Ondansetron

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What is ondansetron

What is ondansetron

Ondansetron is a drug used to prevent nausea and vomiting caused by chemotherapy and radiation therapy. Ondansetron is also used to prevent nausea and vomiting after surgery. Ondansetron hydrochloride blocks the action of the chemical serotonin, which binds to certain nerves and may trigger nausea and vomiting. Blocking serotonin may help lessen nausea and vomiting. Ondansetron is a competitive serotonin type 3 receptor (5-hydroxytryptamine-3, 5-HT₃) antagonist and a type of antiemetic. Ondansetron effects are thought to be on both peripheral and central nerves. One part is to reduce the activity of the vagus nerve, which is a nerve that activates the vomiting center in the medulla oblongata, the other is a blockage of serotonin receptors in the chemoreceptor trigger zone. Ondansetron does not have much effect on vomiting due to motion sickness.

Ondansetron is a well tolerated drug with few side effects. Headache, constipation, and dizziness are the most commonly reported side effects associated with its use. There have been no significant drug interactions reported with this drugs use.

Ondansetron is also called Zofran, Zofran ODT and Zuplenz.

Ondansetron mechanism of action

Ondansetron is a serotonin-3 (5-hydroxytryptamine-3, 5-HT₃) receptor antagonist, have been shown to have a good antiemetic effect in patients receiving chemotherapy and in situations with vomiting after surgery ¹. Ondansetron is one of the best known 5-HT₃ receptor antagonists, blocking receptors at vagal and sympathetic nerves and the chemoreceptor triggering zone ². However, 5-HT₃ receptor antagonists not only inhibit transmission of signals to the CNS, they also decrease intestinal motility, presumably by interfering with serotonergic neurotransmission within the enteric nervous system (ENS) and blocking the initiation of reflexes ³. Ondansetron effects are thought to be on both peripheral and central nerves. One part is to reduce the activity of the vagus nerve, which is a nerve that activates the vomiting center in the medulla oblongata, the other is a blockage of serotonin receptors in the chemoreceptor trigger zone.

How to take ondansetron

Ondansetron comes as a tablet, a rapidly disintegrating (dissolving) tablet, and an oral solution (liquid) to take by mouth. The first dose of ondansetron is usually taken 30 minutes before the start of chemotherapy, 1 to 2 hours before the start of radiation therapy, or 1 hour before surgery. Additional doses are sometimes taken one to three times a day during chemotherapy or radiation therapy and for 1 to 2 days after the end of treatment. Follow the directions on your prescription label carefully, and ask your doctor or pharmacist to explain any part you do not understand. Take ondansetron exactly as directed. Do not take more or less of it or take it more often than prescribed by your doctor.

If you are taking the rapidly disintegrating tablet, remove the tablet from the package just before you take your dose. To open the package, do not try to push the tablet through the foil backing of the blister. Instead, use dry hands to peel back the foil backing. Gently remove the tablet and immediately place the tablet on the top of your tongue. The tablet will dissolve in a few seconds and can be swallowed with saliva.

Ondansetron can be taken with or without food.

The first dose 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.

Ondansetron special precautions

Before taking ondansetron:

tell your doctor and pharmacist if you are allergic to ondansetron, alosetron (Lotronex), dolasetron (Anzemet), granisetron (Kytril), palonosetron (Aloxi, in Akynzeo), any other medications, or any of the ingredients in ondansetron tablets or liquid. Ask your pharmacist for a list of the ingredients.

tell your doctor if you are receiving apomorphine (Apokyn). Your doctor will probably tell you not to take ondansetron if you are receiving this medication.

tell your doctor and pharmacist what prescription and nonprescription medications, vitamins, nutritional supplements, and herbal products you are taking or plan to take. Be sure to mention any of the following: certain medications for seizures such as carbamazepine (Carbatrol, Epitol, Equetro, Tegretol) or phenytoin (Dilantin); clarithromycin (Biaxin, in Prevpac); erythromycin (E.E.S., Erythrocin, others); fentanyl (Abstral, Actiq, Duragesic, Fentora, Lazanda, Onsolis, Subsys); lithium (Lithobid); medications for irregular heart beat; medications for mental illness; medications to treat migraines such as almotriptan (Axert), eletriptan (Relpax), frovatriptan (Frova), naratriptan (Amerge), rizatriptan (Maxalt), sumatriptan (Imitrex), and zolmitriptan (Zomig); methylene blue; mirtazapine (Remeron); monoamine oxidase (MAO) inhibitors including isocarboxazid (Marplan), linezolid (Zyvox), phenelzine (Nardil), selegiline (Eldepryl, Emsam, Zelapar), and tranylcypromine (Parnate); moxifloxacin (Avelox); selective serotonin reuptake inhibitors (SSRIs) such as citalopram (Celexa), escitalopram (Lexapro), fluoxetine (Prozac, Sarafem, in Symbyax), fluvoxamine (Luvox), paroxetine (Brisdelle, Paxil, Pexeva), and sertraline (Zoloft); and tramadol (Conzip, Ultram, in Ultracet). Your doctor may need to change the doses of your medications or monitor you more carefully for side effects. Many other medications may also interact with ondansetron, so be sure to tell your doctor about all the medications you are taking, even those that do not appear on this list.

tell your doctor if you or anyone in your family has or has ever had long QT syndrome (condition that increases the risk of developing an irregular heartbeat that may cause fainting or sudden death), or another type of irregular heart beat or heart rhythm problem, or if you have or have ever had low blood levels of magnesium or potassium in your blood, heart failure (HF; condition in which the heart cannot pump enough blood to other parts of the body), or liver disease.

tell your doctor if you are pregnant, plan to become pregnant, or are breast-feeding. If you become pregnant while taking ondansetron, call your doctor.

if you have phenylketonuria (PKU, an inherited condition in which a special diet must be followed to prevent mental retardation), you should know that the orally disintegrating tablets contain aspartame that forms phenylalanine.

Ondansetron while pregnant

Ondansetron has also been prescribed during pregnancy to reduce symptoms of nausea and vomiting in pregnancy. Nausea and vomiting in pregnancy is also referred to as “morning sickness”. Ondansetron is sold under the brand name Zofran^®.

Nausea and vomiting in pregnancy or “morning sickness” is the most common medical condition in pregnancy. It affects 50-80% of pregnant women. Nausea and vomiting in pregnancy symptoms can range from mild to severe. The symptoms can happen at any time during the day or at night. Symptoms can include nausea, dry heaves, retching and/or vomiting. Nausea and vomiting in pregnancy usually begins between 4-9 weeks of pregnancy, and peaks between 7-12 weeks. In most women, symptoms go away between 12-16 weeks of pregnancy. Up to 15% of women will continue to have symptoms up to 20 weeks of pregnancy or until delivery.

The most severe form of nausea and vomiting in pregnancy is known as hyperemesis gravidarum, which affects up to 3% of pregnant women. Hyperemesis gravidarum is when there is severe nausea and constant vomiting that causes weight loss and dehydration (not getting enough water). Women with hyperemesis gravidarum can require hospitalization.

Whether symptoms of nausea and vomiting in pregnancy are mild, moderate or severe, it can have a major impact on a woman’s quality of life. If nausea and vomiting in pregnancy is affecting your ability to eat, sleep and perform your daily activities, speak with your healthcare provider. If the symptoms of nausea and vomiting in pregnancy first start at the 10th week of pregnancy or later they may be due to other causes and should be discussed with your healthcare provider.

Eating small meals often, drinking plenty of clear fluids, and avoiding triggers (such as odors, heat, and spicy or high fat foods) can help control nausea and vomiting during pregnancy.

Does taking ondansetron increase the chance for miscarriage?

One study did not find a higher rate of miscarriage among women who reported using ondansetron in the first trimester of pregnancy.

Can taking ondansetron during pregnancy cause birth defects?

Probably not. Most studies have found no increased chance for birth defects among thousands of women who used ondansetron in the first trimester. However, one study reported an association with cleft palate. This study used interviews with the mothers to learn about the medications taken during pregnancy. This study found a small increased chance for cleft palate (an opening in the roof of the mouth that may be repaired with surgery). Two other studies reported an association with heart defects.

Can taking ondansetron during pregnancy cause other pregnancy complications?

Studies did not find a higher chance of miscarriage, premature delivery (being born before 37 weeks of pregnancy), or low birth weight when women used ondansetron during pregnancy.

At higher doses, there have been reports that ondansetron use might cause a heart rhythm problem (called QT interval prolongation) in the person taking ondansetron. In severe cases, this could become an abnormal heart rhythm known as Torsades de Pointes. You can discuss how to monitor for QT interval prolongation with your healthcare provider is you are using this medication.

I take ondansetron. Can it make it harder for me to get pregnant?

Studies on women have not yet been done to see if ondansetron could make it harder for a woman to get pregnant. However, studies in animals did not find that ondansetron would affect the ability to get pregnant.

Can I take ondansetron while I am breastfeeding?

There have been no studies in humans looking at the use of ondansetron during breastfeeding. Studies in animals suggest that ondansetron enters breast milk, but the effects of ondansetron on a breastfeeding infant are not known. If ondansetron use is necessary, this is not a reason to stop breastfeeding but a different drug may be considered, especially while breastfeeding a newborn or preterm infant. Be sure to talk to your health care provider about all your choices for breastfeeding.

Ondansetron uses

Ondansetron is used to prevent nausea and vomiting that may be caused by surgery, cancer chemotherapy, or radiation treatment.

Ondansetron dose

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/m2
Moderately Emetogenic Cancer Chemotherapy	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.
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 4 mg three times a day for 1 to 2 days after completion of chemotherapy.

Adult Dose for Nausea/Vomiting – Chemotherapy Induced

Uses:

Prevention of nausea and vomiting associated with highly emetogenic cancer chemotherapy or moderately emetogenic cancer chemotherapy
Prevention of nausea and vomiting associated with initial and repeat courses of emetogenic chemotherapy

Oral ondansetron:

Highly Emetogenic Cancer Chemotherapy (HEC): -Recommended dose: 24 mg orally 30 minutes before the start of single-day highly emetogenic cancer chemotherapy (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 ondansetron:

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 highly emetogenic cancer chemotherapy has not been studied.
The injection formulation should be diluted prior to IV administration.

Adult Dose for Nausea/Vomiting

Uses:

Prevention of nausea and vomiting associated with highly emetogenic cancer chemotherapy or moderately emetogenic cancer chemotherapy
Prevention of nausea and vomiting associated with initial and repeat courses of emetogenic chemotherapy

Oral ondansetron:

Highly Emetogenic Cancer Chemotherapy (HEC): Recommended dose: 24 mg orally 30 minutes before the start of single-day highly emetogenic cancer chemotherapy (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 ondansetron:

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 highly emetogenic cancer chemotherapy has not been studied.
The injection formulation should be diluted prior to IV administration.

Adult Dose for Nausea/Vomiting – Postoperative

Use: Prevention of postoperative nausea and vomiting

Oral ondansetron:

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

Parenteral ondansetron:

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.

Adult Dose for Nausea/Vomiting-Radiation Induced

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

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

Pediatric Dose for Nausea/Vomiting – Postoperative

Use: Prevention of postoperative nausea and vomiting

Parenteral ondansetron:

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)

Pediatric Dose for Nausea/Vomiting – Chemotherapy Induced

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

Oral ondansetron:

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 ondansetron:

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.

Renal Dose Adjustments

No adjustment recommended.

Liver Dose Adjustments

Mild to moderate hepatic impairment (Child-Pugh less than 10): No adjustment recommended.
Severe hepatic impairment: (Child-Pugh 10 or greater): 8 mg IV over 30 minutes before the start of emetogenic chemotherapy; maximum 8 mg per day

What should I do if I forget a dose?

Take the missed dose as soon as you remember it. However, if it is almost time for the next dose, skip the missed dose and continue your regular dosing schedule. Do not take a double dose to make up for a missed one.

Ondansetron side effects

The most frequently reported side effects are headache, constipation, and diarrhea.

More common side effects:

confusion
dizziness
fast heartbeat
fever
headache
shortness of breath
weakness

Tell your doctor if any of these symptoms are severe or do not go away:

headache
constipation
weakness
tiredness
chills
drowsiness

Some side effects can be serious. If you experience any of the following symptoms, call your doctor immediately or seek emergency medical treatment:

blurred vision or vision loss
rash
hives
itching
swelling of the eyes, face, lips, tongue, throat, hands, feet, ankles, or lower legs
hoarseness
difficulty breathing or swallowing
chest pain
shortness of breath
dizziness, light-headedness, or fainting
fast, slow or irregular heartbeat
agitation
hallucinations (seeing things or hearing voices that do not exist)
fever
excessive sweating
confusion
nausea, vomiting, or diarrhea
loss of coordination
stiff or twitching muscles
seizures
coma (loss of consciousness)

Nervous system

Dizziness occurred during rapid IV administration.
Headache occurred more often in the oral dissolving tablet formulation when taken with water.
Very common (10% or more): Headache (up to 27%), drowsiness/sedation (up to 23%)
Common (1% to 10%): Dizziness, paresthesia
Uncommon (0.1% to 1%): Seizures, movement disorders/extrapyramidal reactions (oculogyric crisis/dystonic reactions, dyskinesia)
Rare (0.01% to 0.1%): Grand mal seizures

Other

Wound problems occurred at the surgical site in patients given this drug for the treatment of postoperative nausea and vomiting.
Very common (10% or more): Wound problem (up to 28%), malaise/fatigue (up to 13%)
Common (1% to 10%): Shivers, pyrexia/fever, cold sensation
Frequency not reported: Pain, ear disorder

Gastrointestinal

Localized anal/rectal burning occurred after insertion of the suppository formulation.
Very common (10% or more): Diarrhea (up to 16%), constipation (up to 11%)
Common (1% to 10%): Xerostomia, nausea, vomiting, localized anal/rectal burning sensation
Uncommon (0.1% to 1%): Throat disorder
Frequency not reported: Gastric symptoms, abdominal pain, flatulence

Ocular

Very common (10% or more): Eye disorder (up to 19%)
Common (1% to 10%): Visual disturbance/transient visual disturbances (e.g., blurred vision)
Uncommon (0.1% to 1%): Oculogyric crisis
Very rare (less than 0.01%): Transient blindness
Frequency not reported: Swollen periocular area
Oculogyric crisis occurred alone and in combination with other dystonic reactions.
Transient visual disturbances, blurred vision, and transient blindness occurred predominantly during rapid IV administration. Many of the cases of blindness resolved from within a few minutes to approximately 28 hours. Most patients were receiving concomitant chemotherapy with cisplatin.

Cardiovascular

Cardiopulmonary arrest and shock occurred during allergic reactions in patients given the IV formulation.
Common (1% to 10%): Sensation of warmth/flushing, bradycardia, hypotension, arrhythmias
Uncommon (0.1% to 1%): Chest pain with/without ST segment depression
Rare (0.01% to 0.1%): Transient ECG changes including QT interval prolongation (Torsade de Pointes), angina/chest pain, vascular occlusive events, tachycardia
Frequency not reported: Hemorrhage
Postmarketing reports: Cardiopulmonary arrest, shock

Respiratory

Common (1% to 10%): Hypoxia, lower respiratory tract disease, expectoration, cough
Uncommon (0.1% to 1%): Hiccups
Rare (0.01% to 0.1%): Bronchospasm/asthma
Postmarketing reports: Shortness of breath, laryngeal edema, stridor, laryngospasm
Laryngospasm occurred during allergic reactions in patients given the IV formulation.

Psychiatric

Common (1% to 10%): Anxiety/agitation, disturbance in behavior/conduct, sleep disturbance

Genitourinary

Common (1% to 10%): Gynecological disorder, urinary retention, urinary tract infection/dysuria

Dermatologic

Common (1% to 10%): Rash, pruritus
Very rare (less than 0.01%): Toxic skin eruption, toxic epidermal necrolysis

Hepatic

Transient, asymptomatic increases in AST/ALT 2 times the upper limit of normal commonly occurred in patients receiving chemotherapy with cisplatin, and did not appear to be related to dose/duration of treatment.
Liver failure and death have been reported in patients with cancer receiving potentially hepatotoxic/cytotoxic chemotherapy and antibiotics; however, the etiology of liver failure is unknown.
Common (1% to 10%): Asymptomatic increases in AST/ALT
Postmarketing reports: Liver failure and death

Local

Common (1% to 10%): Injection site reactions

Hypersensitivity

Rare (0.01% to 0.1%): Immediate hypersensitivity reactions (sometimes severe), anaphylaxis/anaphylactoid reactions
Postmarketing reports: Angioedema

Metabolic

Rare (0.01% to 0.1%): Hypokalemia
Frequency not reported: Poor oral intake

Ondansetron may cause other side effects. Call your doctor if you have any unusual problems while you are taking this medication.

Symptoms of overdose may include:

sudden loss of vision for a short time
dizziness or lightheadedness
fainting
constipation
irregular heart beat

Single-dose ondansetron prevents postoperative vomiting in pediatric outpatients. Patel RI, Davis PJ, Orr RJ, Ferrari LR, Rimar S, Hannallah RS, Cohen IT, Colingo K, Donlon JV, Haberkern CM, McGowan FX, Prillaman BA, Parasuraman TV, Creed MR. Anesth Analg. 1997 Sep; 85(3):538-45.[↩]
An overview of the clinical use of ondansetron in preschool age children. Cohen IT. Ther Clin Risk Manag. 2007 Jun; 3(2):333-9. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1936315/[↩]
Review article: serotonin receptors and transporters — roles in normal and abnormal gastrointestinal motility. Gershon MD. Aliment Pharmacol Ther. 2004 Nov; 20 Suppl 7():3-14. https://www.ncbi.nlm.nih.gov/pubmed/15521849/[↩]