Buprenorphine with naloxone oromucosal
- Drugs List
- Therapeutic Indications
- Dosage
- Administration
- Contraindications
- Precautions and Warnings
- Pregnancy and Lactation
- Side Effects
- Monograph
Presentation
Sublingual formulations containing buprenorphine and naloxone.
Drugs List
Therapeutic Indications
Uses
Substitution treatment for opioid drug dependence
Dosage
During treatment initiation, daily dispensing is recommended. After stabilisation, a reliable patient may be given a supply for several days treatment, however it is recommended that this is limited to 7 days.
Consideration should be given to the type of opioid dependence (long or short acting), the time since last opioid use and the degree of dependence. In order to avoid precipitating withdrawal symptoms, initiation of treatment should only be undertaken when objective and clear signs of opioid withdrawal are evident.
Adults
Treatment Initiation
Tablets
The recommended starting dose is two 2mg + 500micrograms tablets. An additional two 2mg + 500micrograms tablets may be administered on day one depending on the patients requirements.
OR
The recommended starting dose is a 1.4mg + 360micrograms tablet or 2.9mg + 710micrograms tablet once daily. An additional 1.4mg + 360micrograms tablet or 2.9mg + 710micrograms tablet may be administered on day one depending on the patients response.
Sublingual films
The recommended starting dose is two 2mg + 500micrograms sublingual films or one 4mg + 1mg sublingual film. Dose may be repeated twice on day one of treatment.
Patients dependent on heroin or short acting opioids
When treatment is started, the first dose should be taken as signs of opiate withdrawal appear or at least 6 to 12 hours after the last use of heroin or other short-acting opioids.
Patients receiving methadone
Before initiating treatment, the dose of methadone should be reduced to a maximum of 30mg daily. The first dose should be taken as signs of withdrawal appear, or not less than 24 hours after the patient last used methadone.
Dosage Adjustment and Maintenance
Dosage should be titrated according to response and reassessment of the clinical and psychological status of the patient. Maximum single daily dose should not exceed 24mg buprenorphine.
OR
Dose titration should occur in steps of 1.4mg to 5.7mg buprenorphine. Maximum single daily dose should not exceed 17.2mg buprenorphine.
Less than daily dosing
Once satisfactory stabilisation has been achieved, the frequency of dosing may be decreased to every other day at twice the individually titrated daily dose. For example, a patient titrated to 8mg/2mg daily may be given 16mg/4mg on alternate days, with no dose on the intervening days. Some patients may be able to have their dosage reduced to 3 times a week, e.g. Monday, Wednesday and Friday. The dose on Monday and Wednesday should be twice the titrated daily dose, and the dose on Friday three times the titrated daily dose. Dosage should never exceed a maximum single daily dose of 24mg buprenorphine. Patients requiring a daily dose of more than 8mg may not tolerate this regimen.
OR
Once satisfactory stabilisation has been achieved, the frequency of dosing may be decreased to every other day at twice the individually titrated daily dose. For example, a patient titrated to 5.7mg + 140micrograms daily may be given 11.4mg + 290micrograms on alternate days, with no dose on the intervening days. Some patients may be able to have their dosage reduced to 3 times a week, e.g. Monday, Wednesday and Friday. The dose on Monday and Wednesday should be twice the titrated daily dose, and the dose on Friday three times the titrated daily dose. Dosage should never exceed a maximum single daily dose of 17.2mg buprenorphine. Patients requiring a daily dose of more than 5.7mg buprenorphine a day may not tolerate this regimen.
Dosage Reduction and Discontinuation of Treatment
Once satisfactory stabilisation has been achieved, if the patient agrees, the dosage may be reduced gradually to a lower maintenance dose. In some favourable cases, treatment may be discontinued. Patients should be monitored following termination of treatment because of the potential for relapse.
Children
For children aged 15 years and over (See Dosage; Adult)
Additional Dosage Information
The bioavailability of some brands differs significantly from other buprenorphine with naloxone products, therefore the dose in mg can differ between products. Product literature must be consulted to determine the dosage before switching the patient to a different buprenorphine with naloxone product.
Sublingual Films
Switching between sublingual and buccal sites of administration
For induction buprenorphine/naloxone should be administered sublingually.
Once induction is complete, the patient can switch between buccal and sublingual administration. Upon switching, patients should be started on the same dose as the previously administered medicinal product. The patient should be monitored for over and underdosing due to the difference in administration bioavailability.
Switching between buprenorphine and buprenorphine/naloxone
When used sublingually, buprenorphine/naloxone and buprenorphine have similar clinical effects and are interchangeable. Before switching the patient should be consulted.
Administration
Tablets
For sublingual administration only.
The tablets should be placed under the tongue until dissolved.
When the dose required is made up with more than one tablet, the tablets may be taken all at the same time or in two divided portions; the second portion to be taken directly after the first portion has dissolved.
Sublingual films
For sublingual and/or buccal use. Sublingual administration is recommended during treatment initiation.
The film should be placed under the tongue or inside the cheek until dissolved. For buccal use, one film should be placed on the inside of the right or left cheek, additional films should be placed on the opposite cheek. If a third film is required it should be placed on the inside of the right or left cheek after the first two films have dissolved. For sublingual use, one film should be placed under the tongue until dissolved, additional films should be placed under the tongue on the opposite side. If a third film is required it should be placed under the tongue after the first two films have dissolved.
When the dose required is made up with more than one film, the films may be taken all at the same time or in two divided portions; the second portion to be taken directly after the first portion has dissolved. No more than two films should be administered at one time.
Contraindications
Acute alcohol intoxication
Children under 15 years
Breastfeeding
Delirium tremens
Head trauma
Long QT syndrome
Raised intracranial pressure
Severe hepatic impairment
Severe respiratory impairment
Torsade de pointes
Precautions and Warnings
Children aged 15 to 18 years
Debilitation
Elderly
Family history of long QT syndrome
Addison's disease
Anorexia nervosa
Asthma
Benign prostatic hyperplasia
Biliary tract disorder
Electrolyte imbalance
Galactosaemia
Glucose-galactose malabsorption syndrome
Hepatitis
Hereditary fructose intolerance
History of alcohol abuse
History of drug misuse
History of psychiatric disorder
History of seizures
History of torsade de pointes
Hypotension
Hypothyroidism
Known or suspected mitochondrial disorder
Kyphoscoliosis with respiratory compromise
Lactose intolerance
Mild hepatic impairment
Myxoedema
Pregnancy
Psychiatric disorder
Renal impairment - creatinine clearance below 30 ml/minute
Respiratory impairment
Urethral stricture
Correct electrolyte disorders before treatment
Reduce dose in patients with hepatic impairment
Advise patient ability to drive or operate machinery may be impaired
Advise patient drowsiness may affect ability to drive or operate machinery
Advise patient not to drive until they know how the medicine affects them
Advise patient this medicine may be subject to driving restrictions
May reduce seizure threshold
Treatment to be initiated and supervised by a specialist
Contains maltitol: unsuitable in hereditary fructose intolerance
Some formulations contain lactose
Some formulations contain sunset yellow (E110); may cause allergic reaction
Perform liver function tests before commencing therapy
Consider monitoring ECG in patients at risk of QT prolongation
May cause respiratory depression
Monitor hepatic function in patients with hepatic impairment
Monitor patients for signs and symptoms of Serotonin Syndrome
Monitor serum electrolytes
Neonate exposed in utero: Monitor for neonatal withdrawal syndrome
Potential for drug abuse
Tolerance and dependence may occur
When used with SSRIs, risk of Serotonin syndrome
Consider discontinuing treatment if hepatotoxicity occurs
Consider dose reduction if sleep-related breathing disorders occur
Consider dose reduction or discontinuation if serotonin syndrome suspected
Increased risk of central sleep apnoea and sleep-related hypoxemia
Withdrawal symptoms precipitated when used in opioid-dependent patients
Avoid abrupt withdrawal
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)
Fatal respiratory depression may occur in patients not tolerant or dependent on opioids.
May cause orthostatic hypotension in ambulatory patients.
Treatment should be initiated in patients who have agreed to be treated for addiction and within a framework of medical, social and psychological treatment.
A strategy for ending the treatment with the opioid should be discussed with the patient before starting the treatment in order to minimise the risk of addiction and drug withdrawal syndrome.
A full patient history should be established to document concomitant medications and past and present medical and psychiatric conditions. The risk of developing tolerance to buprenorphine with naloxone should be explained to the patient prior to treatment. All patients should be closely observed for signs of misuse, abuse or addiction. Patients at risk of opioid misuse may require additional support and monitoring.
Cases of acute hepatic injury have been reported, pre-existing mitochondrial impairment e.g. liver enzyme abnormalities and hepatitis B or C, and ongoing drug use by injection may have a causative or contributory role. The underlying factors must be taken into consideration before and during treatment. Buprenorphine/naloxone may be discontinued cautiously to avoid withdrawal symptoms and reduce the patients return to illicit drug use. Hepatic function should be closely monitored closely if treatment is continued.
Pregnancy and Lactation
Pregnancy
Use buprenorphine with naloxone with caution during pregnancy.
The manufacturer recommends buprenorphine with naloxone hydrochloride is not used in pregnancy unless the potential benefit to the mothers outweighs the potential risk to the foetus. Animal studies have shown reproductive toxicity. Risks are unknown.
Treatment may induce respiratory depression in the newborn infant towards the end of pregnancy, even after a short administration. Long term administration during the last three weeks of pregnancy may induce a withdrawal syndrome in the neonate. The syndrome may be delayed for several hours to several days after birth.
Neonatal monitoring for several days should be considered at the end of pregnancy due to the long half life of buprenorphine, to prevent the risk of respiratory depression or withdrawal syndrome in neonates.
Lactation
Buprenorphine with naloxone is contraindicated during breastfeeding.
Use of buprenorphine with naloxone hydrochloride when breastfeeding is contraindicated by the manufacturer. Effects on exposed infants is unknown.
The presence of naloxone in human breast milk is unknown, however buprenorphine and its metabolites are excreted in human milk. In rats buprenorphine has been found to inhibit lactation.
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.
Counselling
Advise patient not to take St John's wort concurrently.
Advise patients to avoid alcohol.
Buprenorphine may cause drowsiness, therefore advise patients to exercise caution when driving or operating machinery.
Advise that effects are potentiated by CNS depressants (including alcohol).
Advise patient not to drive until they know how the medicine affects them.
Advise patient the ability to drive and operate machinery may be impaired.
Advise patient this medicine may be subject to driving restrictions.
Side Effects
Abnormal ejaculation
Abnormal thinking
Accidental injury
Acne
Agitation
Albuminuria
Allergic reaction
Alopecia
Amblyopia
Amenorrhoea
Amnesia
Anaemia
Angina pectoris
Anorexia
Anxiety
Apathy
Arthralgia
Arthritis
Asthenia
Asthma
Bradycardia
Conjunctivitis
Constipation
Convulsions
Cough
Decreased appetite
Dependence
Depersonalisation
Depression
Diarrhoea
Dizziness
Dream abnormalities
Dry skin
Dyspepsia
Dyspnoea
Dysuria
Euphoria
Exfoliative dermatitis
Fever
Flatulence
Haematuria
Headache
Heat stroke
Hostility
Hyperglycaemia
Hyperkinesia
Hyperlipidaemia
Hypertension
Hypertonia
Hypoglycaemia
Hypotension
Hypothermia
Impotence
Increase in creatinine
Infections
Influenza-like syndrome
Insomnia
Lacrimation disorder
Leg cramps
Leucopenia
Leukocytosis
Liver function disturbances
Lymphadenopathy
Malaise
Menorrhagia
Metrorrhagia
Migraine
Miosis
Myalgia
Myocardial infarction
Nausea
Pain
Palpitations
Paraesthesia
Peripheral oedema
Pharyngitis
Pruritus
Rash
Reduced libido
Renal calculus
Rhinitis
Skin nodules
Somnolence
Speech disturbances
Sweating
Tachycardia
Thrombocytopenia
Tongue discolouration
Tremor
Ulcerative stomatitis
Urinary retention
Urinary tract infections
Urine abnormality
Urticaria
Vaginitis
Vasodilatation
Vomiting
Weight loss
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.
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: August 2021
Reference Sources
Summary of Product Characteristics: Suboxone sublingual film 2mg/0.5mg. Indivior UK Ltd. Revised January 2022.
Summary of Product Characteristics: Suboxone sublingual film 8mg/2mg. Indivior UK Ltd. Revised January 2022.
Summary of Product Characteristics: Suboxone tablets 2mg/0.5mg. Indivior UK Ltd. Revised August 2020.
Summary of Product Characteristics: Suboxone tablets 8mg/2mg. Indivior UK Ltd. Revised August 2020.
Summary of Product Characteristics: Suboxone tablets 16mg/4mg. Indivior UK Ltd. Revised August 2020.
Summary of Product Characteristics: Zubsolv 1.4mg/0.36mg sublingual Tablets. Accord UK Ltd. Revised August 2021.
Summary of Product Characteristics: Zubsolv 2.9mg/0.71mg sublingual Tablets. Accord UK Ltd. Revised August 2021.
Summary of Product Characteristics: Zubsolv 5.7mg/1.4mg sublingual Tablets. Accord UK Ltd. Revised August 2021.
Summary of Product Characteristics: Zubsolv 8.6mg/2.1mg sublingual Tablets. Accord UK Ltd. Revised August 2021.
Summary of Product Characteristics: Zubsolv 11.4mg/2.9mg sublingual Tablets. Accord UK Ltd. Revised August 2021.
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Medscape UK | Univadis prescription drug monographs & interactions are based on FDB Multilex Content
FDB Disclaimer : FDB Multilex is intended for the use of healthcare professionals and is provided on the basis that the healthcare professionals will retain FULL and SOLE responsibility for deciding what treatment to prescribe or dispense for any particular patient or circumstance.