From off to on: 5 drugs that went from off label to on label

November 6, 2025

Summary

Off label prescribing is when doctors prescribe medicine for a condition or use a dose form that has not been approved by the Food and Drug Administration (FDA).
About 21% to 32% of prescribed drugs are for conditions not approved by the FDA.
Off label uses initially rely on clinical judgment and emerging evidence, but some off-label treatments are so effective that they eventually get formal approval.
The process—from off label to on label—can change the trajectory of a drug and its use for patients.

Introduction

Medicines that transition from off label to on label represent a key step in ensuring both safety and efficacy for new indications. Formal approval is important to establish dosing parameters and minimize risks. Moving from off label to on label can combine innovation with the requisite oversight.

Here’s a look at five drugs that went from off label to on label.

Sildenafil

More commonly known as Viagra®, sildenafil was created in 1989 and initially approved to treat high blood pressure and chest pain due to heart disease. While in clinical trials, it was found to have the side effect of causing erections and was used off label. In 1998, the FDA approved it to treat erectile dysfunction, and the drug became known as Viagra. In 2009, sildenafil was approved to treat another condition, pulmonary arterial hypertension, and it was marketed as Revatio®.

Minoxidil

Minoxidil is a pill that was originally used to treat high blood pressure and was approved by the FDA in the 1970s. The FDA approved it to treat hair loss in 1988. It is now available as an over-the-counter medication that comes in two strengths and various formulations like spray, foam, and topical solution.

Bupropion

Bupropion was approved in the 1980s to treat depression under the name Wellbutrin. It was later found to treat smoking cessation and approved for this use in 1997, marketed under the name Zyban (it has since been discontinued under this name). Additionally, bupropion is now being studied for its potential use in treating stimulant use disorder.

Semaglutide

Semaglutide, widely known as Ozempic®, was approved to treat type 2 diabetes by the FDA in 2017. It was also used off label for weight loss. In 2021, semaglutide was approved as an anti-obesity medication and marketed under the name Wegovy®.

Ketamine

Ketamine is an anesthetic and was approved for use in 1970 the U.S. It has been used off label for a variety of conditions, including depression, post-traumatic stress disorder, Lyme disease, and alcohol use disorder. In 2019, the FDA approved a nasal spray which contains esketamine, a form of ketamine, called Spravato® to treat major depression.