Ondansetron

Ondansetron

Ondansetron was invented in the 1980’s in an English laboratory affiliated with the pharmaceutical company GlaxoSmithKline (GSK) The FDA approved ondansetron in January of 1991 under the name Zofran, and the generic ondansetron hit the market in the United States in 2007 (Brodhead). Zofran is primarily used to prevent nausea and vomiting due to chemotherapy, radiation treatment, or anesthetics (Cunha). Ondansetron has also shown to be effective in treating various other ailments including irritable bowel syndrome, vertigo, drug withdrawal, depression, and chronic diarrhea.

Ondansetron is a 5-hydroxytryptamine₃ (5-HT₃) antagonist. 5-HT, a monoaminergic neurotransmitter, helps control many physiological functions such as contraction and relaxation in muscles in respiratory and gastrointestinal systems, mood changes, and sleep induction. Ondansetron targets 5-HT-rich areas of the body to prevent vomiting from occurring. Ondansetron also affects the central nervous system and encourages cells to release dopamine, which helps block the 5-HT receptors from acting (Ye et al).

Available to be administered orally or via injection, ondansetron is a hydrochloride dehydrate base. The drug is absorbed easily and can be taken with food or antacids. The half-life of ondansetron is only two to four hours with a clearance rate of 541 mL/min. The adverse effects reported with ondansetron use are mild but common. Patients may have a headache, but this is most commonly found in patients who are prone to migraines or are experiencing caffeine withdrawal due to pre-surgical diet limitations. Some patients may experience an increased heart rate or blood pressure, and fatigue has been noted to be associated with ondansetron. (Ye et al)

An older form of this medication, promethazine, was almost equally as efficient in treating nausea and vomiting in patients. However, promethazine was frequently associated with severe sedation and did not allow patients to continue with their daily routines uninterrupted. Ondansetron is a much weaker sedative and is able to be taken without great risk of sedation. Akathisia was also reported in patients who took promethazine, while ondansetron does not seem to produce this adverse effect (Braude, Crandall)

In 2011, the FDA recalled all 32 mg doses of intravenous Zofran due to cardiac risks. The drug seemed to cause an arrhythmia called AT interval prolongation, which is potentially fatal. GSK was required to begin a study into why the drug was causing this heart rhythm, and the 32 mg dose was taken off the market by 2013 (FDA).

Ondansetron is a popular drug sold by many companies like Teva, Hospira, and Pfizer, and it is available in almost all pharmacies. It is a relatively low cost drug, available for just under 10 USD, while the name brand Zofran can cost hundreds of dollars without health insurance. Currently, several patents are under review for various ways of administering ondansetron. A research group in America is currently trying to make an aerosol version of ondansetron that can be administered as a mouth spray. This form of ondansetron would have a stable shelf life and a quick response time (Vangara et al). Another researcher in China has invented a type of “water-free swallowing granule” that tastes better and is more digested (Gongye).

Ondansetron is currently not approved for treatment of morning sickness in pregnant women. The issue arises in that ondansetron may cause birth defects, but tests are still being run to produce reliable results (Brodhead).

Works Cited

Braude, D, and C Crandall. “Ondansetron versus Promethazine to Treat Acute Undifferentiated Nausea in the Emergency Department: a Randomized, Double-Blind, Noninferiority Trial.” Current Neurology and Neuroscience Reports., U.S. National Library of Medicine, Mar. 2008, www.ncbi.nlm.nih.gov/pubmed/18304050.

Brodhead, Peter J. “The History of Zofran.” Spangenberg Shibley & Liber LLP, 2015, www.spanglaw.com/blog/2015/february/the-history-of-zofran/

Cunha, John. “Ondansetron (Zofran): Side Effects, Dosages, Treatment, Interactions, Warnings.” RxList, 2017, www.rxlist.com/consumer_ondansetron_zofran/drugs-condition.html

“Drug Safety and Availability - FDA Drug Safety Communication: Abnormal Heart Rhythms May Be Associated with Use of Zofran (Ondansetron).” U S Food and Drug Administration Home Page, Center for Drug Evaluation and Research, 2011, www.fda.gov/Drugs/DrugSafety/ucm271913.htm.

“Drug Safety and Availability - FDA Drug Safety Communication: Updated Information on 32 Mg Intravenous Ondansetron (Zofran) Dose and Pre-Mixed Ondansetron Products.” U S Food and Drug Administration Home Page, Center for Drug Evaluation and Research, 4 Dec. 2012, www.fda.gov/Drugs/DrugSafety/ucm330049.htm.

Vangara, et al. “SUBLINGUAL ONDANSETRO SPRAY.” Patentscope.wipo.int, 16 Feb. 2018, patentscope.wipo.int/search/en/detail.jsf?docId=WO2018031292&tab=PCTBIBLIO&office=&prevFilter=&sortOption=Pub%2BDate%2BDesc&queryString=FP%3A%28ondansetron%29&recNum=2&maxRec=478.

Gongye, Xiangxin. “Ondansetron Water-Free-Swallowing Granules.” WIPO - Search International and National Patent Collections, 2018, patentscope.wipo.int/search/en/detail.jsf?docId=CN212110820&tab=NATIONALBIBLIO&office=&prevFilter=&sortOption=Pub%2BDate%2BDesc&queryString=FP%3A%28ondansetron%29&recNum=4&maxRec=478.

Ye, Jiang-Hong, Rex Ponnudurai, and Rebecca Shaefer. “Ondansetron: A Selective 5-HT₃ Receptor Antagonist and Its Applications in CNS-Related Disorders.” CNS Drug Reviews. Vol 7. No. 2. Department of Anesthesiology, UMDNJ, 2001.