Summary
This paper comprehensively reviews the worldwide situation regarding acute overdosage of dextropropoxyphene (propoxyphene). The changing epidemiology of this type of poisoning over the last 20 years is described with discussion of concurrent trends and, in particular, the effects of different preventive measures adopted in various countries. The clinical pharmacology of dextropropoxyphene relevant to the clinical toxic effects resulting from acute overdosage is described, and the management is detailed. In particular, the importance of early diagnosis and treatment is stressed in view of the potentially lethal complications that may suddenly occur with this poisoning. Recommendations for the correct use of the specific narcotic antagonist, naloxone, are made, together with other intensive supportive measures.
As dextropropoxyphene is frequently taken together with other toxic agents, the concomitant effects of alcohol and sedative drugs are described and the treatment of paracetamol (acetaminophen) in combination with dextropropoxyphene is emphasised. The most effective preventive measures for the future are suggested, but caution is advised regarding the prescription for ‘at risk’ patients of alternative analgesics, which may be no safer in overdosage.
Similar content being viewed by others
References
Abernethy DR, Greenblatt DJ, Steel K, Shader RI. Impairment of hepatic drug oxidation by propoxyphene. Annals of Internal Medicine 97: 223–224, 1982
Bailey RR. Analgesia and dextropropoxyphene. New Zealand Medical Journal 96: 1031, 1983
Barclay WR. Propoxyphene. Journal of the American Medical Association 241: 1689, 1979
Barraclough CJ, Lowe RA. Failure of naloxone to reverse the cardiotoxicity of Distalgesic overdose. Postgraduate Medical Journal 58: 667–668, 1982
Baselt RC, Wright JA, Turner JA, Cravey RH. Propoxyphene and norproxyphene tissue concentrations in fatalities associated with propoxyphene hydrochloride and propoxyphene napsylate. Archives of Toxicology 34: 145–149, 1975
Beattie JO, Chen CP, MacDonald TH. Neonatal distalgesic poisoning. Lancet 1: 49, 1981
Bogartz LJ, Miller WC. Pulmonary oedema associated with propoxyphene intoxication. Journal of the American Medical Association 215: 259–261, 1971
Bradberry JC, Raebel MA. Continuous infusion of naloxone in the treatment of narcotic overdose. Drug Intelligence and Clinical Pharmacy 15: 945–950, 1981
Brewer C, Farmer H. Self poisoning in 1984: a prediction that didn’t come true. British Medical Journal 290: 391, 1985
Cann HM, Verhulst HL. Convulsions as a manifestation of acute dextropropoxyphene intoxication. American Journal of Diseases of Children 99: 380–381, 1960
Carson DJL, Carson ED. Fatal dextropropoxyphene poisoning in Northern Ireland. Lancet 1: 894–897, 1977
Christensen H. Dodelige forgisteninger med dekstropropoksifen. Ugeskrift for laeger 137: 2571–2576, 1975
Dwyer PS, Jones IF. An investigation into self-poisoning with analgesic drugs in Scotland. Acta Medicinae Legalis et Socialis (Liege) 33(1): 779–784, 1983
Editorial. Dangers of dextropropoxyphene. British Medical Journal 1: 668, 1977
Editorial. Treatment of dextropropoxyphene poisoning. Lancet 2: 542, 1977
Edwards IR. Analgesia and dextropropoxyphene. New Zealand Medical Journal 96: 989, 1983
Elmes PC. The contribution of prescribed drugs to the incidence of accidental and deliberate poisoning in the community. Acta Pharmacologica et Toxicologica 41 (Suppl.): 517–521, 1977
Evans JM, Hogg IJ, Lunn JN, Rosen M. Degree and duration of reversal by naloxone of effects of morphine in conscious subjects. British Medical Journal 2: 589–591, 1974
Finkle BS. Self-poisoning with dextropropoxyphene and dextropropoxyphene compounds: the USA experience. Human Toxicology 3 (Suppl.): 115S–134S, 1984
Food and Drug Administration, Department of Health, Education and Welfare. Propoxyphene. Federal Regulations 44: 11837, 1979
Gardener R, Hanka R, O’Brien VC, Page AJF, Rees R. Psychological and social evaluation in cases of deliberate self-poisoning admitted to a general hospital. British Medical Journal 2: 1567–1570, 1977
Garriott JC, DiMaio VJM, Petty CS. Death by poisoning: a ten-year survey of Dallas County. Journal of Forensic Sciences 27: 868–879, 1982
Giacomini KM, Giacomini JC, Gibson TP, Levy G. Propoxyphene and norpropoxyphene plasma concentrations after oral propoxyphene in cirrhotic patients with and without surgically constructed portacaval shunt. Clinical Pharmacology and Therapeutics 28: 417–424, 1980
Gibson TP, Giacomini KM, Briggs WA, Whitman W, Levy G. Propoxyphene and norpropoxyphene plasma concentrations in the anephric patient. Clinical Pharmacology and Therapeutics 27: 665–670, 1980
Gibson TP, Nelson HA. Drug kinetics and artificial kidneys. Clinical Pharmacokinetics 2: 403–426, 1977
Giertson JC, Dibb VL. Dodelige forgiftninger med dextropropoksyfen. Tidsskrift for Praktisk Laegegering 100: 283–285, 1980
Gourlay GK, Coulthard K. The role of naloxone infusions in the treatment of overdoses of long half-life narcotic agonists: application to normethadone. British Journal of Clinical Pharmacology 15: 269–272, 1983
Gram LF, Show J, Way WL, Heltberg J, Bodin NO. d-Propoxyphene kinetics after single oral and intravenous doses in man. Clinical Pharmacology and Therapeutics 26: 473–482, 1979
Gwilt PR, Perrier D. Plasma protein binding and distribution characteristics of drugs as indices of their haemodialyzability. Clinical Pharmacology and Therapeutics 24: 154–161, 1978
Hardwick C, Holt L, James R, Smith AJ. Trends in self-poisoning with drugs in Newcastle, New South Wales, 1980–1982. Medical Journal of Australia 144: 453–454, 1986
Holding TA, Buglass D, Duffy JC, Kreitman N. Parasuicide in Edinburgh: a seven year review 1968–74. British Journal of Psychiatry 130: 534–543, 1977
Holland DR, Steinberg MI. Electrophysiologic properties of propoxyphene and norpropoxyphene in canine cardiac conducting tissues in vitro and in vivo. Toxicology and Applied Pharmacology 47: 123–133, 1979
Hunt V. Treatment of dextropropoxyphene poisoning. British Medical Journal 1: 554, 1973
Inturissi CE, Colburn WA, Vereby K, Dayton HE, Woody GE, et al. Propoxyphene and norpropoxyphene kinetics after single and repeated doses of propoxyphene. Clinical Pharmacology and Therapeutics 31: 157–167, 1982
Jacobsen D, Frederichsen PS, Knutsen KM, Sørum T, Talseth T, et al. A prospective study of 1212 cases of acute poisoning: general epidemiology. Human Toxicology 3: 93–106, 1984
James O, Lesna M, Roberts SH, Pulman L, Douglas AP, et al. Liver damage after paracetamol overdose. Lancet 2: 579–581, 1975
Johns MW. Self-poisoning with barbiturates in England and Wales during 1959–1974. British Medical Journal 1: 1128–1130, 1977
Kersh ES. Treatment of dextropropoxyphene overdosage with naloxone. Chest 63: 112–114, 1973
Lawson AAH. Acute poisoning: common errors of management. Care of the Critically 111 2: 71–80, 1986b
Lawson AAH. Acute poisoning. In MacLeod J (Ed.) Davidson’s principles and practice of medicine, 15th ed., Churchill Livingstone, Edinburgh, 1986a
Lawson AAH. Acute poisoning: management principles. Medicine Digest 13: 10–18, 1987
Litovitz TL, Norman SA, Veltri JC. 1985 annual report of the American association of poison control centres national data collection system. Annals of Emergency Medicine 4: 427–458, 1986
Lovejoy FH, Mitchell AA, Goldman P. The management of propoxyphene poisoning. Journal of Paediatrics 58: 98–100, 1974
Lund A, Nielson GD. Dextropropoxyphene concentrations in blood in cases of fatal poisoning. Zeitschrift Für Rechtsmedizin 71: 148–150, 1972
Lund-Jacobsen H. Cardio-respiratory toxicity of propoxyphene and norpropoxyphene in conscious rabbits. Acta Pharmacologica et Toxicologica 42: 171–178, 1978
Matthew H, Lawson AAH. Treatment of common acute poisonings, 4th ed., Churchill Livingstone, Edinburgh, 1979
McBay AJ. Propoxyphene and norpropoxyphene concentrations in blood and tissues in cases of fatal overdose. Clinical Chemistry 22: 1319–1321, 1976
McBay AJ, Turk RF, Corbett BW, Hudson P. Determination of propoxpyhene in biological materials. Journal of Forensic Science 19: 81, 1974
McCarthy WH, Keenan RL. Propoxyphene hydrochloride poisoning: report of the first fatality. Journal of the American Medical Association 187: 460–461, 1964
McMahon RE, Rodolfo AS, Culp RW. The fate of radiocarbon labelled propoxyphene in rat, dog and human. Toxicology and Applied Pharmacology 19: 427–444, 1971
Meredith TJ, Vale JA. Epidemiology of analgesic overdose in England and Wales. Human Toxicology 3 (Suppl.): 61S-74S, 1984
Messick RT. Evaluation of acetaminophen, propoxyphene and their combination in office practice. Journal of Clinical Pharmacology 19: 227–230, 1979
Miller RR, Feingold A, Paxinos J. Propoxyphene hydrochloride: a critical review. Journal of the American Medical Association 213: 996–1006, 1970
Mitchell AA, Lovejoy FH, Goldman P. Drug ingestions associated with miosis in comatose children. Journal of Paediatrics 89: 303–305, 1976
Monforte JR, Spitz WU. Drug deaths involving propoxyphene: an assessment in metropolitan Detroit. Preventive Medicine 5: 573–575, 1976
Moore RA, Rumack BH, Conner CS, Peterson RG. Naloxone: underdosage after narcotic poisoning. American Journal of Diseases of Children 134: 156–158, 1980
Musa MN, Lyons LL. Effect of food and liquid on the pharmacokinetics of propoxyphene. Current Therapeutic Research 19: 669–674, 1976
Myers JB, Smith AJ, Elliot RL, MacAskill P. Self-poisoning with drugs: a 3 1/2 -year study in Newcastle, NSW. Medical Journal of Australia 2: 402–405, 1981
National Poisons Information Service Monitoring Group: Analgesic poisoning: a multicentre prospective study. Human Toxicology 1: 7–23, 1981
Nickander R, Smits SE, Steinberg MI. Propoxyphene and norpropoxyphene: pharmacologic and toxic effects in animals. Journal of Pharmacology and Experimental Therapeutics 200: 245–253, 1977
Orguma T, Levy G. Acute effect of ethanol on hepatic first pass elimination of propoxyphene in rats. Journal of Pharmacology and Experimental Therapeutics 219: 7–13, 1981
Osselton MD, Blackmore RC, King LA, Moffat AC. Poisoning-associated deaths for England and Wales between 1973 and 1980. Human Toxicology 3: 201–221, 1984
Parker SG, Thomas DG. Dihydrocodeine overdose treated with naloxone infusion. British Medical Journal 287: 1547, 1983
Pohland A, Sullivan HR. Analgesics: esters of 4-dialhylamino-1, 2-d phenyl-2-d phenyl-2-butanols. Journal of the American Chemical Association 75: 4458–4461, 1953
Prescott LF. Paracetamol overdosage: pharmacological considerations and clinical management. Drugs 25: 290–314, 1983
Prescott LF. Treatment of severe acetaminophen poisoning with intravenous acetylcysteine. Archives of Internal Medicine 141: 386–389, 1981
Prescott LF, Highley MS. Drugs prescribed for self poisoners. British Medical Journal 290: 1633–1636, 1985
Prescott LF, Park J, Ballantyne A, Adriaensseus P, Proudfoot AT. Treatment of paracetamol (acetaminophen) poisoning with N-acetylcysteine. Lancet 2: 432–434, 1977
Prescott LF, Park J, Sutherland GR, Smith IJ, Proudfoot AT. Cysteamine, methionine and penicillamine in the treatment of paracetamol poisoning. Lancet 2: 109–113, 1976
Proudfoot AT. Clinical features and management of distalgesic overdose. Human Toxicology 3 (Suppl.): 85S–94S, 1984
Redfern N. Dihydrocodeine overdose treated with naloxone infusion. British Medical Journal 287: 751–752, 1983
Robbins EB. Pharmacological effects of new analgesics alpha-4-dimethyl-amino-2-d phenyl-3-methyl-4-propionyl oxybutane. Journal of the American Pharmacological Association 44: 497–499, 1955
Shenfield GM, Jones AN, Paterson JW. Effect of restrictions on prescribing patterns for dextropropoxyphene. British Medical Journal 281: 651–653, 1980
Simonsen J. Accidental fatal drug poisoning with particular reference to dextropropoxyphene. Forensic Science 10: 127–132, 1977
Starkey IR, Lawson AAH. Acute poisoning with Distalgesic. British Medical Journal 2: 1468, 1978
Statistics Division, Department of Health and Social Security, London, (personal communication), 1985
Strong JM. Changing trends in drug overdose over a six-year period. Military Medicine 148: 17–20, 1984
Sturner WQ, Garriott JC. Deaths involving propoxyphene: a study of 41 cases over a two year period. Journal of the American Medical Association 223: 1125–1130, 1973
Sundvist L, Petrovics J. Fatal poisoning with dextropropoxyphene containing analgesics: suicide or not? Acta Medica Scandinavica 196: 467–472, 1974
Tarala R, Forrest JAH. Treatment of dextropropoxyphene poisoning. British Medical Journal 2: 550, 1973
Tennant FS. Complications of propoxyphene abuse. Archives of Internal Medicine 132: 191–194, 1973
Therapeutic category report on National Prescription Audit. Gosselin and Company, Dedham, Massachusetts, 18 December 1969
Vale JA, Buckley BM, Meredith TJ. Deaths from paracetamol and dextropropoxyphene (Distalgesic) poisoning in England and Wales in 1979. Human Toxicology 3 (Suppl.): 135S–143S, 1984
Vale JA, Meredith TJ. Acute poisoning due to non-steroidal anti-inflammatory drugs: clinical features and management. Medical Toxicology 1: 12–31, 1986
Verebely K, Inturrisi CE. Disposition of propoxyphene and norpropoxyphene in man after a single oral dose. Clinical Pharmacology and Therapeutics 15: 302–309, 1974
Waife SP, Gruber CM, Rodda BE, Nash JF. Analgesia, plasma levels, and dosage of propoxyphene. International Journal of Clinical Pharmacology 13: 177–181, 1976
Waife SP, Gruber CM, Rodda BE, Nash JF. Problems and solutions to single dose testing of analgesics. Comparison of propoxyphene, codeine and fenoprofen. International Journal of Clinical Pharmacology 12: 301–304, 1975
Wall R, Linford SMJ, Akhter M. Addiction to Distalgesic (dextropropoxyphene). British Medical Journal 280: 1213–1214, 1980
Welling PG, Lyons FL, Tse FLS, Craig WA. Propoxyphene and norpropoxyphene: influence of diet and fluid on plasma levels. Clinical Pharmacology and Therapeutics 19: 559–565, 1976
Wetli CV, Bednarczyk LR. Deaths related to propoxyphene overdose: a ten-year assessment. Southern Medical Journal 73: 1205–1209, 1980
Whittington RM. Dextropropoxyphene (Distalgesic) overdosage in the West Midlands. British Medical Journal 2: 172–173, 1977
Wiseman MS, Chapman S, Huldstock GE, Loehry CA. Dextropropoxyphene overdosage and naloxone. British Medical Journal 1: 1159, 1977
Wolen RL, Gruber CM, Kiplinger GF, Scholz NE. Concentration of propoxyphene in human plasma following oral, intramuscular and intravenous administration. Toxicology and Applied Pharmacology 19: 480–492, 1971
Young DJ. Propoxyphene suicides. Archives of Internal Medicine 129: 62–66, 1972
Young RJ. Dextropropoxyphene overdosage: pharmacological considerations and clinical management. Drugs 26: 70–79, 1983
Young RJ, Lawson AAH. Distalgesic poisoning: cause for concern. British Medical Journal 281: 1045–1047, 1980
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Lawson, A.A.H., Northridge, D.B. Dextropropoxyphene Overdose. Med Toxicol Adverse Drug Exp 2, 430–444 (1987). https://doi.org/10.1007/BF03259877
Published:
Issue Date:
DOI: https://doi.org/10.1007/BF03259877