Safety Profile

The adverse reactions most frequently reported for buprenorphine are headache, nausea, hyperhidrosis, insomnia, drug withdrawal syndrome and pain.

Contraindications

Hypersensitivity to the active substance or to any of the excipients

Severe respiratory insufficiency

Severe hepatic impairment

Acute alcoholism or delirium tremens

Special warnings and precautions for use

Administration

Care must be taken to avoid inadvertent injection of Buvidal®. The dose must not be administered intravascularly (intravenously), intramuscularly or intradermally.

To minimise the risk of misuse, abuse and diversion, appropriate precautions should be taken when prescribing and dispensing buprenorphine.

Healthcare professionals should administer Buvidal directly to the patient.

Take-home use or self-administration of the product by patients is not allowed. Any attempts to remove the depot should be monitored throughout treatment.

Prolonged-release properties

The prolonged-release properties of the product should be considered during treatment including initiation and termination.

In particular, patients with concomitant medicinal products and/or co-morbidities, should be monitored for signs and symptoms of toxicity, overdose or withdrawal caused by increased or decreased levels of buprenorphine.

Respiratory depression

A number of cases of death due to respiratory depression have been reported for patients being treated with buprenorphine, particularly when used in combination with benzodiazepines or when buprenorphine was not used according to prescribing information.

Deaths have also been reported in association with concomitant administration of buprenorphine and other depressants such as alcohol, gabapentinoids (such as pregabalin and gabapentin) or other opioids.

Buprenorphine should be used with care in patients with respiratory insufficiency (e.g. chronic obstructive pulmonary disease, asthma, cor pulmonale, decreased respiratory reserve, hypoxia, hypercapnia, pre-existing respiratory depression or kyphoscoliosis).

Buprenorphine may cause severe, possibly fatal, respiratory depression in children and non-opioid dependent persons who accidentally or deliberately use it.

CNS depression

Buprenorphine may cause drowsiness particularly when taken together with alcohol or central nervous system depressants such as benzodiazepines, tranquilisers, sedatives, gabapentinoids or hypnotics.

Dependence

Buprenorphine is a partial agonist at the mu-opiate receptor and chronic administration can produce opioid dependence.

Hepatitis and hepatic events

Baseline liver function tests and documentation of viral hepatitis status are recommended prior to starting therapy. Patients who are positive for viral hepatitis, on certain concomitant medicinal products and/or who have existing liver dysfunction are at greater risk of liver injury. Regular monitoring of the liver function is recommended.

Cases of acute hepatic injury have been reported in opioid-dependent patients both in clinical studies and in post-marketing adverse reaction reports with medicinal products containing buprenorphine.

When a hepatic event is suspected, further biological and aetiological evaluation is required. Depending on the findings, Buvidal may be discontinued. Monitoring beyond the weekly and monthly treatment period may be needed. If treatment is continued, hepatic function should be monitored closely.

Precipitation of opioid withdrawal syndrome

When initiating treatment with buprenorphine, it is important to be aware of the partial agonist profile of buprenorphine. Buprenorphine products have caused precipitated withdrawal symptoms in opioid-dependent patients when administered before the agonist effects resulting from recent opioid use or misuse have subsided.

To avoid precipitated withdrawal, induction must be undertaken when objective signs and symptoms of mild to moderate withdrawal are evident.

Discontinuation of treatment may result in a withdrawal syndrome that may be delayed in onset.

Hepatic impairment

Buprenorphine is extensively metabolised in the liver.

Patients with moderate hepatic impairment should be monitored for signs and symptoms of precipitated opioid withdrawal, toxicity or overdose caused by increased levels of buprenorphine.

Buprenorphine should be used with caution in patients with moderate hepatic impairment. Hepatic function should be monitored regularly whilst on treatment.

The use of buprenorphine is contraindicated in patients with severe hepatic impairment.

QT prolongation

Caution should be exercised when co-administering Buvidal with other medicinal products that prolong the QT interval and in patients with a history of long QT syndrome or other risk factors for QT prolongation.

Renal impairment

Metabolites of buprenorphine accumulate in patients with renal failure.

Caution is recommended when dosing patients with severe renal impairment (creatinine clearance <30 ml/min).

Acute pain management

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.

Use in children and adolescents

The safety and efficacy of buprenorphine in children below the age of 16 years have not been established.

Due to limited data in adolescents (aged 16 or 17 years), patients in this age group should be monitored closely during treatment.

Class effects

Opioids may cause orthostatic hypotension.

Opioids may elevate cerebrospinal fluid pressure, which may cause seizures. Therefore, opioids should be used with caution in patients with head injury, intracranial lesions, other circumstances where cerebrospinal pressure may be increased, or history of seizure.

Opioids should be used with caution in patients with hypotension, prostatic hypertrophy or urethral stenosis.

Opioid-induced miosis, changes in the level of consciousness or changes in the perception of pain as a symptom of disease may interfere with patient evaluation or obscure the diagnosis or clinical course of concomitant disease.

Opioids should be used with caution in patients with myxoedema, hypothyroidism, or adrenal cortical insufficiency (e.g. Addison’s disease).

Opioids have been shown to increase intracholedochal pressure and should be used with caution in patients with dysfunction of the biliary tract.

Adverse reactions

The table below presents adverse reactions reported for buprenorphine, including Buvidal. The following terms and frequencies are applied: very common (≥ 1/10), common (≥ 1/100 to < 1/10), uncommon (≥ 1/1000 to < 1/100) and frequency not known (cannot be estimated from available data).

Adverse reactions listed by body system

System Organ Class Very common Common Uncommon Not known
Infections and infestations Infection
Influenza
Pharyngitis
Rhinitis

Injection site cellulitis

 

Blood and lymphatic system disorders Lymphadenopathy
Immune system disorders Hypersensitivity
Metabolism and nutrition disorders Decreased appetite
Psychiatric disorders Insomnia Anxiety
Agitation
Depression
Hostility
Nervousness
Thinking abnormal
Paranoia
Medical dependence
Hallucinations
Euphoric mood
Nervous system disorders

Headache

 

Somnolence
Dizziness
Migraine Paraesthesia
Syncope
Tremor
Hypertonia
Speech disorders
Eye disorders Lacrimal disorder
Mydriasis
Miosis
Ear and labyrinth disorders Vertigo
Cardiac disorders Palpitations
Vascular disorders Vasodilation
Hypotension
Respiratory, thoracic and mediastinal disorders Cough
Dyspnoea
Yawning
Asthma
Bronchitis
Gastrointestinal disorders Nausea Constipation
Vomiting
Abdominal pain
Flatulence
Dyspepsia
Dry mouth
Diarrhoea
Gastrointestinal disorder
Hepatobiliary disorders Alanine aminotransferase increased
Aspartate aminotransferase increased
Hepatic enzymes increased
Skin and subcutaneous tissue disorders Rash
Pruritus
Urticaria
Rash macular Erythema
Musculoskeletal and connective tissue disorders Arthralgia
Back pain
Myalgia
Muscle spasms
Neck pain
Bone pain
Renal and urinary disorders Urinary retention
Reproductive system and breast disorders Dysmenorrhoea
General disorders and administration site conditions Hyperhidrosis
Drug withdrawal syndrome
Pain
Injection site pain
Injection site pruritus
Injection site erythema
Injection site swelling
Injection site reaction
Injection site induration
Injection site mass
Oedema peripheral
Asthenia
Malaise
Pyrexia
Chills
Neonatal withdrawal syndrome
Chest pain
Injection site inflammation
Injection site bruising
Injection site urticaria
Investigations Abnormal liver function tests
Injury, poisoning and procedural complications Procedural dizziness

Reporting of suspected adverse reactions

Reporting suspected adverse reactions after authorisation of the medical product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via their national reporting system.

 

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© 2020 Camurus AB. All rights reserved | INT-BUV-1900007 | Date of preparation: February 2019

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