Zofran – Birth Defects, Cleft Palate

Zofran is the brand name for the generic medication, odansetron hydrochloride.  It is manufactured by the UK-based pharmaceutical giant, GlaxoSmithKline (GSK) which has operations in 115 countries and estimated annual revenue of $35 Billion.

Zofran is approved to treat or prevent nausea and vomiting in patients receiving chemotherapy or radiation therapy for cancer treatment and in surgery or post-operative related nausea.  It is available as an oral tablet, oral solution, oral disintegrating tablet and as an injection for intravenous use.

Zofran works by blocking the 5-HT3, serotonin receptors on the vagal nerves which run from the stomach to the throat and in the “chemoreceptor trigger zone” or CTZ in the brain and is often very effective when used as prescribed.

Zofran has also been used as an “off-label” treatment for pregnancy associated nausea and vomiting.  Physicians are allowed to use medications as off-label treatment if they feel that risks outweigh the benefits however drug manufacturers are not allowed to promote or market medications for this type of use.

GSK has paid $3 Billion to the Department of Justice to settle allegations of improper marketing of Zofran and studies have shown that Zofran increases the risk of severe birth defects when used in pregnant women.

Zofran Side Effects

Like many medications, Zofran may cause side effects.  Most of these side effects are mild or temporary, however some can be more severe and may cause significant injury.

The most common side effects of Zofran include:

  • Rash and itching
  • Constipation

More severe side effects may indicate changes in heart rhythm including:

  • Swelling
  • Irregular heartbeat
  • Dizziness
  • Shortness of Breath
  • Fainting

In some cases, patients who take Zofran may experience EKG changes such as QT prolongation which may cause a serious and possibly fatal heart arrhythmia known as Torsades de Pointes.  This possible risk prompted the FDA to issue warnings about dosages over 16 mg and led to the recall and discontinuation of the 32 mg dosage of Zofran.

Zofran Birth Defects

Zofran is listed as a Category B medication for pregnancy.  Pregnancy Category B indicates that the medication has not been proven safe for uses in pregnancy but many women have been prescribed Zofran for morning sickness.

About 15 percent of all pregnant women experience “morning sickness” which is severe enough to warrant medication.  Nausea and vomiting may persist throughout a pregnancy and in some cases, may be severe.  However, most nausea and vomiting occurs during the first trimester of a pregnancy when the developing fetus is most vulnerable to damage caused by medications.

Studies have shown that Zofran readily crosses the human placenta and most women who have taken Zofran during pregnancy used it during the first trimester.

Zofran use during pregnancy has been shown to double the risk of cleft palate and fetal heart defects and may increase the overall birth defect rate by as much as 34 percent.

Potential birth defects caused by Zofran may include:

  • Congenital heart defects
  • Cleft palate
  • Kidney malformation
  • Skeletal defects
  • Fetal growth restriction
  • Spontaneous abortion
  • Stillbirth

(odansetron hydrochloride) is approved for the treatment of nausea and vomiting caused by chemotherapy and radiation therapy in cancer and for the treatment of post-operative nausea.  It is available in tablet and solution forms for oral use and inject-able form for intravenous use.

Zofran is produced by GlaxoSmithKline (GSK), a large multi-national pharmaceutical company based in the UK.  In 2014, the company had estimated annual revenue of over $35 billion.

Zofran is the brand name for the generic medication, odansetron hydrochloride.  It is manufactured by the UK-based pharmaceutical giant, GlaxoSmithKline (GSK) which has operations in 115 countries and estimated annual revenue of $35 Billion.

Though it is approved for only cancer and surgery related nausea and vomiting, it has been used to treat nausea and vomiting in pregnancy.  This “off-label” use is allowed by the Food and Drug Administration if a physician feels that the drug is effective and safe enough, however the manufacturer is not allowed to promote or market the drug for unapproved uses.

GSK has settled claims of improper marketing of Zofran, including for use in pregnancy, with a payment of $3 billion.  The medication has caused a number of birth defects in women who used the medication while pregnant and has been shown to double the risk of certain congenital abnormalities including cleft lip and palate and congenital heart defects.

Birth Defects

Zofran is not approved to be used during pregnancy.  Despite this fact, many women have taken the medication for morning sickness or nausea and vomiting during pregnancy.

Nausea and vomiting most commonly occur during the first trimester or first 3 months of pregnancy.  Up to 15 percent of women experience nausea that is severe enough to require the use of medication.  The first trimester is also the period of time when a developing fetus is most vulnerable to damage caused by medication.  Zofran taken during pregnancy may have caused damage to the developing fetus, resulting in congenital malformation or birth defects.

Zofran Cleft Lip and Cleft Palate

In 2012, the Centers for Disease control concluded that Zofran taken during pregnancy may double the risk of development of cleft lip or palate.

Cleft lip or palate is a skeletal abnormality that may result from Zofran use during pregnancy.  Cleft lip and palate are caused by incomplete or improper development of the bones in the palate or roof of the mouth.  This may leave a hole in this portion of the skull, exposing the sinuses.  This may make it impossible for the child to nurse or eat and may leave the brain unprotected from infection.  Many children with cleft lip have an incomplete front jaw, lip, and nose, making it difficult to breathe properly.

Cleft lip or palate also results in significant facial disfigurement and will require surgery to correct.  Even with surgical correction, in many cases, the malformation cannot be completely repaired and the child may have permanent facial dis-figuration with continuing medical problems.  Other retrospective studies have also shown that Zofran may double the risk of cleft lip or palate.

Zofran Heart Defects

Zofran was shown in a 2013 study to double the risk of a congenital heart defect.  Birth defects caused by Zofran that may affect the heart include:

Atrial Septal Defect (ASD) – incomplete formation of the wall of tissue separating the two upper chambers (atria) from one another.  This “hole” in the heart may severely compromise proper circulation and must be repaired with surgery.  Surgery is sometimes but rarely conducted in utero (while the mother is still pregnant) or more often, shortly after the infant is born.  Some infants may require several surgeries performed over a period of months to years.  Until the condition is adequately repaired, the child’s development may be inhibited and in some cases may not be completely resolved and result in lifelong disability.

Ventral Septal Defect (VSD) – similar to ASD, but involving incomplete formation fo the wall between the two lower chambers of the heart or ventricles.  VSD is generally considered more serious and will also require surgical correction.  Many children with VSD may experience slow or inhibited physical and mental development.  Some children will have a lifelong disability due to congenital VSD.

Heart Murmur – heart murder is caused when the conduction system of the heart does not function properly.  It may result in inefficient circulation of the blood and may cause physical distress or an inability to perform physical activities.  It may also decrease effective blood and oxygen supply to the brain, limiting cognitive function.  Heart murmur may be mild to severe but is often not correctable by surgery and will be permanently disabling.

Multiple retrospective studies conducted in several countries, including the U.S. have shown that Zofran may increase the risk of other birth defects by as much as 34 percent.  Other potential birth defects caused by Zofran may include:

  • Kidney malformation
  • Skeletal defects
  • Fetal growth restriction
  • Spontaneous abortion
  • Stillbirth

Zofran Recall and Settlement

GSK was warned by the Food and Drug Administration as early as 1999 regarding improper marketing practices of Zofran.  The FDA cited the company for inadequate representation of side effects and risks of the medication.

In 2011 , GSK was required to conduct a cardiac effects study which concluded that doses over 16 mg of Zofran increased the risk of the potentially fatal cardiac arrhythmia, Toursades de Point.  GSK was forced to recall a 32 mg injectable dosage formulation of the medication in 2012.

In 2012, GSK paid $3 billion in criminal and civil penalties to settle Department of Justice allegations that the company had promoted Zofran for off-label use in pregnant women and had unlawfully paid kickbacks to physicians for prescribing the medication.

Zofran Lawsuits

Even though GlaxoSmithKline has paid a settlement of $3 Billion, this has not released the company from liability for damages or injuries that may have occurred due to Zofran use.

A child or the family of a child who was injured because the mother was given Zofran during pregnancy may be entitled to compensation for damages.  Monetary damages awarded to those injured by medications may include coverage of medical costs, lost wages and pain and suffering.  In some cases, victims may be awarded punitive damages, which are intended to punish the manufacturer for knowingly promoting or selling a harmful medication.

Many lawsuits against GlaxoSmithKline regarding Zofran use during pregnancy may be expected, potentially resulting in $Millions in damages to be awarded.

Notwithstanding claims relating to this product, the drug/medical device remains approved by the U.S. FDA. 

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