Key takeaways:
Today, the FDA needs to approve new prescription medications before they can be marketed. But some medications were on the market before current standards were in place. And they’re still available even though they’re not FDA approved.
There are several reasons why an unapproved drug is still available. For example, it may be used to treat a serious condition that doesn’t have FDA-approved treatments.
The FDA has been working to remove higher-risk unapproved drugs from the market. They also encourage manufacturers to obtain FDA approval for unapproved drugs.
Save on related medications
From medications and supplements to tobacco and cosmetics, the Food and Drug Administration (FDA) oversees many products that we use every day. But you may be surprised that certain things aren’t approved by the FDA before they hit the market.
This is the case for products like infant formula, dietary supplements, and cosmetics. And it’s also true for certain older prescription medications. A few examples include phenazopyridine (Pyridium, AZO) for urinary tract infection (UTI) pain and phenobarbital for seizures.
Many of these medications were on the market before 1962. This was before manufacturers needed to show that a new medication was safe and effective for its intended use. Today, some of these medications are still on the market without FDA approval.
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Here, we’ll learn more about the FDA and unapproved drugs.
When was the FDA created?
The FDA may seem like it has been around forever. But it was only created just over 100 years ago, and it wasn’t officially called the FDA until 1930.
The FDA was created as a result of the Pure Food and Drugs Act of 1906, which prohibited the sale of adulterated (contaminated) or misbranded (misleading) drugs. At that time though, the law didn’t yet require the FDA to approve new drugs.
What are unapproved drugs?
Short answer: Unapproved drugs are prescription medications that haven’t been approved by the FDA.
Today, the FDA needs to approve new prescription medications before they’re available. But this wasn’t always the case. The Food, Drug, and Cosmetic Act of 1938 required new drugs to show they’re safe. And it wasn’t until 1962 that they would also need to prove they’re effective.
However, there were medications already on the market before these requirements were in place. Many of them have since been discontinued. But there are several unapproved drugs that are still available today.
Why are unapproved drugs still on the market?
There are a number of reasons why an unapproved drug would still be on the market. For example, the FDA might allow it to be marketed if it’s used to treat a serious medical condition. This is especially the case when an FDA-approved medication isn’t available or is in low supply.
Presently, the FDA has processes in place to remove harmful unapproved drugs and review others for safety and effectiveness. More on that later.
List of current and previously unapproved drugs
Below, we’ll cover several examples of drugs that missed initial FDA review. Several have since been approved by the FDA, while others are still unapproved.
1. Colchicine
Colchicine (Colcrys, Mitigare) is used to treat and prevent gout, which is a type of painful arthritis. This medication was on the market before 1938. The FDA approved a brand-name colchicine product called Colcrys in 2009. After that, all other companies were ordered to stop making unapproved colchicine products.
2. Nitroglycerin
Nitroglycerin (Nitrostat) sublingual (under the tongue) tablets are used to relieve angina (chest pain). These tablets were on the market before 1938. In 2000, the FDA approved brand-name Nitrostat nitroglycerin tablets. Ten years later, it ordered other companies to stop making unapproved nitroglycerin tablets.
3. Morphine
Morphine is an opioid medication used to treat pain that’s not relieved by non-narcotic options. Morphine immediate-release (IR) tablets, oral solution, and injection have been around since before 1938.
The FDA approved morphine IR tablets and oral solution in 2008, followed by the injection 3 years later. In 2009, companies were ordered to stop making unapproved morphine products, along with several other unapproved opioid medications.
4. Phenazopyridine
Phenazopyridine is used to relieve UTI-related discomfort or pain. Healthcare providers have recommended it since before 1938. As of 2022, phenazopyridine is still an unapproved drug. It’s available as both prescription and over-the-counter products.
5. Phenobarbital
Phenobarbital has been used to treat seizures since before 1938. As of 2022, phenobarbital is still an unapproved drug that’s available with a prescription.
6. Potassium chloride
Potassium chloride (Klor-Con) is used to treat hypokalemia (low potassium). The potassium chloride solution has been around since before 1962. The FDA granted its approval in 2014.
7. Sodium fluoride
Sodium fluoride (Prevident) has been used to prevent cavities since the 1940s. As of 2022, prescription-strength sodium fluoride products are still unapproved.
Are generic medications considered unapproved?
No. The FDA approves generic prescription medications before they’re marketed. But they don’t go through the same process as brand-name medications for approval. Still, generic medications must show that they work the same in the body as the brand-name medication.
How do I know if my medication is FDA approved?
If you want to double check if your medication is FDA approved, you can use the FDA-Approved Drug tool. If you don’t see your medication, it may be unapproved. Your pharmacist is a great resource if you have any questions, or if you’re unsure about your specific medication.
Is the FDA doing anything about these unapproved medications?
Yes. As previously mentioned, the FDA has processes in place to vet unapproved medications. One process is called the DESI program. This is for unapproved drugs that came to market between 1938 and 1962. These medications were already proven to be safe. And the FDA is using the DESI program to make sure that they’re also effective.
In 2006, the FDA also started the Unapproved Drug Initiative (UDI) to remove unapproved drugs from the market. It also created incentives for companies to take their unapproved drugs through the approval process. Since then, the FDA has removed hundreds of these drugs using a risk-based approach. And over 20 medications have received FDA approval.
However, the UDI program was terminated in 2020. This is because, in some cases, it resulted in higher medication prices and drug shortages. Today, the FDA uses a risk-based approach to remove unapproved drugs from the market.
Are there any downsides to unapproved drugs getting FDA approval?
Yes and no.
For the most part, it’s a good thing — it means the FDA has found the medication you’re taking to be safe and effective. But as mentioned above, there were some unintended consequences.
Colchicine, for example, is a gout medication that wasn’t FDA approved until 2009. And before its approval, the cost per tablet was around $0.09. After its approval, it was only available as brand-name Colcrys for some time after that at around $5 per tablet.
Where can I find more information on unapproved medications?
Here are a few references to get you started:
The bottom line
It wasn’t until 1962 that new drugs needed to show they’re safe and effective for their intended use. But there were many drugs already on the market prior to this requirement. Today, some of these unapproved drugs are still on the market.
The FDA has used several different programs to address this issue, including DESI and UDI. Currently, the FDA uses a risk-based approach for removing unapproved drugs from the market.
If you’re wondering if any medications you’re taking are unapproved, there are many resources available — including your pharmacist or healthcare provider. They can address any questions or concerns you may have.
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References
Azar, A. M. (2020). Termination of the Food and Drug Administration’s unapproved drug initiative; request for information regarding drugs potentially generally recognized as safe and effective. U.S. Department of Health and Human Services.
Bryant Ranch Prepack. (2022). Phenobarbital [prescribing information].
Fierce Biotech. (2009). FDA acts to halt marketing of certain unapproved prescription narcotic drugs.
Gunter, S. J., et al. (2021). Market exclusivity and changes in competition and prices associated with the US Food and Drug Administration unapproved drug initiative. JAMA Internal Medicine.
Gupta, R., et al. (2017). The FDA unapproved drugs initiative: an observational study of the consequences for drug prices and shortages in the United States. Journal of Managed Care & Specialty Pharmacy.
HealthChoice. (2021). FDA unapproved products.
The International Journal of Pharmaceutical Compounding. (n.d.). Do you take unapproved drugs?.
The International Journal of Pharmaceutical Compounding. (n.d.). Pre-1938 drugs not approved by FDA.
Kesselheim, A. S., et al. (2015). Reductions in use of colchicine after FDA enforcement of market exclusivity in a commercially insured population. Journal of General Internal Medicine.
Kinch, M. S., et al. (2019). Lost medicines: A longer view of the pharmaceutical industry with the potential to reinvigorate discovery. Drug Discovery Today.
MedlinePlus. (2018). Phenazopyridine.
Melehani, J. (2021). The unapproved-drugs initiative is coming to an end. The Rheumatologist.
Preferred Pharmaceuticals. (2022). Phenazopyridine hydrochloride [prescribing information].
Roxane Laboratories, Inc. (2008). Roxane Laboratories, Inc. announces the approval of morphine sulfate tablets and oral solution.
U.S. Food and Drug Administration. (n.d.). Drugs@FDA: FDA-approved drugs.
U.S. Food and Drug Administration. (2001). Nitrostat (nitroglycerin sublingual) tablets.
U.S. Food and Drug Administration. (2010). FDA orders two companies to stop marketing unapproved nitroglycerin tablets.
U.S. Food and Drug Administration. (2015). Potassium chloride oral solution.
U.S. Food and Drug Administration. (2015). Questions & answers: FDA’s removal of unapproved prescription drug products containing codeine and dihydrocodeine from the market.
U.S. Food and Drug Administration. (2015). Unapproved prescription cough, cold, and allergy products.
U.S. Food and Drug Administration. (2018). FDA history.
U.S. Food and Drug Administration. (2018). Milestones in U.S. Food and Drug Law.
U.S. Food and Drug Administration. (2018). Summary of NDA approvals & receipts, 1938 to the present.
U.S. Food and Drug Administration. (2021). FDA activities to remove unapproved drugs from the market.
U.S. Food and Drug Administration. (2021). Unapproved drugs.
U.S. Food and Drug Administration. (2022). Drug efficacy study implementation (DESI).
U.S. Food and Drug Administration. (2022). Is it really ‘FDA approved’?.
Yasiry, Z., et al. (2012). How phenobarbital revolutionized epilepsy therapy: the story of phenobarbital therapy in epilepsy in the last 100 years. Epilepsia.
Zampetti, P., et al. (2021). Historical and bibliometric notes on the use of fluoride in caries prevention.
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