Supporting patients throughout their treatment journey
Treatment with Buvidal
Like all opioid dependence medications, Buvidal should be used within a framework of medical, social and psychological treatment.
Before starting the treatment journey
Before commencing buprenorphine treatment, it is recommended to obtain baseline liver function tests and to document viral hepatitis status. Patients who are positive for viral hepatitis, taking other medicines and/or with existing liver dysfunction are at greater risk of liver injury. Regular monitoring of liver function is recommended.
The prolonged-release properties of weekly and monthly Buvidal should be considered during treatment, including initiation and termination.
Appropriate precautions, such as conducting patient follow-up visits with clinical monitoring according to the patient’s needs, should be taken when prescribing and dispensing buprenorphine.
When initiating Buvidal, it’s important to be aware of the partial agonist profile of buprenorphine.
Precipitated withdrawal may occur when buprenorphine is first administered to an opiate-dependent person with opioid agonist drugs circulating within their system. In this situation, buprenorphine can inhibit the opioid actions of the full agonist without adequately replacing them, leading to the appearance of withdrawal signs and symptoms.
To avoid precipitating symptoms of withdrawal, treatment with Buvidal should be started when objective and clear signs of mild to moderate withdrawal are evident.
Consideration should be given to the types of opioid used (that is long- or short-acting opioid), time since last opioid use and the degree of opioid dependence.
- For patients using heroin or short-acting opioids, the initial dose of Buvidal must not be administered until at least 6 hours after the patient last used opioids.
- For patients receiving methadone, the methadone dose should be reduced to a maximum of 30 mg/day before starting treatment with Buvidal which should not be administered until at least 24 hours after the patient last received a methadone dose.
The rationale for this requirement and consequences of ignoring it should be explained to the patient in a way that they understand. Clinical care should include planning for how the patient will manage this period of withdrawal in the lead up to their first injection.
Please refer to the Summary of Product Characteristics for more information: UK, NI
- Elderly
The efficacy and safety of buprenorphine in elderly patients >65 years have not been established. No recommendation on posology can be made. In general, the recommended dosing for elderly patients with normal renal function is the same as for younger adult patients with normal renal function. However, because elderly patients may have diminished renal/hepatic function, dose adjustment may be necessary.
- Hepatic impairment
Buprenorphine is extensively metabolised in the liver.
Buprenorphine should be used with caution in patients with moderate hepatic impairment. Monitor for signs and symptoms of precipitated opioid withdrawal, toxicity or overdose.
In patients with severe hepatic impairment, the use of buprenorphine is contraindicated.
- Renal impairment
Modification of the buprenorphine dose is not required for patients with renal impairment. Caution is recommended when dosing patients with severe renal impairment (creatinine clearance <30 ml/min)
- Paediatrics
The safety and efficacy buprenorphine in children and adolescents below 16 years of age have not been established. No data are available.
Please refer to the Summary of Product Characteristics (UK/NI) for more information relating to use of Buvidal and:
• Pregnancy
• Breast-feeding
• Fertility
• Respiratory insufficiency
• QT prolongation
• Acute pain management
• Sleep-related breathing disorders
• Driving and operating machinery
• Serotonin syndrome
• Other clinical situations
- Hypersensitivity to buprenorphine or to any of the excipients in Buvidal:
- Weekly Buvidal – soybean phosphatidylcholine, glycerol dioleate, ethanol anhydrous
- Monthly Buvidal – soybean phosphatidylcholine, glycerol dioleate, N‑Methylpyrrolidone
- Severe respiratory insufficiency
- Severe hepatic impairment
- Acute alcoholism or delirium tremens
No interaction studies have been conducted with Buvidal.
Buprenorphine should be used with caution if co-administered with:
- naltrexone and nalmefene
- alcoholic drinks or medicinal products containing alcohol
- benzodiazepines
- gabapentinoids
- Serotonergic medicinal products, such as MAO inhibitors, selective serotonin re-uptake inhibitors (SSRIs), serotonin norepinephrine re-uptake inhibitors (SNRIs) or tricyclic antidepressants
- other central nervous system depressants:
- other opioid derivatives (e.g. methadone, analgesics and antitussives)
- certain antidepressants, sedative H1-receptor antagonists, barbiturates, anxiolytics other than benzodiazepines, antipsychotics, clonidine and related substances
- CYP3A4 inhibitors (e.g. protease inhibitors like ritonavir, nelfinavir or indinavir, or azole antifungals such as ketoconazole or itraconazole, or macrolide antibiotics)
- CYP3A4 inducers (e.g. phenobarbital, carbamazepine, phenytoin or rifampicin)
- UGT1A1 inhibitors
- monoamine oxidase inhibitors (MAOI)
Please refer to the Summary of Product Characteristics for more information UK, NI
Beginning the treatment journey
Treatment with Buvidal should be started when objective and clear signs of mild-to-moderate withdrawal are evident – this is to avoid precipitating symptoms of withdrawal.
Starting dose recommendations
| Day 1 | During week 1 | Week 2 |
|---|---|---|
| 16 mg injection | One or two additional 8 mg doses at least one day apart. The target dose during the first week of treatment is 24 mg or 32 mg. | The recommended dose for the second treatment week is the total dose administered during the week of initiation. |
Recommended dose conversion when switching from weekly to monthly dosing:
| Weekly dose of Buvidal | Monthly dose of Buvidal |
|---|---|
| 16 mg | 64 mg |
| 24 mg | 96 mg |
| 32 mg | 128 mg |
| 160 mg |
Conventional SL-BPN or LYO-BPN daily treatment dose and recommended corresponding doses of weekly and monthly Buvidal¹
| Dose of daily SL-BPN | Dose of weekly Buvidal | Dose of monthly Buvidal |
|---|---|---|
| 2-6 mg | 8 mg | – |
| 8-10 mg | 16 mg | 64 mg |
| 12-16 mg | 24 mg | 96 mg |
| 18-24 mg | 32 mg | 128 mg |
| 26-32 mg | – | 160 mg |
| Dose of daily LYO-BPN* | Dose of weekly Buvidal | Dose of monthly Buvidal |
|---|---|---|
| 2-4 mg | 8 mg | – |
| 6-8 mg | 16 mg | 64 mg |
| 10-12 mg | 24 mg | 96 mg |
| 14-18 mg | 32 mg | 128 mg |
| – | – | 160 mg |
*25-30% higher bioavailability for Espranor than for SL Subutex tablet (MHRA Public Assessment Report Decentralised Procedure Espranor 2 mg and 8 mg lyophilisate). The maximum single dose of Espranor is 18 mg (Espranor 2 mg oral lyophilisate Summary of Product Characteristics and Espranor 8 mg oral lyophilisate Summary of Characteristics).
SL-BPN: sublingual buprenorphine; LYO-BPN: oral lyophilisate buprenorphine.
For patients receiving methadone:
- The methadone dose should be reduced to a maximum of 30 mg/day before starting treatment with buprenorphine
- Buprenorphine can only be administered at least 24 hours after the patient last received a methadone dose.
- Buprenorphine may trigger withdrawal symptoms in methadone-dependent patients.
Monthly Buvidal may be started after the patient has been stabilised on weekly Buvidal treatment for 4 weeks or more. This should be in accordance with the dose conversion table (see below).
Following switching, patients may need closer monitoring.
Recommended dose conversion when switching from weekly to monthly dosing:
| Weekly dose of Buvidal | Monthly dose of Buvidal |
|---|---|
| 16 mg | 64 mg |
| 24 mg | 96 mg |
| 32 mg | 128 mg |
| 160 mg |
HCP Quick Reference Tool – Treatment Initiation
Buvidal Dosing Card
1. MHRA. Public Assessment Report Espranor 2mg & 8mg oral lyophilisate (buprenorphine hydrochloride).
During the treatment journey
Doses may be adjusted up or down, and patients can be switched between weekly and monthly products. Flexible dosing allows use across the different treatment phases, from initiation and stabilisation to maintenance treatment.
Buvidal should be administered weekly or monthly according to:
- Individual patients’ needs
- Clinical judgement
- Doses established during treatment initiation or before switching between treatments
A maximum of one supplemental Buvidal 8 mg dose may be administered at an unscheduled visit between regular weekly and monthly doses (except 160 mg), based on an individual patient’s temporary needs.
The maximum dose per week for patients who are on weekly Buvidal treatment is 32 mg with an additional 8 mg dose.
The maximum dose per month for patients who are on monthly Buvidal treatment is 160 mg.
To avoid missed doses:
- Weekly Buvidal doses may be administered up to two days before or after the weekly scheduled appointment
- Monthly Buvidal doses may be administered up to one week before or after the monthly scheduled appointment
If a dose is missed, the next dose should be administered as soon as practically possible.
For management of acute pain during continued use of Buvidal, a combination of use of opioids with high mu-opioid receptor affinity (e.g. fentanyl), non-opioid analgesics and regional anaesthesia might be necessary.
Titration of oral or intravenous short-acting opioid pain medicinal products (immediate-release morphine, oxycodone or fentanyl) to the desired analgesic effect in patients treated with Buvidal might require higher doses. Patients should be monitored during treatment and caution should be exerecised due to the potential risk of overdose and / or death.
Use with other medications – Patients 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. The prolonged-release properties of Buvidal should be considered during treatment.
Common side effects
Most of the side effects of Buvidal treatment are similar to those reported for sublingual buprenorphine. However, Buvidal can have other side effects, such as reactions around the injection site.1,2
Injection site-related adverse reactions of abscess, ulceration and necrosis have been reported during postmarketing use with Buvidal.
The most common adverse reactions reported for Buvidal in a double-blind, phase III efficacy trial were injection site pain, injection site pruritus and injection site erythema.1
The injection site reactions were all mild or moderate in severity, and most events were transient.
Very common adverse reactions (≥1/10 people) are insomnia, headache, nausea, hyperhidrosis, drug withdrawal syndrome and pain.
There are other common side effects. These are listed in the prescribing information.
You can also refer to the Summary of Product Characteristics for more information:
– Click here to read the UK Buvidal SmPC
– Click here to read the NI Buvidal SmPC
HCP Quick Reference Tool – Dosing Windows
1. Lofwall MR, et al. JAMA Intern Med 2018;178(6):764-773
2. Frost M, et al. Addiction 2019;114:1416–26
Completing the treatment journey
Termination of treatment
If Buvidal treatment is discontinued, its prolonged-release characteristics and any withdrawal symptoms experienced by the patient must be considered.
If the patient is switched to treatment with sublingual buprenorphine, this should be done one week after the last weekly dose or one month after the last monthly dose of Buvidal, according to the recommendations in the table above.
