Zofran has been linked to craniofacial/mouth birth defects including cleft lip and/or palate. One study suggests that the drug doubles the chance of babies being born with a cleft palate. A cleft lip and/or palate are congenital deformities that produce a fissure or opening of the lip or palate. A cleft lip is formed at the top of the lip causing a small gap or indentation in the lip up to the nose. While a cleft palate occurs when the two palates of the skull, which form the roof of the mouth, do not completely join and leave a hole in the roof of the mouth. The mouth is then connected directly to the nasal cavity. This causes velopharyngeal inadequacy (VPI) allowing air to leak into the nasal cavity from the oral cavity resulting in a hypernasal speech.

Zofran is also known to cause serious heart problems, including congenital heart defects. It can lead to fatal heart rhythms, such as Torsade de Pointes, or “twisting of the spikes.” This is a form of polymorphic ventricular tachycardia that if continual may lead to ventricular fibrillation and sudden death. Additionally, Torsade de Pointes is associated with long QT syndrome. This is an irregular heartbeat where the heart’s electrical wave presents with a long wave between the Q wave and the end of the T wave when shown on an ECG.

Another study shows that if Zofran is taken during the first trimester, there is an increased risk that a child will be born with a cardiac septum defect. The cardiac septum is the portion of the heart dividing the right and left sides.

The FDA has received reports of serotonin syndrome linked to the use of Zofran. Zofran may raise the risk of this syndrome in pregnant women who take a selective serotonin reuptake inhibitor (SSRI) at the same time as Zofran. Symptoms of serotonin syndrome include confusion, agitation, rapid heart rate and high blood pressure, heavy sweating, tremors, headache, and diarrhea. Severe serotonin syndrome can be deadly.