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Aaron Evans
Aaron Evans

Buy Diamorphine Ampoules

The United Kingdom is unusual internationally in that it is one of few countries able to prescribe diamorphine for the treatment of opiate dependence. Prescribing diamorphine has been part of the UK response to drug problems since the 1920s. Despite this, little is known about who receives diamorphine and how treatment is delivered. This study aims to describe the characteristics and treatment regimes of opiate-dependent drug users receiving a prescription for diamorphine in the United Kingdom in 2000, and report on their status in 2002. A retrospective case-note review was conducted in England and Wales. Two hundred and ten (72%; 210/292) patients' sets of case-notes were reviewed at 27 of the 42 (64%) drug clinics where diamorphine was prescribed by the doctor. Patients had been receiving a prescription for diamorphine for a median length of six years. The majority were unemployed white males, with a median age of 44 years. Illicit drug use and criminal activity, while low, had not been eliminated totally. The majority were prescribed ampoules and few had significant health problems. In some cases patients had been transferred to injectable diamorphine from injectable methadone to reduce injection related problems. There were wide variations in dose. The majority of patients had no serious drug, health or social problems. Diamorphine prescribing was a long-term commitment. The experience from the United Kingdom has been one of long-term prescribing with the aim of retaining patients in treatment and reducing the harms caused by illicit drug use. Prospective studies are needed to determine the long-term consequences of receiving a diamorphine prescription.

buy diamorphine ampoules

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Prior to starting treatment with opioids, a discussion should be held with patients to put in place a strategy for ending treatment with diamorphine hydrochloride in order to minimise the risk of addiction and drug withdrawal syndrome (see section 4.4).

Diamorphine is a potent opiate analgesic which has a more rapid onset of activity than morphine as the first metabolite, monoacetylmorphine, more readily crosses the blood brain barrier. In man, diamorphine has a half-life of two to three minutes. Its first metabolite, monoacetylmorphine, is more slowly hydrolysed in the blood to be concentrated mainly in skeletal muscle, kidney, lung, liver and spleen. Monoacetylmorphine is metabolised to morphine. Morphine forms conjugates with glucuronic acid. The majority of the drug is excreted via the kidney as glucuronides and to a much lesser extent as morphine. About 7-10% is eliminated via the biliary system into the faeces.

Physical incompatibility has been reported with mineral acids and alkalis and with chlorocresol. Mixtures of diamorphine with cyclizine, haloperidol or dexamethasone may result in precipitation. Mixtures of diamorphine and metoclopramide may become discoloured and should be discarded. Specialised references should be consulted for specific compatibility information.

Whilst unsupervised injectable methadone and diamorphine treatment has been part of the British treatment system for decades, the numbers receiving injectable opioid treatment (IOT) has been steadily diminishing in recent years. In contrast, there has been a recent expansion of supervised injectable diamorphine programs under trial conditions in a number of European and North American cities, although the evidence regarding the safety, efficacy and cost effectiveness of this treatment approach remains equivocal. Recent British clinical guidance indicates that IOT should be a second-line treatment for those patients in high-quality oral methadone treatment who continue to regularly inject heroin, and that treatment be initiated in newly-developed supervised injecting clinics.

However, in the past decade, the role of IOT for heroin dependence has been steadily diminishing in Britain. Injected methadone ampoules accounted for 8.7% of NHS opioid prescriptions for heroin dependence in England and Wales in 1995, but only 1.9% in 2003 [4]. In 1995, diamorphine accounted for two per cent of all opioid prescriptions for opiate dependence [5], and by 2000 this had fallen to approximately 1% [6]. Whilst exact numbers are unavailable, we estimate that in 2006, there are between 2,000 to 3,000 patients prescribed injectable methadone ampoules, and up to 500 patients prescribed diamorphine in the NHS for opioid dependence. This total number in IOT has remained relatively static over the past decade, with little 'turn-over' and few new patients commencing IOT. Yet during this same period there has been a marked expansion of numbers in opioid substitution (largely oral methadone and buprenorphine) treatment in Britain, from fewer than 50,000 to over 100,000, reflecting both a probable increase in the number of heroin users and the proportion in treatment. Thus, whilst the number of heroin dependent users and the number of patients entering substitution treatment in Britain appears to be steadily increasing over the past decade, the role of IOT has proportionally diminished, with few new patients commencing this form of treatment. The diminishing role of IOT in the UK may be due to a number of factors [6, 7]:

There have been several recent reviews of the evidence base for IOT [20, 21]. Three published RCTs have compared injectable diamorphine to oral methadone; and one has compared injectable methadone to oral methadone.

Hartnoll and colleagues [15] reported on treatment retention and self-reported heroin use in 96 heroin users entering treatment, randomised to either take-away diamorphine ampoules (n = 44), or oral methadone (n = 52). Overall, self-reported heroin use was comparable between the two groups. Whilst the injectable diamorphine group had significantly better treatment retention at 12 months, the majority continued to use illicit heroin in small amounts. In contrast, there was greater treatment drop out in the oral methadone group, and some patients stopped using illicit heroin, whilst others continued to use larger amounts of heroin. The results did not demonstrate a clear superiority for either treatment, and it was almost 20 years before the next controlled trial.

Perneger and colleagues ([12]) reported on the first RCT of supervised injectable diamorphine, in which 51 Swiss heroin users with a history of poor performance in prior methadone programs were randomised to either injectable heroin (n = 24) or oral methadone (n = 27). Treatment retention was high in both groups, and the heroin treatment group self-reported significantly less heroin use than the methadone group. However, a considerable proportion of those randomised to oral methadone responded well (33% achieving abstinence and 19% had very low levels of heroin use), and 38% of patients randomised to the oral methadone (wait list) Control group chose not to enrol in diamorphine treatment when available six months later. Initiating IOT would have been unnecessary (and costly) in this patient group.

The experience from this RCT led to an understanding that IOT should be seen as a 'second line' treatment approach, generally confined to those patients who are failing to respond to their current episode of methadone treatment. This was the basis for the next RCT [14] conducted by the CCBH in the Netherlands, in which 174 methadone patients with a history of regular heroin injecting were randomly allocated to either continue their oral methadone treatment (n = 98), or to commence injectable diamorphine (n = 76) (with oral methadone doses also available). Treatment retention was comparable, and the injectable diamorphine group were reported to have had a better global response in parameters such as social functioning, psychological health and criminality.

Of particular relevance to the British setting is the limited evaluation of injectable methadone treatment. The majority of IOT in the UK is in the form of injectable methadone, and yet there has been only one RCT of injectable methadone, a pilot study in which 40 heroin users entering treatment were randomly allocated to either equivalent doses of oral methadone or injectable methadone. There was no significant difference in treatment retention, illicit heroin use or other outcomes between the two groups [19]. The use of injectable methadone rather than diamorphine may have particular advantages (e.g. only one daily injection, less expensive) or disadvantages (e.g. side effects, inadequate substitute for heroin). Further research is required to establish the role of different injectable opioids.

The development of the Randomised Injectable Opioid Treatment Trial occurred as a response to calls from the Home Office to expand IOT in Britain [24], the need to better establish an evidence base for IOT, and to examine the role of injectable methadone and diamorphine treatment delivered under the conditions identified in new UK national guidance [25]. Specifically, the central question to be addressed is whether efforts should be made to optimise conventional treatment for such patients (e.g. encouraging high doses, supervised dosing, psychosocial interventions, and regular attendance) in order to reduce regular illicit heroin use, or whether such patients should be treated with injected methadone or injected heroin in newly developed supervised injecting clinics. To date, this has not been addressed in published RCTs of IOT.

The aim of the study is to examine the safety, efficacy and cost effectiveness of treatment with optimised oral methadone compared to injectable methadone or injectable diamorphine, for patients in maintenance treatment who continue to inject illicit heroin regularly. The trial is not designed to directly compare injectable methadone to injectable diamorphine treatment, which are both 'experimental' conditions. Hence, the research hypotheses for injectable heroin treatment are:

Injectable Diamorphine group: the dose conversions between oral methadone and injected diamorphine are based upon the work of Seidenberg and colleagues [34], developed for the Swiss, and more recently used by the German and Canadian heroin trials. The dose equivalence between oral methadone and diamorphine is not linear. At low doses, the conversion rate from oral methadone (total daily dose) to injected heroin (total daily dose) is approximately 1:3; whilst at higher doses, the conversion rate approximates 1:5. Other factors that impact upon methadone metabolism (e.g. concomitant medications, medical conditions) are taken into consideration at transfer. Doses are subsequently titrated and individualised with the aim of reducing illicit opiate use. Patients are encouraged to retain a small oral methadone dose (e.g. 20 to 40% of their initial dose) in order to prevent opiate withdrawal between injecting sessions, and to facilitate any transitions between oral methadone and injected diamorphine (effectively having a 'loading dose' of methadone). It is expected that most patients will use injected diamorphine doses in the range of 300 to 600 mg per day, with an upper total daily dose of 900 mg (450 mg per injection). Patients can also have up to 100 mg oral methadone supplementary to diamorphine, making their total oral methadone equivalent dose approximately 300 mg. 041b061a72


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