Fentanyl buccal tablets and films, and sublingual tablets
- Drugs List
- Therapeutic Indications
- Dosage
- Administration
- Contraindications
- Precautions and Warnings
- Pregnancy and Lactation
- Side Effects
- Monograph
Presentation
Buccal/sublingual formulations containing fentanyl.
Drugs List
Therapeutic Indications
Uses
Management of breakthrough cancer pain in patients receiving opiates
Dosage
Fentanyl buccal/sublingual preparations should only be administered to patients considered to be on maintenance opioid therapy (defined as 60mg oral morphine per day, at least 25micrograms of transdermal fentanyl per hour, at least 30mg of oxycodone daily, at least 8mg of oral hydromorphone daily or an equianalgesic dose of another opioid for a week or longer).
Adults
Titration
The optimal dose should be determined by upward titration, on an individual patient basis. Monitor patients carefully until a dose is reached that provides adequate analgesia with acceptable adverse reactions.
Sublingual tablets
No more than four sublingual tablets should be administered for a single episode of breakthrough pain during the titration phase.
Initial dose: 100micrograms, titrated upwards as necessary. If adequate analgesia is not obtained within 15 to 30 minutes of administration, a second 100microgram tablet may be administered.
If inadequate pain relief is obtained, consider an increase in dose to the next available higher strength for the next breakthrough pain episode.
Continue dose escalation in a stepwise manner until adequate analgesia is achieved, using the schedules outlined below. Supplemental dose to be taken 15 to 30 minutes after first tablet if required.
Initial tablet per episode of breakthrough pain: 100micrograms.
Strength of supplemental tablet: 100micrograms.
Initial tablet per episode of breakthrough pain: 200micrograms.
Strength of supplemental tablet: 100micrograms.
Initial tablet per episode of breakthrough pain: 300micrograms.
Strength of supplemental tablet: 100micrograms.
Initial tablet per episode of breakthrough pain: 400micrograms.
Strength of supplemental tablet: 200micrograms.
Initial tablet per episode of breakthrough pain: 600micrograms.
Strength of supplemental tablet: 200micrograms.
Initial tablet per episode of breakthrough pain: 800micrograms.
Doses higher than 800micrograms have not been evaluated in clinical studies.
If adequate analgesia is achieved at the higher dose, but undesirable effects are considered unacceptable, an intermediate dose (using the 100microgram sublingual tablet where appropriate) may be administered.
Buccal tablets
Initial dose: 100micrograms, to be titrated upwards as necessary. If adequate analgesia is not obtained within 30 minutes of administration, a second 100microgram tablet may be administered.
If inadequate pain relief is obtained consider an increase in dose to the next available higher strength for the next breakthrough pain episode.
Continue dose escalation in a stepwise manner until adequate analgesia is achieved using the schedule below. Supplemental dose to be taken 30 minutes after first tablet if required.
During titration multiple tablets may be used (up to four 100micrograms or up to four 200micrograms tablets) to treat a single episode of breakthrough pain.
Initial tablet per episode of breakthrough pain: 100micrograms
Strength of supplemental tablet: 100micrograms
Treat the next episode with two 100microgram tablets, one placed in each side of the mouth. If this dose is effective, treatment should then continue with a single 200microgram tablet.
Initial tablet per episode of breakthrough pain: 200micrograms (or two 100micrograms tablets)
Strength of supplemental tablet: 200micrograms (or two 100micrograms tablets)
Treat the next episode with two 200microgram tablets, one placed in each side of the mouth. If this dose is effective, treatment should then continue with a single 400microgram tablet.
For titration to 600micrograms and 800micrograms, tablets of 200micrograms should be used.
No more than two tablets should be used to treat any single episode of breakthrough pain, except when titrating using up to four tablets, as described above.
Doses higher than 800micrograms have not been evaluated in clinical studies.
Maintenance
Once an appropriate dose has been established, maintain the patient on this dose and limit consumption to a maximum of four doses per day. Patients should wait at least 2 hours before treating another episode of pain during maintenance therapy. Consider a dose adjustment if the response to the dose markedly changes to ensure an optimal dose is maintained.
Re-adjustment
If more than four episodes of breakthrough pain are experienced per day over a period of more than four consecutive days, the dose of long-acting opioid used for persistent pain should be re-evaluated. Fentanyl dose should then be re-evaluated and re-titrated as necessary. Any dose re-titration must be monitored by a health professional.
Discontinuation
Fentanyl may be discontinued if no longer required for breakthrough pain. However if withdrawing or reducing opioid maintenance therapy, the dose used for breakthrough pain should be taken into consideration before a gradual downward titration of opioids to minimise withdrawal effects.
Patients with Renal Impairment
The Renal Drug Handbook recommends the following
GFR 10 to 50 ml/minute: 75% of normal dose, titrate according to response.
GFR less than 10 ml/minute: 50% of normal dose, titrate according to response.
Additional Dosage Information
Due to different absorption profiles, switching must not be done at a 1:1 ratio from one oral fentanyl citrate product to another.
Independent dose titration is required as bioavailability between products differs significantly.
Administration
Sublingual tablets
Administer directly under the tongue at the deepest part. The tablets should not be swallowed, but allowed to completely dissolve without chewing or sucking. Patients should not eat or drink anything until the tablet is completely dissolved. Patients should be advised not to eat or drink anything until the sublingual tablet is completely dissolved.
Buccal tablets
Tablets should not be crushed or split, neither should patients attempt to push the tablet through the blister package as this could damage the tablet. Upon opening the blister unit, the entire tablet should immediately be placed in the upper portion of the buccal cavity (near a molar between the cheek and gum), and retained until the tablet has disintegrated (usually about 14 to 25 minutes). The tablet should not be sucked, chewed or swallowed, but if after 30 minutes remnants remain, they may be swallowed with a glass of water. Patients should not eat or drink anything until the tablet is completely dissolved.
If using more than one buccal tablet these should be placed in each side of the mouth.
Tablet placement within the buccal cavity should be altered if buccal mucosa irritation occurs.
Patients who have a dry mouth may use water to moisten the buccal mucosa before using fentanyl sublingual or buccal tablets.
Contraindications
Children under 18 years
Opioid-naive patients
Risk of paralytic ileus
Within 2 weeks of discontinuing MAOIs
Acute asthma
Brain neoplasm
Breastfeeding
Coma
Head trauma
Labour
Raised intracranial pressure
Severe obstructive pulmonary disease
Severe respiratory depression
Precautions and Warnings
Cachexia
Damaged mucosa
Debilitation
Impaired consciousness
Patients over 65 years
Predisposition to respiratory failure
Adrenal insufficiency
Asthma
Benign prostatic hyperplasia
Biliary tract disorder
Bradyarrhythmia
Chronic obstructive pulmonary disease
Epileptic disorder
Gastrointestinal obstruction
Hepatic impairment
History of alcohol abuse
History of drug misuse
History of psychiatric disorder
Hypotension
Hypothyroidism
Hypovolaemia
Inflammatory bowel disease
Myasthenia gravis
Pregnancy
Renal impairment - glomerular filtration rate below 50ml/minute
Respiratory depression
Urethral stricture
Not suitable for acute pain relief
Reduce dose in hypothyroidism
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
Treatment to be initiated and supervised by a specialist
Brands may not be bioequivalent
Moisten buccal mucosa in dry mouth
Monitor for signs of tolerance and dependence
Monitor patient closely during titration of dose
Monitor patient for signs and symptoms of respiratory depression
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 dose reduction if sleep-related breathing disorders occur
Increased risk of central sleep apnoea and sleep-related hypoxemia
Prolonged use at high doses may result in hyperalgesia
Avoid abrupt withdrawal
Discontinue if serotonin syndrome develops
Consider dose reduction or alternative opioid in cases of hyperalgesia
Consider reducing dose in elderly
Reduce dose in debilitated patients
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
Tolerance, physical dependence and psychological dependence may develop upon repeated administration of opioids such as fentanyl. Iatrogenic addiction following opioid administration is rare. Fentanyl can be abused in a manner similar to other opioid agonists. Abuse or intentional misuse of fentanyl may result in overdose and/or death. Patients at increased risk of opioid abuse may still be appropriately treated with modified-release opioid formulations; however, these patients will require monitoring for signs of misuse, abuse, or addiction.
The use of fentanyl in opioid naive patients has been associated with very rare cases of respiratory depression and/or fatality when used as initial opioid therapy, even with the lowest dose. It is recommended that fentanyl should be used in patients who have demonstrated opioid tolerance.
Pregnancy and Lactation
Pregnancy
Use fentanyl with caution during pregnancy.
The manufacturers do not recommend the use of fentanyl during labour and delivery and should only be used during pregnancy when clearly necessary and is not indicated for acute pain. Animal studies have indicated reproductive toxicity. Placental transfer of fentanyl has been demonstrated in the first and second trimesters, and at term, and is detectable in foetal blood. The potential risk for humans is unknown. There is also a risk of respiratory depression in the foetus or neonate with prolong use of fentanyl. The neonate should be observed closely for withdrawal syndrome.
Lactation
Fentanyl is contraindicated during breastfeeding.
The manufacturer does not recommend using fentanyl during breastfeeding and breastfeeding should not occur until 5 days after the last administration. Fentanyl is excreted into breast milk, this may cause respiratory depression and sedation in the infant. Infants should be monitored for drowsiness, adequate weight gain and developmental milestones. A physician should be contacted immediately if the infant experiences difficulty in breastfeeding, breathing difficulties or limpness.
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). This medicine may be subject to police testing and has specified maximum blood levels for driving.
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 patients that their ability to drive or operate machinery may be affected by side effects.
Advise patients not to use more than one short acting fentanyl product at a time, for breakthrough cancer pain.
Advise patients and their carers that fentanyl tablets and films contain an active substance in an amount that can be fatal especially to a child. Instruct them to keep all units out of the reach of children and to discard of open units and fentanyl products no longer required, appropriately.
Advise patients to alter tablet placement within the buccal cavity if buccal mucosa irritation occurs.
Advise patients that the buccal tablets contain sodium.
Advise patients that no more than two tablets should be used to treat an individual episode of breakthrough pain.
Advise patients to wait at least 2 or 4 hours between doses depending on the brand and not to exceed 4 doses in any one day.
Patients who have a dry mouth may use water to moisten the buccal mucosa before using fentanyl tablets or films.
Side Effects
Abdominal pain
Abnormal thinking
Abnormal vision
Accidental injury
Agitation
Alopecia
Amnesia
Anaemia
Anorexia
Anxiety
Apnoea
Arrhythmias
Asthenia
Asystole
Ataxia
Biliary spasm
Bradycardia
Cardiovascular depression
Circulatory depression
Circumoral paraesthesia
Confusion
Constipation
Decrease in haematocrit
Delirium
Dependence
Depersonalisation
Depression
Diarrhoea
Difficulty in micturition
Dizziness
Dream abnormalities
Drowsiness
Dry mouth
Dysarthria
Dyspepsia
Dysphagia
Dysphoria
Dyspnoea
Emotional lability
Enlarged abdomen
Euphoria
Fasciculation
Flatulence
Flushing
Gait abnormality
Haemoptysis
Hallucinations
Headache
Hiccups
Hyperacusis
Hypoaesthesia
Hypotension
Hypoventilation
Inco-ordination
Insomnia
Irritation at application site
Laryngospasm
Malaise
Miosis
Mood changes
Mouth ulcers
Muscle rigidity
Muscle weakness
Myoclonus
Nausea
Neutropenia
Oedema
Palpitations
Paraesthesia
Paralytic ileus
Pharyngitis
Postural hypotension
Pruritus
Psychosis
Pyrexia
Rash
Reduced platelet count
Respiratory depression
Seizures
Sexual dysfunction
Shock
Sleep disturbances
Somnolence
Stomatitis
Sweating
Tachycardia
Taste disturbances
Thirst
Tinnitus
Tongue disorder
Tremor
Ureteric spasm
Urinary retention
Urticaria
Vasodilation
Vertigo
Vomiting
Withdrawal Symptoms and Signs
The opioid withdrawal syndrome is characterised by the presence of some or all of the following symptoms including restlessness, yawning, lacrimation, perspiration, rhinorrhoea, myalgia, chills, palpitations, and mydriasis. Additional symptoms may develop such as agitation, irritability, anxiety, tremor, hyperkineasia, weakness, anorexia, insomnia, nausea, abdominal cramps, vomiting, increased blood pressure, diarrhoea, increased heart rate or respiratory rate. Discuss strategy for ending treatment with patient prior to initiating treatment. It is recommended to reduce the dose gradually to minimise symptoms of opioid withdrawal syndrome, 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: October 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.
Medications and Mothers' Milk, Sixteenth Edition (2014) Hale, T and Rowe, H, Hale Publishing, Plano, Texas.
Summary of Product Characteristics: Abstral sublingual tablets. Kyowa Kirin Ltd. Revised August 2019.
Summary of Product Characteristics: Effentora buccal tablets. Teva Pharma BV. Revised August 2019.
Summary of Product Characteristics: Fenhuma 100 microgram sublingual tablets. Glenmark Pharmaceuticals Europe Limited. January 2022.
Summary of Product Characteristics: Fenhuma 200 microgram sublingual tablets. Glenmark Pharmaceuticals Europe Limited. January 2022.
Summary of Product Characteristics: Fenhuma 300 microgram sublingual tablets. Glenmark Pharmaceuticals Europe Limited. January 2022.
Summary of Product Characteristics: Fenhuma 400 microgram sublingual tablets. Glenmark Pharmaceuticals Europe Limited. January 2022.
Summary of Product Characteristics: Fenhuma 600 microgram sublingual tablets. Glenmark Pharmaceuticals Europe Limited. January 2022.
Summary of Product Characteristics: Fenhuma 800 microgram sublingual tablets. Glenmark Pharmaceuticals Europe Limited. January 2022.
The Renal Drug Handbook. Fourth Edition (2014) ed. Ashley, C and Dunleavy, A, Radcliffe Publishing Ltd, London.
NICE Evidence Services Available at: www.nice.org.uk Last accessed: 12 August 2022
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
Fentanyl Last revised: 15 May 2022
Last accessed: 12 August 2022
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: 11 April 2019
New drug driving offence: implications for medicines packaging. Medicines Regulatory News. 10 December 2013. Available at: https://www.mhra.gov.uk Last accessed: 11 April 2019
Medscape UK | Univadis prescription drug monographs & interactions are based on FDB Multilex Content
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