Ondansetron

Ondansetron is approved to prevent nausea and vomiting in several specific clinical situations. The exact approvals depend on the form used:

• Oral tablets, orally disintegrating tablets, and oral solution: prevent nausea and vomiting from highly emetogenic cancer chemotherapy (including high-dose cisplatin)
• Oral tablets, orally disintegrating tablets, and oral solution: prevent nausea and vomiting from moderately emetogenic cancer chemotherapy
• Oral tablets, orally disintegrating tablets, and oral solution: prevent nausea and vomiting in patients receiving radiation therapy — total body irradiation, single high-dose abdominal radiation, or daily abdominal fractions
• Oral tablets, orally disintegrating tablets, and oral solution: prevent postoperative nausea and vomiting
• Ondansetron injection (intravenous or intramuscular): prevents nausea and vomiting from emetogenic cancer chemotherapy, including high-dose cisplatin, in adults and children aged 6 months and older
• Ondansetron injection: prevents postoperative nausea and vomiting in adults and children

Ondansetron is a selective 5-HT3 receptor antagonist — meaning it specifically blocks a type of serotonin receptor called the 5-HT3 receptor. When the body is exposed to chemotherapy, radiation, or the stress of surgery, cells in the small intestine release serotonin. That serotonin activates nearby nerve fibers and signals the brain's vomiting center (called the chemoreceptor trigger zone) to trigger nausea and vomiting. Ondansetron blocks those 5-HT3 receptors at both sites — in the gut and in the brain — interrupting the chain reaction before full-blown nausea sets in. It does not block dopamine receptors, which distinguishes it from some older anti-nausea drugs.

Ondansetron comes in several forms — oral tablets, orally disintegrating tablets, oral solution, and injectable forms — each with specific timing instructions. Oral forms are generally taken about 30 minutes before chemotherapy or radiation begins, and additional doses may be taken later that day and for 1–2 days after chemotherapy, depending on the regimen. The injectable form is given by a healthcare professional before chemotherapy or surgery, following a specific schedule. Patients with severe liver disease have a lower maximum daily dose — your prescriber will set this for you. Always follow the exact schedule your prescriber provides, and do not skip or double doses without guidance.

Most people tolerate ondansetron well. Common side effects include:

• Headache
• Constipation
• Diarrhea
• Dizziness
• Fatigue
• Flushing (feeling of warmth or redness)

More serious reactions to watch for include an irregular or pounding heartbeat (a sign of QT prolongation), signs of a severe allergic reaction (hives, facial swelling, difficulty breathing), and signs of serotonin syndrome (confusion, agitation, rapid heart rate, high fever, muscle twitching). Seek medical help right away if any of these occur.

• QT prolongation and heart rhythm changes: Ondansetron can alter the heart's electrical rhythm in a dose-related way. In rare cases, this can cause a dangerous arrhythmia called Torsade de Pointes. People with congenital long QT syndrome should avoid the injectable form. ECG monitoring may be needed if you have heart failure, low potassium or magnesium, a slow heart rate, or take other QT-prolonging drugs.
• Serotonin syndrome: Combining ondansetron with other serotonin-raising drugs can cause a rare but serious reaction with symptoms like agitation, rapid heart rate, high fever, and muscle twitching. Some reported cases have been fatal. Tell every provider about all your medications.
• Myocardial ischemia (reduced blood flow to the heart): Cases have been reported, particularly with intravenous use. Do not exceed the recommended infusion rate. Report chest pain or pressure right away.
• Masking bowel problems: After abdominal surgery or chemotherapy, ondansetron can hide signs of a slowing or blocked bowel. Your care team will monitor your bowel activity if this is a concern.
• Hypersensitivity: Severe allergic reactions, including anaphylaxis and bronchospasm, have been reported, particularly in people who have reacted to similar anti-nausea drugs.

Ondansetron can interact with several medications and substances — always share your full medication list with your prescriber and pharmacist:

• Apomorphine — combining with ondansetron is contraindicated; it can cause profound low blood pressure and loss of consciousness
• SSRIs and SNRIs (antidepressants like fluoxetine, sertraline, venlafaxine) — raise the risk of serotonin syndrome
• MAO inhibitors (such as phenelzine or linezolid) — raise the risk of serotonin syndrome
• Tramadol — ondansetron may reduce tramadol's effectiveness for pain relief; monitoring is needed
• Fentanyl, lithium, mirtazapine, intravenous methylene blue — increased serotonin syndrome risk
• Phenytoin, carbamazepine, rifampin — these drugs speed up ondansetron's breakdown, potentially making it less effective
• Other QT-prolonging drugs — combining with ondansetron increases the risk of dangerous heart rhythm changes

This is not a complete list of interactions. Always talk with your doctor or pharmacist before starting, stopping, or changing any medication.

• Do not take ondansetron if you have had a hypersensitivity (allergic) reaction to it or to other 5-HT3 receptor antagonists such as granisetron or dolasetron
• Do not take ondansetron with apomorphine — this combination is contraindicated
• Tell your doctor if you have congenital long QT syndrome, congestive heart failure, bradyarrhythmias (slow heart rhythm), or low potassium or magnesium levels
• Tell your doctor if you have severe liver disease (hepatic impairment) — your daily dose must be limited
• Tell your doctor if you are pregnant: studies have shown inconsistent findings about the risk of birth defects, including possible associations with oral clefts and cardiac septal defects with first-trimester use; discuss the risks and benefits with your provider
• If you are breastfeeding, ondansetron passes into breast milk at low levels; available data suggest limited exposure to the infant, but discuss with your provider
• Infants younger than 4 months clear ondansetron more slowly and require close monitoring
• Adults older than 75 may also clear ondansetron more slowly; no routine dose change is required, but sensitivity may be greater
• People with severe renal impairment (kidney disease) do not typically need a dose adjustment, but your provider should know

There is no specific antidote for an ondansetron overdose. Supportive care is the main treatment. Reported effects of overdose include sudden brief vision loss, severe constipation, low blood pressure, and — particularly in young children who accidentally ingested large amounts — symptoms consistent with serotonin syndrome such as agitation, rapid heart rate, seizures, and muscle movements. If you suspect an overdose, seek emergency medical help immediately.

At normal doses, ondansetron does not significantly affect esophageal or gastric movement, lower esophageal sphincter pressure, or small intestinal transit time. It does not affect heart rate, blood pressure, cardiac output, or stroke volume at single standard doses, and it has no effect on prolactin (a hormone) levels. However, it can slow movement through the colon with extended use, which explains why constipation is a common side effect. At higher intravenous doses, ondansetron prolongs the QT interval on an ECG in a dose-dependent manner — meaning the effect on heart rhythm grows with increasing dose.

After an intravenous dose, ondansetron reaches peak blood levels quickly; after an intramuscular injection, peak levels are reached in about 40 minutes. The drug is 70–76% bound to proteins in the blood and also distributes into red blood cells. Ondansetron is broken down extensively by the liver using enzymes called CYP3A4, CYP1A2, and CYP2D6, with only about 5% leaving the body unchanged in the urine. In healthy adults, the elimination half-life (the time it takes for blood levels to fall by half) is roughly 3.5 hours, extending to about 5.5 hours in adults over 75. In young infants (under 4 months), the half-life is notably longer, meaning the drug stays in their system considerably longer than in older children or adults.

Store at 20 to 25°C (68 – 77°F) . Dispense in a tight, light-resistant container as defined in the USP, with a child-resistant closure (as required).