Skip to main content
SpringerLink
Log in

Intravenous Paracetamol (Acetaminophen)

  • Adis Drug Profile
  • Published:
Drugs Aims and scope Submit manuscript

Abstract

  • ▴ Intravenous paracetamol (rINN)/intravenous acetaminophen (USAN) is an analgesic and antipyretic agent, recommended worldwide as a first-line agent for the treatment of pain and fever in adults and children.

  • ▴ In double-blind clinical trials, single or multiple doses of intravenous paracetamol 1 g generally provided significantly better analgesic efficacy than placebo treatment (as determined by primary efficacy endpoints) in adult patients who had undergone dental, orthopaedic or gynaecological surgery.

  • ▴ Furthermore, where evaluated, intravenous paracetamol 1 g generally showed similar analgesic efficacy to a bioequivalent dose of propacetamol, and a reduced need for opioid rescue medication.

  • ▴ In paediatric surgical patients, recommended doses of intravenous paracetamol 15 mg/kg were not significantly different from propacetamol 30 mg/kg for the treatment of pain, and showed equivocal analgesic efficacy compared with intramuscular pethidine 1 mg/kg in several randomized, active comparator-controlled studies.

  • ▴ In a randomized, noninferiority study in paediatric patients with an infection-induced fever, intravenous paracetamol 15 mg/kg treatment was shown to be no less effective than propacetamol 30 mg/kg in terms of antipyretic efficacy.

  • ▴ Intravenous paracetamol was well tolerated in clinical trials, having a tolerability profile similar to placebo. Additionally, adverse reactions emerging from the use of the intravenous formulation of paracetamol are extremely rare (<1/10000).

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Table I
Table II

Similar content being viewed by others

References

  1. Walder B, Schafer M, Henzi I, et al. Efficacy and safety of patient-controlled opioid analgesia for acute postoperative pain. Acta Anaesthesiol Scand 2001; 45(7): 795–804

    PubMed  CAS  Google Scholar 

  2. Sinatra RS, Jahr JS, Reynolds LW, et al. Efficacy and safety of single and repeated administration of 1 gram intravenous acetaminophen injection (paracetamol) for pain management after major orthopedic surgery. Anesthesiology 2005 Apr; 102(4): 822–31

    PubMed  CAS  Google Scholar 

  3. Haas D. An update on analgesics for the management of acute postoperative dental pain. J Can Dent Assoc 2002; 68(8): 476–82

    PubMed  Google Scholar 

  4. Malaise O, Bruyere O, Reginster JY. Intravenous paracetamol: a review of efficacy and safety in therapeutic use. Future Neurol 2007; 2(6): 673–88

    CAS  Google Scholar 

  5. Kehlet H, Werner MU. Role of paracetamol in acute pain management. Drugs 2003; 63 (Spec. Iss. 2): 15–22

    PubMed  CAS  Google Scholar 

  6. Graham GG, Scott KF, Day RO. Tolerability of paracetamol. Drugs 2003; 63 (Spec. Iss. 2): 43–6

    PubMed  Google Scholar 

  7. Allegaert K, Rayyan M, De Rijdt T, et al. Hepatic tolerance of repeated intravenous paracetamol administration in neonates. Paediatr Anaesth 2008 May; 18(5): 388–92

    PubMed  Google Scholar 

  8. Holmer Pettersson P, Jakobsson J, Owall A. Plasma concentrations following repeated rectal or intravenous administration of paracetamol after heart surgery. Acta Anaesthesiol Scand 2006 Jul; 50(6): 673–7

    PubMed  CAS  Google Scholar 

  9. Arana A, Morton NS, Hansen TG. Treatment with paracetamol in infants. Acta Anaesthesiol Scand 2001 Jan; 45(1): 20–9

    PubMed  CAS  Google Scholar 

  10. Electronic Medicines Compendium. Ketorolac 30mg/ml solution for injection (Beacon pharmaceuticals): summary of product characteristics [online]. Available from URL: http://emc.medicines.org.uk/emc/assets/c/html/DisplayDoc.asp?DocumentID=20922 [Accessed 2008 Dec 12]

  11. Murat I, Baujard C, Foussat C, et al. Tolerance and analgesic efficacy of a new i.v. paracetamol solution in children after inguinal hernia repair. Paediatr Anaesth 2005; 15(8): 663–70

    PubMed  CAS  Google Scholar 

  12. Bjorkman R, Hallman KM, Hedner J, et al. Acetaminophen blocks spinal hyperalgesia induced by NMDA and substance P. Pain 1994 Jun; 57(3): 259–64

    PubMed  CAS  Google Scholar 

  13. Muth-Selbach US, Tegeder I, Brune K, et al. Acetaminophen inhibits spinal prostaglandin E2 release after peripheral noxious stimulation. Anesthesiology 1999 Jul; 91(1): 231–9

    PubMed  CAS  Google Scholar 

  14. Pickering G, Loriot MA, Libert F, et al. Analgesic effect of acetaminophen in humans: first evidence of a central serotonergic mechanism. Clin Pharmacol Ther 2006 Apr; 79(4): 371–8

    PubMed  CAS  Google Scholar 

  15. Aronoff DM, Oates JA, Boutaud O. New insights into the mechanism of action of acetaminophen: its clinical pharmacologic characteristics reflect its inhibition of the two prostaglandin H2 synthases. Clin Pharmacol Ther 2006 Jan; 79(1): 9–19

    PubMed  CAS  Google Scholar 

  16. Graham GG, Scott KF. Mechanism of action of paracetamol. Am J Ther 2005; 12(1): 46–55

    PubMed  Google Scholar 

  17. Electronic Medicines Compendium. Perfalgan 10mg/ml solution for infusion: summary of product characteristics [online]. Available from URL: http://emc.medicines.org.uk/emc/assets/c/html/DisplayDoc.asp?DocumentID=14288 [Accessed 2008 Aug 19]

  18. Bonnefont J, Courade JP, Alloui A, et al. Mechanism of the antinociceptive effect of paracetamol. Drugs 2003; 63 (Spec. Iss. 2): 1–4

    PubMed  Google Scholar 

  19. Bonnefont J, Daulhac L, Etienne M, et al. Acetaminophen recruits spinal p42/p44 MAPKs and GH/IGF-1 receptors to produce analgesia via the serotonergic system. Mol Pharmacol 2007 Feb; 71(2): 407–15

    PubMed  CAS  Google Scholar 

  20. Kumpulainen E, Kokki H, Halonen T, et al. Paracetamol (acetaminophen) penetrates readily into the cerebrospinal fluid of children after intravenous administration. Pediatrics 2007 Apr; 119(4): 766–71

    PubMed  Google Scholar 

  21. Viscusi E, Royal M, Leclerc A, et al. Pharmacokinetics, efficacy and safety of IV acetaminophen in the treatment of pain following total hip arthroplasty: results of a double-blind, randomized, placebo-controlled, single-dose study [abstract no. 215 plus poster]. 24th Annual Meeting of the American Academy of Pain Medicine; 2008 Feb 12–16; Orlando (FL)

  22. Gelotte CK, Auiler JF, Lynch JM, et al. Disposition of acetaminophen at 4, 6, and 8 g/day for 3 days in healthy young adults. Clin Pharmacol Ther 2007 Jun; 81(6): 840–8

    PubMed  CAS  Google Scholar 

  23. Gregoire N, Hovsepian L, Gualano V, et al. Safety and pharmacokinetics of paracetamol following intravenous administration of 5 g during the first 24 h with a 2-g starting dose. Clin Pharmacol Ther 2007 Mar; 81(3): 401–5

    PubMed  CAS  Google Scholar 

  24. Schutz RA, Fong L, Chang Y, et al. Open-label, 4-period, randomized crossover study to determine the comparative pharmacokinetics of oral and intravenous acetaminophen administration in healthy male volunteers [poster only]. 32nd Annual Regional Anesthesia Meeting; 2007 Apr 19–22; Vancouver (BC)

  25. Flouvat B, Leneveu A, Fitoussi S, et al. Bioequivalence study comparing a new paracetamol solution for injection and propacetamol after single intravenous infusion in healthy subjects. Int J Clin Pharmacol Ther 2004 Jan; 42(1): 50–7

    PubMed  CAS  Google Scholar 

  26. Bannwarth B, Netter P, Lapicque F, et al. Plasma and cerebrospinal fluid concentrations of paracetamol after a single intravenous dose of propacetamol. Br J Clin Pharmacol 1992; 34(1): 79–81

    PubMed  PubMed Central  CAS  Google Scholar 

  27. Clements JA, Critchley JA, Prescott LF. The role of sulphate conjugation in the metabolism and disposition of oral and intravenous paracetamol in man. Br J Clin Pharmacol 1984; 18(4): 481–5

    PubMed  PubMed Central  CAS  Google Scholar 

  28. Manyike PT, Kharasch ED, Kalhorn TF, et al. Contribution of CYP2E1 and CYP3A to acetaminophen reactive metabolite formation. Clin Pharmacol Ther 2000; 67(3): 275–82

    PubMed  CAS  Google Scholar 

  29. Koch-Weser J. Medical intelligence: drug therapy. N Engl J Med 1976; 295(23): 1297–300

    PubMed  CAS  Google Scholar 

  30. Jayasinghe KSA, Roberts CJC, Read AE. Is biliary excretion of paracetamol significant in man? Br J Clin Pharmacol 1986; 22(3): 363–6

    PubMed  PubMed Central  CAS  Google Scholar 

  31. Abernethy DR, Greenblatt DJ, Ameer B, et al. Probenecid impairment of acetaminophen and lorazepam clearance: direct inhibition of ether glucuronide formation. J Pharmacol Exp Ther 1985; 234(2): 345–9

    PubMed  CAS  Google Scholar 

  32. Levy G, Khanna NN, Soda DM, et al. Pharmacokinetics of acetaminophen in the human neonate: formation of acetaminophen glucuronide and sulfate in relation to plasma bilirubin concentration and D-glucaric acid excretion. Pediatrics 1975 Jun; 55(6): 818–25

    PubMed  CAS  Google Scholar 

  33. Wurthwein G, Koling S, Reich A, et al. Pharmacokinetics of intravenous paracetamol in children and adolescents under major surgery. Eur J Clin Pharmacol 2005 Feb; 60(12): 883–8

    PubMed  Google Scholar 

  34. van Lingen RA, Deinum JT, Quak JM, et al. Pharmacokinetics and metabolism of rectally administered paracetamol in preterm neonates. Arch Dis Child Fetal Neonatal Ed 1999 Jan; 80(1): F59–63

    PubMed  PubMed Central  Google Scholar 

  35. van der Marel CD, Anderson BJ, van Lingen RA, et al. Paracetamol and metabolite pharmacokinetics in infants. Eur J Clin Pharmacol 2003 Jul; 59(3): 243–51

    PubMed  Google Scholar 

  36. Palmer GM, Atkins M, Anderson BJ, et al. I.V. acetaminophen pharmacokinetics in neonates after multiple doses. Br J Anaesth 2008 Oct; 101(4): 523–30

    PubMed  CAS  Google Scholar 

  37. Pineiro-Carrero VM, Pineiro EO. Liver. Pediatrics 2004 Apr; 113 (4 Suppl): 1097–106

    PubMed  Google Scholar 

  38. Candiotti K, Singla N, Wininger S, et al. A randomized, double-blind, placebo-controlled, multi-center, parallel-group, multiple-dose study of the efficacy and safety of intravenous acetaminophen over 48 hours for the treatment of postoperative pain after gynecologic surgery [abstract no. A-13 plus poster]. 33rd Annual Regional Anesthesia Meeting; 2008 May 1–4; Cancun

  39. Juhl GI, Norholt SE, Tonnesen E, et al. Analgesic efficacy and safety of intravenous paracetamol (acetaminophen) administered as a 2 g starting dose following third molar surgery. Eur J Pain 2006 May; 10(4): 371–7

    PubMed  CAS  Google Scholar 

  40. Moller PL, Juhl GI, Payen-Champenois C, et al. Intravenous acetaminophen (paracetamol): comparable analgesic efficacy, but better local safety than its prodrug, propacetamol, for postoperative pain after third molar surgery. Anesth Analg 2005 Jul; 101(1): 90–6

    PubMed  CAS  Google Scholar 

  41. Atef A, Fawaz AA. Intravenous paracetamol is highly effective in pain treatment after tonsillectomy in adults. Eur Arch Otorhinolaryngol 2008 Mar; 265(3): 351–5

    PubMed  Google Scholar 

  42. Kemppainen T, Kokki H, Tuomilehto H, et al. Acetaminophen is highly effective in pain treatment after endoscopic sinus surgery. Laryngoscope 2006; 116(12): 2125–8

    PubMed  CAS  Google Scholar 

  43. Gimbel J, Royal M, Leclerc A, et al. Efficacy and safety of IV acetaminophen in the treatment of pain following primary total hip arthroplasty: results of a double-blind, randomized, placebo-controlled, multiple-dose, 24 hour study [poster only]. 24th Annual Meeting of the American Academy of Pain Medicine; 2008 Feb 12–16; Orlando (FL)

  44. Minkowitz H, Royal M, Leclerc A, et al. Efficacy and safety of IV acetaminophen in the treatment of pain following vaginal hysterectomy: results of a double-blind, randomized, placebo-controlled, multiple-dose, 24hour study [poster only]. 24th Annual Meeting of the American Academy of Pain Medicine; 2008 Feb 12–16; Orlando (FL)

  45. Marty J, Benhamou D, Chassard D, et al. Effects of single-dose injectable paracetamol versus propacetamol in pain management after minor gynecologic surgery: a multicenter, randomized, double-blind, active-controlled, two-parallel-group study. Curr Ther Res Clin Exp 2005 Jul; 66(4): 294–306

    PubMed  PubMed Central  CAS  Google Scholar 

  46. Grundmann U, Wornle C, Biedler A, et al. The efficacy of the non-opioid analgesics parecoxib, paracetamol and metamizol for postoperative pain relief after lumbar microdiscectomy. Anesth Analg 2006 Jul; 103(1): 217–22

    PubMed  CAS  Google Scholar 

  47. Alhashemi JA, Alotaibi QA, Mashaat MS, et al. Intravenous acetaminophen vs oral ibuprofen in combination with morphine PCIA after Cesarean delivery. Can J Anaesth 2006 Dec; 53(12): 1200–6

    PubMed  Google Scholar 

  48. Khan ZU, Iqbal J, Saleh H, et al. Intravenous paracetamol is as effective as morphine in knee arthroscopic day surgery procedures. Pakistan J Med Sciences 2007; 23(6): 851–3

    Google Scholar 

  49. Arellano F, Sacristan JA. Metamizole: reassessment of its therapeutic role. Eur J Clin Pharmacol 1990; 38(6): 617–9

    PubMed  CAS  Google Scholar 

  50. Cattabriga I, Pacini D, Lamazza G, et al. Intravenous paracetamol as adjunctive treatment for postoperative pain after cardiac surgery: a double blind randomized controlled trial. Eur J Cardiothorac Surg 2007 Sep; 32(3): 527–31

    PubMed  Google Scholar 

  51. Canbay O, Celebi N, Arun O, et al. Efficacy of intravenous acetaminophen and lidocaine on propofol injection pain. Br J Anaesth 2008 Jan; 100(1): 95–8

    PubMed  CAS  Google Scholar 

  52. El-Radaideh KM. Effect of pretreatment with lidocaine, intravenous paracetamol and lidocaine-fentanyl on propofol injection pain: comparative study. Rev Bras Anestesiol 2007; 57(1): 32–8

    PubMed  CAS  Google Scholar 

  53. Alhashemi JA, Daghistani MF. Effects of intraoperative i.v. acetaminophen vs i.m. meperidine on post-tonsillectomy pain in children. Br J Anaesth 2006 Jun; 96(6): 790–5

    PubMed  CAS  Google Scholar 

  54. Alhashemi JA, Daghistani MF. Effect of intraoperative intravenous acetaminophen vs. intramuscular meperidine on pain and discharge time after paediatric dental restoration. Eur J Anaesthesiol 2007 Feb; 24(2): 128–33

    PubMed  CAS  Google Scholar 

  55. Capici F, Ingelmo PM, Davidson A, et al. Randomized controlled trial of duration of analgesia following intravenous or rectal acetaminophen after adenotonsillectomy in children. Br J Anaesth 2008 Feb; 100(2): 251–5

    PubMed  CAS  Google Scholar 

  56. Duhamel JF, Le Gall E, Dalphin ML, et al. Antipyretic efficacy and safety of a single intravenous administration of 15mg/kg paracetamol versus 30mg/kg propacetamol in children with acute fever due to infection. Int J Clin Pharmacol Ther 2007 Apr; 45(4): 221–9

    PubMed  CAS  Google Scholar 

  57. Singla N, Viscusi E, Candiotti K, et al. A review of the intravenous acetaminophen placebo-controlled clinical trial safety experience: a focus on hepatic transsaminases [poster only]. 33rd Annual Regional Anesthesia Meeting; 2008 May 1–4; Cancun

  58. Cadence Pharmaceuticals Inc. Cadence pharmaceuticals announces FDA concurrence with clinical development plan for acetavance™ [online]. Available from URL: http://cadx.client.shareholder.com/releases.cfm [Accessed 2008 Sep 1]

  59. Electronic medicines compendium. Perfalgan 10mg/ml solution for infusion, 50 ml vial: patient information leaflet [online]. Available from URL: http://xpil.medicines.org.uk/ViewPil.aspx?DocID=19321 [Accessed 2008 Aug 19]

Download references

Acknowledgements

The manuscript was reviewed by: B. Bannwarth, Department of Rheumatology, Victor Segalen University, Bordeaux, France; G.G. Graham, Faculty of Medicine, University of New South Wales, Sydney, New South Wales, Australia.

The preparation of this review was not supported by any external funding. During the peer review process, the manufacturer of the agent under review was offered an opportunity to comment on this article. Changes resulting from comments received were made on the basis of scientific and editorial merit.

Author information

Authors and Affiliations

  1. Wolters Kluwer Health ¦ Adis, 41 Centorian Drive, Private Bag 65901, Mairangi Bay, North Shore 0754, Auckland, New Zealand

    Sean T. Duggan

  2. Wolters Kluwer Health, Conshohocken, Pennsylvania, USA

    Sean T. Duggan

Authors
  1. Sean T. Duggan
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Lesley J. Scott
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Sean T. Duggan.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Duggan, S.T., Scott, L.J. Intravenous Paracetamol (Acetaminophen). Drugs 69, 101–113 (2009). https://doi.org/10.2165/00003495-200969010-00007

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.2165/00003495-200969010-00007

Keywords

Search

Navigation