Home > Lofexidine and naloxone in the management of opiate dependence: increasing choice.

Long, Jean (2004) Lofexidine and naloxone in the management of opiate dependence: increasing choice. Drugnet Ireland, Issue 10, March 2004, p. 11.

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Opiate dependency continues to be a cause of morbidity and premature mortality among the inhabitants of the European Union. Although many treatment modalities have been used, methadone therapy (maintenance and detoxification) has proved most beneficial to date and is the mainstay of treatment in the Irish setting.

The Working Party at the National Medicines Information Centre at St James’s Hospital in Dublin were commissioned by the National Advisory Committee on Drugs to review the use of lofexidine and naloxone in the management of opiate dependence.

A systematic review was undertaken in order to evaluate the potential usefulness of lofexidine and naloxone treatment options in the management of opiate dependency.  All available data were retrieved by means of a comprehensive search of the published literature. Contact was made with experts nationally and internationally to evaluate the practical issues associated with use of these drugs in a clinical setting. The authors’ findings are presented by pharmaceutical agent. 


According tothe Working Party at the National Medicines Information Centre 1,evaluation of clinical trials data for lofexidine showed that it appeared to be at least as effective as clonidine and reducing doses of methadone, the other treatment regimens currently used in the treatment of opiate withdrawal. It was not possible to define the optimal dosage regimen for this indication because of the lack of data from clinical trials but, in general, incremental dosing was used reaching a maximum of around 2.2mg per day by day three or four, with gradual tapering-off to zero by day ten.

The authors also reviewed studies of its use in clinical practice and showed that it was considered as effective as clonidine for managed withdrawal but had a better safety profile (that is, lower number of cases experienced low blood pressure).  Experts have suggested that lofexidine detoxification requires intensive input from all members of the drug treatment team and should be followed up by further treatment to prevent relapse.  Although there were insufficient data to evaluate its use in specific subgroups, most workers have suggested that lofexidine was more effective in younger patients and those who had a shorter, less entrenched history of opiate use.

The authors reviewed the availability and, where data were available, treatment outcomes. 

In Dublin, three outpatient treatment centres and one inpatient facility were offering lofexidine to clients.  Staff at one of the outpatient centres recorded and analysed the treatment outcome data.  In total, 84 clients (98 cases) participated in the ten-day treatment regime between December 2000 and December 2002.  Successful detoxification was achieved if the client’s urine was free of opiates at the end of the programme.  Lofexidine was administered in conjunction with full medical and counselling support and patients were seen on a daily basis, including weekends.  Following successful detoxification, patients were offered naltrexone and counselling to prevent relapse.  The overall treatment completion rate for cases was 38 per cent (37/98).  Success was highest among those stable on methadone (8/10) and heroin smokers (13/33).  Cases that had not yet stabilised on methadone had a very low success rate (2/14).  There were no serious episodes of hypotension (low blood pressure). 

According to the authors, lofexidine may be useful as an additional treatment for managed opiate withdrawal in Ireland.


There are two clinical indications for the use of naloxone: to facilitate withdrawal for opiates and as part of the management of an opiate overdose.  The review of naloxone in the management of opiate withdrawals is presented here.  (A review of the use of naloxone in the management of overdose is presented elsewhere is this issue).

According tothe Working Party at the National Medicines Information Centre, 2naloxone had been used, with or without naltrexone, to effect rapid opiate withdrawal. Results of studies have shown that the withdrawal occured earlier and was more severe with use of naloxone compared with alpha2-adrenergic agents such as clonidine or lofexidine. However, it resolved more quickly leading to a quicker transition to maintenance antagonistic treatment. According to the authors, the long-term benefits of rapid withdrawal had not been compared with those from standard withdrawal regimens. Data were insufficient to identify the most appropriate dosage regimen.

The authors reported that a combination preparation of buprenorphine and naloxone (4:1 ratio) for sublingual use has recently been developed. It was shown to be effective as a maintenance treatment for opiate dependence, while the presence of naloxone reduced the risk of misuse of the buprenorphine component. Data were insufficient to identify the optimal treatment regimen. The combination was shown to be equipotent to buprenorphine alone. Subutex® is authorised for use in opiate dependence in Ireland, but there is no combination of buprenorphine and naloxone currently authorised.

There are no published data on the use of naloxone to effect rapid opiate withdrawal in Ireland. 


 1. National Medicines Information Centre (2003a) Use of Lofexidine in the Management of Opiate Dependence Syndrome. Dublin: National Advisory Committee on Drugs.

2. National Medicines Information Centre. (2003b) Use of Naloxone in the Management of Opiate Dependence Syndrome. Dublin: National Advisory Committee on Drugs. 

Item Type
Publication Type
Irish-related, Open Access, Article
Drug Type
Intervention Type
Treatment method
Issue Title
Issue 10, March 2004
March 2004
Page Range
p. 11
Health Research Board
Issue 10, March 2004
Accession Number
HRB (Available)

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