Acetaminophen & NSAIDS : Synergistic or Polypharmacy

• Polypharmacy is the concurrent use of multiple medications. It can be associated with the prescription and use of too many or unnecessary medicines at dosages or frequencies higher than therapeutically essential.
• However, multiple medications are often necessary and can constitute best care for patients.

• Based on WHO analgesic ladder , If pain occurs, there should be prompt oral administration of drugs in the following order: nonopioids (aspirin and paracetamol); then, as necessary, mild opioids (codeine); then strong opioids such as morphine, until the patient is free of pain
• In another modified  “analgesic ladder” recommendations for musculoskeletal pain, according to the Boger and Jones (2005), recommended stepwise approach is as follows.

• According to the analgesic ladder (Figure 1) paracetamol should first be tried: if ineffective, when taken as recommended, codeine should be added, and only after that (step 2) should NSAIDs be considered. It has been recommended that NSAIDs not be started until 48 hours after injury (Braund 2006).

• When an NSAID is used, consideration should be given to the relative toxicity and those with a safer toxicity profile should be chosen (i.e diclofenac or ibuprofen). Precaution should always be taken in those patients with a history of gastric upset, asthma exacerbation and sensitivity to other NSAIDs and a realisation that these may still occur in susceptible patients even at low doses.

• NSAIDs have their greatest benefit in pain that is the result of excessive or uncontrolled inflammation such as rheumatoid arthritis. The analgesic benefits of NSAIDs in acute musculoskeletal conditions may be best realised after inflammation needed to initiate healing has passed. 

Other evidence & findings

Study by Doherty 2011

• Ibuprofen /paracetamol combination analgesia, confers modest short tem benefit for knee pain /oesteorthritis,  but at the expense of an increase in side effects, namely gastrointestinal bleeding
• While the group taking the high-dose combination pill experienced the biggest improvements in pain relief, stiffness, function and quality of life at both check-ups, that pain relief came at a cost. At the end of the 13-week trial, 38.4 percent of patients in the high-dose combination group saw their hemoglobin levels drop compared with 24.1 percent in the group taking low-dose combination pills, 20.3 percent on acetaminophen alone and 19.6 percent on ibuprofen alone. Hemoglobin is the main component of red blood cells, and a drop in hemoglobin can be a sign of gastrointestinal bleeding; however, the study results didn’t conclusively link the drop to hemoglobin to GI bleeding.

Review by Ong et al 2010

• In acute post operative pain, combining paracetamol and an NSAID confers additional analgesic efficacy over either drug alone. The combination of paracetamol and an NSAID was more effective than paracetamol or an NSAID alone in 85% and 64% of the studies, respectively.

Based on study by Miranda et al 2005

• Paracetamol combined with NSAIDs produces a supra-additive or synergic analgesic effect. It is possible to suggest that the combinations of paracetamol and NSAIDs will be effective for the clinical treatment of pain.
• In addition, it is demonstrated that the effect of the combinations paracetamol/NSAIDs is superior to that of either component alone.
• The mechanisms responsible for the synergism in the analgesic activity of paracetamol/NSAIDs combinations are not clear; however, according to the information in the literature, different systems are partially involved and further experiments are required to completely characterize the pharmacological basis of the synergic effect.

Based on Study by Phero et al 2004

• Acetaminophen's site of action differs from that of NSAIDs, and acetaminophen's analgesic effect is considered synergistic when combined with NSAIDs and opioids.

Based on SIGN UK

• Paracetamol (1,000-4,000 mg/day) should be considered alone or in combination with NSAIDs in the management of pain in patients with hip or knee osteoarthritis in addition to non-pharmacological treatments.

Reference : 

1. http://pharmacist.com/sites/default/files/files/15-183_PainReliefBrief_FINAL%20with%20SME%20statement%20070215.pdf
2. A randomised controlled trial of ibuprofen, paracetamol or a combination tablet of ibuprofen/paracetamol in community-derived people with knee pain. Retrieved from : http://ard.bmj.com/content/70/9/1534.full
3. Combining Paracetamol (Acetaminophen) with Nonsteroidal Antiinflammatory Drugs: A Qualitative Systematic Review of Analgesic Efficacy for Acute Postoperative Pain. Retrieved from: http://www.endoexperience.com/documents/APAPOngetal_000.pdf
4. Synergism between paracetamol and nonsteroidal anti-inflammatory drugs in experimental acute pain Retrieved from : http://repositorio.uchile.cl/bitstream/handle/2250/127840/Miranda_Hugo.pdf?sequence=1
5. Contemporary trends in acute pain management. Retrieved from https://www.ncbi.nlm.nih.gov/pubmed/15167031
6. http://sign.ac.uk/guidelines/fulltext/136/section5.html
7. Analgesic recommendations when treating musculoskeletal sprains and strains http://physiotherapy.org.nz/assets/Professional-dev/Journal/2007-July/2007Julycommentary.pdf
8. https://www.nps.org.au/__data/assets/pdf_file/0003/15780/news13_polypharmacy_1200.pdf
9. Pain Assessment and Pharmacologic Management https://books.google.com.my