The number of serious adverse drug reactions reported in the US is growing at four times the rate of the number of prescriptions, according to the Archives of Internal Medicine. The increasing use of certain biopharmaceuticals and a minority of other drugs account for most of the rise.
Thomas Moore, from the Institute for Safe Medication Practices, Pennsylvania, and colleagues analysed all serious adverse drug events and medication errors reported to the Food and Drug Administration between 1998 and 2005. The analysis excluded medical devices, vaccines, dietary supplements and illegal drugs.
Between 1998 and 2005, the number of serious and fatal adverse drug events increased 2.6-fold and 2.7-fold respectively. The number of reported serious events rose four times faster than the total number of outpatient prescriptions.
In 17.3% of cases the patients died, while 7% of the adverse reactions ended in permanent disability or a birth defect. The proportion of adverse events associated with mortality remained fairly constant: 15.8% in 1998 and 16.8% in 2005. Women experienced 56% of the adverse events, a proportion that also remained constant. Patients aged 65 years and over accounted for 12.6% of the US population but 33.6% of the reported adverse events.
Changes in the population and more intensive treatment were blamed for 25% of the increase in the number of serious adverse events. Serious adverse reactions associated with 13 biotechnology products (anti-tumour necrosis factor agents, interferon alfa and interferon beta), which increased 15.8-fold between 1998 and 2005, accounted for 15% of the increase, with a relatively small proportion of drugs making up the rest.
The analysis linked 1,489 products with serious adverse events. However, 20% of these drugs caused 87% of the events. Among the 15 drugs most commonly named in fatal events, seven were for pain and four acted on the immune system. Oxycodone, fentanyl (both opioid analgesics) and clozapine (an antipsychotic that can disrupt white blood cell counts) were the three drugs most frequently linked to death.
Oestrogens, insulin and infliximab were the three agents most commonly linked to disability or another serious outcome. The top 15 also included antidepressants (paroxetine and venlafaxine), lipid lowerers (atorvastatin and simvastatin) and COX-2 inhibitors (rofecoxib and celecoxib). Nevertheless, drugs linked to withdrawals for safety reasons accounted for only 10% of the serious adverse reactions overall, and their importance declined over time.
The authors suggest that “substantially growing numbers of patients are experiencing serious injuries from drug therapy”. In response, they called for “more accurate and capable systems” to monitor post-marketing adverse events.
Moore TJ, Cohen MR, Furberg CD Serious adverse drug events reported to the Food and Drug Administration, 1998-2005 Arch Intern Med 2007;167:1752-9
