1,036
Views
5
CrossRef citations to date
0
Altmetric
Pain

Clinical update on benefit versus risks of oral paracetamol alone or with codeine: still a good option?

&
Pages 289-304 | Received 03 Oct 2016, Accepted 24 Oct 2016, Published online: 15 Nov 2016

References

  • PIC 2016. Paracetamol Information Centre. Available at: www.pharmweb.net [Last accessed 27 June 2016]
  • O’Neil CK, Hanlon JT, Marcum ZA. Adverse effects of analgesics commonly used by older adults with osteoarthritis: focus on non-opioid and opioid analgesics. Am J Geriatr Pharmacother 2012;10:331-42
  • Fulton RL, Walters MR, Morton R, et al. Acetaminophen use and risk of myocardial infarction and stroke in a hypertensive cohort. Hypertension 2015;65:1008-14
  • American Geriatrics Society. 2015 Updated Beers Criteria for potentially inappropriate medication use in older adults. J Am Geriatr Soc 2015;64:1-20
  • WHO Model List of Essential Medicines, 19th Edition. 2015. Available at: http://www.who.int/medicines/publications/essentialmedicines/EML2015_8-May-15.pdf?ua=1 [Last accessed 20 July 2016]
  • McAlindon TE, Bannuru RR, Sullivan MC, et al. OARSI guidelines for the non-surgical management of knee osteoarthritis. Osteoarthritis Cartilage 2014;22:363-88
  • Hochberg MC, Altman RD, April KT, et al. American College of Rheumatology 2012 recommendations for the use of nonpharmacologic and pharmacologic therapies in osteoarthritis of the hand, hip, and knee. Arthritis Care Res 2012;64:465-74
  • Zhang W, Moskowitz RW, Nuki G, et al. OARSI recommendations for the management of hip and knee osteoarthritis, part II: OARSI evidence-based, expert consensus guidelines. Osteoarthritis Cartilage 2008;16:137-62
  • Zhang W, Nuki G, Moskowitz RW, et al. OARSI recommendations for the management of hip and knee osteoarthritis, part III: changes in evidence following systematic cumulative update of research published through January 2009. Osteoarthritis Cartilage 2010;18:476-99
  • Zhang W, Doherty M, Leeb BF, et al. EULAR evidence based recommendations for the management of hand osteoarthritis: report of a task force of the EULAR standing committee for international clinical studies including therapeutics (ESCISIT). Ann Rheum Dis 2007;66:377-88
  • Zhang W, Doherty M, Arden N, et al. EULAR evidence based recommendations for the management of hip osteoarthritis: report of a task force of the EULAR standing committee for international clinical studies including therapeutics (ESCISIT). Ann Rheum Dis 2005;64:669-81
  • Worthington I, Pringsheim T, Gawel MJ, et al., Canadian Headache Society Acute Migraine Treatment Guideline Development Group. Canadian Headache Society Guideline: acute drug therapy for migraine headache. Can J Neurol Sci 2013;40(Suppl 3):S1-S80
  • Marmura MJ, Silberstein SD, Schwedt TJ. The acute treatment of migraine in adults: the American Headache Society Evidence Assessment of migraine pharmacotherapies. Headache 2015;55:3-20
  • NICE guidelines [CG177]: Osteoarthritis: care and management 2014. National Clinical Guideline Centre. Available at: https://www.nice.org.uk/guidance/cg177/evidence [Last accessed 20 July 2016]
  • Brune K, Renner B, Tiegs G. Acetaminophen/paracetamol: a history of errors, failures and false decisions. Eur J Pain 2014;19:953-65
  • Roberts E, Delgado Nunes V, Buckner S, et al. Paracetamol: not as safe as we thought? A systematic literature review of observational studies. Ann Rheum Dis 2016;75:552-9
  • Wise J. True risks of paracetamol may be underestimated, say researchers. BMJ 2015;350:h1136
  • Aminoshariae A, Khan A. Acetaminophen: old drug, new issues. J Endod 2015;41:588-93
  • Straube C, Derry S, Jackson KC, et al. Codeine, alone and with paracetamol (acetaminophen), for cancer pain. Cochrane Database Syst Rev 2014;9:CD006601
  • Heintze K, Fuchs W. Codeine ultra-rapid metabolizers: age appears to be a key factor in adverse effects of codeine. Drug Res (Stuttg) 2015;65:640-4
  • Review of Codeine Containing Medicines Started. European Medicines Agency, 2012. Available at: http://www.ema.europa.eu/ema/index.jsp?curl=pages/medicines/human/referrals/Codeine_containing_medicinal_products/human_referral_prac_000008.jsp&mid=WC0b01ac05805c516f [Last accessed 20 July 2016]
  • United States Food and Drug Administration. Drug Safety Communication. Safety Review Update of Codeine use in Children; A New Boxed Warning and Contraindication on Use after Tonsillectomy and or Adenoidectomy. United States Food and Drug Administration, 2013. Available at: www.fda.gov/Drugs/Drugsafety/ucm339112.htm [Last accessed 20 July 2016]
  • Bond GR, Ho M, Woodward RW. Trends in hepatic injury associated with unintentional overdose of paracetamol (acetaminophen) in products with and without opioid. Drug Saf 2012;35:149-57
  • Larson AM, Polson J, Fontana RJ, et al.; Acute Liver Failure Study Group. Acetaminophen-induced acute liver failure: results of a United States multicenter, prospective study. Hepatology 2005;42:1364-72
  • Krenzelok EP. 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;47:784-9
  • Department of Health and Human Services, Food and Drug Administration (Docket No. FDA–2011–N–0021) Prescription Drug Products Containing Acetaminophen; Actions To Reduce Liver Injury From Unintentional Overdose. Federal Register 2011;76, No. 10/Notices 2691
  • Wehling M. Paracetamol. Efficacious and safe for all ages. Schmerz 2013;27:20-5
  • Petersen KU. Acetaminophen and the liver: damage at therapeutic dose levels? MMW-Fortschr Med 2011;153:137-42
  • Twycross R, Pace V, Mihalyo M, Wilcock A. Therapeutic reviews: acetaminophen (paracetamol). J Pain Symptom Manage 2013;46:747
  • Prescott LF. Paracetamol (acetaminophen): a critical bibliographic review. London: Taylor & Francis, 1996
  • Liukas A, Kuusniemi K, Aantaa R, et al. Pharmacokinetics of intravenous paracetamol in elderly patients. Clin Pharmacokinet 2011;50:121-9
  • Zhao L, Pickering G. Paracetamol metabolism and related genetic differences. Drug Metab Rev 2011;43:41-52
  • Dong H, Haining RL, Thummel KE, et al. Involvement of human cytochrome P4502D6 in the bioactivation of acetaminophen. Drug Metab Dispos 2000;28:1397-400
  • Miranda HF, Puig MM, Prieto JC, Pinardi G. Synergism between paracetamol and nonsteroidal antiinflammatory drugs in experimental acute pain. Pain 2006;121:22-8
  • Ong CK, Seymour RA, Lirk P, Merry AF. Combining paracetamol (acetaminophen) with nonsteroidal antiinflammatory drugs: a qualitative systematic review of analgesic efficacy for acute postoperative pain. Anesth Analg 2010;110:1170-9
  • Moore UJ, Seymour RA, Rawlins MD. The efficacy of locally applied aspirin and acetaminophen in postoperative pain after third molar surgery. Clin Pharmacol Ther 1992;52:292-6
  • Pini LA, 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 SS, Lee JK, Suh HW. Antinociceptive profiles of aspirin and acetaminophen in formalin, substance P and glutamate pain models. Brain Res 2001;921:233-9
  • Crawley B, Saito O, Malkmus S, et al. Acetaminophen prevents hyperalgesia in central pain cascade. Neurosci Lett 2008;442:50-3
  • Björkman R, Hallman K, Hedner J, et al. Acetaminophen blocks spinal hyperalgesia induced by NMDA and substance P. Pain 1994;57:259-64
  • Zygmunt PM, 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, Francois A, et al. Cav3.2 calcium channels: the key protagonist in the supraspinal effect of paracetamol. Pain 2014;155:764-72
  • McQuay HJ, Moore RA. Using numerical results from systematic reviews in clinical practice. Ann Intern Med 1997;126:712-20
  • Acute pain Bandolier – evidenced based health care. Available at: http://www.medicine.ox.ac.uk/bandolier/Extraforbando/APain.pdf [Last accessed 1 October 2014]
  • Moore RA, Moore OA, Derry S, McQuay HJ. Numbers needed to treat calculated from responder rates give a better indication of efficacy in osteoarthritis trials than mean pain scores. Arthritis Res Ther 2008;10:R39
  • Straube S, Derry S, McQuay HJ, Moore RA. Enriched enrolment: definition and effects of enrichment and dose in trials of pregabalin and gabapentin in neuropathic pain. A systematic review. Br J Clin Pharmacol 2008;66:266-75
  • 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
  • Barden J, Edwards JE, McQuay HJ, et al. Relative efficacy of oral analgesics after third molar extraction. Br Dent J 2004;197:407-11
  • Moore RA, Straube S, Paine J, et al. Minimum efficacy criteria for comparisons between treatments using individual patient meta-analysis of acute pain trials: examples of etoricoxib, paracetamol, ibuprofen, and ibuprofen/paracetamol combinations after third molar extraction. Pain 2011;152:982-9
  • 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;37:531-41
  • Wells LK, 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;37:1608-12
  • 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;216:451-5
  • Bailey E, Worthington HV, 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
  • Moore PA, Hersh EV. 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
  • Derry CJ, Derry S, Moore RA. Single dose oral ibuprofen plus paracetamol (acetaminophen) for acute postoperative pain. Cochrane Database Syst Rev 2013;6:CD010210
  • Elia N, Lysakowski C, Tramer MR. 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;103:1296-304
  • Mason L, Edwards JE, Moore RA, McQuay HJ. Single-dose oral naproxen for acute postoperative pain: a quantitative systematic review. BMC Anesthesiol 2003;3:4
  • Bandolier – evidenced based health care. Available at: http://www.medicine.ox.ac.uk/bandolier/booth/painpag/Acutrev/Analgesics/AP028.html [Last accessed 1 October 2014]
  • Moore RA. Bandolier’s Little Book of Pain. New York: Oxford University Press, 2003
  • Moore RA, Derry S, Wiffen PJ, et al. Evidence for efficacy of acute treatment of episodic tension-type headache: methodological critique of randomised trials for oral treatments. Pain 2014;155:2220-8
  • Stephens G, Derry S, Moore RA. Paracetamol (acetaminophen) for acute treatment of episodic tension-type headache in adults. Cochrane Database Syst Rev 2016;6:CD011889
  • Schachtel BP, Furey SA, Thoden WR. Nonprescription ibuprofen and acetaminophen in the treatment of tension-type headache. J Clin Pharmacol 1996;36:1120-5
  • Packman B, Packman E, Doyle G, et al. Solubilized ibuprofen: evaluation of onset, relief and safety of a novel formulation in the treatment of episodic tension-type headache. Headache 2000;40:561-7
  • Derry S, Wiffen PJ, Moore RA, et al. Ibuprofen for acute treatment of episodic tension-type headache in adults. Cochrane Database Syst Rev 2015;31:CD011474
  • Rabbie R, Derry S, Moore RA. Ibuprofen with or without an antiemetic for acute migraine headaches in adults. Cochrane Database Syst Rev 2013;4:CD008039
  • Derry S, Moore RA. Paracetamol (acetaminophen) with or without an antiemetic for acute migraine headaches in adults. Cochrane Database Syst Rev 2013;4:CD008040
  • Termine C, Özge A, Antonaci F, et al. Overview of diagnosis and management of paediatric headache. Part II: therapeutic management. J Headache Pain 2011;12:25-34
  • Richer L, Billinghurst L, Linsdell MA, et al. Drugs for the acute treatment of migraine in children and adolescents. Cochrane Database Syst Rev 2016;4:CD005220
  • NICE Clinical Guidelines, CG150: Headaches: Diagnosis and Management of Headaches in Young People and Adults. National Clinical Guideline Centre (UK). London: Royal College of Physicians (UK) http://www.nice.org.uk/guidance/cg150 [Last accessed 20 July 2016]
  • Towheed TE, Maxwell L, Judd MG, et al. Acetaminophen for osteoarthritis. Cochrane Database Syst Rev 2006;1:CD004257
  • Verkleij SP, Luijsterburg PA, Bohnen AM, et al. NSAIDs versus acetaminophen in knee and hip osteoarthritis: a systematic review regarding heterogeneity influencing the outcomes. Osteoarthritis Cartilage 2011;19:921-9
  • Machado GC, Maher CG, Ferreira PH, et al. Efficacy and safety of paracetamol for spinal pain and osteoarthritis: systematic review and meta-analysis of randomized placebo controlled trials. BMJ 2015;350:h1225
  • Prior MJ, Harrison DD, Frustaci ME. A randomized, double-blind, placebo-controlled 12 week trial of acetaminophen extended release for the treatment of signs and symptoms of osteoarthritis. Curr Med Res Opin 2014;30:2377-87
  • Lee C, Straus WL, Balshaw R, et al. A comparison of the efficacy and safety of nonsteroidal antiinflammatory agents versus acetaminophen in the treatment of osteoarthritis: a meta-analysis. Arthritis Rheum 2004;51:746-54
  • Williams CM, Maher CG, Latimer J, et al. Efficacy of paracetamol for acute low-back pain: a double-blind, randomised controlled trial. Lancet 2014;384:1586-96
  • Rainsford KD, Roberts SC, Brown S. Ibuprofen and paracetamol: relative safety in non-prescription dosages. J Pharm Pharmacol 1997;49:345-76
  • Doherty M, Hawkey C, Goulder M, et al. A randomised controlled trial of ibuprofen, paracetamol or a combination tablet of ibuprofen/paracetamol in community-derived people with knee pain. Ann Rheum Dis 2011;70:1534-41
  • Baigent C; Coxib and traditional NSAID Trialists’ (CNT) Collaboration. Vascular and upper gastrointestinal effects of non-steroidal anti-inflammatory drugs: meta-analyses of individual participant data from randomised trials. Lancet 2013;382:769-79
  • Lee WM. Acute liver failure. Semin Respir Crit Care Med 2012;33:36-45
  • Claridge LC, Eksteen B, Smith A, et al. Acute liver failure after administration of paracetamol at the maximum recommended daily dose in adults. BMJ 2010;341:6764
  • Craig DG, Bates CM, Davidson JS, et al. Staggered overdose pattern and delay to hospital presentation are associated with adverse outcomes following paracetamol induced hepatotoxicity. Br J Clin Pharmacol 2012;73:285-94
  • Acetaminophen safety – deja vu. Med Lett Drugs Ther 2009;51:53-4
  • von Mach MA, Hermanns-Clausen M, Koch I, et al. Experiences of a poison center network with renal insufficiency in acetaminophen overdose: an analysis of 17 cases. Clin Toxicol (Phila) 2005;43:31-7
  • Rumack B, Heard K, Green J, et al. The effect of acetaminophen on serum alanine aminotransferase activity in subjects who consume ethanol: a systematic review and meta-analysis of published randomized, controlled trials. Pharmacotherapy 2012;32:784-91
  • Rumack BH. Acetaminophen misconceptions. Hepatology 2004;40:10-15
  • Hayward KL, Powell EE, Irvine KM, Martin JH. Can paracetamol (acetaminophen) be administered to patients with liver impairment? Br J Clin Pharmacol 2015;81:210-22
  • Gomez-Moreno G, Guardia J, Cutando A. Interaction of paracetamol in chronic alcoholic patients. Importance for odontologists. Med Oral Patol Oral Cir Bucal 2008;13:E235-8
  • Riordan SM, Williams R. Alcohol exposure and paracetamol-induced hepatotoxicity. Addict Biol 2002;7:191-206
  • Dart RC, Bailey E. Does therapeutic use of acetaminophen cause acute liver failure? Pharmacotherapy 2007;27:1219-30
  • Benson GD, Koff RS, Tolman KG. The therapeutic use of acetaminophen in patients with liver disease. Am J Ther 2005;12:133-41
  • Zimmerman HJ, Maddrey WC. Acetaminophen (paracetamol) hepatotoxicity with regular intake of alcohol: analysis of instances of therapeutic misadventure. Hepatology 1995;22:767-73
  • Riley T 3rd, Bhatti AM. Preventive strategies in chronic liver disease: part I. Alcohol, vaccines, toxic medications and supplements, diet and exercise. Am Fam Physician 2001;64:1555-60
  • Dwyer JP, Jayasekera C, Nicoll A. Analgesia for the cirrhotic patient: a literature review and recommendations. J Gastroenterol Hepatol 2014;29:1356-60
  • Prescott L. Effects of non-narcotic analgesics on the liver. Drugs 1986;32:129-47
  • Jones AL. Recent advances in the management of late paracetamol poisoning. Emerg Med 2000;12:14-21
  • O’connor N, Dargan PI, Jones AL. Hepatocellular damage from non-steroidal antiinflammatory drugs. QJM 2003;96:787-91
  • Graham GG, Davies MJ, Day RO, et al. The modern pharmacology of paracetamol: therapeutic actions, mechanism of action, metabolism, toxicity and recent pharmacological findings. Inflammopharmacology 2013;21:201-32
  • Benson GD. Acetaminophen in chronic liver disease. Clin Pharmacol Ther 1983;33:95-101
  • Khalid SK, Lane J, Navarro V, Garcia-Tsao G. Use of over-the-counter analgesics is not associated with acute decompensation in patients with cirrhosis. Clin Gastroenterol Hepatol 2009;7:994-9
  • Schilling A, Corey R, Leonard M, Eghtesad B. Acetaminophen: old drug, new warnings. Cleve Clin J Med 2010;77:19-27
  • Heard K, Green JL, Bailey JE, et al. A randomized trial to determine the change in alanine aminotransferase during 10 days of paracetamol (acetaminophen) administration in subjects who consume moderate amounts of alcohol. Aliment Pharmacol Ther 2007;26:283-90
  • Kuffner EK, Green JL, Bogdan GM et al. The effect of acetaminophen (four grams a day for three consecutive days) on hepatic tests in alcoholic patients – a multicenter randomized study. BMC Med 2007;5:13
  • Horsmans Y, Sempoux C, Detry R, Geubel AP. Paracetamol-induced liver toxicity after intravenous administration. Liver 1998;18:294-5
  • FDA. Liver injury related to the use of acetaminophen in both over-the-counter and prescription products. Advisory Committee Meeting (transcript). 2009. Available at: http://www.fda.gov/Drugs/DrugSafety/InformationbyDrugClass/ucm165107.htm [Last accessed 20 July 2016]
  • FDA. Prescription acetaminophen products to be limited to 325 mg per dosage unit; boxed warning will highlight potential for severe liver failure. Drug Saf Commun 2011. Available at: http://www.fda.gov/Drugs/DrugSafety/ucm239821.htm [Last accessed 27 July 2016]
  • Kheradpezhouh E, Ma L, Morphett A, et al. TRPM2 channels mediate acetaminophen-induced liver damage. Proc Natl Acad Sci USA 2014;111:3176-81
  • MHRA. Paracetamol overdose: new guidance on treatment with intravenous acetylcysteine. Drug Safety Update 2012;6:A1
  • Acetadote (acetylcysteine) package insert. Available at: http://www.accessdata.fda.gov/drugsatfda_docs/label/2013/021539s012lbl.pdf [Last accessed 27 September 2013]
  • British National Formulary Emergency treatment of poisoning. London: BMJ Group and Pharmaceutical Press. Available at: www.bnf.org [Last accessed 15 March 2013]
  • Ferner RE, Dear JW, Bateman DN. Management of paracetamol poisoning. BMJ 2011;342:968-72
  • Sawdy R, Slater D, Fisk N, et al. Use of a cyclo-oxygenase type-2-selective non-steroidal anti-inflammatory agent to prevent preterm delivery. Lancet 1997;350:265-6
  • Vane JR, Botting RM. Anti-inflammatory drugs and their mechanism of action. Inflamm Res 1998;47(Suppl 2):S78-S87
  • Bessone F. Non-steroidal anti-inflammatory drugs: what is the actual risk of liver damage? World J Gastroenterol 2010;16:5651-61
  • Davidson DG, Eastham WN. Acute liver necrosis following overdose of paracetamol. Br Med J 1966;2:497-9
  • Mitchell JR, Jollow DJ, Potter WZ, et al. Acetaminophen-induced hepatic necrosis. I. Role of drug metabolism. J Pharmacol Exp Ther 1973;187:185-94
  • Schapira D, Bassan L, Nahir AM, Scharf Y. Diclofenac-induced hepatotoxicity. Postgrad Med J 1986;62:63-5
  • Banks AT, Zimmerman HJ, Ishak KG, Harter JG. Diclofenac-associated hepatotoxicity: analysis of 180 cases reported to the Food and Drug Administration as adverse reactions. Hepatology 1995;22:820-7
  • Walker AM. Quantitative studies of the risk of serious hepatic injury in persons using nonsteroidal anti-inflammatory drugs. Arthritis Rheum 1997;40:201-8
  • Traversa G, Bianchi C, Da Cas R, et al. Cohort study of hepatotoxicity associated with nimesulide and other non-steroidal anti-inflammatory drugs. BMJ 2003;327:18-22
  • Castellsague J, Pisa F, Rosolen V, et al. Risk of upper gastrointestinal complications in a cohort of users of nimesulide and other nonsteroidal anti-inflammatory drugs in Friuli Venezia Giulia, Italy. Pharmacoepidemiol Drug Saf 2013;22:365-75
  • Castellsague J, Riera-Guardia N, Calingaert B, et al. Individual NSAIDs and upper gastrointestinal complications: a systematic review and meta-analysis of observational studies (the SOS project). Drug Saf 2012;35:1127-46
  • Gulmez SE, Larrey D, Pageaux GP, et al. Transplantation for acute liver failure in patients exposed to NSAIDs or paracetamol (acetaminophen): the multinational case–population SALT study. Drug Saf 2013;36:135-44
  • Kress HG, Baltov A, Basinski A, et al. Acute pain: a multifaceted challenge – the role of nimesulide. Curr Med Res Opin 2016;32:23-36
  • Rahme E, Barkun A, Nedjar H, et al. Hospitalizations for upper and lower GI events associated with traditional NSAIDs, and acetaminophen among the elderly in Quebec, Canada. Am J Gastroenterol 2008;103:872-82
  • CMDh. Updated advice on use of high-dose ibuprofen. European Medicines Agency EMA/325007/2015. Available at: http://www.ema.europa.eu/docs/en_GB/document_library/Press_release/2015/05/WC500187108.pdf [Last accessed 10 July 2016]
  • Chan AT, Manson JE, Albert CM, et al. Nonsteroidal antiinflammatory drugs, acetaminophen, and the risk of cardiovascular events. Circulation 2006;113:1578-87
  • Sudano I, Flammer AJ, Périat D, et al. Acetaminophen increases blood pressure in patients with coronary artery disease. Circulation 2010;122:1789-96
  • Hinz B, Cheremina O, Brune K. Acetaminophen (paracetamol) is a selective cyclooxygenase-2 inhibitor in man. FASEB J 2008;22:383-90
  • Antman EM, Bennett JS, Daugherty A, et al.; American Heart Association. Use of nonsteroidal antiinflammatory drugs: an update for clinicians: a scientific statement from the American Heart Association. Circulation 2007;115:1634-42
  • Curry RW Jr, Robinson JD, Sughrue MJ. Acute renal failure after acetaminophen ingestion. JAMA 1982;247:1012-14
  • Mazer M, Perrone J. Acetaminophen-induced nephrotoxicity: pathophysiology, clinical manifestation, and management. J Med Toxicol 2008;4:2-6
  • Werler MM, Mitchell A, Hernandez-Diaz S, Honein MA. Use of over-the-counter medications during pregnancy. Am J Obstet Gynecol 2005;193:771-7
  • Briggs GG, Freeman RK, Yaffe SJ. Drugs in Pregnancy and Lactation, 9th edn. Philadelphia, PA: Lippincott Williams and Wilkins, 2011
  • Tylenol professional product information. McNeil Consumer Healthcare, 2010
  • Thiele K, Kessler T, Arck P, et al. Acetaminophen and pregnancy: short- and long-term consequences for mother and child. J Reprod Immunol 2013;97:128-39
  • Liew Z, Ritz B, Rebordosa C, et al. Acetaminophen use during pregnancy, behavioral problems, and hyperkinetic disorders. JAMA Pediatr 2014;168:313-20
  • Brandlistuen RE, Ystrom E, Nulman I, et al. Prenatal paracetamol exposure and child neurodevelopment: a sibling-controlled cohort study. Int J Epidemiol 2013;42:1702-13
  • Sordillo JE, Scirica CV, Rifas-Shiman SH, et al. Prenatal and infant exposure to acetaminophen and ibuprofen and the risk for wheeze and asthma in children. J Allergy Clin Immunol 2015;135:441-8
  • Shaheen SO, Newson RB, Ring SM et al. Prenatal and infant acetaminophen exposure, antioxidant gene polymorphisms, and childhood asthma. J Allergy Clin Immunol 2010;126:1141-8
  • 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;41:482-9
  • Shaheen S, Newson R, Sherriff A, et al. Paracetamol use in pregnancy and wheezing in early childhood. Thorax 2002;57:958-63
  • Scialli AR, Ang R, Breitmeyer J, Royal MA. Childhood asthma and use during pregnancy of acetaminophen. A critical review. Reprod Toxicol 2010;30:508-19
  • 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;28:1890-8
  • Colborn T. Neurodevelopment and endocrine disruption. Environ Health Perspect 2004;112:944-9
  • Howdeshell KL. A model of the development of the brain as a construct of the thyroid system. Environ Health Perspect 2002;110:337-48
  • Rubinow DR, Schmidt PJ. Androgens, brain, and behavior. Am J Psychiatry 1996;153:974-84
  • Jensen MS, Rebordosa C, Thulstrup AM, et al. Maternal use of acetaminophen, ibuprofen, and acetylsalicylic acid during pregnancy and risk of cryptorchidism. Epidemiology 2010;21:779-85
  • Cheelo M, Lodge CJ, Dharmage SC, et al. Paracetamol exposure in pregnancy and early childhood and development of childhood asthma: a systematic review and meta-analysis. Arch Dis Child 2015;100:81-9
  • Heintze K, Petersen KU. The case of drug causation of childhood asthma: antibiotics and paracetamol. Eur J Clin Pharmacol 2013;69:1197-209
  • Pharmacovigilance Risk Assessment Committee (PRAC) of the European Medicines Agency (EMA). EMA/PRAC/324055/2014 [Last accessed 20 July 2016]
  • Cooper M, Langley K, Thapar A. Antenatal acetaminophen use and attention-deficit/hyperactivity disorder: an interesting observed association but too early to infer causality. JAMA Pediatr 2014;168:306-7
  • Health and Social Care Information Centre, Prescribing, Primary Care. Prescription Cost Analysis, England 2012. The Health and Social Care Information Centre, 2013
  • Cascarbi I. Pharmacogenetics of cytochrome P4502D6: genetic background and clinical implication. Eur J Clin Investig 2003;33(Suppl 2):17-22
  • Derry S, Moore RA, McQuay HJ. Single dose oral codeine, as a single agent, for acute postoperative pain in adults. Cochrane Database Syst Rev 2010;4:CD008099
  • Edwards JE, McQuay HJ, Moore RA. Combination analgesic efficacy: individual patient data meta-analysis of single-dose oral tramadol plus acetaminophen in acute postoperative pain. J Pain Symptom Manage 2002;23:121-30
  • Toms L, Derry S, Moore RA, McQuay HJ. Single dose oral paracetamol (acetaminophen) with codeine for postoperative pain in adults. Cochrane Database Syst Rev 2011;1:CD001547
  • Tzortzopoulou A, McNicol ED, Cepeda MS, et al. Single dose intravenous propacetamol or intravenous paracetamol for postoperative pain. Cochrane Database Syst Rev 2011;10:CD007
  • Axelsson B, Christensen S. Is there an additive analgesic effect of paracetamol at step 3? A double-blind randomized controlled study. Palliat Med 2003;17:724-5
  • Israel FJ, Parker G, Charles M, Reymond L. Lack of benefit from paracetamol (acetaminophen) for palliative cancer patients requiring high-dose strong opioids: a randomized, double-blind, placebo-controlled, crossover trial. J Pain Symptom Manage 2010;39:548-54
  • Formby FT. Re: Lack of benefit from paracetamol (acetaminophen) for palliative cancer patients. J Pain Symptom Manage 2010;40:e6, author reply e6-7
  • Stockler M, Vardy J, Pillai A, Warr D. Acetaminophen (paracetamol) improves pain and well-being in people with advanced cancer already receiving a strong opioid regimen: a randomized, double-blind, placebo-controlled cross-over trial. J Clin Oncol 2004;22:3389-94
  • Moore RA, Derry S, McQuay HJ, Wiffen PJ. Single dose oral analgesics for acute postoperative pain in adults. Cochrane Database Syst Rev 2011;9:CD008659
  • World Health Organization. WHO Cancer Pain Relief – a guide to opioid availability, 2nd edn. Geneva: WHO, 1996
  • Franceschi F, Iacomini P, Marsiliani D, et al. Safety and efficacy of the combination acetaminophen–codeine in the treatment of pain of different origin. Eur Rev Med Pharmacol Sci 2013;17:2129-35
  • Rodriguez RF, Castillo JM, Del Pilar Castillo M, et al. Codeine/acetaminophen and hydrocodone/acetaminophen combination tablets for the management of chronic cancer pain in adults: a 23-day, prospective, double-blind, randomized, parallel-group study. Clin Ther 2007;29:581-7
  • Tassinari D, Drudi F, Rosati M, et al. The second step of the analgesic ladder and oral tramadol in the treatment of mild to moderate cancer pain: a systematic review. Palliat Med 2011;25:410-23
  • Corsinovi L, Martinelli E, Fonte G, et al. Efficacy of oxycodone/acetaminophen and codeine/acetaminophen vs. conventional therapy in elderly women with persistent, moderate to severe osteoarthritis-related pain. Arch Gerontol Geriatr 2009;49:378-82
  • Colini Baldeschi G, Cobianchi MR. Study of codeine–paracetamol combination treatment compared with tramadol-paracetamol in the control of moderate-to-severe low back pain. Minerva Med 2012;103:177-82
  • Moore RA, Straube S, Aldington D. Pain measures and cut-offs – "no worse than mild pain" as a simple, universal outcome. Anaesthesia 2013;68:400-12
  • Lipton RB, Hamelsky SW, Dayno JM. What do patients with migraine want from acute migraine treatment? Headache 2002;42(Suppl 1):3-9
  • Kress HG, Ahlbeck K, Aldington D, et al. Managing chronic pain in elderly patients requires a CHANGE of approach. Curr Med Res Opin 2014;30:1153-64

Reprints and Corporate Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

To request a reprint or corporate permissions for this article, please click on the relevant link below:

Academic Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

Obtain permissions instantly via Rightslink by clicking on the button below:

If you are unable to obtain permissions via Rightslink, please complete and submit this Permissions form. For more information, please visit our Permissions help page.