Zofran (ondansetron) is one of the most commonly prescribed anti-nausea medications, and is even on the World Health Organization’s List of Essential Medications. Over 10 million prescriptions for ondansetron are written in the US each year! 

How Does Zofran Work for Nausea?

Ondansetron works by binding to chemical receptors in both the brain and the intestine. These receptors work to turn off the nausea signals that the intestines send to the brain, and to stop the brain from triggering vomiting.

Zofran is quickly absorbed, and is often taken as a dissolving tablet that goes on the tongue. When someone is experiencing nausea and vomiting, not needing to swallow a pill can be very helpful. However, just like all medications, ondansetron has side effects. Some are more mild, while others can be severe.

Common Zofran Side Effects: What to Expect

Zofran has some common side effects, such as fatigue, dry mouth, and constipation. More than 10% of adults who take ondansetron experience these side effects. Zofran can also commonly cause malaise and headaches. Less commonly, liver function can be negatively impacted by ondansetron. 

Zofran and GLP-1 Medications: Overlapping Side Effects

If you’ve taken a GLP-1 medication, those side effects may sound familiar. GLP-1 medications like semaglutide (Ozempic/Wegovy) and tirzepatide (Mounjaro/Zepbound) can also cause headaches, fatigue, malaise, and constipation. When GLP-1 medications cause nausea or vomiting, some patients take ondansetron for relief.

Unfortunately, the side effects of Zofran can overlap with those of GLP-1 or GIP-1/GIP medications like semaglutide and tirzepatide. It is especially important to be aware of this overlap, and manage symptoms as they occur. If possible, patients may want to consider treating their nausea with a medication that is less likely to worsen their other side effects.

Serious Zofran Side Effects: Cardiac Risks and Heart Health

One of the more serious potential side effects of ondansetron relates to the heart. To understand why this is especially important for patients on GLP-1s, it helps to understand how the heart functions on a cellular level. The normal heart rhythm is maintained by a precise balance of electrolytes like sodium, potassium, and magnesium. Those same electrolytes can be lost with vomiting and diarrhea, which is often experienced by patients on GLP-1 medications like semaglutide and tirzepatide. 

This increased likelihood of electrical imbalances means patients on GLP-1 medications may be at higher risk of cardiac rhythm abnormalities related to ondansetron. The risk is small, but still very real. In patients who may be at increased risk of electrolyte abnormalities, some experts recommend checking an EKG before starting the medication, 

Alternatives to Zofran for Nausea

What alternatives are there for managing nausea or vomiting while on GLP-1 medications? The options fall into two main categories: non-medication and medication. Your healthcare provider can help you determine which approaches are appropriate for your specific situation.

One surprising option for managing nausea is to smell isopropyl alcohol! This is the ingredient in alcohol wipes, and is sold in bottles at drugstores. Several studies have directly compared it to ondansetron given in an IV, and found equivalent effectiveness and faster onset of relief with smelling isopropyl alcohol. One study found that improvement in nausea was twice as fast with smelling isopropyl alcohol as it was with ondansetron (Cotton et al., 2007). 

Dietary changes like consuming crackers, apples, mint, or ginger-based drinks 30 minutes after taking a GLP-1 medication can also help prevent nausea! Small, frequent meals can help prevent vomiting. These suggestions come from a multidisciplinary expert panel on dietary changes to manage the GI side effects of GLP-1 medications (Gorgojo-Martínez et al., 2022). 

There are also medication alternatives for nausea management. Reglan (metoclopramide) has the advantage of also being used to relieve gastroparesis. Over-the-counter options include Pepto-Bismol (bismuth subsalicylate), or Dramamine (dimenhydrinate), among others. One study of patients presenting to the ER with nausea or vomiting found “no definite evidence to support the superiority of any one drug over any other drug” (Furyk et al., 2015).

If you're experiencing nausea or vomiting as a side effect of your GLP-1 medication, you're not alone! Talk to your doctor about the options before trying any new medications or supplements. It's important to share your medical history with your healthcare provider, so they can suggest a safe and effective option for you.

References

Cotton JW, Rowell LR, Hood RR, Pellegrini JE. A comparative analysis of isopropyl alcohol and ondansetron in the treatment of postoperative nausea and vomiting from the hospital setting to the home. AANA J. 2007;75:21–6

Furyk JS, Meek RA, Egerton-Warburton D. Drugs for the treatment of nausea and vomiting in adults in the emergency department setting. Cochrane Database Syst Rev. 2015;2015(9):CD010106. Published 2015 Sep 28. doi:10.1002/14651858.CD010106.pub2

Gorgojo-Martínez, J. J., Mezquita-Raya, P., Carretero-Gómez, J., Castro, A., Cebrián-Cuenca, A., de Torres-Sánchez, A., García-de-Lucas, M. D., Núñez, J., Obaya, J. C., Soler, M. J., Górriz, J. L., & Rubio-Herrera, M. Á. (2022). Clinical Recommendations to Manage Gastrointestinal Adverse Events in Patients Treated with Glp-1 Receptor Agonists: A Multidisciplinary Expert Consensus. Journal of clinical medicine, 12(1), 145. 

Griddine A, Bush JS. Ondansetron. [Updated 2023 Feb 15]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2024 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK499839/

Winston AW, Rinehart RS, Riley GP, Vacchiano CA, Pellegrini JE. Comparison of inhaled isopropyl alcohol and intravenous ondansetron for treatment of postoperative nausea. AANA J. 2003;71(2):127-132.