Paracetamol

  Issues for Surgery

Loss of pain control if omitted.

Inadvertent paracetamol overdose if continued due to risk of multiple paracetamol-containing medicines being administered.

Risk of fatality if weight, renal impairment, and risk of hepatotoxicity are not considered when prescribing intravenous (IV), and potentially oral, paracetamol (see Further Information).

Difficulties with post-operative weaning / deprescribing of opioids if combination analgesic preparations containing paracetamol and an opioid are used.

  Advice in the Perioperative period

Elective and Emergency Surgery
Continue if taken regularly and needed prior to surgery (including combination products).

Combination products: -

• Co-codamol – contains paracetamol + codeine (see also Opioids monograph)
• Co-dydramol – contains paracetamol + dihydrocodeine (see also Opioids monograph)
• Tramacet® – contains paracetamol + tramadol (see also Opioids monograph)
• Paracetamol + isometheptene
• Migraleve® – contains paracetamol + codeine + / - buclizine (see also Opioids monograph)

Consider checking liver function tests (LFTs) if patient has risk factors for hepatotoxicity (see Further Information).

Consideration should be given to prescribing the components of combination products as separate medicines perioperatively, to facilitate review of their appropriateness and encourage deprescribing (see Opioids monograph).

If dose(s) taken on day of surgery, ensure theatre staff are aware of timing of last dose to avoid inadvertent overdosing.

Intraoperative Considerations
Before administering IV paracetamol: -

• check if a dose has already been taken in last 6 hours
• check weight and adjust dose if less than 50kg (see Further Information).

Combination analgesics such as tablets containing paracetamol with an opioid (e.g. co-codamol) should be avoided post-operatively as the fixed doses do not allow for titration to patient need, or the flexibility required for weaning (see Opioids monograph).

  Interaction(s) with Common Anaesthetic Agents

 
None^{1, 2, 3}; however, care should be taken to avoid inadvertent overdose of paracetamol if patient has already received a dose of paracetamol-containing medication in the previous six hours.

  Interaction(s) with other Common Medicines used in the Perioperative Period

 
Antimicrobials
Concomitant use of paracetamol with clavulanic acid (found in co-amoxiclav), doxycycline, flucloxacillin or tigecycline can increase the risk of hepatotoxicity¹; whilst single surgical prophylactic doses should not pose a problem, bear this interaction in mind if a patient develops signs of hepatotoxicity with continued post-operative treatment.

Antiemetics
The prokinetic action of metoclopramide and domperidone may increase the rate of paracetamol absorption², particularly in those with delayed gastric emptying, however the total amount absorbed is unchanged and therefore unlikely to be clinically significant³. Concurrent use need not be avoided².

Analgesia
When prescribing analgesia care should be taken to avoid duplication of paracetamol-containing medicines, which could lead to unintentional overdose. This risk can be reduced by prescribing individual components, rather than combination products.

  Further Information

Safe Prescribing and Administration of IV Paracetamol
There is a risk of overdose, hepatotoxicity, and fatality if IV paracetamol is dosed incorrectly. Dose adjustment is required in the following circumstances^{1, 4}: -

• patients weighing less than 50kg require both a reduced dose and reduced cumulative dose in 24 hours
• patients with renal impairment (e.g. creatinine clearance <30ml/min) require an extended minimum dosing interval
• patients with risk factors for hepatotoxicity (e.g. hepatocellular insufficiency, chronic alcoholism, chronic malnutrition, dehydration) require a reduced cumulative dose in 24 hours

Consult product literature and / or British National Formulary for dosing advice.

Reducing Oral Paracetamol Doses in Adults (for IV route see above)
Unlike IV paracetamol, the evidence for oral paracetamol dose reduction is limited. Low body weight appears not to be directly correlated with an increased risk of oral paracetamol toxicity. However, it is an indicator that the patient may have other conditions (e.g. chronic malnutrition, anorexia or high alcohol consumption), which require a reduction in oral paracetamol cumulative dose⁵.

There are case reports of malnourished patients, frail elderly patients, and patients with a history of liver disease developing acute liver failure following administration of oral paracetamol at dose of 4g daily. A reduction of the cumulative dose of oral paracetamol to 3g in 24 hours should be considered for malnourished patients or patients with Child Pugh C cirrhosis, irrespective of weight⁵.

In addition, a reduction in clearance of paracetamol has been associated with increased age and frailty^{1, 5}. If a patient has a low body weight, increased age and / or frailty the risks and benefits of oral paracetamol, including the risks of hepatotoxicity and the potential risks of alternative treatments (e.g. Non-Steroidal Anti-inflammatory Drugs [NSAIDs], opioids), should be considered.

If a reduced oral paracetamol dose is prescribed, pain control should be monitored, and alternative management strategies offered if needed⁵. Patients should also be advised of the rationale for the lower dose as this will differ from the dosing advice on over-the counter paracetamol-containing products.

  References

1. Joint Formulary Committee. British National Formulary (online) London: BMJ Group and Pharmaceutical Press http://www.medicinescomplete.com [Accessed on 13^th March 2022]
2. Summary of Product Characteristics – Paracetamol tablets 500mg. Accord Healthcare Limited. Accessed via www.medicines.org.uk 13/03/2022 [date of revision of the text December 2020]
3. Baxter K, Preston CL (eds), Stockley’s Drug Interactions (online) London: Pharmaceutical Press. http://www.medicinescomplete.com [Accessed on 16^th September 2021]
4. Summary of Product Characteristics – Paracetamol 10mg/ml Solution for Infusion. Accord-UK Ltd. Accessed via www.medicines.org.uk 29/09/2021 [date of revision of the text December 2020]
5. NHS Leeds Teaching Hospitals NHS Foundation Trust (2020) Reducing oral paracetamol doses in adults. Leeds Teaching Hospitals NHS Foundation Trust. http://www.leedsformulary.nhs.uk [Accessed on 13^th March 2022]