22 January 2006

Combination buprenorphine widely abused in New Zealand in early 1990s

Drug Alcohol Dependence (1993) 33;1:81-6


The misuse of buprenorphine and a buprenorphine-naloxone combination in Wellington, New Zealand. Robinson GM, Dukes PD, Robinson BJ, Cooke RR, Mahoney GN.



Dear Colleagues,

This 1993 study from Wellington, New Zealand, has relevance to us today with the recent approval of the buprenorphine combination product containing naloxone. According to my reading there have only been two published comparative studies of the combination product in recent years and neither compared unsupervised combination treatment with traditional methadone treatment. Nor did either examine community diversion in any systematic way. After TGA approval and PBS funding process, the States and Territories are responsible for introducing the combination into clinical practice (we are told from April 2006). An absence of good research evidence on the product led me to look into older literature for knowledge about the subject.

To his great credit, Dr Robinson saw an opportunity in 1991 to monitor a naturalistic experiment in Wellington, New Zealand when pure buprenorphine tablets were withdrawn and replaced with a combination product due to reports of abuse. The replacement combination product contained approximately the same quantity of naloxone (the modern version has only one quarter of this proportion). Owing to the widespread abuse of prescribed analgesics (and almost absence of heroin) in New Zealand in the early 1990s, the combination product was introduced in an attempt to make it unpopular with addicts. Although the analgesic tablet was only one tenth of the strength of the common 2mg tablet used for maintenance, it was dispensed in quantities of 50 in a pack (10mg total � 8.5mg naloxone).

What the article does NOT say is that shortly after publication, the combination drug was also withdrawn by the company after the widespread abuse including injecting reported here. After years in the 'therapeutic wilderness', I understand that NZ authorities have licensed the drug(s) again for addiction treatment, presumably with more formal assessments, structure and supervision this time around.

Robinson interviewed a sample of new methadone treatment applicants 12 months apart during which the pure product was withdrawn and replaced with the combination. This revealed the surprising original rate of 81% of patients had abused buprenorphine in the previous 4 weeks. The rate was still 57% 12 months later when only combination product was available in New Zealand (nearly all of these had used the combination drug intravenously). Both figures were corroborated with consistent urine tests, a testimony to Robinson�s thoroughness (it is not easy to get buprenorphine toxicology performed even now). At the same time, between the two surveys it apparently became easier to obtain the prescribed Reckitts' tablets, the proportion stating it was 'easy' rising from 35% to 52%.

Two thirds of patients who had injected the combination product reported no withdrawal reactions. One third reported possible withdrawals after injecting, yet this experience did not appear to discourage injecting generally and the drug was subsequently withdrawn. Thus the combination product appears to have been less popular with addicts but was still widely abused, albeit at lower levels. The lower street price reported may be been due to the naloxone, increased supply or lower demand (or a combination of the three factors).

There is now a burgeoning literature on diversion of prescribed opiates, both from Australia and overseas. Cicero writes in October�s New England Journal of Medicine that, after numerous provisos, �� its [buprenorphine combinations] availability as new product lines led to an almost immediate increase in buprenorphine use for nontherapeutic purposes.�). In recent cross-jurisdictional comparisons, both Ritter et al. from Australia and EMC from Europe found that there was little correlation between �take-away� policy and the extent of methadone or buprenorphine diversion reported across borders.

Clearly one way for us as dependency workers to address the issue of diversion is to ensure addicted citizens have access to appropriate, flexible treatments of high quality, including detoxification, maintenance as well as attention to other medical and social problems.

Comments by Andrew Byrne ..



References:



Fudala PJ, Bridge TP, Herbert S, Williford WO, Chiang CN et al. Office-Based Treatment of Opiate Addiction with a Sublingual-Tablet Formulation of Buprenorphine and Naloxone. NEJM (2003) 349:949-958

Cicero TJ, Inciardi JA. Potential for Abuse of Buprenorphine in Office-Based Treatment of Opioid Dependence. NEJM (2005) 353;17:1863-5

Cicero T, Inciardi J, Mu�oz A. Trends in Abuse of OxyContin� and Other Opioid Analgesics in the United States: 2002-2004. The Journal of Pain 2005 6;10:662-672

Inciadi JA, Surratt HL, Kurtz SP, Burke JJ. The Diversion of Prescription Drugs by Health Care Workers in Cincinnati, Ohio. Substance Use & Misuse 2005 41:255-264

Jenkinson RA, Clark NC, Fry CL, Dobbin M. Buprenorphine diversion and injection in Melbourne, Australia: an emerging issue? Addiction (2005) 100;2:197-205

Ritter A, Di Natale R. The relationship between take-away methadone policies and methadone diversion. Drug Alcohol Rev (2005) 24;4:347-352

Robinson GM, Dukes PD, Robinson BJ, Cooke RR, Mahoney GN. The misuse of buprenorphine and a buprenorphine-naloxone combination in Wellington, New Zealand. Drug Alcohol Dependence (1993) 33;1:81-6

Prevalence of buprenorphine misuse. EMCDDA2005 (web site accessed 22-1-06)