Guidance

Injectable opioid treatment: clinical and operational elements

Published 19 March 2021

Applies to England

Introduction

The clinical elements in this section of the guidance reflect practice and procedures as they evolved in the injectable opioid treatment (IOT) service at the South London and Maudsley NHS Foundation Trust (SLaM) as part of the Randomised Injectable Opiate Treatment Trial (RIOTT), and after its completion. Some aspects of developing the service have already been described in several research papers, including:

• Lintzeris and others on the methods of RIOTT
• Zador and others on groin injecting
• Strang, Groshkova and Metrebian on new heroin-assisted treatment
• Bell, van der Waal and Strang on a clinical perspective of supervised injectable heroin

This guidance also draws on the later evolution of the treatment.

Providers of IOT will be responsible for developing their own protocols and procedures, ensuring that these cover all eventualities and are fit for purpose. They will be responsible for ensuring their IOT service complies with legislation and guidance, and their commissioners will need to make sure that the services they commission are complying with the legislation and guidance.

Supervised IOT is designed to engage patients who have continued to inject street heroin despite being on optimised oral methadone or buprenorphine treatment. It involves supervised self-injection of pharmaceutical opioids (usually diamorphine), supplemented by oral opioid preparations (most commonly methadone solution but sometimes slow-release oral morphine and other opioids instead).

IOT is a highly structured, intensive treatment in which patients are closely monitored and regularly reviewed. The model of care has shown it to be clinically effective and safe. It usually involves starting treatment with twice-daily injecting, 7 days a week, under supervision of experienced nurses. Strang and others compared injectable treatment to oral treatment and Strang, Groshkova and Metrebian published an overview of the evidence for heroin-assisted treatment.

Supervision is required for safety, but is also important for providing the structure and support that contribute to the initial therapeutic efficacy of IOT. Clinical monitoring, empathic daily interaction, and clear clinic requirements and expectations are important elements of treatment as found by Bell and others in their paper on supervised injectable heroin.

Many patients do not need, and often do not want, such intense interaction long term. Supervised injecting, 7 days a week, twice a day, can interfere with plans for moving on from injecting drug use.

Once a patient’s initial injectable opioid dose is stabilised, there should be an early focus on stopping (or significantly reducing) their non-prescribed heroin use. Once the patient has stopped using street heroin, the focus usually shifts to gradually and cautiously reducing the frequency of injecting prescribed opioids. Reduced frequency of injecting is usually more important than reducing the dose since it helps a patient to return to a life without injecting.

Most patients in SLaM managed to reduce their frequency of injecting, initially to once daily then, gradually, to less than daily. Several long-term patients were injecting just 3 to 4 times a week and taking oral opioids on the other days. Some patients eventually managed to stop all injectable prescribing and were supported to return to full oral opioid maintenance. However, not everyone can follow this course, and not all at the same rate. In Europe many patients have achieved and sustained benefits on diamorphine and remain on a prescription of daily or twice-daily injectable medication for many years.

Eligibility criteria

When deciding who should receive IOT, you should consider the following eligibility criteria.

1. Age: you should provide IOT based on individual patient need so eligibility criteria will not usually include a fixed age range. But it would be unusual to start IOT on a patient younger than mid-20s.
2. Opioid injecting history: only patients with a significant history of injecting opioids and evidence of regular injecting opioid use in preceding months will usually be eligible.
3. Treatment history: only patients currently in unsuccessful optimised oral treatment and who have a history of unsuccessful attempts at such treatment will usually be eligible.
4. Other conditions: active, significant medical or psychiatric conditions can make IOT unsafe or interfere with the patient’s ability to engage in treatment, such as severe lung or liver disease, or severe and psychiatric illness.
5. Alcohol dependence and misuse of other GABA-ergic drugs including benzodiazepines, pregabalin or gabapentin, and zopiclone or zolpidem may make IOT unsafe for the patient, interfere with their ability to engage in treatment or disrupt it for others.
6. Pregnancy, breastfeeding, or plans to become pregnant may exclude patients, or at least require special attention, because of the effect the opioid would have on the foetus.
7. Willingness to participate: the patient must be able and willing to participate in the treatment schedule as required. This can include attending the clinic 2 to 3 times a day at the start of treatment and once a day, 7 days a week, for the rest of the time in treatment.

Initial assessment

You should schedule an appointment for an initial assessment for newly referred patients. At this meeting, you should provide comprehensive information about the programme.

Following this initial assessment, you can decide whether and when you might transfer the patient’s treatment to the IOT service, or whether you need further information about the patient.

Pre-IOT period

Before starting IOT, and if the IOT service is separate to the standard drug misuse service, patients who are eligible can have their OST dosing transferred to the IOT service. They can then be inducted onto injectables as long as they have:

• attended daily and have become familiar with the clinic’s routine
• taken a supervised and optimised oral dose daily for 4 to 5 days, without evidence of toxicity (patients on methadone doses of less than 60 milligrams (mg) a day will usually have their dose incrementally raised to 60mg or more in line with clinical guidance before starting diamorphine)
• provided at least one drug test positive for morphine
• had a negative pregnancy test (women only)

On confirming eligibility to start IOT, you should give the patient a start date for beginning injectable treatment. In preparation patients should receive an introduction to specific injecting procedures, including a comprehensive injecting assessment and plan.

Treatment stages

Treatment stages in IOT are defined according to the frequency of supervised injecting. The stages include:

• high frequency
• medium frequency
• low frequency

New patients will start at the high frequency stage in general, followed by the medium and low frequency stages. Transfer between the stages is subject to a patient achieving treatment goals as outlined in table 1.

Domain	High frequency	Medium frequency	Low frequency
Street heroin use	Frequent and regular	Nil or infrequent	Nil or infrequent
Benzodiazepine use	Prescribed or non-prescribed	Nil or infrequent	Nil or infrequent
Alcohol use	Dependent drinking or heavy binges	No misuse or managed	No misuse or managed
Street drug use	Frequent	Infrequent	Nil
Sedation or overdose	Recent (within past month)	Nil within past 3 months	Nil within past 3 months
Missed doses	Regular missed doses	No missed doses	No missed doses
Mental health	Concerns	Concerns or no concerns	No concerns
Physical health	Concerns	Concerns or no concerns	No concerns
Accommodation	Unstable	No concerns	No concerns

Table 1: Treatment stage checklist

Note: the patient will normally be expected to move from high frequency to low frequency.

High frequency

New patients start IOT at the high frequency stage. It is likely that patients will need to remain at this stage for at least the first 3 months of treatment or until they achieve satisfactory treatment outcomes. Some patients may choose to remain at this stage beyond the initial 3 months. The high frequency stage involves:

• optimising the injectable and oral opioid medication
• supervised self-administration of all doses of injectable (usually twice a day) and oral opioid medication on every day of the week
• usually no prescribing or dispensing of oral medication outside the clinic

The focus at the high frequency stage is on:

• stopping street heroin use
• stopping or stabilising benzodiazepine use that makes administering diamorphine unsafe
• stopping or controlling use of alcohol within NICE guidelines
• stopping other drug use that makes administering diamorphine unsafe or regularly prevents a dose of diamorphine being administered
• identifying other street drug use (such as stimulants) not directly interfering with diamorphine being administered, and planning to reduce it
• resolving structural problems that may affect the patient’s ability to adhere to the treatment requirements, such as a lack of stable accommodation or homelessness
• resolving immediate physical health problems that may interfere with treatment, including injecting-related harm
• resolving immediate mental health problems that may interfere with treatment

Medium frequency

This stage applies to patients who have stopped:

• using street heroin
• hazardous alcohol and drug use that interferes with the safe administration of diamorphine
• using other street drugs, or use them infrequently

Flexible dosing schedules will enable patients to reduce attendance for supervised injecting, but patients will still be injecting on most days of the week at this stage. There is no defined time frame for the medium stage. Medium frequency involves gradually reducing injecting frequency:

• from twice to once daily, unless already only attending once
• from all days to most days of the week

Oral opioid doses should be maintained at a therapeutic level while a patient reduces their injectable opioids. Supervised administration at a community pharmacy is optional depending on a patient’s progress in treatment.

The focus at the medium frequency stage is on:

• preventing relapse
• maintaining abstinence from street heroin use
• maintaining abstinence from hazardous drug and alcohol use
• working towards stopping other street drug use
• maintaining stable accommodation
• managing or maintaining physical and mental health
• exploring opportunities, such as for voluntary work, education, training or employment

Low frequency

Patients who have successfully completed the medium stage are encouraged to further reduce supervised injecting and then increase the number of days on oral opioid medication only. Low frequency involves:

• supervised administration of injectables on some days of the week
• mostly oral opioid medication

The focus at the low frequency stage is on:

• preventing relapse
• maintaining abstinence from street heroin use
• maintaining abstinence from hazardous drug and alcohol use
• stopping other street drug use
• managing or maintaining physical and mental health
• moving to collect oral doses from a community pharmacy and to take these unsupervised, and then moving out of IOT
• exploring options for detox or return to full oral substitution treatment
• engaging in voluntary work, education or employment

Treatment response and progress

As already mentioned, there is a clear goal of movement within IOT. New patients will start at the high frequency stage and, if they are responding well to treatment, they will be encouraged to progress to the medium and low frequency stages. For patients who have made this progress, a return to oral opioid maintenance may be an appropriate and achievable option to consider. However, not all patients will be able to follow this course and progress will not always be linear.

Some patients do not respond to IOT (for example when the patient continues to use street heroin regularly, or regularly uses other drugs or alcohol to a level that interferes with administering IOT) and do not progress beyond the high frequency stage. In those cases, you need to carefully consider whether IOT has added value compared to OST, or if returning to OST is more appropriate.

Some patients may not want to reduce injecting frequency or dose beyond a certain threshold because they are afraid of relapsing. For example, there are patients who reduced the frequency of their injecting to just 3 or 4 times a week but would not reduce further. Others may wish to remain on twice-daily injections.

There may be times when a temporary return to a higher stage of attendance is necessary, for example in case of a crisis. Once the crisis is resolved and the patient is ready, it may again be possible to reduce the frequency of attendance. If crises occur frequently then you need to consider if it may be counter-productive to keep trying to reduce the frequency of attendance and injecting.

Occasionally, the patient may request a temporary return to OST (for example, when going on holiday). If the patient is doing well and in the medium or low frequency stage, then, on their return, the patient can restart IOT at the same stage. But if the treatment team initiates the break for therapeutic or other reasons then the patient should return to the high frequency stage on restarting IOT.

Safety measures

Like other opioids, diamorphine is a potent respiratory depressant and patients administering a dose of diamorphine will typically see their SpO2 (blood oxygen level) fall below normal, sometimes for an extended period. This means it is critical to monitor them post-injection (ideally for up to half an hour) and to have overdose remedies readily available.

To reduce the risks of IOT, safety measures should be implemented. Safety in IOT is not just related to injecting and its immediate effects, but also to other factors, such as drug testing, regular clinical assessment, interaction with other healthcare providers and relevant pathology reports.

Direct safety measures might include:

• standard observation, by a suitably qualified professional, before and after injecting to reduce the risk of serious adverse reactions
• extended observation of vital signs (particularly breathing pattern and SpO2) during induction and at dose increases to ensure that patients are not subject to respiratory depression
• ensuring that the patient applies appropriate hygienic standard to prevent infections
• ensuring that the patient applies appropriate and competent injecting technique to prevent injecting related harm
• withholding injectables if any concerns have been identified at standard or extended observation
• initiating extended observations if any concerns have been identified after administering to ensure patient wellbeing
• point-of-care drug testing if there are concerns about presentation, to exclude use of contra-indicated medication and street drugs
• assessment of alcohol use and intoxication (with breath testing available if needed) before administering to reduce risk of respiratory depression

Indirect safety measures might include:

• random lab drug testing to monitor treatment efficacy and establish type and pattern of drug use (sample sent to pathology for street heroin testing)
• safe titration of diamorphine and oral opioid medication according to clinical guidelines
• prescribing adequate doses of oral opioids, supervised to ensure that patient takes the full dose daily (usually methadone doses of 60mg a day or greater but preferably 80 to 100mg a day)
• regular medical review
• regular planning of keywork sessions
• pregnancy testing for female patients
• electrocardiogram (ECG) for patients, especially if on doses of methadone equivalent to 100mg or more in oral solution
• baseline investigations, for example ECG, full blood count (FBC), electrolytes (sodium, potassium and chloride), urea, creatinine (EUC), liver function tests (LFTs), HIV and hepatitis screening (if recent results are not available)
• liaising with other involved healthcare providers and regularly communicating with the patient’s GP
• liaising with other agencies involved in the patient’s care

Standard observation

Before injecting

On arrival in the injecting room, usually 2 people (both staff or one volunteer) will observe the patient for any obvious contraindications to administering oral and injectable opioids and to check for signs of opioid withdrawal. Experienced clinical staff can usually do this quickly and unobtrusively in a conversation with the patient.

Potential contraindications include intoxication or sedation due to alcohol or drug use, or severe physical or mental health conditions.

After injecting

Following injection of diamorphine, staff will observe the patient briefly for signs of adverse reactions, like excessive sedation. Experienced clinical staff can usually do this by having a conversation with the patient.

A patient who is capable of a coherent conversation may be safe to leave within 5 to 10 minutes. But services usually prefer to have patients stay longer, perhaps up to half an hour, and in a separate, more relaxed, area than the injecting booth.

There is evidence by Tas and others in their paper on heroin‐induced respiratory depression that, even an hour after diamorphine dosing, some patients’ breathing and SpO2 have not returned to normal. Staff should usually ask patients to wait for longer if they appear impaired or sedated, especially if their dose has been changed.

Extended observation

Extended observation involves monitoring a patient’s:

• alcohol use
• vital signs (peripheral oxygen saturation, pulse and blood pressure)
• consciousness
• response to the diamorphine (drug effect) at specific time intervals (the objective and subjective effects)

All observations should be documented in line with local procedures (see procedures section).

Extended observation is required for patients:

• during the first week of IOT
• after their dose of injectable medication is increased
• if concerns have been identified at standard assessment
• if a serious adverse reaction occurred at the last dose
• if a serious reaction is observed immediately following injecting
• after missing a period of injectable treatment (for example, the patient has been on holiday and has been taking unsupervised oral medication for some time)

Side effects and adverse reactions

Patients can experience side effects and adverse reactions in IOT, mainly after injecting diamorphine. These reactions can be categorised based on 2 features.

1. How common the side effects are.

Common side effects and adverse reactions include localised transient red rashes, itchiness, swellings and transient sedation.

Rare side effects and adverse reactions include overdose, in which staff will need to monitor and treat patients with naloxone and oxygen.

2. How rare the side effects are.

Minor side effects and adverse reactions usually have no clinical concern.

Moderate side effects and adverse reactions require staff to monitor patients for up to half an hour after dosing.

Severe side effects and adverse reactions require staff to monitor patients after dosing and they may need to administer oxygen or naloxone.

If staff have serious concerns during standard or extended observation of the patient, either before or after injection, they should bring these to the attention of senior clinical staff. If there are serious concerns before injecting, staff should withhold medication until consultation with a prescriber has taken place.

Benzodiazepine and other GABA-ergic drug use

In general, supervised injection of diamorphine does not present a risk if the clinical safety measures are followed. However, IOT services have occasionally seen patients experience serious adverse reactions. This was often related to undisclosed benzodiazepine use (or other GABA-ergic drug use) before administration, which only became evident after injecting.

Undisclosed benzodiazepine or other sedative GABA-ergic drug use may present a problem for clinicians as patients may not show any signs of sedation before diamorphine administration. However, signs of sedation (‘gouching’, slurred speech and disinhibited behaviour) may be seen immediately afterwards in patients who have used benzodiazepines or pregabalin.

Patients who are still using illicit benzodiazepines can start IOT while they are on a reducing benzodiazepine prescription, as long as they are not intoxicated to the point of interfering with treatment.

Following a serious adverse reaction, patients will need an assessment by a competent medical professional, and a treatment review will take place. You may need to temporarily stop injectable prescribing until the assessment and review have taken place. If the assessment shows that risks outweigh benefits, you may have to permanently stop injectable prescribing.

Injecting assessment and plan

At the start of IOT, you will need to assess the patient’s injecting skills, injecting sites and any injecting-related complications. The outcome of this assessment will result in an individualised injecting plan, which you should document in the care plan. You should regularly review and update the injecting plan.

The plan will provide guidance on:

• injecting route (intravenous (IV), intramuscular (IM) or subcutaneous (SC))
• appropriate injecting sites
• injecting related harm (previous and current)
• injecting complications (for example collapsed veins, abscesses, ulcers and deep vein thrombosis (DVT))
• injecting practice
• equipment (for example needles and tourniquet size)

PHE’s ‘Wound aware’ guidance might be useful when you are assessing the patient and creating the injecting plan.

Supervision of injecting process

The injecting process is supervised to ensure that:

• the injection route complies with the injecting plan
• the injecting site is uncompromised (for example no evidence of local infection)
• adequate hygiene is applied
• the injection is competently administered
• the needle is suitable for the injecting route
• the full dose is injected and none is taken away
• no other drugs are taken at the same time
• sharps are safely disposed of

Patients will inject according to their individual injecting plan, but the choice of injecting route and sites will be subject to an additional daily assessment by the nursing staff. Patients may be advised to use a different route or site, for example in the case of evidence of local infection at the site (which should be treated).

Injecting route

Most new patients present with injecting related harm, for example collapsed veins, abscesses, scars or DVT. Some patients may use dangerous techniques at the time of referral, such as injecting in the groin or neck, which should be prohibited in the clinic. The options available to new patients are dependent on an assessment of injecting related harm and associated risks and injecting competency.

In theory, 3 injecting routes are possible:

1. Intravenous.
2. Intramuscular.
3. Subcutaneous.

Many patients in SLaM’s IOT clinic injected intramuscularly only. The clinic actively encouraged the use of intramuscular injecting. For most patients with vein damage, it was the default option if they wished to join the IOT programme.

Intravenous injecting

You can allow IV injecting if patients have shown good injecting skills, have good veins and show no evidence of injecting related complications.

However, injecting into deep veins is not permitted. Techniques such as inserting a needle at a 90° angle to access deep veins are also not allowed.

Clinic staff should not encourage IV injecting and they should not teach patients how to inject intravenously (though they can correct unsafe and damaging technique). If patients do intravenously inject they:

• must rotate veins
• should include IM injections (so if they were previously unfamiliar with the technique, staff will need to introduce them to it)
• are not allowed to ’dig’ for a vein repeatedly
• can only attempt IV injection once on each occasion (so if unsuccessful, and blood-contaminated, the syringe with diamorphine has to be discarded)

Intramuscular injecting

IM injecting should be encouraged over IV injecting because:

• it takes less time
• it is easy to instruct patients
• the risk of overdose is reduced
• it is less reinforcing than IV injection (for example, the hit is not quite as intense, the patient does not associate IM injecting with heroin)
• there is no risk of losing the diamorphine injection due to a failed injection attempt

Overall, feedback from patients about IM injecting from the RIOTT site was positive. Some considered it less stressful than attempting to inject intravenously, others commented that they preferred the slower onset of diamorphine compared to IV use.

Patients who are unfamiliar with IM injecting will need education and practical advice on suitable and safe sites for IM injections.

It is important that staff remind patients to rotate sites each time they inject. Repeated IM injections in the same site can result in hard and painful lumps which can interfere with administering the medication into the muscle.

Subcutaneous injecting

Patients with a history of SC injecting before starting IOT should be allowed to continue this if their technique is good and there are no complications. However, you should encourage patients to introduce IM injecting as a way of rotating sites.

Drug and alcohol use

Drug screens

Biological drug testing plays an important role in monitoring patients’ drug use, and in evaluating the treatment’s effectiveness.

You should use tests to differentiate street heroin from pharmaceutical heroin. You can do this by looking for markers of street heroin such as papaverine metabolites, noscapine and ATM4G.

Collecting samples

You should collect samples randomly and at a frequency reflecting the patient’s treatment intensity. So, samples for patients at a:

• high frequency stage should be collected weekly
• medium frequency stage should be collected weekly or fortnightly
• low frequency stage should be collected fortnightly or monthly

Point of care testing

At times it may be necessary to test for contraindicated substances before or after an injection, for example when the patient appears excessively sedated and an immediate result is needed.

Alcohol use

Alcohol use should be monitored at all stages of treatment. This may involve:

• a patient self-reporting use, as part of the Treatment Outcomes Profile (TOP)
• the Alcohol Use Disorders Identification Test (AUDIT)
• a clinician’s assessment
• pathology results (such as LFTs) and physical examination
• breath alcohol (BrAl) testing, if needed

You can apply a BrAl limit for administering opioid medication (oral and injectable) but a single, fixed limit for all patients is not advised.

If you suspect a patient is intoxicated or they are showing signs of intoxication, you should usually withhold diamorphine. You will need to repeat an assessment or test every 10 to 15 minutes until the result suggests it is safe to administer diamorphine. If the patient does not meet the conditions for administering diamorphine by the end of the session, you can give them oral opioid medication as long as they are not intoxicated (judged by an assessment or by a BrAl test).

If patients miss regular injectable doses due to alcohol use you should carry out a treatment review.

Medicines and regimens

Opioid medication regimens in supervised IOT in England consist of a combination of injectable opioids (mainly diamorphine, occasionally methadone) and long acting oral opioids (mainly methadone, under special conditions oral modified-release morphine).

If you include an adequate dose of long acting oral opioid medication as part of IOT, it can:

• prevent opioid withdrawal and cravings during the 24 hour period
• make it easier for occasional transitions between injectable opioids and oral opioids during periods when the patient does not attend for supervised dosing of injectables.
• help permanent transition to less frequent injecting.
• help the transition to oral substitution treatment.
• reduce the likelihood of symptomatic respiratory depression.

Opioid prescribing regimens

You can use 3 ‘flexible’ opioid prescribing regimens:

Regimen 1 involves patients attending twice daily for supervised injecting and administration of oral opioids.

Regimen 2 involves patients attending once daily for supervised injecting and administration or oral opioids. The oral opioid dose is slightly higher than in regimen 1 to compensate for the reduced dose of diamorphine.

Regimen 3 involves administering oral opioids only. The oral opioid dose is slightly higher than in regimen 2 to compensate for the absence of diamorphine.

The regimens offer a planned reduction of injecting frequency (also see section on treatment stages). You should routinely record weekly injecting regimens on the medication cards as part of treatment planning. Patients are expected to plan ahead for any change to the agreed regimen, although unforeseen circumstances can result in last minute changes.

If a patient requests a change to their regimen, you should consider their treatment stage and outcomes at the time of the request. If patients cannot attend at all and ask for oral medication only (regimen 3), you need to decide if this can be provided as a take home dose or dispensed under supervision at a local pharmacy.

Induction onto and optimisation of injectable diamorphine

The initial diamorphine dose is usually 50mg, though it may need to be lower if the patient’s recent regular drug use is uncertain. The following guidance is based on twice daily attendance.

1. For the first 2 days 50mg diamorphine is administered, then the dose can be increased (at intervals of 2 days or 4 attendances) in alternating increments of 20mg and 30mg (that is, increasing to 70mg on day 3, 100mg day 5, 120mg day 7) so long as the patient does not appear intoxicated after the dose and is happy to increase.
2. Doses should be increased beyond 120mg in patients continuing to inject street opioids and requesting an increase. As a precaution, dose increments are only planned for days when experienced staff are available.

An example of an induction dosing regimen based on twice daily attendance for the first 4 weeks is provided in table 2. In this example, methadone dose is also increased to hold the patient overnight, but this may not be necessary.

Day	Diamorphine (mg): morning	Diamorphine (mg): afternoon	Methadone (mg)
Monday	50	50	60
Tuesday	50	50	60
Wednesday	70	70	60
Thursday	70	70	60
Friday	100	100	60
Weekend – no dose change	100	100	60
Monday	120	120	70
Tuesday	120	120	70
Wednesday	150	150	70
Thursday	150	150	70
Friday	170	170	70
Weekend – no dose change	170	170	70
Monday	200	200	80
Tuesday	200	200	80
Wednesday	200	200	80
Thursday	200	200	80
Friday	200	200	80
Weekend – no dose change	200	200	80
Monday	200	200	90
Tuesday	200	200	90
Wednesday	200	200	90
Thursday	200	200	90
Friday	200	200	90

Table 2: IOT dose induction example

In general, there is little or no additional opioid effect from doses above 200mg per injection. However, sometimes patients ask for higher doses. Usually, if offered a trial period on doses of 230mg to 250mg per injection, patients will acknowledge that higher doses have little added effect.

Flexible dosing: diamorphine to methadone

Once patients reach a dose of diamorphine at which they feel comfortable, many choose to attend less frequently, reducing to once daily injecting and sometimes having days when they have oral methadone only.

When receiving only one injection daily (regimen 2) or no injection (regimen 3), patients receive more methadone to compensate for the reduced dose of diamorphine on that day. Table 3 suggests the appropriate adjustments, table 4 provides dosing examples.

	Methadone dose	Methadone dose
Regimen 1	60 to 80mg	More than 80mg
Regimen 2	+ 20mg (80 to 100mg)	+ 10mg (more than 90mg)
Regimen 3	+ 30mg (90mg to 110mg)	+ 20mg (more than 100mg)

Table 3: Flexible dosing adjustment – diamorphine to methadone

Examples	Regimen 1: diamorphine	Regimen 1: methadone	Regimen 2: diamorphine	Regimen 2: methadone	Regimen 3: methadone
1	am 200mg pm 200mg	80mg	200mg	90mg	100mg
2	am 150mg pm 150mg	80mg	150mg	90mg	100mg
3	am 100mg pm 100mg	80mg	100mg	90mg	100mg
4	am 50mg pm 50mg	70mg	50mg	80mg	90mg

Table 4: Dosing examples – diamorphine and methadone

Induction onto and optimisation of injectable methadone

Very occasionally patients request injectable methadone. A possible advantage is that methadone is much longer acting than diamorphine (more than 24 hours compared to less than 4 hours), which is more compatible with a once-daily injection schedule.

Most patients starting injectable methadone treatment will already be in oral methadone treatment. When inducting someone on oral methadone onto injectable methadone, the conversion ratio is 1.2 to 1. For example, 60mg oral methadone is equivalent to 50mg injectable methadone. So, if a patient has been on 60mg a day of oral methadone, they would initially be given 50mg of injectable methadone and no oral dose. You can increase the methadone dose at weekly intervals in increments of 10mg (given either as oral or injected methadone). Maintenance doses of injectable methadone are generally around 100mg per day.

Most patients on injectable methadone should only need once a day administration. However, some patients may benefit from a second methadone dose administered later in the day. This usually involves providing an oral methadone supplement (supervised or to take home for stable patients).

Induction onto and optimisation of oral opioids

Oral methadone

Before starting IOT, patients should be maintained on at least 60mg a day of methadone, with daily supervised consumption. Patients new to IOT, who have been on lower doses of methadone, or on unsupervised consumption, need at least 4 days of supervised methadone at 60mg a day before starting diamorphine.

In general, higher doses of methadone are to be encouraged. Methadone doses can be increased by 10mg increments at weekly intervals until around 100mg a day, at which point patients should have an ECG performed.

It is recommended that patients remain on supervised administration of oral methadone in the high frequency stage (see table 1). In the medium frequency and low frequency stages you can increase the patients’ access to take home doses or supervised dispensing at community pharmacies.

In SLaM, on non-injecting days, most patients preferred to have their methadone dispensed and observed at a pharmacy, rather than attending the injecting clinic, which was strongly associated in their minds with using diamorphine.

You may need to relax the requirement for observation when patients go on holidays (only for patients in the medium or low frequency stage), or if they have compelling reasons for being unable to attend the clinic on certain days.

Modified-release morphine sulfate

In some cases, you can prescribe a different type of opioid medication called modified-release morphine sulfate. This is authorised for treating pain in the UK but not for addiction treatment. It is often misused if consumption is not supervised. However, it is licensed in other countries and used successfully so you can consider it for off-label use. It is not made available to new patients and the case to prescribe must be considered on an individual basis according to the following criteria:

1. Patient preference.
2. Patient actively engaged in reducing injectables.
3. Patient considering moving to oral medication only.
4. Patient is not using excessive quantities of street drugs.
5. Patient is not misusing alcohol.
6. Patient agrees to supervised consumption.

Table 5 provides guidance on converting doses between methadone and modified-release morphine sulfate. This represents an initial conversion, but doses may need to be titrated depending on the individual patient’s response.

Oral methadone (mg)	Modified-release morphine sulfate (mg)
50	250
60	300
65	320
70	340
75	360
80	380
85	400
90	430
95	450
100	470

Table 5: Conversion of oral methadone to modified-release morphine sulfate

Note: Bond and others (2012) estimated a conversion ratio of 4.7 to 1.

Flexible dosing: diamorphine to modified-release morphine sulfate

Once patients reach a dose of diamorphine at which they feel comfortable, many seek to attend the clinic less frequently. This sometimes includes reducing their injecting to once daily and having days on modified-release morphine sulfate only.

When receiving only one injection daily (regimen 2) or no injection (regimen 3), patients receive additional modified-release morphine sulfate to ensure they are stable and suppress withdrawal symptoms for 24 hours. The additional modified-release morphine sulfate dose does not have to fully substitute for the morphine-equivalent dose of diamorphine administered when injections are given. However, these conversion ratios are a guide and doses may need to be adjusted according to the patient’s response.

	Modified release morphine sulfate dose	Modified release morphine sulfate dose
Regimen 1	300 to 380mg	More than 400mg
Regimen 2	+ 80 to 100mg (380 to 480mg)	+ 40 to 50mg (more than 440mg)
Regimen 3	+ 40 to 50mg (340 to 430mg)	+ 40 to 50mg (more than 440mg)

Table 6: Flexible dosing adjustment: diamorphine to modified release morphine sulfate

Note: Dosing has to take into account available capsules (such as 200mg, 150mg, 90mg, 60mg or 30mg) so, for example, a dose of 530mg is impossible to dispense.

Demonstration examples	Regimen 1: diamorphine	Regimen 1: modified release morphine sulfate	Regimen 2: diamorphine	Regimen 2: modified release morphine sulfate	Regimen 3: Modified release morphine sulfate
1	am 200mg pm 200mg	380mg	200mg	480mg	520mg
2	am 150mg pm 150mg	380mg	150mg	480mg	520mg
3	am 100mg pm 100mg	380mg	100mg	480mg	520mg
4	am 50mg pm 50mg	340mg	50mg	440mg	480mg

Table 7: Dosing examples - diamorphine or modified release morphine sulfate

Note: Dosing has to take into account available capsules (such as 200mg, 150mg, 90mg, 60mg or 30mg) so, for example, a dose of 530mg is impossible to dispense.

Monitoring efficacy

For the patient, an effective oral and injectable opioid dose regimen is defined by not using street heroin and not having withdrawal symptoms over 24 hours.

Patients who experience withdrawal symptoms before each dose are likely to benefit from increasing their oral opioid medication or their diamorphine dose. Increasing their oral opioid dose is more likely to prevent withdrawal symptoms between doses, whereas increasing their diamorphine doses is more likely to reduce use of or cravings for illicit heroin.

Patients who say they have had effective doses during the day, but complain of withdrawal symptoms at night or early morning before their first diamorphine dose, may benefit from an increase in their oral opioid dose (or converting some diamorphine dose to oral opioid medication).

Missed doses

Patients who erratically attend clinic for dosing are less likely to achieve optimal outcomes. More importantly, there are safety concerns in administering very large doses of injectables where the patient’s methadone ingestion has not been consistent.

In this situation, patients may have lower tolerance than expected. This is particularly the case where a patient fails to attend for methadone dosing for several days. The risk of overdose is greater in patients receiving large doses of heroin, especially when they frequently miss doses of their oral maintenance. So, for patients who miss their oral medication doses, the service could consider reducing their diamorphine dose.

The prescriber should review all patients who have missed 3 (or more) consecutive days of opioid medication before restarting their medication. Table 8 has a suggested dosing algorithm for patients who miss consecutive days of treatment.

The dose can be increased to the previous maintenance dose over subsequent days (using dosing increments discussed in section 10.2) if the clinician and patient think it is appropriate.

Patients who repeatedly miss doses should have their treatment plan reviewed.

Number of consecutive days missed	Diamorphine dose administered on resumption of treatment	Oral substitution dose administered on resumption of treatment
1	100%	100%
2	75%	100%
3	50%	50%
4 or more	Re-induct into treatment	Re-induct into treatment

Table 8: Responding to missed doses

Planned reduction of injecting frequency and dose

The recommended approach to reducing injecting is to reduce from twice daily to once daily injections. Initially this could be reduced on just 1 or 2 days per week Then you can reduce the total number of days injecting, while at all times maintaining oral medication at a therapeutic level.

It is important to appreciate that the time frame in which reduction takes place can vary and that patients have different reasons for wanting to reduce their injecting frequency. Requests for reducing injecting frequency should follow the treatment stages table (table 1).

Recommended dose reductions of diamorphine are in the range of 20mg to 30mg per injection. Reduction should be a gradual process and carefully planned and executed. During diamorphine reductions, you should not reduce the oral opioid maintenance dose unless it is part of the treatment plan. This is because it is intended to reduce the likelihood of withdrawal symptoms.

Other non-opioid medication

In addition to supervised administration of opioids it may be beneficial to administer other non-opioid medication in the clinic. For example this can include antidepressants, anticonvulsants, mood stabilisers, vitamins, TB therapy and hepatitis C treatment, especially if there are concerns about patient adherence.

You should pay attention to any risks of interactions between opioids and these medicines. See the clinical guidelines for more information on drug interactions.

Stopping treatment

Stopping treatment may be planned or unplanned, permanent or temporary, and can either involve stopping all prescribing or injectable opioids only. In the latter case, patients might stay in treatment at the clinic but are prescribed oral substitution only.

Temporary stop to all prescribing

In this case there is no prescribing of oral or injectable opioids by the clinic. For example, this could be when patients are admitted to a general or psychiatric hospital or are subject to a short-term custodial sentence. In both these cases patients will be under the care of hospital or prison doctors. The IOT service should provide details of the patient’s medication regimen 3 (oral only).

When the patient returns to the clinic, the normal safety procedures will apply if injectables are re-introduced.

Temporary stop to injectable prescribing

In this case prescribing of injectable opioids is stopped temporarily but the patient is still maintained on oral substitution opioids by the clinical team. This may be needed for example in the case of safety concerns, therapeutic reasons or short holiday breaks.

Permanently stopping injectable prescribing

In this case, patients will be transferred back to standard treatment services when they permanently stop injectable prescribing. Reasons for stopping injectable prescribing include:

• having a successful treatment outcome and returning to standard OST
• having an unsuccessful treatment outcome on IOT
• voluntarily withdrawing from IOT
• medical concerns (such as pregnancy)
• dropping out (no contact for more than 28 days)
• a custodial sentence longer than 28 days
• safety concerns (for example, the patient using in a risky way, or of there are safety concerns for staff or other service users)