Guidance

Injectable opioid treatment: commissioning and developing a service

Published 19 March 2021

Applies to England

The name of the treatment

The treatment covered by this guidance involves medically supervised, prescribed, injectable doses of an opioid substitute (usually diamorphine) for the treatment of opioid use disorder.

In different places and at different times this sort of treatment (and variations on it) has had different names, all with different issues which are described in acknowledgements and appendices. For the purposes of this guidance, we considered many alternatives but decided to use the widely used and well-understood term, injectable opioid treatment or IOT.

The nature of the treatment

The general principles of good clinical management of drug misuse and dependence, and the particular principles for opioid substitution treatment (OST), apply equally to IOT. These are described extensively in Drug misuse and dependence: UK guidelines on clinical management (also called the Orange Book).

There are particular and additional considerations for providing an intensive treatment with an injectable opioid, but the Orange Book should be the reference for any issues not covered in this guidance.

Assessing local need for IOT

When assessing local need for IOT, you should be clear about what outcomes you want to achieve, and that the evidence supports IOT as the service that can achieve these outcomes.

Some areas propose to introduce IOT with the goal of reducing crime, but this should be seen as a secondary benefit of providing a clinical service whose primary aim is improving health outcomes.

Reasons for wanting to provide IOT may include:

• achieving improved outcomes for people with long term opioid use and complex problems
• reducing the harm associated with injecting drug use for people who are in treatment but continue to inject illicit opioids
• reducing blood-borne virus transmission and injection-site damage and infections
• tackling opioid related deaths in areas where they are especially high
• engaging populations with major health needs that are not currently in standard oral OST and are unwilling to enter or return to such treatment

IOT should be viewed as an additional option in an optimised treatment system, not as a fix for systems that are inadequate or ineffective. Some patients will need long term treatment, so planning and funding commitments should be based on this expectation.

Financial considerations for IOT

Costs to be met

IOT is more expensive than oral OST and you will need to consider a wide range of costs before commissioning and providing IOT. These additional costs will come on top of the usual costs of running a drug treatment service.

Premises

Extra costs for premises include:

• buildings that meet Home Office requirements
• Home Office licence fees
• safe, secure storage for medication
• physical and video security
• space for preparation of medicines
• space and furniture for pre-injection handwashing, for injecting and for post-injection monitoring
• space to provide ancillary support, such as physical healthcare, counselling and advice
• alarm system for patient and staff safety

Equipment

Extra costs for equipment include:

• Home Office-approved controlled drugs cabinet and installation
• fridge with suitable lock or locked cabinet inside, as agreed with police
• laminar flow cabinet, if needed for sterile preparation
• vein finder
• pulse oximeter
• oxygen, defibrillator and emergency bag
• supplies for medicines preparation and injecting
• recording systems for attendance and medication

Staff

Extra costs for skilled staffing to safely cover 7 days a week of at least twice-daily supervised dispensing and injecting, include:

• medical staff, including doctors licensed to prescribe diamorphine
• nursing staff
• pharmacy staff
• administration and reception staff

Medicines

Extra costs for medicines include:

• oral and injectable OST
• emergency medicines, such as naloxone

Testing

Extra costs for testing include:

• biological testing for drugs at the point-of-care and in a laboratory
• alcohol breathalyser
• microbiological testing of operator, environment and reconstituted injectable medicines

Monitoring and evaluation

An IOT service will also have extra costs for monitoring and evaluating the service and its outcomes.

Cost effectiveness of IOT

When deciding whether to commission IOT, you may consider a range of factors, including whether it is likely to be more cost-effective than offering only mainstream OST. This question is complicated. Although several randomised control trials (RCTs), including the Randomised Injectable Opiate Treatment Trial (RIOTT), have found IOT to be more clinically effective than oral methadone (and, by extension, oral buprenorphine), for some patients who have not benefited from oral treatment, research summarised by Strang, Groshkova and Metrebian found it incurs higher intervention costs.

There are also different perspectives on which other costs should be included in cost-effectiveness calculations and the perspective used may have a large effect on the result. Two studies that looked at short-term cost-effectiveness found IOT to be less cost-effective than oral methadone if counting only health and social services costs. Both studies reported IOT as more cost-effective than oral methadone if using a broad perspective of cost-effectiveness that includes the costs borne by victims of crime. However, researchers have encountered methodological challenges, particularly on measuring costs related to crime, which are reflected in the limitations of the studies.

Variability in costs and how to reduce them

The cost of delivering IOT can vary considerably. Public Health England’s (PHE) experience of working with IOT services that no longer operate suggests the following factors may be important in keeping costs low:

1. Making efficient use of premises and staff time. Offering IOT through a standalone clinic is likely to be more expensive than doing so as a prescribing option within mainstream services.
2. Achieving planned capacity. The design of services should be informed by a robust assessment of the level of local demand or they may be unable to operate near their capacity, resulting in higher per-person costs.
3. Quickly identifying and transferring patients not responding to IOT, back to standard OST. Not everyone who meets the suitability criteria for referral to IOT responds to it. A clinical decision needs to be made, usually with the patient, to end the more expensive treatment if no significant benefit is being achieved from it.

IOT medications are available in single dose and multi-dose products, with the latter being cheaper per milligram (mg). So, using multi-dose products may seem likely to reduce costs. However, multi-dose products will likely need aseptic preparation by a pharmacist, which may make this a more expensive option than using single dose ampoules (which can be prepared for immediate use by a nurse).

The reduction in costs borne by victims of crime may be enough to make IOT cost-effective from a societal perspective, but decisions to fund it should be made with an understanding that doing so will involve a net cost to public sector budgets.

IOT service models

You should consider the nature of the IOT service and other services provided. Physical health care on-site is likely to be important for patients whose drug use has caused extensive damage. Mental health care will be important for patients with co-occurring mental health and alcohol or drug use conditions. Support for housing may be important if new patients are drawn from homeless populations. For more information, see the section on premises and the section on eligibility in the clinical and operational guidance.

It will also likely be appropriate to provide injecting equipment for patients who continue to inject street drugs. You should offer take-home naloxone to all patients, as well as having naloxone available on the premises.

You will need to consider the relationship between IOT and other drug treatment services. It may be necessary, such as for reasons of patient expectations or security, to keep oral OST and IOT patients and provision separate. But there may also be advantages in having the 2 services close, especially if each is drawing patients from the other. Co-location may reduce costs and will also allow the service to work together with other services such as hepatitis C treatment, housing support and smoking cessation.

Patient pathways

Pathways into and out of IOT should be clear. Pathways in should usually only be for patients currently receiving optimised OST (see chapter 4 in the clinical guidelines) and not achieving the desired benefit from it.

There should be clear criteria for assessing whether someone has benefitted from IOT and for deciding whether someone should leave treatment. There should also be clear pathways into other treatment or support, with protocols for transferring patients off injectables.

There should be clear pathways for patients who transfer quickly to another setting where IOT may not be available, such as prison, acute hospital or a psychiatric unit. IOT service staff should advise the receiving service on transferring patients from injectable opioids.

Eligibility for IOT

Supervised IOT is a second line treatment. Typically, before engaging in IOT, patients will have a significant treatment history of repeatedly failing to complete standard oral OST. This should include attempts to administer optimal, evidence-based doses of OST under supervision.

A detailed list of suggested eligibility criteria is in the operational and clinical guidance but should cover issues such as:

• age
• opioid injecting status and history
• treatment status and history
• medical or psychiatric conditions
• alcohol dependence and misuse of other GABA-ergic agents
• pregnancy, breastfeeding, or plans to become pregnant
• ability and willingness to take part for the duration of treatment as required

IOT has sometimes been seen as only suitable for people living in stable accommodation, but you should assess patients for suitability for IOT even if they are homeless.

Some European sites report that their IOT services worked well for some homeless people. But homeless people were a minority of the patient population in these sites (between 10% and 20%) and some met a technical definition of being homeless but were not sleeping rough.

Recent IOT sites in the UK focused on enrolling homeless service users who had been accessing oral OST and reported early success in improving their health and stability.

Fully supervised IOT and older ‘British system’ take-home IOT

A small number of patients already receive IOT on an unsupervised basis (under what is known as the ‘British system’ of opioid treatment, started in the early 1900s). Many of these patients have long-term chronic health problems and have been on this treatment for a long time. Clinical guidance is that the quality of care for these patients should be reviewed regularly and, where there is clear evidence of benefit, treatment should continue and be improved.

Stable patients on this long-term treatment are very different to the often high-risk, heavy drug-using and complex patients who might respond positively to supervised IOT.

There may be some challenges for service providers in continuing to provide for the small number of ‘British system’ patients while developing supervised-only IOT for new patients. These challenges need to be managed to protect the benefits to the ‘British system’ patients.

IOT service premises

You should carefully consider the location of any proposed IOT site, paying particular attention to:

• whether the intended patient group can access the service geographically
• whether the service should be close to, or separate from, other services that patients might also use or be referred to or from
• safety and security of staff, patients and controlled drugs

You will need a Home Office licence to hold controlled drugs on the premises. A licence will only be granted when compliance officers are satisfied that requirements for safety and security have been met. These are described in documents at the Home Office’s drugs licencing collection page. The compliance officers will look at site and building security, controlled drugs storage, and keys and locking mechanisms.

Licensing of doctors

Any doctor prescribing diamorphine to treat opioid dependence must be licensed by the Home Office on the advice, in England, of PHE (or its successor) clinicians (acting as proxy for the Department of Health and Social Care). Doctors can find more information about applying for a licence to prescribe diamorphine on the government’s domestic drugs licence page.

The licence will specify the premises from which the doctor is allowed to prescribe.

Only doctors on the Specialist Register of the General Medical Council (usually consultant psychiatrists specialising in addiction) will be approved to prescribe diamorphine without supervision. Other doctors may also be granted licences, but they will need to be supervised by a doctor who is on the Specialist Register and is also licensed. They will usually not be able to start patients on diamorphine or increase doses without the direct involvement of the supervisor.

Arranging licences to prescribe diamorphine in Scotland and Wales is different and should be checked early on in planning for an IOT service.

Staffing cover and competence

IOT services are designed to operate 7 days a week, 365 days a year. Some patients may choose to stop coming in at weekends, and take oral medication only on these days instead, but this should be an individual and flexible arrangement. No IOT service should be designed without weekend attendance. Minimum staffing with the required competences will need to be worked out and provided for. Some of the procedures (and staff) necessary to run an IOT service are governed by law or guidance, including:

• the 1968 Medicines Act and associated regulations and guidance
• Royal Pharmaceutical Society standards on safe preparation of injectable medications

These are not specifically focused on IOT but apply to all medicines. All providers of IOT need to be aware of the legislation and guidance and their implications for safely providing IOT.

Any IOT service should conduct a risk assessment and aim to meet the standards set out in the guidance. Guidance applies to all clinical services, whether they are commissioned or provided by the NHS or the local authority. The responsibility for regulating and inspecting these services (such as controlled drugs accountable officers, pharmacy and quality assurance leads) often lies outside local authorities, in NHS bodies.

Medical, nursing and pharmacy staff may all be required on site or within fast reach of the IOT service when it is operating.

Core minimum training beyond what is expected in a standard drug treatment service for all staff working in an IOT service might include:

• assessment of injecting sites
• management of overdose and emergency situations, including ability to provide resuscitation
• security processes
• controlled drug management and governance
• IT systems for patient records and dispensing

Staff preparing medicines may need training in aseptic preparation, and validation.

Broader profession-specific competences for drug treatment are described in the following documents.

The Royal College of Psychiatrists and the Royal College of General Practitioners has published ‘Delivering quality care for drug and alcohol users: the roles and competencies of doctors – a guide for commissioners, providers and clinicians’.

PHE’s ‘The role of addiction specialist doctors in recovery orientated treatment systems: A resource for commissioners, providers and clinicians’.

British Psychological Society’s ‘The contribution of clinical psychologists to recovery-orientated drug and alcohol treatment systems’.

PHE and the Royal College of Nursing have published ‘The role of nurses in alcohol and drug treatment services: a resource for commissioners, providers and clinicians’.

Patient safety and responding to incidents

You should make plans and develop protocols for ensuring patient safety and responding to incidents, especially overdose events. These should be in line with Resuscitation Council guidelines but, because of the nature of opioid overdose, will often focus more on the artificial ventilation (pulmonary) than chest compression (cardio) elements of CPR (cardiopulmonary resuscitation).

On-site provision will usually include:

• staff trained in Immediate Life Support (ILS) or equivalent
• a readily identifiable first aid box or bag (marked with a white cross, usually on a green background)
• an oxygen cylinder and non-rebreather face masks
• naloxone and any other appropriate emergency medication
• a defibrillator

In some settings an opioid overdose may not be noticed until some minutes after it started, and naloxone will need to be administered urgently. In IOT clinics overdose events are identified and responded to almost immediately. As a result, most IOT services report that overdoses are usually treated with oxygen only and rarely need other more intensive measures.

Patients who have overdosed and been treated should continue to be closely monitored in case overdose recurs.

The medicines and their administration

The guidance applies to any injectable opioid prescribed as substitution treatment. In England injectable diamorphine and injectable methadone have been used. There is also some interest in injectable hydromorphone though it is not currently licensed in the UK for addiction treatment. Oral medicines (usually methadone solution) are usually provided as part of the medication regimens for patients on IOT but this section focuses only on injectable medicines.

Products and sourcing

Single dose ampoules are generally recommended for injectable medicines. NHS England and NHS Improvement has confirmed that this is also the case for IOT medicines.

Ampoules are available containing 5mg, 10mg, 30mg, 100mg and 500mg diamorphine powder for solution for injection. These can be made up for immediate use by nurses. The Drug Tariff shows the current NHS prices for these.

Multi-dose products are also available that cost less per milligram of diamorphine but preparation of doses from these products will usually need to be done by a pharmacist in aseptic conditions.

Some multi-dose diamorphine products used in other countries do not have a marketing authorisation for the UK and would need to be imported and used by special arrangement. You should then follow the usual conditions and precautions for using an unlicensed medicine, which are outlined in appendix A3 in the clinical guidelines and the General Medical Council’s guidance on prescribing and managing medicines.

Storage and preparation

Services and commissioners need to make sure that the protocol, environment and procedures for making up solutions and daily injections meet the requirements of legislation, professional standards, and infection control standards.

These should cover:

• making up, capping and storing multi-dose vials if these are to be used
• making up daily injections, such as who, when, how and where they are kept if made in advance

Only pharmacists are allowed to make up medicines in advance of use (Medicines Act 1968).

The Nursing and Midwifery Council’s standards for medicines management says that nurses “must not prepare substances for injection in advance of their immediate use or administer medication drawn into a syringe or container by another practitioner when not in their presence” unless medications have been prepared in pharmacy and labelled for an individual patient. The definition of “immediate use” in these circumstances should be the natural interpretation, likely extending to a single IOT session but no longer.

General aseptic precautions should be the norm. Although European sites often use multi-dose vials for multiple patients with nurses making up doses, the UK has stricter controls on reconstituting and storing medicines for injection.

General advice from NHS England and NHS Improvement is that multi-dose ampoules should be used for a single patient, dated on opening and only retained for as long as is indicated by the manufacturer’s recommended in-use storage time. Advice should be sought from the local lead for infection control.

You need to store controlled drugs that are not reconstituted in a suitable locked cabinet. Reconstituted medicines will usually have to be stored in a locked refrigerator.

If medicines are kept in a refrigerator, they should be removed ahead of drawing up and injection to avoid pain at the injection site.

Administration routes

Clinics should consider the injection routes they will encourage and permit. New patients will often have had difficulty accessing superficial veins and may have resorted to injecting in deep veins such as the groin or neck. This should not be permitted in an IOT service, which will limit patients to using sites described in the operating procedures guidance.

Intravenous injection more generally may not be necessary since drugs of known strength and quality are being supplied. Intramuscular or subcutaneous injection may be a preferred and recommended route as long as the patient’s injecting technique is adequate. For more information on injecting see the clinical and operational guidance.

After a patient has been in IOT for a week or so, clinics might want to introduce a limit on the time spent on trying to inject intravenously, or the number of attempts. After this limit, you should encourage intramuscular injection.

Dosing amount and frequency

Although treatment should always be tailored to the individual, clinics will usually benefit from a range of pre-prepared medication schedules specifying the average doses and frequency of injectable medicines and oral ‘background’ OST. Suggested regimens are in the clinical and operational guidance.

Patients should not usually be allowed to take any other drugs or medicines at the same time as they take their diamorphine.

Drug testing for treatment effectiveness and adherence

IOT services will want to assure themselves that patients’ use of street heroin is reduced or ended by the treatment they provide. So, biological testing will need to distinguish between the prescribed diamorphine and street heroin. The markers for street heroin vary depending on how it has been manufactured.

Research by Paterson and others on detecting illicit heroin use in patients showed that papaverine (or its metabolites) could be successfully used as a marker for street heroin.

Testing for other chemicals associated only with illicit heroin production may help to differentiate the use of street heroin from prescribed diamorphine. Research by Maas and others on confirming recent heroin use found that these chemicals include 6-monoacetylmorphine, acetylcodeine and codeine, noscapine and ATM4G, although codeine and derivatives may be detected because the patient took codeine.

The combination to be tested for may need to be determined locally according to the particular characteristics of the local heroin supply.

It may be most effective and cost-effective to test for a wide range of chemicals initially before narrowing down to a handful of proven heroin ‘indicator’ chemicals that will be regularly tested for.

However, heroin supplies change, so the chemical constituents may change, and it will be necessary to repeat the broad chemical test occasionally to check the validity of any narrower testing.

It may also be appropriate to test for the intentional or inadvertent (through their addition to illicit heroin) use of other opioids, including dihydrocodeine, oxycodone and fentanyl.

All these approaches will require the services of a competent laboratory rather than relying on point-of-care tests, though these may still be useful for testing for other drugs, such as benzodiazepines.

Informed consent

As for any treatment it is essential that IOT is fully explained to patients to help them share in the decision-making. You should provide information to the patient as appropriate to their needs and preferences. Patients should be assessed as competent to give their informed consent to the agreed treatment, and that consent should be documented.

Risk assessment

Extensive risk assessments will be needed for any proposed IOT service, covering many of the issues described above. A specific pharmacy risk assessment might include:

• compliance with Medicines Act (Section 10) exemption requirements and associated guidance and sterility assurance of diamorphine dispensed or supplied by the IOT service
• identification and appropriate management of patients receiving diamorphine from the IOT service if they are admitted to NHS or other services (such as an acute hospital admission via A&E)
• sustainability of pharmacy service
• sustainability of diamorphine supply
• supply of supplementary medicines from the IOT service (as there is potential for reduced levels of scrutiny, checks and duplicate supplies)
• patient identification before receiving medication in the IOT service