Table 1.

Selected Clinical Studies Using Paracetamol Plus Opioids for Acute Post-Operative Pain

Study, Year	Type of Surgery	Design	N	Treatment Groups, Doses (mg)	Doses/Timing	Outcome
Fricke et al, 2002130	Oral surgery	Double-blind RCT	200	Tramadol/Paracetamol 37.5 mg/325 mg Tramadol/ Paracetamol 75 mg/650 mg Hydrocodone/Paracetamol 10 mg/650 mg Placebo	Single dose, postoperative	Comparable analgesia, but better tolerability for tramadol/Paracetamol than hydrocodone/ Paracetamol
MacLeod et al, 2002131	Dental	Double-blind RCT	82	Codeine/Paracetamol 30 mg/1000 mg Paracetamol 1000 mg	3 doses over 8 hours	Better analgesia with combination, with a similar rate of adverse events
Smith et al, 2004132	Orthopedic and abdominal surgery	Double-blind RCT	305	Tramadol/Paracetamol 75 mg/650 mg Codeine/Paracetamol 60 mg/600 mg Placebo	1 to 2 tablets every 4 to 6 hours as needed for pain for 6 days.	Both active combinations provided significantly greater pain relief than placebo; scores were similar for tramadol/ Paracetamol and codeine/paracetamol.
Daniels et al, 2011122	Dental	Double-blind RCT	678	Ibuprofen/Paracetamol 400 mg/1000 mg Ibuprofen/Paracetamol 200 mg/500 mg Ibuprofen/Codeine 400 mg/25.6 mg Codeine/ Paracetamol 30 mg/1000 mg Placebo	Single dose, postoperative	Ibuprofen/Paracetamol groups were superior in pain reduction to ibuprofen/codeine; ibuprofen/Paracetamol, and noninferior to ibuprofen/codeine
Rawal et al 2011133	Ambulatory hand surgery	Double-blind RCT	462	Tramadol/Paracetamol 37.5 mg/325 mg Tramadol 50 mg	Before and immediately after surgery and every 6 hours thereafter	Comparable analgesic efficacy, fewer adverse events with tramadol/paracetamol, and reduced tramadol consumption by 24%
Sniezek et al, 2011123	Mohs surgery and cutaneous reconstruction	Double-blind RCT	210	Paracetamol 1000 mg Ibuprofen/Paracetamol 400 mg/1000 mg Codeine/Paracetamol 30 mg/ 325 mg	Immediately after surgery and every 4 hours for up to 4 doses	Ibuprofen/paracetamol is superior to other 2 treatments in pain control; Higher rate of AEs under codeine/Paracetamol compared with ibuprofen/Paracetamol and Paracetamol alone
Aweke et al, 2020134	Abdominal surgery	Single blind RCT	63	Paracetamol 1000 mg Diclofenac /Paracetamol 75 mg/1000 mg Tramadol/Paracetamol 100 mg/1000 mg	Single dose, postoperative	Paracetamol–tramadol and Paracetamol–diclofenac reduce cumulative postoperative analgesic consumption and prolongs the time to first rescue analgesic
Liu et al, 2021112	Arthroscopic knee surgery	Open-label RCT	232	Oxycodone/Paracetamol 10 mg/650 mg Celecoxib	Single dose, postoperative	Oxycodone–Paracetamol increased analgesic efficacy, with comparable safety profiles compared with celecoxib.
Singh et al, 2021135	Rotator cuff repair	Open-label RCT	57	Oxycodone/Paracetamol 5 mg/1000 mg Oxycodone 5 mg Paracetamol 1000 mg	Combinations every 6 hours postoperative as needed Paracetamol 1000 mg perioperative	Perioperative acetaminophen significantly decreased opioid consumption and improved overall pain control.

Abbreviation: RCT, randomized controlled trial.