Opioid Therapy

Treatment options for postoperative pain are limited and opioids are used most often[1], [2]. However;

  • Inadequate analgesia still affects one in two patients treated
  • Opioids use exposes patients to dependence and addiction risks and hospitals to diversion by staff and patients alike. The societal cost of dependence and addiction to prescription opioids is well understood in North America today[3] while the costs for hospital of mitigating diversion can be considerable[4].
  • Opioid use dramatically increases treatment costs[5] each adverse opioid event increasing the median cost of care by $568 and the length of stay by 0.6 days[6].

 

As a result there are continuing calls to find alternative treatments for postoperative pain that either replace opioids or reduce their required dosage and frequency of administration[7],[8].

Non-Opioid Therapy

Non-Steroidal Anti-Inflammatory Drugs (NSAIDS) acetaminophen and COX-2 medications (a class of NSAID) are the second most frequently used drugs for postoperative pain with around 55% of patients receiving them[9]; about 50% of treatments are administered intravenously.

The best-selling and most commonly used intravenous non-opioid analgesics are listed in the table below along with their benefits and draw-backs[10].

PPI-1501 is listed alongside these therapies to contrast its unique value proposition

 

Drug Name (Manufacturer) Active Ingredient Administration Formulation Details Comments
Ofirmev (Mallinckrodt) Acetaminophen 100mL Infusion Large volume liquid Slow large volume administration reduces peak concentrations and efficacy potential. New venous access needed adding to cost and patient discomfort.
Drug Name (Manufacturer) Active Ingredient Administration Formulation Details Comments
Caldolor (Cumberland) Ibuprofen Long infusion time Large volume liquid Slow large volume administration reduces peak concentrations and efficacy potential. New venous access needed adding to cost and patient discomfort.
Drug Name (Manufacturer) Active Ingredient Administration Formulation Details Comments
Dyloject

(Pfizer)

Diclofenac Rapid injection Liquid prone to instability and recalls Manufacturing problems caused by product instability have led to recalls and market shortages.
Drug Name (Manufacturer) Active Ingredient Administration Formulation Details Comments
Dynostat

(Pfizer)

Paracoxib Rapid injection Lyophilized powder of COX-2 pro-drug Stable low volume injection but pro-drug formulation may slow onset of analgesia. Not approved in N. America due to safety concerns.
Drug Name (Manufacturer) Active Ingredient Administration Formulation Details Comments
Toradol

(Pfizer)

Keterolac 15 second injection Liquid prone to instability and recalls Manufacturing problems caused by product instability have led to recalls and market shortages

 

Drug Name (Manufacturer) Active Ingredient Administration Formulation Details Comments
 

PPI-1501

 

Flurbiprofen Rapid Injection and sustained blood levels Lyophilized powder of native flurbiprofen with SmartCelle technology Rapid injection reduces cost of care and patient inconvenience. Stable dry powder formulation is simple to manufacture and ship. Sustained blood levels enhance opioid sparring effect, safety and efficacy.

 

[1] http://www.utasip.com/files/articlefiles/pdf/2nd%20article.pdf

[2] Decision Resources Acute Pain Report 2010

[3] https://www.drugabuse.gov/related-topics/trends-statistics

[4] Diversion of Drugs Within Health Care Facilities, a Multiple-Victim Crime: Patterns of Diversion, Scope, Consequences, Detection, and Prevention Keith H. Berge, Kevin R. Dillon, Karen M.       Sikkink Timothy K. Taylor, and William L. Lanier. Mayo Clin. Proc. 2012 Jul; 87(7): 674–682. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3538481/

[5] Wheeler, M., Oderda, G. M., Ashburn, M. A. & Lipman, A. G. Adverse events associated with postoperative opioid analgesia: A systematic review. The journal of pain: official  Journal of the American Pain Society 3, 159-180 (2002).

[6] Practice guidelines for acute pain management in the perioperative setting: an updated report by the American Society of Anesthesiologists Task Force on Acute Pain Management. Anesthesiology 116, 248-273, doi:10.1097/ALN.0b013e31823c1030 (2012).

[7] Postoperative Pain Control (2013) Clin Colon Rectal Surg 2013;26:191–196

[8] The burden of acute postoperative pain and the potential role of the COX-2-specific inhibitors (2003) J. Stephens, B. Laskin, C. Pashos , B. Pen˜a2 and J. Wong. Rheumatology Vol. 42 Suppl. 3

[10] Ofirmev® is a registered tradename of Mallinckrodt Pharmaceuticals; Caldolor® is a registered tradename of Cumberland Pharmaceuticals; Dyloject®, Dynastat® and Torodol® are registered tradename of Pfizer.