Skip to main content
SpringerLink
Log in

Dextromethorphan

An Overview of Safety Issues

  • Review Article
  • Drug Experience
  • Published:
Drug Safety Aims and scope Submit manuscript

Summary

Dextromethorphan is a highly effective and widely used nonopioid antitussive drug. As it has been in use for more than 30 years, a large body of clinical experience has been used to formulate a safety profile. An anthology of adverse drug events has been analysed, drawn both from published case records and a data base recording dextromethorphan-related adverse events spontaneously reported by physicians or pharmacists. The resulting safety profile indicates that adverse drug reactions are infrequent and usually not severe. The predominant symptoms are usually dose related and include neurological, cardiovascular and gastrointestinal disturbances.

Particular safety concerns arise when monoamine oxidase inhibiting (MAOI) drugs and dextromethorphan are coadministered. In addition to adverse drug reactions, the safety profile of dextromethorphan is affected by episodic and sporadic abuse. In fact, abuse appeared to be the most significant hazard identified by analysis of spontaneous adverse event reporting. No evidence could be found that the well documented pharmacokinetic polymorphism observed with dextromethorphan is correlated with any clinically significant safety risk if it is used for short term treatment. In summary, the safety profile of dextromethorphan is reassuring, particularly relating to overdose in adults and children.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  • Bazire S. MAOIs and narcotic analgesics. British Journal of Psychiatry 151: 701–701, 1987

    PubMed  CAS  Google Scholar 

  • Bickerman HA. Antitussive drugs. In Modell W (Ed.) Drugs of Choice 1984–1985, pp. 483–499, CV Mosby Company, St Louis, 1984

    Google Scholar 

  • Boeckx RL. False positive EMIT® D.A.U. phencyclidine assay as a result of an overdose of dextromethorphan. Clinical Chemistry 33: 974–975, 1987

    Google Scholar 

  • Bornstein S, Czermak M, Postel J. A propos a case of voluntary drug poisoning with dextromethorphan hydrobromide. Annals of Medical Psychology 1: 447–451, 1968

    CAS  Google Scholar 

  • Brosen K, Gram LF. Clinical significance of the sparteine/debri-soquine oxidation polymorphism. European Journal of Clinical Pharmacology 36: 537–547, 1989

    Article  PubMed  CAS  Google Scholar 

  • Browne B, Unter S. Monoamine oxidase inhibitors and narcotic analgesics. British Journal of Psychiatry 151: 210–212, 1987

    Article  PubMed  CAS  Google Scholar 

  • Chen ZR, Somogyi A, Bochner F. Dextromethorphan: pharmacogenetics, and a pilot study to determine its disposition and antitussive effect in poor and extensive metabolisers. European Journal of Clinical Pharmacology 183: 1573–1574, 1990a

    Article  Google Scholar 

  • Chen ZR, Somogyi A, Bochner F. Simultaneous determination of dextromethorphan and three metabolites in plasma and urine using high-performance liquid chromatography with application to their disposition in man. Therapeutic Drug Monitoring 12: 97–104, 1990b

    Article  CAS  Google Scholar 

  • Choi DW. Dextrorphan and dextromethorphan attenuate glutamate neurotoxicity. Brain Research 403: 333–336, 1987

    Article  PubMed  CAS  Google Scholar 

  • Eddy NB. The National Research Council involvement in the opiate problem: 1928–1971. National Academy of Sciences, Washington, D.C. 1973

  • Eichelbaum M. Genetic polymorphism of sparteine-debrisoquine oxidation. ISI Atlas of Science, pp. 243–251, ISI Press, Philadelphia, 1988

    Google Scholar 

  • Engbar TM, Chase TN. Dextromethorphan does not protect against quinolinic acid neurotoxicity in rat striatum. Neuroscience Letters 95: 269–274, 1988

    Article  Google Scholar 

  • Federal Register 484: 203, 1983

  • Fleming PM. Dependence on dextromethorphan hydrobromide. British Medical Journal 293: 597, 1986

    Article  PubMed  CAS  Google Scholar 

  • Guess HA. Limitations of available data on prescription drug safety. In Horisberger B & Dinkel R (Eds) The perception and management of drug safety risks, pp. 52–53, Springer-Verlag, New York, 1989

    Google Scholar 

  • Harrison WM, McGrath PJ, Stewart JW, Quitkin F. MAOIs and hypertensive crises: the role of OTC drugs. Journal of Clinical Psychiatry 50: 64–65, 1989

    PubMed  CAS  Google Scholar 

  • Henreting F, Cugini D, Durbin D, Kearney V, Voignier B, et al. Dextromethorphan (DM) overdose in children. Veterinary and Human Toxicology 30: 364, 1988

    Google Scholar 

  • Jasinski DR. Assessment of the abuse potentiality of morphinelike drugs (methods used in man). In Martin WR (Ed.) Drug addiction: I. Handbook of experimental pharmacology, Vol. 45, pp. 197–258, Springer-Verlag, Berlin, 1977

    Chapter  Google Scholar 

  • Jasinski DR. Morphine and nonaddicting analgesics: a current perspective. In Beers RF & Basset EG (Eds) Mechanisms of pain and analgesic compounds, Raven Press, New York, 1979

    Google Scholar 

  • Karttunen P, Tukiainen H, Silvasti M, Kolonen S. Antitussive effect of dextromethorphan and dextromethorphan salbutamol combination in healthy volunteers with artificially induced cough. Respiration 52: 49–53, 1987

    Article  PubMed  CAS  Google Scholar 

  • Katona B, Mason S, Weir JH. Dextromethorphan danger. New England Journal of Medicine 314: 993, 1986

    PubMed  CAS  Google Scholar 

  • Kupfer A, Schmid B, Pfaff G. Pharmacogenetics of dextromethorphan o-demethylation in man. Xenobiotica 16: 421–433, 1986

    Article  PubMed  CAS  Google Scholar 

  • Kupfer A, Schmid B, Prisig R, Pfaff G. Dextromethorphan as a safe probe for debrisoquine hydroxylation polymorphism. Lancet 2: 517–518, 1984

    Article  PubMed  CAS  Google Scholar 

  • Martin WR. General problems of drug abuse and drug dependence. In Martin WR (Ed.) Drug addiction I: Handbook of experimental pharmacology, Vol. 45, pp. 3–40, Springer-Verlag, Berlin, 1977

    Chapter  Google Scholar 

  • Matthys H, Bleicher B, Bleicher U. Dextromethorphan and codeine: objective assessment of antitussive activity in patients with chronic cough. Journal of International Medical Research 11: 92–100, 1983

    PubMed  CAS  Google Scholar 

  • McCarthy JP. Some less familiar drugs of abuse. Medical Journal of Australia 20: 1078–1081, 1971

    Google Scholar 

  • McElwee NE, Veltri JC. Intentional abuse of dextromethorphan (DM) products: 1985 to 1988 statewide data. Veterinary and Human Toxicology 4: 355, 1990

    Google Scholar 

  • McElwee NE, Veltri JC. Dextromethorphan exposures reported by emergency departments to the drug abuse warning network, 1987–1990. Journal of Clinical and Research Pharmacology 5: 167–168, 1991a

    Google Scholar 

  • McElwee NE, Veltri JC. Medical examiner reports of dextromethorphan exposures in the drug abuse warning network. Journal of Clinical and Research Pharmacology 5: 167, 1991b

    Google Scholar 

  • Meyer UA, Zanger UM, Grant D. Genetic polymorphism of drug metabolism. In Tesa B (Ed.) Advances in drug research, Vol. 19, pp. 197–241, Academic Press, London, 1989

    Google Scholar 

  • Musacchio JM, Klein M, Canoll PD. Dextromethorphan and sigma ligands: common sites but diverse effects. Life Sciences 45: 1721–1732, 1989

    Article  PubMed  CAS  Google Scholar 

  • Nakamura K, Goto F, Ray WA, McAllister CB, Jacqz E, Wilkinson GR, Branch RA. Interethnic differences in genetic polymorphism of debrisoquin and mephenytoin hydroxylation between Japanese and Caucasian populations. Clinical Pharmacology and Therapy 38: 402–408, 1985

    Article  CAS  Google Scholar 

  • Olney JW, Labruyere J, Price MT. Pathological changes induced in cerebrocortical neurons by phencyclidine and related drugs. Science 244, 1360–1362, 1989

    Article  PubMed  CAS  Google Scholar 

  • Orrell MW, Campbell PG. Dependence on dextromethorphan hydrobromide. British Medical Journal 293: 1242–1243, 1986

    Article  Google Scholar 

  • Perault MC, Bouquet S, Bertschy G, Vandel S, Chakroun R, et al. Debrisquine and dextromethorphan phenotyping and anti-depressant treatment. Therapie 46: 1–3, 1991

    PubMed  CAS  Google Scholar 

  • Pfaff G, Briegel P, Lamprecht I. Inter-individual variation in the metabolism of dextromethorphan. International Journal of Pharmaceutics 14: 173–189, 1983

    Article  CAS  Google Scholar 

  • Prince DA, Feeser HR. Dextromethorphan protects against cerebral infarction in a rat model of hypoxia-ischemia. Neuroscience Letters 85: 291–296, 1988

    Article  PubMed  CAS  Google Scholar 

  • Rammer L, Holmgren P, Sandler H. Fatal intoxication by dextromethorphan: a report on two cases. Forensic Science International 37: 233–236, 1988

    Article  PubMed  CAS  Google Scholar 

  • Reynolds EF (Ed). Martindale: the extra pharmacopoeia, 29th ed., p. 908, Pharmaceutical Press, London, 1989

    Google Scholar 

  • Rivers N, Horner B. Possible lethal reaction between Nardil and dextromethorphan. Canadian Medical Association Journal 103: 85, 1970

    PubMed  CAS  Google Scholar 

  • Schmid B, Bircher J, Prisig R, Kupfer A. Polymorphic dextromethorphan metabolism: co-segregation of oxidative O-de-methylation with debrisoquine hydroxylation. Clinical and Pharmacological Therapy 38: 618–624, 1985

    Article  CAS  Google Scholar 

  • Seventeenth Report of WHO Expert Committee on Drug Dependence, Technical Report Service WHO no. 437, 1970

  • Shamsie SJ, Barriga C. The hazards of use of monoamine oxidase inhibitors in disturbed adolescents. Canadian Medical Association Journal 104: 715, 1971

    PubMed  CAS  Google Scholar 

  • Shaul WL, Wandell M, Robertson WO. Dextromethorphan toxicity: reversal by Naloxone. Pediatrics 59: 117–119, 1977

    PubMed  CAS  Google Scholar 

  • Sinclair JB. Dextromethorphan-monoamine oxidase inhibitor interaction in rabbits. Journal of Pharmaceutics and Pharmacology 25: 803–808, 1973

    Article  CAS  Google Scholar 

  • Steinberg GK, Bell T. Clinical dose escalation safety study of the NMDA antagonist dextromethorphan in neurosurgical patients. Stroke 22: 141, 1991

    Google Scholar 

  • Tortella FC, Pellicano M, Bowery NG. Dextromethorphan and neuromodulation: old drug coughs up new activities. Trends in Pharmacological Sciences 10: 501–507, 1989

    Article  PubMed  CAS  Google Scholar 

  • Weisand MP, Meard D, Ferney DM. Neuropathology in the re-trosplenal cortex of rats after dextromethorphan administration. Society for Neuroscience Abstracts 16: 1116, 1990

    Google Scholar 

  • Younes RB. Exhilarant cough remedies. New England Journal of Medicine 280: 391, 1969

    PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Pharma Division, Drug Safety, F. Hoffmann-La Roche Ltd, Basel, CH-002, Switzerland

    Jerzy L. Bem & Richard Peck

Authors
  1. Jerzy L. Bem
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Richard Peck
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Bem, J.L., Peck, R. Dextromethorphan. Drug-Safety 7, 190–199 (1992). https://doi.org/10.2165/00002018-199207030-00004

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.2165/00002018-199207030-00004

Keywords

Search

Navigation