Annual Report Issue- September 2018

In this issue of QuarterWatch™, we survey the full year of new adverse drug event reports received by the U.S. Food and Drug Administration (FDA) during 2017 to identify drugs most frequently named as suspects in four distinctive and severe adverse drug events. While these adverse events are apparently uncommon, all four are life-threatening medical emergencies. The drugs implicated in these events include many different classes, including antidepressants, antibiotics, and drugs for pain, multiple sclerosis, epilepsy, and psychosis. Rapid diagnosis, identification, and cessation of suspect drugs are central to the treatment of all four disorders.

These are the four adverse events examined:

• Rhabdomyolysis. This disorder occurs when drugs directly or indirectly damage or destroy skeletal muscle cells, which then release such large quantities of cellular proteins that they overwhelm the kidney’s filtering capacity to remove them. Notably, this is the most extreme subset of the spectrum of muscle damage induced by therapeutic drugs.
• Serotonin or Neuroleptic Malignant Syndrome. In serotonin syndrome, an overdose or combination of drugs that increase the levels of this neurotransmitter produces a rapid onset of abnormal behavior and thought, muscle spasms, and compromises of the autonomic nervous system. Neuroleptic malignant syndrome is largely similar except that drugs blocking dopamine receptors trigger the syndrome, and the abnormal muscle contractions are described as lead pipe rigidity.
• Stevens Johnson Syndrome/Toxic Epidermal Necrolysis (SJS/TEN). In this disorder, the body’s immune system attacks and destroys the skin, producing a condition similar to severe burns. The difference between SJS and TEN is the extent of body surface area affected, with SJS limited to less severe cases where less than 10% of body surface is compromised.
• Progressive Multifocal Leukoencephalopathy (PML). This is an often-fatal viral infection of the brain that occurs when immunosuppressive drugs compromise the body’s ability to hold a widely prevalent virus in check. Antibody studies indicate that the virus–John Cunningham virus or JCV–can be found in 50%-70% of the adult population. But both the initial infection and later latency are without symptoms until immune compromise allows the virus to attack and destroy the white matter of the brain.

QuarterWatch™ is an independent publication of the Institute for Safe Medication Practices (ISMP). We analyze computer excerpts from the Food and Drug Administration’s Adverse Event Reporting System (FAERS). These reports (best known as MedWatch reports) are a cornerstone of the nation’s system for monitoring the safety of prescription drugs after FDA marketing approval.