The most common and most pressing reason for pulling a drug off the market is if there have been valid and documented reports that the medicine has become unreasonably dangerous to those who take them.
The US Food and Drug Administration determines whether the drug should be withdrawn if it has a reason to believe that the drug is no longer useful or may be causing more harm than good. The FDA will notify the manufacturer and ask them to voluntarily withdraw the drug from the market. If the manufacturer did not comply, the FDA will bring an action to formally require the company to pull out their product.
There are a lot of factors that may contribute to the withdrawal of a medicine from the market. Some of them may occur together in one way or another and affect how a decision for withdrawal is reached.
Rare, Unpredictable Problems
Drugs are tested on thousands of subjects before being released to the market. This way, certain side effects will be known and warnings will be issued accordingly. However, there are some side effects that are too unpredictable since they rarely occur. Sometimes these rare effects are seen in trials, but they usually show only after more people have taken the drug when it is released to the general market.
More Toxic than Expected
Just like unpredictable side effects, there are times when the drug’s toxicity is not known during trial and would only be found after it has been used by a larger number of people and/or other ways.
An example is Baycol (cerivastatin) which was initially approved by the FDA in 1997. Baycol belongs to a class of statins or medicines for lowering cholesterol. Along with Lipitor (atorvastatin), Lescol (fluvastatin), Mevacor (lovastatin), Pravachol (pravastatin), and Zocor (simvastatin), Baycol has been linked to rhabdomyolysis or the breakdown of muscle cells which could lead to deadly kidney failure and other health problems.
This risk was not seen in Baycol at the time of its initial approval. It is only when the higher dose has been approved and circulated to a larger market that they saw the higher risk of developing rhabdomyolysis in users of the Baycol than in users of other medicines in the same class. Baycol has been voluntarily withdrawn in 2001 from the US market.
When Safer Options Are Available
Seldane (terfenadine) was approved by the FDA in 1985. It is the first prescription antihistamine drug that did not cause drowsiness, which is a side effect of other drugs in its class. However, years after its approval, it has been found that Seldane increases the risk of development of fatal heart rhythm irregularities in patients with liver disease or if it is used with other drugs, specifically those that slows down the elimination of the drug from the body.
Efforts were made to warn the public and the medical community of this side effect, but there has been an increase in reports of cases of fatal heart rhythm abnormalities in its users. Although removal of Seldane was considered because of this side effect, it remained in the market because there is only one other non-sedating antihistamine on the market.
In 1997, Allegra was released to the market, and it has been found to have the same benefits as other terfenadine without causing fatal heart abnormalities. Because of the release of an alternative like Allegra, it contributed to the decision to finally withdraw Seldane from the market.
Like a lot of other drugs, Posicor (mibefradil) causes side effects and health problems if used with other drugs. Posicor on its own is not toxic but in 1998 it has been withdrawn from the market because of its unusual and dangerous interactions with at least 25 other drugs.
Upon its release in 1997, the warning on the label of Posicor indicated possible interactions with only three drugs, then two more were later added, but more reports came in of cases of interactions with more drugs. It became difficult for prescribing physicians to let their patients use Posicor safely because of the numerous medicines it interacts with. Since Posicor did not offer any special benefit in comparison with other drugs in the same class, it has been decided by the FDA to remove the Posicor from the market.
Some drugs, like Seldane, may even interact not just with other drugs but as well as foods and vitamins. Seldane has been reported to have an interaction with grapefruit juice.
When Other Risk Management Options Fail
Sometimes ordinary people would get surprised of a sudden pull-out of a drug from the market. However, such an act is not sudden at all—it is the final step after all other options have been exhausted to manage the risks involved or associated with the drug.
The FDA uses information to healthcare professionals, known as Dear Doctor letters, to educate them about certain drugs. Changes in labeling may also be made to indicate warnings or caution about the medicine and medication guides for the use of patients, informing them of the health risks of taking the medicine and how to avoid or detect any problems.
There are some drugs labelled as second line, or those that will only be used if all else fail. For this reason, some drugs may still be made available even if it is known to be dangerous and they will only be used under very restricted distribution possibly as a last resort.
There are times when the risk management methods work and the drug need not be pulled out from the market. However, there are still medicines that fail after all the techniques have been applied, thus causing their removal from the market.