Should the Pediatric Use of Acetaminophen Be Banned?
Banning or drug withdrawal is a regulatory issue. Only regulatory agencies have the lawful right and the power to modify drug indications and prescription status. Regulatory agencies must perform a strict and permanent surveillance of drug safety issues. It is absolutely clear that the scientific literature is sending a large and consistent signal that challenges the traditional excellent safety profile of acetaminophen in children. Moreover, regulatory agencies have access to a more comprehensive body of information than ordinary doctors or researchers have. They have access to full reports of clinical trials, the full content of drug dossiers used for regulatory issues, including approval, they can request all the information needed from sponsors (the so-called data on file, unavailable to the scientific community) and third parties and the opinion and help of external advisors. To the best of our knowledge, no regulatory agency has announced any formal review of the safety profile of acetaminophen in children. We humbly believe that the time has come to do so.
Acetaminophen is a widely used drug with only one widely recognized alternative, ibuprofen. However, practicing pediatricians know very well that acetaminophen is the only antipyretic and analgesic drug available in some clinical settings in children: infants below 3 months of age (ibuprofen not approved in this age range); intravenous use, necessary when the oral route is not appropriate (there is no intravenous presentation of ibuprofen, except the tiny one approved for the treatment of persistent ductus arteriosus in premature infants); children with a variety of digestive conditions that contraindicate ibuprofen; and the presence of NSAID intolerance. In several European countries, metamizol, a propyphenazone derivative, is approved as an antipyretic and analgesic drug in children and enjoys a good reputation as a second line antipyretic, with appropriate oral and intravenous presentations. However, it is not available in many other countries due to safety concerns.
Therefore, acetaminophen withdrawal would produce an actual lack of any antipyretic and analgesic drug available in these clinical situations in which ibuprofen cannot be used. Contrary to what happened with aspirin in the early 2000s, when it was eventually and smoothly withdrawn from any clinical use in pediatrics (although still in use in some infrequent indications, as an antiplatelet drug) due to the availability of a perfect substitute, ibuprofen, acetaminophen withdrawal is not for free.
However, withdrawal may be unnecessary for now. A widespread, professional-based recommendation of limiting acetaminophen use to those cases in which ibuprofen cannot be administered would reduce the childhood population exposure to a minimum and would provide a good opportunity to minimize the detrimental effect of acetaminophen. The size of this opportunity will vary with the overall pediatric population exposure to acetaminophen in each geographic area. For instance, in our health district of Cartagena, Spain, the defined daily dose per 1000 children (0–14 years) per day for ibuprofen and acetaminophen in children were 310 and 64 respectively, in 2011. It seems, therefore, that use of ibuprofen is higher than that of acetaminophen and room for improvement in wheezing disorders prevalence or severity is less than in other geographic areas with a larger acetaminophen exposure. In the ISAAC studies, the proportion of acetaminophen exposure in different countries ranged from 2 to 68% in adolescents and from 11 to 93% in children aged 6–7 years. Therefore, the room for improvement by limiting acetaminophen exposure will vary among geographical areas, depending on previous acetaminophen use.
Expert Rev Resp Med. 2013;7(2):113-122. © 2013 Expert Reviews Ltd.