Buprenorphine hydrochloride oral
- Drugs List
- Therapeutic Indications
- Dosage
- Contraindications
- Precautions and Warnings
- Pregnancy and Lactation
- Side Effects
- Monograph
Presentation
Sublingual and lyophilisate tablets containing buprenorphine
Drugs List
Therapeutic Indications
Uses
Pain - moderate to severe
Substitution treatment for opioid drug dependence
Dosage
Baseline liver function tests and viral hepatitis status documentation are recommended prior to commencing therapy.
Prior to treatment induction, consider whether the opioid dependence is with a long- or short-acting opioid, the degree of dependence and the time since last opioid use. Avoid precipitating withdrawal by initiating treatment when clear objective signs of withdrawal are evident.
Adults
Substitution treatment for opioid drug dependence
Treatment must be under the supervision of a physician experienced in the management of opiate dependence/addiction. The result of treatment depends on the dosage prescribed as well as on the combined medical, psychological, social and educational measures taken in monitoring the patient.
Induction therapy - sublingual
The initial dose is 800 micrograms to 4 mg, administered as a single daily dose.
Opioid dependent drug addicts that have not undergone withdrawal - sublingual
One dose of buprenorphine administered sublingually at least 6 to 12 hours after the last use of heroin (or other short-acting opioid), or 24 to 48 hours after the last dose of methadone.
Patients receiving methadone - sublingual
Before initiating buprenorphine therapy, the dose of methadone should be reduced to a maximum of 30 mg per day. Buprenorphine may precipitate symptoms of withdrawal in patients dependent upon methadone.
Dosage of buprenorphine should be increased according to response and should not exceed a maximum single daily dose of 32 mg.
After a satisfactory period of stabilisation, the dosage may be reduced to a lower maintenance dose, or when deemed appropriate treatment may be discontinued.
Induction therapy - lyophilisates
The initial dose is 2 mg administered as a single daily dose. An additional one to two 2 mg oral lyophilisates may be taken on day one depending on the individual patients requirements.
Opioid dependent drug addicts that have not undergone withdrawal - lyophilisates
One dose of buprenorphine administered sublingually at least 6 hours after the last use of heroin (or other short-acting opioid), or 24 hours after the last dose of methadone.
Patients receiving methadone - lyophilisates
Before initiating buprenorphine therapy, the dose of methadone should be reduced to a maximum of 30 mg per day. Buprenorphine may precipitate symptoms of withdrawal in patients dependent upon methadone.
Dosage of buprenorphine should be increased in steps of 2 mg to 6 mg according to response and should not exceed a maximum single daily dose of 18 mg.
After a satisfactory period of stabilisation, the dosage may be reduced to a lower maintenance dose, or when deemed appropriate treatment may be discontinued.
Relief of moderate to severe pain - licensed in some sublingual brands only
Buprenorphine should not be used for longer than is absolutely necessary. If longer term pain management is required, dosage should be reassessed at regular and frequent intervals.
The dosage should generally be adjusted to the intensity of the pain and the individual sensitivity of the patient. In severe chronic pain, the dose should be administered in accordance with a fixed schedule corresponding to the duration of effects.
200 to 400 micrograms to be dissolved under the tongue every 6 to 8 hours or as required for patients weighing more than 45 kg.
The recommended starting dose for moderate to severe pain of the type typically presenting in general practice is 200 to 400 micrograms 8 hourly.
Elderly
(See Dosage; Adult)
Children
Substitution treatment for opioid drug dependence
Contraindicated in children under 15 years of age.
Relief of moderate to severe pain
There is currently insufficient clinical experience of longer term use of buprenorphine in children.
Children over 12 years
200 to 400 micrograms to be dissolved under the tongue every 6 to 8 hours or as required.
The recommended starting dose for moderate to severe pain of the type typically presenting in general practice is 200 to 400 micrograms 8 hourly.
Children aged 2 to 12 years
16 to 25 kg - 100 micrograms
25 to 37.5 kg - 100 to 200 micrograms
37.5 to 50 kg - 200 to 300 micrograms
Over 50 kg - 200 to 400 micrograms
Another manufacturer suggests:
16 to 35 kg - 100 micrograms
35 to 45 kg - 200 micrograms
The recommended dose should be administered every 6 to 8 hours.
Sublingual administration is not suitable for children under 2 years or weighing less than 16 kg.
Patients with Renal Impairment
The Renal Drug Handbook contains the following dosage recommendations:
GFR 10 to 20 ml/minute - dose as in normal renal function, but avoid very large doses
GFR less than 10 ml/minute - reduce dose by 25 to 50% initially and increase as tolerated, avoid very large single doses
Additional Dosage Information
Less than daily dosing - sublingual
After a satisfactory stabilisation has been achieved, the frequency of dosing may be decreased to dosing every other day at twice the individually titrated dose. For example, a patient stabilised to receive a daily dose of 8 mg may be given 16 mg on alternate days, with no dose on the intervening days. In some patients, the frequency of dosing may be decreased to 3 times a week.
The dose on any one day should not exceed 24 mg.
Less than daily dosing - lyophilisates
After satisfactory stabilisation has been achieved the frequency of dosing may be decreased to dosing every other day at twice the individually titrated daily dose. For example, a patient stabilised to receive a daily dose of 8 mg may be given 16 mg on alternate days, with no dose on the intervening days. In some patients, the frequency of dosing may be decreased to 3 times a week (for example on Monday, Wednesday and Friday). The dose on Monday and Wednesday should be twice the individually titrated daily dose, and the dose on Friday should be three times the individually titrated daily dose, with no dose on the intervening days.
The dose given on any one day should not exceed 18 mg. Patients requiring a titrated daily dose greater than 8 mg per day may not find this regimen adequate.
Contraindications
Acute alcohol intoxication
Children under 2 years
Risk of paralytic ileus
Weight below 16kg
Within 2 weeks of discontinuing MAOIs
Acute asthma
Acute respiratory impairment
Breastfeeding
Chronic obstructive pulmonary disease
Coma
Delirium tremens
Head trauma
Pregnancy
Raised intracranial pressure
Severe hepatic impairment
Precautions and Warnings
Children aged 2 to 6 years
Debilitation
Elderly
Impaired consciousness
Adrenal insufficiency
Asthma
Biliary tract disorder
Central nervous system depression
Cerebral trauma
Drug misuse
Galactosaemia
Glucose-galactose malabsorption syndrome
Hepatitis
History of drug misuse
Hypotension
Hypothyroidism
Inflammatory bowel disease
Intracranial lesion
Kyphoscoliosis with respiratory compromise
Lactose intolerance
Mild hepatic impairment
Myasthenia gravis
Myxoedema
Opioid dependence
Phenylketonuria
Prostate disorder
Renal impairment
Respiratory impairment
Seizures
Toxic psychosis
Urinary system disorder
Can precipitate withdrawal symptoms in patients dependent on methadone
Consider reducing initial dose in hepatic impairment
Reduce dose in hypothyroidism
Some formulations contain aspartame - caution in phenylketonuria
Advise ability to drive/operate machinery may be affected by side effects
Advise patient not to drive until they know how the medicine affects them
Advise patient this medicine may be subject to driving restrictions
Not all available brands are licensed for all indications
Treatment to be initiated and supervised by a specialist
Some formulations contain lactose
Be vigilant for medicines diversion
May cause respiratory depression
Monitor liver function. Withdraw if evidence of hepatotoxic reaction
Monitor patients for signs and symptoms of Serotonin Syndrome
Potential for drug abuse
When used with SSRIs, risk of Serotonin syndrome
Consider dose reduction if sleep-related breathing disorders occur
Consider dose reduction or discontinuation if serotonin syndrome suspected
Discontinue if hepatitis develops
Increased risk of central sleep apnoea and sleep-related hypoxemia
May cause dependence
May cause postural hypotension
Discontinue if jaundice or other evidence of hepatic impairment occurs
Bioavailability differs with preparations;caution on changing formulations
Not licensed for all indications in all age groups
Reduce dose in debilitated patients
Reduce dose in elderly
Advise patient not to take St John's wort concurrently
Advise patient to avoid alcohol during treatment
Baseline liver function tests and viral hepatitis status documentation are recommended prior to commencing therapy. Patients who are positive for vial hepatitis, on concomitant medication and/or have existing liver dysfunction are at risk of accelerated liver injury. Regular monitoring of liver function is recommended. Cases of acute hepatic injury have been reported in opioid-dependent addicts ranging from transient asymptomatic elevated hepatic transaminases to hepatic failure. Pre-existing liver enzyme abnormalities, hepatitis B or C infection, concomitant use of hepatotoxic drugs or on going injecting drug use may all have a causative or contributory role and must be taken into consideration before prescribing buprenorphine sublingual tablets, and during treatment. If hepatic necrosis or jaundice occur, discontinue as rapidly as the patient's clinical condition permits.
Can precipitate withdrawal symptoms in opioid-dependent patients, particularly if administered less than 6 hours after the last use of heroin or other short-acting opioids, or if administered less than 24 hours after the last dose of methadone. Withdrawal symptoms may also be associated with suboptimal dosing.
The risk of serious adverse effects or treatment dropout is greater if a patient continues to self medicate withdrawal symptoms (with opioids, alcohol, or sedative-hypnotics, particularly benzodiazepines) whilst being treated with buprenorphine.
Potential for abuse, especially by the IV route. Serious cases of acute hepatic injury and local reactions including sepsis have been associated with IV misuse of buprenorphine.
In cases of concomitant illness, symptoms maybe masked by analgesic effects of buprenorphine.
There is a possibility of diversion of buprenorphine into the illicit market by patients or individuals who obtain it by theft from patients or pharmacies. This may lead to new addicts using it as a primary drug of abuse, with the risk of overdose, spread of blood borne viral infections, respiratory depression and hepatic injury.
Pregnancy and Lactation
Pregnancy
Buprenorphine is contraindicated in pregnancy.
Studies in rats and rabbits have evidenced foetotoxicity including post-implantation loss. In humans there is currently not sufficient data to evaluate potential malformative or foetotoxic effects when administered during pregnancy. Because there is substantially more published human pregnancy experience for other narcotic analgesics, they are preferred to buprenorphine, especially during early gestation (Briggs 2015).
When administered during the last trimester buprenorphine can cause respiratory depression and withdrawal symptoms in neonates. There is also a risk of gastric stasis and inhalation pneumonia in the mother during labour.
Due to the long half-life of buprenorphine, neonatal monitoring for several days should be considered at the end of pregnancy, to prevent the risk of respiratory depression or withdrawal syndrome in neonates
The use of all medication in pregnancy should be avoided whenever possible; particularly in the first trimester. Non-drug treatments should also be considered. When essential, a medication with the best safety record over time should be chosen, employing the lowest effective dose for the shortest possible time. Polypharmacy should be avoided. Teratogens taken in the pre-embryonic period, often quoted as lasting until 14 to 17 days post-conception, are believed to have an all-or-nothing effect. Where drugs have a short half-life, and when the date of conception is certain, this may allow women to be reassured where drug exposure has occurred within this time frame. Further advice may be available from the UK National Teratology Information Service (NTIS) and through ToxBase, available via password on the internet ( www.toxbase.org ) or if this is unavailable at the backup site ( www.toxbasebackup.org ).
Lactation
Buprenorphine is contraindicated in breastfeeding.
Buprenorphine has the potential to inhibit lactation or milk production. In addition, buprenorphine passes into the milk.
However LactMed states its use is acceptable with monitoring of the infant for drowsiness, adequate weight gain, and developmental milestones, especially in younger, exclusively breastfed infants. This is because of the low levels of buprenorphine in breastmilk and its poor oral bioavailability in infants.
Neonates, infants born prematurely, those with low birth weight, those with an unstable gastrointestinal function or who have serious illnesses may require special consideration. For any infant, if a drug is prescribed to the nursing mother, it should be at the lowest practical dose and for the shortest time. When drug administration is unavoidable and breastfeeding is to continue, minimisation of exposure of the infant to the drug may sometimes be achieved by timing the maternal doses to just after a feeding episode. Infants exposed to drugs via breast milk should be monitored for unusual signs or symptoms. Interactions between the drug received by the infant from the mother's milk and medication prescribed for the infant should also be considered, for example, when the drug given to the infant may prevent metabolism of the drug received via breast milk. Specialist advice is available from the UK Drugs in Lactation Advisory Service at https://www.midlandsmedicines.nhs.uk/content.asp?section=6&subsection=17&pageIdx=1
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
Sublingual: Patients should be advised not to chew or swallow the tablets. The tablet should be kept under the tongue until dissolved, which usually occurs within 5 to10 minutes.
Lyophilisates: Patients should be advised to take the tablet with dry fingers from the packaging and place the tablet whole on the tongue until dispersed, which usually occurs within 15 seconds and then to avoid swallowing for 2 minutes as well as not consuming food or drink for 5 minutes.
Buprenorphine may cause drowsiness, therefore patients should be advised to exercise caution until they are certain they can tolerate the drug.
Athletes should be advised that treatment with buprenorphine may cause a reaction to anti-doping tests.
Patients should avoid alcohol, opiates, benzodiazepines and hypnotics due to the possible deadly risks of combination with buprenorphine, and should be informed on the risks of IV misuse.
Patients should be advised about the loss of opioid tolerance after discontinuation and subsequent dangerous impact on relapse.
Side Effects
Agitation
Allergic reaction
Anaphylactic shock
Angina
Angioneurotic oedema
Anorexia
Anxiety
Apnoea
Asthenia
Atrioventricular block
Biliary spasm
Bradycardia
Bronchospasm
Chills
Circulatory disturbances
Coma
Concentration disturbances
Confusion
Constipation
Convulsions
Cough
Cyanosis
Decreased appetite
Dependence
Depersonalisation
Depression
Diarrhoea
Disorientation
Dizziness
Drowsiness
Dry mouth
Dry skin
Dysarthria
Dyspepsia
Dysphagia
Dyspnoea
Exhaustion
Eye disorder
Fasciculation
Fatigue
Flatulence
Flushing
Hallucinations
Headache
Hepatic necrosis
Hepatitis
Hiccups
Hypertension
Hyperventilation
Hypoaesthesia
Hypotension
Hypoxia
Impaired memory
Inco-ordination
Influenza-like symptoms
Insomnia
Mood changes
Mucosal irritation
Muscle cramps
Muscle rigidity
Nausea
Nervousness
Oedema
Pain
Pallor
Palpitations
Paraesthesia
Paralytic ileus
Postural hypotension
Prolongation of QT interval
Pruritus
Psychosis
Psychotomimetic effects
Pyrexia
Rash
Respiratory depression
Restlessness
Retching
Rhinitis
Rigors
Sexual dysfunction
Sleep disturbances
Slurred speech
Sweating
Syncope
Tachycardia
Taste disturbances
Tinnitus
Tiredness
Tremor
Urinary tract disorders
Urticaria
Vasodilatation
Vertigo
Vomiting
Wheezing
Withdrawal symptoms
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: October 2016
Reference Sources
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.
Joint Formulary Committee. British National Formulary (online) London: BMJ Group and Pharmaceutical Press https://www.medicinescomplete.com Accessed on 26 October 2016.
Martindale: The Complete Drug Reference, 37th edition (2011) ed. Sweetman, S. Pharmaceutical Press, London.
Paediatric Formulary Committee. BNF for Children (online) London: BMJ Group, Pharmaceutical Press, and RCPCH Publications https://www.medicinescomplete.com Accessed on 26 October 2016.
Summary of Product Characteristics: Espranor 2mg and 8mg oral lyophilisate. Martindale pharmaceuticals LTD. June 2015
Summary of Product Characteristics: Gabup 0.4mg, 1mg, 2mg, 4mg, 6mg and 8mg sublingual tablets. Martindale pharmaceuticals LTD. October 2014
Summary of Product Characteristics: Natzon 0.4mg, 2mg and 8mg sublingual tablets. Morningside healthcare Limited. March 2012
Summary of Product Characteristics: Prefibin sublingual tablets 0.4mg. Sandoz Ltd. November 2021.
Summary of Product Characteristics: Prefibin sublingual tablets 2mg. Sandoz Ltd. December 2021.
Summary of Product Characteristics: Prefibin sublingual tablets 8mg. Sandoz Ltd. December 2021.
Summary of Product Characteristics: Subutex 0.4mg, 2mg and 8mg sublingual tablets. RB Pharmaceuticals Ltd. Revised February 2012
Summary of Product Characteristics: Temgesic sublingual tablets 0.2mg. RB Pharmaceuticals Ltd. Revised September 2010
Summary of Product Characteristics: Temgesic sublingual tablets 0.4mg. RB Pharmaceuticals Ltd. Revised September 2010
Summary of Product Characteristics: Tephine 200 microgram Sublingual Tablets. Sandoz Limited. Revised October 2021.
Summary of Product Characteristics: Tephine 400 microgram Sublingual Tablets. Sandoz Limited. Revised October 2021.
The Renal Drug Handbook. Fourth Edition (2014) ed. Ashley, C and Dunleavy, A, Radcliffe Publishing Ltd, London.
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: 01 September 2016
Last accessed: 26 October 2016
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
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