Fentanyl sublingual (Abstral)

• This guideline is for the use of Abstral – a dispersible, sublingual fentanyl tablet (available as 100, 200, 300, 400, 600, 800 micrograms).
• Most NHS boards have only approved one or two rapid acting fentanyl products for use in their area. Refer to your local Formulary (see Effentora and PecFent medicine information sheets).
• Rapid acting fentanyl products have different absorption and elimination characteristics and are not interchangeable. Start with the lowest dose and titrate very carefully if the patient is changed to a different product.
• The brand name should always be included in the prescription.

• Rapid acting fentanyl preparations are SMC approved for restricted use in NHS Scotland; for the management of opioid responsive, breakthrough pain in adults requiring regular opioid therapy for chronic cancer pain.
• Use is restricted to patients where other oral opioids (immediate release morphine or immediate-release oxycodone) are unsuitable, ineffective or not tolerated.
• Patients must have been on a stable dose of a regular opioid for at least 7 days equivalent to at least 60mg of oral morphine or 30mg of oral oxycodone in 24 hours or a 25 micrograms/hour fentanyl patch before rapid acting fentanyl is used.
• Opioids with a rapid onset of action can be effective in breakthrough pain where background cancer pain is well controlled but the patient has:
• pain related to a particular event (for example movement, dressing changes).
• pain that occurs spontaneously, is sudden in onset, is moderate to severe, but may not last long.

• Hepatic metabolism to an inactive metabolite is slower when higher doses of fentanyl are used.
• Rapid acting fentanyl products can have a variable and unpredictable half life which in some products can be up to 22 hours.
• Liver impairment: lower doses and slower titration are needed in severe liver disease.
• Renal impairment: no initial dose reduction. May accumulate gradually over time in patients with Grade 4 to 5 chronic kidney disease. Fentanyl is not removed by dialysis.
• Monitor patients with liver or renal impairment and reduce the dose if side effects develop.
• Avoid in patients with severe chronic obstructive pulmonary disease or respiratory depression.
• Mouth ulcers or mucositis can affect absorption.

Drug interactions

• Hepatic metabolism is reduced by grapefruit juice and a number of medications
  (for example fluconazole, QTclarithromycin, QTerythromycin) – refer to British National
  Formulary (BNF).
• Alcohol and central nervous system depressants increase side effects.
• Manufacturers warn of a risk of serotonin toxicity when fentanyl is used in combination with other serotoninergic drugs.

Side effects

Similar to other opioids: nausea, dizziness, sedation, delirium.

• Rapid acting fentanyl preparations can accumulate if repeated doses are given.
• Monitor the patient closely for opioid side effects; review the dose and dosing interval.

Titrated naloxone is only indicated in life-threatening, opioid induced respiratory depression (refer to Naloxone guideline).

• Rapid acting fentanyl preparations must be individually titrated to an effective dose; patients should be monitored closely during the initial dose titration period.
• The effective dose of rapid acting fentanyl cannot be predicted from the dose of regular opioid being used to manage background pain.
• The licensed titration regimen may be too complex for some care settings and too rapid for some patients. In specialist palliative care there is little consensus on the most appropriate way to titrate the rapid acting fentanyl preparations – refer to local specialist advice. The regimen below is used by some specialists but is unlicensed (patients under specialist palliative care may have the dose escalated more quickly):
• Start with the lowest dose of the sublingual fentanyl tablet (Abstral 100 micrograms):
• one dose of Abstral can be given to treat an episode of pain or 5 to 10 minutes before an event anticipated to cause pain
• if the patient can be monitored and is not at risk of opioid toxicity, a second tablet of 100 micrograms can be given after 15 to 30 minutes, if required
• if the patient is still in pain after taking one or two tablets of Abstral as above, a dose of their usual immediate release oral opioid can be given
• wait for 2 hours before treating another episode of breakthrough pain with Abstral – see table below.

Tables are best viewed in landscape mode on mobile devices

• A maximum of 4 episodes of breakthrough pain in 24 hours should be treated with sublingual fentanyl tablets.
• The dose of Abstral can be increased in a stepwise manner if it is showing some effect and is well tolerated, usually after 24 to 48 hours. Palliative care specialists may recommend an individualised titration regimen.
  • Continue to monitor the patient carefully.
• Make sure background pain is well controlled with regular opioids and other analgesics.
• If pain remains poorly controlled, review the patient, reassess the background analgesia, and consider other approaches to pain management.
• Rapid acting fentanyl should be discontinued if it is ineffective or no longer needed.

• Seek advice from a specialist about use of rapid acting fentanyl products.
• Fentanyl is 100 to 150 times more potent than oral morphine; titrate and monitor carefully.
• Even the lowest strength preparations can accumulate and cause opioid toxicity.
• Different rapid acting fentanyl products should not be used at the same time.
• The GP, community nurse and community pharmacist should be informed.
• The unscheduled care service should be informed that the patient is receiving a third-line opioid under specialist supervision.
• Fentanyl sublingual tablets (Abstral®) can be prescribed by the patient’s GP in liaison with local palliative care specialists.
• The patient should have information about who to contact if there are any queries or problems relating to use of Abstral® in the community. 

Summary of product characteristics for Abstral from the electronic medicines compendium

Davies A. The management of cancer related breakthrough pain: recommendations of a task group of the Association for Palliative Medicine. European Journal of Pain; 2009, 13 (4): 331-338.