Are Off-Label Prescriptions Safe?

The U.S Food and Drugs Administration (FDA) approval of drugs is based on what they will be used to treat, cure or prevent. But physicians often prescribe medicines for conditions not specified on the label. While that may come with some risks, in many cases, it provides patients multiple benefits.

A pharmaceutical drug’s journey to approval begins with the sponsor. Usually, the manufacturer or marketer gathers all collected data, including animal tests and proposes labelling, and submits a new drug application or biologics license application to the FDA. The animal and toxicology studies results must show that the drug is reasonably safe before testing it on us.

When the company has completed testing, it sends all data to FDA’s Center for Drug Evaluation and Research (CDER). A team of CDER, physicians, statisticians, chemists, and pharmacologists reviews the data and proposed labelling and then decides if the drug is safe and effective in its proposed use and if its benefits outweigh its known risks. If all boxes are checked, FDA will approve the drug.

What about Off-Label Uses?

There are clinical situations in which a patient may benefit from an investigational drug outside a clinical trial or from using a medicinal product outside the authorization conditions. Drugs used in this context are grouped under the term of off-label.

FDA’s role is to ensure the quality of products in the U.S. marketplace so that physicians and patients can rely on them to treat a given indication. Once a drug is approved and released, the FDA doesn’t play a part in defining its standard of care or how it is prescribed.

A physician prescribing a drug exactly as approved by FDA is doing so on-label. When a physician veers from that path, including in a different way or different dose, he or she is prescribing a drug off-label.

What Are the Most Common Off-Label Drugs?

Drugs commonly prescribed off-label include antidepressants, antipsychotics, immune globulin (IG), chemotherapy, and pediatric medications. Many prescriptions in pediatrics are written off-label because children are less likely to be included in clinical trials.

Are Off-Label Uses Safe?

Just because an indication isn’t listed on a drug’s approved label doesn’t mean FDA disapproves the off-label use. Instead, the agency just hasn’t reviewed that use.

While prescribing off-label can be challenging for physicians, they have the discretion to do so; however, they are not free to promote the off-label use.
Off-label drugs are safe and effective in many cases because the theory generally suggests that the drug is effective for the condition. The problem is that clinical trials and safety and efficacy testing are expensive and have limitations, leaving out many indications.

Why Is FDA Approval So Necessary?

One of the most tragic aftermaths of off-label prescribing was in the 1960s when doctors began prescribing the sedative thalidomide to pregnant women to relieve morning sickness. They quickly discovered that the drug caused severe congenital disabilities in the infants born to women who had taken thalidomide while pregnant. At the time, clinical trials in the U.S. did not require FDA approval or oversight.

The control and quality of prescription drugs in the United States have come a long way since the early days of the FDA. Today, drugs must go through a rigorous process to get on-label approval. Those strict guidelines ensure that medications are safe and effective for human use.


  1. Claverie, H. (2016). Off-Label vs. On-Label Drug Prescribing. IG Living, 28–31.
  2. Office of the Commissioner. (2019). Understanding Unapproved Use of Approved Drugs “Off Label.” Retrieved May 16, 2021, from website: