More About Zofran

What Is Zofran?

Zofran (ondansetron) is an antinausea drug frequently used to mitigate the effects of cancer treatments, including chemotherapy and radiation therapy. It has also been used as an off-label treatment for morning sickness, although such use is controversial and may lead to birth defects.

Originally developed in the 1980s by the English pharmaceutical company GlaxoSmithKline, Zofran was later approved in the United States by the FDA. Upon the drug’s U.S. patent expiration in 2006, it was the 20th highest-selling brand name drug in the country. In 2015, GlaxoSmithKline’s oncology division was sold to Novartis, who acquired the trademark rights to Zofran as part of the transaction. Other companies sell ondansetron – the active ingredient in Zofran – under various other names. In the U.S., the second-most common brand name for ondansetron is Zuplenz.

The World Health Organization has included ondansetron on it’s list of essential medicines needed for a country’s basic health-care system. Since the patent on ondansetron expired more than a decade ago, it is available in many generic forms throughout the world.

Zofran Side Effects and Risks

There are a number of safety concerns related to ondansetron. The most common Zofran side effects, according to the FDA, are headache, fatigue, constipation, and diarrhea. However, much more severe conditions can result from taking Zofran, including serotonin syndrome and arrhythmia, each of which can result in death.

Some of the most severe side effects include:

  • Serotonin Syndrome – A severe medical condition caused by the physiological effects of blocking serotonin in the brain.
  • Abnormal Hearth Rhythms – Zofran can affect the heart’s QT interval (electrical cycle), in turn affecting the rhythm of the heart and potentially causing death.
  • Birth Defects – Zofran can cause birth defects in the fetuses of women who take the drug while pregnant.

The most common adverse side effects of Zofran include headache, fatigue, anxiety, irritability, weakness, dry mouth, chills, drowsiness, insomnia, constipation, and diarrhea. As your body gets used to the medication, these symptoms may disappear, but if they persist, you should tell your doctor. If you or someone you know experiences any of the following more serious side effects of Zofran, call your doctor immediately or seek emergency medical treatment.

Common Zofran Side Effects

  • Agitation
  • Blurred vision or vision loss
  • Chest pain
  • Coma (loss of consciousness)
  • Confusion
  • Difficulty breathing or swallowing
  • Dizziness, lightheadedness, or fainting
  • Excessive sweating
  • Fast, slow or irregular heartbeat
  • Fever
  • Hallucinations
  • Hives
  • Hoarseness
  • Itching
  • Loss of coordination
  • Nausea, vomiting, or diarrhea
  • Rash
  • Seizures
  • Shortness of breath
  • Stiff or twitching muscles
  • Swelling of the eyes, face, lips, tongue, throat, hands, feet, ankles, or lower legs

Much more severe conditions can result from taking Zofran, including serotonin syndrome and arrhythmia, both of which can result in death.

Serotonin Syndrome

Researchers believe that the primary trigger of nausea and vomiting is rising levels of serotonin, a chemical produced naturally in the gastrointestinal tract and other areas of the body. Zofran helps prevent nausea and vomiting by blocking serotonin from reaching brain cells. When serotonin is prevented from reaching corresponding receptors in the brain, the chemical quickly accumulates. This buildup can lead to serotonin syndrome, which is essentially a type of poisoning that is life threatening.

Due to the physiological effects of blocking serotonin in this way, taking Zofran may lead to severe side effects and conditions (in addition to the ones listed above), including:

  • Autonomic instability
  • Delirium
  • Diaphoresis
  • Hyperreflexia
  • Hyperthermia
  • Flushing
  • Labile blood pressure
  • Myoclonus
  • Neuromuscular problems
  • Other mental status changes
  • Rigidity
  • Tachycardia
  • Tremors

These Zofran side effects are most frequently reported in patients who are taking other types of drugs that affect serotonin levels, including selective serotonin reuptake inhibitors (SSRIs), serotonin and norepinephrine reuptake inhibitors (SNRIs), monoamine oxidase inhibitors, mirtazapine, fentanyl, lithium, tramadol, and intravenous methylene blue.

Zofran and Abnormal Heart Rhythms

In 2011, the FDA issued a safety warning that Zofran can affect the heart’s electrical cycle (known as the QT interval), which can impact the rhythm of the heart. Specifically, Zofran can increase the QT interval, leading to an abnormal heart condition known as torsades de pointes or “twisting of the points.” This is a life-threatening cardiac condition that causes a rapid heartbeat and may lead to sudden death by heart attack.

While this condition can occur with any form and dosage of Zofran, it is most closely linked with the intravenous (IV) 32 mg dosage. In 2012, the FDA issued a safety warning about the dangers of IV ondansetron, and as a result, several manufacturers took their versions of the drug off the market, including Baxter Healthcare, Hospira, Teva, Bedford Labs, and Claris.

For people with underlying heart conditions, such as long QT syndrome, taking Zofran may increase their already high risk for developing torsade de pointes. It is important to tell your doctor if you or your family members have this syndrome, or if you’ve ever had fainting spells due to an irregular heartbeat. Electrocardiogram (ECG) monitoring is recommended in patients with conditions such as congestive heart failure.

Zofran and Pregnancy

Although it has not been approved by the FDA for use by pregnant women in combating pregnancy-related nausea, Zofran has been prescribed by many doctors as an off-label treatment for morning sickness. Worldwide attention was brought to this off-label use of Zofran in 2012 and 2014 when Kate Middleton, the Duchess of Cambridge and wife of Prince William of England, was prescribed the drug for each of her two pregnancies. The risks related to pregnant women and fetuses are disputed and still largely unknown.

The FDA has stated that studies report “inconsistent outcomes,” and many have had problems with their methodologies that prevent the agency from making a determination about the drug’s safety. Research continues to link the medication with birth defects, prompting mothers to file Zofran lawsuits against the manufacturers.

Cleft Palate

A 2011 study by Boston University’s Slone Epidemiology Center and the Centers for Disease Control and Prevention found “possible risks” of Zofran, particularly for cleft palate. The researchers said they found statistical evidence that warranted further investigation.

Cardiac Septum Defect

In 2012, another study reviewed data from the Swedish Medical Birth Register and the Swedish Register of Prescribed Drugs on over 1,000 infants delivered by women who took ondansetron in early pregnancy between 1998 and 2012. After statistical analysis on the incidence of congenital malformations, researchers found a low but increased risk for a cardiac septum defect, but no increased risk for a major malformation.

Congenital Heart Defects

Two 2013 studies that used data from the Medical Birth Registry and National Patient Register in Denmark yielded conflicting results. Published in the New England Journal of Medicine, the first study analyzed data collected from 2004 to 2011, with an average fetus age exposed to Zofran at 10 weeks – past the window of time when malformations could develop. The study concluded there was no increased risk of adverse fetal outcomes. The second study look at data from 1997 to 2010, and found 58 women out of 1,248 that took ondansetron in the first trimester had a baby with a birth defect, representing a 30 percent increased risk.

Kidney Malformations

A separate 2013 study examined birth records from 2002 to 2005 in Western Australia, and found no adverse outcomes but could not conclude that Zofran is safe to use in pregnancy. Researchers noted that although the study was too small to assess risks of individual birth defects, they did see a seven-fold increase in the risk for kidney malformations associated with the drug.

Zofran Drug Interactions

It is important to tell your doctor about all drugs you are taking, including over-the-counter medications, herbs, and supplements. Some drugs may affect the way Zofran works or may affect other medications you are taking. Drugs known to interact with Zofran, which may cause problems include:

  • Apomorphine
  • Beta blockers, or drugs used to slow the heart rate, such as acebutolol (Sectral), atenolol (Tenormin), bisoprolol (Zebeta), and others
  • Medications to treat irregular heartbeat, such as amiodarone (Cordarone, Pacerone), disopyramide (Norpace), dofetilide (Tikosyn) and others
  • Other serotonin 5-HT3 antagonists, including Lotronex, Anzemet, Kytril, and Aloxi Some antibiotics, such as clarithromycin (Biaxin, in Prevpac) and erythromycin (E.E.S., Erythrocin)
  • Some anti-seizure medications, such as phenytoin (Dilantin)
  • Some antipsychotic medications, including thioridazine (Mellaril), haloperidol (Haldol), and mesoridazine (Serentil)
  • Some drugs used to treat depression, including venlafaxine (Effexor) and amitriptyline (Elavil)
  • The pain medicine tramadol (Ultram, Ultracet)

Additionally, you should use caution while taking Zofran if you have certain health conditions. Let your doctor know if you have or ever had any of the following conditions:

  • Inherited phenylketonuria, PKU
  • Heart rhythm problems, including congenital long QT syndrome
  • History of congestive heart failure
  • Low magnesium or low potassium
  • Liver disease

Zofran Dosage and Medical Information

While Zofran is most commonly prescribed during cancer treatment, it may also be used to prevent nausea and vomiting during or after surgery. As a prophylactic treatment, Zofran is typically given to the patient approximately 30 minutes before their cancer treatment or 1 hour before being given anesthesia in preparation for surgery. It will usually be administered for up to 8 hours after the cancer treatment or surgery.

Morning Sickness

Although it has not been approved by the FDA for use by pregnant women in combating pregnancy-related nausea, Zofran has been prescribed by many doctors as an off-label treatment for morning sickness. Worldwide attention was brought to this off-label use of Zofran in 2012 and 2014 when Kate Middleton, the wife of Prince William of England, was prescribed the drug for each of her two pregnancies. The risks of Zofran for pregnant women and fetuses are disputed and still largely unknown. The FDA has stated that studies have reported “inconsistent outcomes,” and that many of the studies have problems with their methodologies that prevent the agency from making a determination about Zofran’s safety.

Off-Label Uses of Zofran

According to a 2013 study published in the Journal of Clinical Outcomes Management, ondansetron is prescribed frequently in hospitals for reasons other than to prevent nausea and vomiting related to treatment of cancer or surgery. The study indicated that elderly patients were more likely to receive ondansetron than standard antiemetic treatment in hospital settings, despite a lack of evidence suggesting its effectiveness at treating nausea and vomiting over other drugs. Separately, a 2006 study looked at the effects of Zofran on children who visited a pediatric emergency department with gastroenteritis (a viral infection that can cause diarrhea and vomiting) and dehydration. According to the results of the study, children who took Zofran were less likely to vomit, and those who vomited did so fewer times than those who took a placebo.

Zofran Drug Details

BRAND NAME Zofran, Zofran ODT, Zuplenz

GENERIC NAME ondansetron, ondansetron hydrochloride

TREATS/PREVENTS Nausea/Vomiting

MANUFACTURER Novartis/GlaxoSmithKline (Zofran), MidaTech Pharma (Zuplenz), others (generic)

COMMON DOSAGES 4 mg (children), 8 mg, 16 mg, 24 mg

FDA HISTORY First approved in 1991; label updated in September 2016

Zofran Lawsuits

GlaxoSmithKline is the subject of hundreds of zofran lawsuits due to the drug’s severe side effects, including the risk of birth defects. In 2015, Novartis purchased the oncology division of GlaxoSmithKline, and as a result Novartis is now also named as a defendant in lawsuits claiming Zofran-related damages after March 23, 2015.