Review Article| Volume 41, ISSUE 5, P588-593, May 2015

Acetaminophen: Old Drug, New Issues

Published:February 28, 2015DOI:


      • Although acetaminophen (APAP) is considered a safe drug, new concerns and warnings because of acetaminophen overdose and liver failure have resulted in the US Food and Drug Administration (FDA) mandating new labeling on acetaminophen packaging.
      • The FDA has asked acetaminophen manufacturers to lower the strength of acetaminophen in prescription drug products to 325 mg in opioid combination products.
      • Recent evidence also suggests that acetaminophen is a hormone disrupter and thus may not be considered a safe drug during pregnancy.
      • APAP may increase the risk of asthma in children, cause serious allergic reaction and toxicity, potentiate the effect of warfarin, and increase the risk of hematologic malignancies.
      • Finally, within the past decade, the mechanism of action of this drug has been reported to have a central analgesic effect, which inhibits prostaglandin synthesis in the central nervous system.



      The purpose of this review was to discuss new issues related to safety, labeling, dosing, and a better understanding of the analgesic effect of acetaminophen.


      The MEDLINE, Embase, Cochrane, and PubMed databases were searched. Additionally, the bibliography of all relevant articles and textbooks were manually searched. Two reviewers independently selected the relevant articles.


      Concerns about acetaminophen overdose and related liver failure have led the US Food and Drug Administration to mandate new labeling on acetaminophen packaging. In addition, large-scale epidemiologic studies increasingly report evidence for second-generation adverse effects of acetaminophen. Prenatal exposure to acetaminophen is associated with neurodevelopmental and behavioral disorders. Recent studies also suggest that acetaminophen is a hormone disrupter (ie, it interferes with sex and thyroid hormone function essential for normal brain development) and thus may not be considered a safe drug during pregnancy. Finally, emerging evidence suggests that although the predominant mechanism by which acetaminophen exerts its therapeutic effect is by inhibition of cyclooxygenase, multiple other mechanisms also contribute to its analgesic effect.


      Available evidence suggests that indiscriminate usage of this drug is not warranted. and its administration to a pregnant patient should be considered with great caution.

      Key Words

      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'


      Subscribe to Journal of Endodontics
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect


        • Guggenheimer J.
        • Moore P.A.
        The therapeutic applications of and risks associated with acetaminophen use: a review and update.
        J Am Dent Assoc. 2011; 142: 38-44
      1. FDA drug safety communication: prescription acetaminophen products to be limited to 325 mg per dosage unit; boxed warning will highlight potential for severe liver failure.
        (Available at:) (Accessed October 1, 2014)
        • Ostapowicz G.
        • Fontana R.J.
        • Schiødt F.V.
        • et al.
        Results of a prospective study of acute liver failure at 17 tertiary care centers in the United States.
        Ann Intern Med. 2002; 137: 947-954
        • Larson A.M.
        • Polson J.
        • Fontana R.J.
        • et al.
        Acetaminophen-induced acute liver failure: results of a United States multicenter, prospective study.
        Hepatology. 2005; 42: 1364-1372
        • Nourjah P.
        • Ahmad S.R.
        • Karwoski C.
        • Willy M.
        Estimates of acetaminophen (Paracetomal)-associated overdoses in the United States.
        Pharmacoepidemiol Drug Saf. 2006; 15: 398-405
        • Bower W.A.
        • Johns M.
        • Margolis H.S.
        • et al.
        Population-based surveillance for acute liver failure.
        Am J Gastroenterol. 2007; 102: 2459-2463
      2. Federal Register. 2009. Available at: Accessed October 1, 2014.

      3. Food and Drug Administration (FDA). 2009. Available at: Accessed October 1, 2014.

        • Food Drug Administration
        All manufacturers of prescription combination drug products with more than 325 mg of acetaminophen have discontinued marketing.
        2014 (Available at:) (Accessed October 1, 2014)
        • Krenzelok E.P.
        The FDA Acetaminophen Advisory Committee Meeting—what is the future of acetaminophen in the United States? The perspective of a committee member.
        Clin Toxicol (Phila). 2009; 47: 784-789
        • Krenzelok E.P.
        • Royal M.A.
        Confusion: acetaminophen dosing changes based on NO evidence in adults.
        Drugs R D. 2012; 12: 45-48
        • McNeil-PPC
        Tylenol Regular Strength (acetaminophen) tablet.
        McNeil Consumer healthcare Div, 2013 (Available at:) (Accessed October 1, 2014)
      4. OFIRMEV. Available at: Accessed October 1, 2014.

        • Smith H.S.
        Potential analgesic mechanisms of acetaminophen.
        Pain Physician. 2009; 12: 269-280
        • Anderson B.J.
        Paracetamol (Acetaminophen): mechanisms of action.
        Pediatr Anesth. 2008; 18: 915-921
        • Nomura D.K.
        • Morrison B.E.
        • Blankman J.L.
        • et al.
        Endocannabinoid hydrolysis generates brain prostaglandins that promote neuroinflammation.
        Science. 2011; 334: 809-813
        • Hanel A.M.
        • Lands W.E.
        Modification of anti-inflammatory drug effectiveness by ambient lipid peroxides.
        Biochem Pharmacol. 1982; 31: 3307-3311
        • Boutaud O.
        • Aronoff D.M.
        • Richardson J.H.
        • et al.
        Determinants of the cellular specificity of acetaminophen as an inhibitor of prostaglandin H2 synthases.
        Proc Natl Acad Sci U S A. 2002; 99: 7130-7135
        • Schildknecht S.
        • Daiber A.
        • Ghisla S.
        • et al.
        Acetaminophen inhibits prostanoid synthesis by scavenging the PGHS-activator peroxynitrite.
        FASEB J. 2008; 22: 215-224
        • Flower R.J.
        • Vane J.R.
        Inhibition of prostaglandin synthetase in brain explains the anti-pyretic activity of paracetamol (4-acetamidophenol).
        Nature. 1972; 240: 410-411
        • Feldberg W.
        • Gupta K.
        Pyrogen fever and prostaglandin-like activity in cerebrospinal fluid.
        J Physiol. 1973; 228: 41-53
        • Muth-Selbach U.S.
        • Tegeder I.
        • Brune K.
        • Geisslinger G.
        Acetaminophen inhibits spinal prostaglandin E2 release after peripheral noxious stimulation.
        Anesthesiology. 1999; 91: 231-239
        • Ayoub S.S.
        • Botting R.M.
        • Goorha S.
        • et al.
        Acetaminophen-induced hypothermia in mice is mediated by a prostaglandin endoperoxide synthase 1 gene-derived protein.
        Proc Natl Acad Sci U S A. 2004; 101: 11165-11169
        • Lee Y.S.
        • Kim H.
        • Brahim J.S.
        • et al.
        Acetaminophen selectively suppresses peripheral prostaglandin E2 release and increases COX-2 gene expression in a clinical model of acute inflammation.
        Pain. 2007; 129: 279-286
        • Marek G.
        • Aghajanian G.
        5-Hydroxytryptamine-induced excitatory postsynaptic currents in neocortical layer V pyramidal cells: suppression by [mu]-opiate receptor activation.
        Neuroscience. 1998; 86: 485-497
        • Ruggieri V.
        • Vitale G.
        • Pini L.A.
        • Sandrini M.
        Differential involvement of opioidergic and serotonergic systems in the antinociceptive activity of N-arachidonoyl-phenolamine (AM404) in the rat: comparison with paracetamol.
        Naunyn Schmiedebergs Arch Pharmacol. 2008; 377: 219-229
        • Högestätt E.D.
        • Jönsson B.A.
        • Ermund A.
        • et al.
        Conversion of acetaminophen to the bioactive N-acylphenolamine AM404 via fatty acid amide hydrolase-dependent arachidonic acid conjugation in the nervous system.
        J Biol Chem. 2005; 280: 31405-31412
        • Dani M.
        • Guindon J.
        • Lambert C.
        • Beaulieu P.
        The local antinociceptive effects of paracetamol in neuropathic pain are mediated by cannabinoid receptors.
        Eur J Pharmacol. 2007; 573: 214-215
        • Pelissier T.
        • Alloui A.
        • Caussade F.
        • et al.
        Paracetamol exerts a spinal antinociceptive effect involving an indirect interaction with 5-hydroxytryptamine3 receptors: in vivo and in vitro evidence.
        J Pharmacol Exp Ther. 1996; 278: 8-14
        • Pini L.A.
        • Sandrini M.
        • Vitale G.
        The antinociceptive action of paracetamol is associated with changes in the serotonergic system in the rat brain.
        Eur J Pharmacol. 1996; 308: 31-40
        • Choi S.S.
        • Lee J.K.
        • Suh H.W.
        Antinociceptive profiles of aspirin and acetaminophen in formalin, substance P and glutamate pain models.
        Brain Res. 2001; 921: 233-239
        • Crawley B.
        • Saito O.
        • Malkmus S.
        • et al.
        Acetaminophen prevents hyperalgesia in central pain cascade.
        Neurosci Lett. 2008; 442: 50-53
        • Björkman R.
        • Hallman K.
        • Hedner J.
        • et al.
        Acetaminophen blocks spinal hyperalgesia induced by NMDA and substance P.
        Pain. 1994; 57: 259-264
        • Zygmunt P.M.
        • Chuang H.
        • Movahed P.
        • et al.
        The anandamide transport inhibitor AM404 activates vanilloid receptors.
        Eur J Pharmacol. 2000; 396: 39-42
        • Kerckhove N.
        • Mallet C.
        • François A.
        • et al.
        Cav3.2 calcium channels: the key protagonist in the supraspinal effect of paracetamol.
        Pain. 2014; 155: 764-772
        • McGilveray I.
        • Mattok G.
        Some factors affecting the absorption of paracetamol.
        J Pharm Pharmacol. 1972; 24: 615-619
        • Nimmo W.
        • Heading R.
        • Wilson J.
        • et al.
        Inhibition of gastric emptying and drug absorption by narcotic analgesics.
        Br J Clin Pharmacol. 1975; 2: 509-513
        • Nimmo J.
        • Heading R.
        • Tothill P.
        • Prescott L.
        Pharmacological modification of gastric emptying: effects of propantheline and metoclopromide on paracetamol absorption.
        Br Med J. 1973; 1: 587-589
        • Prescott L.
        Kinetics and metabolism of paracetamol and phenacetin.
        Br J Clin Pharmacol. 1980; 10: 291S-298S
        • Renner B.
        • Clarke G.
        • Grattan T.
        • et al.
        Caffeine accelerates absorption and enhances the analgesic effect of acetaminophen.
        J Clin Pharmacol. 2007; 47: 715-726
        • Gazzard B.
        • Ford-Hutchinson A.
        • Smith M.
        • Williams R.
        The binding of paracetamol to plasma proteins of man and pig.
        J Pharm Pharmacol. 1973; 25: 964-967
        • Hinderling P.H.
        Red blood cells: a neglected compartment in pharmacokinetics and pharmacodynamics.
        Pharmacol Rev. 1997; 49: 279-295
        • Mallet C.
        • Barrière D.A.
        • Ermund A.
        • et al.
        TRPV1 in brain is involved in acetaminophen-induced antinociception.
        PLoS One. 2010; 5: e12748
        • Jensen M.S.
        • Rebordosa C.
        • Thulstrup A.M.
        • et al.
        Maternal use of acetaminophen, ibuprofen, and acetylsalicylic acid during pregnancy and risk of cryptorchidism.
        Epidemiology. 2010; 21: 779-785
        • Mazaud-Guittot S.
        • Nicolaz C.N.
        • Desdoits-Lethimonier C.
        • et al.
        Paracetamol, aspirin, and indomethacin induce endocrine disturbances in the human fetal testis capable of interfering with testicular descent.
        J Clin Endocrinol Metab. 2013; 98: E1757-E1767
        • Forrest J.A.
        • Clements J.
        • Prescott L.
        Clinical pharmacokinetics of paracetamol.
        Clin Pharmacokinet. 1982; 7: 93-107
        • Benson G.D.
        • Koff R.S.
        • Tolman K.G.
        The therapeutic use of acetaminophen in patients with liver disease.
        Am J Ther. 2005; 12: 133-141
        • Potter W.
        • Davis D.
        • Mitchell J.
        • et al.
        Acetaminophen-induced hepatic necrosis. III. Cytochrome P-450-mediated covalent binding in vitro.
        J Pharmacol Exp Ther. 1973; 187: 203-210
        • Jollow D.J.
        • Thorgeirsson S.-S.
        • Potter W.Z.
        • et al.
        Acetaminophen-induced hepatic necrosis. VI. Metabolic disposition of toxic and nontoxic doses of acetaminophen.
        Pharmacology. 1973; 12: 251-271
        • Potter W.
        • Thorgeirsson S.
        • Jollow D.
        • Mitchell J.
        Acetaminophen-induced hepatic necrosis V. Correlation of hepatic necrosis, covalent binding and glutathione depletion in hamsters.
        Pharmacology. 1974; 12: 129-143
        • Mitchell J.R.
        • Thorgeirsson S.S.
        • Potter W.Z.
        • et al.
        Acetaminophen-induced hepatic injury: protective role of glutathione in man and rationale for therapy.
        Clin Pharmacol Ther. 1974; 16: 676-684
        • Moore A.
        • Collins S.
        • Carroll D.
        • McQuay H.
        Paracetamol with and without codeine in acute pain: a quantitative systematic review.
        Pain. 1997; 70: 193-201
        • Moore A.
        • Collins S.
        • Carroll D.
        • et al.
        Single dose paracetamol (acetaminophen), with and without codeine, for postoperative pain.
        Cochrane Database Syst Rev. 2000; 2: CD001547
        • Barden J.
        • Edwards J.
        • Moore A.
        • McQuay H.
        Single dose oral paracetamol (acetaminophen) for postoperative pain.
        Cochrane Database Syst Rev. 2004; 1: CD004602
        • Mason L.
        • Edwards J.E.
        • Moore R.A.
        • McQuay H.J.
        Single-dose oral naproxen for acute postoperative pain: a quantitative systematic review.
        BMC Anesthesiol. 2003; 3: 4
        • Toms L.
        • McQuay H.J.
        • Derry S.
        • Moore R.A.
        Single dose oral paracetamol (acetaminophen) for postoperative pain in adults.
        Cochrane Database Syst Rev. 2008; 4: CD004602
        • Toms L.
        • Derry S.
        • Moore R.A.
        • McQuay H.J.
        Single dose oral paracetamol (acetaminophen) with codeine for postoperative pain in adults.
        Cochrane Database Syst Rev. 2009; 1: CD001547
        • McQuay H.J.
        • Moore R.A.
        Using numerical results from systematic reviews in clinical practice.
        Ann Intern Med. 1997; 126: 712-720
      5. Acute pain Bandolier—evidenced based health care. 2003 (Available at:) (Accessed October 1, 2014)
      6. Bandolier—evidenced based health care. 2003 (Available at:) (Accessed October 1, 2014)
        • Krisanaprakornkit S.
        • Kimball J.R.
        • Dale B.A.
        Regulation of human β-defensin-2 in gingival epithelial cells: the involvement of mitogen-activated protein kinase pathways, but not the NF-κB transcription factor family.
        J Immunol. 2002; 168: 316-324
        • Moore R.A.
        Bandolier's Little Book of Pain.
        Oxford University Press, New York2003
        • Moore P.A.
        • Hersh E.V.
        Combining ibuprofen and acetaminophen for acute pain management after third-molar extractions: translating clinical research to dental practice.
        J Am Dent Assoc. 2013; 144: 898-908
        • Hyllested M.
        • Jones S.
        • Pedersen J.
        • Kehlet H.
        Comparative effect of paracetamol, NSAIDs or their combination in postoperative pain management: a qualitative review.
        Br J Anaesth. 2002; 88: 199-214
        • Bailey E.
        • Worthington H.
        • Coulthard P.
        Ibuprofen and/or paracetamol (acetaminophen) for pain relief after surgical removal of lower wisdom teeth, a Cochrane systematic review.
        Br Dent J. 2014; 216: 451-455
        • Bailey E.
        • Worthington H.V.
        • van Wijk A.
        • et al.
        Ibuprofen and/or paracetamol (acetaminophen) for pain relief after surgical removal of lower wisdom teeth.
        Cochrane Database Syst Rev. 2013; 12: CD004624
        • Menhinick K.
        • Gutmann J.
        • Regan J.
        • et al.
        The efficacy of pain control following nonsurgical root canal treatment using ibuprofen or a combination of ibuprofen and acetaminophen in a randomized, double-blind, placebo-controlled study.
        Int Endod J. 2004; 37: 531-541
        • Wells L.K.
        • Drum M.
        • Nusstein J.
        • et al.
        Efficacy of ibuprofen and ibuprofen/acetaminophen on postoperative pain in symptomatic patients with a pulpal diagnosis of necrosis.
        J Endod. 2011; 37: 1608-1612
        • Ong C.K.
        • Seymour R.A.
        • Lirk P.
        • Merry A.F.
        Combining paracetamol (acetaminophen) with nonsteroidal antiinflammatory drugs: a qualitative systematic review of analgesic efficacy for acute postoperative pain.
        Anesth Analg. 2010; 110: 1170-1179
        • Derry C.J.
        • Derry S.
        • Moore R.A.
        Single dose oral ibuprofen plus paracetamol (acetaminophen) for acute postoperative pain.
        Cochrane Database Syst Rev. 2013; 6: CD010210
        • Elia N.
        • Lysakowski C.
        • Tramer M.R.
        Does multimodal analgesia with acetaminophen, nonsteroidal antiinflammatory drugs, or selective cyclooxygenase-2 inhibitors and patient-controlled analgesia morphine offer advantages over morphine alone?: meta-analyses of randomized trials.
        Anesthesiology. 2005; 103: 1296-1304
        • Merry A.
        • Gibbs R.
        • Edwards J.
        • et al.
        Combined acetaminophen and ibuprofen for pain relief after oral surgery in adults: a randomized controlled trial.
        Br J Anaesth. 2010; 104: 80-88
        • Mehlisch D.R.
        • Ashley S.
        • Daniels S.E.
        • Bandy D.P.
        Comparison of the analgesic efficacy of concurrent ibuprofen and paracetamol with ibuprofen or paracetamol alone in the management of moderate to severe acute postoperative dental pain in adolescents and adults: a randomized, double-blind, placebo-controlled, parallel-group, single-dose, two-center, modified factorial study.
        Clin Ther. 2010; 32: 882-895
        • FDA
        FDA warns of rare but serious skin reactions with the pain reliever/fever reducer acetaminophen.
        2013 (Available at:) (Accessed October 1, 2014)
        • Kim E.J.
        • Lim H.
        • Park S.Y.
        • et al.
        Rapid onset of Stevens-Johnson syndrome and toxic epidermal necrolysis after ingestion of acetaminophen.
        Asia Pac Allergy. 2014; 4: 68-72
        • Kuehn B.M.
        FDA: acetaminophen may trigger serious skin problems.
        JAMA. 2013; 310: 785
        • Etminan M.
        • Sadatsafavi M.
        • Jafari S.
        • et al.
        Acetaminophen use and the risk of asthma in children and adults: a systematic review and metaanalysis.
        Chest. 2009; 136: 1316-1323
        • Beasley R.
        • Clayton T.
        • Crane J.
        • et al.
        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; 372: 1039-1048
        • Shaheen S.O.
        • Newson R.B.
        • Ring S.M.
        • et al.
        Prenatal and infant acetaminophen exposure, antioxidant gene polymorphisms, and childhood asthma.
        J Allergy Clin Immunol. 2010; 126: 1141-1148.e7
        • Eyers S.
        • Weatherall M.
        • Jefferies S.
        • Beasley R.
        Paracetamol in pregnancy and the risk of wheezing in offspring: a systematic review and meta-analysis.
        Clin Exp Allergy. 2011; 41: 482-489
        • Settipane R.A.
        • Schrank P.J.
        • Simon R.A.
        • et al.
        Prevalence of cross-sensitivity with acetaminophen in aspirin-sensitive asthmatic subjects.
        J Allergy Clin Immunol. 1995; 96: 480-485
        • Beasley R.W.
        • Clayton T.O.
        • Crane J.
        • et al.
        Acetaminophen use and risk of asthma, rhinoconjunctivitis, and eczema in adolescents: International Study of Asthma and Allergies in Childhood Phase Three.
        Am J Respir Crit Care Med. 2011; 183: 171-178
        • Amberbir A.
        • Medhin G.
        • Alem A.
        • et al.
        The role of acetaminophen and geohelminth infection on the incidence of wheeze and eczema: a longitudinal birth-cohort study.
        Am J Respir Crit Care Med. 2011; 183: 165-170
        • McBride J.T.
        The association of acetaminophen and asthma prevalence and severity.
        Pediatrics. 2011; 128: 1181-1185
        • Lai M.W.
        • Klein-Schwartz W.
        • Rodgers G.C.
        • et al.
        2005 Annual Report of the American Association of Poison Control Centers' national poisoning and exposure database.
        Clin Toxicol. 2006; 44: 803-932
        • Clark R.
        • Borirakchanyavat V.
        • Davidson A.
        • et al.
        Hepatic damage and death from overdose of paracetamol.
        Lancet. 1973; 301: 66-70
      7. Acetaminophen safety - deja vu.
        Med Lett Drugs Ther. 2009; 51 (56): 53-54
        • Zimmerman H.J.
        • Maddrey W.C.
        Acetaminophen (paracetamol) hepatotoxicity with regular intake of alcohol: analysis of instances of therapeutic misadventure.
        Hepatology. 1995; 22: 767-773
        • Riley 3rd, T.
        • Bhatti A.M.
        Preventive strategies in chronic liver disease: part I. Alcohol, vaccines, toxic medications and supplements, diet and exercise.
        Am Fam Physician. 2001; 64: 1555-1560
        • Schilling A.
        • Corey R.
        • Leonard M.
        • Eghtesad B.
        Acetaminophen: old drug, new warnings.
        Cleve Clin J Med. 2010; 77: 19-27
        • Prescott L.
        Effects of non-narcotic analgesics on the liver.
        Drugs. 1986; 32: 129-147
        • Jones A.L.
        Recent advances in the management of late paracetamol poisoning.
        Emerg Med. 2000; 12: 14-21
        • O'connor N.
        • Dargan P.I.
        • Jones A.L.
        Hepatocellular damage from non-steroidal anti-inflammatory drugs.
        QJM. 2003; 96: 787-791
        • Graham G.G.
        • Davies M.J.
        • Day R.O.
        • et al.
        The modern pharmacology of paracetamol: therapeutic actions, mechanism of action, metabolism, toxicity and recent pharmacological findings.
        Inflammopharmacology. 2013; 21: 201-232
        • Kheradpezhouh E.
        • Ma L.
        • Morphett A.
        • et al.
        TRPM2 channels mediate acetaminophen-induced liver damage.
        Proc Natl Acad Sci U S A. 2014; 111: 3176-3181
        • Thiele K.
        • Kessler T.
        • Arck P.
        • et al.
        Acetaminophen and pregnancy: short-and long-term consequences for mother and child.
        J Reprod Immunol. 2013; 97: 128-139
        • Liew Z.
        • Ritz B.
        • Rebordosa C.
        • et al.
        Acetaminophen use during pregnancy, behavioral problems, and hyperkinetic disorders.
        JAMA Pediatr. 2014; 168: 313-320
        • Brandlistuen R.E.
        • Ystrom E.
        • Nulman I.
        • et al.
        Prenatal paracetamol exposure and child neurodevelopment: a sibling-controlled cohort study.
        Int J Epidemiol. 2013; 42: 1702-1713
        • Albert O.
        • Desdoits-Lethimonier C.
        • Lesné L.
        • et al.
        Paracetamol, aspirin and indomethacin display endocrine disrupting properties in the adult human testis in vitro.
        Hum Reprod. 2013; 28: 1890-1898
        • Colborn T.
        Neurodevelopment and endocrine disruption.
        Environ Health Perspect. 2004; 112: 944-949
        • Howdeshell K.L.
        A model of the development of the brain as a construct of the thyroid system.
        Environ Health Perspect. 2002; 110: 337-348
        • Rubinow D.R.
        • Schmidt P.J.
        Androgens, brain, and behavior.
        Am J Psychiatry. 1996; 153: 974-984
        • Shaheen S.
        • Newson R.
        • Sherriff A.
        • et al.
        Paracetamol use in pregnancy and wheezing in early childhood.
        Thorax. 2002; 57: 958-963
        • Scialli A.R.
        • Ang R.
        • Breitmeyer J.
        • Royal M.A.
        Childhood asthma and use during pregnancy of acetaminophen. A critical review.
        Reprod Toxicol. 2010; 30: 508-519
        • Parra D.
        • Beckey N.P.
        • Stevens G.R.
        The effect of acetaminophen on the international normalized ratio in patients stabilized on warfarin therapy.
        Pharmacotherapy. 2007; 27: 675-683
        • Mahé I.
        • Bertrand N.
        • Drouet L.
        • et al.
        Interaction between paracetamol and warfarin in patients: a double-blind, placebo-controlled, randomized study.
        Haematologica. 2006; 91: 1621-1627
        • Walter R.B.
        • Milano F.
        • Brasky T.M.
        • White E.
        Long-term use of acetaminophen, aspirin, and other nonsteroidal anti-inflammatory drugs and risk of hematologic malignancies: results from the prospective Vitamins and Lifestyle (VITAL) study.
        J Clin Oncol. 2011; 29: 2424-2431
        • Robak P.
        • Smolewski P.
        • Robak T.
        The role of non-steroidal anti-inflammatory drugs in the risk of development and treatment of hematologic malignancies.
        Leuk Lymphoma. 2008; 49: 1452-1462
        • Becker N.
        • Fortuny J.
        • Alvaro T.
        • et al.
        Medical history and risk of lymphoma: results of a European case–control study (EPILYMPH).
        J Cancer Res Clin Oncol. 2009; 135: 1099-1107
        • Herring B.O.
        • Ader S.
        • Maldonado A.
        • et al.
        Impact of intravenous acetaminophen on reducing opioid use after hysterectomy.
        Pharmacotherapy. 2014; 34: 27S-33S
        • Smith A.N.
        • Hoefling V.C.
        A retrospective analysis of intravenous acetaminophen use in spinal surgery patients.
        Pharm Pract (Granada). 2014; 12: 417
        • Hall N.S.
        • Le B.
        Postmarketing review of intravenous acetaminophen dosing based on Food and Drug Administration prescribing guidelines.
        Pharmacotherapy. 2014; 34: 34S-39S
        • Pickering G.
        • Macian N.
        • Libert F.
        • et al.
        Buccal acetaminophen provides fast analgesia: two randomized clinical trials in healthy volunteers.
        Drug Des Devel Ther. 2014; 8: 1621-1627