We request that the FDA withdraw acetaminophen’s (aka Tylenol’s) over-the-counter status and make acetaminophen a prescription only medication.  As a prescription only medication, we request that acetaminophen should also include a Black Box Warning indicating that use of acetaminophen has been linked to Autism, ADHD, and Asthma. 

Multiple peer-reviewed medical research studies, dating back more than 10 years, have linked acetaminophen use to autism spectrum disorder and to asthma, and medical research has linked acetaminophen use to attention deficit hyperactivity disorder since 2014.  Despite this, acetaminophen unfortunately remains widely available over-the-counter, in numerous different formulations, and apparently acetaminophen is still recommended by numerous misguided or irresponsible physicians for routine use during pregnancy and also for routine use by infants and children.  Patients and parents are often completely unaware of the risks and unaware of the links between acetaminophen use and autism spectrum disorder, asthma, and attention deficit hyperactivity disorder.  A prescription only status for acetaminophen, along with a Black Box Warning would serve to protect the public.  The FDA needs to withdraw acetaminophen's over-the-counter status immediately to protect infants and children from needless harm.

Before acetaminophen replaced aspirin for use in the pediatric population, due to concerns of risk for Reye's syndrome  (concerns which now appear to have been unfounded) the autism rate in the United States was only 2 - 4 in 10,000.  Now the autism rate  is 1 in 44.  The rates of ADHD and asthma have also skyrocketed during the same time period.  Research indicates acetaminophen induces oxidative stress and depletes the body of glutathione, an important antioxidant, and this is thought to be part of the mechanism by which acetaminophen contributes to autism, asthma, and ADHD. 

We implore the FDA to please act immediately!  Withdraw acetaminophen’s over-the-counter status and include a Black Box Warning regarding acetaminophen’s link to Autism, ADHD, and Asthma.  We ask that the FDA please act immediately to protect infants and children from needless harm!

 

References:

Cendejas-Hernandez J, Sarafian JT, Lawton VG, Palkar A, Anderson LG, Larivière V, Parker W. Paracetamol (acetaminophen) use in infants and children was never shown to be safe for neurodevelopment: a systematic review with citation tracking. Eur J Pediatr. 2022 May;181(5):1835-1857. doi: 10.1007/s00431-022-04407-w. Epub 2022 Feb 17. PMID: 35175416; PMCID: PMC9056471. https://pubmed.ncbi.nlm.nih.gov/35175416/ 

Philippot G, Hosseini K, Yakub A, Mhajar Y, Hamid M, Buratovic S, Fredriksson R. Paracetamol (Acetaminophen) and its Effect on the Developing Mouse Brain. Front Toxicol. 2022 Mar 22;4:867748. doi: 10.3389/ftox.2022.867748. PMID: 35391823; PMCID: PMC8981466.  https://pubmed.ncbi.nlm.nih.gov/35391823/

Bauer AZ, Swan SH, Kriebel D, Liew Z, Taylor HS, Bornehag CG, Andrade AM, Olsen J, Jensen RH, Mitchell RT, Skakkebaek NE, Jégou B, Kristensen DM. Paracetamol use during pregnancy - a call for precautionary action. Nat Rev Endocrinol. 2021 Dec;17(12):757-766. doi: 10.1038/s41574-021-00553-7. Epub 2021 Sep 23. PMID: 34556849; PMCID: PMC8580820. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8580820/

Ji Y, Azuine RE, Zhang Y, Hou W, Hong X, Wang G, Riley A, Pearson C, Zuckerman B, Wang X. Association of Cord Plasma Biomarkers of In Utero Acetaminophen Exposure With Risk of Attention-Deficit/Hyperactivity Disorder and Autism Spectrum Disorder in Childhood. JAMA Psychiatry. 2020 Feb 1;77(2):180-189. doi: 10.1001/jamapsychiatry.2019.3259. PMID: 31664451; PMCID: PMC6822099. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6822099/ 

Maenner MJ, Shaw KA, Bakian AV, et al. Prevalence and Characteristics of Autism Spectrum Disorder Among Children Aged 8 Years --- Autism and Developmental Disabilities Monitoring Network, 11 Sites, United States, 2018. MMWR Surveill Summ 2021;70(No. SS-11):1-16. https://www.cdc.gov/mmwr/volumes/70/ss/ss7011a1.htm 

Parker W, Hornik CD, Bilbo S, et al. The role of oxidative stress, inflammation and acetaminophen exposure from birth to early childhood in the induction of autism. J Int Med Res. 2017;45(2):407-438. doi:10.1177/0300060517693423 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5536672/

Philippot G, Gordh T, Fredriksson A, Viberg H. Adult neurobehavioral alterations in male and female mice following developmental exposure to paracetamol (acetaminophen): characterization of a critical period. J Appl Toxicol. 2017 Oct;37(10):1174-1181. doi: 10.1002/jat.3473. Epub 2017 Apr 27. PMID: 28448685. https://pubmed.ncbi.nlm.nih.gov/28448685/ 

Stergiakouli E, Thapar A, Davey Smith G. Association of Acetaminophen Use During Pregnancy With Behavioral Problems in Childhood: Evidence Against Confounding. JAMA Pediatr. 2016 Oct 1;170(10):964-970. doi: 10.1001/jamapediatrics.2016.1775. PMID: 27533796; PMCID: PMC5300094. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5300094/

Committee to Evaluate the Supplemental Security Income Disability Program for Children with Mental Disorders;  Boat TF,  Wu JT,  editors. Mental Disorders Among Low-Income Children.  National Academies Press (US);  2015 Oct 28. 14, Prevalence of Autism Spectrum Disorder. https://www.ncbi.nlm.nih.gov/books/NBK332896/

Thompson JM, Waldie KE, Wall CR, Murphy R, Mitchell EA; ABC study group. Associations between acetaminophen use during pregnancy and ADHD symptoms measured at ages 7 and 11 years. PLoS One. 2014 Sep 24;9(9):e108210. doi: 10.1371/journal.pone.0108210. PMID: 25251831; PMCID: PMC4177119. https://pubmed.ncbi.nlm.nih.gov/25251831/

Liew Z, Ritz B, Rebordosa C, Lee PC, Olsen J. Acetaminophen use during pregnancy, behavioral problems, and hyperkinetic disorders. JAMA Pediatr. 2014 Apr;168(4):313-20. doi: 10.1001/jamapediatrics.2013.4914. PMID: 24566677.  https://pubmed.ncbi.nlm.nih.gov/24566677/

Posadas I, Santos P, Blanco A, Muñoz-Fernández M, Ceña V. Acetaminophen induces apoptosis in rat cortical neurons. PLoS One. 2010 Dec 10;5(12):e15360. doi: 10.1371/journal.pone.0015360. PMID: 21170329; PMCID: PMC3000821. https://pubmed.ncbi.nlm.nih.gov/21170329/

Becker KG, Schultz ST. Similarities in features of autism and asthma and a possible link to acetaminophen use. Med Hypotheses. 2010;74(1):7-11. doi:10.1016/j.mehy.2009.08.033 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3261751/ 

Beasley R, Clayton T, Crane J, von Mutius E, Lai CK, Montefort S, Stewart A; ISAAC Phase Three Study Group. Association between paracetamol use in infancy and childhood, and risk of asthma, rhinoconjunctivitis, and eczema in children aged 6-7 years: analysis from Phase Three of the ISAAC programme. Lancet. 2008 Sep 20;372(9643):1039-48. doi: 10.1016/S0140-6736(08)61445-2. PMID: 18805332. https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(08)61445-2/fulltext 

Schultz ST, Klonoff-Cohen HS, Wingard DL, Akshoomoff NA, Macera CA, Ji M. Acetaminophen (paracetamol) use, measles-mumps-rubella vaccination, and autistic disorder: the results of a parent survey. Autism. 2008 May;12(3):293-307. doi: 10.1177/1362361307089518. PMID: 18445737. https://pubmed.ncbi.nlm.nih.gov/18445737/ 

Dimova S, Hoet PH, Dinsdale D, Nemery B. Acetaminophen decreases intracellular glutathione levels and modulates cytokine production in human alveolar macrophages and type II pneumocytes in vitro. Int J Biochem Cell Biol. 2005 Aug;37(8):1727-37. doi: 10.1016/j.biocel.2005.03.005. Epub 2005 Apr 26. PMID: 15878691. https://pubmed.ncbi.nlm.nih.gov/15878691/

Orlowski JP, Hanhan UA, Fiallos MR. Is aspirin a cause of Reye's syndrome? A case against. Drug Saf. 2002;25(4):225-31. doi: 10.2165/00002018-200225040-00001. PMID: 11994026. https://pubmed.ncbi.nlm.nih.gov/11994026/