MATRIFEN Transdermal patch Ref.[7247] Active ingredients: Fentanyl

Posology

Matrifen doses should be individualised based upon the status of the patient and should be assessed at regular intervals after application. The lowest effective dose should be used. The patches are designed to deliver approximately 12, 25, 50, 75, and 100 mcg/h fentanyl to the systemic circulation, which represent about 0.3, 0.6, 1.2, 1.8, and 2.4 mg per day respectively.

Initial dosage selection

The appropriate initiating dose of Matrifen should be based on the patient’s current opioid use. It is recommended that Matrifen 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 Matrifen refer to Equianalgesic potency conversion below. The dosage may subsequently be titrated upwards or downwards, if required, in increments of either 12 or 25 mcg/h to achieve the lowest appropriate dosage of Matrifen depending on response and supplementary analgesic requirements.

Opioid-naive patients

Generally, the transdermal route is not recommended in opioid-naïve patients. Alternative routes of administration (oral, parenteral) should be considered. To prevent overdose it is recommended that opioid-naïve patients receive low doses of immediate-release opioids (e.g. morphine, hydromorphone, oxycodone, tramadol, and codeine) that are to be titrated until an analgesic dosage equivalent to Matrifen with a release rate of 12 mcg/h or 25 mcg/h is attained. Patients can then switch to Matrifen.

In the circumstance in which commencing with oral opioids is not considered possible and Matrifen is considered to be the only appropriate treatment option for opioid-naïve patients, only the lowest starting dose (ie, 12 mcg/h) should be considered. In such circumstances, the patient must be closely monitored. The potential for serious or life-threatening hypoventilation exists even if the lowest dose of Matrifen is used in initiating therapy in opioid-naïve patients (see sections 4.4 and 4.9).

Equianalgesic potency conversion

In patients currently taking opioid analgesics, the starting dose of Matrifen should be based on the daily dose of the prior opioid. To calculate the appropriate starting dose of Matrifen, follow the steps below.

1. Calculate the 24-hour dose (mg/day) of the opioid currently being used.
2. Convert this amount to the equianalgesic 24-hour oral morphine dose using the multiplication factors in Table 1 for the appropriate route of administration.
3. To derive the Matrifen dosage corresponding to the calculated 24-hour, equianalgesic morphine dosage, use dosage-conversion Table 2 or 3 as follows:
   • Table 2 is for adult patients who have a need for opioid rotation or who are less clinically stable (conversion ratio of oral morphine to transdermal fentanyl approximately equal to 150:1).
   • Table 3 is for adult patients who are on a stable, and well-tolerated, opioid regimen (conversion ratio of oral morphine to transdermal fentanyl approximately equal to 100:1).

Table 1. Conversion Table – Multiplication Factors for Converting the Daily Dose of Prior Opioids to the Equianalgesic 24-hour Oral Morphine Dose (mg/day Prior Opioid x Factor = Equianalgesic 24-hour Oral Morphine Dose):

^a The oral/IM potency for morphine is based on clinical experience in patients with chronic pain.
^b Based on single-dose studies in which an IM dose of each active substance listed was compared with morphine to establish the relative potency. Oral doses are those recommended when changing from a parenteral to an oral route.

Table 2. Recommended starting dosage of Matrifen based upon daily oral morphine dose (for patients who have a need for opioid rotation or for clinically less stable patients: conversion ratio of oral morphine to transdermal fentanyl is approximately equal to 150:1)¹:

¹ In clinical studies these ranges of daily oral morphine doses were used as a basis for conversion to Matrifen

Table 3. Recommended starting dosage of Matrifen based upon daily oral morphine dosage (for patients on stable and well tolerated opioid therapy: conversion ratio of oral morphine to transdermal fentanyl is approximately equal to 100:1):

Initial evaluation of the maximum analgesic effect of Matrifen cannot be made before the patch is worn for 24 hours. This delay is due to the gradual increase in serum fentanyl concentration in the 24 hours following initial patch application.

Previous analgesic therapy should therefore be gradually phased out after the initial dose application until analgesic efficacy with Matrifen is attained.

Dose titration and maintenance therapy

The Matrifen patch should be replaced every 72 hours.

The dose should be titrated individually on the basis of average daily use of supplemental analgesics, until a balance between analgesic efficacy and tolerability is attained. Dosage titration should normally be performed in 12 mcg/h or 25 mcg/h increments, although the supplementary analgesic requirements (oral morphine 45/90 mg/day ≈ Matrifen 12/25 mcg/h) and pain status of the patient should be taken into account. After an increase in dose, it may take up to 6 days for the patient to reach equilibrium on the new dose level. Therefore after a dose increase, patients should wear the higher dose patch through two 72-hour applications before any further increase in dose level is made.

More than one Matrifen patch may be used for doses greater than 100 micrograms/hour. Patients may require periodic supplemental doses of a short-acting analgesic for breakthrough pain. Some patients may require additional or alternative methods of opioid administration when the Matrifen dose exceeds 300 micrograms/hour.

If analgesia is insufficient during the first application only, the Matrifen patch may be replaced after 48 hours with a patch of the same dose, or the dose may be increased after 72 hours.

If the patch needs to be replaced (eg, the patch falls off) before 72 hours, a patch of the same strength should be applied to a different skin site. This may result in increased serum concentrations (see section 5.2) and the patient should be monitored closely.

Discontinuation of Matrifen

If discontinuation of Matrifen 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 Matrifen is removed. It may take 20 hours or more for the fentanyl serum concentrations to decrease 50%. In general, the discontinuation of opioid analgesia should be gradual in order to prevent withdrawal symptoms (see section 4.8).

Opioid withdrawal symptoms are possible in some patients after conversion or dose adjustment.

Tables 1, 2, and 3 should only be used to convert from other opioids to Matrifen and not from Matrifen to other therapies to avoid overestimating the new analgesic dose and potentially causing overdose.

Special populations

Elderly patients

Elderly patients should be observed carefully and the dose should be individualised based upon the status of the patient (see section 4.4 and 5.2).

In opioid-naïve elderly patients, treatment should only be considered if the benefits outweigh the risks. In these cases, only Matrifen 12 mcg/h dosage should be considered for initial treatment.

Renal and hepatic impairment

Patients with renal or hepatic impairment should be observed carefully and the dose should be individualised based upon the status of the patient (see sections 4.4 and 5.2).

In opioid-naïve patients with renal or hepatic impairment, treatment should only be considered if the benefits outweigh the risks. In these cases, only Matrifen 12 mcg/h dosage should be considered for initial treatment.

Paediatric population

Children aged 16 years and above: Follow adult dosage.

Children aged 2 to 16 years old: Matrifen should be administered only to those 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 or parenteral opioids to Matrifen, refer to Equianalgesic potency conversion (Table 1), and Recommended initial Matrifen dose based upon daily oral morphine dose (Table 4).

Table 4. Recommended Matrifen dosage for paediatric patients1 based upon daily oral morphine dose²:

¹ Conversion to Matrifen dosages greater than 25 mcg/h is the same for paediatric patients as it is for adult patients (see Table 2).
² In clinical studies these ranges of daily oral morphine doses were used as a basis for conversion to Matrifen.

In two 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 transdermal fentanyl 12 microgram/hour patch. It should be noted that this conversion schedule for children only applies to the switch from oral morphine (or its equivalent) to fentanyl transdermal patches. The conversion schedule could not be used to convert from transdermal fentanyl into other opioids, as overdosing could then occur.

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

Monitoring of the patient for adverse events, which may include hypoventilation, is recommended for at least 48 hours after initiation of Matrifen therapy or up-titration of the dose (see section 4.4).

Matrifen should not be used in children aged less than 2 years because the safety and efficacy have not been established.

Dose titration and maintenance in children:

The Matrifen patch should be replaced every 72 hours. The dose should be titrated individually until a balance between analgesic efficacy and tolerability is attained. Dosage must not be increased in intervals of less than 72 hours. If the analgesic effect of Matrifen 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 micrograms/hour steps.

Method of administration

Matrifen is for transdermal use.

Matrifen should be applied to non-irritated and non-irradiated skin on a flat surface of the torso or upper arms.

In young children, the upper back is the preferred location to apply the patch, to minimize the potential of the child removing the patch.

Hair at the application site (a non-hairy area is preferred) should be clipped (not shaved) prior to application. If the site of Matrifen application requires to be cleansed prior to application of the patch, this should be done with clear 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 application of the patch. Patches should be inspected prior to use. Patches that are cut, divided, or damaged in any way should not be used.

Matrifen should be applied immediately upon removal from the sealed package. To remove the patch from the protective sachet, locate the pre-cut notch (indicated by an arrow on the patch label) along the edge of the seal. Fold the sachet at the notch, then carefully tear the sachet material. Further open the sachet along both sides, folding the sachet open like a book. The release liner for the patch is slit. Fold the patch in the middle and remove each half of the liner separately. Avoid touching the adhesive side of the patch. Apply the patch to the skin by applying light pressure with the palm of the hand for about 30 seconds. Make certain that the edges of the patch are adhering properly. Then wash hands with clean water.

Matrifen may be worn continuously for 72 hours. A new patch should 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 the skin.

Symptoms and signs

The manifestations of fentanyl overdose are an extension of its pharmacological actions, the most serious effect being respiratory depression.

Treatment

For management of respiratory depression immediate countermeasures include removing the Matrifen patch and physically or verbally stimulating the patient. These actions can be followed by administration of a specific opioid antagonist such as naloxone.

Respiratory depression following an overdose may outlast the duration of action of the opioid antagonist. The interval between IV antagonist doses should be carefully chosen because of the possibility of re-narcotization after the patch is removed; repeated administration or a continuous infusion of naloxone may be necessary. Reversal of the narcotic effect may result in acute onset of pain and release of catecholamines.

If the clinical situation warrants, a patent airway should be established and maintained, possibly with an oropharyngeal airway or endotracheal tube, and oxygen should be administered and respiration assisted or controlled, as appropriate. Adequate body temperature and fluid intake should be maintained.

If severe or persistent hypotension occurs, hypovolaemia should be considered, and the condition should be managed with appropriate parenteral fluid therapy.

Shelf life: 3 years.

This medicinal product does not require any special storage conditions.

Each patch is packed in a heat-sealed sachet made of paper, aluminium and acrylonitrile-methyl acrylate-butadiene (AMAB) or made of paper, aluminium, polyethylene terephthalate (PET), polyethylene (PE) and cyclic olefin copolymer (LAS Pol A).

Pack sizes: 1, 2, 3, 4, 5, 8, 10, 16, and 20 patches.

Not all pack sizes may be marketed.

Instructions for disposal: Used patches should be folded so that the adhesive side of the patch adheres to itself and then they should be safely discarded. Any unused medicinal product or waste material should be discarded of in accordance with local requirements.

Wash hands with water after applying or removing the patch.