Drugs List

Therapeutic Indications

Uses

Substitution treatment for opioid drug dependence

Substitution treatment for opioid dependence in clinically stable adult patients who require no more than 8mg/day of sublingual buprenorphine, and who are also receiving medical, social and psychological support.

Administration

To be administered by a healthcare professional who has been appropriately trained and accredited in the procedure. Ultrasound and MRI facilities need to be available to the clinical site at which the insertion and removal of the implants occurs.

Four implants are inserted subcutaneously according to manufacturer's instructions in the inner side of the upper arm approximately 8 to 10cm above the medial epicondyle, in the sulcus between the biceps and triceps muscle.

Immediately after insertion, verify the presence of the implant by palpation. If it cannot be palpated, or its presence is doubtful, confirm its presence with other methods to confirm the presence of the implant.

When removing the implant verify the location by palpation of the arm. After removal of all implants, confirm that the entire 26.5mm long implant has been removed by measuring its length.

Contraindications

Children under 18 years
Alcoholism
Breastfeeding
Delirium tremens
Head trauma
History of keloid formation
Pregnancy
Raised intracranial pressure
Severe hepatic impairment
Severe respiratory impairment

Precautions and Warnings

Anaesthesia
Debilitation
Females of childbearing potential
History of recurrent methicillin-resistant Staphylococcus aureus infections
Patients over 65 years
Adrenal insufficiency
Asthma
Benign prostatic hyperplasia
Biliary tract disorder
Connective tissue disorder
History of seizures
Hypotension
Hypothyroidism
Mild hepatic impairment
Myxoedema
Renal impairment - creatinine clearance below 30 ml/minute
Respiratory impairment
Urethral stricture

Before initiating screen all patients for viral hepatitis
Advise ability to drive/operate machinery may be affected by side effects
Pre-treatment medical history and clinical examination
Treatment to be initiated and supervised by a specialist
Aseptic technique should be used throughout
Expulsion may occur if inserted incorrectly
Evaluate treatment efficacy regularly
Examine insertion site one week after implant and regularly thereafter
Monitor for signs of dependence
Monitor liver function. Withdraw if evidence of hepatotoxic reaction
Potential for drug abuse
Abuse may cause serious adverse events, dependence and withdrawal symptoms
Advise patient to seek advice at first indications of pregnancy
Advise patient not to take St John's wort concurrently
Advise patient to avoid alcohol during treatment
Advise that effects are potentiated by CNS depressants (including alcohol)
Advise patient grapefruit products may increase plasma level
Female: Ensure adequate contraception during treatment
Remind patient of importance of carrying Alert Card with them at all times

There may be situations during treatment with buprenorphine where patients need acute pain management or anaesthesia. Patients should be treated with a non-opioid analgesic whenever possible. Patients requiring opioid therapy for analgesic may be treated with a high-affinity full opioid analgesic under the supervision of a healthcare professional, with particular attention to respiratory function. Higher doses may be required for analgesic effect, therefore there is a higher risk of toxicity with opioid administration. If opioid therapy is required as part of anaesthesia, patients should be continuously monitored in an anaesthesia care setting by persons not involved in the conduct of the surgical or diagnostic procedure.

Patients with mild to moderate hepatic impairment or patients that develop hepatic impairment during treatment should be monitored for signs and symptoms of toxicity or overdose caused by increased levels of buprenorphine (miosis, lip cyanosis, sedation, bradycardia, hypotension, respiratory depression). If toxicity or overdose is observed, buprenorphine implants should be removed and transition to a medicinal product that allows dose adjustment are required.

The insertion site should be examined one week following insertion and regularly thereafter for signs of infections, any problems with wound healing, including evidence of implant extrusion from the skin as well as misuse or abuse. Recommended visit schedule for most patients is no less than once a month for continued counselling and psychosocial support.

Nerve damage and migration, resulting in embolism and death, may occur after improper insertion of drug implants in the upper arm. Other complications include, local migration, protrusion, expulsion and implant breakage after insertion or during removal. Surgical intervention is necessary for removing an implant that has migrated. Implants that have been placed too deeply may lead to neural or vascular injury upon insertion or removal.

Insertion and removal of the buprenorphine implants must be performed by a physician who is competent in minor surgery and has had the relevant training to conduct the insertion and removal procedure.

Pregnancy and Lactation

Pregnancy

Buprenorphine is contraindicated during pregnancy.

The manufacturer does not recommend using buprenorphine during pregnancy and in women of child bearing potential not using contraception. There is limited available data regarding the use of buprenorphine in pregnant women. Studies in animals have shown reproductive toxicity. The potential risk for humans is unknown.

Long-term administration of buprenorphine during the last three months of pregnancy may cause withdrawal syndrome in the neonate. The syndrome is generally delayed for several hours to several days after birth. Due to the long half-life of buprenorphine, neonatal monitoring should be considered at the end of pregnancy to prevent the risk of respiratory depression or withdrawal syndrome in neonates.

Lactation

Buprenorphine is contraindicated during breastfeeding.

The manufacturer does not recommend breastfeeding whilst using the buprenorphine implant. Buprenorphine and its metabolites are excreted in human milk, therefore effects on breastfed infants are likely.

Side Effects

Abdominal pain
Abnormal thinking
Abscess
Agitation
Alanine aminotransferase increased
Anxiety
Apathy
Arthralgia
Asthenia
Atrial flutter
Blurred vision
Bone pain
Bradycardia
Bronchitis
Cellulitis
Chills
Cold sweat
Constipation
Cough
Decreased appetite
Dehydration
Dependence
Depression
Diarrhoea
Discomfort in limb
Dizziness
Dry mouth
Dry skin
Dysmenorrhoea
Dyspepsia
Dyspnoea
Ecchymosis
Erectile dysfunction
Euphoria
Eye disorder
Fatigue
Flatulence
Gastrointestinal disorder
Haematochezia
Headache
Hostility
Hot flushes
Hyperhidrosis
Hypersomnia
Hypertension
Hypertonia
Hypoaesthesia
Impaired consciousness
Implant expulsion
Implant site abscess
Implant site erythema
Implant site haematoma
Implant site haemorrhage
Implant site infection
Implant site pain
Implant site pruritus
Implant site rash
Increased appetite
Infections
Influenza
Insomnia
Irritability
Lacrimal gland disorder
Lymphadenopathy
Micturition disorders
Migraine
Muscle spasm
Myalgia
Mydriasis
Nausea
Nervousness
Neutropenia
Orgasmic dysfunction
Pain
Palpitations
Paraesthesia
Paranoia
Pharyngitis
Pollakiuria
Procedural pain
Rash
Reduced libido
Respiratory depression
Restlessness
Rhinitis
Skin infection
Skin lesions
Sleep disorders
Somnolence
Syncope
Tooth disorder
Tremor
Urinary hesitancy
Urinary tract infections
Vasodilation
Viral infection
Vomiting
Vulvovaginal infections
Weight gain
Yawning

Presentation

Implant containing buprenorphine.

Drugs List

Therapeutic Indications

Uses

Substitution treatment for opioid drug dependence

Substitution treatment for opioid dependence in clinically stable adult patients who require no more than 8mg/day of sublingual buprenorphine, and who are also receiving medical, social and psychological support.

Dosage

Patients that have had previous treatment with sublingual buprenorphine or sublingual buprenorphine and naloxone, must be on stable doses of between 2 to 8mg/day for at least 30 days and deemed clinical stable by the treating healthcare professional.

The buprenorphine implant should only be used in patients who are opioid tolerant.

Adults

Additional Dosage Information

Administration

To be administered by a healthcare professional who has been appropriately trained and accredited in the procedure. Ultrasound and MRI facilities need to be available to the clinical site at which the insertion and removal of the implants occurs.

Four implants are inserted subcutaneously according to manufacturer's instructions in the inner side of the upper arm approximately 8 to 10cm above the medial epicondyle, in the sulcus between the biceps and triceps muscle.

Immediately after insertion, verify the presence of the implant by palpation. If it cannot be palpated, or its presence is doubtful, confirm its presence with other methods to confirm the presence of the implant.

When removing the implant verify the location by palpation of the arm. After removal of all implants, confirm that the entire 26.5mm long implant has been removed by measuring its length.

Contraindications

Children under 18 years
Alcoholism
Breastfeeding
Delirium tremens
Head trauma
History of keloid formation
Pregnancy
Raised intracranial pressure
Severe hepatic impairment
Severe respiratory impairment

Precautions and Warnings

Anaesthesia
Debilitation
Females of childbearing potential
History of recurrent methicillin-resistant Staphylococcus aureus infections
Patients over 65 years
Adrenal insufficiency
Asthma
Benign prostatic hyperplasia
Biliary tract disorder
Connective tissue disorder
History of seizures
Hypotension
Hypothyroidism
Mild hepatic impairment
Myxoedema
Renal impairment - creatinine clearance below 30 ml/minute
Respiratory impairment
Urethral stricture

Before initiating screen all patients for viral hepatitis
Advise ability to drive/operate machinery may be affected by side effects
Pre-treatment medical history and clinical examination
Treatment to be initiated and supervised by a specialist
Aseptic technique should be used throughout
Expulsion may occur if inserted incorrectly
Evaluate treatment efficacy regularly
Examine insertion site one week after implant and regularly thereafter
Monitor for signs of dependence
Monitor liver function. Withdraw if evidence of hepatotoxic reaction
Potential for drug abuse
Abuse may cause serious adverse events, dependence and withdrawal symptoms
Advise patient to seek advice at first indications of pregnancy
Advise patient not to take St John's wort concurrently
Advise patient to avoid alcohol during treatment
Advise that effects are potentiated by CNS depressants (including alcohol)
Advise patient grapefruit products may increase plasma level
Female: Ensure adequate contraception during treatment
Remind patient of importance of carrying Alert Card with them at all times

There may be situations during treatment with buprenorphine where patients need acute pain management or anaesthesia. Patients should be treated with a non-opioid analgesic whenever possible. Patients requiring opioid therapy for analgesic may be treated with a high-affinity full opioid analgesic under the supervision of a healthcare professional, with particular attention to respiratory function. Higher doses may be required for analgesic effect, therefore there is a higher risk of toxicity with opioid administration. If opioid therapy is required as part of anaesthesia, patients should be continuously monitored in an anaesthesia care setting by persons not involved in the conduct of the surgical or diagnostic procedure.

Patients with mild to moderate hepatic impairment or patients that develop hepatic impairment during treatment should be monitored for signs and symptoms of toxicity or overdose caused by increased levels of buprenorphine (miosis, lip cyanosis, sedation, bradycardia, hypotension, respiratory depression). If toxicity or overdose is observed, buprenorphine implants should be removed and transition to a medicinal product that allows dose adjustment are required.

The insertion site should be examined one week following insertion and regularly thereafter for signs of infections, any problems with wound healing, including evidence of implant extrusion from the skin as well as misuse or abuse. Recommended visit schedule for most patients is no less than once a month for continued counselling and psychosocial support.

Nerve damage and migration, resulting in embolism and death, may occur after improper insertion of drug implants in the upper arm. Other complications include, local migration, protrusion, expulsion and implant breakage after insertion or during removal. Surgical intervention is necessary for removing an implant that has migrated. Implants that have been placed too deeply may lead to neural or vascular injury upon insertion or removal.

Insertion and removal of the buprenorphine implants must be performed by a physician who is competent in minor surgery and has had the relevant training to conduct the insertion and removal procedure.

Pregnancy and Lactation

Pregnancy

Buprenorphine is contraindicated during pregnancy.

The manufacturer does not recommend using buprenorphine during pregnancy and in women of child bearing potential not using contraception. There is limited available data regarding the use of buprenorphine in pregnant women. Studies in animals have shown reproductive toxicity. The potential risk for humans is unknown.

Long-term administration of buprenorphine during the last three months of pregnancy may cause withdrawal syndrome in the neonate. The syndrome is generally delayed for several hours to several days after birth. Due to the long half-life of buprenorphine, neonatal monitoring should be considered at the end of pregnancy to prevent the risk of respiratory depression or withdrawal syndrome in neonates.

Lactation

Buprenorphine is contraindicated during breastfeeding.

The manufacturer does not recommend breastfeeding whilst using the buprenorphine implant. Buprenorphine and its metabolites are excreted in human milk, therefore effects on breastfed infants are likely.

Side Effects

Abdominal pain
Abnormal thinking
Abscess
Agitation
Alanine aminotransferase increased
Anxiety
Apathy
Arthralgia
Asthenia
Atrial flutter
Blurred vision
Bone pain
Bradycardia
Bronchitis
Cellulitis
Chills
Cold sweat
Constipation
Cough
Decreased appetite
Dehydration
Dependence
Depression
Diarrhoea
Discomfort in limb
Dizziness
Dry mouth
Dry skin
Dysmenorrhoea
Dyspepsia
Dyspnoea
Ecchymosis
Erectile dysfunction
Euphoria
Eye disorder
Fatigue
Flatulence
Gastrointestinal disorder
Haematochezia
Headache
Hostility
Hot flushes
Hyperhidrosis
Hypersomnia
Hypertension
Hypertonia
Hypoaesthesia
Impaired consciousness
Implant expulsion
Implant site abscess
Implant site erythema
Implant site haematoma
Implant site haemorrhage
Implant site infection
Implant site pain
Implant site pruritus
Implant site rash
Increased appetite
Infections
Influenza
Insomnia
Irritability
Lacrimal gland disorder
Lymphadenopathy
Micturition disorders
Migraine
Muscle spasm
Myalgia
Mydriasis
Nausea
Nervousness
Neutropenia
Orgasmic dysfunction
Pain
Palpitations
Paraesthesia
Paranoia
Pharyngitis
Pollakiuria
Procedural pain
Rash
Reduced libido
Respiratory depression
Restlessness
Rhinitis
Skin infection
Skin lesions
Sleep disorders
Somnolence
Syncope
Tooth disorder
Tremor
Urinary hesitancy
Urinary tract infections
Vasodilation
Viral infection
Vomiting
Vulvovaginal infections
Weight gain
Yawning

Overdosage

It is strongly recommended that the UK National Poisons Information Service be consulted on cases of suspected or actual overdose where there is doubt over the degree of risk or about appropriate management.

The following number will direct the caller to the relevant local centre (0844) 892 0111

Information may be obtained if you have access to ToxBase the primary clinical toxicology database of the National Poisons Information Service. This is available via password on the internet ( www.toxbase.org ) or if this is unavailable at the backup site ( www.toxbasebackup.org ).

Further Information

Last Full Review Date: June 2021

Reference Sources

Summary of Product Characteristics: Sixmo 74.2 mg implant. L. Molteni & C. dei F.lli Alitti Soc.Es.S.p.A. Revised January 2021.