Feature Article

Codeine rescheduling and the GP


Longer-term treatment with buprenorphine–naloxone should be considered when there is a clear diagnosis of opioid dependence, including difficulty controlling use, continued codeine use despite harm, clear tolerance and withdrawal symptoms on cessation. For some people with codeine dependence, ongoing treatment with buprenorphine–naloxone or methadone has been lifesaving. 


Over the next few months, as patients present to their GPs requesting codeine or reporting previous OTC codeine use, careful assessment may identify unmanaged tolerance or opioid dependence. The change in codeine availability may provide an opportunity for better management of chronic pain conditions. Depending on the pattern of codeine use, different management strategies may be appropriate. For most patients who report infrequent codeine use, alternative nonopioid analgesia will be appropriate. Where patterns of high-dose use are identified, medication-assisted treatment in consultation with drug and alcohol experts may be required. Where the level of opioid tolerance and dependence is unclear, supporting the patient to cease codeine in the short term is recommended in the first instance.     MT




COMPETING INTERESTS: Dr Nielsen has been an investigator on projects supported by untied educational grants from Indivior, and has received travel expenses and/or received honoraria to speak on codeine dependence or related topics from Indivior, Pharmaceutical Society of Australia, TGA, Pharmacy Guild of Australia, Royal Australian College of General Practitioners, Primary Health Networks and Drug and Alcohol Networks around Australia. She is currently the recipient of an NHMRC Fellowship (#1132433).  Dr Wilson has been paid honoraria by Indivior to present educational activities. Associate Professor Clark and Dr Reynolds: None. 




1.    Alstadhaug K, Ofte H, Kristoffersen E. Preventing and treating medication overuse headache. Pain Rep 2017; 2: e612.
2.    Chang AK, Bijur PE, Esses D, Barnaby DP, Baer J. Effect of a single dose of oral opioid and nonopioid analgesics on acute extremity pain in the emergency department: A randomized clinical trial. JAMA 2017; 318: 1661-1667.
3.    Gasche Y, Daali Y, Fathi M, et al. Codeine intoxication associated with ultrarapid CYP2D6 metabolism. N Engl J Med 2004; 351: 2827-2831.
4.    Zhou SF. Polymorphism of human cytochrome P450 2D6 and its clinical significance: Part I. Clin Pharmacokinet 2009; 48: 689-723.
5.    Gowing L, Ali R, Dunlop A, Farrell M, Lintzeris N. National guidelines for medication-assisted treatment of opioid dependence. Canberra: National Drug Strategy; 2014.
6.    Nielsen S, Larance B, Degenhardt L, Gowing L, Kehler C, Lintzeris N. Opioid agonist treatment for pharmaceutical opioid dependent people. Cochrane Database Syst Rev 2016; (5): CD011117.
7.    Nielsen S, Macdonald T, Johnson J. Identification and treatment of codeine dependence: a systematic review. Med J Aust 2018. In Press.
8.    Mattick RP, Breen C, Kimber J, Davoli M. Buprenorphine maintenance versus placebo or methadone maintenance for opioid dependence. Cochrane Database Syst Rev 2014; (2): CD002207.
9.    Lofwall MR, Babalonis S, Nuzzo PA, Siegel A, Campbell C, Walsh SL. Efficacy of extended-release tramadol for treatment of prescription opioid withdrawal: a two-phase randomized controlled trial. Drug Alcohol Depend 2013; 133:  188-197.
10.    Sobey PW, Parran TV, Grey SF, Adelman CL, Yu J. The use of tramadol for acute heroin withdrawal. J Addict Dis 2004; 22: 13-25.
11.    Zarghami M, Masoum B, Shiran MR. Tramadol versus methadone for treatment of opiate withdrawal: a double-blind, randomized, clinical trial. J Addict Dis 2012; 31: 112-117.
12.    Dunn KE, Tompkins DA, Bigelow GE, Strain EC. Efficacy of tramadol extended-release for opioid withdrawal: a randomized clinical trial. JAMA Psychiatry 2017; 74: 885-893.
13.    Evans C, Chalmers-Watson TA, Gearry RB. Combination NSAID-codeine preparations and gastrointestinal toxicity. N Z Med J 2010; 123: 92-93.
14.    Van Hout MC, Horan A, Santlal K, Rich E, Bergin M. ‘Codeine is my companion’: misuse and dependence on codeine containing medicines in Ireland. Ir J Psych Med 2015; 1-14.
15.    Gowing L, Farrell M, Ali R, White JM. Alpha(2)-adrenergic agonists for the management of opioid withdrawal. Cochrane Database Syst Rev 2016; (5): CD002024.
16.    Gowing L, Ali R, White JM, Mbewe D. Buprenorphine for managing opioid withdrawal. Cochrane Database Syst Rev 2017; (2): CD002025.
17.    Nielsen S, Bruno R, Murnion B, et al. Treating codeine dependence with buprenorphine: dose requirements and induction outcomes from a retrospective case series in New South Wales, Australia. Drug Alcohol Rev 2015; 35: 70-75.
18.    Walsh SL, Preston KL, Bigelow GE, Stitzer ML. Acute administration of buprenorphine in humans: partial agonist and blockade effects. J Pharmacol Exp Ther 1995; 274: 361-372.
19.    Wesson DR, Ling W. The Clinical Opiate Withdrawal Scale (COWS). J Psychoactive Drugs 2003; 35: 253-259.


Dr Nielsen is a Senior Research Fellow at the National Drug and Alcohol Research Centre, UNSW Sydney; and a Pharmacist at South Eastern Sydney Local Health District Drug And Alcohol Services, Sydney. Dr Reynolds is Clinical Director of the Alcohol and Drug Service, Tasmanian Health Services, Hobart, Tas. Dr Wilson is a Staff Specialist at South Eastern Sydney Local Health District Drug And Alcohol Services, Sydney, NSW. Associate Professor Clark is Clinical Director of Drug And Alcohol Services South Australia, Adelaide, SA.