1.Miller RR, Feingold A, Paxinos, J. Propoxyphene Hydrochloride, A Critical Review. JAMA 213 996-1006 (1972).

      The authors reviewed the published literature on propoxyphene and concluded that propoxyphene was not superior to codeine or aspirin in terms of analgesic effect. The authors concluded:“It appears that factors other than intrinsic therapeutic value are responsible for the commercial success of propoxyphene.” They concluded that they could make no definite statement as to relative incidence of side effects. [It should be noted that of the 243 literature references they reviewed, only 20 reported double-blind studies. The rest had deficiencies in design, conduct and reporting.]

2.Moertel CG, Ahmann, DL, Taylor WF and Schwartau N. Relief of pain by oral medications. JAMA 229: 55-59 (1974).

      They compared nine analgesics in patients with inoperable cancer. They found that 100 mg of propoxyphene napsylate did not show significant advantage in analgesia over aspirin alone. This was a single dose study so it is not surprising that the authors found no difference in side effects of the various drugs.

3.A Li Wan Po. Systemic overview of co-proxamol to assess analgesic effects of addition of dextropropoxyphene to paracetamol [paracetamol is the British term for acetaminophen] British Medical Journal 315:1565-1571 (1997).

      He reviewed the results reported in 26 randomized controlled trials.A total of 3321 patients with postsurgical pain, arthritis and musculoskeletal pain were subjects of the trials.His conclusion “there is little objective evidence to support prescribing a combination of acetaminophen and dextropropoxyphene in preference to acetaminophen alone in moderate pain such as that after surgery.”

4.Nickander RC, Emmerson JL, Hynes MD, Steinberg MI and Sullivan HR. Pharmacologic and toxic effects in animals of dextropropoxyphene and its major metabolite norpropoxyphene:A Review. Human Toxicology 3: 13S-36S (1984).The metabolite has a longer half-life than the parent drug and has the potential to cause CNS and cardiac effects.

5.Brosen K, Gram LF, Schou J, Larsen NE and Thayssen P. Dextropropoxyphene kinetics after single and repeated oral doses in man.Eur J Clin Pharmacol 29: 79-84 (1985).

6.Young RJ.Dextropropoxyphene overdosage:pharmacological considerations and clinical management.Drugs 26: 70-79 (1983).
 

7.Beers MH, Ouslander JG, Rollingher I, Reuben DB, Brooks J and Beck JC.Explicit criteria for determining inappropriate medication use in nursing home residents.Arch Intern Med 151: 1825-1832 (1991).

Authors used a two-round survey, based on Delphi methods, with 13 nationally recognized experts to reach consensus on explicit criteria defining the inappropriate use of medications in a nursing home population.The 30 factors agreed on by this method identified 17 categories of inappropriate medications including the analgesics propoxyphene andpentazocine.The statement made about propoxyphene is that “All use should be avoided; other narcotics are safer and more effective.”

8.Willcox SM, Himmelstein DU and Woolhandler S.Inappropriate drug prescribing for the community-dwelling elderly.JAMA 272: 272-296 (1994).These authors again identified propoxyphene as contraindicated in the elderly, but found propoxyphene among the most prescribed drugs in the “inappropriate” category.
 

9.Please note that propoxyphene is not even mentioned in Clinical Practice Guideline, Number 1 Acute Pain Management Operative or Medical Procedures and Trauma, which were published by AHCPR in March 1992.
 

10.Propoxyphene is mentioned only once (page 71) in the Clinical Practice Guideline, Number 9 Management of Cancer Pain which was published by AHCPR in March 1994.Reference is made to the fact that the drug and its metabolite could accumulate if patients have hepatic or renal dysfunction.
 

11.AGS Panel on Chronic Pain in Older Persons.The management of chronic pain in older persons.J Am Ger Soc 46: 635-651 (1998).There is no mention of propoxyphene in this reference.
 

12.American Medical Directors Association.Chronic Pain Management in the Long-Term Care Setting.Clinical Practice Guideline, 1999.Page 21:“Propoxyphene is not recommended for treatment of chronic pain in long-term care patients.Its efficacy is no better than that of acetaminophen and it has undesirable central nervous system side effects.However, it may be acceptable to continue patients on propoxyphene if they have been taking the drug for a long time and have difficulty obtaining the same degree of pain relief with other medications.”
 

13.Principles of Analgesic Use in the Treatment of Acute Pain and Cancer Pain.Fourth Edition, American Pain Society, 1999.
 

14.AHCPR Clinical Practice Guideline:Acute Pain Management: Operative or Medical Procedures and Trauma (AHCPR 92-0032, 1992; p. 18):
 

15.AHCPR Clinical Practice Guideline: Management of Cancer Pain (AHCPR 94-0592, 1994; p. 50
 

16.Agency for Health Care Policy and Research: Acute Pain Management: Operative or Medical Procedure and Trauma. Clinical Practice Guideline No 1. Rockville, Md: AHCPR Publication no. 92-0032, 1992.

17.Agency for Health Care Policy and Research: Management of Cancer Pain. Clinical Practice Guideline No 3. Rockville, Md: AHCPR Publication no. 94-0592, 1994.

18.American Pain Society. Principles of Analgesic Use in the Treatment of Acute Pain and Cancer Pain 4th Edition, American Pain Society, Glenview, Il, pp 31, 1999.

19.Danziger LH, Martin, SJ and Blum RA.Central nervous system toxicity associated with meperidine use in hepatitis disease.Pharmacotherapy 14: 235-8, 1994.

20.Kaiko RF, Foley KM, Grabinski PY, Heidrich G, Roger AG, Inturrisi CE, Reidenberg MM: Central nervous system excitatory effects of meperidine in cancer patients. Annals of Neurology 13 (2): 180-185, 1983.

21.Lee F, Cundiff, D.Meperidine vs. morphine in pancreatitis and cholecystitis.Arch Intern Med 158: 2339, 1988.

22.Mather LE, Meffin PJ: Clinical pharmacokinetics of pethidine. Clinical Pharmacokinetics 3: 352-368, 1978.

23.Mather LE: Pharmacokinetic studies of meperidine. Advance in Pain Research and Therapy, vol 8 Eds., KM Foley, CE Inturrisi: Raven Press, New York pp 155-165, 1986.

24.Mauro VF, Bonfiglio MF, Spunt AL: Meperidine-induced seizure in a patient without renal dysfunction or sickle cell anemia. Clinical Pharmacy 5:837-839, 1986.

25.Sherman S, Lehman GA: Opioids and the sphincter of Oddi. Gastrointestinal Endoscopy 40:1, 105-6, 1994.