Posology : מינונים

4.2     Posology and method of administration

For transdermal use.

Fenta should be applied to non-irritated and non-irradiated skin on a flat surface of the torso or upper arm. In young children, the upper back is the preferred location to apply the patch, to minimise the potential of the child removing the patch. A non-hairy area should be selected. If this is not possible, hair at the application site should be clipped (not shaved) prior to application. If the site of Fenta application requires to be cleansed prior to application of the patch, this should be done with water. Soaps, oils, lotions or any other agent that might irritate the skin or alter its characteristics should not be used. The skin should be completely dry before the patch is applied. Patches should be inspected prior to use. Patches that are cut, divided, or damaged in any way should not be used.

Fenta should be applied immediately after removal from the sealed sachet (pouch). Avoid touching the adhesive side of the patch. Following removal of both parts of the protective liner, the transdermal patch should be pressed firmly in place with the palm of the hand for approximately 30 seconds, making sure the contact is complete, especially around the edges. Then wash hands with clean water.

Fenta should be worn continuously for 72 hours. A new patch should then be applied to a different skin site after removal of the previous transdermal patch. Several days should elapse before a new patch is applied to the same area of skin.

The need for continued treatment should be assessed at regular intervals.

Initial dose selection
The appropriate initiating dose of Fenta should be based on the patient's current opioid use. Fenta should be used in patients who have demonstrated opioid tolerance. Other factors to be considered are the current general condition and medical status of the patient, including body size, age, and extent of debilitation as well as degree of opioid tolerance.

Adults:

Opioid-tolerant patients
To convert opioid-tolerant patients from oral or parenteral opioids to Fenta refer to Equianalgesic potency conversion below. The dosage may subsequently be titrated upwards or downwards, if required, in increments of either 12.5 or 25 mcg/hr to achieve the lowest appropriate dose of Fenta depending on response and supplementary analgesic requirements.

Equianalgesic potency conversion

1. Calculate the previous 24-hour analgesic requirement.
2. Convert this amount to the equianalgesic oral morphine dose using Table 1. All IM and oral doses in this chart are considered equivalent to 10 mg of IM morphine in analgesic effect.

3. To derive the dosage of Fenta corresponding to the calculated 24-hour, equianalgesic morphine dosage, use the dosage-conversion Table 2 or Table 3 as follows:

Table 2 is for adult patients who have been stabilised on oral morphine or another immediate-release opioid over several weeks and who need opioid rotation (conversion ratio of oral morphine to transdermal fentanyl approximately equal to 150:1).

Table 3 is for highly opioid-tolerant adult patients who have been on a stable and well-tolerated opioid regimen for a long period, and who need opioid rotation (conversion ratio of oral morphine to transdermal fentanyl approximately equal to 100:1).

Tables 2 and 3 should not be used to switch from transdermal fentanyl to another opioid treatment.
Table 1 Equianalgesic potency conversion

Drug name                                  Equianalgesic dose (mg)
IM*                           Oral morphine                                   10                            30-40 (assuming repeated dosing)** hydromorphone                              1.5                           7.5 methadone                                  10                            20 oxycodone                                  15                            30 levorphanol                                2                             4 oxymorphone                                1                             10 (rectal) diamorphine                                5                             60 pethidine                                  75                            — codeine                                    130                           200 buprenorphine                             0.4                          0.8 (sublingual) * Based on single-dose studies in which an IM dose of each drug listed was compared with morphine to establish the relative potency. Oral doses are those recommended when changing from a parenteral to an oral route.

** The oral/IM potency for morphine is based on clinical experience in patients with chronic pain.

Reference: Adapted from Foley KM. The treatment of cancer pain. NEJM 1985; 313 (2): 84-95, with updates.
Table 2: Recommended starting dosage of Fenta based upon daily oral morphine dosage 1 (for patients stabilised on oral morphine or immediate release opioid for several weeks and who need opioid rotation) 
Fenta

Oral 24-hour              Dosage morphine
(mcg/hr)
(mg/day)
<135                      25
135-224                   50
225-314                   75
315-404                   100
405-494                   125
495-584                   150
585-674                   175
675-764                   200
765-854                   225
855-944                   250
945-1034                  275
1035-1124                   300
1 Inclinical trials these ranges of daily oral morphine dosages were used as a basis for conversion to fentanyl transdermal patch.
Table 3: Recommended starting dosage of Fenta based upon daily oral morphine dosage (for patients on stable and well tolerated opioid therapy for long periods and who need opioid rotation) 
Fenta

Oral 24-hour               Dosage morphine
(mcg/hr)
(mg/day)
≤ 44                       12.5 (Fenta 12)
45-89                      25
90-149                     50
150-209                    75
210-269                    100
270-329                    125
330-389                    150
390-449                    175
450-509                    200
510-569                    225
570-629                    250
630-689                    275
690-749                    300

Previous analgesic therapy should be phased out gradually from the time of the first patch application until analgesic efficacy with Fenta is attained. For opioid tolerant patients, the initial evaluation of the analgesic effect of Fenta should not be made until the patch has been worn for 24 hours due to the gradual increase in serum fentanyl concentrations up to this time.

Dose titration and maintenance therapy

The Fenta patch should be replaced every 72 hours. The dose should be titrated individually until a balance between analgesic efficacy and tolerability is attained. In patients who experience a marked decrease in the period 48-72 hours after application, replacement of fentanyl after 48 hours may be necessary. If analgesia is insufficient at the end of the initial application period, the dose may be increased. Dose adjustment, when necessary, should normally be performed in the following titration steps from 25 mcg/hr up to 75 mcg/hr: 25 mcg/hr, 37 mcg/hr, 50 mcg/hr, 62 mcg/hr and 75 mcg/hr; thereafter dose adjustments should normally be performed in 25 mcg/hr increments, although the supplementary analgesic requirements (oral morphine 90 mg/day ≈ Fenta 25 mcg/hr) and pain status of the patient should be taken into account. More than one Fenta patch may be used to achieve the desired dose. Patients may require periodic supplemental doses of a short-acting analgesic for 'breakthrough' pain. Additional or alternative methods of analgesia should be considered when the Fenta dose exceeds 300 mcg/hr.

Discontinuation of Fenta

If discontinuation of Fenta is necessary, any replacement with other opioids should be gradual, starting at a low dose and increasing slowly. This is because fentanyl concentrations fall gradually after Fenta is removed, it takes 17 hours or more for the fentanyl serum concentrations to decrease 50% (see Section 5.2, Pharmacokinetic Properties). As a general rule, the discontinuation of opioid analgesia should be gradual, in order to prevent withdrawal symptoms.

Opioid withdrawal symptoms (See section 4.8, Undesirable effects) are possible in some patients after conversion or dose adjustment.

Table 2 and Table 3 should not be used to convert from Fenta to other therapies to avoid overestimating the new analgesic dose and potentially causing overdose.
Use in elderly patients

Data from intravenous studies with fentanyl suggest that elderly patients may have reduced clearance, a prolonged half-life and they may be more sensitive to the drug than younger patients. Elderly, cachectic, or debilitated patients should be observed carefully for signs of fentanyl toxicity and the dose reduced if necessary (see section 5.2 Pharmacokinetic properties).

Paediatric population

Children aged 16 years and above: follow adult dosage
Children aged 2 to16 years old:

Fenta should be administered only to opioid-tolerant paediatric patients (ages 2 to 16 years) who are already receiving at least 30 mg oral morphine equivalents per day. To convert paediatric patients from oral opioids to Fenta refer to Table 4, Recommended Fenta dose based upon daily oral morphine dose.

Table 4: Recommended Fenta dose based upon daily oral morphine dose1

Oral 24-Hour Morphine (mg/day)                      Fenta (mcg/hr)
For paediatric   patients2
30 - 44                                             12.5 (Fenta 12)
45 - 134                                                25
1 In clinical trials these ranges of daily oral morphine doses were used as a basis for conversion to fentanyl transdermal patch.

2    Conversion to Fenta doses greater than 25 mcg/hr is the same for adult and paediatric patients

For children who receive more than 90 mg oral morphine a day, only limited information is currently available from clinical trials. In the paediatric studies, the required fentanyl transdermal patch dose was calculated conservatively: 30 mg to 44 mg oral morphine per day or its equivalent opioid dose was replaced by one fentanyl transdermal patch of 12.5 mcg/hr (Fenta12). It should be noted that this conversion schedule for children only applies to the switch from oral morphine (or its equivalent) to Fenta patches.

The conversion schedule should not be used to convert from Fenta into other opioids, as overdosing could then occur.

The analgesic effect of the first dose of Fenta patches will not be optimal within the first 24 hours. Therefore, during the first 12 hours after switching to Fenta, the patient should be given the previous regular dose of analgesics. In the next 12 hours, these analgesics should be provided based on clinical need.

Since peak fentanyl levels occur after 12 to 24 hours of treatment, monitoring of the patient for adverse events, which may include hypoventilation, is recommended for at least 48 hours after initiation of Fenta therapy or up-titration of the dose (see also section 4.4, Special warnings and precautions for use).

Dose titration and maintenance

If the analgesic effect of Fenta is insufficient, supplementary morphine or another short-duration opioid should be administered. Depending on the additional analgesic needs and the pain status of the child, it may be decided to increase the dose. Dose adjustments should be done in 12.5 mcg/hr steps.