What is Zofran?
Zofran (generic: ondansetron) is used to prevent nausea and vomiting caused by chemotherapy and radiation treatment, as well as after certain types of surgery. The drug works by blocking one of the body’s natural substances (serotonin) that causes vomiting. Zofran is made by GlaxoSmithKline (GSK), and was approved by the U.S. Food & Drug Administration (FDA) in January 1991.
What’s the Problem?
Pregnant women who take Zofran “off-label” for morning sickness may be unknowingly exposing their unborn babies to an increased risk for a large number of severe, potentially life-threatening birth defects.
Zofran Birth Defects
From January 1, 1991 to April 30, 2015, FDA received at least 8,682 reports of adverse events linked to Zofran. Of these, 475 cases (5.4%) involved birth defects including:
- Heart Defects
- Heart Murmur
- Atrial Septal Defect (ASD)
- Ventricular Septal Defect (VSD)
- Atrioventricular Septal Defect (AVSD)
- Cerebral Hemorrhage or Cerebral Hemorrhage Fetal
- Anomalous Pulmonary Venous Connection
- Pulmonary Valve Stenosis
- Pulmonary Artery Stenosis
- Arterial Stenosis
- Pulmonary Artery Atresia
- Pulmonary Hypertension
- Hypertension Neonatal
- Patent Ductus Arteriosus (PDA)
- Left Ventricular Hypertrophy
- Ventricular Hypoplasia (also known as “Hypoplastic Left Heart Syndrome,” or HLHS)
- Coarctation of the Aorta (COA)
- Bicuspid Aortic Valve
- Congenital Aortic Valve Incompetence
- Congenital Tricuspid Valve Atresia
- Tetralogy of Fallot (TOF)
- Mitral Valve Disease
- Shone’s Complex
- Ebstein’s Anomaly
- Wolff-Parkinson-White Syndrome
- Arterial Thrombosis
- Cardiac Flutter or “Atrial Flutter”
- Cardiac Murmur
- Fetal Arrhythmia
- Persistent Fetal Circulation
- Peripheral Venous Disease
- Fetal Heart Rate Abnormal, “Fetal Heart Rate Deceleration Abnormal” or “Heart Rate Dereased”
- Heart Rate Increased
- Platelet Count Increased
- Reticulocyte Count Increased
- Hemoglobin Increased
- Hemoglobin Decreased
- Blood Potassium Increased
- Blood Potassium Decreased
- Hematocrit Decreased or “Haematocrit Decreased”
- Naevus Flammeus
- Musculoskeletal Anomaly
- Mouth Deformity
- Cleft Palate
- Cleft Lip
- Deafness Congenital
- Pierre Robin Syndrome
- Cleft Uvula
- Ankyloglossia Congenital or “Tongue-Tie”
- Upper Airway Obstruction
- Congenital Nose Malformation or Deformity
- Ear Malformation
- Deafness Congenital
- Otitis Media Chronic
- Eustachian Tube Dysfunction
- Low Set Ears
- Skull Malformation
- Congenital Jaw Malformation
- Speech Disorder or “Speech Disorder Developmental”
- Tooth Disorder
- Dental Caries
- Lip Ulceration
- Intrauterine Growth Restriction, or IUGR (also known as “Fetal Growth Restriction”)
- Poor Peripheral Circulation
- Kidney Defects
- Bladder Defects
- Metabolic Acidosis or “Late Metabolic Acidosis of Prematurity”
- Renal Cyst
- Pelvic Kidney
- Kidney Duplex
- Single Function Kidney
- Bartter’s Syndrome
- Urinary Tract Disorder
- Congenital Bladder Anomaly
- Urinary Tract Infection (UTI)
- Gastrointestinal Defects
- Anal Atresia
- Anorectal Disorder
- Congenital Intestinal Malformation
- Gastrointestinal Disorder Congenital
- Abdominal Wall Anomaly
- Inguinal Hernia
- Intestinal Obstruction
- Intestinal Fistula
- Anal Fistula
- Duodenal Atresia
- Large Intestinal Atresia
- Ileal Atresia
- Abdominal Pain
- Oesophageal Atresia
- Pyloric Stenosis
- Gastric Ulcer
- Gastroesophageal Reflux Disease or “Acid Reflux”
- Necrotising Enterocolitis Neonatal
- Respiratory Defects
- Neonatal Respiratory Distress Syndrome
- Respiratory Arrest
- Lung Disorder
- Neonatal Respiratory Depression
- Neonatal Apnea or “Apnea of Prematurity” (AOP)
- Tachypnoea or “Transient Tachypnoea of the Newborn”
- Congenital Pneumonia
- Obstructive Airway Disorder or “Obstructive Lung Disease”
- Cyanosis Neonatal
- Pulmonary Hypoplasia
- Pulmonary Hyperplasia
- Neonatal Hypoxia
- Congenital Diaphragmatic Anomaly or Disorder
- Diaphragmatic Aplasia
- Immature Respiratory System
- Bronchopulmonary Dysplasia
- Neonatal Aspiration
- Meconium Stain or “Meconium in the Amniotic Fluid”
- Limb Defects
- Clubfoot or “Talipes”
- Reproductive Defects
- Fetal Death
- Spontaneous Abortion
- Missed Abortion
- Unspecified Congenital Anomalies
- Other Birth Defects
The following studies have linked the maternal use of Zofran during pregnancy to congenital heart defects:
- A study presented at the 2013 International Conference on Pharmacoepidemiology in Montreal found that babies exposed to Zofran during the first trimester were 2.1 times more likely to have atrial septal defects, 2.3 times more likely to have ventricular septal defects, and 4.8 times more likely to have atrioventricular septal defects.
- In December 2014, a study published in Reproductive Toxicology concluded that use of Zofran during the first trimester correlated with a 1.62 times increased risk of “cardiac septum defects,” a category of birth defects that includes atrial septal defects, ventricular septal defects and atrioventricular septal defects.
- ‘Animal teratogenicity studies’ GSK allegedly performed in Japan after Zofran was approved in the U.S. found a link between Zofran and congenital heart defects.
A November 2011 study published in Birth Defects Research linked the use of Zofran during pregnancy to a 2.4-fold increased risk of cleft palate. The results were based on data from approximately 9,000 pregnancies, and the research was conducted in conjunction with the Centers for Disease Control and Prevention (CDC).
A study published in the Toronto Star in June 2014 found at least 20 women in Canada who had children with birth defects after they took Zofran during pregnancy. Four of the babies weighed 4.5 lbs or less, and in 6 cases the condition was listed as “fetal growth restriction.” Other problems identified by the researchers included congenital kidney defects.
In November 2013, a study published in BioMed Research International looked at birth outcomes of women who took Zofran during pregnancy in Western Australia from 2002 to 2005. The researchers found a “20% increased risk of a major birth defect amongst children exposed to ondansetron in the first trimester,” while acknowledging a relatively small sample size (251 live births) that prevented their findings from being more accurate. While “the study was too small to assess risks of individual birth defects,” the study’s authors also identified a 7-fold increased risk for kidney defects associated with Zofran use during pregnancy.
Side Effects in Users
In addition to the risk of birth defects in babies exposed in the womb, Zofran may also cause the following serious side effects in pregnant women who use the drug:
- Serotonin syndrome
- Irregular heart rhythm
- QT Interval prolongation
- Torsades de pointes
- Cardiac arrest
January 1991 – Approved by the FDA
January 1991 – Zofran (ondansetron) first approved by the U.S. Food & Drug Administration (FDA).
November 19, 2011 – Birth Defects Research study published
November 19, 2011 – Study published in Birth Defects Research links Zofran to a 2.4-fold increased risk of cleft palate.
June 29, 2012 – FDA warning
June 29, 2012 – FDA warns that Zofran may affect the electrical activity of the heart (QT interval prolongation).
August 2013 – Study presented at the International Conference on Pharmacoepidemiology
August 2013 – Study presented at the International Conference on Pharmacoepidemiology links Zofran to an increased risk for atrial septal defects, ventricular septal defects and atrioventricular septal defects.
November 19, 2013 – Biomed Research International study published
November 19, 2013 – Study published in Biomed Research International finds a 20% increased risk of major birth defects associated with Zofran use during the first trimester, as well as a 7-fold increased risk of kidney defects.
June 25, 2014 – Toronto Star study published
June 25, 2014 – Study published in the Toronto Star finds at least 20 women in Canada who gave birth to babies with severe birth defects (low birth weight, fetal growth restriction, kidney defects) after taking Zofran during pregnancy.
December 2014 – Reproductive Toxicology study published
December 2014 – Study published in Reproductive Toxicology concludes that use of Zofran during the 1st trimester of pregnancy correlates with a “increased and statistically significant” increased risk of cardiovascular birth defects.
- “What Clinicians Should Know About the QT Interval”. The Journal of the American Medical Association (JAMA). April 23, 2003.
- “Medications Used to Treat Nausea and Vomiting of Pregnancy and the Risk of Selected Birth Defects”. Birth Defects Research. November 19, 2011.
- “FDA Drug Safety Communication: New information regarding QT prolongation with ondansetron (Zofran)”. U.S. Food & Drug Administration (FDA). June 29, 2012.
- “How to Survive Morning Sickness Successfully”. Motherisk. August 2013.
- “Off-Label Use of Ondansetron in Pregnancy in Western Australia”. BioMed Research International. September 19, 2013.
- “Birth defects blamed on unapproved morning sickness treatment”. The Toronto Star. June 25, 2014.
- “Serotonin-3 (5-HT3) Receptor Antagonists”. U.S. Food & Drug Administration (FDA). September 2014.
- “Use of ondansetron during pregnancy and congenital malformations in the infant”. Reproductive Toxicology. December 2014.
- “Long QT Syndrome and Torsades de Pointes Ventricular Tachycardia”. Merck Manuals: Professional Version. July 2015.
- “Ondansetron (marketed as Zofran) Information”. U.S. Food & Drug Administration (FDA). July 17, 2015.