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Medicines Q&As
What is the evidence to support the use of IV paracetamol for the
short-term treatment of moderate to severe pain in adults?
Prepared by UK Medicines Information (UKMi) pharmacists for NHS healthcare professionals
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Date prepared: 17/12/2016
Background
Intravenous (IV) paracetamol is licensed for the short-term treatment of moderate pain, especially
following surgery and for the short-term treatment of fever, when administration by intravenous route
is clinically justified by an urgent need to treat pain or hyperthermia and/or when other routes of
administration are not possible. Intravenous paracetamol is only indicated for short-term use;
manufacturers recommend the use of a suitable oral treatment as soon as this route is possible (1,2).
Intravenous paracetamol was first licensed in the UK in 2002 (1). Since that time it has become widely
used in clinical practice and incorporated into clinical guidelines including the NICE guideline
‘Fractures (non-complex): assessment and management’ (3). Prior to this, paracetamol for IV use was
only available (not licensed in the UK) in the form of propacetamol, a pro-drug of paracetamol (4). A
dose of 2g of propacetamol is hydrolysed to 1g of paracetamol within 7 minutes of administration (5).
A large amount of the efficacy data on IV paracetamol is derived from studies of IV propacetamol.
Answer
Key References
There are vast numbers of studies assessing the efficacy of IV paracetamol in various clinical
situations. Systematic reviews and meta-analyses are listed below, grouped according to clinical use.
Surgery
 Hyllested M, Jones S, Pedersen JL, et al. Comparative effect of paracetamol, NSAIDs or their
combination in postoperative pain management: a qualitative review. British Journal of
Anaesthesia. 2002; 88(2); 199-214.
 Montané E, Vallano A, Aguilera C, et al. Analgesics for pain after traumatic or orthopaedic
surgery: what is the evidence-a systematic review. European Journal of Clinical
Pharmacology. 2006; 62; 971-988.
 Macario A, Royal MA. A Literature Review of Randomized Clinical Trials of Intravenous
Acetaminophen (Paracetamol) for Acute Postoperative Pain. Pain Practice. 2011; 11(3); 290296.
 McNicol ED, Tzortzopoulou A, Cepeda MS, et al. Single-dose intravenous paracetamol or
propacetamol for prevention or treatment of postoperative pain: a systematic review and
meta-analysis. British Journal of Anaesthesia. 2011; 106(6); 764-775.
 Jones S, Merrill A. Effectiveness of intravenous acetaminophen for pain management in
orthopedic surgery patients: A systematic review. JBI Library of Systematic Reviews. 2012;
Vol 10; No 37.
 Apfel CC, Souza K, Portillo J, et al. Patient Satisfaction with Intravenous Acetaminophen: A
Pooled Analysis of Five Randomized, Placebo-Controlled Studies in the Acute Postoperative
Setting. Journal for Healthcare Quality. 2014; 00; 1-7.
 De Oliveira Jr GS, Castro-Alves LJ, McCarthy RJ. Single-dose Systemic Acetaminophen to
Prevent Postoperative Pain. A Meta-analysis of Randomized Controlled Trials. Clinical
Journal of Pain. 2015; 31(1); 86-93.
 Wang J, Liu GT, Mayo HG, et al. Pain Management for Elective Foot and Ankle Surgery: A
Systematic Review of Randomized Controlled Trials. The Journal of Foot & Ankle Surgery.
2015; 54; 625-635.
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Medicines Q&As

McNicol ED, Ferguson MC, Haroutounian S, et al. Single dose intravenous paracetamol or
intravenous propacetamol for postoperative pain (Review). Cochrane Database of Systematic
Reviews. 2016; Issue 5. Art.No.:CD007126. DOI: 10.1002/14651858.CD007126.pub3.
Surgery to Reduce the Adverse Effects of Opioids
 Remy C, Marret E, Bonnet F. Effects of acetaminophen on morphine side-effects and
consumption after major surgery: meta-analysis of randomized controlled trials. British
Journal of Anaesthesia 2005; 94(4); 505-513.
 McDaid C, Maund E, Rice S, et al. Paracetamol and selective and non-selective non-steroidal
anti-inflammatory drugs (NSAIDs) for the reduction of morphine-related side effects after
major surgery: a systematic review. Health Technology Assessment NIHR HTA programme.
2010; Vol 14: No17.
 Maund E, McDaid C, Rice S, et al. Paracetamol and selective and non-selective non-steroidal
anti-inflammatory drugs for the reduction in morphine-related side-effects after major surgery:
a systematic review. British Journal of Anaesthesia 2011; 106(3); 292-7.
 Apfel CC, Turan A, Souza K, et al. Intravenous acetaminophen reduces postoperative nausea
and vomiting: A systematic review and meta-analysis. Pain. 2013; 154; 677-689.
 Jebaraj B, Maitra S, Baidya DK et al. Intravenous Paracetamol Reduces Postoperative Opioid
Consumption after Orthopedic Surgery: A Systematic Review of Clinical Trials. Pain Research
and Treatment. 2013. Article ID 402510, 6 pages.
Migraine in the Emergency Setting
 Orr SL, Aubé M, Becker WJ, et al. Canadian Headache Society systematic review and
recommendations on the treatment of migraine pain in emergency settings. Cephalalgia.
2015; 35(3); 271-284.
 Orr SL, Friedman BW, Christie S, et al. Management of Adults With Acute Migraine in the
Emergency Department: The American Headache Society Evidence Assessment of
Parenteral Pharmacotherapies. Headache. 2016; 56; 911-940.
Acute Emergency Medicine
 National Institute for Health and Care Excellence. Sickle cell disease: managing acute painful
episodes in hospital. Clinical guideline CG143. Published date: June 2012.
 Falch C, Vicente D, Häberle H, et al. Treatment of acute abdominal pain in the emergency
room: A systematic review of the literature. European Journal of Pain. 2014; 18; 902-913.
 Dijkstra BM, Berben SAA, van Dongen RTM, et al. Review on pharmacological pain
management in trauma patients in (pre-hospital) emergency medicine in the Netherlands.
European Journal of Pain. 2014; 18; 3-19.
 Navaratnam R, Parker S. Systematic review: Intravenous paracetamol versus intravenous
morphine in the management of acute renal colic. RCEM Abstracts 006. Emergency Medicine
Journal. 2015; 32 (12); 978. Published as an abstract only.
 Sin B, Wai M, Tatunchak T, et al. The Use of Intravenous Acetaminophen for Acute Pain in
the Emergency Department. Academic Emergency Medicine. 2016; 23; 543-553.
 National Institute for Health and Care Excellence. Fractures (non-complex): assessment and
management. NICE guideline NG38. Published date: February 2016.
Systematic Reviews to Support Clinical Decision Making
 Yeh Y-C, Reddy P. Clinical and Economic Evidence for Intravenous Acetaminophen.
Pharmacotherapy 2012; 32(6); 559-579.
 Jibril F, Sharaby S, Mohamed A, et al. Intravenous versus Oral Acetaminophen for Pain:
Systematic Review of Current Evidence to Support Clinical Decision-Making. Canadian
Journal of Hospital Pharmacy. 2015; 68(3); 238-47.
Safety Concerns and Risk Minimisation
 MHRA Drug Safety Update. July 2010. Intravenous paracetamol (Perfalgan ▼): risk of
accidental overdose (6).
 This article highlights the safety concerns surrounding accidental overdose of adult
patients with low body weight (<50kg) who require a reduced dosage (1,2).
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Medicines Q&As
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Adults with hepatocellular insufficiency, chronic alcoholism, chronic malnutrition (low reserves
of hepatic glutathione) and dehydration must have a reduced maximum daily dose (MDD). In
these patients the MDD must not exceed 3g (1,2).
Patients with severe renal impairment (CrCl≤30mL/min) should have an increased interval
between subsequent administrations of intravenous paracetamol. In these patients there
should be a minimum dosing interval of 6hours (1,2).
Take care to avoid dosing errors due to confusion between milligram (mg) and millilitre (mL),
which could result in accidental overdose and death (1,2).
Educational Risk Minimisation Materials are available to help reduce the risk associated with
using this medicine (1,2).
Summary

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There is a large volume of data to support the use of intravenous paracetamol for the shortterm treatment of moderate to severe pain in adults. IV paracetamol has become widely used
in clinical practice and incorporated into clinical guidelines including some NICE guidelines.
There are a number of systematic reviews, which are detailed above, that are available on the
following subjects:
 Surgery
 Surgery to reduce the adverse effects of opioids
 Migraine in the emergency setting
 Acute emergency medicine
IV paracetamol is only indicated for short-term use; manufacturers recommend the use of a
suitable oral treatment as soon as this route is possible.
Users should be aware of the risks of medication errors and accidental overdose associated
with the use of paracetamol in its IV form.
Limitations
Due to the magnitude of data available for IV paracetamol in various clinical situations this Q&A
directs the reader to only the evidence available in the form of meta-analyses or systematic reviews.
The analysis of these reviews and the inclusion of individual clinical trials or case reports is outside of
the scope of this document. Therefore this document will not provide complete coverage of the
efficacy data for IV paracetamol in every clinical condition for which it is used. This Q&A does not
include evidence for the use of IV paracetamol in children, or when used for the management of fever.
References
(1) Bristol-Myers Squibb Pharmaceutical Limited. Summary of Product Characteristics. Perfalgan
10mg/ml solution for infusion. Last Updated on eMC 05-Apr-2017 Accessed via
www.emc.medicines.org.uk on 06/04/17.
(2) Actavis UK Ltd. Summary of Product Characteristics. Paracetamol 10mg/ml Solution for Infusion.
Last updated on eMC 18-Dec-2015. Accessed via: www.emc.medicines.org.uk on 17/01/2017.
(3) National Institute for Health and Care Excellence. Nice Guideline 38. Fractures (non-complex):
assessment and management. Published 17 February 2016. Accessed online via
www.nice.org.uk/guidance/ng38 on 20/05/16.
(4) Brayfield A (ed). Martindale: The Complete Drug Reference [online]. London:
Pharmaceutical Press. Accessed online via www.medicinescomplete.com on 20/05/16.
(5) McNicol ED, Ferguson MC, Haroutounian S et al. Single dose intravenous paracetamol or
intravenous propacetamol for postoperative pain (Review). Cochrane Database of Systematic
Reviews 2016, Issue 5. Art. No.: CD007126. DOI: 10.1002/14651858.CD007126.pub3. Accessed via
http://onlinelibrary.wiley.com/doi/10.1002/14651858.CD007126.pub3/full on 07/02/17.
(6) MHRA Drug Safety Update. July 2010. Intravenous paracetamol (Perfalgan ▼): risk of accidental
overdose. Accessed online via: https://www.gov.uk/drug-safety-update/intravenous-paracetamolperfalgan-risk-of-accidental-overdose on 07/02/17.
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Medicines Q&As
Quality Assurance
Prepared by
Michèle Skipp, South West Medicines Information & Training, Bristol.
Date Prepared
17/12/2016
Checked by
Julia Kuczynska, South West Medicines Information & Training, Bristol
Date of check
06/04/2017Search strategy
1. Embase via HDAS (PARACETAMOL/iv,pa OR (*PARACETAMOL/ AND ("INTRAVENOUS INFUSION"/ OR
"INTRAVENOUS DRUG ADMINISTRATION"/)) OR (*PAIN/ AND (PARACETAMOL/iv,pa OR (*PARACETAMOL/
AND ("INTRAVENOUS INFUSION"/ OR "INTRAVENOUS DRUG ADMINISTRATION"/))))) [English language]
[Human age groups Adult 18 to 64 years OR Aged 65+ years] [Humans] [Evidence based medicine Meta Analysis
OR Systematic Review]"
2. Medline via PubMed ((("infusions, intravenous"[MeSH Terms] OR "injections, intravenous"[MeSH Terms]) OR
"injections"[MeSH Terms]) OR "injections, intravenous"[MeSH Terms]) AND "acetaminophen"[MeSH Terms] AND
((Meta-Analysis[ptyp] OR Review[ptyp] OR systematic[sb]) AND "humans"[MeSH Terms] AND ("adult"[MeSH Terms]
OR "adult"[MeSH Terms:noexp] OR "aged"[MeSH Terms]))
3.
4.
5.
6.
In-house database/ resources
Bristol Myers Squibb Pharmaceuticals Limited. Email. 24/02/16.
Internet Search (Google; intravenous paracetamol systematic review)
Cochrane Library
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