OPIODUR

4). Posology Opiodur/Fentanyl Zentiva 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 dose selection The appropriate initiating dose of fentanyl should be based on the patient’s current opioid use. It is recommended that Opiodur/Fentanyl Zentiva 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 Opiodur/Fentanyl Zentiva 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/hr to achieve the lowest appropriate dose of Opiodur/Fentanyl Zentiva 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. 5 mcg/h or 25 mcg/h is attained. Patients can then switch to Opiodur/Fentanyl Zentiva.

, 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 Opiodur/Fentanyl Zentiva should be based on the daily dose of the prior opioid.

To calculate the appropriate starting dose of Opiodur/Fentanyl Zentiva, 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. 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 Opiodur/Fentanyl Zentiva based on daily oral morphine dose (for patients who have a need for opioid rotation or for clinically less stable patients: conversion ratio for oral morphine to transdermal fentanyl is approximately equal to 150:1)1 Oral 24-hour morphine (mg/ day) Opiodur/Fentanyl Zentiva Dosage (mcg/h) < 90 12 90-134 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 In clinical studies these ranges of daily oral morphine doses were used as a basis for conversion to transdermal Opiodur/Fentanyl Zentiva.

Table 3:

Recommended starting dosage of Opiodur/Fentanyl Zentiva based on 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-morphine (mg/day ) Opiodur/Fentanyl Zentiva dosage (mcg/h) < 44 12 45-89 25 […]

The safety of transdermal fentanyl patches was evaluated in 1565 adult and 289 paediatric subjects who participated in 11 clinical trials (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 transdermal fentanyl patches and provided safety data. 8%). The adverse reactions reported with the use of transdermal fentanyl patches from these clinical trials, including the above-mentioned ADRs, 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 Opiodur/Fentanyl Zentiva, 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 Opiodur/Fentanyl Zentiva contains an active substance in an amount that can be fatal, especially to a child. Therefore, they must keep all patched 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 Opiodur/Fentanyl Zentiva in a safe and secure place, not accessible by others.

Opioid-naive and not opioid-tolerant states Use of fentanyl transdermal patches in the opioid-naive patient 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 Opiodur/Fentanyl Zentiva is used in initiating therapy in opioid-naive 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 Opiodur/Fentanyl Zentiva and patients must be observed for these effects.

Respiratory depression may persist beyond the removal of the Opiodur/Fentanyl Zentiva 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 Opiodur/Fentanyl Zentiva 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 Opiodur/Fentanyl Zentiva 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 Opiodur/Fentanyl Zentiva 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.

Opioid use disorder (abuse and dependence) Repeated use of Opiodur/Fentanyl Zentiva 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 Opiodur/Fentanyl Zentiva may result in overdose and/or death.

g. major depression, anxiety and personality disorders). 2). Before and during treatment the patient should also be informed about the risks and signs of OUD. If these signs occur, patients should be advised to contact their physician.

g. too early requests for refills), particularly with patients at increased risk. This includes the review of concomitant opioids and psycho-active drugs (like benzodiazepines). For patients with signs and symptoms of OUD, consultation with an addiction specialist should be considered.

4). Drug withdrawal syndrome Prior to starting treatment with any opioids, a discussion should be held with patients to put in place a withdrawal strategy for ending treatment with fentanyl.. Drug withdrawal syndrome may occur upon abrupt cessation of therapy or dose reduction.

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.

If women take this drug during pregnancy, there is a risk that their newborn infants will experience neonatal withdrawal syndrome. Hyperalgesia Hyperalgesia may be diagnosed if the patient on long-term opioid therapy presents with increased pain.

This might be […]

1. Acute or postoperative pain because there is no opportunity for dose titration during short-term use and because serious or life threatening hypoventilation could result. Severe respiratory depression. Contraindicated in opioid naive patients.