Ondansetron: Fast relief for nausea and vomiting, but what about toxicity?
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The bottom line
Ondansetron (sometimes referred to as Zofran) treats nausea and vomiting. Side effects include headache, dizziness, drowsiness, tiredness, anxiety, and constipation or diarrhea. More serious side effects are prolonged QT interval on EKG with abnormal heart rhythms, serotonin syndrome, and allergic reactions. Ondansetron has many drug interactions, so check if it is safe to take it with your other drugs.
Prevention tips
Store ondansetron up, away, and out of reach of children.
Take as prescribed.
Use dry hands when peeling back foil on orally disintegrating tablets. Do not chew or swallow these tablets.
Check with your doctor or pharmacist to be sure it is safe to take ondansetron with medications you are currently taking or plan to take.
Do not take a double dose. If you miss a dose and feel sick, take it right away. Otherwise skip that dose and wait for the next scheduled dose.
Store away from light, excess heat, and moisture.
This really happened
A 35-year-old pregnant woman presented to the emergency department at approximately 8 weeks of pregnancy with nausea, recurrent vomiting, and weight loss due to decreased oral intake. Her past medical history included hyperemesis gravidarum (severe nausea and vomiting in pregnancy that leads to weight loss, dehydration and electrolyte imbalances) during a previous pregnancy for which she was hospitalized for 3 months. She was taking sumatriptan for migraines.
An obstetric ultrasound revealed no fetal cardiac heartbeat suggesting possible pregnancy loss. Most of her laboratory findings were normal, although she tested positive for COVID-19. She was admitted and treated with numerous anti-emetic drugs including intravenous ondansetron and prochlorperazine. She received a dose of sumatriptan for her migraine.
On the 11th day in the hospital, she no longer had nausea or vomiting so was scheduled for discharge. She suddenly experienced sweating, tremors, muscle aches and stiffness, with increased heart rate and temperature, increased reflexes and bilateral inducible clonus (involuntary rhythmic muscle contractions) of her feet. Serotonin syndrome was suspected. All antiemetics and sumatriptan were stopped and she was given a dose of intravenous lorazepam. Within 20 minutes her condition improved. She was admitted to the intensive care unit and treated with lorazepam every 6 hours for 24 hours and then orally as needed. She remained stable and her symptoms did not recur.
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What is ondansetron (Zofran)?
Ondansetron is a prescription drug that blocks serotonin. Serotonin is a chemical messenger in the body that, among other things, activates the brain’s vomiting center and peripheral nerves to the digestive system that cause vomiting. Zofran, the original brand name, is no longer sold in the US but the generic ondansetron is widely available with a prescription.
What is ondansetron used for?
Ondansetron is used to prevent nausea and vomiting. Its FDA-approved indications are for nausea and vomiting due to chemotherapy, radiation therapy, and after surgery. It is sometimes used off-label for nausea and vomiting from morning sickness in pregnancy, obsessive-compulsive disorder, schizophrenia, itching due to liver or kidney disease, tardive dyskinesia (movement disorder associated with chronic antipsychotic treatment) and other illnesses.
What to do if you take too much ondansetron
If you take a double dose by mistake, you will most likely experience only mild side effects. However, a double dose or higher can sometimes cause cardiac and neurologic toxicity. If you take too much ondansetron, you should seek medical attention, especially if you are dizzy or if youfaint, have difficulty breathing, or are experiencing other more serious symptoms.
Get expert help
If you have questions regarding an overdose of ondansetron or want advice on using ondansetron safely, use the webPOISONCONTROL® online tool to get help, or call your poison center at 1-800-222-1222. Whether online or by phone, expert guidance is always free, confidential, and available 24 hours a day.
What are the side effects of ondansetron?
Side effects include headache, dizziness, drowsiness, tiredness, anxiety, and constipation or diarrhea. A more serious adverse effect is dose-dependent prolongation of the QT interval on the EKG which can lead to abnormal heart rhythms such as second-degree heart block, ventricular tachycardia, and atrial fibrillation. This is more common with intravenous ondansetron, or if you use other QT-prolonging medications while taking ondansetron, or if you have preexisting heart disease or electrolyte disorders such as low potassium or magnesium.
Serotonin syndrome is possible if taken with other serotonergic drugs (see drug interactions below). Allergic reactions (rash, hives, itching, swelling, difficulty breathing) are possible. Rarely, dystonic reactions (sudden involuntary movement disorder) can occur. When used intravenously, pain and redness at the injection site, liver toxicity, and temporary blindness have been reported.
What happens if you take too much ondansetron?
If you take too much ondansetron, you may experience headache, drowsiness, and constipation or diarrhea. If you take a very high dose, you can develop prolonged QT on EKG with abnormal heart rhythms and/or too much serotonin circulating in your body leading to serotonin syndrome.
Symptoms of an ondansetron overdose
Symptoms of an ondansetron overdose include dizziness, fainting, drowsiness, stiff or twitching muscles, seizures, and coma. Other symptoms include low blood pressure, irregular heartbeat (fast, slow, other rhythm abnormalities), and chest pain.
Is ondansetron safe for children?
Yes, it is approved by the FDA for children ages 4 and older and is sometimes prescribed off-label for children 6 months and older. Depending on the child’s age, it can be prescribed as an oral solution, dissolving tablets or regular tablets.
Does ondansetron interact with other medicines?
Yes, ondansetron interacts with other medicines. Some drugs (rifampin, carbamazepine, phenytoin) affect the metabolism of ondansetron in the liver, such that it is metabolized too quickly making it less effective.
If ondansetron and another drug that causes prolonged QT on EKG are taken together, the risk of serious abnormal cardiac rhythms is increased. Examples of drugs that cause prolonged QT include drugs for abnormal cardiac rhythms (such as amiodarone, sotalol), some antibiotics and antifungals (such as azithromycin, erythromycin, ketoconazole), antipsychotics and antidepressants (such as quetiapine, amitriptyline, citalopram and other serotonin reuptake inhibitors) and methadone.
If ondansetron is taken with other drugs that affect serotonin, a condition known as serotonin syndrome can occur. There are many serotonergic medications including some antidepressants, pain relievers and migraine drugs. Serotonin syndrome symptoms include agitation, confusion, sweating, fever, disorientation, seizures, increased heart rate and blood pressure, dilated pupils, diarrhea, tremors, muscle twitching and rigidity. Serotonin syndrome can be fatal.
Ondansetron is contraindicated for patients on apomorphine. Apomorphine, a drug used for Parkinson’s disease, causes severe nausea and vomiting but ondansetron does not work for apomorphine-induced nausea and vomiting and the two drugs together cause a severe drop in blood pressure and coma.