Buprenorphine prolonged release injection
- Drugs List
- Therapeutic Indications
- Dosage
- Administration
- Contraindications
- Precautions and Warnings
- Pregnancy and Lactation
- Side Effects
- Monograph
Presentation
Weekly prolonged release injections of buprenorphine (8mg/0.16ml, 16mg/0.32ml, 24mg/0.48ml and 32mg/0.64ml preparations).
Monthly prolonged release injections of buprenorphine (64mg/0.18ml, 96mg/0.27ml, 128mg/0.36ml and 160mg/0.45ml preparations).
Drugs List
Therapeutic Indications
Uses
Opioid drug dependency - treatment
Dosage
Adults
Initial treatment
Patients not previously receiving buprenorphine:
Prior to starting treatment, confirm tolerability to buprenorphine by administering 4mg of sublingual buprenorphine followed by an hour of observation.
To avoid precipitated withdrawal, initiate treatment once the patient is showing signs of mild to moderate opioid withdrawal. This will vary depending on the type of opioid used (long or short acting), length of time since last opioid use and the degree of opioid dependence.
As a guide, for patients using heroin or other short acting opioids, administer the initial dose of buprenorphine at least 6 hours after the last opioid dose. For patients receiving methadone, reduce the methadone dose to 30mg per day before transferring to buprenorphine prolonged release injection and administer the initial dose of buprenorphine at least 24 hours after the last methadone dose.
Using weekly buprenorphine prolonged release injection:
Week One: 16mg with one or two additional 8mg doses at least 1 day apart aiming for a total dose of 24mg to 32mg during the first week.
Week Two: The total dose administered during the first week of treatment.
Continue treatment with weekly buprenorphine prolonged release injection for at least 4 weeks, adjusting the dose as required. Once stabilised, treatment can be transferred to monthly buprenorphine prolonged release injection (See Maintenance treatment).
Maintenance treatment
Doses can be increased or decreased and switched between the weekly and monthly preparations as clinically indicated. Closer monitoring may be required after any changes. Approximate equivalent doses are provided above.
Supplemental doses
Supplemental doses can be given if required. A maximum of one supplemental dose of 8mg is permitted between each weekly or monthly dose.
Maximum total dose for patients on weekly buprenorphine prolonged release injection is 32mg with one additional 8mg dose.
Maximum total dose for patients on monthly buprenorphine prolonged release injection is 160mg.
Additional Dosage Information
Missed doses
Weekly buprenorphine prolonged release injection: Doses may be administered up to 2 days before or after the scheduled dose.
Monthly buprenorphine prolonged release injection: Doses may be administered up to 1 week before or after the scheduled dose.
Discontinuing treatment
Withdrawal symptoms may occur which due to the prolonged release nature of the preparation may have a delayed onset.
Switching to sublingual buprenorphine
From weekly buprenorphine prolonged release injection: Initiate sublingual buprenorphine 1 week after the last injection.
From monthly buprenorphine prolonged release injection: Initiate sublingual buprenorphine 1 month after the last injection.
Switching from sublingual buprenorphine:
Switch directly to either weekly or monthly buprenorphine prolonged release injection. Administer the initial dose the day after the last dose of sublingual buprenorphine.
The following equivalent doses are provided by the manufacturer to guide dose conversion:
2mg to 6mg per day of sublingual buprenorphine is equivalent to an 8mg weekly buprenorphine prolonged release injection;
8mg to 10mg per day of sublingual buprenorphine is equivalent to a 16mg weekly buprenorphine prolonged release injection or a 64mg monthly buprenorphine prolonged release injection;
12mg to 16mg per day of sublingual buprenorphine is equivalent to a 24mg weekly buprenorphine prolonged release injection or a 96mg monthly buprenorphine prolonged release injection;
18mg to 24mg per day of sublingual buprenorphine is equivalent to a 32mg weekly buprenorphine prolonged release injection or a 128mg monthly buprenorphine prolonged release injection;
26mg to 32mg per day of sublingual buprenorphine is equivalent to a 160mg monthly buprenorphine prolonged release injection.
Administration
For subcutaneous injection only.
Contraindications
Acute alcohol intoxication
Children under 16 years
Risk of paralytic ileus
Within 2 weeks of discontinuing MAOIs
Coma
Delirium tremens
Head trauma
Long QT syndrome
Raised intracranial pressure
Severe hepatic impairment
Severe respiratory impairment
Torsade de pointes
Precautions and Warnings
Children aged 16 to 18 years
Family history of long QT syndrome
Patients over 65 years
Adrenal insufficiency
Alcoholism
Anorexia nervosa
Asthma
Benign prostatic hyperplasia
Biliary tract disorder
Breastfeeding
Cardiac failure secondary to pulmonary disorder
Chronic obstructive pulmonary disease
Electrolyte imbalance
Hepatitis B
Hepatitis C
History of seizures
History of torsade de pointes
Hypercapnia
Hypotension
Hypothyroidism
Hypoxia
Intracranial lesion
Kyphoscoliosis with respiratory compromise
Moderate hepatic impairment
Pregnancy
Reduced respiratory reserve
Renal impairment - creatinine clearance below 30 ml/minute
Respiratory depression
Respiratory impairment
Urethral stricture
Correct electrolyte disorders before treatment
Advise patient ability to drive or operate machinery may be impaired
Advise patient not to drive until they know how the medicine affects them
Advise patient this medicine may be subject to driving restrictions
Contains soya or soya derivative
Some formulations may contain alcohol
Avoid accidental intravascular injection
Rotate injection sites. Allow 8 weeks before weekly dose to same site
Perform liver function tests before commencing therapy and during therapy
Be vigilant for medicines diversion
Consider monitoring ECG in patients at risk of QT prolongation
If hepatic impairment symptoms occur monitor LFT & consider discontinuation
Monitor patients for signs and symptoms of Serotonin Syndrome
Monitor serum electrolytes
Neonate exposed in utero: Monitor for neonatal withdrawal syndrome
When used with SSRIs, risk of Serotonin syndrome
Consider dose reduction or discontinuation if serotonin syndrome suspected
May cause dependence
Potential for withdrawal symptoms
Withdraw treatment gradually under supervision of a specialist
Consider reducing dose in elderly
Advise patient not to take St John's wort concurrently
Advise that effects are potentiated by CNS depressants (including alcohol)
Hepatic injury may occur during treatment. This risk is higher in patients who are positive for viral hepatitis, with existing liver dysfunction and in those on concomitant hepatotoxic medicines. Reported cases are thought to have been precipitated by the presence of pre-existing liver-enzyme abnormalities, genetic disease, infection with hepatitis B or C, alcohol abuse, anorexia, concomitant hepatotoxic drugs or ongoing injecting drug use. If a hepatic event is suspected, evaluate for potential causes and consider discontinuing treatment. If treatment is to continue, monitor hepatic function closely.
Accumulation may occur in patients with moderate hepatic impairment. As such, these patients should be monitored closely for signs of precipitated opioid withdrawal, toxicity or overdose.
Experience is limited in patients aged 16 to 18 years. Close monitoring is advised.
If analgesia for acute pain is required during treatment with buprenorphine a combination of opioids with high mu-opioid receptor affinity (e.g. fentanyl), non-opioid analgesics and regional anaesthesia may be necessary. Oral or intravenous short-acting opioids (e.g. immediate release morphine, oxycodone or fentanyl) may require higher doses and should be titrated carefully with close monitoring.
Take care to avoid accidental intravascular injection. Buprenorphine prolonged release injection forms a solid mass upon contact with body fluids which could cause a blood vessel injury, occlusion or thromboembolic event. Buprenorphine prolonged release injection must be administered directly to the patient by a healthcare professional. Due to the risk of diversion, it is not available for take home use or self administration.
Due to the prolonged release nature of this product, initial onset of effects may be delayed. As such, monitor patients closely for signs of toxicity, overdose or withdrawal.
Before commencing treatment with buprenorphine, a strategy should be constructed with the patient for ending treatment in order to reduce the risk of drug withdrawal syndrome.
Pregnancy and Lactation
Pregnancy
Use buprenorphine prolonged release injection with caution during pregnancy.
The manufacturer advises that buprenorphine prolonged release injection should only be used during pregnancy where the benefits outweigh potential risks to the foetus.
Information regarding the use of buprenorphine during human pregnancy is limited including no specific data around the use of buprenorphine as a prolonged release subcutaneous injection. Available animal studies regarding this presentation of buprenorphine indicate no reproductive toxicity but wider evidence is limited and as such the risk during early pregnancy is unclear. When administered via other routes of administration, buprenorphine is known to cross the placenta but transfer is thought to be lower than with other opioids.
Long term use of buprenorphine during the third trimester may cause withdrawal symptoms in the neonate including hypertonia, tremor, agitation, myoclonus and convulsions. Symptoms typically present several hours to days after birth. Use during the late stages of pregnancy, even for short periods, is also associated with a risk of respiratory depression in the neonate. Exposed infants should be monitored closely for several days after birth for signs of respiratory depression or withdrawal syndrome.
Due to the prolonged release nature of this product, any adverse effects may be longer lasting. As such, management with a shorter acting oral preparation may be more appropriate. This should be balanced against the risk of maternal relapse.
Lactation
Use buprenorphine prolonged release injection with caution during breastfeeding.
The manufacturer advises caution.
Buprenorphine and its metabolites are excreted in breast milk but quantities are small and buprenorphine is poorly absorbed by infants. Long term effects on breastfed infants have not been well studied but LactMed (2018) suggests that stabilised patients should be encouraged to breastfeed. Due to the prolonged release nature of this product, any adverse effects may be longer lasting. As such, management with a shorter acting oral preparation may be more appropriate but this should be balanced against the risk of maternal relapse.
If used, infants should be monitored for drowsiness, respiratory depression, adequate weight gain and developmental milestones. Advise patients to seek immediate medical advice if the infant shows signs of increased sleepiness, difficulty breastfeeding, breathing difficulties or limpness. If breast feeding is stopped abruptly, observe the infant for signs of withdrawal.
Effects on Ability to Drive and Operate Machinery
This class of medicine is in the list of drugs included in regulations under 5a of the Road Traffic Act 1988 (England and Wales). When prescribing this medicine: Advise patient the medicine can affect cognitive function and is likely to affect ability to drive. Advise patient not to drive until they know how the medicine affects them.
Side Effects
Abdominal pain
Abnormal liver function tests
Abnormal thinking
Acute hepatic injury
Agitation
Anxiety
Arthralgia
Asthenia
Asthma
Back pain
Bone pain
Bronchitis
Bruising at injection site
Cellulitis (injection site)
Chest pain
Chills
Constipation
Cough
Cytolytic hepatitis
Decreased appetite
Dependence
Depression
Diarrhoea
Dizziness
Drowsiness
Dry mouth
Dysmenorrhoea
Dyspepsia
Dyspnoea
Erythema
Erythema at injection site
Euphoria
Flatulence
Gastrointestinal disorder
Hallucinations
Headache
Hepatic encephalopathy
Hepatic failure
Hepatic necrosis
Hepato-renal syndrome
Hostility
Hyperhidrosis
Hypersensitivity reactions
Hypertonia
Hypotension
Increased cerebrospinal fluid pressure
Increases in hepatic enzymes
Induration (injection site)
Infection
Inflammation (injection site)
Influenza
Injection site reactions
Insomnia
Itching (injection site)
Lacrimation disorder
Local pain (injection site)
Localised urticaria
Lymphadenopathy
Macular rash
Malaise
Migraine
Miosis
Muscle spasm
Myalgia
Mydriasis
Nausea
Neck pain
Neonatal withdrawal symptoms
Nervousness
Orthostatic hypotension
Pain
Palpitations
Paraesthesia
Paranoia
Peripheral oedema
Pharyngitis
Pruritus
Pyrexia
Rash
Rhinitis
Seizures
Somnolence
Speech disturbances
Swelling (injection site)
Syncope
Tremor
Urinary retention
Urticaria
Vasodilation
Vertigo
Vomiting
Withdrawal symptoms
Yawning
Withdrawal Symptoms and Signs
Some or all of the opioid drug withdrawal syndrome side effects are: restlessness, lacrimation, rhinorrhoea, yawning, perspiration, chills, myalgia, mydriasis and palpitations. Other symptoms may also develop including irritability, agitation, anxiety, hyperkinesia, tremor, weakness, insomnia, anorexia, abdominal cramps, nausea, vomiting, diarrhoea, increased blood pressure, increased respiratory rate or heart rate.
When a patient no longer requires treatment, it is advisable to taper the dose gradually to minimise symptoms of withdrawal. Tapering from a high dose may take weeks to months.
Further Information
Last Full Review Date: March 2019
Reference Sources
Drugs During Pregnancy and Lactation: Treatment Options and Risk Assessment, 3rd edition (2015) ed. Schaefer, C., Peters, P. and Miller, R. Elsevier, London.
Drugs in Pregnancy and Lactation: A Reference Guide to Fetal and Neonatal Risk, 10th edition (2015) ed. Briggs, G., Freeman, R. Wolters Kluwer Health, Philadelphia.
Summary of Product Characteristics: Buvidal 8/16/24/32 mg prolonged-release solution for injection. Camurus AB. Revised September 2020.
Summary of Product Characteristics: Buvidal 64/96/128 mg prolonged-release solution for injection. Camurus AB. Revised September 2020.
Summary of Product Characteristics: Buvidal 160 mg prolonged-release solution for injection. Camurus AB. Revised June 2021.
Gov.uk. Government departments. Department for Transport. Publications. Drug driving and medicine: Advice for healthcare professionals. Drug driving: Guidance for healthcare professionals on drug driving. Available at: https://www.gov.uk/ Last accessed: 6 January 2015
New drug driving offence: implications for medicines packaging. Medicines Regulatory News. 10 December 2013. Available at: https://www.mhra.gov.uk Last accessed: 6 January 2015
US National Library of Medicine. Toxicology Data Network. Drugs and Lactation Database (LactMed).
Available at: https://toxnet.nlm.nih.gov/cgi-bin/sis/htmlgen?LACT
Buprenorphine. Last revised: 03 December 2018
Last accessed: 13 March 2019
Medscape UK | Univadis prescription drug monographs & interactions are based on FDB Multilex Content
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