TILOTRANS

Posology Tilotrans transdermal patch 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. 4 mg per day respectively.

Initial dosage selection:

The appropriate initiating dose of Tilotrans transdermal patch should be based on the patient's current opioid use. It is recommended that Tilotrans transdermal patch 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 Tilotrans transdermal patch 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 Tilotrans transdermal patch depending on response and supplementary analgesic requirements.

Opioid-naïve patients Generally, the transdermal route is not recommended in opioid-naïve patients. Alternative routes of administration (oral, parenteral) should be considered. g. morphine, hydromorphone, oxycodone, tramadol, and codeine) that are to be titrated until an analgesic dosage equivalent to Tilotrans transdermal patches with a release rate of 12 mcg/h or 25 mcg/h is attained.

Patients can then switch to Tilotrans transdermal patches. e. 12 mcg/h) should be considered. In such circumstances, the patient must be closely monitored. 9) Equianalgesic potency conversion In patients currently taking opioid analgesics, the starting dose of Tilotrans transdermal patch should be based on the daily dose of the prior opioid.

To calculate the appropriate starting dose of Tilotrans transdermal patch 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 Tilotrans transdermal patch dosage corresponding to the calculated 24-hour, equianalgesic morphine dosage, use dosage-conversion Table 2 or 3 as follows: a) 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) b) 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).

3 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.

Reference:

Adapted from 1) Foley KM. The treatment of cancer pain. NEJM 1985; 313 (2): 84-95 and 2) McPherson ML. Introduction to opioid conversion calculations.

In: Demystifying Opioid Conversion Calculations:

A Guide for Effective Dosing.

Bethesda, MD:

American Society of Health-System Pharmacists; 2010:1-15.

Table 2:

Recommended starting dosage of Tilotrans transdermal patch 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 Oral 24-hour morphine (mg/day) Tilotrans transdermal patch Dosage (mcg/h) 90-134 135-224 225-314 315-404 405-494 495-584 585-674 675-764 765-854 855-944 945-1034 1035-1124 25 50 75 100 125 150 175 200 225 250 275 300 1 In clinical studies these ranges of daily oral morphine doses were used as a basis for conversion to Tilotrans transdermal patches.

Table 3:

Recommended starting dosage of Tilotrans transdermal patch 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) Oral 24-hour morphine (mg/day) Tilotrans transdermal patch Dosage (mcg/h) 45-89 90-149 150-209 210-269 270-329 330-389 25 50 75 100 125 150 390-449 450-509 510-569 570-629 630-689 690-749 175 200 225 250 275 300 Initial evaluation of the maximum analgesic effect of […]

The safety of Tilotrans transdermal patches was evaluated in 1,565 adult and 289 paediatric subjects who participated in 11 clinical studies (1 double-blind, placebo- controlled; 7 open-label, active-controlled; 3 open-label, uncontrolled) used for the management of chronic malignant or non-malignant pain.

These subjects received at least one dose of Tilotrans transdermal patch and provided safety data. e. 8%). The adverse reactions reported with the use of Tilotrans transdermal patches from these clinical studies, including the above-mentioned adverse reactions, and from post-marketing experiences are listed below in Table

Patients who have experienced serious adverse events should be monitored for at least 24 hours after removal of Tilotrans transdermal patch, or more, as clinical symptoms dictate, because serum fentanyl concentrations decline gradually and are reduced by about 50% 20 to 27 hours later.

Patients and their carers must be instructed that Tilotrans transdermal patches contains an active substance in an amount that can be fatal, especially to a child. Therefore, they must keep all patches out of the sight and reach of children, both before and after use.

Because of the risks, including fatal outcome, associated with accidental ingestion, misuse, and abuse, patients and their carers must be advised to keep Tilotrans transdermal patches in a safe and secure place, not accessible by others.

Opioid-naïve and not opioid-tolerant states Use of Tilotrans transdermal patch in opioid-naïve patients has been associated with very rare cases of significant respiratory depression and/or fatality when used as initial opioid therapy, especially in patients with non-cancer pain.

The potential for serious or life-threatening hypoventilation exists even if the lowest dose of Tilotrans transdermal patch is used in initiating therapy in opioid-naïve patients, especially in elderly or patients with hepatic or renal impairment.

The tendency of tolerance development varies widely among individuals. 2). Respiratory depression Some patients may experience significant respiratory depression with Tilotrans transdermal patches; patients must be observed for these effects.

Respiratory depression may persist beyond the removal of the Tilotrans transdermal patch. 9). Opioids can cause sleep-related breathing disorders including central sleep apnoea (CSA) and sleep-related hypoxia. Opioid use increases the risk of CSA in a dose- dependent fashion.

In patients who present with CSA consider decreasing the total opioid dosage. Risk from concomitant use of central nervous system (CNS) depressants, including sedative medicines such as benzodiazepines or related drugs, alcohol and CNS depressant narcotic drugs Concomitant use of Tilotrans transdermal patch and sedative medicines such as benzodiazepines or related drugs, alcohol, or CNS depressant narcotic drugs may result in sedation, respiratory depression, coma and death.

Because of these risks, concomitant prescribing with sedative medicines should be reserved for patients for whom alternative treatment options are not possible. If a decision is made to prescribe Tilotrans transdermal patch concomitantly with sedative medicines, the lowest effective dose should be used, and the duration of treatment should be as short as possible.

The patients should be followed closely for signs and symptoms of respiratory depression and sedation. 5). Chronic pulmonary disease Tilotrans may have more severe adverse effects in patients with chronic obstructive or other pulmonary disease.

In such patients, opioids may decrease respiratory drive and increase airway resistance. Long-term treatment effects and tolerance In all patients, tolerance to the analgesic effects, hyperalgesia, physical dependence, and psychological dependence may develop upon repeated administration of opioids, whereas incomplete tolerance is developed for some side effects like opioid induced constipation.

Particularly in patients with chronic non cancer pain, it has been reported that they may not experience a meaningful amelioration in pain intensity from continuous opioid treatment in the long term. 2). When it is decided that there is no benefit for continuation, gradual down titration should be applied to address withdrawal symptoms.

Do not abruptly discontinue Tilotrans transdermal patch in a patient physically dependent on opioids. Drug withdrawal syndrome may occur upon abrupt cessation of therapy or dose reduction. 8). When a patient no longer requires therapy, it is advisable to taper the dose gradually to minimise symptoms of withdrawal.

Tapering from a high dose may take weeks to months. The opioid drug withdrawal syndrome is characterised by some or all of the following: restlessness, lacrimation, rhinorrhoea, yawning, perspiration, chills, myalgia, mydriasis and palpitations.

Other symptoms may also develop including irritability, agitation, anxiety, hyperkinesia, tremor, weakness, insomnia, anorexia, abdominal cramps, nausea, vomiting, diarrhoea, increased blood pressure, increased respiratory rate or heart rate.

Opioid use disorder (abuse and dependence) Repeated use of Tilotrans transdermal patch may lead to Opioid use disorder (OUD). A higher dose and longer duration of opioid treatment can increase the risk of developing OUD. Abuse or intentional misuse of Tilotrans transdermal patch may result in overdose and/or death.

The risk of developing OUD is increased in patients with a personal or a family history (parents or siblings) of substance use disorders (including alcohol use disorder), in current tobacco users or in patients with a personal history of other mental health disorders (eg major depression, anxiety and personality disorders).

Before initiating treatment with <fentanyl transdermal patch> and during the treatment, treatment goals and a discontinuation plan should be agreed with the […]

1. - Acute pain because there is no opportunity for dose titration during short-term use, or postoperative pain because persistent post-operative opioid use or serious or life- threatening hypoventilation could result. - Severe respiratory depression.

- Contraindicated in opioid naive patients.