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Dangers of Off-Label Drug Use

We recently reported on the possible dangers of the anti-nausea drug Zofran® and equivalent generics when they are used off-label. But what does “off label” really mean?

What is Off-Label Use of Medications?

As we explained in an earlier post, “When a drug is used in a way that is different from that described in the FDA-approved drug label, it’s said to be an ‘off-label’ use.” The FDA issues instructions and warnings based on clinical studies that drug makers submit to the FDA. If researchers have not tested a drug for a particular use, instructions, dosages and warnings do not appear on the insert or label.

Many drugs are prescribed for off-label use, but is it safe?FDA Does Not Regulate What Doctors Can Prescribe

The bottom line is this:  The FDA regulates drug approvals and thus the ability of the drug manufacturer to make a medication available for sale. It does not control how doctors actually prescribe drugs.  As a consequence, doctors can essentially do whatever they want with drugs, and one medical ethicist has said that off-label use is so common that almost every drug available today has been used off label for something.

Off-Label Use has Benefits, But…

This isn’t necessarily bad, say the experts. And in some cases, drugs that were first used off-label to treat a particular condition eventually receive FDA approval. Beta-blockers are one example of this.  First approved for treatment of high blood pressure, doctors now use some approved beta-blockers to treat patients with heart failure after having been used off-label for this purpose for many years. And using even unapproved beta-blockers now represents the standard of care for treatment of heart failure.

Despite success stories such as this one – and there are others – using drugs in unapproved ways is controversial. Medical ethicists remind physicians that off-label prescribing can expose patients to unnecessary risk.  It can also leave medical providers vulnerable to legal action when an unapproved drug causes injury, illness or death.

Research has showed that even doctors are often not aware that they are prescribing a drug unapproved for a particular use. Sadly, this puts the burden on patients to determine whether the medications they were prescribed received FDA approval for a particular use or not.

No Clear Research Results for One Drug Used Off-Label, the Anti-Nausea Drug Zofran®

In the case of Zofran (ondansetron), doctors learned about the off-label uses in pregnancy from other doctors, at conferences, and, in some instances, from sales reps who allegedly provided kickbacks. The drug, which was approved in 1991 for controlling nausea and vomiting in chemotherapy patients, has not been the subject of many studies for off-label use in pregnancy. The studies that do exist are somewhat contradictory, with some saying that there is no link between Zofran and birth defects in infants while others say that taking the drug during pregnancy can cause birth defects that include heart and kidney problems, cleft palate and other mouth defects, and musculoskeletal problems.

In 2012, GlaxoSmithKline pleaded guilty[1] to “unlawful promotion” and paying kickbacks to physicians to prescribe Zofran and other drugs. As part of a global resolution, GSK consented to pay $3 billion to settle a number of charges. However, in recently filed lawsuits, plaintiffs allege the pharmaceutical giant continued marketed and urged physicians to prescribe Zofran to pregnant women. Since the FDA cannot prevent doctors from prescribing the drug, many physicians still use it for nausea and vomiting in pregnancy.

Recently, there has been enough publicity about Zofran (ondansetron) that some parents whose babies were born with birth defects after taking Zofran have filed lawsuits against GlaxoSmithKline. More are expected.


Zofran® is a registered trademark of GlaxoSmithKline, PLC.

Do not stop taking medications except on your doctor’s advice.


[1] GlaxoSmithKline to Plead Guilty and Pay $3 Billion to Resolve Fraud Allegations and Failure to Report Safety Data. U.S. Department of Justice, Office of Public Affairs. Washington: Press Release, July 2, 2012. (Civil Division, Consumer Protection, 12-842).