association between ondansetron and fetal outcomes have

reported inconsistent findings and have important methodological limitations hindering interpretation (

see Data). Reproductive studies in rats and rabbits did not show evidence of harm to the fetus when

ondansetron was administered during organogenesis at approximately 6 and 24 times the maximum

recommended human oral dose of 24 mg/day, based on body surface area, respectively ( see Data).

The background risk of major birth defects and miscarriage for the indicated population is unknown. In

the U.S. general population, the estimated background risk of major birth defects and miscarriages in

clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively.

Data

Human Data

Methodological limitations of the epidemiology studies preclude a reliable evaluation of the potential

risk of adverse fetal outcomes with the use of ondansetron in pregnancy.

Two large retrospective cohort studies of ondansetron use in pregnancy have been published. In one

study with 1,349 infants born to women who reported the use of ondansetron or received an ondansetron

prescription in the first trimester, no increased risk for major congenital malformations was seen in

aggregate analysis. In this same study, however, a sub-analysis for specific malformations reported an

association between ondansetron exposure and cardiovascular defect (odds ratio (OR) 1.62 [95% CI

(1.04, 2.14)]) and cardiac septal defect (OR 2.05 [95% CI (1.19, 3.28)]). The second study examined

1970 women who received ondansetron prescription during pregnancy and reported no association

between ondansetron exposure and major congenital malformations, miscarriage or stillbirth, and infants

of low-birth weight or small for gestational age. Important methodological limitations with these

studies include the uncertainty of whether women who filled a prescription actually took the medication,

the concomitant use of other medications or treatments, and other unadjusted confounders that may

account for the study findings.

A case-control study evaluating associations between several common non-cardiac malformations and

multiple antiemetic drugs reported an association between maternal use of ondansetron and isolated cleft

palate (reported adjusted OR = 2.37 [95% CI (1.18, 4.76)]). However, this association could be a chance

finding, given the large number of drugs-birth defect comparisons in this study. It is unknown whether

ondansetron exposure in utero in the cases of cleft palate occurred during the time of palate formation

(the palate is formed between the 6

and 9

weeks of pregnancy) or whether mothers of infants with

cleft palate used other medications or had other risk factors for cleft palate in the offspring. In addition,

no cases of isolated cleft palate were identified in the aforementioned 2 large retrospective cohort

studies. At this time, there is no clear evidence that ondansetron exposure in early pregnancy can cause

cleft palate.

Animal Data

In embryo-fetal development studies in rats and rabbits, pregnant animals received oral doses of

ondansetron up to 15 mg/kg/day and 30 mg/kg/day, respectively, during the period of organogenesis.

With the exception of a slight decrease in maternal body weight gain in the rabbits, there were no

significant effects of ondansetron on the maternal animals or the development of the offspring. At doses

of 15 mg/kg/day in rats and 30 mg/kg/day in rabbits, the maternal exposure margin was approximately 6

and 24 times the maximum recommended human oral dose of 24 mg/day, respectively, based on body

surface area.

In a pre- and postnatal developmental toxicity study, pregnant rats received oral doses of ondansetron up

to 15 mg/kg/day from Day 17 of pregnancy to litter Day 21. With the exception of a slight reduction in

maternal body weight gain, there were no effects upon the pregnant rats and the pre- and postnatal

development of their offspring, including reproductive performance of the mated F1 generation. At a

dose of 15 mg/kg/day in rats, the maternal exposure margin was approximately 6 times the maximum

recommended human oral dose of 24 mg/day, based on body surface area.

8.2 Lactation

Risk Summary

It is not known whether ondansetron is present in human milk. There are no data on the effects of

It is not known whether ondansetron is present in human milk. There are no data on the effects of

ondansetron on the breastfed infant or the effects on milk production. However, it has been demonstrated

that ondansetron is present in the milk of rats.

The developmental and health benefits of breastfeeding should be considered along with the mother’s

clinical need for ondansetron and any potential adverse effects on the breast fed infant from ondansetron

or from the underlying maternal condition.

8.4 Pediatric Use

The safety and effectiveness of orally administered ondansetron have been established in pediatric

patients 4 years and older for the prevention of nausea and vomiting associated with moderately

emetogenic cancer chemotherapy. Use of ondansetron in these age-groups is supported by evidence

from adequate and well- controlled studies of ondansetron in adults with additional data from 3 open-

label, uncontrolled, non-US trials in 182 pediatric patients aged 4 to 18 years with cancer who were

given a variety of cisplatin or noncisplatin regimens [see Dosage and Administration (2.2), Clinical

Studies (14.1)] .

Additional information on the use of ondansetron in pediatric patients may be found in Ondansetron

Injection prescribing information.

The safety and effectiveness of orally administered ondansetron have not been established in pediatric

patients for:

prevention of nausea and vomiting associated with highly emetogenic cancer chemotherapy

prevention of nausea and vomiting associated with radiotherapy

prevention of postoperative nausea and/or vomiting

8.5 Geriatric Use

Of the total number of subjects enrolled in cancer chemotherapy-induced and postoperative nausea and

vomiting in U.S.- and foreign-controlled clinical trials, for which there were subgroup analyses, 938

(19%) were aged 65 years and older.

No overall differences in safety or effectiveness were observed between subjects 65 years of age and

older and younger subjects. A reduction in clearance and increase in elimination half-life were seen in

patients older than 75 years compared with younger subjects [see Clinical Pharmacology (12.3)] . There

were an insufficient number of patients older than 75 years of age and older in the clinical trials to

permit safety or efficacy conclusions in this age-group. Other reported clinical experience has not

identified differences in responses between the elderly and younger patients, but greater sensitivity of

some older individuals cannot be ruled out. No dosage adjustment is needed in elderly patients.

8.6 Hepatic Impairment

No dosage adjustment is needed in patients with mild or moderate hepatic impairment.

In patients with severe hepatic impairment, clearance is reduced and the apparent volume of distribution

is increased, resulting in a significant increase in the half-life of ondansetron. Therefore, do not exceed

a total daily dose of 8 mg in patients with severe hepatic impairment (Child-Pugh score of 10 or

greater) [see Dosage and Administration (2.2), Clinical Pharmacology (12.3)] .

8.7 Renal Impairment

No dosage adjustment is recommended for patients with any degree of renal impairment (mild, moderate,

or severe). There is no experience beyond first-day administration of ondansetron [see Clinical

Pharmacology (12.3)] .

9 DRUG ABUSE AND DEPENDENCE

Animal studies have shown that ondansetron is not discriminated as a benzodiazepine nor does it

substitute for benzodiazepines in direct addiction studies.

10 OVERDOSAGE

There is no specific antidote for ondansetron overdose. Patients should be managed with appropriate

supportive therapy.

In addition to the adverse reactions listed above, the following adverse reactions have been described

in the setting of ondansetron overdose: “Sudden blindness” (amaurosis) of 2 to 3 minutes’ duration plus

severe constipation occurred in one patient that was administered 72 mg of ondansetron intravenously as

a single dose. Hypotension (and faintness) occurred in a patient that took 48 mg of ondansetron tablets.

Following infusion of 32 mg over only a 4-minute period, a vasovagal episode with transient second-

degree heart block was observed. In all instances, the adverse reactions resolved completely.

Pediatric cases consistent with serotonin syndrome have been reported after inadvertent oral overdoses

of ondansetron (exceeding estimated ingestion of 5 mg per kg) in young children. Reported symptoms

included somnolence, agitation, tachycardia, tachypnea, hypertension, flushing, mydriasis, diaphoresis,

myoclonic movements, horizontal nystagmus, hyperreflexia, and seizure. Patients required supportive

care, including intubation in some cases, with complete recovery without sequelae within 1 to 2 days.

11 DESCRIPTION

The active ingredient in ondansetron tablets, USP is ondansetron hydrochloride as the dihydrate, the

racemic form of ondansetron and a selective blocking agent of the serotonin 5-HT

receptor type.

Chemically it is (±) 1, 2, 3, 9-tetrahydro-9-methyl-3-[(2-methyl-1H-imidazol-1-yl)methyl]-4H-carbazol-

4-one, monohydrochloride, dihydrate. It has the following structural formula:

The molecular formula is C

OHCl2H

O, representing a molecular weight of 365.9.

Ondansetron hydrochloride USP (dihydrate) is a white to off-white powder that is soluble in water and

normal saline.

Ondansetron tablets, USP for oral administration contain ondansetron hydrochloride USP (dihydrate)

equivalent to 4 mg or 8 mg or 24 mg of ondansetron. Each film-coated tablet also contains the inactive

ingredients anhydrous lactose, microcrystalline cellulose, pregelatinized starch (maize), magnesium

stearate, triacetin, titanium dioxide and hypromellose. In addition 8 mg tablet also contains iron oxide

yellow and 24 mg tablet also contains iron oxide red.

Meets USP dissolution test 6.

12 CLINICAL PHARMACOLOGY

12.1 Mechanism of Action

Ondansetron is a selective 5-HT

receptor antagonist. While its mechanism of action has not been fully

characterized, ondansetron is not a dopamine-receptor antagonist. Serotonin receptors of the 5-HT

type are present both peripherally on vagal nerve terminals and centrally in the chemoreceptor trigger

zone of the area postrema. It is not certain whether ondansetron’s antiemetic action is mediated centrally,

peripherally, or in both sites. However, cytotoxic chemotherapy appears to be associated with release

of serotonin from the enterochromaffin cells of the small intestine. In humans, urinary 5-

hydroxyindoleacetic acid (5-HIAA) excretion increases after cisplatin administration in parallel with the

onset of emesis. The released serotonin may stimulate the vagal afferents through the 5-HT

receptors

and initiate the vomiting reflex.

12.2 Pharmacodynamics

In healthy subjects, single intravenous doses of 0.15 mg/kg of ondansetron had no effect on esophageal

motility, gastric motility, lower esophageal sphincter pressure, or small intestinal transit time. Multiday

administration of ondansetron has been shown to slow colonic transit in healthy subjects. Ondansetron

has no effect on plasma-prolactin concentrations.

Cardiac Electrophysiology

QTc interval prolongation was studied in a double-blind, single-intravenous dose, placebo- and

positive- controlled, crossover trial in 58 healthy subjects. The maximum mean (95% upper confidence

bound) difference in QTcF from placebo after baseline correction was 19.5 (21.8) milliseconds and 5.6

(7.4) milliseconds after 15- minute intravenous infusions of 32 mg and 8 mg of ondansetron injection,

respectively. A significant exposure- response relationship was identified between ondansetron

concentration and ΔΔQTcF. Using the established exposure-response relationship, 24 mg infused

intravenously over 15 minutes had a mean predicted (95% upper prediction interval) ΔΔQTcF of 14.0

(16.3) milliseconds. In contrast, 16 mg infused intravenously over 15 minutes using the same model had

a mean predicted (95% upper prediction interval) ΔΔQTcF of 9.1 (11.2) milliseconds. In this study, the

8 mg dose infused over 15 minutes did not prolong the QT interval to any clinically relevant extent.

12.3 Pharmacokinetics

Absorption

Ondansetron is absorbed from the gastrointestinal tract and undergoes some first-pass metabolism. Mean

bioavailability in healthy subjects, following administration of a single 8 mg tablet, is approximately

56%.

Ondansetron systemic exposure does not increase proportionately to dose. The area under curve (AUC)

from a 16 mg tablet was 24% greater than predicted from an 8 mg tablet dose. This may reflect some

reduction of first-pass metabolism at higher oral doses.

Food Effects: Bioavailability is also slightly enhanced by the presence of food.

Distribution

Plasma protein binding of ondansetron as measured in vitro was 70% to 76% over the concentration

range of 10 to 500 ng/mL. Circulating drug also distributes into erythrocytes.

Elimination

Metabolism and Excretion: Ondansetron is extensively metabolized in humans, with approximately 5% of

a radiolabeled dose recovered as the parent compound from the urine. The metabolites are observed in

the urine. The primary metabolic pathway is hydroxylation on the indole ring followed by subsequent

glucuronide or sulfate conjugation.

In vitro metabolism studies have shown that ondansetron is a substrate for human hepatic cytochrome P-

450 enzymes, including CYP1A2, CYP2D6, and CYP3A4. In terms of overall ondansetron turnover,

CYP3A4 played the predominant role. Because of the multiplicity of metabolic enzymes capable of

metabolizing ondansetron, it is likely that inhibition or loss of one enzyme (e.g., CYP2D6 genetic

deficiency) will be compensated by others and may result in little change in overall rates of ondansetron

elimination.

Although some nonconjugated metabolites have pharmacologic activity, these are not found in plasma at

concentrations likely to significantly contribute to the biological activity of ondansetron.

Specific Populations

Age: Geriatric Population: A reduction in clearance and increase in elimination half-life are seen in

patients older than 75 years compared to younger subjects [see Use in Specific Populations (8.5)] .

Sex: Gender differences were shown in the disposition of ondansetron given as a single dose. The

extent and rate of absorption are greater in women than men. Slower clearance in women, a smaller

apparent volume of distribution (adjusted for weight), and higher absolute bioavailability resulted in

higher plasma ondansetron concentrations. These higher plasma concentrations may in part be explained

by differences in body weight between men and women. It is not known whether these sex-related

differences were clinically important. More detailed pharmacokinetic information is contained in Tables

5 and 6.

Table 5: Pharmacokinetics in Male and Female Healthy Subjects after a Single Dose of a

Ondansetron 8 mg Tablet

Age-group

(years)

Sex

(M/F)

Mean

Weight

(kg)

N

Peak Plasma

Concentration

(ng/mL)

Time of

Peak Plasma

Concentration

(h)

Mean

Elimination

Half-life

(h)

Systemic

Plasma

Clearance

L/h/kg

Absolute

Bioavailability

18 to 40 M

69.0

62.7

26.2

42.7

0.403

0.354

0.483

0.663

61 to 74 M

77.5

60.2

24.1

52.4

0.384

0.255

0.585

0.643

≥75 M

78.0

67.6

37.0

46.1

0.277

0.249

0.619

0.747

Table 6: Pharmacokinetics in Male and Female Healthy Subjects after a Single Dose of a

Ondansetron 24 mg Tablet

Age-group

(years) Sex

(M/F)

Mean Weight

(kg)

N

Peak Plasma

Concentration

(ng/mL)

Time of Peak

Plasma

Concentration

(h)

Mean Elimination

Half-life

(h)

18 to 43 M

84.1

71.8

125.8

194.4

Renal Impairment: Renal impairment is not expected to significantly influence the total clearance of

ondansetron as renal clearance represents only 5% of the overall clearance. However, the mean plasma

clearance of ondansetron was reduced by about 50% in patients with severe renal impairment (creatinine

clearance less than 30 mL/min). The reduction in clearance was variable and not consistent with an

increase in half-life [see Use in Specific Populations (8.7)] .

Hepatic Impairment: In patients with mild-to-moderate hepatic impairment, clearance is reduced 2-fold

and mean half-life is increased to 11.6 hours compared with 5.7 hours in healthy subjects. In patients

with severe hepatic impairment (Child-Pugh score of 10 or greater), clearance is reduced 2-fold to 3-

fold and apparent volume of distribution is increased with a resultant increase in half-life to 20 hours

[see Dosage and Administration (2.2), Use in Specific Populations (8.6)] .

Drug Interaction Studies

CYP 3A4 Inducers: Ondansetron elimination may be affected by cytochrome P-450 inducers. In a

pharmacokinetic trial of 16 epileptic patients maintained chronically on CYP3A4 inducers,

carbamazepine, or phenytoin, a reduction in AUC, C

, and t

of ondansetron was observed. This

resulted in a significant increase in the clearance of ondansetron. However, this increase is not thought

to be clinically relevant [see Drug Interactions (7.2)] .

Chemotherapeutic Agents: Carmustine, etoposide, and cisplatin do not affect the pharmacokinetics of

ondansetron [see Drug Interactions (7.4)] .

Antacids: Concomitant administration of antacids does not alter the absorption of ondansetron.

13 NONCLINICAL TOXICOLOGY

13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility

Carcinogenic effects were not seen in 2-year studies in rats and mice with oral ondansetron doses up to

10 mg/kg per day and 30 mg/kg per day, respectively (approximately 4 and 6 times the maximum

recommended human oral dose of 24 mg per day, based on body surface area).

Ondansetron was not mutagenic in standard tests for mutagenicity.

Oral administration of ondansetron up to 15 mg/kg per day (approximately 6 times the maximum

recommended human oral dose of 24 mg per day, based on body surface area) did not affect fertility or

general reproductive performance of male and female rats.

14 CLINICAL STUDIES

14.1 Prevention of Chemotherapy-Induced Nausea and Vomiting

Highly Emetogenic Chemotherapy

In 2 randomized, double-blind, monotherapy trials, a single 24 mg oral dose of ondansetron was

superior to a relevant historical placebo control in the prevention of nausea and vomiting associated

with highly emetogenic cancer chemotherapy, including cisplatin greater than or equal to 50 mg/m

Steroid administration was excluded from these clinical trials. More than 90% of patients receiving a

cisplatin dose greater than or equal to 50 mg/m

in the historical-placebo comparator, experienced

vomiting in the absence of antiemetic therapy.

The first trial compared oral doses of ondansetron 24 mg as a single dose, 8 mg every 8 hours for 2

doses, and 32 mg as a single dose in 357 adult cancer patients receiving chemotherapy regimens

containing cisplatin greater than or equal to 50 mg/m

. The first or single dose was administered 30

minutes prior to chemotherapy. A total of 66% of patients in the ondansetron 24 mg once-a-day group,

55% in the ondansetron 8 mg twice-a-day group, and 55% in the ondansetron 32 mg once-a-day group,

completed the 24-hour trial period with 0 emetic episodes and no rescue antiemetic medications, the

primary endpoint of efficacy. Each of the 3 treatment groups was shown to be statistically significantly

superior to a historical placebo control.

In the same trial, 56% of patients receiving a single 24 mg oral dose of ondansetron experienced no

nausea during the 24-hour trial period, compared with 36% of patients in the oral ondansetron 8 mg

twice-a-day group ( P = 0.001) and 50% in the oral ondansetron 32 mg once-a-day group. Dosage

regimens of ondansetron 8 mg twice daily and 32 mg once daily are not recommended for the prevention

of nausea and vomiting associated with highly emetogenic chemotherapy [see Dosage and

Administration (2.1)] .

In a second trial, efficacy of a single 24 mg oral dose of ondansetron for the prevention of nausea and

vomiting associated with highly emetogenic cancer chemotherapy, including cisplatin greater than or

equal to 50 mg/m

, was confirmed.

Moderately Emetogenic Chemotherapy

A randomized, placebo-controlled, double-blind trial was conducted in the U.S. in 67 patients receiving

a cyclophosphamide-based chemotherapy regimen containing doxorubicin. The first 8 mg dose of

ondansetron was administered 30 minutes before the start of chemotherapy, with a subsequent dose 8

hours after the first dose, followed by 8 mg of ondansetron twice a day for 2 days after the completion

of chemotherapy.

Ondansetron was significantly more effective than placebo in preventing vomiting. Treatment response

was based on the total number of emetic episodes over the 3-day trial period. The results of this trial

are summarized in Table 7.

Table 7: Emetic Episodes - Treatment Response in Patients Receiving Moderately Emetogenic

Chemotherapy (Cyclophosphamide-based Regimen Containing Doxorubicin)

Median undefined since at least 50% of the patients were withdrawn or had more than 2 emetic

episodes.

Median undefined since at least 50% of patients did not have any emetic episodes.

Ondansetron

(n = 33)

Placebo

(n = 34)

P Value

Treatment response

0 Emetic episodes

1 to 2 Emetic episodes

More than 2 emetic episodes/withdrawn

20 (61%)

6 (18%)

7 (21%)

2 (6%)

8 (24%)

24 (71%)

<0.001

<0.001

Median number of emetic episodes

Undefined

Median time to first emetic episode (hours)

Undefined

In a double-blind, U.S. trial in 336 patients receiving a cyclophosphamide-based chemotherapy regimen

containing either methotrexate or doxorubicin, ondansetron 8 mg administered twice a day, was as

effective as ondansetron 8 mg administered 3 times a day in preventing nausea and vomiting.

Ondansetron 8 mg three times daily is not a recommended regimen for the treatment of moderately

emetogenic chemotherapy [see Dosage and Administration (2.1)] .

Treatment response was based on the total number of emetic episodes over the 3-day trial period. See

Table 8 for the details of the dosage regimens studied and results of this trial.

Table 8: Emetic Episodes - Treatment Response after Ondansetron Tablets Administered Twice

a Day and Three Times a Day

The first 8 mg dose was administered 30 minutes before the start of emetogenic chemotherapy, with a

subsequent 8 mg dose 8 hours after the first dose, followed by 8 mg administered twice a day for 2

days after the completion of chemotherapy.

The first 8 mg dose was administered 30 minutes before the start of emetogenic chemotherapy, with

subsequent 8 mg doses at 4 hours and 8 hours after the first dose, followed by 8 mg administered 3

times a day for 2 days after the completion of chemotherapy.

Median undefined since at least 50% of patients did not have any emetic episodes.

Visual analog scale assessment: 0 = no nausea, 100 = nausea as bad as it can be.

Ondansetron Tablets

8 mg Twice Daily

(n = 165)

8 mg Three Times a Day

(n = 171)

Treatment response

0 Emetic episodes

1 to 2 Emetic episodes

More than 2 emetic

episodes/withdrawn

101 (61%)

16 (10%)

48 (29%)

99 (58%)

17 (10%)

55 (32%)

Median number of emetic episodes

Median time to first emetic episode

Undefined

Undefined

Median nausea scores (0 to 100)

Re-treatment

In single-arm trials, 148 patients receiving cyclophosphamide-based chemotherapy were re-treated with

ondansetron 8 mg three times daily during subsequent chemotherapy for a total of 396 re-treatment

courses. No emetic episodes occurred in 314 (79%) of the re-treatment courses, and only 1 to 2 emetic

episodes occurred in 43 (11%) of the re-treatment courses.

Pediatric Trials

Three open-label, single-arm, non-U.S. trials have been performed with 182 pediatric patients aged 4 to

18 years with cancer who were given a variety of cisplatin or noncisplatin regimens. The initial dose of

ondansetron injection ranged from 0.04 to 0.87 mg per kg (total dose of 2.16 mg to 12 mg) followed by

the administration of oral doses of ondansetron ranging from 4 to 24 mg daily for 3 days. In these trials,

58% of the 170 evaluable patients had a complete response (no emetic episodes) on Day 1. In 2 trials,

the response rates to ondansetron 4 mg three times a day in patients younger than 12 years was similar to

ondansetron 8 mg three times daily in patients 12 to 18 years. Prevention of emesis in these pediatric

patients was essentially the same as for adults.

14.2 Radiation-Induced Nausea and Vomiting

Total Body Irradiation

In a randomized, placebo-controlled, double-blind trial in 20 patients, 8 mg of ondansetron administered

1.5 hours before each fraction of radiotherapy for 4 days was significantly more effective than placebo

in preventing vomiting induced by total body irradiation. Total body irradiation consisted of 11 fractions

(120 cGy per fraction) over 4 days for a total of 1,320 cGy. Patients received 3 fractions for 3 days,

then 2 fractions on Day 4.

Single High-Dose Fraction Radiotherapy

a

b

In an active-controlled, double-blind trial in 105 patients receiving single high-dose radiotherapy (800

to 1,000 cGy) over an anterior or posterior field size of greater than or equal to 80 cm

to the

abdomen, ondansetron was significantly more effective than metoclopramide with respect to complete

control of emesis (0 emetic episodes). Patients received the first dose of ondansetron (8 mg) or

metoclopramide (10 mg) 1 to 2 hours before radiotherapy. If radiotherapy was given in the morning, 8

mg of ondansetron or 10 mg of metoclopramide was administered in the late afternoon and repeated

again before bedtime. If radiotherapy was given in the afternoon, patients took 8 mg of ondansetron or

10 mg of metoclopramide only once before bedtime. Patients continued the doses of oral medication

three times daily for 3 days.

Daily Fractionated Radiotherapy

In an active-controlled, double-blind trial in 135 patients receiving a 1- to 4-week course of fractionated

radiotherapy (180 cGy doses) over a field size of greater than or equal to 100 cm

to the abdomen,

ondansetron was significantly more effective than prochlorperazine with respect to complete control of

emesis (0 emetic episodes). Patients received the first dose of ondansetron (8 mg) or prochlorperazine

(10 mg) 1 to 2 hours before the first daily radiotherapy fraction, with subsequent 8 mg doses

approximately every 8 hours on each day of radiotherapy.

14.3 Postoperative Nausea and Vomiting

In 2 placebo-controlled, double-blind trials (one conducted in the U.S. and the other outside the U.S.) in

865 females undergoing inpatient surgical procedures, ondansetron 16 mg as a single dose or placebo

was administered one hour before the induction of general balanced anesthesia (barbiturate, opioid,

nitrous oxide, neuromuscular blockade, and supplemental isoflurane or enflurane), ondansetron tablets

was significantly more effective than placebo in preventing postoperative nausea and vomiting.

No trials have been performed in males.

16 HOW SUPPLIED/STORAGE AND HANDLING

Ondansetron Tablets USP, 4 mg are white to off-white, oval shaped, film-coated tablets debossed

with F on one side and 91 on the other side.

NDC 68071-5047-3 BOTTLES OF 30

Store at 20° to 25°C (68° to 77°F); excursions permitted to 15° to 30°C (59° to 86°F) [see USP

Controlled Room Temperature]. Protect from light.

17 PATIENT COUNSELING INFORMATION

QT Prolongation

Inform patients that ondansetron tablets may cause serious cardiac arrhythmias such as QT prolongation.

Instruct patients to tell their healthcare provider right away if they perceive a change in their heart rate,

if they feel lightheaded, or if they have a syncopal episode.

Hypersensitivity Reactions

Inform patients that ondansetron tablets may cause hypersensitivity reactions, some as severe as

anaphylaxis and bronchospasm. Instruct patients to immediately report any signs and symptoms of

hypersensitivity reactions, including fever, chills, rash, or breathing problems to their healthcare

hypersensitivity reactions, including fever, chills, rash, or breathing problems to their healthcare

provider.

Masking of Progressive Ileus and Gastric Distension

Inform patients following abdominal surgery or those with chemotherapy-induced nausea and vomiting

that ondansetron tablets may mask signs and symptoms of bowel obstruction. Instruct patients to

immediately report any signs or symptoms consistent with a potential bowel obstruction to their

healthcare provider.

Drug Interactions

Instruct the patient to report the use of all medications, especially apomorphine, to their healthcare

provider. Concomitant use of apomorphine and ondansetron may cause a significant drop in blood

pressure and loss of consciousness.

Advise patients of the possibility of serotonin syndrome with concomitant use of ondansetron and

another serotonergic agent such as medications to treat depression and migraines. Advise patients to

seek immediate medical attention if the following symptoms occur: changes in mental status,

autonomic instability, neuromuscular symptoms with or without gastrointestinal symptoms.

Distributed by:

Aurobindo Pharma USA, Inc.

279 Princeton-Hightstown Road

East Windsor, NJ 08520

Manufactured by:

Aurobindo Pharma Limited

Hyderabad–500 038, India

Revised: 06/2018

PACKAGE LABEL-PRINCIPAL DISPLAY PANEL -

ONDANSETRON HYDROCHLORIDE

ondansetron hydrochloride tablet, film coated

NuCare Pharmaceuticals,Inc.

Product Information

Product T ype

HUMAN PRESCRIPTION DRUG

Ite m Code (Source )

NDC:6 8 0 71-50 47(NDC:6 58 6 2-18 7)

Route of Administration

ORAL

Active Ingredient/Active Moiety

Ingredient Name

Basis of

Stre ng th

Stre ng th

O NDANSETRO N HYDRO CHLO RIDE (UNII: NMH8 4OZK2B) (ONDANSETRON -

UNII:4AF30 2ESOS)

ONDANSETRON

4 mg

Inactive Ingredients

Ingredient Name

Stre ng th

ANHYDRO US LACTO SE (UNII: 3SY5LH9 PMK)

MICRO CRYSTALLINE CELLULO SE (UNII: OP1R32D6 1U)

STARCH, CO RN (UNII: O8 232NY3SJ)

MAGNESIUM STEARATE (UNII: 70 0 9 7M6 I30 )

TRIACETIN (UNII: XHX3C3X6 73)

TITANIUM DIO XIDE (UNII: 15FIX9 V2JP)

HYPRO MELLO SE 2 9 10 ( 6 MPA.S) (UNII: 0 WZ8 WG20 P6 )

Product Characteristics

Color

white (White to Off-white)

S core

no sco re

S hap e

OVAL

S iz e

6 mm

Flavor

Imprint Code

F;9 1

Contains

Packag ing

#

Item Code

Package Description

Marketing Start Date

Marketing End Date

1

NDC:6 8 0 71-50 47-3

30 in 1 BOTTLE; Type 0 : No t a Co mbinatio n Pro duct

0 9 /0 4/20 19

Marketing Information

Marke ting Cate gory

Application Numbe r or Monograph Citation

Marke ting Start Date

Marke ting End Date

ANDA

ANDA0 78 539

0 7/31/20 0 7

Labeler -

NuCare Pharmaceuticals,Inc. (010632300)

Establishment

Name

Ad d re s s

ID/FEI

Busine ss Ope rations

NuCare Pharmaceuticals,Inc.

0 10 6 3230 0

re la be l(6 8 0 71-50 47)

Revised: 9/2019

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