Ibuprofen Paracetamol Combination in Paediatric Pain Management- Review

Paracetamol is a common analgesic and antipyretic drug for the management of mild-to-moderate pain in children, and it is considered as first-line therapy according to various international guidelines and recommendations .(3) Ibuprofen - a nonsteroidal anti-inflammatory drug (NSAID); together with paracetamol, is the recommended analgesic drug with additional antipyretics effects.(4)

The published prescribing trends of healthcare professionals indicate that for pain, ibuprofen is the most commonly utilised agent among the paediatric population, followed by paracetamol. For clinical conditions where inflammation is associated, ibuprofen is the most commonly prescribed among paediatric and adult patients.(5) The efficacy of ibuprofen and paracetamol has been clinically proven in common acute pain syndromes in children. These include sore throat, ear pain, toothache, headache, adenoid-tonsillectomy pain, post minor surgical procedure pains and musculoskeletal pains. In most of these clinical conditions, the efficacy of ibuprofen is reported to be superior to paracetamol(6)

Prescribing NSAIDs in Children – Considering Safety First: Meta-analyses by Catherine A Pierce and Bryan Voss included eighty-five studies, from which sixty-six contained safety data; confirmed that the tolerability profile of paracetamol and ibuprofen in managing children's pain and fever are similar and that both drugs are associated with rare adverse events .(7) Due to this valuable clinical advantage, ibuprofen, reportedly, can be administered to children aged above three-months(4)

Tonsillitis and Pharyngitis: A randomized, double-blind, multicenter, controlled trial was conducted on the efficacy of ibuprofen versus paracetamol and placebo for treatment of symptoms of tonsillitis and pharyngitis in children. Two hundred thirty-one children were included in this study aged between 6 and 12 years. Patients were randomly assigned to one of three parallel treatment groups – ibuprofen, paracetamol and placebo. After 48 hours of treatment, results demonstrated that spontaneous pain resolved completely in 80% of children treated with ibuprofen, as compared with 70.5% and 55% of children receiving paracetamol and placebo, respectively. It is noteworthy, that a similar pattern was also noted on pain during swallowing. The study concluded that ibuprofen, added to standard care is an effective and well-tolerated short-term treatment of pain related to acute tonsillitis and pharyngitis.(8)

Acute Otitis Media: Two hundred and nineteen children participated in a qualitatively conducted randomized, double-blind, multicentre controlled trial designed by G Pons et al, to assess the efficacy and safety of ibuprofen among children with otoscopically proven acute otitis media. The study participants comprised of children aged 1 to 6 years old. The intervention in the three treatment arms was ibuprofen (n=71), paracetamol (n=73) or placebo (n=75) thrice daily for 48 hours. The study results indicated that after 48 hours of treatment, otalgia persistence was least in the group treated with ibuprofen compared to paracetamol and placebo (7% vs. 10% vs. 25%) respectively. The study inferred that ibuprofen, when added to standard care treatment could benefit in the short-term management of pain related to acute otitis media in children(9)

Toothaches: Ibuprofen may have clinical applicability in children with dental caries and for the control of toothache after dental procedures.(10)  A paediatric study including children aged 5 to 12 years with toothache showed that pain control with ibuprofen was as good as the combination of paracetamol and codeine.(11) In yet another randomized clinical trial published by Bradley R et al, which compared ibuprofen and paracetamol in adolescent paediatric patients (aged 12–16 years) undergoing dental procedures; reported that a combination of preoperative and postoperative ibuprofen is more effective than paracetamol in the control of orthodontic pain(12)

Headaches: Paracetamol and ibuprofen are the most used pain drugs for the treatment of acute phase headaches Several placebo-controlled studies demonstrated the efficacy of ibuprofen to provide pain relief within 2 hours of administration. (13)  A study published by Hamalainen et al compared both paracetamol (15 mg/kg) and ibuprofen (10 mg/kg) with a placebo. While both drugs were found more effective than a placebo within 2 hours, an intention-to-treat analysis, suggested that the therapeutic success of ibuprofen was greater compared to paracetamol.(14) However, it is suggested to prudently evaluate organic and secondary causes of headaches in the pediatric population before initiation of pain relief treatment.

Indian Guidelines: The Ministry of Health and Family Welfare Government of India guidelines on the use of paracetamol following vaccinations(15)  has the following statements favouring the use of Paracetamol

• Administer an age-appropriate dose of paracetamol syrup when there is fever (axillary temperature > 38oC /100.4o F or child feels hot to touch)

• A statistically valuable representation published by Brit Long and Michael Gottlieb summarised that 1 in 4 patients receiving ibuprofen vs. paracetamol had reduced pain at 4 to 24 hours and a 25.2% reduction in pain at 4 to 24 hours could be achieved with ibuprofen vs. paracetamol

• Lastly, an 18.5% reduction in fevers was observed during the same time duration with ibuprofen compared to paracetamol(16)

Acute pain is a frequent symptom association in paediatric illnesses and, probably, the most worrying for both, children and parents. Because children cannot express the intensity of their pain, it becomes increasingly challenging. The most common clinical settings associated with acute pain in children are sore throat, ear pain, toothache, post-traumatic musculoskeletal pain, headache and postoperative pain. Ibuprofen and Paracetamol are amongst the most widely used analgesics with additional antipyretic effects. (6) Ibuprofen and Paracetamol combination may be considered of clinical value in the management of pain among a paediatric population with the potential of offering faster and greater pain relief – a valuable clinical goal in this population with the endeavour to comforting the child.

Adapted from:

2. Frederick T. O'Donnell et al, Pediatric Pain Management: A Review, Missouri Medicine 2014;111(3):231-237

3. de Martino M, Chiarugi A. Recent Advances in Pediatric Use of Oral Paracetamol in Fever and Pain Management. Pain Ther. 2015 Dec;4(2):149-68. doi: 10.1007/s40122-015-0040-z. Epub 2015 Oct 30. PMID: 26518691; PMCID: PMC4676765.

4. Barbagallo M, Sacerdote P. Ibuprofen in the treatment of children's inflammatory pain: a clinical and pharmacological overview. Minerva Pediatr 2019;71:82-99. DOI: 10.23736/S0026-4946.18.05453-1)

5. Kanabar DJ. A clinical and safety review of paracetamol and ibuprofen in children. Inflammopharmacology. 2017 Feb;25(1):1-9. doi: 10.1007/s10787-016-0302-3..

6. Poddighe D, Brambilla I, Licari A, Marseglia GL. Ibuprofen for Pain Control in Children: New Value for an Old Molecule. Pediatr Emerg Care. 2019 Jun;35(6):448-453. doi: 10.1097/PEC.0000000000001505..

7. Pierce CA, Voss B. Efficacy and safety of ibuprofen and acetaminophen in children and adults: a meta-analysis and qualitative review. Ann Pharmacother. 2010 Mar;44(3):489-506. doi: 10.1345/aph.1M332. Epub 2010 Feb 11. PMID: 20150507.

8. Schachtel BP, Thoden WR. A placebo-controlled model for assaying systemic analgesics in children. Clin Pharmacol Ther. 1993 May;53(5):593-601. doi: 10.1038/clpt.1993.75. PMID: 8491069.

9. Bertin L, Pons G, d'Athis P, Duhamel JF, Maudelonde C, Lasfargues G, Guillot M, Marsac A, Debregeas B, Olive G. A randomized, double-blind, multicentre controlled trial of ibuprofen versus acetaminophen and placebo for symptoms of acute otitis media in children. Fundam Clin Pharmacol. 1996;10(4):387-92. doi: 10.1111/j.1472-8206.1996.tb00590.x. PMID: 8871138.

10. Ashley PF, Parekh S, Moles DR, et al. Preoperative analgesics for additional pain relief in children and adolescents having dental treatment. Cochrane Database Syst Rev. 2016:CD008392

11. Moore PA, Acs G, Hargreaves JA. Postextraction pain relief in children: a clinical trial of liquid analgesics. Int J Clin Pharmacol Ther Toxicol. 1985;23:573–577.

12. Bradley RL, Ellis PE, Thomas P, et al. A randomized clinical trial comparing the efficacy of ibuprofen and paracetamol in the control of orthodontic pain. Am J Orthod Dentofacial Orthop. 2007;132:511–517

13. Bushra R, Aslam N. An overview of clinical pharmacology of ibuprofen. Oman Med J. 2010;25:155–1661.

14. Hämäläinen ML, Hoppu K, Valkeila E, et al. Ibuprofen or acetaminophen for the acute treatment of migraine in children: a double-blind, randomized, placebo-controlled, crossover study. Neurology. 1997;48:103–107.

15. Ministry of Health and Family Welfare Government of India guidelines on use of syrup paracetamol following vaccinations

16. Long B, Gottlieb M. Ibuprofen vs. Acetaminophen for Fever or Pain in Children Younger Than Two Years. Am Fam Physician. 2021 May 1;103(9):Online. PMID: 33929814.