Drugs are often approved with less than ideal data, suggesting that they are, on balance, reasonably safe and effective. Later, experience during clinical use after approval may show that some drugs are much less safe than apparent at the time of approval. When sufficient data accumulate, the Food and Drug Administration (FDA) may decide to remove approval of the drug or issue a “black box” warning for physicians to heed when prescribing the drug. There are 4 conditions in which the FDA may issue such a black box warning: (1) there are potentially fatal, life threatening or disabling side effects, (2) the clinician can avoid harmful effects by unusually careful management of the patient’s reaction to the drug, (3) the use is restricted, and (4) the drug is less effective or more dangerous to a specific population such as children, adolescents or the elderly. The patient may assume that such drugs are rare and that their doctor will tell them about the safety concerns and manage these well. However, only half of clinicians order laboratory testing specified by black box warnings. As of 2013 there were 760 drugs on the black box list according to a table compiled by Micromedex Solutions. Occasionally, drugs such as Avandia, which is for treatment of type 2 diabetes, may have their black box labelling removed as a result of new, high-quality studies.
What does ignoring a black box warning look like in some specific cases? I know of a physician whose 15-year-old son was prescribed Zoloft for mild depression. Sadly, after taking the drug for only 2 weeks, the adolescent got in his father’s closet, found a shot gun and destroyed his brain. Another story of dangerously prescribing Zoloft despite its black box warning comes from a mother whose 19-year-old daughter committed what she calls “medicide.” She was suffering from akathisia. Her mother’s words concerning her daughter’s death were these:
Two days after taking the maximum Zoloft dose as prescribed, Natalie was dead. She had valiantly raged against the dying light for nearly half her life, but was no match for 200 mg of Zoloft. She died of violent self-sustained injury, but did not die by her own hand: She was chemically tortured, suffered and died at the hands of her doctors. Their negligence was medical violence. As is typical of akathisia-induced death, Natalie, who was born a gentle soul, did not go gently into that good night. https://rxisk.org/kidnapped-natalies-story-2/.
One of the most frightening side effects from black box drug use is bleeding issues that can occur even when taking a drug as prescribed. Pradaxa is one of those drugs. Its black box warning informs of a statistically significant trend of internal bleeding associated with use of the drug. There are a host of other serious side effects which have caused the manufacturer of this drug to come under fire from both regulators and consumers.
Fluoroquinolone antibiotics are another source of harm from drugs that have earned the “black box” warning. A foundation has been formed to help those harmed by this class of antibiotics. The primary side effects are increased risk of inflammatory conditions like tendonitis and nervous system damage resulting in neuropathy. Rachel Brummert has become a champion of restricting use of fluoroquinolones as a result of the suffering she experienced after taking Levaquin and Cipro, originally for a sinus infection. She has had multiple tendon ruptures and associated repair surgeries after starting the first medication.
Clopidogrel (Plavix), which is used to reduce the risk of heart attack and stroke, has a black box warning because it may cause excessive bleeding. It seems even pioneering doctors are not immune from the harm caused by black box medications. In a sorrowful tale, a her physician husband tells the story of the death of his wife, Barbara Starfield, MD. She was the first I know of to declare that medical errors are the third leading cause of death in the U.S. Her husband writes that she had been on an anticoagulant longer than she should have been, and this is likely to have contributed to her death. A massive brain hemorrhage was found on autopsy. He notes many shortcomings in her treatment history.
The message to patients is to ask if any medication prescribed to you has a black box warning, and if so, ask why the warning was issued. This information will also be on the label of the drug. Ask if there are any less risky medications for the condition the drug is targeted to help. You do not need to have a sad story to tell about a black box drug.