Buprenorphine modified-release injections (Bivudal weekly and monthly) for opiate dependence

• On 1 May 2022, the PBS clinical criteria for weekly buprenorphine modified-release injections (Buvidal Weekly) for opiate dependence were changed.
  The requirement that patients must be stabilised on sublingual buprenorphine or sublingual buprenorphine/naloxone prior to commencing treatment was removed. The change was based on evidence of efficacy and safety, and is in alignment with the medicine’s recently changed TGA-approved indication.
  

• On 1 May 2022, the PBS clinical criteria for monthly buprenorphine modified-release injections (Buvidal Monthly) were changed.
  Stabilisation on weekly buprenorphine modified-release injection was added to the existing requirement to be stabilised on sublingual buprenorphine or sublingual buprenorphine/naloxone prior to commencing treatment. The change aligned the listing with the medicine’s recently changed TGA-approved indication.
  

• On 1 May 2022, 160 mg/0.45 mL monthly buprenorphine modified-release injection (Buvidal Monthly) for opiate dependence was listed on the PBS.
  This is the highest strength available and maximum recommended dose per month of this medicine. The listing will help address the clinical needs of patients who require supplemental doses if they experience opioid withdrawal, cravings or persistent unsanctioned opioid use.
  

• Buprenorphine modified-release injection has a boxed warning of risks to patients.
  These warnings include only administering the medicine subcutaneously, that concomitant use with central nervous system depressants can lead to sedation, respiratory depression, coma and death, and the importance of monitoring for respiratory depression.
  

• Buprenorphine modified-release injections can reduce the efficacy of opioids such as morphine or oxycodone used in the management of severe acute pain.
  GPs may need to consult with local drug and alcohol advisory services for advice on acute pain management for patients using buprenorphine modified-release injection.
  

On 1 May 2022 the clinical criteria were changed for the Opiate Dependence Treatment (ODT) Program (S100) listings of weekly and monthly buprenorphine modified-release injections (Buvidal Weekly and Buvidal Monthly) for opiate dependence.¹

For all strengths of weekly buprenorphine modified-release injection, the requirement that patients must be stabilised on sublingual buprenorphine or sublingual buprenorphine/naloxone prior to commencing treatment was removed from the clinical criteria.^1,2

For all strengths of monthly buprenorphine modified-release injection, stabilisation on weekly buprenorphine modified-release injection was added to sublingual buprenorphine or sublingual buprenorphine/naloxone as a requirement prior to commencing treatment.^1,2 See Table 1 below for the PBS listing changes.

On 1 May 2022, 160 mg/0.45 mL monthly buprenorphine modified-release injection (Buvidal Monthly) for opiate dependence was listed on the ODT Program (S100).¹

The clinical criteria for this medicine are the same for all other strengths of monthly buprenorphine modified-release injection listed on the PBS.¹ See Table 1 for the new PBS listing.

Table 1. PBS listings for weekly and monthly buprenorphine modified-release injections before and after 1 May 2022^1,5

^a Care must be taken to comply with the provisions of state and territory laws when prescribing weekly and monthly buprenorphine modified-release injection.¹

See the PBS website for complete details for each item.

May be prescribed by nurse practitioners

Authorised nurse practitioners may prescribe this medicine where care of a patient is shared between a nurse practitioner and medical practitioner in a formalised arrangement with an agreed management plan (shared care model).¹

See the PBS website for more information on nurse practitioner PBS prescribing.

Buprenorphine is a high-infinity partial opioid agonist at the human μ-opioid (mu-opioid) receptor. It reduces withdrawal symptoms and craving for opioids for people with opiate dependence.^4,6,7

Its activity is attributed to its slowly reversible properties with the μ-opioid receptors which, over a prolonged period, might minimise the need for illicit opioids among patients with opiate dependence.^6,7

Modified-release buprenorphine is administered via subcutaneous injection in the upper arm (if sufficient tissue), abdomen, thigh or buttock.^4,6,7

When the modified-release formulation is injected into the subcutaneous tissue it is transformed into a highly viscous liquid crystal with buprenorphine encapsulated in the matrix. A combination of simple diffusion and biodegradation of the matrix results in a slow and consistent release of buprenorphine, either for a week or a month.^8,9

See the product information for complete details of weekly modified-release buprenorphine injection and monthly modified-release buprenorphine injection.

Weekly and monthly buprenorphine modified-release injections (Buvidal Weekly and Buvidal Monthly) are one of a number of medicines available to treat opiate dependence under the PBS.³

Sublocade (100 mg/0.5 mL and 300 mg/1.5 mL) is another brand of monthly buprenorphine modified-release injection that is PBS listed.^3,4 Generally, switching between Buvidal and Sublocade should be avoided, due to the lack of published data and clinical experience, unless the situation arises where it’s impossible to continue with one brand. Specialist advice should be sought when switching is required.⁸

The other medicines available to treat opiate dependence under the PBS are buprenorphine sublingual tablets, buprenorphine with naloxone sublingual films and methadone oral liquid.³

Shared decision-making based on the patient’s history, preferences and goals should determine the choice of medicine.¹⁰ Patient engagement as a result of use of these medicines also provides an opportunity to provide further treatment with other medical, psychological and social interventions.^8,10

Changed listings

At the November 2021 meeting, the Pharmaceutical Benefits Advisory Committee (PBAC) recommended changing the clinical criteria for weekly buprenorphine modified-release injection to allow for direct initiation (ie, not first requiring stabilisation on sublingual buprenorphine or sublingual buprenorphine/naloxone, which require daily dosing, prior to commencing treatment) based on evidence of non-inferior efficacy and safety. This recommendation was also consistent with the change to the TGA-approved indication for the medicine that was made in April 2021.²

The PBAC also recommended changing the clinical criteria for monthly buprenorphine modified-release injection to include stabilisation on weekly buprenorphine modified-release injection, as well as sublingual buprenorphine or sublingual buprenorphine/naloxone. This made the listing consistent with the TGA-approved indication for the medicine, which was changed in April 2021.²

However, the PBAC did not recommend the sponsor’s submission for direct initiation of monthly buprenorphine modified-release injection because it is not a TGA-approved indication for this medicine.²

The PBAC also deferred a decision on the sponsor’s submission for a dual listing on the General Schedule (Section 85) and ODT Program (S100) for weekly and monthly buprenorphine modified-release injection. The PBAC determined that this decision should be informed by the findings of the PBS Post-market Review of Opiate Dependence Treatment Program medicines, which is still in progress.²

New listing

At the November 2021 Meeting, the PBAC supported the listing of 160 mg/0.45 mL monthly buprenorphine modified-release injection based on the PBAC Economics Sub Committee finding that there was evidence supporting the efficacy and safety of this strength of medicine.²

Changed listings

The changed PBS listings for weekly buprenorphine modified-release injection can be expected to reinforce direct initiation, which is consistent with the recently changed TGA-approved indication, as well as clinical guidelines and international studies for this medicine.^8,11,12

Direct initiation may be beneficial for patients, particularly in rural areas. Benefits include removing the need to attend a clinic or pharmacy for daily dosing of sublingual buprenorphine or sublingual buprenorphine/naloxone, avoiding adherence challenges during induction, and removing associated patient cost and travel burdens. Direct initiation may also help to reduce exposure to infection during the COVID-19 pandemic and decrease the demand on service delivery in areas that have been negatively impacted by the pandemic.¹³

New listing

The new PBS listing of 160 mg/0.45 mL monthly buprenorphine modified-release injection is expected to help address the clinical needs of patients who require supplemental doses if they experience opioid withdrawal, cravings, or persistent unsanctioned opioid use.⁸ The maximum TGA-approved monthly dose is 160 mg. Previously the maximum available strength was 128 mg/0.36 mL. The 160 mg/0.45 mL strength enables dosing at the TGA-approved monthly dose and avoids supplemental doses that would exceed the maximum dose.^5,6

Boxed warning

The TGA-approved product information for weekly and monthly buprenorphine modified-release injections contains a boxed warning of risks for patients, including:^6,7

• The medicine should only be given subcutaneously. Serious harm or death could result if administered intravenously due to the transformation of the injected liquid into a gel depot, which may cause occlusion, local tissue damage and thrombo-embolic events.
• Patients and their carers should be explicitly informed of the potential harm from concomitant use of benzodiazepines and other central nervous system depressants, including alcohol, which may cause sedation, respiratory depression, coma and death.
• Patients should be closely monitored for symptoms of respiratory depression, especially on initiation or following a dose increase. Buprenorphine modified-release injection should be used with caution in patients with significantly compromised respiratory function.

Emergency analgesia

Buprenorphine modified-release injection can reduce the efficacy of opioids such as morphine or oxycodone used in the management of severe acute pain. Its effects may persist for many months after the last dose. In emergencies, such as accidents, weekly and monthly buprenorphine modified-release injections (Buvidal Weekly and Buvidal Monthly only) cannot be removed nor easily reversed.^4,14

GPs may need to consult with local drug and alcohol advisory services for advice on acute pain management, or refer the patient to an emergency department for acute pain management.¹⁴

Effects continue after stopping treatment

The effects of weekly and monthly buprenorphine modified-released injections may continue for many months after stopping them. Prescribers are advised to continue to monitor for side effects and consider potential drug interactions.⁴

Supply

Buprenorphine modified-release injections cannot be directly dispensed to patients under any circumstances.^8,14-20

Prescribers can access stock either directly from the manufacturer or through a pharmacy with a prescription.²¹

Transfer of care and clinical handover

Many health professionals may not be familiar with the different brands of buprenorphine modified-release injections and their dosing intervals.⁸

To safeguard optimal care, documents and clinical handover should accurately state the following:⁸

• The brand, strength, dose and date of the medicine that was administered.
• Details of the prescriber, location of the clinic or the drug and alcohol service administering the medicine.
• Injection site location on the patient’s body, to avoid injecting into the same site.
• Potential risks, including previous adverse effects and likely drug interactions.

Talk with patients and carers about these points:^6,7

• This medicine is an injection into the skin. Injecting it into your vein can cause serious harm or death.

• Using this medicine at the same time as:
  • alcohol
  • cannabis or
  • medicines for sleep problems, nerve pain, allergy and mental health

can cause drowsiness, breathing problems, coma and death.

• This medicine may affect how you drive or use machines. This may happen when starting to use it. It may also happen when adding to the amount you use.

• Side effects may happen with this medicine. Side effects may be finding it hard to move your bowels, heartburn, low blood pressure, nausea and vomiting. These side effects can seem like opioid withdrawal symptoms.⁴

• Using this medicine may stop other medicines for very strong, short-term pain from working well.

• This medicine may continue affecting you for many months after stopping it. Continue checking for side effects. Talk with your doctor about its effect on other medicines.⁴

State and territory guidelines for weekly and monthly buprenorphine modified-release injections

ACT Buprenorphine depot products: Information for pharmacists and prescribers

NT Medicines and poisons

NSW Clinical guidelines for use of depot buprenorphine (Buvidal^® and Sublocade^®) in the treatment of opioid dependence

QLD Long-acting injection buprenorphine in the treatment of opioid dependence

SA Medication assisted treatment for opioid dependence (MATOD) – Prescribing resources

TAS Opioid pharmacotherapy program

VIC Brief clinical guidelines for use of depot buprenorphine (Buvidal^® and Sublocade^®) in the treatment of opioid dependence

WA Clinical guidelines for use of depot buprenorphine (Buvidal^® and Sublocade^®) in the treatment of opioid dependence