Update: GSK Wants Generic Zofran Lawsuits Dismissed
November 9, 2016 – GSK has filed a motion with a Massachusetts federal court requesting that all lawsuits alleging birth defects from the generic version of Zofran — ondansetron — be dismissed.
GSK argued in the motion that Judge F. Dennis Saylor IV should dismiss at least 27 lawsuits filed on behalf of women who allege they had children with birth defects after they were prescribed generic ondansetron for morning sickness during pregnancy. The company claims the suits were filed under state laws that “do not permit a defendant to be held liable for a product it did not manufacture, sell, or distribute.”
In a second motion filed the same day, GSK requested that all fraud-based lawsuits be removed from the MDL, arguing that any “contention that GSK, through its marketing, promotion, and labeling, somehow misrepresented facts about Zofran […] lacks basic factual detail.”
Plaintiffs have opposed the move, calling GSK’s motions a “sweeping” and inappropriate attempt to delay the litigation. Additionally, plaintiffs contend that both dismissal motions are invalid because they require judgments on state law, and thus cannot lead to rulings common to every complaint.
The U.S. JPML consolidated all federal Zofran lawsuits because they contain similar allegations, that:
- GSK fraudulently misrepresented Zofran to doctors re. safety of the medication during pregnancy.
- GSK knew and concealed Zofran’s alleged link with severe congenital birth defects, and failed to provide the public and medical communities with information about this risk.
- GSK marketed Zofran to pregnant women “off-label” for uses not approved by the FDA.
Zofran is an FDA-approved anti-nausea drug that blocks the actions of chemicals in the body that can trigger nausea and vomiting. Zofran is approved to prevent these symptoms in patients undergoing certain types of surgery or cancer treatment (chemotherapy or radiation).
Nausea and vomiting are complex biological processes involving numerous chemicals and body parts, including the brain, heart, and small intestines. Zofran is designed to block serotonin – a chemical produced by the body that is associated with upset stomach and vomiting – at a specific receptor known as the 5-HT3 receptor.
What’s the Problem?
Women who take the anti-nausea medication Zofran (generic: ondansetron) during pregnancy may be unknowingly exposing their babies to an increased risk for severe side effects including congenital heart problems, cleft lip/cleft palate, and gastrointestinal defects.
Although Zofran is not approved to treat morning sickness, it is commonly prescribed “off-label” for this purpose, according to Medscape. In fact, it has been estimated that approximately 1 million pregnant women are prescribed Zofran each year to relieve the symptoms of morning sickness, specifically nausea and vomiting. Off-label prescribing is legal and done at the doctor’s discretion; however, when used in this capacity, Zofran has been linked to birth defects.
Zofran Birth Defects
From January 1, 1991 to April 30, 2015, the 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
- Persistent Pulmonary Hypertension of the Newborn, or PPHN
- 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 Decreased”
- 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 Carries
- 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
- Esophageal 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
What is Intrauterine Growth Restriction (IUGR)?
Intrauterine growth restriction is typically defined as a fetal weight below the 10th percentile for gestational age. The defect may also be referred to as small-for-gestational age (SGA) or fetal growth restriction. There are 2 main types of IUGR:
- Symmetric or Primary IUGR – Characterized by a reduction in size of all internal organs. This form of the defect accounts for approximately 20% to 25% of all cases of IUGR.
- Asymmetric or Secondary IUGR – Head and brain are normal in size, but the abdomen is smaller. This form of IUGR is typically not observable until the 3rd trimester of pregnancy.
Signs and symptoms of intrauterine growth restriction may include:
- Low birth weight
- Difficulty handling delivery
- Decreased oxygen levels
- Low blood sugar (hypoglycemia)
- Low resistance to infection
- Low Apgar scores
- Trouble maintaining body temperature
- High red blood cell count
Even with recent advances in medical technology, effective treatment for intrauterine growth restriction remains problematic. Treatment options depend on how far the patient is along in her pregnancy.
If gestational age is 34 weeks or more, healthcare providers may recommend inducing an early delivery. If under 34 weeks, the fetus will be monitored for amniotic fluid levels and general well-being. If either of these becomes a problem, immediate delivery may be recommended. If delivery is advised before 34 weeks, an amniocentesis may be performed to help evaluate fetal lung maturity.
Zofran Birth Defect Studies
- A Hong Kong-based study published in 2006 found that Zofran readily crosses the human placenta during the 1st trimester of pregnancy. Traces of the drug were found in every sample of fetal tissue taken from 41 test subjects.
- Epidemiological study of more than 10,000 birth records by researchers at Harvard and Boston University links Zofran to a 2.37-fold increased risk of cleft palate.
- In Feb. 2013, a study published in the New England Journal of Medicine found no evidence of birth defects associated with Zofran. However, critics of the study contend that the sample size was too small and the study period too short to accurately determine the risk. A second group of researchers used the same Danish registry used in the first study, expanded the sample size, and found that use of ondansetron during pregnancy doubled the risk of heart defects, and increased the risk of general birth defects by 30%.
- Zofran was associated with a 20% increased risk of kidney defects and other birth defects in a study published in BioMed Research International.
- A 2013 Danish Study titled “Ondansetron use in early pregnancy and the risk of congenital malformations” found a 2-fold increased risk of heart defects in babies whose mothers used ondansetron in pregnancy. The study’s authors looked at nearly 900,000 pregnancies in Denmark that occurred between 1997 and 2010. About 1,250 women reported taking Zofran during their first trimester, including 58 (4.7%) who had a baby with a birth defect. The rate of birth defects was 30% higher for Zofran users compared to non-users, mostly due to the 2-fold increased rate of heart defects.
- In June 2014, a review of Zofran published in the Toronto Star found that “… at least 20 Canadian women treated with ondansetron for vomiting in pregnancy experienced serious suspected side-effects, including two infant deaths and multiple cases of newborns with heart defects and kidney malformations.”
- In December 2014, the ‘Anderson Study’ links ondansetron use during the 1st trimester to a doubled risk for atrial and ventricular septal heart defects, collectively known as “hole in the heart” defects.
- Medical practice guidelines advise physicians to use caution when prescribing Zofran, saying the drug should be used only after all other options for treating morning sickness have been exhausted.
A review of FDA adverse event data for Zofran identified at least 52 references to craniofacial birth defects and associated anomalies, including:
- 7 references to Cleft Lip and Cleft Palate occurring together
- 4 references to Isolated Cleft Palate – Split or opening in the roof of the mouth.
- 7 references to Microcephaly – Condition in which the baby’s head is abnormally small due to insufficient brain growth.
- 5 references to Deafness Congenital – Hearing loss present at birth.
- 4 references of Otitis Media – Chronic middle ear infection often caused by cleft palate.
- 3 references to Pierre Robin syndrome – Series of associated defects in which one malformation leads to another, then another, etc. Pierre Robbin involves a cleft palate and either micrognathia (abnormally smaller lower jaw), retrognathia (lower jaw that is set further back than normal) or glossopteris (tongue that sits far back in the throat, obstructing the airway).
- 3 references to Eustachian Tube Dysfunction – The eustachian tube links the middle ear to the cavity above the roof of the mouth.
- 3 references to unspecified Ear Formation
- 2 references to Micrognathia
- 3 references to Ankyloglossia Congenital or Tongue-Tie – Tongue is “tethered” to floor of mouth by abnormally long strip of tissue.
- 2 references to Cleft Uvula – The uvula, a teardrop of flesh hanging above the opening to the throat, is “forked” or split.
- 2 references to unspecified Congenital Nose Malformation or Deformity
- 2 references to unspecified Speech Disorder or Speech Disorder Developmental
- 2 references to unspecified Tooth Disorder or Malformation
- 2 references to Dental Caries – Tooth decay.
- 1 reference to Retrognathia
- 1 references to Glossopteris – Irregular tongue that obstructs the airway due to its abnormal position far back in the throat.
- 1 reference to Upper Airway Obstruction – Occurs when the upper breathing passages become narrowed or blocked, making it hard to breathe.
- 1 reference to Low Set Ears – Ears are positioned lower on the head than normal.
- 1 reference to unspecified Skull Malformation
- 1 reference to unspecified Jaw Malformation
- 1 reference to Craniosynostosis – Joints between skull bones fuse prematurely.
- 1 references to Otitis Media Acute – Acute middle ear infection.
- 1 reference to Lip Ulceration – Small lesions that develop in the lip.
What is a Cleft Palate?
Cleft palate is a congenital birth defect that occurs when a baby’s mouth does not form correctly in the womb, according to the U.S. Centers for Disease Control and Prevention (CDC). The roof of the mouth, or palate, forms between the sixth and ninth weeks of pregnancy. A cleft palate occurs if the tissue in the roof of the mouth does not join together completely in utero.
In some babies with a cleft palate, both the front and back parts of the palate are open. In others, only a portion of the palate remains open after birth. According to the CDC, about 2,650 babies are born with a cleft palate each year in the United States. Isolated orofacial clefts, or clefts that occur with no other major birth defects, are among the most common types of birth defects in the U.S., the agency found.
Depending on the severity of the cleft defect, treatment usually requires several years and multiple surgeries to provide a satisfactory outcome, according to the American Speech-Language-Hearing Association (ASHA). Cleft palate repair requires a number of surgeries, the first of which should be performed when the child is between 6 months and 1 year old. The first surgery typically involves repairing the defect in the palate, which improves feeding and weight gain, and reduces hearing loss / ear infections. Palate repair also improves development of the upper jaw and facial bones, according to Baylor University Medical Center Proceedings (2002).
At about 8 years of age, a bone graft is done to support the upper jaw structure and help with speech articulation, according to MedicineNet. Braces may be used to straighten permanent teeth, and surgical scar removal may be performed later in life to improve cosmetic appearance.
Zofran Heart Defects
Of the 475 birth defects linked to Zofran, 170 involved malformations of the heart and/or cardiovascular system, including:
- 44 references to Cardiac Septal Defects – Involve cardiac walls that failed to form properly in the womb.
- 21 references to Ventricular Septal Defects – Holes in the wall that separate the heart’s lower chambers, or ventricles.
- 16 references to Atrial Septal Defects – Occurs when a hole remains in the wall that would normally separate the heart’s 2 upper chambers, the atria.
- 12 references to Cerebral Hemorrhage – Type of stroke in which the bursting of an artery within the brain leaks blood into surrounding tissue.
- 7 references to Haemangioma – Birthmark that often appears red and rubbery, caused by the excessive growth of cells lining arteries and veins.
- 6 references to Atrioventricular Septal Defects (ASVD) – Hole in the heart’s center, where the atria on top meet the ventricles below.
- 6 references to Cardiac Murmur – Abnormal sound of blood flowing improperly through the heart; often a symptom of underlying cardiac septal defect.
- 5 references to Hypotension – Abnormally low blood pressure.
- 5 references to Fetal Heart Rate Abnormal – Fetal heart rates that are irregular.
- 4 references to Platelet Count Increased – Platelets are a type of blood cell that allow the blood to clot after injury.
- 4 references to Cardiac Flutter or Atrial Flutter – Abnormal heart rhythm that begins in the heart’s atria.
- 3 references to Pulmonary Valve Stenosis – Malformation that restricts blood flow from the heart to the lungs, typically caused by a valve that is thicker than normal or fails to open properly.
- 3 references to Reticulocyte Count Increased – Reticulocytes are immature red blood cells that develop in bone marrow.
- 3 references to Coarctation of the Aorta (COA) – Abnormally narrow aorta (large blood vessel that transports blood from the heart to the rest of the body).
- 3 references to Hypertension Neonatal – Abnormally high blood pressure.
- 3 references to Bradycardia – Abnormally slow heart action.
- 3 references to Heart Rate Increased – Elevated heart rate.
- 2 references to Pulmonary Artery Stenosis – Abnormal narrowing in the pulmonary artery.
- 2 references to Pulmonary Hypertension – High blood pressure affecting the heart’s right side and arteries in the lungs.
- 2 references to Patent Ductus Arteriosus (PDA) – The ductus arteriosus is a blood vessel that allows blood to circumvent the lungs while babies are in the womb. After birth, the vessel closes within a couple days. In children with PDA, the vessel does not close.
- 2 references to Left Ventricular Hypertrophy – Thickening and enlargement of walls in the heart’s left ventricle.
- 2 references to Ventricular Hypoplasia or Hypoplastic Left Heart Syndrome (HLHS) – Occurs when the heart’s left ventricle is severely underdeveloped.
- 2 references to Congenital Aortic Valve Incompetence – Aortic valve defect in which blood leaks back in the left ventricle after being pumped into the aorta.
- 2 references to Congenital Tricuspid Valve Atresia – In a healthy heart, blood flow between the right ventricle and atrium is controlled by the tricuspid valve. Babies born with tricuspid valve atresia don’t have this valve, but a solid sheet of tissue instead.
- 2 references to Tetralogy of Fallot – Series of the following 4 congenital heart defects occurring together: Ventricular Septal Defect, Pulmonary Stenosis, Right Ventricular Hypertrophy and an Overriding Aorta, in which the aortic valve is enlarged.
- 2 references to Shone’s Complex – Combination of defects on the heart’s left side occurring together: Coarctation of the Aorta, Subaortic Stenosis, Parachute Mitral Valve (abnormal ring of tissue surrounding the mitral valve).
- 2 references to Thrombocytopenia – Abnormally low platelet count.
- 2 references to Fetal Arrhythmia – Abnormal heart rhythm.
- 2 references to Hemoglobin Decreased – Hemoglobin levels below lowest level for age and sex.
- 1 reference to Anomalous Pulmonary Venous Connection – Occurs when veins that transport blood from the lungs to the heart attach at abnormal locations.
- 1 reference to Arterial Stenosis – Abnormal narrowing in an artery.
- 1 reference to Pulmonary Artery Atresia – Malformation of the pulmonary valve in which the valve orifice fails to develop.
- 1 reference to Bicuspid Aortic Valve – The aortic valve, which lies between the heart and aorta, normally has 3 flaps or “leaflets.” In this defect, the valve only has 2 flaps and cannot open properly.
- 1 reference to Mitral Valve Disease – The mitral valve is located between the left ventricle and atrium, controlling blood flow between the 2 chambers.
- 1 reference to Dextrocardia – The heart points to the body’s right side, rather than to its left as is normal.
- 1 reference to Wolff-Parkinson-White Syndrome – Extra electrical pathway leading between the atria and ventricles, often resulting in tachycardia (abnormally fast heartbeat).
- 1 reference to Arterial Thrombosis – Blood clot in artery.
- 1 reference to Persistent Fetal Circulation – Condition that occurs when the body fails to change from the circulation patterns before birth to those that normally develop shortly after birth.
- 1 reference to Peripheral Venous Disease – Malformation which involves defects that prevent blood from pumping up from the hands and feet to the heart properly.
- 1 reference to Poor Peripheral Circulation – Inadequate blood flow to the body’s extremities and skin.
- 1 reference to Thrombocytosis – Disorder in which the body produces too many platelets.
- 1 reference to Coagulopathy – Disorder in which the blood’s ability to clot is impaired.
- 1 reference to Hemoglobin Increased – Hemoglobin is a protein that allows red blood cells to carry oxygen.
- 1 reference to Blood Potassium Increased – Potassium is both a mineral and electrolyte that helps maintain the amount of water inside and outside of cells.
- 1 reference to Hematocrit Decreased or “Haematocrit” Decreased – Hematocrit is the volume percentage of red blood cells in blood.
- 1 reference to Nevus Flammeus – Birthmark caused by abnormally stretched capillaries.
- 1 reference to unspecified Cardiac Septal Defect
Symptoms of a Heart Defect
- Heart murmur
- Shortness of breath
- Rapid heartbeat
- Sweating while feeding
- Cyanosis (blue tint to the skin, lips and/or fingernails)
(Courtesy Mayo Clinic)
Treatment and Care
Not all babies born with heart defects require medical intervention. Some may only need to be observed and visit their cardiologist. In other cases, surgery or a cardiac catheterization may be required to repair the defect. Unfortunately, even when a defect is treated during childhood, additional conditions may develop that require further medical treatment.
Babies born with heart defects may be at risk of developing additional problems in the future. These children typically experience delays with physical coordination (i.e. walking and talking), and may have learning difficulties caused by a poor oxygen supply during early life, which affects development of the brain. Natural intelligence is usually unaffected, but some children with congenital heart defects perform well below standard academic levels.
Atrial Septal Defect
An atrial septal defect, or ASD, is a congenital (present at birth) abnormality characterized by a hole in the upper 2 chambers of the heart (atria). As a baby develops in the womb, a wall called the interatrial septum forms which divides the upper chamber into a left and right atrium. An abnormal formation of the interatrial septum may result in a hole, or atrial septal defect.
Signs and symptoms of an atrial septal defect may include:
- Difficulty breathing (dyspnea)
- Respiratory infections
- Heart palpitations
- Shortness of breath with activity
Atrial septal defects may not require treatment in patients who are asymptomatic, or who have minor symptoms. Surgery to close the ASD may be recommended if the hole causes a large amount of shunting, the heart is swollen, or other symptoms occur.
In recent years, a procedure has been developed to close an atrial septal defect without surgery. The procedure involves placing a closure device into the heart through catheters. The physician makes a small incision in the groin, then inserts the catheters into a blood vessel and up into the heart. The closure device is then placed across the defect and the hole is closed.
What is a Heart Murmur?
Normal heartbeats make a “lub-dupp” or “lub-dub” sound. This is the sound of the heart valves closing as blood moves through the organ. A heart murmur is an unusual whooshing or swishing sound heard during a heartbeat. Depending on the severity of the defect, the sound of the murmur may range from faint to very loud.
Signs and symptoms of a heart murmur in a newborn baby may include:
- Rapid breathing
- Difficulty feeding
- Blueness in the lips (cyanosis)
- Failure to thrive
Symptoms in older patients may include:
- Difficulty exercising or doing physical activity
- Chest pain
To assess whether a heart murmur is normal (“innocent”) or something more serious, a doctor will check the child’s pulse and blood pressure, and listen to his or her heart with a stethoscope. The doctor will then attempt to determine where in the heart the murmur is coming from, when in the heartbeat cycle it occurs, how loud it is and whether it changes when the child moves.
If the murmur is determined to be abnormal or “non-innocent,” it may be caused by a congenital heart defect such as a leaking valve, narrow artery or hole in the heart. If a problem is found, treatment may include drugs to regulate the heart’s rhythm or surgery to correct a structural defect. Many congenital defects are minor and don’t require treatment, as they do not affect the heart’s function.
Zofran has been linked to at least 60 cases of kidney and associated defects, including:
- 48 references to Congenital Kidney and Bladder Defects and Abnormalities
- 12 references to Hydronephrosis or Hydroureter – Obstruction in the kidneys blocks the flow of urine, causing the organ to swell.
- 8 references to Metabolic Acidosis or Late Metabolic Acidosis of Prematurity – Kidneys are unable to remove sufficient amounts of acids from the blood.
- 4 references to Pelvic Kidney – Kidney that remains in the pelvic area, rather than ascending upward as in normal fetal development.
- 3 references to Renal Cyst – Sac of fluid in the kidneys.
- 2 references to Urinary Tract Infection (UTI) – Infection in one or more parts of the urinary system — kidneys, ureters, bladder or urethra. Most infections involve the lower urinary tract — the bladder and urethra.
- 3 references to unspecified Urinary Tract Disorder or Malformation
- 2 references to unspecified Congenital Bladder Anomaly
- 1 reference to unspecified Kidney Malformation.
- 1 reference to Kidney Duplex – 2 ureters attached to a single kidney.
- 1 reference to Single Kidney Function – Only 1 kidney works.
- 1 reference to Bartter’s Syndrome – Malformation that inhibits kidney function.
Kidney Defect Overview
Certain abnormalities may occur in the development of the kidneys or urinary tract in babies whose mothers use Zofran during pregnancy. In some cases, 1 or both kidneys may not develop correctly. In others, an abnormality may occur that blocks the outflow of urine, causing it to back up into the kidneys. This is called hydronephrosis, and causes the kidneys to appear enlarged on the ultrasound test.
Another common kidney-related birth defect is called reflux. This condition occurs when a mechanism near where the ureter joins the bladder does not work, causing urine to wash back up into the kidneys.
Australian Study Finds Increase In Kidney Defects
In Nov. 2013, a study was published in the journal BioMed Research International called “Off-Label Use of Ondansetron in Pregnancy in Western Australia”. The researchers looked at all birth records filed in Western Australia from 2002 to 2005. They then determined how many women had been prescribed Zofran through Australia’s Pharmaceutical Benefits Scheme (PBS), a federal program like Medicare in the U.S.
Of 96,968 live births, only 251 pregnant women were prescribed Zofran during that three year period. The study’s authors noted that Zofran users were typically of higher socioeconomic status, and thus could afford private health insurance. Since the research only included who were women enrolled in a public healthcare program, they suspect that “more pregnant women were diagnosed ondansetron as a private prescription.”
For the study, researchers compared the birth outcomes of women who took Zofran during pregnancy to those who had not. They 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 researchers also found a 7-fold increased risk for kidney defects associated with Zofran.
FDA adverse event data lists 72 references to gastrointestinal defects and related abnormalities which included:
- 9 references to Gastroschisis – Portions of the intestines protrude outside the body through a hole in the abdominal wall.
- 9 references to Anal Atresia – Anus is either completely absent or in an abnormal place.
- 7 references to Intestinal Obstruction – Partial or total blockage in the bowels.
- 6 references to Gastroesophageal Reflux Disease or Acid Reflux – Stomach contents leak from stomach back into esophagus.
- 5 references to unspecified Gastrointestinal Disorder Congenital
- 5 references to Anal Fistula – Infected tunnel between the skin and anus.
- 3 references to Necrotising Enterocolitis Neonatal – Defect in which portions of the bowel tissue undergo premature cell death.
- 3 references to unspecified Anorectal Disorder
- 2 references to Duodenal Atresia – First part of the intestine is either absent or abnormally closed.
- 2 references to Pyloric Stenosis – The valve between the stomach and small intestine is abnormally thick, blocking the flow of blood.
- 2 references to Enterocolitis – Inflammation of the small intestine and colon.
- 2 references to unspecified Abdominal Wall Anomaly
- 2 references to Abdominal Pain
- 2 references to Dyspepsia – Indigestion.
- 1 reference to Congenital Inguinal Hernia – Opening in groin muscles, causes intestinal muscles to push forward, creating a bulge.
- 1 reference to Intestinal Fistula – Abnormal passage or connection between 2 body parts that are not normally connected.
- 1 reference to Hematochezia – Passage of fresh blood through the anus, usually in or with stool.
- 1 reference to Large Intestinal Atresia – Large intestine is either absent or abnormally closed.
- 1 reference to Ileal Atresia – The small intestine’s small segment, the ileum, is either absent or abnormally closed.
- 1 reference to Esophageal Atresia – The esophagus or “gullet” connects the throat to the stomach. In this defect, the esophagus ends in a closed pouch rather than connecting to the stomach.
- 1 reference to Dysphagia – Difficulty swallowing.
- 1 reference to Gastric Ulcer – A break or sore in the lining of the intestines, esophagus or stomach.
- 1 reference to unspecified Congenital Intestinal Malformation
At least 20 cases of congenital limb defects and abnormalities have been linked to Zofran, including 7 cases of clubfoot or “talipes,” a condition in which one or both of the baby’s feet appear twisted inward.
At least 86 reports of congenital respiratory defects have been linked to Zofran, including:
- 24 references to Neonatal Respiratory Distress Syndrome – Inadequately developed lungs causing breathing difficulties.
- 17 references to Neonatal Apnea or Apnea of Prematurity – Problems with temperature regulation, acquisition of oral feeding skills and the normal control of respiration.
- 5 references to Congenital Diaphragmatic Anomaly or Disorder – Malformation of the diaphragm, a sheet of muscle that separates the chest from the abdomen.
- 5 references to Pulmonary Hypoplasia – Incomplete development of the lungs.
- 3 references to Neonatal Respiratory Depression – Dangerous low breathing rate in newborns.
- 3 references to Tachypnoea or “Transient Tachypnoea of the Newborn” – Temporary rapid breathing of the newborn.
- 3 references to Congenital Pneumonia – Lung infection in a neonate.
- 3 references to Cyanosis Neonatal – Blue or purple skin coloration due to insufficient levels of oxygen reaching the skin.
- 3 references to Tracheomalacia – Improper development of the cartilage in the windpipe (trachea).
- 2 references to unspecified Respiratory Disorder Neonatal
- 2 references to Respiratory Arrest – Complete cessation of normal breathing.
- 2 references to Asthma – Condition in which the airways become inflamed, narrow and swell, producing extra mucus.
- 2 references to Neonatal Respiration – Defect in which babies are born with meconium (a baby’s first feces) in the lungs.
- 2 references to Meconium Stain or Meconium in the Amniotic Fluid – Symptom of neonatal aspiration.
- 1 reference to Bradypnoea – Abnormally slow breathing rate.
- 1 reference to Obstructive Airway Disorder or Obstructive Lung Disease – Respiratory condition in which breathing is impaired.
- 1 reference to Dyspnoea – Difficult or labored breathing.
- 1 reference to Bronchospasm – Sudden constriction of the passageways that deliver air from the nose or mouth to the lungs.
- 1 reference to Neonatal Hypoxia – Oxygen levels insufficient to meet physical demands.
- 1 reference to Diaphragmatic Aplasia – Failure of the diaphragm to develop or function properly.
- 1 reference to Immature Respiratory System – Irregular breathing caused by underdeveloped lungs.
- 1 reference to Pneumothorax – Collapsed lung.
- 1 references to Bronchopulmonary Dysplasia – Inflammation and scarring of the lungs.
- 1 reference to unspecified Lung Disorder
Reproductive System Defects
Zofran has been associated with 39 cases of reproductive system birth defects including:
- 18 reports of Hypospadias – Condition in males in which the opening of the urethra is on the underside of the penis.
- 6 cases of Cryptorchidism – Absence of one or both testes from the scrotum.
Other Adverse Fetal Outcomes
382 references to “other adverse fetal outcomes” including:
- 55 references to Fetal Death, Stillbirth, Spontaneous Abortion or Missed Abortion
- 73 references to Premature Babies
- 63 references to Fetal Growth Restriction (fetal weight below tenth percentile for gestational age)
- 21 reports of unspecified congenital anomalies
Have Any Medications Been Approved to Treat Morning Sickness?
Yes. In April 2013, Diclegis (generic: doxylamine and vitamin B6) became the first FDA-approved drug to treat nausea and vomiting in pregnancy. Diclegis was originally introduced in 1956, but it was pulled off the market in 1983 amid product liability lawsuits, only to return again nearly 3 decades later with the FDA’s approval.
“Now that a safe and effective drug is available in the United States, there is no reason for women to be exposed to a drug of unproven maternal and fetal safety,” said Canadian physician and medical researcher Dr. Gideon Koren, who was part of a research team that investigated birth defects associated with ondansetron.
Has Zofran Been Linked to Effects in Users?
In addition to being linked to birth defects in babies exposed to the drug in the womb, Zofran may cause a number of serious side effects in users. Specifically, Zofran has been linked to cardiac arrhythmias and serotonin syndrome, which can be harmful to both the mother and fetus. In June 2012, FDA issued a warning regarding a potential link between Zofran and an increased risk of prolongation of the QT interval, which can cause the potentially fatal arrhythmia Torsade de pointes. FDA warned physicians to avoid prescribing Zofran to patients with congenital long-QT syndrome, and recommended ECG monitoring for users with electrolyte abnormalities, such as hypokalemia or hypomagnesemia.
Zofran Side Effects
- Heart problems
- Cardiac arrhythmias
- Prolongation of the QT Interval
- Torsades de Pointes
- Serotonin Syndrome
- And more
(Courtesy U.S. Food & Drug Administration)
Timeline of Events
- January 1991 – FDA approves Zofran for the treatment of chemotherapy-related nausea and vomiting.
- January 1993 – Pill form of Zofran approved.
- June 1995 – GlaxoWellcome submits New Drug Application for a 4mg/5mL dose of Zofran.
- June 1997 – FDA approves application.
- March 1999 – FDA sends Glaxo warning letter re. its marketing of Zofran. According to the letter, the company failed to warn about the drug’s adverse side effects while touting its effectiveness.
- August 2011 – GSK conducts study titled “A Randomized, Double-blind, Four-period Crossover Study to Investigate the Effect of Intravenous Ondansetron, a 5-HT3 Antagonist, on Cardiac Conduction as Compared to Placebo and Moxifloxacin in Healthy Adult Subjects.”
- September 2011 – FDA issues Drug Safety Communication stating that Zofran may change the heart’s electrical activity, which could lead to abnormal heart rhythms such as Torsade de Pointes. The agency required Zofran labels to be updated to include information about these risks.
- January 2012 – GSK completes its study of Zofran heart risks.
- January 2012 – The National Center on Birth Defects and Developmental Disabilities publishes a report finding that when taken during the 1st trimester, Zofran doubles the risk of cleft palate.
- June 2012 – FDA issues a second Drug Safety Communication stating that the 32 mg dose of Zofran “may affect the electrical activity of the heart (QT interval prolongation).”
- July 2012 – U.S. Department of Justice issues a press release stating that GSK would pay a $3 billion settlement after pleading guilty to improperly marketing Zofran off-label for morning sickness and paying doctors to prescribe the drug.
- December 2012 – FDA issues another Drug Safety Communication stating that 32 mg brand name and generic versions of Zofran were being recalled because of the drug’s potential to cause abnormal heart rhythms.
- August 2013 – Two papers relating to Zofran birth defects are presented at the International Society for Pharmacoepidemiology (ISPE). The 1st paper finds that Zofran was not linked to an increased risk of adverse fetal outcomes. The 2nd paper includes data from the 1st, but covered more years and test subjects, and reached the opposite conclusion: that there is a doubled risk of cardiac malformations. Specifically, there was a significant increase in the occurrence of major congenital heart defects in children whose mothers took Zofran during in the 1st trimester of pregnancy.
- July 2014 – American researchers confirm prior reports that Zofran crosses the placental barrier during pregnancy in relatively high concentrations after just 3 oral doses. The study’s authors conclude that the high lipid solubility of Zofran increases its ability to be taken up into fetal tissue in larger amounts.
- August 2014 – A Swedish study investigating Zofran birth defects reports that the drug poses a significantly increased risk for cardiac septum defects in babies born to women who used Zofran in the 1st trimester of pregnancy.
Cluster of Rare Birth Defects in Washington State May Be Linked to Zofran
Three counties in Washington State are struggling to explain a dramatic increase in a severe neural tube birth defect called anencephaly seen by area hospitals over the past 5 years, according to the Seattle Times. Anencephaly is typically so rare that it is written off as a fluke, but rates in Yakima, Benton and Franklin counties are so high that researchers have begun to speculate that use of certain prescription drugs during pregnancy — including Zofran — may be the cause or a contributing factor.
At least 41 women have lost babies to anencephaly since 2010 in the 3 counties. This rate is nearly 5 times higher than the national average, and the discovery has highlighted a number of government policies that may actually conceal these types of birth defect clusters, rather than help identify and investigate them.
Interviews and tests aren’t required by law, but both are considered “standard protocol […] by researchers from the Centers for Disease Control and Prevention,” according to the Times.
Meanwhile, Washington’s Medicaid program continues to follow a set of rules that limit pregnant women’s access to folic acid, a B vitamin known to decrease the risk for birth defects like anencephaly, the authors found.
Allison Ashley-Koch, a researcher at Duke University, noticed the state’s high anencephaly numbers early, but she says government officials never followed up on her concerns.
Analyzing birth defect records from across the U.S., Ashley-Koch says she identified Washington’s cluster of anencephaly 2 years ago. But when she contacted the CDC to investigate the matter, the agency seemed uninterested. “Basically, they just said, ‘Thank you, but no thank you,’ Ashley-Koch said.
Less than half of U.S. states have an “active” birth defect surveillance system, which specifically filters medical records for birth defects. Washington isn’t one of them. Instead, the state’s health department relies on doctors to take the initiative and voluntarily report defects themselves.
Zofran Hypospadias Lawsuit
June 29, 2019 – A product liability lawsuit has been filed against GSK on behalf of a woman who allegedly gave birth to a baby boy with hypospadias after she took Zofran during pregnancy.
The plaintiff, Amanda, took Zofran for morning sickness during her second trimester (week 13 through the end of week 26), according to the lawsuit.
“My son was born with hypospadias, where the urethra forms abnormally and is not at the top of his penis,” Amanda said. “The urologist told me that it is a birth defect.”
Hypospadias can occur anywhere from just below the end of the penis to the scrotum, and there are different forms of the defect, ranging from minor to severe. Mild cases typically do not cause symptoms; however, if it’s more severe, the patient may have problems such as spraying urine, difficulty directing the urine stream, and having curved erections.
Amanda’s son had surgery when he was 2 months old to correct the problem, but he still suffers from the defect.
“I don’t know if I can put my son through another surgery,” Amanda said. “I first noticed that his penis wasn’t normal after his circumcision – he wasn’t urinating properly. Now he is three years old and still having problems: he says it hurts. I’m scared about putting him through another surgery in case it doesn’t get corrected again. But I am getting a second opinion.”
When Amanda discovered that Zofran may have caused her son’s condition, she was outraged. “I cried so much, and the guilt is overwhelming. I am constantly dealing with this issue. You think that taking a drug is safe, especially for something ‘simple’ like morning sickness. Finding out the danger of this drug really is devastating, and very scary. And to top it off, I heard that the Zofran manufacturer was aware of Zofran birth defects yet didn’t recall it.”
A 2004 study published in An International Journal of Obstetrics and Gynaecology (BJOG) found a potential link between Zofran and hypospadias. In a cohort of 176 live pregnancies, researchers found 3 cases of the defect among mothers who took Zofran for morning sickness. The sample size was too small to indicate a 6-fold increase in hypospadias; however, the study’s authors cautioned that additional research needs to be performed, and that GSK lacks safety data for Zofran.
“When my son pees, his penis points down at an angle. He has two holes, and urinates from one of them. He is a healthy boy except for this,” Amanda said. “I didn’t take Zofran with my second child and he is fine… I can’t believe there is a drug on the market that can harm innocent babies. I’d like to see that come off the shelf. I hope this message serves as a warning to pregnant women who are considering taking Zofran.”
defects linked to Zofran are musculoskeletal anomalies, which affect bone and muscle development in the skull, trunk and/or limbs.
What are Musculoskeletal Anomalies?
Musculoskeletal birth defects are congenital abnormalities that occur in the bones and/or muscles. Although they can develop anywhere in the body, these types of defects are most often found in the skull, face, spine, hips, legs and feet. In some babies, bones and muscles may develop incompletely; in others, bone and muscle defects result in abnormal appearance or function of the affected body part.
- Facial Defects – The most common congenital malformations involving the skull and face are orofacial defects such as cleft lip and cleft palate. These problems occur when a baby’s lip or mouth do not fuse together properly in the womb. Children of mothers who use Zofran while pregnant may be born with a cleft lip, a cleft palate, or both.
- Limb and Joint Defects – Limbs or joints may be missing, deformed, or abnormally developed. For example, bones in the hand and forearm may be missing, fingers may stop growing prematurely, or hips may be dislocated. Thalidomide, a drug used to treat morning sickness in the 1950s and 1960s, caused a variety of limb defects — usually short, poorly functioning appendages in place of arms and legs. Babies born with limb and joint defects are likely to have other congenital malformations.
- Hand Defects – In some babies, a hand may not form completely, or it may be missing altogether. In other cases, the baby may have too few fingers, or they may fail to separate, producing a web-like hand. Some hand defects involve extra fingers. Surgery is usually performed to correct these types of defects and provide as much hand function as possible.
- Developmental Dysplasia of the Hip – Baby’s hip socket and thighbone, which normally form a joint, become separated. This defect is most common among girls, babies born in a breech (buttocks-first) position, and among children who have relatives with congenital hip dysplasia.
- Clubfoot – Defect in which the foot and ankle are twisted out of place. In most cases, the feet are positioned down and the foot and ankle are twisted inward. The bones of the leg and foot, as well as the muscles of the calf, are often underdeveloped.
Zofran Side Effects Lawsuit Filed in Virginia
A Virginia woman has filed a lawsuit against GSK in New Jersey federal court alleging that her use of Zofran during pregnancy caused her son’s heart, lung and abdominal birth defects. According to the lawsuit, Plaintiff’s son was born on January 2, 2015, and subsequently diagnosed with the following birth defects after being exposed to Zofran in the womb:
- Complete Atrioventricular Canal Defect (CAVC) – Large hole in center of the heart, affecting all 4 chambers where they would normally be divided. The defect allows oxygenated (red) blood to mix with oxygen-depleted (blue) blood, and causes the chambers / valves to improperly circulate blood, according to the American Heart Association.
- Doublet Outlet Right Ventricle (DORV) – Defect that occurs when the pulmonary artery and the aorta—the heart’s 2 great arteries—both arise from the right ventricle, according to Boston’s Children’s Hospital.
- Heterotaxy of the Lungs – Rare defect in which the lungs are situated improperly in the chest.
- Malrotation of the Intestines – Twisting of the intestines caused by abnormal development of the fetus in utero. Malrotation occurs in about 1 in 500 births in the U.S., according to KidsHealth.
As a result of these problems, the boy has had to undergo open-heart surgery, according to the lawsuit.
The complaint is unique in that along with naming GSK as a defendant, plaintiff also names Glenmark Generics, an Indian company that produces a generic version of Zofran, as a defendant.
The lawsuit was filed September 28 in the U.S. District Court of New Jersey under case number 2:15-cv-07134, and transferred to the Zofran MDL in Boston on October 23 as case number 15-13712.
Zofran Lawsuit Filed in Tennessee
A Tennessee woman has filed a lawsuit against GSK alleging that Zofran caused her daughter to be born with catastrophic heart defects that led to her death at the age of just 11 weeks. According to the complaint, plaintiff started taking Zofran in August 2000 for morning sickness during her first trimester, and subsequently gave birth to a girl with severe heart defects including pulmonary valve stenosis and atrial septal defect. The woman claims that neither she nor anyone else in her family have a history of heart defects, and that in an earlier pregnancy which did not involve the use of Zofran she gave birth to a healthy baby girl.
Plaintiff further alleges that she took Zofran for morning sickness throughout her first trimester of pregnancy (a time when fetus heart tissue is at a critical stage of development), and was even administered the drug through an IV at a hospital on ‘several occasions.’ Her daughter, ‘N.R.’, was born on June 23, 2014, and subsequently diagnosed with the following heart defects:
- Heterotaxy Syndrome (Isomerism) – Heart on the right side of her body, rather than on left as normal.
- Atrioventricular Septal Defect (AVSD) – Defect in which there are holes in the chambers of the heart, and the valves that control the flow of blood between the chambers may not be formed correctly.
- Aortic Insufficiency (AI) – Leaking of the aortic valve which causes blood to flow in the reverse direction during ventricular diastole, from the aorta into the left ventricle.
As a result of these problems, N.R. was transferred immediately after her birth to a neonatal intensive care unit (NICU) and placed on life support machines. Sadly, the baby died at 11 weeks old, just before a heart transplant surgery was scheduled.
Like other plaintiffs in Zofran lawsuits, the Tennessee mother claims her daughter’s exposure to the drug was the result of a fraudulent marketing campaign run by GSK. She sites a 2012 lawsuit filed by the U.S. Justice Department which charged the drugmaker with illegally promoting Zofran and other medications to OB / GYNs.
GSK’s marketing campaign portrayed Zofran as a ‘safe and effective’ treatment for morning sickness, even though the drug had never been tested or approved for this purpose, according to the lawsuit.
The complaint was filed September 4 in U.S. District Court for the State of Tennessee, Middle District, Nashville, under case #3:15-cv-00958. Since the initial filing, this case was transferred to Boston, MA. to be consolidated in the Zofran multidistrict litigation.
GSK Files Motion to Toss Fraud Claims in Zofran Litigation
May 10, 2017 – GSK has asked a federal judge in Massachusetts to strike fraud-based claims over its marketing of Zofran from MDL No. 2567, saying that it will be prejudiced if consumers are allowed to obtain discovery on those claims.
U.S. District Judge F. Dennis Sayor ruled last month that the suits’ marketing campaign allegations were too broad; however, those “now untethered” marketing fraud allegations are still in the master complaints, GSK stated in a motion to strike the claims.
“Striking these allegations is appropriate, given that the adequately pleaded claims — and the allegations underpinning them — define the scope of discovery,” the company said. “GSK will be significantly prejudiced if plaintiffs are permitted to obtain discovery on these inadequately pleaded allegations.”
In Sayor’s ruling, he said that although Plaintiffs said GSK knowingly misrepresented the safety of Zofran for morning sickness in its marketing campaigns, the class hasn’t provided a specific allegation about any advertisements, brochures, or presentations.
Sayor also ruled that claims GSK sales reps misrepresented the safety of Zofran during pregnancy to doctors are also expressed in extremely vague terms.
Since Plaintiffs didn’t specify their fraud theories as separate counts, allegations about “off-label” marketing, promotional schemes and statements by GSK sales representatives remain in the master complaints, even after the court found them inadequate, GSK said in the motion.
Zofran Multidistrict Litigation
Lawsuits filed against GSK alleging that Zofran caused birth defects have been consolidated into a multidistrict litigation (MDL) in the District of Massachusetts before Judge Dennis F. Saylor, IV.
GlaxoSmithKline is requesting the liberty to redact what it considers “highly confidential” information from the documents produced for plaintiffs to inspect in the Zofran litigation. Plaintiffs countered the request in a memorandum (PDF) filed earlier this month, stating that “information GSK believes is a trade secret or otherwise highly confidential or irrelevant should be produced in unredacted form and designated as Confidential Information in accordance with the proposed Protective Order, which expressly allows such qualifying material to be designated confidential.”
MDLs are designed to speed up the litigation process by consolidating all federal cases citing similar allegations before a single judge. This eliminates duplicative discovery and conflicting pretrial rulings from different judges. Consolidation may also encourage large-scale settlements after bellwether trials, should jurors find GSK liable. However, each case will be decided on an individual basis, and in the event that a large-scale settlement is not reached, each suit will be returned to the court where it was originally filed.
Utah Mother Blames Zofran for Daughter’s Hip Dysplasia
A Utah mother has filed a products liability lawsuit against GSK alleging that Zofran caused her daughter to be born with bilateral hip dysplasia, a musculoskeletal birth defect in which the hip joint has not formed properly.
According to the lawsuit, the mother was prescribed Zofran for morning sickness during her first trimester of pregnancy. Her daughter, “A.C.D.”, was born in 2011, and forced to undergo surgery to correct the misalignment of her hip bones 3 years later, according to the complaint.
The mother claims surgery did not correct the defect, and that A.C.D. has failed to meet developmental milestones and fallen behind other children her age, which have “prevented her from thriving physically and developmentally.”
The hip is a “ball-and-socket” joint. In a normal hip, the ball at the upper end of the thighbone (femur) fits firmly into the socket, which is part of the large pelvis bone. In babies with bilateral hip dysplasia, both side of the hip joint have not formed correctly, and the ball is loose in the socket and may be easy to dislocate.
The family is seeking damages for psychological and emotional trauma, including fear and anxiety, along with past and future medical expenses, as well as lost time at work. Their suit was filed yesterday as a Short Form complaint, and is registered as document 333 in the Zofran multidistrict litigation in the District of Massachusetts.
Texas Mom Claims Zofran Caused Daughter’s Death
August 17, 2015 – A Texas couple has filed a lawsuit against GlaxoSmithKline alleging that the mother’s use of Zofran during pregnancy caused the death of their first daughter and severe kidney defects in their second.
According to the lawsuit, which was filed in U.S. District Court for the District of Delaware under case number 1:15-cv-00637-UNA, the mother became pregnant with her first daughter in November 2000. She underwent an ultrasound, which showed no signs of congenital malformations or other problems.
At some point after the ultrasound, the mother was prescribed Zofran “off-label” to treat the symptoms of morning sickness. She later underwent additional diagnostic testing which revealed the presence of abnormalities including heart defects, which the plaintiffs allege were caused by the mother’s use of Zofran.
The baby was born via C-section on July 12, 2000, and immediately transferred to a neonatal intensive care unit (NICU) at a children’s hospital. Sadly, the child died on August 2 as a result of having a malformed aorta and hypoplastic left heart syndrome (HLHS). Her heart was just one-fifth the size it should be.
Then in May 2002, the plaintiff again became pregnant with another daughter. She suffered from morning sickness, and was again prescribed Zofran off-label. Like the first child, the second was classified as a high-risk birth.
The baby was born in February 2003 at a Texas hospital, and immediately began displaying excessive vomiting, reflux and an inability to retain necessary nutrients. She required extended hospitalization and was diagnosed with reflux, congenital kidney defects and urinary tract defects.
Plaintiffs claim that Zofran was directly responsible for the death of their first daughter and the birth defects of their second. The parents are seeking damages in excess of $75,000 from GSK, as well as a label change regarding the risks involved with using Zofran during pregnancy.
Illinois Mother Blames Zofran for Son’s Heart Defect
A lawsuit filed against GlaxoSmithKline (GSK) by a single mother from Illinois alleges that the anti-nausea drug Zofran caused her son to be born with a life-threatening congenital heart defect.
In the lawsuit, plaintiff alleges she began taking Zofran early in the 1st semester of a 2011 pregnancy. Her son “T.H.” was born in 2012 and quickly diagnosed with hypoplastic right heart syndrome (HRHS), a rare congenital birth defect that occurs when the right side of the heart fails to develop completely. In patients with the condition, the right side structures of the heart – chambers, valves and blood vessels – are malformed, forcing the heart to work harder to supply the body with oxygen.
According to the lawsuit, H.T. underwent a pediatric heart transplant shortly after his birth – his heart was removed and replaced with a donor organ. The complaint provides no details regarding the outcome or H.T.’s progress since the surgery.
The lawsuit was filed July 16 in U.S. District Court for the Southern District of Illinois under case # 3:15-cv-00769.
North Dakota Couple Says Zofran in Pregnancy Caused Baby’s Kidney Defects
July 17, 2016 – A family from Bismarck, North Dakota, has filed a lawsuit against GSK alleging that prenatal exposure to Zofran caused their son to be born without one kidney.
According to the lawsuit, plaintiff was prescribed Zofran for morning sickness early in her first trimester, which she continued to take in both pill form and intravenously throughout her pregnancy. Her son, referred to in court documents as “G.K.”, was born in 2007, but it would be another 6 years before the boy was diagnosed with kidney defects.
In Oct. 2013, G.K. suffered a kidney injury at home and was taken to a hospital emergency room. There, a diagnostic examination revealed that the child was missing the other kidney. According to the lawsuit, “the only kidney G.K. was born with, which was injured in the accident, was significantly damaged.” The boy was airlifted to a Minneapolis hospital, where he underwent “extensive treatment.”
G.K.’s birth defect, known as unilateral renal agenesis, occurs when the kidney fails to develop from earlier cellular structures, because those earlier structures were themselves absent. In this case, the boy was born not only missing a kidney, but also missing the connective tissues required to support a kidney transplant. Those tissues should have developed from the same cellular structures as the kidney itself, according to the lawsuit.
G.K.’s parents also say the boy was born without a vas deferens, the tube that connects the testes with the urethra. While few studies have investigated the link between the 2 defects, a January 2000 German study published in Andrologia found that of 105 patients, 74% of males missing a vas deferens were also missing a kidney.
According to the lawsuit, G.K.’s lack of vas deferens means he may never achieve normal sexual function, and the missing kidney has caused a “serious threat” to his “health and enjoyment of life.”
The complaint was filed July 27 in the U.S. District Court of North Dakota, Southwestern Division under case number 1:15-cv-00102-CSM.
Utah Couple Claims Zofran Caused Daughter’s Cleft Lip/Cleft Palate
March 16, 2016 – A Utah couple has filed a product liability lawsuit against GSK alleging that Zofran caused their daughter to be born with a cleft lip and cleft palate.
According to the complaint, the mother was prescribed Zofran during early pregnancy in 1995, which she took through January 1996. Her daughter, referred to in court documents as ‘E.M.’, was born on February 24, 1996, and immediately diagnosed with a “wide right unilateral complete cleft lip and palate,” a large split in her upper lip that extended all the way through the roof of her mouth. As a result of these problems, she was forced to undergo a number of unspecified corrective surgeries, according to the lawsuit.
Now 20 years old, E.M. “exhibits physical malformations resulting from the clefts and subsequent surgeries,” according to her parents. She “is unable to participate fully in life,” they say, “and has “required […] speech, occupational and physical therapy.”
GSK “marketed and sold Zofran without adequate warning to healthcare providers and consumers that Zofran was causally associated with increased risks of birth defects,” according to the lawsuit.
The complaint was filed Feb. 19 in the U.S. District Court for the District of Utah, Central Division, under case number 2:16-cv-00131-EJF. On March 2, the U.S. Judicial Panel on Multidistrict Litigation issued a Conditional Transfer Order (PDF) to move the case to the Boston Zofran MDL.
Zofran Cleft Lip Lawsuit Filed in Arkansas
An Arkansas couple has filed a lawsuit against GSK alleging that Zofran caused their son to be born with a cleft lip.
The lawsuit, which was filed in the U.S. District Court for the Eastern District of Arkansas, Western Division on May 21, alleges that the mother was prescribed Zofran for morning sickness during her first trimester of pregnancy, “around September of 2011.”
The couple’s son was born on June 1, 2012, and immediately diagnosed with a partial cleft lip. Three months later, the boy underwent surgery to correct the defect, according to the lawsuit.
The parents allege that their son “suffered a permanent scar from the repair that is often red and inflamed,” and that his lip is “not symmetrical.” To make matters worse, the boy now has developmental delays as a result of sedatives used during the surgery, plaintiffs claim, and that “it took him longer to speak and walk than the average infant, and he has visited a speech therapist, a developmental therapist, and a physical therapist.”
The Arkansas family has filed what is believed to be the nation’s second Zofran lawsuit over oral cleft birth defects. The first, brought by a Montana couple on April 3, alleged that the mother’s use of Zofran during pregnancy caused their daughter to be born with a cleft lip and cleft palate. The girl, now 16, “has been forced to undergo ten surgeries […] and more are planned and likely,” according to the lawsuit.
As in other similar complaints, the Arkansas family alleges that GSK disregarded studies and other “warning signs.” Rather than alert the public and medical community about the link between Zofran and birth defects, plaintiffs argue the company “fail[ed] to issue sufficiently strengthened warnings following the existence of reasonable evidence association Zofran use with the increased risk of birth defects.”
Plaintiffs further accuse GSK of failing to test the effects of Zofran on pregnant women, and of illegally promoting the drug to healthcare professionals for off-label use. The lawsuit is: case number 4:15-cv-00284-BRW.
SF Couple Claims Zofran Caused Heart Defect
A San Francisco couple has filed a product liability lawsuit against GSK alleging that Zofran caused their baby to born with a life-threatening congenital heart defect.
According to the lawsuit, the plaintiffs’ baby was born in 2009 and subsequently diagnosed with bicuspid aortic stenosis, a congenital heart defect characterized by a narrowing of the bicuspid aortic valve. The parents claim that Zofran, which the mother took ‘off-label’ for morning sickness during her first trimester of pregnancy, caused the defect.
Bicuspid aortic stenosis occurs early in fetal development, typically during the first trimester, around the same time the mother is likely to experience symptoms of morning sickness. According to the lawsuit, the mother was prescribed Zofran early in her first trimester “to alleviate the symptoms of morning sickness.” The complaint notes that Zofran is not and has never been approved by the FDA to treat morning sickness.
However, according to the plaintiffs’ allegations, GSK “launched a marketing scheme to promote Zofran to obstetrics and gynecology […] healthcare practitioners, among others, as a safe treatment alternative for morning sickness in pregnant women” soon after the drug was released in 1991.
The plaintiffs further claim that since at least 1992, GSK has been aware of evidence indicating that Zofran can cause birth defects, and the company has failed to adequately warn about this risk.
According to the lawsuit, GSK has received more than 200 reports of birth defects associated with the use of Zofran during pregnancy, most of which were congenital heart defects like bicuspid aortic valve, which the plaintiffs’ son was born with.
Plaintiffs say that “GSK has failed […] to disclose these severe adverse events to healthcare providers or expectant mothers.”
The complaint, which was filed March 5 in the Superior Court for the State of California, San Francisco, is believed to be the nation’s fourth lawsuit alleging that Zofran caused birth defects. The case number is CGC-15-544524.
Zofran Lawsuit Allegations Eerily Similar to Thalidomide Claims
Concerns raised by plaintiffs in Zofran birth defect lawsuits echo those of parents a generation earlier, whose children were injured by the drug thalidomide.
Like Zofran, thalidomide was hailed as a “wonder drug,” and prescribed off-label to pregnant women for morning sickness. Unfortunately, use of the drug in this capacity resulted in numerous adverse birth defects including blindness, phocomelia, and cleft palate.
Like plaintiffs in the Zofran litigation, numerous families filed lawsuits against drug companies alleging they were negligent for marketing thalidomide as a treatment for morning sickness. New complaints over the drug are still being filed today, both by parents and their now adult children whose lives were affected by the drug. New evidence has emerged indicating that Smith, Kline & French — which is now owned by GSK — may have hidden evidence of a 1956 clinical trial which found that the medicine was toxic to unborn babies.
The cases of thalidomide and Zofran are so similar that even the defendants have reacted to the charges in similar fashion. In 2013, U.S. District Judge Paul Diamond denied the defendants’ motion to dismiss in the thalidomide litigation. Last month, Judge F. Dennis Saylor denied a motion to dismiss GSK’s Zofran multidistrict litigation (MDL) in Boston.
GSK Fined $3 Billion for Off-Label Drug Promotion
In 2012, the U.S. Justice Department reached a $3 billion settlement with GSK after the drugmaker was accused of promoting several medications – including Zofran – for “off-label” uses. Court documents alleged GSK gave doctors kickbacks to prescribe Zofran for morning sickness, and disseminated false information about the drug’s safety and effectiveness.
Zofran Linked to Deaths of 2 Children: Study
In addition to being linked to birth defects in babies born to mothers who take the drug during pregnancy, Zofran is now suspected of playing a part in the deaths of 2 children who were given the drug for nausea.
A new study suggests that side effects of ondansetron may be fatal for some pediatric patients. The research, which was published in the journal Pediatric Emergency Care, looked at reports on 2 children who died of heart problems after being administered Zofran.
The first case involved a previously healthy 10-year-old boy who was admitted to an emergency room with symptoms of gastroenteritis. He was given an IV, morphine, antibiotics and 2 doses of Zofran. Shortly after receiving the drug, the boy became unresponsive, exhibiting symptoms of tachycardia (faster than normal heart rate).
The second case presented was that of an 86-day-old infant who had previously undiagnosed congenital cardiomyopathy. The child was admitted to the ER with symptoms of gastroenteritis and administered Zofran. As in the first case, the infant developed tachycardia and subsequently died.
Of particular concern to the researchers was the lack of studies regarding the use of Zofran in children. The study’s authors noted that the two deaths join a pair of earlier fatalities in pediatrics who were administered Zofran for gastroenteritis. Additionally, the researchers note that patients with underlying risk factors could have heart problems made worse by Zofran, putting them at risk of a fatal cardiac event.
Zofran Cleft Palate Lawsuit Filed in Massachusetts
October 7, 2016 – A New York mother whose son was allegedly born with a cleft lip and cleft palate after she took Zofran during pregnancy has filed a products liability suit against GSK. According to the lawsuit, the woman was prescribed generic Zofran for morning sickness during her first and second trimesters of pregnancy. Her son, “P.B.”, was born with “a cleft hard palate [and] unilateral right cleft lip.”
Zofran Master Complaint Filed; Novartis Named as New Defendant
June 15, 2016 – Plaintiffs’ attorneys in the Ondansetron MDL in Boston, Mass., have filed a Master Long Form Complaint in an attempt to unify the numerous allegations that each lawsuit shares. Of particular note is that in addition to GSK, Novartis Pharmaceutical Corporation has been named as a defendant in the litigation.
Zofran (generic: ondansetron) was approved by the FDA in 1991, and GSK served as its New Drug Application (NDA) sponsor. As such, the company was responsible for testing, marketing and labeling Zofran, in addition to establishing a post-marketing vigilance program to monitor the drug’s continued safety.
That all changed on March 23, 2015, when Novartis bought out GSK’s oncology division and became Zofran’s New Drug Application sponsor. Novartis now owns the right to sell Zofran in the U.S., and is responsible for maintaining the drug’s labeling. GSK will continue to manufacture the brand name medication, but Novartis “became involved in the research, manufacture, testing, packaging, labeling, advertising, promoting, marketing, and selling of Zofran in the United States,” according to the Master Complaint.
In purchasing the GSK oncology division, plaintiffs now claim that:
“Novartis gained knowledge of the false and misleading promotion of Zofran for treating pregnancy-related nausea, sometimes referred to as morning sickness, and of the risks of prenatal exposure to Zofran. Novartis had a duty and continues to have a duty to warn adequately and to correct GSK’s misrepresentations and has failed to do so.”
However, according to the Master Complaint, Novartis will only be included as a defendant in complaints filed after March 23, 2015.
Plaintiffs Fight GSK Over Zofran ‘Product Identification’
April 19, 2016 – GlaxoSmithKline has petitioned a Boston court to require “product identification” before initial discovery in the Zofran MDL in hopes of separating birth defect cases involving brand name Zofran from those naming its generic equivalent, ondansetron.
GSK is not the only company to produce a generic version of Zofran. In fact, GSK currently only controls about 12% of the global market for the drug, and there are over 30 other companies that manufacture generic ondansetron.
Plaintiffs in the MDL have vigorously opposed GSK’s petition for product identification, calling the move “unwarranted” and “unfairly prejudicial.” They agree that product identification is important in mass tort litigation involving allegedly defective medications. But this process, in which plaintiffs state whether they used a brand name or generic, is only one component of discovery, and “with the rarest of exception,” this step “is obtained initially through the Plaintiff and Defense fact sheet process.”
The opposing parties are currently drafting their “fact sheets,” documents that often take the place of individualized discovery in MDLs. With the large number of plaintiffs involved, it would be inefficient and overly time consuming for GSK to question each one individually. It would also be inefficient for each plaintiff to question GSK employees one by one. Instead of obtaining data in this fashion, the company will compile a master list of questions it wants to ask each plaintiff. Attorneys representing families will create their own list, requesting information relevant to each case from the drugmaker.
Plaintiffs believe the fact sheet is the appropriate place to ask about product identification, and that it would be extremely unusual for Judge Saylor to grant GSK’s request, calling it “a departure from countless MDL product liability litigations.”
Additionally, plaintiffs argue that the Zofran MDL is unlike any other pharmaceutical case involving generic drugs. GSK wants generic ondansetron cases to be thrown out, and in other multidistrict litigations this can happen. Courts often rule that brand name drug manufacturers can’t be held accountable for injuries allegedly caused by their generic equivalents. However, as the U.S. Justice Department claimed in 2012, GSK illegally marketed Zofran “off-label” as a treatment for morning sickness, and that this began prior to any generic versions becoming available.
Louisiana Couple Allege Son’s Birth Defects from Zofran
April 14, 2016 – A man and woman from Louisiana have filed a products liability lawsuit against GSK alleging that its wrongful conduct and fraudulent misrepresentation regarding Zofran caused their son to be born with severe heart defects.
According to the lawsuit, the mother was prescribed Zofran for morning sickness during her first trimester of pregnancy, which she took as prescribed. She claims to have never been warned that the drug could cause birth defects.
She gave birth to a baby boy on Nov. 7, 2012, who was subsequently diagnosed with multiple congenital heart defects including an enlarged right ventricle and pulmonary atresia. Shortly after his birth, the boy was forced to undergo emergency surgery and required extensive follow-up medical care after the procedure, according to the lawsuit.
The boy has since suffered from delayed development, required additional surgeries, and has an impaired “enjoyment of a normal life at home and at school,” the complaint states.
Plaintiffs are seeking damages stemming from GSK’s alleged negligence, fraudulent misrepresentation, failure to warn, and other counts. The suit further claims it was the defendant’s responsibility to adequately warn of the potential health risks of using Zofran in pregnancy, and that although the company had received hundreds of reports of adverse events associated with the drug, it failed to disclose this information to the public.
The lawsuit was filed in the U.S. District Court for the Western District of Louisiana Lafayette Division. Plaintiffs are demanding a jury trial and compensation for medical expenses, pain and suffering, and punitive damages.
MDL Plaintiffs Fight GSK’s Request to Redact Documents
March 21, 2016 – Plaintiffs involved in MDL 2657 in Boston have filed a motion arguing that GSK should not be granted the right to unilaterally redact documents it deems “highly confidential.”
Although the plaintiffs and GSK did reach an agreement over a Protective Order (PDF) which would keep the drugmaker’s internal corporate documents and any personal information of the plaintiffs confidential, GSK is now seeking the ability to single-handedly decide what it chooses to redact. If this is allowed, the company will be able to censor information which could be relevant to the case, without anyone outside the company knowing it even exists.
Plaintiffs responded to the request by stating that “information GSK believes is a trade secret or otherwise highly confidential or irrelevant should be produced in unredacted form and designated as Confidential Information in accordance with the proposed Protective Order, which expressly allows such qualifying material to be designated confidential.”
Plaintiffs & GSK Create ‘Protective Order’ to Keep Zofran Birth Defect Docs Confidential
March 7, 2016 – In collaboration, GlaxoSmithKline and plaintiffs in the Zofran MDL have crafted a protective order (PDF) to secure both internal corporate documents and patients’ personal information gathered during the course of discovery. The proposed order, according to court documents, is designed “to expedite the flow of discovery material; facilitate the prompt resolution of disputes over confidentiality; and adequately protect Confidential Information.” The document was submitted to the U.S. District Court of Massachusetts today, and is now awaiting approval from Judge F. Dennis Saylor IV.
GSK Pushes to Split Generic and Brand Name Zofran Lawsuits
February 25, 2016 – In a new court filing (PDF), GlaxoSmithKline has requested a “product identification” mandate for the ondansetron MDL that would require plaintiffs to identify whether they were prescribed the brand name version of the drug or its generic equivalent.
The Zofran product identification mandate would “will allow for a meaningful and fair assessment of the viability (or lack thereof) of the cases before time and money are expended on cases and claims that can and should be dismissed at an early stage,” GSK wrote in a separate memorandum.
Courts have traditionally ruled that brand name drug manufacturers cannot be held liable for injuries caused by their generic counterparts. However, a dilemma arises due to the fact that generic manufacturers are unable to update their products’ warning labels with new risks until the brand name manufacturer does so first. This is especially problematic considering the fact that at least 30 different companies make their own version of an active ingredient, as is the case with Zofran.
Sales of generic Zofran have severely cut into GSK’s profits. In 2007, a year after generic equivalents hit the U.S. market, brand name sales dropped by 88%, according to court documents (PDF) submitted in support of the company’s proposed mandate.
Adverse event reports are often submitted to a manufacturer before they reach the U.S. Food & Drug Administration (FDA). Where ondansetron (the active ingredient contained in Zofran) is concerned, those reports are likely split between the 30 different companies that manufacture generic versions of the drug. Therefore, it’s possible that each manufacturer has a different view of the medication’s potential health risks. But only GSK, who no longer controls the market, is legally allowed to warn the public of these risks.
FDA is aware of this dilemma, and has even proposed a fix – to allow generic manufacturers to update their products’ warning labels. But the companies don’t want that, since it would open them up to increased liability.
The other solution is to hold brand name manufacturers liable for failure to warn in their own labeling, even when a plaintiff took the generic. That’s the theory behind “innovator liability,” which contends that since brand name manufacturers control the labeling for generic companies, the former should be held accountable for injuries caused by an active ingredient, no matter who made the drug. Unfortunately, innovator liability is currently recognized in only California, Illinois and Vermont.
GSK acknowledges innovator liability in its recent court filing, saying: “the fact that some Plaintiffs may claim that GSK is liable for injuries allegedly caused by a generic manufacturer’s product does not relieve them of their obligation to identify the product they allegedly ingested.” Defining whether or not a plaintiff took generic ondansetron will “promote efficiency and preserve the resources of the parties and the Court,” the company asserts.
Canadian Zofran Labels Warn of Birth Defects, Plaintiffs Find
February 10, 2016 -Plaintiffs involved in the Zofran multidistrict litigation (MDL 2657) in Boston have discovered that labels of the drug in Canada warn against use during pregnancy, unlike the U.S. label.
The Canadian Zofran label reads that “the safety of ondansetron for use in human pregnancy has not been established,” and “use in pregnancy is not recommended.”
Plaintiffs in the MDL who allege birth defects from Zofran are wondering why the same warnings were not provided to American patients.
More than 200 lawsuits have been consolidated against GSK in MDL 2657. The complaints allege that Zofran caused plaintiffs’ children to be born with a wide variety of severe birth defects including atrial septal defect, ventricular septal defect, transposition of the great vessels, respiratory distress syndrome, clubfoot, kidney defects and cleft palate.
The U.S. Judicial Panel on Multidistrict Litigation (JPML) determined that consolidation of Zofran lawsuits was appropriate because each complaint contains similar ‘questions of fact,’ including:
- Was a birth defect the result of Zofran use during pregnancy?
- Did GSK illegally market the drug for the treatment of morning sickness?
- Did the company fail to disclose evidence linking Zofran to birth defects?
Before any trials can begin, the discovery phase must take place. Discovery is a procedure in which each party can obtain evidence from the other party or parties by means of discovery devices such as a request for answers to interrogatories, request for production of documents, request for admissions and/or depositions. The discovery phase of the MDL has not yet begun, although it is expected soon. Judge F. Dennis Saylor has appointed co-lead counsel and will soon appoint the Plaintiff’s Steering Committee. After that, it is likely the litigation process will proceed quickly.
Judge Denies Motion to Dismiss Zofran Lawsuits
February 2, 2016 – Judge Dennis F. Saylor, IV., the federal judge overseeing the ondansetron multidistrict litigation in Boston, has denied a request by GSK to throw the lawsuits out of court. Saylor cited a 2008 supreme court ruling which found that a failed citizen’s petition urging the FDA to increase label warnings on Zofran was not “clear evidence” of preemption by federal law.
MDL Plaintiffs Discover CDC Tracks Birth Defects
January 11, 2016 – Plaintiffs in Zofran lawsuits have discovered that the CDC has been tracking birth defect records in 41 states across the U.S.
As litigation continues to move forward with more than 200 complaints in the MDL currently underway in Boston, plaintiffs have been made aware of a birth defect tracking system used by the CDC in 41 U.S. states.
The purpose of the system, according to the CDC, is to:
- Track if birth defects are increasing or decreasing over time;
- Attempt to identify what may be causing the malformations;
- Bring public awareness to any causes or risk factors identified, and
- Help parents whose children have defects find the assistance they need.
Plaintiffs are now questioning whether this system may show what previous studies have indicated – that use of Zofran during pregnancy increases the risk of birth defects.
Zofran is classified as a “Pregnancy Category B” drug, which means that animal studies have not demonstrated a risk to the fetus, and there were no adequate and well-controlled studies in pregnant women at the time the drug was approved. The pregnancy category assigned to Zofran was based on a review of less than 200 births. However, more recent studies of hundreds of thousands of births (see above) show that the drug may in fact cause harm to the fetus.
Guidance Information for Expecting Mothers
FDA has issued the following guidelines for patients who have been prescribed Zofran:
- Discuss the drug with your physician or healthcare professional and to not stop taking the drug without first discussing it with your doctor or healthcare professional.
- Be aware that physicians might order an electrocardiogram (ECG, EKG) to monitor heart rate and rhythm. Moreover, physicians might order such tests for patients with electrolyte abnormalities, congestive heart failure, or bradyarrhythmias.
- Immediately contact your healthcare professional or seek emergency care if you experience an irregular heartbeat, shortness of breath, dizziness, or fainting while taking Zofran / Ondansetron.
Zofran May Affect Electrical Activity of Heart
June 29, 2012 – The U.S. Food & Drug Administration (FDA) issued a press release today warning the public that 32 mg single intravenous doses of the widely-prescribed anti-nausea drug Zofran (generic: ondansetron) may significantly affect the electrical activity of the heart (QT interval prolongation). Patients being treated with this dose of Zofran may be at risk of developing a potentially-fatal heart rhythm condition known as Torsades de Pointes (TdP). Signs and symptoms of Zofran-induced TdP may include fainting, heart palpitations, and heart muscle spasms.
Drugmaker GlaxoSmithKline (GSK) recently announced that it will remove the 32 mg single intravenous dose indication from Zofran labels. The updated verbiage will state that Zofran can continue to be used at the lower dose of 0.15 mg/kg administered every four hours for three doses; however, no single dose should exceed 16 mg. Information from the recently-completed clinical study will be included in the updated drug label.
Zofran belongs to a class of medications known as 5-HT3 receptor antagonists that are prescribed to prevent nausea and vomiting caused by cancer chemotherapy, radiation therapy, and surgery. The FDA will continue to analyze the results of the final study and work in tandem with GSK to determine an optimal single dose regimen that is both safe and effective for users.
Please Note: The new Zofran indication does not affect any of the recommended oral dose regimens of the drug. It also does not change the lower dose intravenous version of Zofran to prevent post-operative nausea and vomiting.
Those who may be at particular risk for Zofran-induced Torsades de Pointes include patients with:
- congenital long QT syndrome
- congestive heart failure
- electrolyte abnormalities
- patients taking concomitant medications that prolong the QT interval
Animal Studies Pivotal in Zofran Birth Defect Lawsuits
February 4, 2016 – Plaintiffs in the Zofran MDL have called attention to several ‘animal teratogenicity studies’ GSK allegedly performed in Japan after the drug was approved in the U.S. which found a link between Zofran and congenital heart defects.
Just three months after more than 200 Zofran lawsuits were consolidated into a multidistrict litigation in Boston, the defendant has asked that the cases be dismissed.
In a motion filed Dec. 11, GlaxoSmithKline said the complaints were preempted by federal law, invalidated since the FDA would have already changed Zofran’s warning labeling if the drug is, in fact, dangerous when taken in pregnancy. Plaintiffs allege that Zofran causes a wide range of severe birth defects, from cleft palate to congenital heart defects.
On Jan.5, plaintiffs fired back at GSK with a blistering response, stating that the drugmaker’s motion was “unripe, unprecedented and violates the established federal law.” Ripeness is a legal term that applies to a claim in which “the facts of the case have matured into an existing substantial controversy warranting judicial intervention,” according to the Cornell University Law Dictionary. However, plaintiffs contend that it is inappropriate for Judge F. Dennis Saylor IV to intervene — either for or against dismissal — at this stage in the litigation.
For one, the discovery phase hasn’t started yet, so plaintiffs haven’t been able to look at GSK’s records. Additionally, little medical evidence on Zofran is available to the public, since the company never attempted to have the drug approved as a treatment for morning sickness. As a result, plaintiffs haven’t been given the opportunity to know what GSK knows about Zofran’s link to birth defects. Before this information is made available, there’s no way to decide what — if anything — the FDA would have done to change the drug’s warning label.
However, there is at least one “reason to believe that GSK has important evidence about the defects alleged […], and the link to Zofran,” according to the plaintiffs’ response.
They proceed to highlight a number of ‘animal teratogenicity studies’ conducted by GSK in Japan which identified a link between Zofran and heart defects. Plaintiffs allege that these studies were done after the FDA approved Zofran in January 1991. In one such study, plaintiffs claim pregnant animals gave birth to offspring with ventricular septal defects (VSD), a congenital heart malformation that has been associated with Zofran.
“Plaintiffs do not know whether GSK ever provided the FDA this or any other evidence of severe heart defects,” the response states. “What Plaintiffs do know, however, is that the Zofran warning labels and available marketing materials were silent as to such evidence.”
Lawsuits Can Now Be Filed Directly into MDL
December 30, 2015 – In a move that will streamline the process of filing Zofran birth defect lawsuits, U.S. District Judge Dennis Saylor has allowed new plaintiffs to enter claims directly into the multidistrict litigation in Boston.
Instead of filing Zofran lawsuits in the federal courts of their specific states, plaintiffs can now join the MDL from the beginning. The order (PDF), Judge Saylor’s sixth to help streamline the MDL, will significantly cut red tape, saving time and resources for all parties involved in the litigation.
However, despite the order, plaintiffs will still have to act as though they were filing the complaint in a separate federal jurisdiction. In order to file directly in the U.S. District Court of Massachusetts, where nearly 300 Zofran birth defect lawsuits are already pending, plaintiffs must specify the district court in which they would have filed, had Saylor not approved direct filing into the MDL.
This means plaintiffs’ attorneys will have to justify the separate venue, even though in actuality their cases aren’t being filed there. If the court finds a problem with their argument, plaintiff will be given 30 days to amend the complaint and re-submit it.
GSK is currently unable to challenge any suits filed directly in Massachusetts on the grounds of venue. In most civil cases, the proper venue is typically the district court closest to where the defendant is located, or where events relevant to the case occurred.
However, in the Zoloft litigation, Saylor has voided this requirement during the course of the MDL. After pretrial proceedings are done, GSK will have the authority to challenge a lawsuit’s venue. The order allows a complaint to be filed directly in Boston without an admission from the court that Massachusetts is the proper venue for that particular suit.
Additionally, plaintiffs will not be required to find local counsel in Massachusetts. Attorneys admitted to practice in any U.S. District Court will be allowed to appear before the MDL court in Boston without going through any of the red tape which can make the process more difficult.
Lawyers will be bound by the standards of the U.S. District Court of Massachusetts, not the jurisdictions where they are technically licensed to practice.
Has Zofran Been Recalled?
The 32-mg dose of Zofran was pulled off the U.S. market in 2012 amid numerous reports of serious cardiac problems in users, according to the FDA. Earlier in the year, the agency issued a press release warning that the 32-mg dose of Zofran had been linked to an increased risk of QT interval prolongation.
Zofran is designed to block serotonin – a neurotransmitter associated with upset stomach and vomiting – at a specific type of receptor known as the 5-HT3 receptor.
New research ordered by the FDA found a maximum mean difference in QTcF (a formula which takes into account the shortening of the QT interval across a range of rates) of 20 milliseconds after the 32-mg IV dose. An IV dose of 8 mg, on the other hand, led to a mean maximum QTcF difference of 6 milliseconds.
FDA ordered that all remaining lots of the 32-mg version of Zofran were to be removed from the market by early 2013, and that the recall should not result in a shortage of the drug, since the 32-mg dose represented a small fraction of the market. The 0.15 mg IV regimen of Zofran continues to be recommended to prevent chemotherapy-induced nausea and vomiting. Additionally, the agency has determined that oral dosing of Zofran remains effective for these purposes.