Buprenorphine injection (Buvidal®) for opioid dependence

NICE evidence summary ES19 states “Buprenorphine prolonged-release injection may be an option where there is a risk of diversion of opioid substitution medicines or concerns about the safety of medicines stored at home. It may also be an option for people who have difficulties adhering to daily supervised opioid substitution medication, such as for people who are working or in education”.

Buprenorphine prolonged-release injection may have a place in treating opioid dependence in people in custodial settings, where the risk of diversion and time needed for supervised consumption currently leads to challenges in supplying supervised medicines safely.

The Scottish Medicines Consortium states: “Use in patients in whom methadone is not suitable and for whom the use of buprenorphine is considered appropriate”.

In a phase III study in patients with opioid dependence, subcutaneous buprenorphine was non-inferior to sublingual buprenorphine / naloxone for the mean percentage of urine samples with test results negative for illicit opioids”.

In line with Medication Assisted Treatment (MAT) standards, patients should be supported to make an informed choice on treatment.

• Buprenorphine is a partial opioid agonist. This means it only partially activates opioid receptors producing a milder, less euphoric and less sedating effect than full opioid agonists such as heroin, morphine and methadone. It has enough opioid activity to reduce cravings and prevent or alleviate opioid withdrawal in opioid dependent people.
  
  
• Buprenorphine has a higher affinity for opioid receptors than heroin, methadone and many other opioid drugs, meaning:
  • it can push other opioid drugs that are present in the body off the opioid receptors and take their place which may cause precipitated withdrawal (see: Drug interaction section).
  • at higher doses more of the opioid receptors are occupied, this will block or reduce the effects of other opioid drugs being administered at the same time.
  • patients may be less likely to use additional opioids on top of their buprenorphine prescription as they will gain little or no additional effect.
  • the analgesic effect achieved can be less than expected, if opioid pain relief is indicated.

• Has a ceiling effect and so continued dose increases will not result in a proportionate increase in effect.
• Has a lower risk of overdose than full agonists. Overdose can still occur particularly with polydrug use. The impact of prescribing other CNS depressant drugs alongside buprenorphine should be considered. Adverse effects such as sedation and respiratory depression should be monitored for and information on overdose and a supply of naloxone given.

The pharmacology of buprenorphine in Buvidal® injections is like that of oral buprenorphine products. The key differences are the route and vehicle. Parenteral products give better bioavailability, and the prolonged-release solution controls the rate of release allowing for reduced dose administration frequencies.

Buvidal® is a long-acting subcutaneous formulation of buprenorphine available in weekly (7 day) and monthly (28 day) depot-type preparations. Buvidal® is available as:

• 8mg, 16mg, 24mg and 32mg doses for WEEKLY (7 day) subcutaneous administration.
• 64mg, 96mg, 128mg & 160mg doses for MONTHLY (28 day) subcutaneous administration.

The mean half-life of weekly Buvidal® is 4 days and the monthly Buvidal® is 22 days.

• Weekly doses reach peak plasma levels after 24 hours
• Monthly doses reach peak plasma levels after 6 to 10 hours. The plasma concentrations will reduce slowly over time until the next administration. 

Buvidal® typically reaches steady state after the fourth dose (Day 22 for Buvidal® weekly and then 4 months for Buvidal® monthly: see Clinical guidelines for use of depot buprenorphine (Buvidal® and Sublocade®) in the treatment of opioid dependence and table below for further details).

The long-acting nature of Buvidal® allows some flexibility in administration schedule which reduces the risk of missing doses:

• The weekly dose (7day) can be administered up to 2 days before or 2 days after the next due administration date.
• The monthly dose (28 day) can be administered up to 1 week before (from day 21 on) or 1 week after the next due administration date (up to day 35).

It is helpful to consider the preparations as their approximate transmucosal buprenorphine daily equivalents (see: Table 2 Equivalent doses of Buprenorphine formulations).

Graph 1 – Weekly Buvidal® compared with daily dose of sublingual buprenorphine

Graph 2 – 'Weekly' Buvidal® compared with ‘Monthly’ Buvidal® over four weeks

Due its higher affinity for opioid receptors buprenorphine has the potential to precipitate symptoms of opioid withdrawal when starting treatment.

This risk is higher when administered to patients that still have full opioid agonists in their systems e.g. Heroin or methadone. Buprenorphine displaces these full agonists from opioid receptors leading to a drop in opioid effect which can precipitate symptoms of withdrawal in opioid dependent patients.

To avoid precipitating withdrawal in patients new to buprenorphine, the first dose of buprenorphine should be taken when the patient shows objective signs of opioid withdrawal. Use of the Clinical Opiate Withdrawal Scale can help assess the extent of withdrawal.

Interactions between Buvidal® and other medications are the same as for transmucosal buprenorphine. Individuals with concomitant medicinal products and / or comorbidities should be monitored for signs and symptoms of toxicity, overdose or withdrawal caused by increased or decreased levels of buprenorphine.
Buprenorphine should not be co-administered with the opioid antagonists naltrexone or nalmefene (see NICE guidelines: Buprenorphine | Interactions | BNF | NICE).

Buprenorphine should be used with caution if co-administered with:

• Sedatives such as benzodiazepines, gabapentinoids, and alcohol
• CNS depressants
• Opioid analgesics
• Monoamine oxidase inhibitors
• CYP3A4 inhibitors and inducers

Buprenorphine is metabolised by cytochrome P450 3A4 so any medication that induces or inhibits this enzyme could theoretically affect buprenorphine levels in the body. Some of the HIV antiretroviral drugs induce this enzyme and other anti-HIV drugs inhibit it. University of Liverpool HIV Drug Interactions is free to access on the link below:

• https://www.hiv-druginteractions.org/checker

There is an increased risk of overdose if buprenorphine is taken with other CNS depressants (like alcohol or benzodiazepines). Individuals requiring opioids for pain relief who are considering OST Buvidal® will require review of pain management.

Buprenorphine prolonged-release injection may be a treatment option:

• Where patients struggle with adhering to, or have been unable to stabilise on, other forms of OST.
• Where patients could benefit from a reduction of necessary pharmacy or clinic attendances, e.g. due to work, education or childcare commitments.
• If significant risk of overdose, treatment failure or treatment drop out is identified.
• Where there is a risk of diversion of OST. This may be by choice but also where pressure or risk of harm from others is identified.
• Where there are concerns about the safety of OST stored at home.
• In custodial settings and subsequent continuation in community settings where this is the preferred option on liberation.
• As a contingency management option, e.g. during pandemic situations.

Services are required to have a Standard Operating Procedure (SOP) which outlines the process for prescribing, supply, administration and assessment of Buvidal®. Sample SOPs and PSDs (see section: Administering Buvidal®: Patient specific directions for administration) can be obtained by contacting the substance misuse team leads / pharmacist.

Patients new to treatment of Buvidal® need to have:

• Been provided with a Buvidal® patient information leaflet along with discussion explaining key points.
• Consented to having the treatment prescribed and administered.
• Be supplied with a Buvidal® alert card following administration of the first dose.

Prescribers should:

• Provide a legal prescription and patient specific direction (PSD). All PoMs require a legal prescription to allow supply. Prescribers will also need to provide a PSD for administration. This is the authorisation and instruction from the prescriber to the healthcare professional who will administer Buvidal® (see section: Administering Buvidal Injection: Health Care Professionals).
  
  
• Agree who will administer the injection, on what day and supply an appropriate PSD which includes this information. A new PSD should be supplied if there is a requirement for any dose changes otherwise the PSD is valid for 6 months. At time of writing a limited pilot of community pharmacy administration is in planning.  If the administrating service is a community pharmacy the PSD should be supplied at the same time as the prescription. This service is not currently available routinely from community pharmacy.
  
  
• Ensure that prescriptions and PSD are written to allow flexibility in administration. Producing individual prescriptions for each dose avoids the need for instalment dispensing directions and may allow more flexibility (see: Prescribing Buvidal Injection).
  
  
• Ensure that the service has a robust system in place for obtaining supply which is outlined in the service’s SOP. Buvidal^® cannot be collected by patients.

If the prescription will be dispensed by a community pharmacy for collection by NHS staff, it is recommended that the pharmacy is contacted to agree a plan. “For collection by NHSH staff” should be written on the prescription. The prescription should be supplied to the pharmacy a minimum of three working days in advance of intended collection date to allow time for stock to be ordered.

• Ensure controlled drug prescription requirements are adhered to, for both the prescription and PSD as Buvidal^® is a schedule 3 controlled drug.

Patients treated with oral forms of buprenorphine can be switched directly to weekly or monthly Buvidal^®, starting on the day after the last daily dose. Weekly administration may be the preferred first step for patients to allow them time to adapt to the new formulation and changes in plasma levels of buprenorphine that may be experienced moving form oral to depot formulations.

Closer review / monitoring of patients is recommended during the period of change from oral buprenorphine to Buvidal^®. This may include follow up phone calls or appointments in the days after administration to assess impact and provide support.

Week 1

• Confirm current daily buprenorphine dose and when the patient had their last dose.
• Switch directly to Buvidal^® starting on the day after the last daily buprenorphine dose.
• Use table 1 to confirm first 'weekly' dose of Buvidal^® administration.
• If required, additional supplemental doses of Buvidal^® 8mg can be administered during a treatment week. A maximum weekly dose of up to 40mg can be administered.
• It should be emphasised that subsequent Buvidal^® doses after the initial dose become more effective with accumulation of BPN plasma levels until steady state is achieved (usually after three to four doses).

Week 2 onwards

• The recommended dose for week 2 is the total all doses administered during week 1, i.e. the starting dose plus any supplementary doses given.
• From week 2 onwards a maximum of one supplemental Buvidal^® 8mg dose maybe administered between the regular 'weekly' or 'monthly' dose, based on patient response and professional judgement. Future weekly or monthly doses should be reviewed whether additional doses are needed.
• Patients can be transferred to a 'monthly' Buvidal® (see: table 2 Equivalent doses of buprenorphine formulations) on reaching a stable dose of ‘weekly’ treatment according to individual need and clinician judgement.

Current practice has evolved from the initial weekly doses for four weeks or more as stated in the SmPC. The document is designed to provide information to assist decision-making and is based on the best available evidence at the time of development. However, if prescribers who are not confident should follow the pharmaceutical company’s advice.

To ensure that withdrawal is not precipitated (see section: Precipitated withdrawal) clinicians should time the first administration of buprenorphine for when symptoms of withdrawal are likely to occur. Consider the type of opioid used (long or short acting), time since last opioid use and the degree of opioid dependence. This does not apply to transfers from oral buprenorphine. A Clinical Opioid Withdrawal Scale (COWS) can be useful in assessing symptoms of withdrawal however other medications or drugs may reduce the signs of withdrawal and patients may score lower than expected. Physical illness or withdrawal from other substances may also present in a similar manner to opioid withdrawal so any scale should be used alongside thorough clinical assessment and history taking. This does not apply to transfers from oral buprenorphine (see section: Initiating patients currently prescribed oral forms of Buprenorphine).

Patients not previously exposed to buprenorphine should receive a sublingual buprenorphine 4mg dose and be observed for an hour before the first administration of weekly Buvidal®. This is to confirm tolerability to buprenorphine and challenge any sensitivities to the medicine

An alternative option is to stabilise patients on oral buprenorphine before starting Buvidal®. This allows the patient more time to test the effects of buprenorphine before committing to a long-acting formulation. Initiation of Buvidal® should then follow guidance detailed in section: Initiating patients currently prescribed oral forms of buprenorphine.

The decision on how to initiate patients should be guided by clinical assessment of the individual’s risk factors, type of opioid currently used, degree of dependence, preferences and circumstances. When commencing Buvidal Weekly from heroin or other short-acting opioids, a starting dose of 16 or 24mg Buvidal weekly is recommended, with the option of additional Buvidal weekly 8mg supplementary or ‘top-up’ doses at least 24 hours apart within the first week as required, to a maximum of 32mg during the first week.

Buvidal is licensed to commence with a 16mg weekly dose, although clinical experience suggests that patients with higher levels of opioid use may require initiation doses of 24mg Buvidal weekly (click on link for further information Long-acting injectable buprenorphine (LAIB) for opioid dependence treatment (nsw.gov.au) Less experienced prescribers should discuss initiation dose with an experienced DARS clinician before starting a naïve client on the first higher dose.

Patients commencing Buvidal treatment should be instructed that the first dose may ‘wear off’ before the proposed seven days (which may be experienced as opioid withdrawal symptoms and / or cravings), and that the patient may have the option of attending earlier to receive their second dose (e.g. at day five or six), or may be able to access supplementary Buvidal weekly 8mg doses.

It should be emphasised that subsequent Buvidal doses after the initial dose become more effective with accumulation of BPN plasma levels until steady state is achieved (usually after three to four doses).

Week 1

• Administer a sublingual buprenorphine 4 mg dose and observe the client for an hour before the first administration (if needed)
• The recommended starting dose is Buvidal® 16mg 'weekly' injection.
• Patients with higher levels of opioid use may require initiation doses of 24mg Buvidal 'weekly'.
• During the first week an additional one or two 8mg doses can be given at least 1 day apart to a target dose of 24mg or 32mg (maximum) if the patient continues to experience opioid withdrawal, cravings or persistent additional opioid use.

Week 2 onwards

• The recommended dose for week 2 is the total all doses administered during week 1, i.e. the starting dose plus any supplementary doses given.
• From week 2 onwards a maximum of one supplemental Buvidal® 8mg dose administered between the regular 'weekly' or 'monthly' dose, based on patient response and patient judgement. Future weekly or monthly doses should be reviewed whether additional doses are needed.
• Patients can be transferred to monthly Buvidal® (see section: Table 2 Equivalent doses of buprenorphine formulations ) on reaching a stable dose of 'weekly' treatment according to individual need and clinician judgement.

Current practice has evolved from the initial weekly doses for four weeks or more as stated in the SmPC. The document is designed to provide information to assist decision-making and is based on the best available evidence at the time of development. However, if prescribers who are not confident should follow the pharmaceutical company’s advice.

• Following review, prescribers can increase or decrease doses or switch between weekly and monthly formulations according to clinical response and patient preference.
  
  
• Weekly dosing can continue if this is the most appropriate option. Drug costs are equivalent.
  
  
• Stepwise increases to the next dose may be required where the patient continues to experience symptoms of withdrawal, craving or additional “on top” use.
  
  
• The preferred approach to supplemental dosing for patients treated with Buvidal is to use supplemental doses of Buvidal (e.g. 8mg weekly top-up doses) to hold a patient until their next scheduled regular dose, and then to adjust the next Buvidal dose accordingly.
  
  
• Decreases may be required if the patient is experiencing adverse effects including over-sedation.
• Changing between weekly and monthly dosing should occur on the date when the next dose is due.
  Table 2 Equivalent doses of buprenorphine formulations should be used to calculate equivalent doses when switching between weekly and monthly formulations.
  
  
• Close monitoring is recommended following dose changes or when switching between weekly and monthly formulations.
  
  
• The maximum weekly dose of Buvidal® is 40mg and the total maximum monthly dose is 160mg.
  Patients on the highest monthly dose (160mg) cannot receive a supplementary 8mg dose.

In general, doses should be maintained if:

• The patient is achieving key treatment goals, is not experiencing opioid withdrawal or cravings and no additional use of opioids.
• There are no significant dose-related adverse events related to buprenorphine (e.g. sedation or lethargy, persistent headaches, nausea).
• The patient is satisfied and is requesting the dose be maintained.

Consider whether dose reduction is required where the patient:

• Reports dose-related buprenorphine adverse events.
• Is ready to reduce the dose with a goal of stopping OST.
• Reports the dose is too high and / or is seeking a dose reduction, and there are no significant concerns regarding deterioration in clinical condition (e.g. substance use, physical or mental health symptoms) that may arise with a dose reduction.
• Is using other CNS depressants to an extent where the combination is felt to increase risk of overdose.

Consider whether dose increase is required where the patient:

• Is not achieving desired treatment goals (e.g. ongoing opioid use, opioid withdrawal symptoms or cravings) and there are no reported adverse events.
• Reports their dose is too low and there are no significant clinical safety concerns in increasing it.

Where Buvidal injection cannot be used:

• Combining different strengths in any way is NOT recommended:
  
  
  • e.g. 2 x weekly 32mg Buvidal is NOT equivalent to Buvidal 64mg monthly
  • or 2 monthly 64mg Buvidal does NOT provide the same peak plasma levels as 1 x 128mg Buvidal ^® injection.
    
    
• If there is no access to a Buvidal 8mg top up dose buprenorphine sublingual can be used instead of Buvidal (e.g. missed Buvidal doses) doses should be prescribed between 2mg to 6mg daily (along with existing Buvidal) until the client’s next Buvidal administration.
  
  
• Buprenorphine oral daily doses should be guided by see section: Table 8 Recommended equivalent doses for transfer to transmucosal buprenorphine until next Buvidal can be administered.
  
  
•  Consult with an experienced DARS Clinician for further advice if required.

Missed doses

If a dose is missed the patient should be reviewed and appropriateness of continuation should be assessed as soon as practically possible. Factors to be considered in the assessment include:

1. Reason for missed dose (e.g. forgot it was due, feeling fine / did not feel that they needed it, missed due to illness, thought they would try and come off, period of lapse, etc.).
2. Changes in physical or mental health or other medicines taken.
3. Current dose, how long prescribed, how long since last administration and administration history (i.e. has reached steady state or not – see section: Table 1 Summary of NHSH formulary OST formulations).
4. Assess any recent substance use.
5. Assess for any adverse effects, signs of intoxication, symptoms of withdrawal etc.
6. Does Buvidal® remain the preferred treatment option?

Treatment options include:

1. Continue with current dose.
2. Consider dose reduction (top up dose available if needed).
3. Consider moving from a monthly back to weekly if not at steady state – i.e. has not received monthly administration for longer than four months.
4. Discuss and agree end of the treatment plan, if patient’s goal is to discontinue treatment.
5. Revert back to oral buprenorphine, or methadone if this is the preferred option.

All named patient scheduled doses that have not been administered due to non-attendance can be held in locally agreed secure storage for 28 days for further attempts at administration (including by proactive outreach approach).
Doses which have not been administered by day 28 should be returned to the community pharmacy where they will be destroyed.

All named patient scheduled doses that have not been administered due to non-attendance can be held in locally agreed secure storage for 28 days for further attempts at administration (including by proactive outreach approach).

Doses which have not been administered by day 28 should be returned to the community pharmacy where they will be destroyed.

Transitions between services such as prison and community-based services or discharge from hospital, are associated with risks such as default from services, overdose and sadly drug related death. Collaboration of services can help reduce these risks. Key points to consider include:

• Product prescribed and current dose
• Date of last administration / date next dose is due
• Ensuring that the patient has an appointment for ongoing care before transfer. This process should take place as soon as admission, transfer, discharge or release dates are known in order that logistical considerations such as arranging a competent health care professional (and venue) to prescribe, order and administer the product can take place.

Buvidal® will leave the body slowly over a number of weeks or months. For the monthly product it could be 3 months or more after last administration before the body clears buprenorphine reserves completely. Symptoms of withdrawal may not be an issue but can occur many weeks after the final dose. Clinicians should assess each patient individually and collaboratively decide on the most suitable intervention. There is now experience both locally and in other areas in Scotland of using Buvidal® for opioid detoxification, though this remains off label and patients should provide informed consent accordingly.

• Stopping from a monthly dose of Buvidal® will provide a more gradual reduction in buprenorphine blood levels than stopping from a weekly dose. It is recommended that the patient is transferred to the lowest dose of ‘monthly’ Buvidal® before stopping the product, e.g. for patients prescribed Buvidal® 128mg transfer from 128mg to 96mg to 64mg before stopping.
• Prescribing each of the lower doses in turn for 3 months before reducing allows the body to adapt to each dose reduction before further reductions are made although there is no set guidance on how quickly to withdraw Buvidal®.
• More rapid reduction will result in a quicker reduction of buprenorphine blood plasma levels.
  The patient should be involved in each stage of planning.
  Patients and treatment plans should be reviewed regularly, include additional psychological support to maintain motivation, cope with cravings, withdrawal and the risk of relapse.
• If symptoms of withdrawal appear, there may be a role for symptomatic treatment however caution should be applied when considering extended use (beyond a few days) of sedative or hypnotic medication.
• Patients should be provided with overdose awareness information and naloxone.
• Due to the delayed nature of possible withdrawal symptoms patients should be monitored and supported for a minimum of 3 months following their last Buvidal® injection. The need for ongoing support and relapse prevention should be assessed and arranged as appropriate. 

If a switch back to an oral form of OST is requested or required, the transfer should occur on the date when the next dose of Buvidal® is due, i.e. one week or one month after the last dose depending on the formulation.

If individuals are to switch from Buvidal to oral buprenorphine, this should be done at least one week after the last weekly dose or at least one month after the last monthly dose of Buvidal, at a dose corresponding to the recommendations in section: Table 9 Equivalent doses for transfer to oral buprenorphine formulations.

Individuals in steady state Buvidal treatment may have long-acting buprenorphine present for months so cautious timing of transmucosal dosing should be balanced with the ability of the individual to tolerate a longer cross-over period. It is advisable to start at the lower end of the dose and titrate up when necessary.

Transfer of Buvidal to methadone has no direct dose equivalent and must consider the cumulative effect of methadone dosing and the long plasma half-life of Buvidal, especially if at steady state. All transfers should be discussed with a senior specialist clinician. Factors to consider include:

Has steady state been reached?

If so:

• Important to consider half-life (3 to 5 days for weekly and 19 to 25 days for monthly) and buprenorphine’s high affinity for mu opioid receptor.
• Risk assess and delay initiation as long as risk allows in agreement with individual.
• 1st dose a minimum of 28 days after last monthly dose or 7 days after weekly injection.
• Start low (consider 10 to 20mls) and titrate very slowly as Buvidal gradually reduces
• Approach should be individualised with regular review of individual’s symptoms to manage any withdrawals and reduce risk of non-prescribed drug use.

If an individual is in steady state Buvidal treatment and requests transfer to methadone, it is likely that methadone will be introduced long before plasma Buvidal has significantly reduced. Methadone should therefore be introduced at a low dose and titrated with caution. We do not have enough clinical experience of this yet to make expert recommendation.

If steady state Buvidal has not yet been reached, the standard methadone titration guidance should be followed.

Administration of Buvidal® is restricted to authorised and appropriately trained health care professionals who have been approved by their professional manager as competent.

Health Care Professionals must:

• Be trained in the administration of subcutaneous injections.
• Demonstrate competence in the use and administration of the Buvidal® injecting device.
• Have completed annual basic life support training.
• Have undertaken NHS e-anaphylaxis training or equivalent (including annual updates) which covers all aspects of the identification and management of anaphylaxis.
• Maintain their skills, knowledge and their own professional level of competence in this area according to their individual Code of Professional Conduct.
• Have knowledge of and familiarity with the service specific Standard Operating Procedure (SOP) and Summary of Medicinal Product Characteristics (SmPC) for Buvidal®.
• Be competent in assessing the patient’s capacity to consent to the administration of Buvidal®.
• Be able to discuss issues associated with administration of Buvidal® with the patient.
• Be competent in the handling and storage of controlled drugs.

Professional manager(s) will be responsible for:

• Ensuring that the service has a SOP for prescribing, obtaining, storing and administering medication tailored to their service.
• Ensuring that the current SOP is available to all staff.
• Ensuring that staff have received adequate training and meet the requirements above.
• Maintaining an up-to-date record of all staff authorised to administer Buvidal®.

Patient specific directions for administration:

Where the prescriber is authorising another health care professional to administer medication a Patient Specific Direction (PSD) is required . The Osprey House Kardex and HMP Inverness Prescription Sheet are examples of PSDs.

If a prescription has been dispensed by a community pharmacy, a separate PSD for administration is also required. The prescription for supply of medication does not fulfil this requirement.

As a minimum a PSD for administration should include:

• Name of patient and / or other individual patient identifiers (CHI, address) including age if a child.
• Name, form and strength of medicine (generic or brand name where appropriate).
• Route of administration.
• Dose and frequency of administration.
• Date of treatment, total number of doses and date treatment ends as applicable.
• Signature of the prescriber. It could be an electronic record made in the patient notes where it is identifiable as the prescriber.

If a PSD is for supply of a controlled drug (CD), the form must also meet the legal requirements for CD prescriptions.

Administration of Buvidal®

Buvidal® is intended for subcutaneous administration only:

• Inject slowly and completely into the subcutaneous tissue of different areas (buttock, thigh, abdomen, or upper arm) at a 90-degree angle.
• Each area can have multiple injection sites.
• Injection sites should be rotated for both weekly and monthly injections.
• A minimum of 8 weeks should be left before re-injecting a previously used injection site (although the same area can be used e.g. left upper buttock, left mid buttock and left lower buttock).
• The dose should be administered as a single injection and not divided.
• A video and instruction leaflet covering administration can be accessed on the Buvidal® site.
• The most common injection site reactions are pain (8.9%), pruritus (6.1%) and erythema (4.7%). All were mild or moderately severe and most were short lived.

Buvidal® administration should be recorded clearly in the patient’s record and as a minimum include:

• Name, address and CHI of the person having the dose administered.
• Name, formulation and strength of the controlled drug administered.
  Dose of the controlled drug administered.
• Date and time of administration.
• Location of site injected (the same site should not be used for 8 weeks).
• Name and signature or initials of the person who administered the dose.
• Name and signature or initials of any witness to administration.
• The batch number and expiry date of the dose.

Consult the SmPC for full product information.

Manufacturer listed contra-indications to use are as follows:

• Allergy or sensitivity to any of the excipients of Buvidal® (buprenorphine, soybean, glycerol dioleate, N-methyl-2-pyrrolidone (monthly formulations only), ethanol anhydrous (weekly formulations only).
• Severe respiratory insufficiency.
• Severe hepatic impairment.
• Acute alcoholism or delirium tremens.

The following groups require specific consideration before prescribing which may require discussion with other specialty areas. They include:

• elderly patients >65 years
• patients with moderate hepatic impairment (see Section 7.2)
• patients with severe renal impairment (creatinine clearance <30ml/min)
• children and adolescents <16 years of age (unlicensed)
• pregnant women
• patients who require pain management where opioid analgesia is indicated.

Buvidal® – side effects

Consult the BNF (British National Formulary) and SmPC for full product information

Studies have shown that side effects of Buvidal® are identical to buprenorphine.

Injection site reactions may follow administration of Buvidal®. These are usually mild to moderate in severity and mostly short lived. Injection site pain, pruritus or injection site erythema are common, whereas cellulitis, bruising and urticaria less so. There are some post–marketing reports of adverse reactions for abscess, ulceration and necrosis.

Hepatitis, Hepatic Events and Liver Disease

There are rare case reports of liver injury in patient prescribed buprenorphine, usually arising within 2 to 20 weeks of starting buprenorphine. This led pharmaceutical companies to recommend routine liver function tests (LFTs). Current available evidence suggests the majority of reports occurred in patients with a diagnosis of hepatitis B or C or following injection of buprenorphine sublingual tablets. This suggests the risk is no longer greater for buprenorphine than for methadone.

Laboratory results, trackcare and GP records (if accessible) should be checked for any evidence of previous / current liver function issues before starting buprenorphine. Due to the longer acting nature of Buvidal® recent LFTs would be preferable, however, if this is not possible then clinicians should highlight to the patient the rare risk of liver injury with buprenorphine in order to support an informed, shared decision on prescribing and the benefits of LFTs prior to commencing Buvidal®.

Regular review of blood borne virus (BBV) status and BBV testing is recommended for all patients and will help identify those who may be at high risk. LFTs should therefore be considered for patient with a diagnosis of hepatitis or evidence of hepatic dysfunction.

All patients should be offered testing and discussion regarding vaccination status in the early stages of treatment. Details on how to access vaccination in HSCP Highland are found on the link.

Where a patient is identified as having clinically relevant liver disease (more than a mild elevation of LFTs) but not severe hepatic impairment, (which is a contraindication to Buvidal® treatment) then an extended period of treatment with oral buprenorphine (e.g. one to three months) may be an option. This allows for monitoring of liver function to ensure that buprenorphine does not worsen hepatic function, and for titration of dose, prior to initiating Buvidal® treatment. If Buvidal® is administered in preference to oral buprenorphine for a patient with moderate hepatic impairment, then a weekly formulation would be pragmatic choice due to its quicker washout period as compared to monthly prolonged-release formulation.

Monitoring of liver function may be considered for patients with mild to moderate liver disease and / or liver impairment after commencing treatment with Buvidal® (e.g. clinical examination, liver function blood tests and exclusion of underlying causes, for example viral hepatitis, or alcohol use). Patients who develop moderate hepatic impairment while being treated with Buvidal® should be monitored for signs and symptoms of precipitated opioid withdrawal, toxicity or overdose caused by increased levels of buprenorphine as the plasma exposure can increase approximately 3-fold in patients with severely impaired hepatic function. Sedation following the initial dose may occur with high doses, and the patient should be warned accordingly.

In patients who develop severe hepatic impairment, Buvidal® should be stopped and patient switched to an alternative OST. The patient should continue to be monitored regularly following cessation of Buvidal®.

Driving

At time of writing the DVLA guidance for Assessment of Fitness to Drive notes that subcutaneous long-acting buprenorphine (Buvidal®) may be eligible for consideration. Patients should be reminded of their legal duty to inform the DVLA of any medical conditions. They should also be advised that buprenorphine may affect their ability to drive or use machinery, and that they should avoid doing so until fully aware of how they are affected by Buvidal®. Up-to-date information can be assessed on the link above.

Pregnancy and Breastfeeding

Specialist support should be sought from specialist midwives within the NHSH Community midwives team when treating pregnant patients.

Buvidal® may be used in pregnancy following discussion with specialist staff if it is felt that the potential benefit outweighs the risk.

There is, however, more experience in using oral buprenorphine in pregnancy. UK clinical guidelines states “Research evidence demonstrates no difference in adverse effects between methadone and buprenorphine with both having no adverse effects in the pregnancy or neonatal outcomes, with incidence of Neonatal Abstinence Syndrome (NAS) similar to methadone exposure (Blandthorn, Forster & Love, 2011, Jones et al 2010). However, there is some evidence that buprenorphine use results in NAS of low severity.”

Given this, switching to oral buprenorphine may be an option for those patients on Buvidal®. It is necessary for women and their clinicians to weigh up the risks and benefits to both the mother and the baby of not taking a specific treatment against those of initiating or continuing the treatment. This will vary from person to person and depend on the severity of the mother’s condition and the complications that could arise if her treatment is altered.

The impact of Buvidal® on pain management plans during labour should be considered.

The manufacturer of Buvidal® recommends that Buvidal®; should be used in caution in those breastfeeding as buprenorphine is excreted in breast milk.

For women on stabilised on a buprenorphine product that wish to breastfeed, an individual risk benefit analysis to inform decision making should be undertaken. Due to lack of evidence of the effects of these drugs on breastfed infants, manufacturers’ advice is to avoid, although expert consensus opinion state that the effects of these medicines on breastfed infants is likely to be minimal and that breastfeeding is not contradicted.

UK Guidance states “Breastfeeding should be encouraged, even if the mother continues to use drugs, except where she uses cocaine or crack cocaine, or very high dose of benzodiazepines. Specialist advice should be sought if she is HIV positive. Hepatitis C is not contraindicated to breastfeeding (HIS, 2013).

Methadone or buprenorphine treatment is not a contraindication to breastfeeding, breastfeeding may reduce the intensity and length of the NAS and has been shown to improve outcomes (Mayet et al, 2008)”  see Patient Specific Directions (PSD) – SPS - Specialist Pharmacy Service – The first stop for professional medicines advice 

Discussions regarding choice of OST should follow the principles of Realistic Medicine where shared decision making and informed consent are central to prescribing decisions to inform person centred care. Where the person wishes, a family member or named person can be involved in discussions. It is important to understand a person’s existing knowledge and understanding of the different OST options prior to offering information. There are a range of leaflets available, tailored to different languages and levels of literacy. They can be found in the Choice and Medication website which is part of NHS Inform. NB: Leaflets for all mental health diagnoses can be searched for in the handy charts, handy fact sheets and patient information leaflet sections:

• Choice and medication/NHS24
• Chart to compare all prescribing options for opioid dependence
• Comparing methadone versus buprenorphine
• Buprenorphine leaflets (injectable, orally administered, different languages). 

Buvidal information leaflets in various reading formats and various levels of health literacy:

• Brief Information leaflet 
• Patient Information leaflet
• Easier on the eye leaflet 
• Very easy to read leaflet

• Buprenorphine 8mg Sublingual Tablets
• Buvidial prolonged release injection

• BBV: Blood borne virus
• BNF: British National Formulary
• CD: Controlled drug
• CNS: Central Nervous System
• DARS: Drug and Alcohol Recovery Services
• HIV: Human immunodeficiency virus
• LAIB: Long-acting injectable buprenorphine
• LFTs: Liver function tests
• SOP: Standard operating procedure
• OST: Opioid substitution treatment
• PSD: patient specific direction
• PoMs: Prescription Only Medicines
• SmPC: Summary of medicinal product characteristics
• SOP: Standard operating procedure