Ondansetron

Ondansetron can cause serious side effects. See "Drug Precautions" section.

Common side effects include:

• headache
• tiredness
• constipation
• diarrhea
• dizziness

This is not a complete list of ondansetron side effects. Ask your doctor or pharmacist for more information.

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

Serious side effects have been reported with ondansetron including:

• hypotension. Ondansetron and apomorphine (Apokyn) should not be taken at the same time as there is a risk of dangerously low blood pressure and loss of consciousness.
• severe allergic reactions. Hypersensitivity (allergic) reactions have been reported in patients who are allergic to other selective 5-HT3 receptor antagonists.
• changes in heart rhythm. ECG changes including QT interval prolongation has been seen in patients receiving ondansetron. 
• masking symptoms of intestinal blockage. Using ondansetron after abdominal surgery or chemotherapy may mask the symptoms of an intestinal blockage (abdominal ileus). 

Do not take ondansetron if you:

• are allergic to ondansetron or any ingredient in it
• are taking apomorphine (Apokyn)
• have long QT syndrome (condition that increases the risk of developing an irregular heartbeat that may cause fainting or sudden death)

Ondansetron can cause drowsiness. Do not drive or operate heavy machinery until you know how ondansetron affects you.

Keep this and all medications out of the reach of children.

You should not use ondansetron if you are also using apomorphine (Apokyn).

Follow all directions on your prescription label. Do not take this medicine in larger or smaller amounts or for longer than recommended.

Ondansetron can be taken with or without food.

The first dose of ondansetron is usually taken before the start of your surgery, chemotherapy, or radiation treatment. Follow your doctor's dosing instructions very carefully.

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

To take the orally disintegrating tablet (Zofran ODT):

• Keep the tablet in its blister pack until you are ready to take it. Open the package and peel back the foil. Do not push a tablet through the foil or you may damage the tablet.

• Use dry hands to remove the tablet and place it in your mouth.

• Do not swallow the tablet whole. Allow it to dissolve in your mouth without chewing.

• Swallow several times as the tablet dissolves.

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 liquid medicine with the dosing syringe provided, or with a special dose-measuring spoon or medicine cup. If you do not have a dose-measuring device, ask your pharmacist for one.

Store at room temperature away from moisture, heat, and light. Store liquid medicine in an upright position.

Usual Adult Dose for Nausea/Vomiting -- Chemotherapy Induced:

Oral:
Highly Emetogenic Cancer Chemotherapy (HEC):
-Recommended dose: 24 mg orally 30 minutes before the start of single-day HEC (including cisplatin doses of 50 mg/m2 or greater)

Moderately Emetogenic Cancer Chemotherapy (MEC):
-Recommended dose: 8 mg orally twice a day, with the first dose administered 30 minutes before the start of chemotherapy and the subsequent dose 8 hours later; then 8 mg orally 2 times a day (every 12 hours) for 1 to 2 days after the completion of chemotherapy

Parenteral:
-Recommended dose: 0.15 mg/kg IV, with the first dose (infused over 15 minutes) 30 minutes before the start of emetogenic chemotherapy and subsequent doses given 4 and 8 hours after the first dose.
-Maximum dose: 16 mg per dose

Comments:
-Multi-day, single-dose administration of 24 mg orally for HEC has not been studied.
-The injection formulation should be diluted prior to IV administration.

Uses:
-Prevention of nausea and vomiting associated with HEC or MEC
-Prevention of nausea and vomiting associated with initial and repeat courses of emetogenic chemotherapy

Usual Adult Dose for Nausea/Vomiting:

Oral:
Highly Emetogenic Cancer Chemotherapy (HEC):
-Recommended dose: 24 mg orally 30 minutes before the start of single-day HEC (including cisplatin doses of 50 mg/m2 or greater)

Moderately Emetogenic Cancer Chemotherapy (MEC):
-Recommended dose: 8 mg orally twice a day, with the first dose administered 30 minutes before the start of chemotherapy and the subsequent dose 8 hours later; then 8 mg orally 2 times a day (every 12 hours) for 1 to 2 days after the completion of chemotherapy

Parenteral:
-Recommended dose: 0.15 mg/kg IV, with the first dose (infused over 15 minutes) 30 minutes before the start of emetogenic chemotherapy and subsequent doses given 4 and 8 hours after the first dose.
-Maximum dose: 16 mg per dose

Comments:
-Multi-day, single-dose administration of 24 mg orally for HEC has not been studied.
-The injection formulation should be diluted prior to IV administration.

Uses:
-Prevention of nausea and vomiting associated with HEC or MEC
-Prevention of nausea and vomiting associated with initial and repeat courses of emetogenic chemotherapy

Usual Adult Dose for Nausea/Vomiting -- Postoperative:

Oral:
-Recommended dose: 16 mg orally 1 hour before the induction of anesthesia

Parenteral:
-Recommended dose: 4 mg IV (undiluted) immediately before induction of anesthesia or postoperatively (nausea and/or vomiting within 2 hours after surgery)
-Alternative route: 4 mg IM (undiluted)

Comment:
-Administration of a second dose does not provide additional control of nausea and vomiting.

Use:
-Prevention of postoperative nausea and vomiting

Usual Adult Dose for Nausea/Vomiting--Radiation Induced:

Recommended dose: 8 mg orally 3 times a day
-Total Body Irradiation: 8 mg orally 1 to 2 hours before each fraction of radiotherapy administered each day
-Single High-dose Fraction Radiotherapy to the Abdomen: 8 mg orally 1 to 2 hours before radiotherapy, with subsequent doses every 8 hours after the first dose for 1 to 2 days after the completion of radiotherapy
-Daily Fractionated Radiotherapy to the Abdomen: 8 mg orally 1 to 2 hours before radiotherapy, with subsequent doses every 8 hours after the first dose for each day radiotherapy is given

Use:
-Prevention of nausea and vomiting associated with radiotherapy, either as total body irradiation, single high-dose fraction, or daily fractions to the abdomen

Usual Pediatric Dose for Nausea/Vomiting -- Postoperative:

Parenteral:
1 month to 12 years:
Less than 40 kg:
-Recommended dose: 0.1 mg/kg IV over 2 to 5 minutes immediately prior to/following anesthesia induction or postoperatively (nausea and/or vomiting occurring shortly after surgery)

40 kg and greater:
-Recommended dose: 4 mg IV over 2 to 5 minutes immediately prior to/following anesthesia induction or postoperatively (nausea and/or vomiting occurring shortly after surgery)

Use:
-Prevention of postoperative nausea and vomiting

Usual Pediatric Dose for Nausea/Vomiting -- Chemotherapy Induced:

Oral:
4 to 11 years:
-Recommended dose: 4 mg orally 3 times a day, with the first dose administered 30 minutes before the start of chemotherapy, and subsequent doses 4 and 8 hours after the first dose; then 4 mg orally 3 times a day (every 8 hours) for 1 to 2 days after the completion of chemotherapy

12 years and older:
-Recommended dose: 8 mg orally twice a day, with the first dose administered 30 minutes before the start of chemotherapy and the subsequent dose 8 hours later; then 8 mg orally 2 times a day (every 12 hours) for 1 to 2 days after the completion of chemotherapy

Parenteral:
6 months to 18 years:
-Recommended dose: 0.15 mg/kg IV, with the first dose (infused over 15 minutes) 30 minutes before the start of emetogenic chemotherapy, and subsequent doses given 4 and 8 hours after the first dose
-Maximum dose: 16 mg (per dose)

Comments:
-The injection formulation should be diluted in 50 mL prior to IV administration.
-This drug should be used to prevent nausea and vomiting associated with moderately to highly emetogenic chemotherapy.

Uses:
-Prevention of nausea and vomiting associated with moderately emetogenic cancer chemotherapy
-Prevention of nausea and vomiting associated with initial and repeat courses of emetogenic chemotherapy

Ondansetron can cause a serious heart problem, especially if you use certain medicines at the same time, including antibiotics, antidepressants, heart rhythm medicine, antipsychotic medicines, and medicines to treat cancer, malaria, HIV or AIDS. Tell your doctor about all medicines you use, and those you start or stop using during your treatment with ondansetron.

Taking ondansetron while you are using certain other medicines can cause high levels of serotonin to build up in your body, a condition called "serotonin syndrome," which can be fatal. Tell your doctor if you also use:

• medicine to treat depression;

• medicine to treat a psychiatric disorder;

• a narcotic (opioid) medication; or

• medicine to prevent nausea and vomiting.

This list is not complete and many other drugs can interact with ondansetron. This includes prescription and over-the-counter medicines, vitamins, and herbal products. Give a list of all your medicines to any healthcare provider who treats you.

The following have been reported as adverse events in clinical trials of patients treated with Ondansetron, the active ingredient of Ondansetron tablets. A causal relationship to therapy with Ondansetron tablets have 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 Ondansetron tablet in 2 trials. These patients were receiving concurrent highly emetogenic cisplatin-based chemotherapy regimens (cisplatin dose ≥ 50 mg/m2).

Table 5. Principal Adverse Events in US Trials: Single Day Therapy With 24 mg Ondansetron tablets (Highly Emetogenic Chemotherapy)

The adverse events in Table 6 have been reported in ≥ 5% of adults receiving either 8 mg of Ondansetron 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 Ondansetron tablets (Moderately Emetogenic Chemotherapy)

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 Ondansetron 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 Ondansetron tablets were unclear.

Radiation-Induced Nausea and Vomiting

The adverse events reported in patients receiving Ondansetron tablets and concurrent radiotherapy were similar to those reported in patients receiving Ondansetron 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 Ondansetron 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 concomitant perioperative and postoperative medications.

Table 7. Frequency of Adverse Events From Controlled Studies With Ondansetron tablets (Postoperative Nausea and Vomiting)

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 Ondansetron tablets. 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 Ondansetron tablets.

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, Steve-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.

SPL Image

Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product

Film, Oral:

Zuplenz: 4 mg (1 ea, 10 ea, 30 ea); 8 mg (1 ea, 10 ea, 30 ea)

Solution, Injection, as hydrochloride [strength expressed as base]:

Zofran: 40 mg/20 mL (20 mL [DSC]) [contains methylparaben, propylparaben]

Generic: 4 mg/2 mL (2 mL); 40 mg/20 mL (20 mL)

Solution, Injection, as hydrochloride [strength expressed as base, preservative free]:

Generic: 4 mg/2 mL (2 mL)

Solution, Oral, as hydrochloride [strength expressed as base]:

Zofran: 4 mg/5 mL (50 mL) [strawberry flavor]

Generic: 4 mg/5 mL (50 mL)

Tablet, Oral:

Generic: 24 mg

Tablet, Oral, as hydrochloride [strength expressed as base]:

Zofran: 4 mg, 8 mg

Generic: 4 mg, 8 mg

Tablet Disintegrating, Oral:

Zofran ODT: 4 mg, 8 mg [contains aspartame, methylparaben sodium, propylparaben sodium; strawberry flavor]

Generic: 4 mg, 8 mg

• Antiemetic
• Selective 5-HT3 Receptor Antagonist

~30 minutes

Time to Peak

Oral: ~2 hours; Oral soluble film: ~1 hour

Half-Life Elimination

Children:

Cancer patients: Children and Adolescents: 4 to 18 years: 2.8 hours

Surgical patients: Infants 1 to 4 months: 6.7 hours; Infants and Children 5 months to 12 years: 2.9 hours

Adults: 3 to 6 hours; Mild-to-moderate hepatic impairment (Child-Pugh classes A and B): 12 hours; Severe hepatic impairment (Child-Pugh class C): 20 hours

Protein Binding

Plasma: 70% to 76%

Mean plasma Cl is reduced by 41% (IV) and 50% (oral) in patients with severe renal impairment (CrCl less than 30 mL/min).

Oral: Oral dosage forms should be administered 30 minutes prior to chemotherapy; 1 to 2 hours before radiotherapy; 1 hour prior to the induction of anesthesia

Orally disintegrating tablets: Do not remove from blister until needed. Peel backing off the blister, do not attempt to push tablet through the foil. Using dry hands, place tablet on tongue and allow to dissolve. Swallow with saliva (no need to administer with liquids).

Oral soluble film: Do not remove from pouch until immediately before use. Using dry hands, place film on top of tongue and allow to dissolve (4 to 20 seconds). Swallow with or without liquid. If using more than one film, each film should be allowed to dissolve completely before administering the next film.

IM: Should be administered undiluted.

IV:

IVPB: Infuse diluted solution over 15 minutes; 24-hour continuous infusions have been reported, but are rarely used.

Chemotherapy-induced nausea and vomiting: Give first dose 30 minutes prior to beginning chemotherapy.

IV push: Prevention of postoperative nausea and vomiting: Single doses may be administered IV injection as undiluted solution over at least 30 seconds but preferably over 2 to 5 minutes

Some products may contain phenylalanine.

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, cancer chemotherapy, or radiation treatment.

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

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

Ondansetron can cause a serious heart problem, especially if you use certain medicines at the same time, including antibiotics, antidepressants, heart rhythm medicine, antipsychotic medicines, and medicines to treat cancer, malaria, HIV or AIDS. Tell your doctor about all medicines you use, and those you start or stop using during your treatment with ondansetron.

Taking ondansetron while you are using certain other medicines can cause high levels of serotonin to build up in your body, a condition called "serotonin syndrome," which can be fatal. Tell your doctor if you also use:

• medicine to treat depression;

• medicine to treat a psychiatric disorder;

• a narcotic (opioid) medication; or

• medicine to prevent nausea and vomiting.

This list is not complete and many other drugs can interact with ondansetron. This includes prescription and over-the-counter medicines, vitamins, and herbal products. Give a list of all your medicines to any healthcare provider who treats you.

• Ondansetron treats and prevents nausea and vomiting by an unknown mechanism, possibly by a direct effect on the CTZ (the area of the brain associated with vomiting), the vagus nerve or both. The neurotransmitter, serotonin, appears to play a role in ondansetron's effect.
• Ondansetron belongs to the class of medicines known as 5-HT3 receptor antagonists.

Ondansetron may be used for the prevention or treatment of nausea and vomiting but it may cause constipation or a headache.

The peak effect of ondansetron is seen within 1.5-2 hours. The onset of the effect is faster with the wafer form of ondansetron.

View as a slideshow