Recently, I was drinking my morning coffee out of my Vioxx mug. When Vioxx came out, it was BIG. Everyone was going crazy for this drug that was supposed to help pain and inflammation without the typical gastrointestinal side effects that those types of drugs usually caused. While Vioxx was pulled off the market a long time ago (more on this shortly), I still do love the mug and could not part with it! It got me thinking about how many drugs that disappeared because they have been pulled off the market since I have been a pharmacist.
To understand the process of drugs being removed from the market, I think it is important to review how drugs are approved in the first place.
FDA’s Drug Approval Process:
After preclinical/animal testing of a new drug, an Investigational New Drug Application (IND) is filed by the drug’s sponsor, asking to proceed with human testing.
If approved by the FDA, Phase 1 studies begin. These studies typically involve only 20-80 people and focus on safety and side effects.
Phase 2 will study several dozen to 300 people and looks at effectiveness.
Phase 3 will study several hundred to 3,000 people. Phase 3 looks at both safety and effectiveness.
Then, a New Drug Application (NDA) asks the FDA for marketing approval. There is a period of time where inspections of the facility used to manufacture drugs occur, labeling is decided, etc.
You can click here (https://www.fda.gov/Drugs/ResourcesForYou/Consumers/ucm143534.htm) for a comprehensive explanation to read about the process in more detail – this link also explains unique situations such as orphan drugs and accelerated approval, which is given to some new drugs for serious and life-threatening illnesses that lack satisfactory treatments.
After Approval:
After a drug is approved, studies are supposed to continue to monitor the drug in Phase 4, the FDA’s post-approval risk assessment system. It is important to continue to look at safety issues even after the drug is on the market, because issues that may not have been predicted could arise. Serious, unexpected adverse events may be detected, and action can be taken when warranted. Although the FDA requires this follow up testing, there are concerns that the testing is not done completely.
MedWatch to Detect Problems:
Doctors and patients can report adverse events through the FDA’s MedWatch system. As risks or adverse events are discovered, they may be added to the drug’s labeling. If serious, use of the drug may be limited or, in rare cases, withdrawn from the market.
Drugs That Disappeared:
Let’s take a look at some of the more notable drugs that disappeared from the market, starting with the subject of my coffee mug.
rofecoxib (Vioxx):
Vioxx, classified as a COX-2 inhibitor, quickly became widely popular for pain and inflammation. In 2004, Merck announced that Vioxx would be withdrawn from the market after a clinical trial showed patients were at increased risk for heart attacks and strokes.
valdecoxib (Bextra):
Bextra, another COX-2 inhibitor, was removed from the market shortly after Vioxx. In 2005, drug maker Pfizer voluntarily withdrew Bextra from the market based on lack of adequate data on cardiovascular safety, and increased risk of cardiovascular events. There were also reports of serious and potentially life-threatening skin reactions from use of Bextra.
Interesting to note, while Vioxx and Bextra were both removed from the market, celecoxib (Celebrex), the other COX-2 inhibitor, remains on the market to this day, and is still very popular.
terfenadine (Seldane):
Seldane (a non-sedating antihistamine) and Seldane-D (terfenadine plus pseudoephedrine, a decongestant), were removed from the market in 1997 due to life-threatening drug interactions (interacting drugs included ketoconazole, erythromycin, clarithromycin, and even grapefruit juice). The company (Hoechst Marion Roussel, now Sanofi-Aventis) later released non-sedating antihistamine fexofenadine (Allegra), which is chemically similar to Seldane but does not cause life threatening drug interactions.
gatifloxacin (Tequin):
A fluoroquinolone antibiotic, chemically similar to well-known drugs such as Levaquin and Cipro, Tequin (made by Bristol Myers Squibb) was removed from the market after it was determined to cause both hyperglycemia and hypoglycemia. Gatifloxacin remains on the market today, but only as an eyedrop.
Ipecac syrup:
Who hasn’t heard of ipecac? Many years ago, this drug was a household staple that parents could buy over the counter and keep at home in case of poisoning. After decades of research, investigators concluded that though this drug indeed caused vomiting, there was little research to show that people who took this medication after poisoning did any better than others. It was also unsafe for anyone who swallowed chemicals that cause burns on contact or medicines that can cause seizures very quickly. Often, people with eating disorders would rely on this medication to induce vomiting, and regular use of this drug was linked to possible heart problems and death. Sometimes, people vomiting after taking this drug could not keep down other drugs that they needed to treat their poisonings. In 2003, the American Academy of Pediatrics issued a statement telling people to throw out this drug and instead focus on poison prevention, as well as calling Poison Control at 1-800-222-1222 for ingestion of a poisonous substance.
cisapride (Propulsid):
Another drug that was widely popular for a time, Janssen stopped marketing this drug in the United States as of 2000. Like Seldane, pharmacists and doctors were not at first aware of the very dangerous effects of this drug.
Use of this drug, which was given for severe nighttime heartburn not relieved by other treatments, was associated with reports of heart rhythm abnormalities, including 80 reports of deaths, many because of underlying conditions. As with Seldane, many of the serious complications were precipitated by interactions with other medicines. Although this drug is not available through pharmacies or wholesalers, doctors can request and obtain the drug through a limited access program.
These are just a few of the more notable drugs that have been withdrawn from the market. Although I searched several sites for a list of withdrawn drugs and reasons why, I actually was surprised to find that Wikipedia has a good summary of these drugs that disappeared (https://en.wikipedia.org/wiki/List_of_withdrawn_drugs)
Words of Advice from a Pharmacist:
It is scary to hear that a drug you or someone you know has been recalled. What can you do? You cannot predict that a drug that was supposed to help you in one way will turn out to be dangerous in another way.
Often, certain conditions can be managed without medication. For example, some people are able to lower their cholesterol and blood pressure through diet and exercise; some are not. It depends on a variety of factors, and everyone is different. Before starting a medication, ask your doctor what else you may be able to try. Usually if you can use a nondrug therapy, you will not be putting yourself at risk for complications.
Older May Be Better:
In general, I have always felt more comfortable with older, tried and true drugs than with new drugs, if only because their risks may be better known. Although I feel like many people are impressed with the promise of a new drug, for many conditions old drugs do the trick. For example, although new cholesterol drugs have since been approved, our most commonly dispensed cholesterol medication is still atorvastatin (generic Lipitor), which has been around for many years. To me, I would just feel more comfortable with a drug that has been studied for many years, especially if it’s a drug my doctor has put hundreds of patients on without issues. Bonus – Not only are they more studied, but they are more reasonably priced as well.
As always, this theory is not perfect. Recently a study came out that a very popular (and very old) drug, hydrochlorothiazide (this drug is prescribed either on its own or as a combination in many other drugs, for blood pressure) was linked to skin cancer.
Read Labels:
Which brings me to another point – read your warning labels. Many patients admit that they do not read the warning labels – those little stickers next to your label with little nuggets of information such as – do not drink alcohol, stay out of the sun, take until finished, etc. Not only is it important to read your warning labels, but it is important to read all of the information that comes with your prescription. I know it can be long and tedious, but it can save your life. Some of the drugs described above may have been safe on their own, but fatal when mixed with an interacting drug.
Avoid Interactions:
On that note, be sure every doctor you see has a full and updated list of all your medications. Keep your prescriptions all in one pharmacy so that interactions can be picked up by the pharmacist. Many commonly prescribed antibiotics can have dangerous drug interactions with common maintenance medications. Often they are prescribed by different doctors and the interaction may not be picked up. This is why it is important that your prescriptions are located in one central pharmacy. When you are starting on a new prescription, it makes sense to ask both the prescriber and the pharmacist to check for interactions. Don’t just take it for granted that they have done this.
Be sure your pharmacy has your correct, up to date, contact information. If you are like me and do not listen to your messages on your home phone, be sure the pharmacy has your cell phone as your primary contact number. There were several times over the years where we had to call patients to tell them their medication was recalled or taken off the market, and as a patient, you want to be sure you are reachable.
Keep Your Drugs Up to Date:
Clean out your medicine cabinet regularly. Discard expired drugs. While it may be tempting to pop an old antibiotic for a new illness, it is not safe.
Follow Your Doctor’s Instructions:
If your doctor tells you that you need to come back in 3 months for blood work, there is a reason and you should do that to make sure all your levels are within appropriate limits. For example, with cholesterol drugs such as Lipitor, your liver function must be monitored.
Listen to Your Body:
you know that saying, if you see something, say something? If you feel something that’s not right, say something – ask your doctor. Drugs that were withdrawn from the market started with patient reports of problems. Those triggered safety studies.
Chances are, your prescription medication will not be withdrawn from the market, and you will do just fine, but knowledge is power. Read the information your pharmacist gives you, communicate with your healthcare providers, and if something doesn’t feel right, speak up.
Information in this article is intended to be general information and is not individualized and is not a recommendation for treatment. Consult your doctor for personalized health information.
