Zofran® is a prescription medication used to treat and prevent nausea and vomiting in people with cancer, those recovering from surgery, and pregnant women with morning sickness. Lawsuits have been filed against the makers of Zofran because many believe fetal exposure to the drug causes serious birth defects, including heart problems and cleft palate.
December 4, 2012The 32 mg, single intravenous (IV) dose of Zofran would be removed from the market due to being associated with an increased risk of serious cardiac issues. However, no official recall was issued from the manufacturer or FDA. A previous Drug Safety Communication, issued on June 29, 2012, warned that the 32 mg, single IV dose should be avoided due to the risk of a specific type of irregular heart rhythm called QT interval prolongation, which can lead to Torsades de Pointes, an abnormal, potentially fatal heart rhythm. (.pdf)
Questions & Answers
Side Effects & Adverse Reactions
Side effects of Zofran include dizziness, stomach aches, oxygen deficiency of tissue (hypoxia), muscle stiffness and spasms, lightheadedness, fatigue, severe skin itching (pruritus), soreness and irritation at the injection site (for the injectable version), anxiety, hiccups, constipation, changes in vision, gynecological problems, and headache. Be cautious when taking this medication and operating dangerous machinery or engaging in other activities that require you to be alert until you are sure of how it affects you. Consumption of alcohol may increase drowsiness and dizziness, and therefore should be limited. Older individuals are more likely to experience these side effects, and should be extra careful when participating in activities that have the potential to be dangerous. (webmd.com) Hypersensitivity reactions have been reported in patients who have exhibited hypersensitivity to other selective 5-HT receptor antagonists.
Serious and Fatal Side EffectsSerious complications that have been reported by patients taking this drug include fainting, chest pain, and irregular heartbeat (too fast or too slow). Stevens-Johnson syndrome, a rare, but serious skin and mucous membrane disorder that can cause blisters, fever, and rash, has also developed in patients that took Zofran. (reference.medscape.com) The development of fatal complications such as serotonin syndrome, Stevens-Johnson syndrome, and long QT syndrome (LQTS) have also been reported.
Pregnancy Risk & Influence on Fetal DevelopmentThe FDA has listed Zofran as a category “B” pregnancy risk. Therefore, there is not enough information on how ondansetron affects a developing fetus or nursing baby, and should be avoided unless deemed necessary by a doctor. In a recent study, surgically removed fetuses that belonged to women who took Zofran during their first trimester of pregnancy were found to contain a significant amount of ondansetron - in fact, every single one that was examined. (ncbi.nlm.nih.gov)
Drug InteractionsTaking ondansetron, especially with other medications that increase serotonin, can result in a serious condition called serotonin syndrome (or serotonin toxicity). Signs of toxicity include twitching muscles, fever, severe loss of coordination, dizziness, hallucinations, fast heartbeat, severe vomiting, nausea, diarrhea, and restlessness/agitation. If you are experiencing the following severe adverse reactions after taking Zofran, get immediate medical attention: swelling and itching of the face, throat, and/or tongue, difficulty breathing, rash, and profound dizziness. Serotonin syndrome is most likely to occur when you start or increase your dose of the medication. Taking antidepressants and other drugs that affect serotonin, including St. John's wart, SSRI’s (such as paroxetine, fluoxetine), SNRI’s (including venlafaxine, duloxetine), and certain street drugs like MDMA (ecstasy) increase the risk of developing this condition. Individuals with a personal or family history of long QT syndrome (QT prolongation), other heart rhythm disorders, or heart failure are advised not to take Zofran, as they are more likely to faint or experience sudden death. Those who currently have, or have had liver disease or low levels of potassium or magnesium in their blood also shouldn’t take Ondansetron. The orally disintegrating tablets contain aspartame (that forms phenylalanine), so people with phenylketonuria (PKU) that follow a special diet may not be a good candidate for this drug. (nlm.nih.gov) People who are allergic to Lotronex (alosetron), Kytril (granisetron), ondansetron, Akynzeo (palonosetron), Aloxi (also palonosetron), and Anzemet (dolasetron), and those taking Apokyn (apomorphine) are more likely to experience negative reactions if they take Zofran. Certain seizure medications, such as Epitol, Carbatrol, Tegretol, and Equetro (carbamazepine) and Dilantin (phenytoin), and Clarithromycin, a medication used to treat infection, also do not interact well with this medication. Migraine medications to avoid while taking this drug include Imitrex (sumatriptan), Relpax (eletriptan), Frova (frovatriptan), Maxalt (rizatriptan), Axert (almotriptan), Zomig (zolmitriptan), and Amerge (naratriptan). Those taking it should not be treated with methylene blue, as complications can occur from this combination. Psychiatric drugs (mental health medications) that shouldn’t be taken with Zofran (unless advised by a doctor because the benefits outweigh the risks) are: lithium, SSRI’s (selective serotonin reuptake inhibitors), including Lexapro (escitalopram), tramadol, Luvox (fluvoxamine), Celexa (citalopram), Paxil, Brisdelle, Pexeva (paroxetine), Prozac, Symbyax, Sarafem (fluoxetine), and Zoloft (sertraline). MAOi’s (monoamine oxidase inhibitors) such as Avelox (moxifloxacin), (Emsam, Zelapar, Eldepryl (selegiline), Parnate (tranylcypromine), Nardil (phenelzine), Zyvox (linezolid), and Marplan (isocarboxazid) should also be avoided. Remeron (mirtazapine), another medication used to treat depression, may also interact negatively.
Women that took Zofran while pregnant blame the drug for serious birth defects, including cleft palate and heart defects. These lawsuits claim that GlaxoSmithKline, the manufacturer of Zofran, hid the risks associated with the drug and improperly marketed it as a medication to treat morning sickness in pregnant women. Families are seeking compensation for medical expenses and losses resulting from surgeries and procedures related to these birth defects. Despite the fact that limited information exists on how ondansetron influences fetal development, more than one million pregnant women are treated with the drug annually. Did You Take Zofran?
FDA Safety Alerts
September 2014Ondansetron (Zuplenz, Zofran ODT), ondansetron hydrochloride (Injection, Tablets, and Oral Solution), and other 5-HT3 receptor antagonists can cause serotonin syndrome, which can be fatal. Symptoms of serotonin syndrome are dizziness, fever, mental health changes, hallucinations, fast heartbeat, nausea, tremors, muscle stiffness, vomiting, diarrhea, seizures, and coma. (fda.gov)
June 29, 2012Following a clinical study suggesting that a 32 mg single intravenous dose of ondansetron (Zofran, ondansetron hydrochloride, and generics) may affect the electrical activity of the heart (QT interval prolongation), which could pre-dispose patients to develop an abnormal and potentially fatal heart rhythm known as Torsades de Pointes, FDA added published this update to the September 2011 Safety Communication. Zofran manufacturer GlaxoSmithKline also suggested label changes recommending ondansetron continue to be used in children and adults with chemotherapy-induced nausea and vomiting at the lower intravenous dose recommended in the drug label. (fda.gov)
September 15, 2011Patients with certain heart conditions should not take the drug because they are more likely to experience serious complications. People with congenital long QT syndrome and those with low levels of magnesium and potassium in their blood have an increased risk of developing Torsade de Pointes, a potentially fatal heart rhythm disorder. (fda.gov)
There is currently no manufacturer warning information available for this drug.
FDA Labeling Changes
December 2013Zofran use can result in the development of toxic epidermal necrolysis (TEN) and Stevens-Johnson syndrome. Toxic epidermal necrolysis, also referred to as Lyell’s syndrome, is a rare, potentially fatal skin condition that is caused by an allergic reaction to medication. Stevens-Johnson syndrome is a rare skin disorder that causes blisters, painful rashes, and flu-like symptoms such as sore throat, fever, and coughing, and can also result in death. (fda.gov)
November 2012Taking ondansetron can cause long QT syndrome (LQTS) and Torsades de Pointes - potentially life-threatening heart rhythm conditions that can lead to fainting, seizures, and cardiac arrest. Individuals with congestive heart failure, electrolyte abnormalities, bradyarrhythmias, or those taking other drugs that can cause QT prolongation should undergo ECG monitoring. (fda.gov)
September 2010Ondansetron should not be taken with apomorphine. Using these drugs together can result in loss of consciousness and dangerously low blood pressure (hypotension). (fda.gov)
Zofran is prescribed alone, or in combination with other medications as an antiemetic (to prevent vomiting and nausea) for people with cancer who are undergoing chemotherapy and/or radiation therapy. Ondansetron is also used to prevent nausea and vomiting in patients who have recently had surgery. The medication belongs to the serotonin 5-HT3 receptor antagonist class of drugs, and works by suppressing the neurotransmitter serotonin, a naturally occurring chemical in the body that is thought to play a role in nausea. It is available as an injection (Zofran), in tablet form (Zofran), in a dissolvable, rapidly disintegrating tablet (Zofran ODT and Zuplenz), and in a liquid solution that is taken by mouth (Zofran Oral Solution). Zofran ODT contains ondansetron, and Zofran and Zuplenz contain ondansetron hydrochloride. (nlm.nih.gov)
- Prevention of nausea and vomiting associated with highly emetogenic cancer chemotherapy, including cisplatin ≥50 mg/m
- Prevention of nausea and vomiting associated with initial and repeat courses of moderately emetogenic cancer chemotherapy.
- Prevention of nausea and vomiting associated with radiotherapy in patients receiving either total body irradiation, single high-dose fraction to the abdomen, or daily fractions to the abdomen.
- Prevention of postoperative nausea and/or vomiting. As with other antiemetics, routine prophylaxis is not recommended for patients in whom there is little expectation that nausea and/or vomiting will occur postoperatively. In patients where nausea and/or vomiting must be avoided postoperatively, ZOFRAN Tablets, ZOFRAN ODT Orally Disintegrating Tablets, and ZOFRAN Oral Solution are recommended even where the incidence of postoperative nausea and/or vomiting is low.
Zofran was developed by GlaxoSmithKline in London in the mid-1980’s, and was patented in the United States in 1988. Novartis Pharms Corp began manufacturing the injectable version in 1991 and the tablet form in 1992. In 1997, the oral solution became available and, in 1999, a higher strength of the tablet form was released. Generic versions came on the market in 2006 when GlaxoSmithKline lost it’s patent for the drug and SICOR Pharmaceuticals and Teva Pharmaceuticals USA started marketing it. In 2010, the FDA approved Zuplenz, an orally soluble film (OSF) that contains ondansetron, and is manufactured by Strativa Pharmaceuticals, a division of Par Pharmaceutical. In 2014, Galena Biopharma began to market Zuplenz and, by 2015, Zofran was being sold by Novartis. (us.gsk.com)
The active ingredient in ZOFRAN Tablets and ZOFRAN Oral Solution is ondansetron hydrochloride (HCl) as the dihydrate, the racemic form of ondansetron and a selective blocking agent of the serotonin 5-HT3 receptor type. Chemically it is (±) 1, 2, 3, 9-tetrahydro-9-methyl-3-[(2-methyl-1H-imidazol-1-yl)methyl]-4H-carbazol-4-one, monohydrochloride, dihydrate. It has the following structural formula:The empirical formula is C18H19N3O•HCl•2H2O, representing a molecular weight of 365.9. Ondansetron HCl dihydrate is a white to off-white powder that is soluble in water and normal saline. The active ingredient in ZOFRAN ODT Orally Disintegrating Tablets is ondansetron base, the racemic form of ondansetron, and a selective blocking agent of the serotonin 5-HT3 receptor type. Chemically it is (±) 1, 2, 3, 9-tetrahydro-9-methyl-3-[(2-methyl-1H-imidazol-1-yl)methyl]-4H-carbazol-4-one. It has the following structural formula: The empirical formula is C18H19N3O representing a molecular weight of 293.4.