Active Ingredient: Fentanyl
Fentanyl is indicated for the management of breakthrough pain (BTP) in adults who are already receiving maintenance opioid therapy for chronic cancer pain. Breakthrough pain is a transitory exacerbation of pain that occurs on a background of otherwise controlled persistent pain.
Patients receiving maintenance opioid therapy are those who are taking at least 60 mg of oral morphine daily, at least 25 micrograms of transdermal fentanyl per hour, at least 30 mg of oxycodone daily, at least 8 mg of oral hydromorphone daily or an equianalgesic dose of another opioid for a week or longer.
For this indication, competent medicine agencies globally authorize below treatments:
Nasal
100 - 400 ug
From 25 To 100 ug 4 time(s) per day every day
Fentanyl should be titrated to an “effective” dose that provides adequate analgesia and minimises adverse reactions without causing undue (or intolerable) adverse reactions, for two consecutively treated episodes of BTP. The efficacy of a given dose should be assessed over the ensuing 30 minute period.
Patients should be carefully monitored until an effective dose is reached.
Fentanyl is available in two strengths: 100 micrograms/spray and 400 micrograms/spray. One dose of Fentanyl may include administration of 1 spray (100 microgram or 400 microgram doses) or 2 sprays (200 microgram or 800 microgram doses) of the same strength (either 100 microgram or 400 microgram strength).
Patients should not use more than 4 doses per day. Patients should wait at least 4 hours after a dose before treating another BTP episode with Fentanyl.
The initial dose of Fentanyl to treat episodes of BTP is always 100 micrograms (one spray), even in patients switching from other fentanyl containing products for their BTP.
Patients must wait at least 4 hours before treating another episode of BTP with fentanyl.
Patients should be prescribed an initial titration supply of one bottle (2 sprays or 8 sprays) of fentanyl 100 micrograms/spray.
Patients whose initial dose is 100 micrograms and who need to titrate to a higher dose due to a lack of effect can be instructed to use two 100 microgram sprays (one in each nostril) for their next BTP episode. If this dose is not successful, the patient may be prescribed a bottle of fentanyl 400 micrograms/spray and instructed to change to one 400 microgram spray for their next episode of pain. If this dose is not successful, the patient may be instructed to increase to two 400 microgram sprays (one in each nostril).
From treatment initiation, patients should be closely followed and the dose titrated until an effective dose is reached and confirmed for two consecutively treated episodes of BTP.
Titration in patients switching between immediate-release fentanyl containing products Substantial differences may exist in the pharmacokinetic profile of immediate-release fentanyl medicinal products, which result in clinically important differences in the rate and extent of absorption of fentanyl. Therefore, when switching between fentanyl containing medicinal products indicated for treatment of breakthrough pain, including intranasal formulations, it is essential that patients are again titrated with the new medicinal product, and not switched on a dose-for-dose (microgram-formicrogram) basis.
Once an effective dose has been established during titration, patients should continue to take this dose up to a maximum of 4 doses per day.
Generally, the maintenance dose of fentanyl should be increased only where the current dose fails to adequately treat the BTP for several consecutive episodes.
A review of the dose of the background opioid therapy may be required if patients consistently present with more than four BTP episodes per 24 hours.
In absence of adequate pain control, the possibility of hyperalgesia, tolerance and progression of underlying disease should be considered.
If adverse reactions are intolerable or persistent, the dose should be reduced or treatment with fentanyl replaced by another analgesic.
Discontinuation of therapy fentanyl should be discontinued immediately if the patient no longer experiences breakthrough pain episodes. The treatment for persistent backgound pain should be kept as prescribed.
If discontinuation of all opioid therapy is required, the patient must be closely followed by the doctor as gradual downward opioid titration therapy is necessary in order to avoid the possibility of abrupt withdrawal effects.
In the fentanyl clinical trial programme, 104 (26.1%) of patients were over 60 years of age, 67 (16.8%) over 65 years and 15 (3.8%) over 75 years. There was no indication that older patients tended to titrate to lower doses or experience more adverse reactions. Nevertheless, in view of the importance of renal and hepatic function in the metabolism and clearance of fentanyl, additional care should be exercised in the use of fentanyl in the elderly. No data on the pharmacokinetics of fentanyl in elderlyฯpatients are available.
Sublingual
100 - 400 ug
From 25 To 100 ug 4 time(s) per day every day
Fentanyl should only be administered to patients who are considered tolerant to their opioid therapy for persistent cancer pain. Patients can be considered opioid tolerant if they take at least 60 mg of oral morphine daily, at least 25 micrograms of transdermal fentanyl per hour, at least 30 mg of oxycodone daily, at least 8 mg of oral hydromorphone daily or an equianalgesic dose of another opioid for a week or longer.
Fentanyl sublingual tablets should be administered directly under the tongue at the deepest part. Fentanyl sublingual tablets should not be swallowed, but allowed to completely dissolve in the sublingual cavity without chewing or sucking.
Patients should be advised not to eat or drink anything until the sublingual tablet is completely dissolved. In patients who have a dry mouth water may be used to moisten the buccal mucosa before taking fentanyl.
The object of dose titration is to identify an optimal maintenance dose for ongoing treatment of breakthrough pain episodes. This optimal dose should provide adequate analgesia with an acceptable level of adverse reactions. The optimal dose of fentanyl will be determined by upward titration, on an individual patient basis. Several doses are available for use during the dose titration phase. The initial dose of Fentanyl used should be 100 micrograms, titrating upwards as necessary through the range of available dosage strengths.
Patients should be carefully monitored until an optimal dose is reached. Switching from other fentanyl containing products to fentanyl must not occur at a 1:1 ratio because of different absorption profiles. If patients are switched from another fentanyl containing product, a new dose titration with fentanyl is required.
The following dose regimen is recommended for titration, although in all cases the physician should take into account the clinical need of the patient, age and concomitant illness. All patients must start therapy with a single 100 microgram sublingual tablet. If adequate analgesia is not obtained within 15-30 minutes of administration of a single sublingual tablet, a supplemental (second) 100 microgram sublingual tablet may be administered. If adequate analgesia is not obtained within 15-30 minutes of the first dose an increase in dose to the next highest tablet strength should be considered for the next episode of breakthrough pain (Refer to figure below).
Dose escalation should continue in a stepwise manner until adequate analgesia with tolerable adverse reactions is achieved. The dose strength for the supplemental (second) sublingual tablet should be increased from 100 to 200 micrograms at doses of 400 micrograms and higher. This is illustrated in the schedule below. No more than two (2) doses should be administered for a single episode of breakthrough pain during this titration phase.
If adequate analgesia is achieved at the higher dose, but undesirable effects are considered unacceptable, an intermediate dose (using the 100 microgram sublingual tablet where appropriate) may be administered.
During titration, patients can be instructed to use multiples of 100 microgram tablets and/or 200 microgram tablets for any single dose. No more than four (4) tablets should be used at any one time.
The efficacy and safety of doses higher than 800 micrograms have not been evaluated in clinical studies in patients.
In order to minimise the risk of opioid–related adverse reactions and to identify the appropriate dose, it is imperative that patients be monitored closely by health professionals during the titration process.
During titration patients should wait at least 2 hours before treating another episode of breakthrough pain with fentanyl.
Once an appropriate dose has been established, which may be more than one tablet, patients should be maintained on this dose and should limit consumption to a maximum of four fentanyl doses per day. During the maintenance period patients should wait at least 2 hours before treating another episode of breakthrough pain with fentanyl.
If the response (analgesia or adverse reactions) to the titrated fentanyl dose markedly changes, an adjustment of dose may be necessary to ensure that an optimal dose is maintained.
If more than four episodes of breakthrough pain are experienced per day over a period of more than four consecutive days, then the dose of the long acting opioid used for persistent pain should be re-evaluated. If the long acting opioid or dose of long acting opioid is changed the fentanyl dose should be re-evaluated and re-titrated as necessary to ensure the patient is on an optimal dose.
It is imperative that any dose re-titration of any analgesic is monitored by a health professional. In absence of adequate pain control, the possibility of hyperalgesia, tolerance and progression of underlying disease should be considered.
Fentanyl should be discontinued immediately if the patient no longer experiences breakthrough pain episodes. The treatment for the persistent background pain should be kept as prescribed. If discontinuation of all opioid therapy is required, the patient must be closely followed by the doctor in order to avoid the possibility of abrupt withdrawal effects.
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