Drugs Details

Drugs Info of Zofran, Zofran ODT, Zuplenz
Drugs Details
  • Drugs Type  : FDA
  • Date : 17th Jul 2015 07:47 am
  • Brand Name : Zofran, Zofran ODT, Zuplenz
  • Generic Name : ondansetron (oral) (Pronunciation: on DAN se tron)
Descriptions

The active ingredient in ZOFRAN® Tablets and ZOFRAN® Oral Solution is ondansetron hydrochloride (HCl) as the dihydrate, the racemic form of ondansetron and a selective blocking agent of the serotonin 5-HT3 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:

 

ZOFRAN® (ondansetron hydrochloride) Structural Formula Illustration

 

The empirical formula is C18H19N3O•HCl•2H2O, representing a molecular weight of 365.9.

Ondansetron HCl dihydrate is a white to off-white powder that is soluble in water and normal saline.

The active ingredient in ZOFRAN ODT® Orally Disintegrating Tablets is ondansetron base, the racemic form of ondansetron, and a selective blocking agent of the serotonin 5-HT3 receptor type. Chemically it is (±) 1, 2, 3, 9-tetrahydro-9-methyl-3-[(2-methyl-1H-imidazol-1-yl)methyl]-4Hcarbazol- 4-one. It has the following structural formula:

 

ZOFRAN® (ondansetron hydrochloride) Structural Formula Illustration

 

The empirical formula is C18H19N3O representing a molecular weight of 293.4.

Each 4-mg ZOFRAN Tablet for oral administration contains ondansetron HCl dehydrate equivalent to 4 mg of ondansetron. Each 8-mg ZOFRAN Tablet for oral administration contains ondansetron HCl dihydrate equivalent to 8 mg of ondansetron. Each tablet also contains theinactive ingredients lactose, microcrystalline cellulose, pregelatinized starch, hypromellose, magnesium stearate, titanium dioxide, triacetin, and iron oxide yellow (8-mg tablet only).

Each 4-mg ZOFRAN ODT Orally Disintegrating Tablet for oral administration contains 4 mg ondansetron base. Each 8-mg ZOFRAN ODT Orally Disintegrating Tablet for oral administration contains 8 mg ondansetron base. Each ZOFRAN ODT Tablet also contains the inactive ingredients aspartame, gelatin, mannitol, methylparaben sodium, propylparaben sodium, and strawberry flavor. ZOFRAN ODT Tablets are a freeze-dried, orally administered formulation of ondansetron which rapidly disintegrates on the tongue and does not require water to aid dissolution or swallowing.

Each 5 mL of ZOFRAN Oral Solution contains 5 mg of ondansetron HCl dihydrate equivalent to 4 mg of ondansetron. ZOFRAN Oral Solution contains the inactive ingredients citric acid anhydrous, purified water, sodium benzoate, sodium citrate, sorbitol, and strawberry flavor.

 

What are the possible side effects of ondansetron (Zofran, Zofran ODT, Zuplenz)?

Get emergency medical help if you have any of these signs of an allergic reaction: hives; difficulty breathing; swelling of your face, lips, tongue, or throat.

Call your doctor at once if you have a serious side effect such as:

  • blurred vision or temporary vision loss (lasting from only a few minutes to several hours);
  • severe dizziness, feeling short of breath, fainting, fast or pounding heartbeats;
  • slow heart rate, trouble breathing;
  • anxiety, agitation, shivering;
  • feeling like you might pass out; or
  • urinating...

Read All Potential Side Effects and See Pictures of Zofran »

What are the precautions when taking ondansetron hydrochloride (Zofran)?

Before taking ondansetron, tell your doctor or pharmacist if you are allergic to it; or to other serotonin blockers (e.g., granisetron); or if you have any other allergies. This product may contain inactive ingredients, which can cause allergic reactions or other problems. Talk to your pharmacist for more details.

Before using this medication, tell your doctor or pharmacist your medical history, especially of: irregular heartbeat, liver disease, stomach/intestinal problems (e.g., recent abdominal surgery, ileus, swelling).

Ondansetron may cause a condition that affects the heart rhythm (QT prolongation). QT prolongation can infrequently result in serious (rarely fatal) fast/irregular heartbeat and other symptoms (such as severe dizziness, fainting) that need medical...

Read All Potential Precautions of Zofran »

Indications

  1. Prevention of nausea and vomiting associated with highly emetogenic cancerchemotherapy, including cisplatin ≥ 50 mg/m .
  2. Prevention of nausea and vomiting associated with initial and repeat courses of moderately emetogenic cancer chemotherapy.
  3. Prevention of 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.
  4. Prevention of postoperative nausea and/or vomiting. As with other antiemetics, routine prophylaxis is not recommended for patients in whom there is little expectation that nausea and/or vomiting will occur postoperatively. In patients where nausea and/or vomiting must be avoided postoperatively, ZOFRAN Tablets, ZOFRAN ODT Orally Disintegrating Tablets, and ZOFRAN Oral Solution are recommended even where the incidence of postoperative nausea and/or vomiting is low.

Dosage Administration

Instructions For Use/Handling ZOFRAN ODT Orally Disintegrating Tablets

Do not attempt to push ZOFRAN ODT Tablets through the foil backing. With dry hands, PEEL BACK the foil backing of 1 blister and GENTLY remove the tablet. IMMEDIATELY place the ZOFRAN ODT Tablet on top of the tongue where it will dissolve in seconds, then swallow with saliva. Administration with liquid is not necessary.

Prevention Of Nausea And Vomiting Associated With Highly Emetogenic Cancer Chemotherapy

The recommended adult oral dosage of ZOFRAN is 24 mg given as three 8-mg tablets administered 30 minutes before the start of single-day highly emetogenic chemotherapy, including cisplatin ≥ 50 mg/m . Multiday, single-dose administration of a 24 mg dosage has not been studied.

Pediatric Use: There is no experience with the use of a 24 mg dosage in pediatric patients.

Geriatric Use: The dosage recommendation is the same as for the general population.

Prevention Of Nausea And Vomiting Associated With Moderately Emetogenic Cancer Chemotherapy

The recommended adult oral dosage is one 8-mg ZOFRAN Tablet or one 8-mg ZOFRAN ODT Tablet or 10 mL (2 teaspoonfuls equivalent to 8 mg of ondansetron) of ZOFRAN Oral Solution given twice a day. The first dose should be administered 30 minutes before the start of emetogenic chemotherapy, with a subsequent dose 8 hours after the first dose. One 8-mg ZOFRAN Tablet or one 8-mg ZOFRAN ODT Tablet or 10 mL (2 teaspoonfuls equivalent to 8 mg of ondansetron) of ZOFRAN Oral Solution should be administered twice a day (every 12 hours) for 1 to 2 days after completion of chemotherapy.

Pediatric Use: For pediatric patients 12 years of age and older, the dosage is the same as for adults. For pediatric patients 4 through 11 years of age, the dosage is one 4-mg ZOFRAN Tablet or one 4-mg ZOFRAN ODT Tablet or 5 mL (1 teaspoonful equivalent to 4 mg of ondansetron) of ZOFRAN Oral Solution given 3 times a day. The first dose should be administered 30 minutes before the start of emetogenic chemotherapy, with subsequent doses 4 and 8 hours after the first dose. One 4-mg ZOFRAN Tablet or one 4-mg ZOFRAN ODT Tablet or 5 mL (1 teaspoonful equivalent to 4 mg of ondansetron) of ZOFRAN Oral Solution should be administered 3 times a day (every 8 hours) for 1 to 2 days after completion of chemotherapy.

Geriatric Use: The dosage is the same as for the general population.

Prevention Of Nausea And Vomiting Associated With Radiotherapy, Either Total Body Irradiation, Or Single High-Dose Fraction Or Daily Fractions To The Abdomen

The recommended oral dosage is one 8-mg ZOFRAN Tablet or one 8-mg ZOFRAN ODT Tablet or 10 mL (2 teaspoonfuls equivalent to 8 mg of ondansetron) of ZOFRAN Oral Solution given 3 times a day.

For total body irradiation, one 8-mg ZOFRAN Tablet or one 8-mg ZOFRAN ODT Tablet or 10 mL (2 teaspoonfuls equivalent to 8 mg of ondansetron) of ZOFRAN Oral Solution should be administered 1 to 2 hours before each fraction of radiotherapy administered each day.

For single high-dose fraction radiotherapy to the abdomen, one 8-mg ZOFRAN Tablet or one 8-mg ZOFRAN ODT Tablet or 10 mL (2 teaspoonfuls equivalent to 8 mg of ondansetron) of ZOFRAN Oral Solution should be administered 1 to 2 hours before radiotherapy, with subsequent doses every 8 hours after the first dose for 1 to 2 days after completion of radiotherapy.

For daily fractionated radiotherapy to the abdomen, one 8-mg ZOFRAN Tablet or one 8-mg ZOFRAN ODT Tablet or 10 mL (2 teaspoonfuls equivalent to 8 mg of ondansetron) of ZOFRAN Oral Solution should be administered 1 to 2 hours before radiotherapy, with subsequent doses every 8 hours after the first dose for each day radiotherapy is given.

Pediatric Use: There is no experience with the use of ZOFRAN Tablets, ZOFRAN ODT Tablets, or ZOFRAN Oral Solution in the prevention of radiation-induced nausea and vomiting in pediatric patients.

Geriatric Use: The dosage recommendation is the same as for the general population.

Postoperative Nausea and Vomiting

The recommended dosage is 16 mg given as two 8-mg ZOFRAN Tablets or two 8-mg ZOFRAN ODT Tablets or 20 mL (4 teaspoonfuls equivalent to 16 mg of ondansetron) of ZOFRAN Oral Solution 1 hour before induction of anesthesia.

Pediatric Use: There is no experience with the use of ZOFRAN Tablets, ZOFRAN ODT Tablets, or ZOFRAN Oral Solution in the prevention of postoperative nausea and vomiting in pediatric patients.

Geriatric Use: The dosage is the same as for the general population.

Dosage Adjustment For Patients With Impaired Renal Function

The dosage recommendation is the same as for the general population. There is no experience beyond first-day administration of ondansetron.

Dosage Adjustment For Patients With Impaired Hepatic Function

In patients with severe hepatic impairment (Child-Pugh score of 10 or greater), clearance is reduced and apparent volume of distribution is increased with a resultant increase in plasma half-life. In such patients, a total daily dose of 8 mg should not be exceeded.

How Supplied

Instructions For Use/Handling ZOFRAN ODT Orally Disintegrating Tablets

Do not attempt to push ZOFRAN ODT Tablets through the foil backing. With dry hands, PEEL BACK the foil backing of 1 blister and GENTLY remove the tablet. IMMEDIATELY place the ZOFRAN ODT Tablet on top of the tongue where it will dissolve in seconds, then swallow with saliva. Administration with liquid is not necessary.

Prevention Of Nausea And Vomiting Associated With Highly Emetogenic Cancer Chemotherapy

The recommended adult oral dosage of ZOFRAN is 24 mg given as three 8-mg tablets administered 30 minutes before the start of single-day highly emetogenic chemotherapy, including cisplatin ≥ 50 mg/m . Multiday, single-dose administration of a 24 mg dosage has not been studied.

Pediatric Use: There is no experience with the use of a 24 mg dosage in pediatric patients.

Geriatric Use: The dosage recommendation is the same as for the general population.

Prevention Of Nausea And Vomiting Associated With Moderately Emetogenic Cancer Chemotherapy

The recommended adult oral dosage is one 8-mg ZOFRAN Tablet or one 8-mg ZOFRAN ODT Tablet or 10 mL (2 teaspoonfuls equivalent to 8 mg of ondansetron) of ZOFRAN Oral Solution given twice a day. The first dose should be administered 30 minutes before the start of emetogenic chemotherapy, with a subsequent dose 8 hours after the first dose. One 8-mg ZOFRAN Tablet or one 8-mg ZOFRAN ODT Tablet or 10 mL (2 teaspoonfuls equivalent to 8 mg of ondansetron) of ZOFRAN Oral Solution should be administered twice a day (every 12 hours) for 1 to 2 days after completion of chemotherapy.

Pediatric Use: For pediatric patients 12 years of age and older, the dosage is the same as for adults. For pediatric patients 4 through 11 years of age, the dosage is one 4-mg ZOFRAN Tablet or one 4-mg ZOFRAN ODT Tablet or 5 mL (1 teaspoonful equivalent to 4 mg of ondansetron) of ZOFRAN Oral Solution given 3 times a day. The first dose should be administered 30 minutes before the start of emetogenic chemotherapy, with subsequent doses 4 and 8 hours after the first dose. One 4-mg ZOFRAN Tablet or one 4-mg ZOFRAN ODT Tablet or 5 mL (1 teaspoonful equivalent to 4 mg of ondansetron) of ZOFRAN Oral Solution should be administered 3 times a day (every 8 hours) for 1 to 2 days after completion of chemotherapy.

Geriatric Use: The dosage is the same as for the general population.

Prevention Of Nausea And Vomiting Associated With Radiotherapy, Either Total Body Irradiation, Or Single High-Dose Fraction Or Daily Fractions To The Abdomen

The recommended oral dosage is one 8-mg ZOFRAN Tablet or one 8-mg ZOFRAN ODT Tablet or 10 mL (2 teaspoonfuls equivalent to 8 mg of ondansetron) of ZOFRAN Oral Solution given 3 times a day.

For total body irradiation, one 8-mg ZOFRAN Tablet or one 8-mg ZOFRAN ODT Tablet or 10 mL (2 teaspoonfuls equivalent to 8 mg of ondansetron) of ZOFRAN Oral Solution should be administered 1 to 2 hours before each fraction of radiotherapy administered each day.

For single high-dose fraction radiotherapy to the abdomen, one 8-mg ZOFRAN Tablet or one 8-mg ZOFRAN ODT Tablet or 10 mL (2 teaspoonfuls equivalent to 8 mg of ondansetron) of ZOFRAN Oral Solution should be administered 1 to 2 hours before radiotherapy, with subsequent doses every 8 hours after the first dose for 1 to 2 days after completion of radiotherapy.

For daily fractionated radiotherapy to the abdomen, one 8-mg ZOFRAN Tablet or one 8-mg ZOFRAN ODT Tablet or 10 mL (2 teaspoonfuls equivalent to 8 mg of ondansetron) of ZOFRAN Oral Solution should be administered 1 to 2 hours before radiotherapy, with subsequent doses every 8 hours after the first dose for each day radiotherapy is given.

Pediatric Use: There is no experience with the use of ZOFRAN Tablets, ZOFRAN ODT Tablets, or ZOFRAN Oral Solution in the prevention of radiation-induced nausea and vomiting in pediatric patients.

Geriatric Use: The dosage recommendation is the same as for the general population.

Postoperative Nausea and Vomiting

The recommended dosage is 16 mg given as two 8-mg ZOFRAN Tablets or two 8-mg ZOFRAN ODT Tablets or 20 mL (4 teaspoonfuls equivalent to 16 mg of ondansetron) of ZOFRAN Oral Solution 1 hour before induction of anesthesia.

Pediatric Use: There is no experience with the use of ZOFRAN Tablets, ZOFRAN ODT Tablets, or ZOFRAN Oral Solution in the prevention of postoperative nausea and vomiting in pediatric patients.

Geriatric Use: The dosage is the same as for the general population.

Dosage Adjustment For Patients With Impaired Renal Function

The dosage recommendation is the same as for the general population. There is no experience beyond first-day administration of ondansetron.

Dosage Adjustment For Patients With Impaired Hepatic Function

In patients with severe hepatic impairment (Child-Pugh score of 10 or greater), clearance is reduced and apparent volume of distribution is increased with a resultant increase in plasma half-life. In such patients, a total daily dose of 8 mg should not be exceeded.

Side Effects

The following have been reported as adverse events in clinical trials of patients treated with ondansetron, the active ingredient of ZOFRAN. A causal relationship to therapy with ZOFRAN has been unclear in many cases.

Chemotherapy-Induced Nausea and Vomiting

The adverse events in Table 5 have been reported in ≥ 5% of adult patients receiving a single 24-mg ZOFRAN Tablet in 2 trials. These patients were receiving concurrent highly emetogenic cisplatin-based chemotherapy regimens (cisplatin dose ≥ 50 mg/m ).

Table 5: Principal Adverse Events in US Trials: Single Day Therapy With 24-mg ZOFRAN Tablets (Highly Emetogenic Chemotherapy)

EVENT ONDANSETRON 24 MG Q.D. 
N = 300
ONDANSETRON 8 MG B.I.D. 
N = 124
ONDANSETRON 32 MG Q.D. 
N = 117
Headache 33 (11%) 16 (13%) 17 (15%)
Diarrhea 13 (4%) 9 (7%) 3 (3%)

 

The adverse events in Table 6 have been reported in ≥ 5% of adults receiving either 8 mg of ZOFRAN Tablets 2 or 3 times a day for 3 days or placebo in 4 trials. These patients were receiving concurrent moderately emetogenic chemotherapy, primarily cyclophosphamide-based regimens.

Table 6: Principal Adverse Events in US Trials: 3 Days of Therapy With 8-mg ZOFRAN Tablets (Moderately Emetogenic Chemotherapy)

EVENT ONDANSETRON 8 MG B.I.D. 
N = 242
ONDANSETRON 8 MG T.I.D. 
N = 415
PLACEBO 
N = 262
Headache 58 (24%) 113 (27%) 34 (13%)
Malaise/fatigue 32 (13%) 37 (9%) 6 (2%)
Constipation 22 (9%) 26 (6%) 1 ( < 1%)
Diarrhea 15 (6%) 16 (4%) 10 (4%)
Dizziness 13 (5%) 18 (4%) 12 (5%)

 

Central Nervous System: There have been rare reports consistent with, but not diagnostic of, extrapyramidal reactions in patients receiving ondansetron.

Hepatic: In 723 patients receiving cyclophosphamide-based chemotherapy in US clinical trials, AST and/or ALT values have been reported to exceed twice the upper limit of normal in approximately 1% to 2% of patients receiving ZOFRAN Tablets. 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 cannot be clearly determined.

There have been reports of liver failure and death in patients with cancer receiving concurrent medications including potentially hepatotoxic cytotoxic chemotherapy and antibiotics. The etiology of the liver failure is unclear.

Integumentary: Rash has occurred in approximately 1% of patients receiving ondansetron.

Other: Rare cases of anaphylaxis, bronchospasm, tachycardia, angina (chest pain), hypokalemia, electrocardiographic alterations, vascular occlusive events, and grand mal seizures have been reported. Except for bronchospasm and anaphylaxis, the relationship to ZOFRAN was unclear.

Radiation-Induced Nausea and Vomiting

The adverse events reported in patients receiving ZOFRAN Tablets and concurrentradiotherapy were similar to those reported in patients receiving ZOFRAN Tablets and concurrent chemotherapy. The most frequently reported adverse events were headache, constipation, and diarrhea.

Postoperative Nausea and Vomiting

The adverse events in Table 7 have been reported in ≥ 5% of patients receiving ZOFRAN Tablets at a dosage of 16 mg orally in clinical trials. With the exception of headache, rates of these events were not significantly different in the ondansetron and placebo groups. These patients were receiving multiple concomitantperioperative and postoperative medications.

Table 7: Frequency of Adverse Events From Controlled Studies With ZOFRAN Tablets (Postoperative Nausea and Vomiting)

ADVERSE EVENT ONDANSETRON 16 MG
(N = 550)
PLACEBO
(N = 531)
Wound problem 152 (28%) 162 (31%)
Drowsiness/sedation 112 (20%) 122 (23%)
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%)
Anxiety/agitation 33 (6%) 29 (5%)
Bradycardia 32 (6%) 30 (6%)
Shiver(s) 28 (5%) 30 (6%)
Urinary retention 28 (5%) 18 (3%)
Hypotension 27 (5%) 32 (6%)
Pruritus 27 (5%) 20 (4%)

 

Preliminary observations in a small number of subjects suggest a higher incidence of headache when ZOFRAN ODT Orally Disintegrating Tablets are taken with water, when compared to without water.

Observed During Clinical Practice

In addition to adverse events reported from clinical trials, the following events have been identified during post-approval use of oral formulations of ZOFRAN. Because they are reported voluntarily from a population of unknown size, estimates of frequency cannot be made. The events have been chosen for inclusion due to a combination of their seriousness, frequency of reporting, or potential causal connection to ZOFRAN.

Cardiovascular: 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., anaphylaxis/anaphylactoid 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.

Special Senses: 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.

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.

Interactions

Ondansetron does not itself appear to induce or inhibit the cytochrome P-450 drug-metabolizing enzyme system of the liver (see CLINICAL PHARMACOLOGY,Pharmacokinetics). 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. On the basis of available data, no dosage adjustment is recommended for patients on these drugs.

Apomorphine

Based on reports of profound hypotension and loss of consciousness when apomorphine was administered with ondansetron, concomitant use of apomorphine with ondansetron is contraindicated (see CONTRAINDICATIONS).

Phenytoin, Carbamazepine, and Rifampicin

In patients treated with potent inducers of CYP3A4 (i.e., phenytoin, carbamazepine, and rifampicin), 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.1,3

Serotonergic Drugs

Serotonin syndrome (including altered mental status, autonomic instability, andneuromuscular symptoms) has been described following the concomitant use of 5-HT3 receptor antagonists and other serotonergic drugs, including selective serotonin reuptake inhibitors (SSRIs) and serotonin and noradrenaline reuptake inhibitors (SNRIs) (see WARNINGS).

Tramadol

Although no pharmacokinetic drug interaction between ondansetron and tramadol has been observed, data from 2 small studies indicate that ondansetron may be associated with an increase in patient controlled administration of tramadol.4,5

Chemotherapy

Tumor response to chemotherapy in the P-388 mouse leukemia model is not affected by ondansetron. In humans, carmustine, etoposide, and cisplatin do not affect the pharmacokinetics of ondansetron.

In a crossover study in 76 pediatric patients, I.V. ondansetron did not increase blood levels of high-dose methotrexate.

Use In Surgical Patients

The coadministration of ondansetron had no effect on the pharmacokinetics and pharmacodynamics of temazepam.

Warnings

Hypersensitivity reactions have been reported in patients who have exhibited hypersensitivity to other selective 5-HT3 receptor antagonists.

ECG changes including QT interval prolongation has been seen in patients receiving ondansetron. In addition, post-marketing cases of Torsade de Pointes have been reported in patients using ondansetron. Avoid ZOFRAN in patients withcongenital long QT syndrome. ECG monitoring is recommended in patients withelectrolyte abnormalities (e.g., hypokalemia or hypomagnesemia), congestive heart failure, bradyarrhythmias or patients taking other medicinal products that lead to QT prolongation.

The development of serotonin syndrome has been reported with 5-HT3 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 ZOFRAN alone has also been reported. The majority of reports of serotonin syndrome related to 5-HT3 receptor antagonist use occurred in a post-anesthesiacare 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, labileblood pressure, dizziness, diaphoresis, flushing, hyperthermia), neuromuscularsymptoms (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 ZOFRAN and other serotonergic drugs. If symptoms of serotonin syndrome occur, discontinue ZOFRAN and initiate supportive treatment. Patients should be informed of the increased risk of serotonin syndrome, especially if ZOFRAN is used concomitantly with other serotonergic drugs (see PRECAUTIONS and OVERDOSAGE).

Precautions

General

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

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 and 30 mg/kg/day, respectively. Ondansetron was not mutagenic in standard tests for mutagenicity. Oral administration of ondansetron up to 15 mg/kg/day did not affect fertility or general reproductive performance of male and female rats.

Pregnancy

Teratogenic Effects - Pregnancy Category B

Reproduction studies have been performed in pregnant rats and rabbits at daily oral doses up to 15 and 30 mg/kg/day, respectively, and have revealed no evidence of impaired fertility or harm to the fetus due to ondansetron. There are, however, no adequate and well-controlled studies in pregnant women. Because animal reproduction studies are not always predictive of human response, this drug should be used during pregnancy only if clearly needed.

Nursing Mothers

Ondansetron is excreted in the breast milk of rats. It is not known whether ondansetron is excreted in human milk. Because many drugs are excreted in human milk, caution should be exercised when ondansetron is administered to a nursing woman.

Pediatric Use

Little information is available about dosage in pediatric patients 4 years of age or younger (see CLINICAL PHARMACOLOGY and DOSAGE AND ADMINISTRATION sections for use in pediatric patients 4 to 18 years of age).

Geriatric Use

Of the total number of subjects enrolled in cancer chemotherapy-induced and postoperative nausea and vomiting in US- and foreign-controlled clinical trials, for which there were subgroup analyses, 938 were 65 years of age and over. No overall differences in safety or effectiveness were observed between these subjects and younger subjects, and 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. Dosage adjustment is not needed in patients over the age of 65 (see CLINICAL PHARMACOLOGY).

REFERENCES

1. Britto MR, Hussey EK, Mydlow P, et al. Effect of enzyme inducers on ondansetron (OND) metabolism in humans. Clin Pharmacol Ther. 1997;61:228.

2. Pugh RNH, Murray-Lyon IM, Dawson JL, Pietroni MC, Williams R. Transection of the oesophagus for bleeding oesophageal varices. Brit J Surg. 1973;60:646-649.

3. Villikka K, Kivisto KT, Neuvonen PJ. The effect of rifampin on the pharmacokinetics of oral and intravenous ondansetron. Clin Pharmacol Ther. 1999;65:377-381.

4. De Witte JL, Schoenmaekers B, Sessler DI, et al. Anesth Analg. 2001;92:1319-1321.

5. Arcioni R, della Rocca M, Romano R, et al. Anesth Analg. 2002;94:1553-1557.

OverDose

There is no specific antidote for ondansetron overdose. Patients should be managed with appropriate supportive therapy. Individual intravenous doses as large as 150 mg and total daily intravenous doses as large as 252 mg have been inadvertently administered without significant adverse events. These doses are more than 10 times the recommended daily dose.

In addition to the adverse events listed above, the following events have been described in the setting of ondansetron overdose: “Sudden blindness” (amaurosis) of 2 to 3 minutes' duration plus severe constipation occurred in 1 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 ZOFRAN 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 events resolved completely.

Pediatric cases consistent with serotonin syndrome have been reported after inadvertent oral overdoses of ondansetron (exceeding estimated ingestion of 5 mg/kg) in young children. Reported symptoms included somnolence, agitation,tachycardia, tachypnea, hypertension, flushing, mydriasis, diaphoresis, myoclonic movements, horizontal nystagmus, hyperreflexia, and seizure. Patients requiredsupportive care, including intubation in some cases, with complete recovery without sequelae within 1 to 2 days.

ContrainDications

The concomitant use of apomorphine with ondansetron is contraindicated based on reports of profound hypotension and loss of consciousness when apomorphine was administered with ondansetron.

ZOFRAN Tablets, ZOFRAN ODT Orally Disintegrating Tablets, and ZOFRAN Oral Solution are contraindicated for patients known to have hypersensitivity to the drug.

Clinical Pharamacology

Pharmacodynamics

Ondansetron is a selective 5-HT3 receptor antagonist. While its mechanism of action has not been fully characterized, ondansetron is not a dopamine-receptor antagonist. Serotonin receptors of the 5-HT3 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 thesmall intestine. In humans, urinary 5-HIAA (5-hydroxyindoleacetic acid) excretion increases after cisplatin administration in parallel with the onset of emesis. The released serotonin may stimulate the vagal afferents through the 5-HT3 receptors and initiate the vomiting reflex.

In animals, the emetic response to cisplatin can be prevented by pretreatment with an inhibitor of serotonin synthesis, bilateral abdominal vagotomy and greater splanchnic nerve section, or pretreatment with a serotonin 5-HT3 receptor antagonist.

In normal volunteers, 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 normal volunteers. Ondansetron has no effect on plasma prolactin concentrations.

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.

Pharmacokinetics

Ondansetron is well 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. 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. Bioavailability is also slightly enhanced by the presence of food but unaffected by antacids.

Ondansetron is extensively metabolized in humans, with approximately 5% of a radiolabeled dose recovered as the parent compound from the urine. The primary metabolic pathway is hydroxylation on the indole ring followed by subsequent glucuronide or sulfate conjugation. 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.

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. Ondansetron elimination may be affected by cytochrome P-450 inducers. In a pharmacokinetic study of 16 epileptic patients maintained chronically on CYP3A4 inducers, carbamazepine, or phenytoin, reduction in AUC, Cmax, and T½ of ondansetron was observed.1 This resulted in a significant increase in clearance. However, on the basis of available data, no dosage adjustment for ondansetron is recommended (see PRECAUTIONS:DRUG INTERACTIONS).

In humans, carmustine, etoposide, and cisplatin do not affect the pharmacokinetics of ondansetron.

Gender differences were shown in the disposition of ondansetron given as a single dose. The extent and rate of ondansetron's absorption is 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 levels. These higher plasma levels may in part be explained by differences in body weight between men and women. It is not known whether these gender-related differences were clinically important. More detailed pharmacokinetic information is contained in Tables 1 and 2 taken from 2 studies.

Table 1: Pharmacokinetics in Normal Volunteers: Single 8-mg ZOFRAN Tablet Dose

View Enlarged Table

 

Table 2: Pharmacokinetics in Norma Volunteers: Single 24-mg ZOFRAN Tablet Dose

AGE-GROUP (YEARS) MEAN WEIGHT (KG) N PEAK PLASMA CONCENTRATION (NG/ML) TIME OF PEAK PLASMA CONCENTRATION(H) MEAN ELIMINATION HALF-LIFE(H)
18-43 M 84.1 8 125.8 1.9 4.7
F 71.8 8 194.4 1.6 5.8

 

A reduction in clearance and increase in elimination half-life are seen in patients over 75 years of age. In clinical trials with cancer patients, safety and efficacy were similar in patients over 65 years of age and those under 65 years of age; there was an insufficient number of patients over 75 years of age to permit conclusions in that age-group. No dosage adjustment is recommended in the elderly.

In patients with mild-to-moderate hepatic impairment, clearance is reduced 2-fold and mean half-life is increased to 11.6 hours compared to 5.7 hours in normals. In patients with severe hepatic impairment (Child-Pugh2 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. In patients with severe hepatic impairment, a total daily dose of 8 mg should not be exceeded.

Due to the very small contribution (5%) of renal clearance to the overall clearance, renal impairment was not expected to significantly influence the total clearance of ondansetron. However, ondansetron oral mean plasma clearance was reduced by about 50% in patients with severe renal impairment (creatinine clearance < 30 mL/min). This reduction in clearance is variable and was not consistent with an increase in half-life. No reduction in dose or dosing frequency in these patients is warranted.

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.

Four- and 8-mg doses of either ZOFRAN Oral Solution or ZOFRAN ODT Orally Disintegrating Tablets are bioequivalent to corresponding doses of ZOFRAN Tablets and may be used interchangeably. One 24-mg ZOFRAN Tablet is bioequivalent to and interchangeable with three 8-mg ZOFRAN Tablets.

Clinical Trials

Chemotherapy-Induced Nausea and Vomiting

Highly Emetogenic Chemotherapy

In 2 randomized, double-blind, monotherapy trials, a single 24-mg ZOFRAN Tablet was superior to a relevant historical placebo control in the prevention of nausea and vomiting associated with highly emetogenic cancer chemotherapy, including cisplatin ≥ 50 mg/m². Steroid administration was excluded from these clinical trials. More than 90% of patients receiving a cisplatin dose ≥ 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 once a day, 8 mg twice a day, and 32 mg once a day in 357 adult cancer patients receiving chemotherapy regimens containing cisplatin ≥ 50 mg/m . 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 study 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 oral ondansetron 24 mg once a day experienced no nausea during the 24-hour study 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. In a second trial, efficacy of the oral ondansetron 24-mg once-a-day regimen in the prevention of nausea and vomiting associated with highly emetogenic cancer chemotherapy, including cisplatin ≥ 50 mg/m , was confirmed.

Moderately Emetogenic Chemotherapy

In 1 double-blind US study in 67 patients, ZOFRAN Tablets 8 mg administered twice a day were significantly more effective than placebo in preventing vomiting induced by cyclophosphamide-based chemotherapy containing doxorubicin. Treatment response is based on the total number of emetic episodes over the 3-day study period. The results of this study are summarized in Table 3:

Table 3: Emetic Episodes: Treatment Response

  ONDANSETRON 8-MG B.I.D. ZOFRAN TABLETSA PLACEBO P VALUE
Number of patients 33 34  
Treatment response
  0 Emetic episodes 20 (61%) 2 (6%) < 0.001
  1-2 Emetic episodes 6 (18%) 8 (24%)  
  More than 2 emetic episodes/withdrawn 7 (21%) 24 (71%) < 0.001
Median number of emetic episodes 0.0 Undefinedb  
Median time to first emetic episode (h) Undefinedc 6.5  
a The first dose was administered 30 minutes before the start of emetogenic chemotherapy, with a subsequent dose 8 hours after the first dose. An 8-mg ZOFRAN Tablet was administered twice a day for 2 days after completion of chemotherapy.
bMedian undefined since at least 50% of the patients were withdrawn or had more than 2 emetic episodes.
c Median undefined since at least 50% of patients did not have any emetic episodes.

 

In 1 double-blind US study in 336 patients, ZOFRAN Tablets 8 mg administered twice a day were as effective as ZOFRAN Tablets 8 mg administered 3 times a day in preventing nausea and vomiting induced by cyclophosphamide-based chemotherapy containing either methotrexate or doxorubicin. Treatment response is based on the total number of emetic episodes over the 3-day study period. The results of this study are summarized in Table 4:

Table 4: Emetic Episodes: Treatment Response

  ONDANSETRON
8-MG B.I.D. ZOFRAN TABLETSA 8-MG T.I.D. ZOFRAN TABLETSB
Number of patients 165 171
Treatment response    
  0 Emetic episodes 101 (61%) 99 (58%)
  1-2 Emetic episodes 16 (10%) 17 (10%)
  More than 2 emetic episodes/withdrawn 48 (29%) 55 (32%)
Median number of emetic episodes 0.0 0.0
Median time to first emetic episode (h) Undefinedc Undefinedc
Median nausea scores (0-100)d 6 6
a The first dose was administered 30 minutes before the start of emetogenic chemotherapy, with a subsequent dose 8 hours after the first dose. An 8-mg ZOFRAN Tablet was administered twice a day for 2 days after completion of chemotherapy.
b The first dose was administered 30 minutes before the start of emetogenic chemotherapy, with subsequent doses 4 and 8 hours after the first dose. An 8-mg ZOFRAN Tablet was administered 3 times a day for 2 days after completion of chemotherapy.
c Median undefined since at least 50% of patients did not have any emetic episodes.
dVisual analog scale assessment: 0 = no nausea, 100 = nausea as bad as it can be.

 

Re-treatment

In uncontrolled trials, 148 patients receiving cyclophosphamide-based chemotherapy were re-treated with ZOFRAN Tablets 8 mg 3 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 Studies

Three open-label, uncontrolled, foreign trials have been performed with 182 pediatric patients 4 to 18 years old with cancer who were given a variety of cisplatin or noncisplatin regimens. In these foreign trials, the initial dose of ZOFRAN® (ondansetron HCl) Injection ranged from 0.04 to 0.87 mg/kg for a total dose of 2.16 to 12 mg. This was followed by the administration of ZOFRAN Tablets ranging from 4 to 24 mg daily for 3 days. In these studies, 58% of the 170 evaluable patients had a complete response (no emetic episodes) on day 1. Two studies showed the response rates for patients less than 12 years of age who received ZOFRAN Tablets 4 mg 3 times a day to be similar to those in patients 12 to 18 years of age who received ZOFRAN Tablets 8 mg 3 times daily. Thus, prevention of emesis in these pediatric patients was essentially the same as for patients older than 18 years of age. Overall, ZOFRAN Tablets were well tolerated in these pediatric patients.

Radiation-Induced Nausea and Vomiting

Total Body Irradiation

In a randomized, double-blind study in 20 patients, ZOFRAN Tablets (8 mg given 1.5 hours before each fraction of radiotherapy for 4 days) were 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

Ondansetron was significantly more effective than metoclopramide with respect to complete control of emesis (0 emetic episodes) in a double-blind trial in 105 patients receiving single high-dose radiotherapy (800 to 1,000 cGy) over ananterior or posterior field size of ≥ 80 cm to the abdomen. Patients received the first dose of ZOFRAN Tablets (8 mg) or metoclopramide (10 mg) 1 to 2 hours before radiotherapy. If radiotherapy was given in the morning, 2 additional doses of study treatment were given (1 tablet late afternoon and 1 tablet before bedtime). If radiotherapy was given in the afternoon, patients took only 1 further tablet that day before bedtime. Patients continued the oral medication on a 3 times a day basis for 3 days.

Daily Fractionated Radiotherapy

Ondansetron was significantly more effective than prochlorperazine with respect to complete control of emesis (0 emetic episodes) in a double-blind trial in 135 patients receiving a 1- to 4-week course of fractionated radiotherapy (180 cGy doses) over a field size of ≥ 100 cm to the abdomen. Patients received the first dose of ZOFRAN Tablets (8 mg) or prochlorperazine (10 mg) 1 to 2 hours before the patient received the first daily radiotherapy fraction, with 2 subsequent doses on a 3 times a day basis. Patients continued the oral medication on a 3 times a day basis on each day of radiotherapy.

Postoperative Nausea and Vomiting

Surgical patients who received ondansetron 1 hour before the induction of general balanced anesthesia (barbiturate: thiopental, methohexital, or thiamylal; opioid: alfentanil, sufentanil, morphine, or fentanyl; nitrous oxide; neuromuscular blockade: succinylcholine/curare or gallamine and/or vecuronium, pancuronium, or atracurium; and supplemental isoflurane or enflurane) were evaluated in 2 double-blind studies (1 US study, 1 foreign) involving 865 patients. ZOFRAN Tablets (16 mg) were significantly more effective than placebo in preventing postoperative nausea and vomiting.

The study populations in all trials thus far consisted of women undergoing inpatient surgical procedures. No studies have been performed in males. No controlled clinical study comparing ZOFRAN Tablets to ZOFRAN Injection has been performed.

REFERENCES

1. Britto MR, Hussey EK, Mydlow P, et al. Effect of enzyme inducers on ondansetron (OND) metabolism in humans. Clin Pharmacol Ther. 1997;61:228.

Patient Information

Phenylketonurics

Phenylketonuric patients should be informed that ZOFRAN ODT Orally Disintegrating Tablets contain phenylalanine (a component of aspartame). Each 4-mg and 8-mg orally disintegrating tablet contains < 0.03 mg phenylalanine.

Patients should be instructed not to remove ZOFRAN ODT Tablets from the blister until just prior to dosing. The tablet should not be pushed through the foil. With dry hands, the blister backing should be peeled completely off the blister. The tablet should be gently removed and immediately placed on the tongue to dissolve and be swallowed with the saliva. Peelable illustrated stickers are affixed to the product carton that can be provided with the prescription to ensure proper use and handling of the product.

Serotonin Syndrome

Advise patients of the possibility of serotonin syndrome with concomitant use of ZOFRAN 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, neuromuscularsymptoms with or without gastrointestinal symptoms.

Consumer Overview Uses

IMPORTANT: HOW TO USE THIS INFORMATION: This is a summary and does NOT have all possible information about this product. This information does not assure that this product is safe, effective, or appropriate for you. This information is not individual medical advice and does not substitute for the advice of your health care professional. Always ask your health care professional for complete information about this product and your specific health needs.

 

ONDANSETRON - ORAL

 

(on-DAN-se-tron)

 

COMMON BRAND NAME(S): Zofran

 

USES: This medication is used alone or with other medications to prevent nausea and vomiting caused by cancer drug treatment (chemotherapy) and radiation therapy. It is also used to prevent and treat nausea and vomiting after surgery. It works by blocking one of the body's natural substances (serotonin) that causes vomiting.

 

HOW TO USE: To prevent nausea from chemotherapy, take this medication by mouth usually within 30 minutes before treatment begins. To prevent nausea from radiation treatment, take this medication by mouth 1 to 2 hours before the start of your treatment. To prevent nausea after surgery, take ondansetron by mouth 1 hour before the start of surgery. This medication may be taken with or without food. However, your doctor may tell you not to eat before chemotherapy, radiation, or surgery.

If you are using the liquid form of this medication, use a special measuring spoon or device to measure out your prescribed dose. Do not use a household spoon because you may not get the correct dose.

Take any other doses as directed by your doctor. Ondansetron may be taken up to 3 times a day for 1 to 2 days after your chemotherapy or radiation treatment is finished. If you are taking this medication on a prescribed schedule, take it regularly in order to get the most benefit from it. To help you remember, take it at the same times each day.

Dosage is based on your medical condition and response to therapy. The dosage for children may also be based on age and weight. The usual maximum dose in patients with severe liver problems is 8 milligrams in 24 hours. Take this medication exactly as directed. Do not take more medication or take it more often than prescribed. Ask your doctor or pharmacist if you have questions.

Inform your doctor if your condition does not improve or if it worsens.

Consumer Overview Side Effect

SIDE EFFECTS: Headache, lightheadedness, dizziness, drowsiness, tiredness, or constipation may occur. If these effects persist or worsen, notify your doctor promptly.

Remember that your doctor has prescribed this medication because he or she has judged that the benefit to you is greater than the risk of side effects. Many people using this medication do not have serious side effects.

Tell your doctor immediately if any of these unlikely but serious side effects occur: stomach pain, muscle spasm/stiffness, vision changes (e.g., temporary loss of vision, blurred vision).

Get medical help right away if any of these rare but very serious side effects occur: chest pain, slow/fast/irregular heartbeat, severe dizziness, fainting.

This medication may increase serotonin and rarely cause a very serious condition called serotonin syndrome/toxicity. The risk increases if you are also taking other drugs that increase serotonin, so tell your doctor or pharmacist of all the drugs you take (see Drug Interactions section). Get medical help right away if you develop some of the following symptoms: fast heartbeat, hallucinations, loss of coordination, severe dizziness, severe nausea/vomiting/diarrhea, twitching muscles, unexplained fever, unusual agitation/restlessness.

A very serious allergic reaction to this drug is unlikely, but stop taking this medication and seek immediate medical attention if it occurs. Symptoms of a serious allergic reaction include: rash, itching/swelling (especially of the face/tongue/throat), severe dizziness, trouble breathing.

This is not a complete list of possible side effects. If you notice other effects not listed above, contact your doctor or pharmacist.

In the US -

Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

In Canada - Call your doctor for medical advice about side effects. You may report side effects to Health Canada at 1-866-234-2345.

 

Read the Zofran (ondansetron hydrochloride) Side Effects Center for a complete guide to possible side effects

Learn More »
 

PRECAUTIONS: Before taking ondansetron, tell your doctor or pharmacist if you are allergic to it; or to other serotonin blockers (e.g., granisetron); or if you have any other allergies. This product may contain inactive ingredients, which can cause allergic reactions or other problems. Talk to your pharmacist for more details.

Before using this medication, tell your doctor or pharmacist your medical history, especially of: irregular heartbeat, liver disease, stomach/intestinal problems (e.g., recent abdominal surgery, ileus, swelling).

Ondansetron may cause a condition that affects the heart rhythm (QT prolongation). QT prolongation can infrequently result in serious (rarely fatal) fast/irregular heartbeat and other symptoms (such as severe dizziness, fainting) that need medical attention right away.

The risk of QT prolongation may be increased if you have certain medical conditions or are taking other drugs that may cause QT prolongation. Before using ondansetron, tell your doctor or pharmacist of all the drugs you take and if you have any of the following conditions: certain heart problems (heart failure, slow heartbeat, QT prolongation in the EKG), family history of certain heart problems (QT prolongation in the EKG, sudden cardiac death).

Low levels of potassium or magnesium in the blood may also increase your risk of QT prolongation. This risk may increase if you use certain drugs (such as diuretics/"water pills") or if you have conditions such as severe sweating, diarrhea, or vomiting. Talk to your doctor about using ondansetron safely.

This drug may make you dizzy or drowsy. Do not drive, use machinery, or do any activity that requires alertness until you are sure you can perform such activities safely. Limit alcoholic beverages.

To minimize dizziness and lightheadedness, get up slowly when rising from a sitting or lying position.

Older adults may be more sensitive to the side effects of this drug, especially QT prolongation (see above).

This medication should be used only when clearly needed during pregnancy. Discuss the risks and benefits with your doctor.

It is not known whether this drug passes into breast milk. Consult your doctor before breast-feeding.

Consumer Overview Missed Dose

DRUG INTERACTIONS: Your healthcare professionals (e.g., doctor or pharmacist) may already be aware of any possible drug interactions and may be monitoring you for them. Do not start, stop or change the dosage of any medicine before checking with them first.

This drug should not be used with the following medication because a very serious interaction may occur: apomorphine.

If you are currently using the medication listed above, tell your doctor or pharmacist before starting ondansetron.

Before using this medication, tell your doctor of all nonprescription and prescription medication you may use, especially of: tramadol.

Ask your doctor or pharmacist for more details.

Many drugs besides ondansetron may affect the heart rhythm (QT prolongation), including dofetilide, pimozide, procainamide, amiodarone, quinidine, sotalol, macrolide antibiotics (such as erythromycin), among others. Therefore, before using ondansetron, report all medications you are currently using to your doctor or pharmacist.

The risk of serotonin syndrome/toxicity increases if you are also taking other drugs that increase serotonin. Examples include street drugs such as MDMA/"ecstasy," St. John's wort, certain antidepressants (including SSRIs such as fluoxetine/paroxetine, SNRIs such as duloxetine/venlafaxine), among others. The risk of serotonin syndrome/toxicity may be more likely when you start or increase the dose of these drugs.

This document does not contain all possible interactions. Therefore, before using this product, tell your doctor or pharmacist of all the products you use. Keep a list of all your medications with you, and share the list with your doctor and pharmacist.

 

OVERDOSE: If overdose is suspected, contact a poison control center or emergency room immediately. US residents can call their local poison control center at 1-800-222-1222. Canada residents can call a provincial poison control center.

 

NOTES: Do not share this product with others.

Laboratory and/or medical tests (such as EKG) should be performed periodically to monitor your progress or check for side effects. Consult your doctor for more details.

 

MISSED DOSE: Try to take each dose at the scheduled time. If you miss a dose, take it as soon as remembered unless it is near the time for the next dose. In that case, skip the missed dose and resume your usual dosing schedule. Do not double the dose to catch up.

 

STORAGE: Tablets may be stored in the refrigerator or at room temperature between 36-86 degrees F (2-30 degrees C). Store the liquid form at room temperature between 59-86 degrees F (15-30 degrees C).

Store away from light and moisture. Do not store in the bathroom. Keep all medicines out of reach of children and pets.

Do not flush medications down the toilet or pour them into a drain unless instructed to do so. Properly discard this product when it is expired or no longer needed. Consult your pharmacist or local waste disposal company for more details about how to safely discard your product.

 

Information last revised November 2014. Copyright(c) 2014 First Databank, Inc.

Patient Detailed Side Effect

Brand Names: Zofran, Zofran ODT, Zuplenz

Generic Name: ondansetron (oral) (Pronunciation: on DAN se tron)

  • What is ondansetron (Zofran)?
  • What are the possible side effects of ondansetron (Zofran)?
  • What is the most important information I should know about ondansetron (Zofran)?
  • What should I discuss with my health care provider before taking ondansetron (Zofran)?
  • How should I take ondansetron (Zofran)?
  • What happens if I miss a dose (Zofran)?
  • What happens if I overdose (Zofran)?
  • What should I avoid while taking ondansetron (Zofran)?
  • What other drugs will affect ondansetron (Zofran)?
  • Where can I get more information?

What is ondansetron (Zofran)?

 

Ondansetron blocks the actions of chemicals in the body that can trigger nausea and vomiting.

Ondansetron is used to prevent nausea and vomiting that may be caused by surgery or by medicine to treat cancer (chemotherapy or radiation).

Ondansetron may be used for purposes not listed in this medication guide.

Ondansetron 8 mg ODT-MYL

round, white, imprinted with M, 734

What are the possible side effects of ondansetron (Zofran)?

 

Get emergency medical help if you have any of these signs of an allergic reaction:hives; difficulty breathing; swelling of your face, lips, tongue, or throat.

Call your doctor at once if you have a serious side effect such as:

  • blurred vision or temporary vision loss (lasting from only a few minutes to several hours);
  • severe dizziness, feeling short of breath, fainting, fast or pounding heartbeats;
  • slow heart rate, trouble breathing;
  • anxiety, agitation, shivering;
  • feeling like you might pass out; or
  • urinating less than usual or not at all.

Less serious side effects may include:

  • diarrhea or constipation;
  • weakness or tired feeling;
  • fever;
  • headache; or
  • dizziness, drowsiness.

This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

Read the Zofran (ondansetron hydrochloride) Side Effects Center for a complete guide to possible side effects

Learn More »
 

What is the most important information I should know about ondansetron (Zofran)?

 

You should not use this medication if you are allergic to ondansetron or to similar medicines such as dolasetron (Anzemet), granisetron (Kytril), or palonosetron (Aloxi). Do not take ondansetron if you are also using apomorphine (Apokyn).

Before taking ondansetron, tell your doctor if you have liver disease, or a personal or family history of Long QT syndrome.

Ondansetron orally disintegrating tablets may contain phenylalanine. Tell your doctor if you have phenylketonuria (PKU).

The serious side effects of this medication include blurred vision or temporary vision loss (lasting from only a few minutes to several hours), slow heart rate, trouble breathing, anxiety, agitation, shivering, feeling like you might pass out, and urinating less than usual or not at all. Stop taking ondansetron and call your doctor at once if you have any of these side effects.

Ondansetron may impair your thinking or reactions. Be careful if you drive or do anything that requires you to be alert.

Patient Detailed How Take

What should I discuss with my health care provider before taking ondansetron (Zofran)?

 

You should not use this medication if you are allergic to ondansetron, to similar medicines such as dolasetron (Anzemet), granisetron (Kytril), or palonosetron (Aloxi). Do not take ondansetron if you are also using apomorphine (Apokyn).

To make sure you can safely take ondansetron, tell your doctor if you have any of these other conditions:

  • liver disease;
  • heart disease, congestive heart failure, a heart rhythm disorder;
  • an electrolyte imbalance (such as low levels of potassium or magnesium in your blood); or
  • a personal or family history of Long QT syndrome.

FDA pregnancy category B. This medication is not expected to be harmful to an unborn baby. Tell your doctor if you are pregnant or plan to become pregnant during treatment.

It is not known whether ondansetron passes into breast milk or if it could harm a nursing baby. Do not use this medication without telling your doctor if you are breast-feeding a baby.

ondansetron should not be given to a child younger than 4 years old.

Ondansetron orally disintegrating tablets may contain phenylalanine. Tell your doctor if you have phenylketonuria (PKU).

How should I take ondansetron (Zofran)?

 

Take exactly as prescribed by your doctor. Do not take in larger or smaller amounts or for longer than recommended. Follow the directions on your prescription label.

Ondansetron can be taken with or without food.

Take the ondansetron regular tablet with a full glass of water.

To take ondansetron orally disintegrating tablet (Zofran ODT):

  • Keep the tablet in its blister pack until you are ready to take the medicine. Open the package and peel back the foil from the tablet blister. Do not push a tablet through the foil or you may damage the tablet.
  • Using dry hands, remove the tablet and place it in your mouth. It will begin to dissolve right away.
  • Do not swallow the tablet whole. Allow it to dissolve in your mouth without chewing.
  • Swallow several times as the tablet dissolves. If desired, you may drink liquid to help swallow the dissolved tablet.

To use ondansetron oral soluble film (strip) (Zuplenz):

  • Keep the strip in the foil pouch until you are ready to use the medicine.
  • Using dry hands, remove the strip and place it on your tongue. It will begin to dissolve right away.
  • Do not swallow the strip whole. Allow it to dissolve in your mouth without chewing.
  • Swallow several times after the strip dissolves. If desired, you may drink liquid to help swallow the dissolved strip.
  • Wash your hands after using Zuplenz.

Measure the liquid form of ondansetron with a special dose-measuring spoon or cup, not a regular table spoon. If you do not have a dose-measuring device, ask your pharmacist for one.

Your heart function may need to be tested with an electrocardiogram (ECG or EKG) on a regular basis. Do not miss any follow-up visits to your doctor.

Store at room temperature away from moisture and heat.

Patient Detailed Avoid Taking

What happens if I miss a dose (Zofran)?

 

Take the missed dose as soon as you remember. Skip the missed dose if it is almost time for your next scheduled dose.Do not take extra medicine to make up the missed dose.

What happens if I overdose (Zofran)?

 

Seek emergency medical attention or call the Poison Help line at 1-800-222-1222.

Overdose symptoms may include sudden loss of vision, severe constipation, feeling light-headed, or fainting.

What should I avoid while taking ondansetron (Zofran)?

 

Ondansetron may impair your thinking or reactions. Be careful if you drive or do anything that requires you to be alert.

What other drugs will affect ondansetron (Zofran)?

 

Tell your doctor about all other medicines you use, especially:

  • arsenic trioxide (Trisenox);
  • tacrolimus (Prograf);
  • tramadol (Ultram, Ultracet);
  • an antibiotic such as clarithromycin (Biaxin), erythromycin (E.E.S., EryPed, Ery-Tab, Erythrocin, Pediazole), levofloxacin (Levaquin), moxifloxacin (Avelox), pentamidine (NebuPent, Pentam), or rifampin (Rifadin, Rimactane, Rifater);
  • an antidepressant such as amitriptylline (Elavil, Vanatrip, Limbitrol), clomipramine (Anafranil), or desipramine (Norpramin);
  • anti-malaria medications such as chloroquine (Aralen) or mefloquine (Lariam);
  • heart rhythm medicine such as amiodarone (Cordarone, Pacerone), dofetilide (Tikosyn), disopyramide (Norpace), dronedarone (Multaq), ibutilide (Corvert), procainamide (Procan, Pronestyl), propafenone (Rythmol), quinidine (Quin-G), or sotalol (Betapace);
  • medicine to prevent or treat nausea and vomiting such as dolasetron (Anzemet), droperidol (Inapsine), or ondansetron (Zofran);
  • medicines to treat psychiatric disorders, such as chlorpromazine (Thorazine), clozapine (FazaClo, Clozaril), haloperidol (Haldol), pimozide (Orap), thioridazine (Mellaril), or ziprasidone (Geodon);
  • migraine headache medicine such as sumatriptan (Imitrex, Treximet) or zolmitriptan (Zomig);
  • narcotic medication such as methadone (Methadose, Diskets, Dolophine); or
  • seizure medication such as carbamazepine (Carbatrol, Tegretol), phenytoin (Dilantin), or phenobarbital (Luminal).

This list is not complete and other drugs may interact with ondansetron. Tell your doctor about all medications you use. This includes prescription, over-the-counter, vitamin, and herbal products. Do not start a new medication without telling your doctor.

Where can I get more information?

 

Your pharmacist can provide more information about ondansetron.


Remember, keep this and all other medicines out of the reach of children, never share your medicines with others, and use this medication only for the indication prescribed.

Every effort has been made to ensure that the information provided by Cerner Multum, Inc. ('Multum') is accurate, up-to-date, and complete, but no guarantee is made to that effect. Drug information contained herein may be time sensitive. Multum information has been compiled for use by healthcare practitioners and consumers in the United States and therefore Multum does not warrant that uses outside of the United States are appropriate, unless specifically indicated otherwise. Multum's drug information does not endorse drugs, diagnose patients or recommend therapy. Multum's drug information is an informational resource designed to assist licensed healthcare practitioners in caring for their patients and/or to serve consumers viewing this service as a supplement to, and not a substitute for, the expertise, skill, knowledge and judgment of healthcare practitioners. The absence of a warning for a given drug or drug combination in no way should be construed to indicate that the drug or drug combination is safe, effective or appropriate for any given patient. Multum does not assume any responsibility for any aspect of healthcare administered with the aid of information Multum provides. The information contained herein is not intended to cover all possible uses, directions, precautions, warnings, drug interactions, allergic reactions, or adverse effects. If you have questions about the drugs you are taking, check with your doctor, nurse or pharmacist.

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