Over-the-Counter Codeine—from Therapeutic Use to Dependence, and the Grey Areas in Between

Part of the Current Topics in Behavioral Neurosciences book series (CTBN, volume 34)


Codeine is a widely used analgesic, that is available for sale in pharmacies over the counter (OTC) in a number of countries including the UK, South Africa, Ireland, France and Australia. In these countries with OTC codeine sales there has been emerging concerns about misuse of and dependence on codeine containing combination analgesics, with increasing numbers of people presenting for help with codeine dependence at primary care and addiction treatment services. This has led to many countries reviewing availability of codeine in OTC available preparations, and considering possible measures to reduce harms from misuse of OTC codeine containing combination analgesics.


Codeine Dependence Opioid use disorder Analgesic Abuse 


Funding Acknowledgement

Suzanne Nielsen is supported by NHMRC fellowship (#1013803). The National Drug and Alcohol Research Centre at the University of NSW is supported by funding from the Australian Government under the Substance Misuse Prevention and Service Improvements Grant Fund. Research leading to these results has received funding from the European Community’s Seventh Framework Programme FP7/2007–2013 under Grant Agreement No 611736.


  1. Agyapong VIO, Singh K, Savage M, Thekiso TB, Finn M, Farren CK et al (2013) Use of codeine-containing medicines by Irish psychiatric inpatients before and after regulatory limitations on their supply. Ir J Psychol Med 30(01):7–12CrossRefGoogle Scholar
  2. Allotey P, Reidpath DD, Elisha D (2004) “Social medication” and the control of children: a qualitative study of over-the-counter medication among Australian children. Pediatrics 114(3):e378–e383CrossRefPubMedGoogle Scholar
  3. Armstrong DJ (1992) The use of over-the-counter preparations by drug users attending an addiction treatment unit. Br J Addict 87(1):125–127CrossRefPubMedGoogle Scholar
  4. Arora S, Roxburgh A, Bruno R, Nielsen S, Burns L (2013) A cross-sectional analysis of over the counter codeine use amongst an Australian sample of people who regularly inject drugs. Drug Alcohol Rev 32(6):574–581CrossRefPubMedGoogle Scholar
  5. Babalonis S, Lofwall MR, Nuzzo PA, Siegel AJ, Walsh SL (2013) Abuse liability and reinforcing efficacy of oral tramadol in humans. Drug Alcohol Depend 129(1–2):116–124CrossRefPubMedGoogle Scholar
  6. Baratta JL, Gandhi K, Viscusi ER (2014) Limited evidence that single-dose oral ibuprofen plus codeine is more effective for postoperative pain than either drug alone. Evid Based Nurs 17(2):51–52CrossRefPubMedGoogle Scholar
  7. Bateman C (2013) Is your prescribing serving a hidden addiction? S Afr Med J 103(6):359–361CrossRefPubMedGoogle Scholar
  8. Boyd CJ, McCabe SE (2008) Coming to terms with the nonmedical use of prescription medications. Subst Abuse Treat Prev Policy 3(1):22CrossRefPubMedPubMedCentralGoogle Scholar
  9. Butler R, Sheridan J (2010a) Innocent parties or devious drug users: the views of primary healthcare practitioners with respect to those who misuse prescription drugs. Harm Reduction J 7(1):21Google Scholar
  10. Butler R, Sheridan J (2010b) Innocent parties or devious drug users: the views of primary healthcare practitioners with respect to those who misuse prescription drugs. Harm Reduction J 7:21Google Scholar
  11. Casati A, Sedefov R, Pfeiffer-Gerschel T (2012) Misuse of medicines in the European union: a systematic review of the literature. Eur Addict Res 18(5):228–245CrossRefPubMedGoogle Scholar
  12. Chee E, Schneberger S (2003) British Colombia’s pharmanet project. University of Western Ontario, LondonGoogle Scholar
  13. Chetty R, Baoku Y, Mildner R, Banerjee A, Vallance D, Haddon A et al (2003) Severe hypokalaemia and weakness due to Nurofen(R) misuse. Ann Clin Biochem 40(4):422–423Google Scholar
  14. Cooper RJ (2011) Over-the-counter medicine abuse—a review of the literature. J Subst Use 18(2):1–26Google Scholar
  15. Cooper RJ (2011) ‘Respectable addiction’—a qualitative study of over the counter medicine abuse in the UKGoogle Scholar
  16. Cooper RJ (2013a) ‘I can’t be an addict. I am.’ Over-the-counter medicine abuse: a qualitative study. BMJ Open 3(6):e002913Google Scholar
  17. Cooper R (2013b) Surveillance and uncertainty: community pharmacy responses to over the counter medicine abuse. Health Soc Care Community 21(3):254–262CrossRefPubMedGoogle Scholar
  18. Dayer P, Desmeules J, Leemann T, Striberni R (1988) Bioactivation of the narcotic drug codeine in human liver is mediated by the polymorphic monooxygenase catalyzing debrisoquine 4-hydroxylation (cytochrome P-450 dbl/bufI). Biochem Biophys Res Commun 152(1):411–416Google Scholar
  19. Dhital R, Whittlesea CM, Norman IJ, Milligan P (2010) Community pharmacy service users’ views and perceptions of alcohol screening and brief intervention. Drug Alcohol Rev 29(6):596–602CrossRefPubMedGoogle Scholar
  20. Dutch MJ (2008) Nurofen plus misuse: an emerging cause of perforated gastric ulcer. Med J Aust 188(1):56–57PubMedGoogle Scholar
  21. Dyer BT, Martin JL, Mitchell JL, Sauven NC, Gazzard B (2004) Hypokalaemia in ibuprofen and codeine phosphate abuse. Int J Clin Pract 58(11):1061–1062CrossRefPubMedGoogle Scholar
  22. Ernest D, Chia M, Corallo CE (2010) Profound hypokalaemia due to nurofen plus and red bull misuse. Crit Care Resusc 12(2):109–110PubMedGoogle Scholar
  23. Evans C, Chalmers-Watson TA, Gearry RB (2010) Combination NSAID-codeine preparations and gastrointestinal toxicity. NZ Med J 23(1324):92–93Google Scholar
  24. Ferner RE, Beard K (2008) Over the counter medicines: proceed with caution. BMJ 336(7646):7694–7696CrossRefGoogle Scholar
  25. Fleming GF, McElnay MJ, Hughes CM (2004) Development of a community pharmacy-based model to identify and treat OTC drug abuse/misuse: a pilot study. Pharm World Sci 26(5):282–288Google Scholar
  26. Frei M, Nielsen S, Tobin C, Dobbin M (2010) Serious morbidity associated with misuse of over-the-counter codeine-ibuprofen analgesics: a series of 27 cases. Med J Aust 193(5):294–296PubMedGoogle Scholar
  27. French DP, James DH (2008) Reasons for the use of mild analgesics among English students. Pharm World Sci 30(1):79–85CrossRefPubMedGoogle Scholar
  28. Gourlay DL, Heit HA, Almahrezi A (2005) Universal precautions in pain medicine: a rational approach to the treatment of chronic pain. Pain Med 6(2):107–112CrossRefPubMedGoogle Scholar
  29. Hamer AM, Spark MJ, Wood PJ, Roberts E (2014) The upscheduling of combination analgesics containing codeine: the impact on the practice of pharmacists. Res Soc Adm Pharm 10(4):669–678Google Scholar
  30. Heather N, Bowie A, Ashton H, McAvoy B, Spencer I, Brodie J et al (2004) Randomised controlled trial of two brief interventions against long-term benzodiazepine use: outcome of intervention. Addict Res Theory 12(2):141–154CrossRefGoogle Scholar
  31. Horsfield E, Sheridan J, Anderson C (2011) What do community pharmacists think about undertaking screening and brief interventions with problem drinkers? Results of a qualitative study in New Zealand and England. Int J Pharm Pract 19(3):192–200CrossRefPubMedGoogle Scholar
  32. Hughes GF, McElnay JC, Hughes CM, McKenna P (1999) Abuse/misuse of non prescription drugs. Pharm World Sci 21(6):251–255CrossRefPubMedGoogle Scholar
  33. International Narcotics Control Board (2012) Narcotic drugs estimated world requirements for 2012. Comments on the reported statistics on narcotic drugsGoogle Scholar
  34. Kahan M, Wilson L, Wenghofer EF, Srivastava A, Resnick A, Janecek E et al (2011) Pharmacists’ experiences with dispensing opioids: provincial survey. Can Fam Phys 57(11):e448–e454Google Scholar
  35. Khan N, Norman I, Dhital R, McCrone P, Milligan P, Whittlesea C (2013) Alcohol brief intervention in community pharmacies: a feasibility study of outcomes and customer experiences. Int J Clin Pharm 35(6):1178–1187CrossRefPubMedGoogle Scholar
  36. Kitabayashi Y, Ueda H, Narumoto J, Kita H, Nakamura K, Tsuchida H et al (2000) A case study of BRON (cough suppressant) tablet dependence–its social psychiatric and biological aspects. Japan J Alcohol Stud Drug Depend 35(5):295–305Google Scholar
  37. Kolodny A (2013) Better late than never: time to up-schedule hydrocodone combination products. Pain Med 14(11):1627–1628CrossRefPubMedGoogle Scholar
  38. Kypri K, Langley JD, Saunders JB, Cashell-Smith ML, Herbison P (2008) Randomized controlled trial of web-based alcohol screening and brief intervention in primary care. Arch Intern Med 168(5):530–536CrossRefPubMedGoogle Scholar
  39. LA Gudin J (2013) The downside of upscheduling. Pain Med 14(11):1628–1629CrossRefPubMedGoogle Scholar
  40. Le Roux K (2013) Marketing of CPS. S Afr Pharm J 80(5):43–47Google Scholar
  41. Leppert W (2011) CYP2D6 in the metabolism of opioids for mild to moderate pain. Pharmacology 87(5–6):274–285CrossRefPubMedGoogle Scholar
  42. Lessenger JE, Feinberg SD (2008) Abuse of prescription and over-the-counter medications. J Am Board Fam Med 21(1):45–54Google Scholar
  43. MacFadyen LED, McGowan T (2001) Community pharmacists’ experience of over-the-counter medicine misuse in Scotland. J R Soc Promot Health 121(3):185–192CrossRefPubMedGoogle Scholar
  44. Madadi P, Amstutz U, Rieder M, Ito S, Fung V, Hwang S et al (2013) Clinical practice guideline: CYP2D6 genotyping for safe and efficacious codeine therapy. J Popul Ther Clin 20(3):e369–e396Google Scholar
  45. Manchia M, Alda M, Calkin CV (2013) Repeated erythromycin/codeine-induced psychotic mania. Clin Neuropharmacol 36(5):177–178Google Scholar
  46. Matheson C, Bond C, Pitcairn J (2002) Misuse of over-the-counter medicines from community pharmacies: a population survey of Scottish pharmacists. Pharm J 269:66–68Google Scholar
  47. Maxwell JC (2011) The prescription drug epidemic in the United States: a perfect storm. Drug Alcohol Rev 30(3):264–270CrossRefPubMedGoogle Scholar
  48. McAvoy BR, Tobin CL (2014) Fatal misuse of codeine-ibuprofen analgesics in Victoria, Australia. Med J Aust 200(3):150–151CrossRefPubMedGoogle Scholar
  49. McAvoy BR, Dobbin MD, Tobin CL (2011) Over-the-counter codeine analgesic misuse and harm: characteristics of cases in Australia and New Zealand. NZ Med J 124(1346):29–33Google Scholar
  50. McBride AJ, Pates R, Ramadan R, McGowan C (2003) Delphi survey of experts’ opinions on strategies used by community pharmacists to reduce over-the-counter drug misuse. Addiction 98(4):487–497CrossRefPubMedGoogle Scholar
  51. McCabe SE, Boyd CJ (2005) Sources of prescription drugs for illicit use. Addict Behav 30(7):1342–1350CrossRefPubMedPubMedCentralGoogle Scholar
  52. McDonough MA (2011) Misuse of codeine-containing combination analgesics. Med J Aust 194(9):486PubMedGoogle Scholar
  53. Medani S, Short S, Wall C (2010) Nurofen plus toxicity—what should nephrologists be alert to? Rare complications of an increasingly misused medication. NDT Plus. 2010 May 11Google Scholar
  54. Medicines and Health Care Products Regulatory Agency (MHRA) (2009) Public assessment report. Codeine and dihydrocodeine-containing medicines: minimising the risk of addiction. MHRA, London (UK). Available from http://www.mhra.gov.uk/. Accessed 6 Oct 2013
  55. Murnion B (2010) Combination analgesics in adults. Austr Prescriber 33:113–115CrossRefGoogle Scholar
  56. Myers B, Siegfried N, Parry CD (2003) Over-the-counter and prescription medicine misuse in Cape Town–findings from specialist treatment centres. S Afr Med J 93(5):367–370PubMedGoogle Scholar
  57. Ng JL, Morgan DJ, Loh NK, Gan SK, Coleman PL, Ong GS et al (2011) Life-threatening hypokalaemia associated with ibuprofen-induced renal tubular acidosis. Med J Aust 194(6):313–316PubMedGoogle Scholar
  58. Nielsen S, Cameron J, Pahoki S (2010) Over the counter codeine dependence. Turning point alcohol and drug centre, Melbourne July 2010. Report NoGoogle Scholar
  59. Nielsen S, Cameron J, Lee N (2011) Characteristics of a non-treatment seeking sample of over-the-counter codeine users: implications for intervention and prevention. J Opioid Manag 7(5):363–370PubMedGoogle Scholar
  60. Nielsen S, Tobin C, Dobbin M (2012) Over the counter codeine: examining the evidence for and against. Austr Pharmacist 31(3):236–240Google Scholar
  61. Nielsen S, Cameron J, Pahoki S (2013) Opportunities and challenges: over the counter codeine supply from the codeine consumer perspective. Int J Pharm Pract 21(3):161–168CrossRefPubMedGoogle Scholar
  62. Nielsen S, Murnion B, Dunlop A, Degenhardt L, Demirkol A, Muhleisen P et al (2014) Comparing treatment-seeking codeine users and strong opioid users: findings from a novel case series. Drug Alcohol Rev 34(3):304–311Google Scholar
  63. Nielsen S, Roxburgh A, Bruno R, Lintzeris N, Jefferson A, Degenhardt L (2015) Changes in non-opioid substitution treatment episodes for pharmaceutical opioids and heroin from 2002 to 2011. Drug Alcohol Depend 149:212–219Google Scholar
  64. Nordmann S, Pradel V, Lapeyre-Mestre M, Frauger E, Pauly V, Thirion X et al (2013) Doctor shopping reveals geographical variations in opioid abuse. Pain Phys 16(1):89–100Google Scholar
  65. Nuesch E, Rutjes AW, Husni E, Welch V, Juni P (2009) Oral or transdermal opioids for osteoarthritis of the knee or hip. Cochrane Database Syst Rev (4):CD003115Google Scholar
  66. O’Donnell A, Anderson P, Newbury-Birch D, Schulte B, Schmidt C, Reimer J et al (2013) The impact of brief alcohol interventions in primary healthcare: a systematic review of reviews. Alcohol Alcohol 13:2013Google Scholar
  67. Orriols L, Gaillard J, Lapeyre-Mestre M, Roussin A (2009) Evaluation of abuse and dependence on drugs used for self-medication: a pharmacoepidemiological pilot study based on community pharmacies in France. Drug Saf 32(10):859–873CrossRefPubMedGoogle Scholar
  68. Otto CCB, Lohrmann I, Zahradnik A, Bischof G, John U et al (2009) Brief intervention in general hospital for problematic prescription drug use: 12-month outcome. Drug Alcohol Depend 105(3):221–226CrossRefPubMedGoogle Scholar
  69. Pates R, McBride A, Li S, Ramadan R (2002) Misuse of over-the-counter medicines: a survey of community pharmacies in a South Wales health authority. Pharm J 268:179–182Google Scholar
  70. Phokeo V, Sproule B, Raman-Wilms L (2004) Community pharmacists’ attitudes toward and professional interactions with users of psychiatric medication. Psychiatr Serv 55(12):1434–1436CrossRefPubMedGoogle Scholar
  71. Pilgrim JL, Dobbin M, Drummer OH (2014) Fatal misuse of codeine-ibuprofen analgesics in Victoria, Australia. Med J Aust 199(5):329–331CrossRefPubMedGoogle Scholar
  72. Reed K, Bond A, Witton J, Cornish R, Hickman M, Strang J (2011) The changing use of prescribed benzodiazepines and z-drugs and of over-the-counter codeine-containing products in England: a structured review of published English and international evidence and available data to inform consideration of the extent of dependence and harm. London: National Addiction Centre, King’s College London, and School of Social and Community Medicine, University of BristolGoogle Scholar
  73. Robinson GM, Robinson S, McCarthy P, Camero C (2010) Misuse of over-the-counter codeine-containing analgesics: dependence and other adverse effects. NZ Med J 123(1317):59–64Google Scholar
  74. Roumie CLGM (2004) Over-the-counter analgesics in older adults, a call for improved labelling and consumer education. Drugs Aging 21(8):485–498CrossRefPubMedGoogle Scholar
  75. Roussin A, Bouyssi A, Pouche L, Pourcel L, Lapeyre-Mestre M (2013) Misuse and dependence on non-prescription codeine analgesics or sedative H1 antihistamines by adults: a cross-sectional investigation in France. PLoS ONE 8(10):e76499CrossRefPubMedPubMedCentralGoogle Scholar
  76. Schatman ME, Darnall BD (2013) A practical and ethical solution to the opioid scheduling conundrum. J Pain Res 7:1–3CrossRefPubMedPubMedCentralGoogle Scholar
  77. Shand F, Campbell G, Hall W, Lintzeris N, Cohen M, Degenhardt L (2013) Real-time monitoring of Schedule 8 medicines in Australia: evaluation is essential. Med J Aust 198(2):80–81CrossRefPubMedGoogle Scholar
  78. Sheridan J, Wheeler A, Ju-Hsing Chen L, Chen-Yun Huang A, Nga-Yee Leung I, Yow-Chyi Tien K (2008) Screening and brief interventions for alcohol: attitudes, knowledge and experience of community pharmacists in Auckland, New Zealand. Drug Alcohol Rev 27(4):380–387Google Scholar
  79. Skurtveit S, Furu K, Borchgrevink P, Handal M, Fredheim O (2011) To what extent does a cohort of new users of weak opioids develop persistent or probable problematic opioid use? Pain 152(7):1555–1561CrossRefPubMedGoogle Scholar
  80. Sproule BA, Busto UE, Somer G, Romach MK, Sellers EM (1999) Characteristics of dependent and nondependent regular users of codeine. J Clin Psychopharmacol 19(4):367–372CrossRefPubMedGoogle Scholar
  81. Strobbe S (2014) Prevention and screening, brief intervention, and referral to treatment for substance use in primary care. Prim Care Clin Off Pract 41(2):185–213Google Scholar
  82. Toms L, Derry S, Moore RA, McQuay HJ (2009) Single dose oral paracetamol (acetaminophen) with codeine for postoperative pain in adults. Cochrane Database Syst Rev (1):CD001547Google Scholar
  83. UVUN (2011) The non medicinal use of prescription drugs. Discussion paper. ViennaGoogle Scholar
  84. Vallejo RBR, Wang VC (2011) Pharmacology of opioids in the treatment of chronic pain syndromes. Pain Phys 14(4):E343–E360Google Scholar
  85. Van Hout MC (2015) Nod and wave: an internet study of the codeine intoxication phenomenon. Int J Drug Policy 26(1):67–77CrossRefPubMedGoogle Scholar
  86. Van Hout MC, Bergin M, Foley M, Rich E, Rapca AI, Harris R et al (2014) A scoping review of codeine use, misuse and dependence, final report. Brussels: CODEMISUSED Project European Commission 7th Framework ProgrammeGoogle Scholar
  87. Vargas-Schaffer G (2010) Is the WHO analgesic ladder still valid? Twenty-four years of experience. Can Fam Physician 56(6):514–517Google Scholar
  88. Wawruch MKM, Foltanova T, Ondriasova E, Luha J, Dukat A et al (2013) Characteristics of elderly patients who consider over-the-counter medications as safe. Int J Clin Pharm 35(1):121–128CrossRefPubMedGoogle Scholar
  89. Wazaify M, Shields E, Hughes CM, McElnay JC (2005) Societal perspectives on over-the-counter (OTC) medicines. Fam Pract 22(2):170–176CrossRefPubMedGoogle Scholar
  90. Wazaify M, Hughes CM, McElnay JC (2006) The implementation of a harm minimisation model for the identification and treatment of over-the-counter drug misuse and abuse in community pharmacies in Northern Ireland. Patient Educ Couns 64(1–3):136–141CrossRefPubMedGoogle Scholar
  91. Wilk AI, Jensen NM, Havighurst TC (1997) Meta-analysis of randomized control trials addressing brief interventions in heavy alcohol drinkers. J Gen Intern Med 12(5):274–283CrossRefPubMedPubMedCentralGoogle Scholar
  92. Wilsey B, Prasad H (2012) Real-time access to prescription drug monitoring databases. CMAJ 184(16):1767–1768CrossRefPubMedPubMedCentralGoogle Scholar
  93. Wrobel JP (2003) Are we ready for the better medication management system? Med J Aust 178(9):448–450PubMedGoogle Scholar
  94. Zahradnik A, Otto C, Crackau B, Löhrmann I, Bischof G, John U et al (2009) Randomized controlled trial of a brief intervention for problematic prescription drug use in non-treatment-seeking patients. Addiction 104(1):109–117CrossRefPubMedGoogle Scholar
  95. Zhou SF (2009) Polymorphism of human cytochrome P450 2D6 and its clinical significance: part I. Clin Pharmacokinet 48(11):689–723CrossRefPubMedGoogle Scholar

Copyright information

© Springer International Publishing Switzerland 2015

Authors and Affiliations

  1. 1.National Drug and Alcohol Research CentreUNSWRandwickAustralia
  2. 2.South East Sydney Local Health District (SESLHD) Drug and Alcohol ServicesSurry HillsAustralia
  3. 3.Department of Health, Sport and Exercise Science, School of Health SciencesWaterford Institute of TechnologyWaterfordIreland

Personalised recommendations