Durogesic 12,25,50,75100MCG/H Durogesic 12,25,50

Transcription

J-C Health Care Ltd.
Kibbutz Shefayim 60990, ISRAEL
tel +972-9-959-1111
fax +972-9-958-3636
0212 ‫דצמבר‬
‫ה‬/‫ה נכבד‬/‫רופא‬
‫ת‬/‫ת נכבד‬/‫רוקח‬
‫ברצו ננו להביא לידיעתכם את העדכונים לעלונים לרופא ולצרכן של תכשיר‬
Durogesic 12,25,50,75,100MCG/H
:‫ראי קישור לאתר משרד הבריאות‬/‫ ראה‬.‫העלונים לרופא ולצרכן מפורסמים במלואם באתר משרד הבריאות‬
http://www.health.gov.il/units/pharmacy/trufot/index.asp?safa
. 00-0101111 ‫ניתן לקבל את העלונים המודפסים בפניה אלינו לטלפון‬
.‫ הטקסט המודגש באדום הוסף לעלון ואילו הטקסט המחוק בכחול נגרע ממנו‬.‫להלן העדכונים‬
‫בברכה‬
‫יוני קרל‬
‫רוקח ממונה‬
Durogesic 12,25,50,75,100MCG/H
Transdermal patch : ‫צורת מינון‬
Fentanyl 12, 25, 50, 75,100 mcg/h :‫הרכב תכשיר‬
:‫התוויה‬
Management of chronic pain and intractable pain requiring
opioid analgesia.
Durogesic should only be used in patients who are already receiving opioid therapy,
who have demonstrated opioid tolerance.
:‫שינויים בעלון לרופא‬
DESCRIPTION
…………….
The composition per unit area of all system size is identical.
Durogesic® is a rectangular transparent unit comprising a protective liner and two functional layers.
Proceeding from the outer surface toward the surface adhering to skin, these layers are:
1) a backing layer of polyester/ethyl vinyl acetate film; 2) a drug-in-adhesive layer. Before use, a protective
liner covering the adhesive layer is removed and discarded.
The active component of the system is fentanyl. The remaining components are pharmacologically
inactive.
CLINICAL PHARMACOLOGY
Pharmacology
………………
In addition to analgesia, alterations in mood, euphoria, dysphoria, and drowsiness
commonly occur. Fentanyl depresses the respiratory centers, depresses the cough
reflex, and constricts the pupils. Analgesic blood levels concentrations of fentanyl
may cause nausea and vomiting directly by stimulating the chemoreceptor trigger
zone, but nausea and vomiting are significantly more common in ambulatory than in
recumbent patients, as is postural syncope.
……………….
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Pharmacokinetics
Absorption
DUROGESIC provides continuous systemic delivery of fentanyl during the
72-hour application period. Fentanyl is released at a relatively constant rate,
determined by the copolymer release membrane and the diffusion of fentanyl
through the skin layers. Fentanyl is released at a relatively constant rate.
The concentration gradient existing between the matrix and the lower
concentration in the skin drives drug release After initial DUROGESIC
application, serum fentanyl concentrations increase gradually, generally
leveling off between 12 and 24 hours and remaining relatively constant for
the remainder of the 72-hour application period. The serum fentanyl
®
concentrations attained are proportional to the DUROGESIC patch size.
After repeated 72-hour applications, patients reach a steady-state serum
concentration that is maintained during subsequent applications of a patch of
the same size.
By the end of the second 72-hour application, a steady-state serum
concentration is reached and is maintained during subsequent applications
of a patch of the same size.
A pharmacokinetic model has suggested that serum fentanyl concentrations
may increase by 14% (range 0- 26%) if a new patch is applied after 24 hours
rather than the recommended 72-hour application.
Distribution
The plasma-protein binding of fentanyl is about 84%.
Metabolism
Fentanyl is a high clearance drug and is rapidly and extensively metabolized primarily by
CYP3A4 in the liver. The major metabolite, norfentanyl, is inactive. Skin does not appear to
metabolize fentanyl delivered transdermally. This was determined in a human keratinocyte cell
assay and in clinical studies in which 92% of the dose delivered from the system was accounted
for as unchanged fentanyl that appeared in the systemic circulation.
Elimination
After DUROGESIC is removed, serum fentanyl concentrations decline
gradually, falling about 50% in about 17 (range 13-22) hours following a 24hour application. Following a 72-hour application, the mean terminal half-life
ranges from 20-25 20-27 hours. Continued absorption of fentanyl from the
skin accounts for a slower disappearance of the drug from the serum than is
seen after an IV infusion, where the apparent half-life is approximately 7
(range 3-12) hours.
Elderly, cachectic, or debilitated patients may have a reduced clearance of
fentanyl and, therefore, the drug may have a prolonged terminal half-life in
them. Adjusting for body weight, clearance in pediatric patients was about
20% higher than that in adults. These findings have been taken into
consideration in determining the dosing recommendations for pediatric
patients.
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Fentanyl is a high clearance drug and is rapidly and extensively metabolized
primarily by CYP3A4 in the liver. Within 72 hours of IV fentanyl
administration, approximately Around 75% of the fentanyl dose is excreted
into the urine, mostly as metabolites, with less than 10% as unchanged drug.
About 9% of the dose is recovered in the feces, primarily as metabolites.
Mean values for unbound fractions of fentanyl in plasma are estimated to be
between 13 and 21%.
Special Populations:
Elderly
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. In a study conducted with
®
DUROGESIC , healthy elderly subjects had fentanyl pharmacokinetics
which did not differ significantly from healthy young subjects although peak
serum concentrations tended to be lower and mean half-life values were
prolonged to approximately 34 hours. Elderly patients should be observed
carefully for signs of fentanyl toxicity and the dose reduced if necessary
(Special warnings and special precautions).
Children
DUROGESIC® was not studied in children under 2 years of age. Studies
conducted in older children found that when adjusting for body weight,
clearance in pediatric patients was about 20% higher than that in adults.
These findings have been taken into consideration in determining the dosing
recommendations for pediatric patients. DUROGESIC® should be
administered only to opioid-tolerant children age 2 years or older (see
Posology and method of administration and Special warnings and special
precautions).
Hepatic Impairment
In a study conducted with patients with hepatic cirrhosis, the
®
pharmacokinetics of a single 50 g/hr application of DUROGESIC were
assessed. Although tmax and t1/2 were not altered, the mean plasma Cmax and
AUC values increased by approximately 35% and 73%, respectively, in
these patients. Patients with hepatic impairment should be observed
carefully for signs of fentanyl toxicity and the dose of DUROGESIC® reduced
if necessary (see Special warnings and special precautions).
Renal Impairment
Data obtained from a study administering IV fentanyl in patients undergoing
renal transplantation suggest that the clearance of fentanyl may be reduced
in this patient population. If patients with renal impairment receive
DUROGESIC®, they should be observed carefully for signs of fentanyl
toxicity and the dose reduced if necessary (see Special warnings and special
precautions).
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Drug interactions
The interaction between ritonavir , a CYP3A4 inhibitor, and fentanyl was
investigated in eleven healthy volunteers in a randomized crossover study. Subjects
received oral ritonavir or placebo for 3 days. The ritonavir dose was 200 mg tid on
Day 1 and 300 mg tid on Day 2 followed by one morning dose of 300 mg on Day 3.
On Day 2, fentanyl was given as a single IV dose at 5 mcg/kg two hours after the
afternoon dose of oral ritonavir or placebo. Naloxone was administered to
counteract the side effects of fentanyl. The results suggested that ritonavir might
decrease the clearance of fentanyl by 67%, resulting in a 174% (range 52%-420%)
increase in fentanyl AUC0-∞. Coadministration of ritonavir in patients receiving
DUROGESIC has not been studied; however, an increase in fentanyl AUC is
expected. (See BOX WARNING, WARNINGS, PRECAUTIONS and DOSAGE AND
ADMINISTRATION.)
Fentanyl is metabolized mainly via the human cytochrome P450 3A4 isoenzyme system
(CYP3A4), therefore, potential interactions may occur when Durogesic®is given concurrently
with agents that affect CYP3A4 activity. Coadminstration with agents that induce CYP3A4
activity may reduce the efficacy of Durogesic®. The concomitant use of transdermal fentanyl
with all CYP3A4 inhibitors (such as ritonavir, ketoconazole, itraconazole, troleandomycin,
clarithromycin, nelfinavir, nefazadone, amiodarmone, amprenavir, aprepitant, diltiazem,
erythromycin, fluconazole, fosamprenavir, and verapamil) may result in an increase in fentanyl
plasma concentrations, which could increase or prolong adverse drug effects and may cause
potentially fatal respiratory depression. Patients receiving Durogesic® and any CYP3A4
inhibitor should be carefully monitored for an extended period of time and dosage adjustments
should be made if warranted (see BOX WARNING, WARNINGS, PRECAUTIONS,and
DOSAGE AND ADMINISTRATION for further information).
WARNINGS
®
Durogesic patches are intended for transdermal use (on intact skin) only. Do not use
®
damaged or cut DUROGESIC patches.
Do not use a DUROGESIC® patch if the pouch seal is broken or the patch is cut,
damaged, or changed in any way.
The safety of DUROGESIC® (fentanyl transdermal system) has not been established in
children under 2 years of age.
.
DUROGESIC is ONLY for use in patients who are already tolerant to opioid
therapy of comparable potency. Use in non-opioid tolerant patients may lead
®
to fatal respiratory depression. Overestimating the DUROGESIC dose when
converting patients from another opioid medication can result in fatal
overdose with the first dose. The mean elimination half-life of DUROGESIC® is
approximately 20-27 hours.17 hours. Therefore, patients who have experienced
serious adverse events, including overdose, will require monitoring for at least 24
hours after DUROGESIC® removal since serum fentanyl concentrations decline
gradually and reach an approximate 50% reduction in serum concentrations 20-27
17 hours after system removal.
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DUROGESIC® should be prescribed only by persons knowledgeable in the
continuous administration of potent opioids, in the management of patients receiving
potent opioids for treatment of pain, and in the detection and management of
hypoventilation including the use of opioid antagonists.
In order to ensure the continuity of different products of fentanyl transdermal
patches in individual patients it should be emphasized that if patients are changed
from one fentanyl transdermal patch to another it should be done only with specific
counseling and monitoring from their healthcare professional.
All patients and their caregivers should be advised to avoid exposing the
®
DUROGESIC application site and surrounding area to direct external heat sources,
such as heating pads or electric blankets, heat or tanning lamps, saunas, hot tubs,
and heated water beds, whirpool spa bath, intensive sunbathing and hot water
bottles prolonged hot baths, etc., while wearing the system. Patients should be
advise against taking hot baths or sunbathing.There is a potential for temperaturedependent increases in fentanyl released from the system resulting in possible
overdose and death.
A clinical pharmacology trial conducted in healthy adult subjects has shown that the
application of heat over the DUROGESIC system increased mean fentanyl AUC
values by 120% and mean Cmax values by 61%.
Based on a pharmacokinetic model, serum fentanyl concentrations could theoretically increase
by approximately one-third for patients with a body temperature of 40°C (104°F) due to
temperature-dependent increases in fentanyl released from the system and increased skin
permeability. Patients wearing DUROGESIC® systems who develop fever or increased
core body temperature due to strenuous exertion should be monitored for opioid side
effects and the DUROGESIC®dose should be adjusted if necessary.
……………………..
Hypoventilation (Respiratory Depression)
Serious or life-threatening hypoventilation may occur at any time during the use of
DUROGESIC® especially during the initial 24-72 hours following initiation of therapy
and following increases in dose.
Because significant amounts of fentanyl continue to be are absorbed from the skin
for 17 20-27 hours or more after the patch is removed, hypoventilation may persist
beyond the removal of DUROGESIC®. …………………………
Interactions with other CNS Depressants
The concomitant use of Durogesic® (fentanyl transdermal system) with other central
nervous system depressants, including but not limited to other opioids, sedatives,
hypnotics, tranquilizers (e.g., benzodiazepines), general anesthetics,
phenothiazines, skeletal muscle relaxants, sedating antihistamins and alcohol, may
cause respiratory depression, hypotension, and profound sedation or potentially
result in coma.or death When such combined therapy is contemplated, the dose of
one or both agents should be significantly reduced and special patient care and
observation is required.
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Interactions with Alcohol and Drugs of Abuse
Fentanyl may be expected to have additive CNS depressant effects when used in
conjunction with alcohol, other opioids, or illicit drugs that cause central nervous
system depression.
Interactions with CYP3A4 Inhibitors
The concomitant use of Durogesic® with All potent cytochrome P450 3A4
inhibitors (such as ritonavir, ketoconazole, itraconazole, troleandomycin,
clarithromycin, nelfinavir, nefazodone, , and amiodarone, amprenavir,
aprepitant, diltiazem ,erythromycin, fluconazole, fosamprenavir, grapefruit
juice and verapamil) may result in an increase in fentanyl plasma
concentrations, which could increase or prolong adverse drug effects and
may cause potentially fatal respiratory depression. Therefore, the concomitant
use of transdermal fentanyl and CYP3A4 inhibitors is not recommended
unless the patient is closely monitored. Patients, especially those who are
receiving.Durogesic® and any potent CYP3A4 inhibitor should be carefully
monitored for an extended period of time and dosage adjustments should be
made if warranted. (See BOX WARNING, CLINICAL PHARMACOLOGY – Drug
Interactions, PRECAUTIONS and DOSAGE AND ADMINISTRATION for further
information.)
PRECAUTIONS
………………….
Cardiac Disease
Fentanyl may produce bradycardia. Fentanyl should be administered with caution to
patients with bradyarrhythmias.
Hepatic Disease and Renal Dedease
Because fentanyl is metabolized to inactive metabolites in the liver, hepatic
disease impairment might delay its elimination. In patients with hepatic
cirrhosis, the pharmacokinetics of a single application of DUROGESIC®
were not altered although serum concentrations tended to be higher in these
patients. If patients with hepatic impairment receive Durogesic they should
be observed carefully for signs of fentanyl toxicity and the dose of
DUROGESIC® reduced if necessary.
Renal Disease
Less than 10% of fentanyl is excreted unchanged by the kidney and, unlike
morphine, there are no known active metabolites eliminated by the kidney. Data
obtained with intravenous fentanyl in patients with renal failure suggest that the
volume of distribution of fentanyl may be changed by dialysis. This may affect serum
concentrations. If patients with renal impairment receive DUROGESIC®, they
should be observed carefully for signs of fentanyl toxicity and the dose reduced if
necessary.
Patients with Fever/External Heat
Based on a pharmacokinetic model, serum fentanyl concentrations could
theoretically increase by approximately one-third for patients with a body
temperature of 40°C (104°F) due to temperature-dependent increases in fentanyl
release from the system and increased skin permeability. Therefore, patients
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wearing DUROGESIC® systems who develop fever should be monitored for opioid
side effects and the DUROGESIC® dose should be adjusted if necessary.
All patients and their caregivers should be advised to avoid exposing the
DUROGESIC® application site to direct external heat sources, such as heating pads
or electric blankets, heat lamps, saunas, hot tubs, whirpool spa bath, heated water
beds, intensive sunbathing and hot water bottles etc., while wearing the system.
There is a potential for temperature-dependent increases in fentanyl release from
the system.
………………………….
Physical Dependence
Physical dependence is a state of adaptation that is manifested by an opioid specific
withdrawal syndrome that can be produced by abrupt cessation, rapid dose
reduction, decreasing blood level concentration of the drug, and/or administration of
an antagonist. The opioid abstinence or withdrawal syndrome is characterized by
some or all of the following: restlessness, lacrimation, rhinorrhea, yawning,
perspiration, chills, piloerection, myalgia, mydriasis, irritability, anxiety, backache,
joint pain, weakness, abdominal cramps, insomnia, nausea, anorexia, vomiting,
diarrhea, or increased blood pressure, respiratory rate, or heart rate. In general,
opioids should not be abruptly discontinued (see DOSAGE AND
ADMINISTRATION – Discontinuation of DUROGESIC ).
Ambulatory Patients
………………………..
Effects on ability to drive and use machines
DUROGESIC® may impair mental and/or physical ability required for the
performance of potentially hazardous tasks such as driving a car or
operating machinery.
Information for Patients
®
A patient information sheet is included in the package of DUROGESIC patches dispensed to
the patient.
………………….
1. Patients should be advised that DUROGESIC® should be applied immediately
upon removal from the sealed pouch package. To remove the patch from the
protective pouch, locate the pre-cut notch (indicated by an arrow on the
patch label) along the edge of the seal. Fold the pouch at the notch, then
carefully tear the pouch material. Further open the pouch along both sides,
folding the pouch open like a book. The release liner for the matrix is slit.
Fold the patch in the middle and remove each half of the liner separately.
Avoid touching the adhesive side of the patch. Additionally the patient should
be advised of the following:
 The DUROGESIC patch should not be used if the seal is broken, or if it is
altered, cut, or damaged in any way prior to application. 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.
®
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The patch should not be folded so that only part of the patch is exposed.
and after removal of the protective liner. Additionally the patient should be advised of the
following:
 The DUROGESIC® patch should not be used if the pouch seal is broken, or if
the patch is cut, damaged, or changed in any way.

The transdermal patch should be pressed firmly in place with the palm of the
hand for 30 seconds, making sure the contact is complete, especially around
the edges.

The patch should not be folded so that only part of the patch is exposed.
5. Patients should be advised that the dose of DUROGESIC® or the number of
patches applied to the skin should NEVER be adjusted without the prescribing
healthcare professional’s instruction.
6. Patients should be advised that while wearing the patch, they should avoid
exposing the DUROGESIC® application site and surrounding area to direct
external heat sources, such as:

heating pads,

electric blankets,

heat or tanning lamps,

saunas,

hot tubs or hot baths , and

intensive sunbathing

heated water beds, etc.

whirpool spa bath

hot water bottles
7. Patients should also be advised that there is of a potential for temperaturedependent increase in fentanyl release from the patch that could result in an
overdose of fentanyl; therefore, if patients who develop a high fever or increased
body temperature due to strenuous exertion while wearing the patch they should
contact their physician.
8. Patients should be advised that if the patch falls off before 72 hours a new patch
may be applied to a different skin site.
8. Patients should be advised to fold (so that the adhesive side adheres to itself) and
®
immediately flush down the toilet used DUROGESIC patches after removal from
the skin.
9. Do not use soap, alcohol, or other chemicals, because these products may
increase the ability of fentanyl to go through the skin.
®
10. Patients should be advised that the dose of DUROGESIC should NEVER be
adjusted without the prescribing health care professional’s instruction.
……………
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Drug Interactions
Agents Affecting Cytochrome P450 3A4 Isoenzyme System
Fentanyl is metabolized mainly via the human cytochrome P450 3A4 isoenzyme
®
system (CYP3A4), therefore potential interactions may occur when DUROGESIC is
given concurrently with agents that affect CYP3A4 activity. Coadminstration with
®
agents that induce 3A4 activity may reduce the efficacy of DUROGESIC . The
concomitant use of transdermal fentanyl with all CYP3A4 inhibitors ( such as such
as ritonavir, or other potent 3A4 inhibitors such as ketoconazole, itraconazole,
troleandomycin, clarithromycin, nelfinavir, nefazodone, , and amiodarone,
amprenavir, aprepitant, diltiazem ,erythromycin, fluconazole, fosamprenavir,
and verapamil) may result in an increase in fentanyl plasma concentrations (see
BOX WARNING, CLINICAL PHARMACOLOGY – Drug Interactions ,
WARNINGS, and DOSAGE AND ADMINISTRATION). The concomitant use of
other CYP3A4 inhibitors such as diltiazem and erythromycin with transdermal
fentanyl may also result in an increase in fentanyl plasma concentrations, which
could increase or prolong adverse drug effects and may cause serious fatal
respiratory depression. In this situation, special patient care and observation are
appropriate.
Patients receiving DUROGESIC® and any CYP3A4 inhibitor should be carefully monitored for
an extended period of time, and dosage adjustments should be made if warranted (see BOX
WARNING, CLINICAL HARMACOLOGY – Drug Interactions, WARNINGS, and DOSAGE AND
ADMINISTRATION for further information).
Central Nervous System Depressants
The concomitant use of DUROGESIC® (fentanyl transdermal system) with other
central nervous system depressants, including but not limited to other opioids,
sedatives, hypnotics, tranquilizers (e.g., benzodiazepines), general anesthetics,
phenothiazines, skeletal muscle relaxants, sedating antihistamins and alcohol, may
cause respiratory depression, hypotension, and profound sedation, or potentially
result in coma or death. When such combined therapy is contemplated, the dose of
one or both agents should be significantly reduced and special patient care and
observation is required.
MAOI Inhibitors
®
DUROGESIC is not recommended for use in patients who require the
concomitant administration of an MAOI or those who received MAOI within
14 days. Severe and unpredictable interactions with MAOIs, involving the
potentiation of opiate effects or the potentiation of serotoninergic effects,
®
have been reported. Therefore, DUROGESIC should not be used within 14
days after discontinuation of treatment with MAOIs.
Carcinogenesis, Mutagenesis, and Impairment of Fertility
In a two-year carcinogenicity study conducted in rats, fentanyl was not associated with an
increased incidence of tumors at subcutaneous doses up to 33 μg/kg/day in males or 100
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μg/kg/day in females (0.16 and 0.39 times the human daily exposure obtained via the 100
mcg/h patch based on AUC0-24h comparison).
Studies in animals to evaluate the carcinogenic potential of fentanyl HCl have not
been conducted. ………………………..
There are no adequate and well-controlled studies in pregnant women although
fentanyl as an IV anesthetic has been found to cross the placenta in early human
pregnancies.. DUROGESIC® should be used during pregnancy only if the potential
benefit justifies the potential risk to the fetus.
Nonteratogenic Effects
Neonatal withdrawal syndrome has been reported in newborn infants with chronic
maternal use of Durogesic® during pregnancy. Chronic maternal treatment with
fentanyl during pregnancy has been associated with transient respiratory
depression, behavioral changes, or seizures characteristic of neonatal abstinence
syndrome in newborn infants. There have been very rare reports of newborn infants
experiencing neonatal withdrawal syndrome when mothers chronically used
Durogesic® during pregnancy. ……………………………..
Labor and Delivery
Use of Durogesic ® during childbirth is not recommended because Durogesic
should not be used in the management of acute or postoperative pain.
Moreover, because Fentanyl readily passes across the placenta to the fetus
the use of Durogesic® during childbirth might result in respiratory depression
in the newborn infant.
; therefore, DUROGESIC® is not recommended for analgesia during labor and
delivery.
Nursing Mothers
Fentanyl is excreted in human milk; therefore, DUROGESIC® is not recommended for use in
nursing women because of the possibility of effects in their infants.
Pediatric Use
The safety of DUROGESIC® was evaluated in three open-label trials in 291 pediatric patients
with chronic pain, 2 years of age through 18 years of age. Starting doses of 25 mcg/h and
higher were used by 181 patients who had been on prior daily opioid doses of at least 45
mg/day of oral morphine or an equianalgesic dose of another opioid. Initiation of DUROGESIC®
therapy in pediatric patients taking less than 60 mg/day of oral morphine or an equianalgesic
dose of another opioid has not been evaluated in controlled clinical trials. Approximately 90% of
®
the total daily opioid requirement (DUROGESIC plus rescue medication) was provided by
®
DUROGESIC
DUROGESIC® was not studied in children under 2 years of age.
To guard against accidental ingestion by children, use caution when choosing the
application site for DUROGESIC® (see DOSAGE AND ADMINISTRATION) and
monitor adhesion of the system closely.
Geriatric Use
Information from a pilot study of the pharmacokinetics of IV fentanyl in
geriatric patients (N=4) indicates that the clearance of fentanyl may be
greatly decreased in the population above the age of 60. The relevance of
these findings to DUROGESIC (fentanyl transdermal system) is unknown
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at this time.
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. If elderly patients receive
DUROGESIC®, they should be observed carefully for signs of fentanyl
toxicity and the dose reduced if necessary (see Pharmacokinetic properties).
Since elderly, cachectic, or debilitated patients may have altered pharmacokinetics
due to poor fat stores, muscle wasting, or altered clearance, they should not be
started on DUROGESIC® doses higher than 25 mcg/h unless they are already
tolerating an around-the-clock opioid at a dose and potency comparable to
DUROGESIC®-25 (see DOSAGE AND ADMINISTRATION).
Respiratory depression is the chief hazard in elderly or debilitated patients, usually following
large initial doses in non-tolerant patients, or when opioids are given in conjunction with other
agents that depress respiration.
DUROGESIC® should be used with caution in elderly, cachectic, or debilitated patients
as they may have altered pharmacokinetics due to poor fat stores, muscle wasting or
altered clearance (see DOSAGE AND ADMINISTRATION).
ADVERSE REACTIONS
In post-marketing experience, deaths from hypoventilation due to
inappropriate use of DUROGESIC® (fentanyl transdermal system) have been
reported (see BOX WARNING and CONTRAINDICATIONS).
Pre-Marketing Clinical Trial Experience
Although DUROGESIC® use in post-operative or acute pain and in patients who are
not opioid-tolerant is CONTRAINDICATED, the safety of DUROGESIC® was
originally evaluated in 357 post-operative adult patients for 1 to 3 days and
153 cancer patients for a total of 510 patients. The duration of DUROGESIC® use
®
varied in cancer patients; 56% of patients used DUROGESIC for over 30 days,
28% continued treatment for more than 4 months, and 10% used DUROGESIC® for
more than 1 year.
Hypoventilation was the most serious adverse reaction observed in 13 (4%) postoperative patients and in 3 (2%) of the cancer patients. Hypotension and
hypertension were observed in 11 (3%) and 4 (1%) of the opioid-naive patients.
Various adverse events were reported; a causal relationship to DUROGESIC® was
not always determined. The frequencies presented here reflect the actual frequency
of each adverse effect in patients who received DUROGESIC®. There has been no
attempt to correct for a placebo effect, concomitant use of other opioids, or to
subtract the frequencies reported by placebo-treated patients in controlled trials.
Adverse reactions reported in 153 cancer patients at a frequency of 1% or greater
are presented in Table 1; similar reactions were seen in the 357 post-operative
patients.
®
In the pediatric population, the safety of DUROGESIC has been evaluated in
291 patients with chronic pain 2-18 years of age. The duration of DUROGESIC® use
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varied; 20% of pediatric patients were treated for ≤ 15 days; 46% for 16-30 days;
16% for 31-60 days; and 17% for at least 61 days. Twenty-five patients were treated
with DUROGESIC® for at least 4 months and 9 patients for more than 9 months.
There was no apparent pediatric-specific risk associated with DUROGESIC® use in
children as young as 2 years old when used as directed. The most common adverse
events were fever (35%), vomiting (33%), and nausea (24%).
Adverse events reported in pediatric patients at a rate of ≥1% are presented in
Table 1.
TABLE 1: ADVERSE EVENTS (at rate of ≥ 1%) Adult (N=380) and Pediatric
(N=291) Clinical Trial Experience
Body
Adults
Pediatrics
System
Body as
a Whole
Abdominal pain*,
headache*, fatigue*,
back pain, fever,
influenza-like
symptoms*, accidental
injury, rigors
Pain*,
headache*,
fever,
syncope,
abdominal
pain, allergic
reaction,
flushing
Cardiova
scular
Arrhythmia, chest pain
Hypertension,
tachycardia
Digestiv
e
Nausea**, vomiting**,
constipation**, dry
mouth**, anorexia*,
diarrhea*, dyspepsia*,
flatulence
Nausea**,
vomiting**,
constipation*,
dry mouth,
diarrhea
Nervous
Somnolence**,
insomnia, confusion**,
asthenia**, dizziness*,
nervousness*,
hallucinations*,
anxiety*, depression*,
euphoria*, tremor,
abnormal coordination,
speech disorder,
abnormal thinking,
abnormal gait,
abnormal dreams,
agitation, paresthesia,
Somnolence*,
nervousness*,
insomnia*,
asthenia*,
hallucinations,
anxiety,
depression,
convulsions,
dizziness,
tremor,
speech
disorder,
agitation,
10
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*
**
amnesia, syncope,
paranoid reaction
stupor,
confusion,
paranoid
reaction
Respirat
ory
Dyspnea*,
hypoventilation*,
apnea*, hemoptysis,
pharyngitis*, hiccups,
bronchitis, rhinitis,
sinusitis, upper
respiratory tract
infection*
Dyspnea,
respiratory
depression,
rhinitis,
coughing
Skin and
Appenda
ges
Sweating**, pruritus*,
rash, application site
reaction – erythema,
papules, itching,
edema
Pruritus*,
application
site reaction*,
sweating
increased,
rash, rash
erythematous,
skin reaction
localized
Urogenit
al
Urinary retention*
Micturition disorder
Urinary
retention
Reactions occurring in 3% - 10% of DUROGESIC® patients
Reactions occurring in 10% or more of DUROGESIC® patients
The following adverse effects have been reported in less than 1% of the 510 adult
post-operative and cancer patients studied:
Cardiovascular: bradycardia
Digestive: abdominal distention
Nervous: aphasia, hypertonia, vertigo, stupor, hypotonia, depersonalization,
hostility
Respiratory: stertorous breathing, asthma, respiratory disorder
Skin and Appendages, General: exfoliative dermatitis, pustules
Special Senses: amblyopia
Urogenital: bladder pain, oliguria, urinary frequency
Post-Marketing Experience - Adults
The following adverse reactions have been reported in association with the use of
DURAGESIC®
and not reported in the pre-marketing adverse reactions section above.
Body as a Whole: edema
Cardiovascular: tachycardia
Metabolic and Nutritional: weight loss
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Special Senses: blurred vision
Urogenital: decreased libido, anorgasmia, ejaculatory difficulty
A multicenter, double-blind, randomized, placebo-controlled clinical study
(FEN-EMA-1) of DUROGESIC® examined patients (>40 years of age) with
severe pain induced by osteoarthritis of the hip or knee and who were in
need of and waiting for joint replacement. Patients were treated for 6 weeks
with DUROGESIC® by titrating to adequate pain control starting from
25 mcg/hr to a maximum dose of 100 mcg /hr in 25 mcg/hr increments. This
treatment was preceded by a 1-week washout period and followed by a
tapering-off period of no more than 12 days. The adverse events, regardless
of causality, reported by 1% or more of the patients treated with
DUROGESIC® during the double-blind period and reported at a frequency
greater than with placebo are presented in Table 3.
Table 3: Adverse Events, Regardless of Causality, Reported by 1%
of Patients and Reported More Frequently with
DUROGESIC® Than With Placebo During Double-Blind
Treatment
Body System/Organ Class
DUROGESIC®a
Placebo
Adverse Event Term
%
%
(N=216)
(N=200)
Metabolism and nutrition disorders
Anorexia
1.4
0.5
Psychiatric Disorders
Somnolence
22.2
4.0
Insomnia
10.2
7.0
Anxiety
3.2
0.5
Depression
1.4
0
Nervous system disorders
Dizziness
12.5
5.5
Muscle contractions
6.5
3.0
involuntary
Hypoaesthesia
1.4
0.5
Eye disorders
Conjunctivitis
1.9
1.0
Cardiac disorders
Palpitations
3.7
1.0
Respiratory, thoracic, and
mediastinal disorders
Yawning
5.1
2.0
Rhinitis
2.3
1.0
Gastrointestinal disorders
Nausea
44.9
19.0
Vomiting
29.6
2.5
Constipation
10.2
1.5
Anorexia
4.6
0
Abdominal Pain
3.3
2.0
Dyspepsia
2.8
2.5
Dry mouth
2.8
1.0
Skin and subcutaneous tissue
disorders
Pruritus
8.3
3.0
Skin disorder
1.4
0.5
Renal and urinary disorders
Urinary tract infection
1.4
1.0
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General disorders and
administration site conditions
Feeling of body temperature
7.4
change
Hyperhidrosis
7.4
Fatigue
6.5
Malaise
3.7
Influenza like illness
2.3
Oedema Peripheral
2.3
Asthenia
2.3
Drug withdrawal syndrome
1.4
a: doses of 25 mcg/hr, 50 mcg/hr, 75 mcg/hr or 100 mcg/hr
Adverse drug reactions from spontaneous reports during the worldwide
postmarketing experience involving all indications with Durogesic that met
threshold criteria are included in Table 4 . The adverse drug reactions are ranked by
frequency, using the following convention:
Very
common
Common
Uncommon
1/10
Rare
1/10,000 and <1/1,000
<1/10,000, including isolated reports
1/100 and <1/10
1/1,000 and <1/100
Very Rare
The frequencies provided below reflect reporting rates for adverse drug reactions
from spontaneous reports, and does not represent more precise estimates that
might be obtained in clinical or epidemiological studies
Body as a Whole: edema
Cardiovascular: tachycardia, bradycardia, hypotension, hypertension
Metabolic and Nutritional: weight loss, anorexia (in very rare cases)
Special Senses: blurred vision
Urogenital: decreased libido, anorgasmia, ejaculatory difficulty, urinary retention
Immune system disorders: (very rare) anaphylactic shock, anaphylactic reaction,
anaphylactoid reaction
Psychiatric Disorders: (very rare) depression, confusional state, hallucination,
anxiety, euphoric mood, agitation, insomnia
Nervous System Disorders: (very rare) convulsions (including clonic convulsions
and grand mal convulsion), amnesia, somnolence, dizziness, headache, tremor,
paraesthesia
Respiratory, Thoracic, and Mediastinal Disorders: (very rare) respiratory
depression (including respiratory distress, apnoea, and bradypnoea, hypoventilation,
dyspnoea
Gastrointestinal Disorders: (very rare) nausea, vomiting, constipation, diarrhoea,
dyspepsia, dry mouth
Skin and Subcutaneous Tissue Disorders: (very rare) rash, erythema, pruritus,
sweating increased
15
2.0
1.0
3.0
1.5
0.5
0.5
0
0
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Reproductive System and Breast Disorders: (very rare) sexual dysfunction
General Disorders and Administration Site Conditions: (very rare) drug
withdrawal syndrome, asthenia, application site reaction
Adverse Reactions
Clinical Trial Data
®
The safety of DUROGESIC was evaluated in 216 subjects who participated
in a multicenter, double-blind, randomized, placebo-controlled clinical trial
(FEN-EMA-1) of DUROGESIC ®. These subjects took at least one dose of
DUROGESIC ® and provided safety data. This trial examined patients over
40 years of age with severe pain induced by osteoarthritis of the hip or knee
and who were in need of and waiting for joint replacement. Patients were
®
treated for 6 weeks with TRADENAME by titrating to adequate pain control
starting from 25 mcg/h to a maximum dose of 100 mcg/h in 25 mcg/h
increments. Adverse drug reactions (ADRs) reported for ≥1% of
DUROGESIC ®-treated subjects and with an incidence greater than placebotreated subjects are shown in Table 1.
16
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Table 1: Adverse Drug Reactions Reported by ≥1% of DUROGESIC ®-treated
Subjects and With an Incidence Greater Than Placebo-treated
Subjects in 1 Double-Blind, Placebo-Controlled Clinical Trial of
®
DUROGESIC
DUROGESIC ®
Placebo
System/Organ Class
%
%
Adverse Reaction
(N=216)
(N=200)
Metabolism and Nutrition Disorders
Anorexia
4.6
0
Depression
1.4
0
Nervous System Disorders
Somnolence
19.0
2.5
Dizziness
10.2
4.0
Insomnia
10.2
6.5
Ear and Labyrinth Disorders
Vertigo
2.3
0.5
Cardiac Disorders
Palpitations
3.7
1.0
Gastrointestinal Disorders
Nausea
40.7
16.5
Vomiting
25.9
2.5
Constipation
8.8
1.0
Abdominal pain upper
2.8
1.5
Dry mouth
2.3
0
Skin and Subcutaneous Tissue
Disorders
Hyperhidrosis
6.5
1.0
Pruritus
3.2
2.0
Rash
1.9
1.0
Musculoskeletal and Connective
Tissue Disorders
Muscle spasms
4.2
1.5
General Disorders and
Administration Site Conditions
Fatigue
6.5
3.0
Feeling cold
6.5
2.0
Malaise
3.7
0.5
Asthenia
2.3
0
Oedema peripheral
1.4
1.0
Adverse drug reactions not reported in Table 1 that were reported by ≥1% of
DUROGESIC ®-treated subjects (N=1854) in 11 clinical trials of
DUROGESIC ® used for the treatment of chronic malignant or nonmalignant
pain (which includes trial FEN-EMA-1) are shown in Table 2. All subjects
®
took at least one dose of DUROGESIC and provided safety data.
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Table 2: Adverse Drug Reactions Reported by ≥1% of DUROGESIC ®-treated
®
Subjects in 11 Clinical Trials of DUROGESIC
DUROGESIC ®
System/Organ Class
%
Adverse Reaction
(N=1854)
Immune System Disorders
Hypersensitivity
1.0
Anxiety
2.5
Confusional state
1.7
Hallucination
1.2
Headache
11.8
Tremor
2.6
Paraesthesia
1.8
Diarrhoea
9.6
Abdominal pain
2.9
Skin and Subcutaneous Tissue Disorders
Erythema
1.2
Renal and Urinary Disorders
Urinary retention
1.4
Adverse drug reactions reported by <1% of DUROGESIC ®-treated subjects
(N=1854) in the above clinical trial dataset are shown in Table 3.
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Table 3: Adverse Drug Reactions Reported by <1% of DUROGESIC ®-treated
®
Subjects in 11 Clinical Trials of DUROGESIC
System/Organ Class
Adverse Reaction
Disorientation
Euphoric mood
Hypoaesthesia
Eye Disorders
Miosis
Cardiac Disorders
Cyanosis
Respiratory, Thoracic and Mediastinal Disorders
Respiratory depression
Subileus
Skin and Subcutaneous Tissue Disorders
Dermatitis
Dermatitis allergic
Dermatitis contact
Eczema
Skin disorder
Musculoskeletal and Connective Tissue Disorders
Muscle twitching
Reproductive System and Breast Disorders
Erectile dysfunction
Sexual dysfunction
General Disorders and Administration Site Conditions
Application site dermatitis
Application site eczema
Application site hypersensitivity
Application site reaction
Drug withdrawal syndrome
Influenza-like illness
Post-marketing Data
Adverse drug reactions from spontaneous reports during the worldwide
post-marketing experience involving all indications with DUROGESIC ® that
met threshold criteria are included in Table 5 . The ADRs are ranked by
frequency, using the following convention:
Very common
Common
Uncommon
Rare
Very Rare
≥1/10
≥1/100 and <1/10
≥1/1,000 and <1/100
≥1/10,000 and <1/1,000
<1/10,000, including isolated reports
The frequencies provided below reflect reporting rates for ADRs from
spontaneous reports, and do not represent more precise estimates that
might be obtained in clinical or epidemiological studies.
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Table 5: Adverse Drug Reactions Identified During Post-marketing
®
Experience with DUROGESIC by Frequency Category Estimated
from Spontaneous Reporting Rates
Immune system disorders
Very rare
Anaphylactic shock, Anaphylactic reaction, Anaphylactoid
reaction
Very rare
Agitation
Very rare
Convulsions (including Clonic convulsions and Grand mal
convulsion), Amnesia
Cardiac Disorders
Very rare
Tachycardia, Bradycardia
Vascular Disorders
Very rare
Hypotension, Hypertension
Respiratory, Thoracic, and Mediastinal Disorders
Very rare
Respiratory distress, Apnoea, Bradypnoea,
Hypoventilation, Dyspnoea (see Overdose, Section 4.9 for
additional information on events related to respiratory
depression)
Very rare
Ileus, Dyspepsia
General Disorders and Administration Site Conditions
Very rare
Feeling of body temperature change
As with other opioid analgesics, tolerance, physical dependence, and
psychological dependence can develop on repeated use of DUROGESIC®
(see Special warnings and special precautions for use).
Opioid withdrawal symptoms (such as nausea, vomiting, diarrhoea, anxiety,
and shivering) are possible in some patients after conversion from their
previous opioid analgesic to DUROGESIC ® or if therapy is stopped
suddenly (see Section 4.2, Posology and method of administration). There
have been very rare reports of newborn infants experiencing neonatal
®
withdrawal syndrome when mothers chronically used DUROGESIC during
pregnancy (see Pregnancy and lactation).
DRUG ABUSE AND ADDICTION
®
…………..DUROGESIC patches are intended for transdermal use (to be applied on the skin)
only. Do not use cut or damaged DUROGESIC® patches. Do not use a DUROGESIC® patch if
the pouch seal is broken or the patch is cut, damaged, or changed in any way.
DOSAGE AND ADMINISTRATION
Special Precautions
DUROGESIC® contains a high concentration of a potent opioid agonist,
fentanyl. Opioid substances which includeing fentanyl, hydromorphone,
02
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methadone, morphine, oxycodone, and oxymorphone have the highest
potential for abuse and associated risk of fatal overdose due to respiratory
depression. Fentanyl can be abused and is subject to criminal diversion. The
®
high content of fentanyl in the patches (DUROGESIC ) may be a particular
target for abuse and diversion.
Durogesic® patches are intended for transdermal use (on intact skin) only. Do not use damaged
®
or cut DUROGESIC patches.
®
The DUROGESIC patch should not be used if the pouch seal is broken, or the patch is
cut, damaged, or changed in any way.
Each DUROGESIC® patch may be worn continuously for 72 hours. The next patch should
be applied to a different skin site after removal of the previous transdermal system. If the
patch falls off before 72 hours, dispose of it by folding in half and flushing down the
toilet. A new patch may be applied to a different skin site.
DUROGESIC is ONLY for use in patients who are already tolerant to opioid
therapy of comparable potency. Use in non-opioid tolerant patients may lead
to fatal respiratory depression. Overestimating the DUROGESIC® dose when
converting patients from another opioid medication can result in fatal
overdose with the first dose. Due to the mean elimination half-life of 17
approximately 20-27 hours of DUROGESIC®, patients who are thought to have
had a serious adverse event, including overdose, will require monitoring and
treatment for at least 24 hours.
The concomitant use of DUROGESIC® with All potent cytochrome P450 3A4
inhibitors (such as ritonavir, ketoconazole, itraconazole, troleandomycin,
clarithromycin, nelfinavir, nefazodone, and amiodarone, amprenavir,
aprepitant, diltiazem ,erythromycin, fluconazole, fosamprenavir and
verapamil) may result in an increase in fentanyl plasma concentrations, which
could increase or prolong adverse drug effects and may cause potentially
fatal respiratory depression. Patients receiving Durogesic® and potent any
CYP3A4 inhibitors should be carefully monitored for an extended period of
time and dosage adjustments should be made if warranted. (See CLINICAL
PHARMACOLOGY – Drug Interactions, WARNINGS, PRECAUTIONS and
DOSAGE AND ADMINISTRATION for further information.)
Respiratory depression is the chief hazard in elderly or debilitated patients, usually
following large initial doses in non-tolerant patients, or when opioids are given in
conjunction with other agents that depress respiration.
DUROGESIC® should be used with caution in elderly, cachectic, or debilitated patients
as they may have altered pharmacokinetics due to poor fat stores, muscle wasting, or
altered clearance (see CLINICAL PHARMACOLOGY – Special Populations, Geriatric Use).
General Principles
®
DUROGESIC is indicated for management of persistent, moderate to severe
chronic pain that:

requires continuous, around-the-clock opioid administration for an
extended period of time
01
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
cannot be managed by other means such as non-steroidal analgesics,
opioid combination products, or immediate-release opioids.
Durogesic is indicated for the management of chronic pain and intractable pain
requiring opioid analgesia. Durogesic should only be used in patients who are
already receiving opioid therapy, who have demonstrated opioid tolerance,
…………………………..
DUROGESIC® should be applied immediately upon removal from the sealed
package. Do not use if the pouch seal is broken. Do not alter the patch (e.g., cut) in
any way prior to application and do not use cut or damaged patches.
To remove the patch from the protective pouch, locate the pre-cut notch (indicated
by an arrow on the patch label) along the edge of the seal. Fold the pouch at the
notch, then carefully tear the pouch material. Further open the pouch along both
sides, folding the pouch open like a book. The release liner for the matrix 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.
The transdermal system should be pressed firmly in place with the palm of the hand for 30
seconds, making sure the contact is complete, especially around the edges.
Do not use soap, alcohol, or other solvents to remove the gel because they may
enhance the drug’s ability to penetrate the skin.
Each DUROGESIC® may be worn continuously for 72 hours. The next patch should
be applied to a different skin site after removal of the previous transdermal system.
………………………..
Dose Selection
Doses must be individualized based upon the status of each patient and
should be assessed at regular intervals after DUROGESIC® application. The
patches are designed to deliver approximately 12, 25, 50, 75 and 100mcg/h
fentanyl to the systemic circulation, which represent about 0.3, 0.6, 1.2, 1.8
and 2.4 mg per day, respectively. Reduced doses of Durogesic® are suggested
for the elderly and other groups discussed in PRECAUTIONS.
……………………..
Initial DUROGESIC® Dose Selection
®
Overestimating the DUROGESIC dose when converting patients from another
opioid medication can result in fatal overdose with the first dose. Due to the
®
mean elimination half-life of approximately 20-27 17 hours of DUROGESIC ,
patients who are thought to have had a serious adverse event, including
overdose, will require monitoring and treatment for at least 24 hours.
®
There has been no systematic evaluation of DUROGESIC as an initial opioid analgesic in the
management of chronic pain, since most patients in the clinical trials were converted to
DUROGESIC® from other narcotics. The efficacy of DUROGESIC®12 mcg/h as an initiating
dose has not been determined. In addition, patients who are not opioid-tolerant have
00
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experienced hypoventilation and death during use of DUROGESIC. Therefore, DUROGESIC®
should be used only in patients who are opioid-tolerant.
®
To convert adult and pediatric patients from oral or parenteral opioids to DUROGESIC ,
use Table D (Equianalgesic potency conversion) and Table E (Recommended initial
®
DUROGESIC dose based upon daily oral morphine dose):
To convert adult patients from oral or parenteral opioids to DUROGESIC®, use Table C:
Alternatively, for adult patients taking opioids or doses not listed in Table C, use the
following methodology:
1. Calculate the previous 24-hour analgesic requirement.
2. Convert this amount to the equianalgesic oral morphine dose using Table D.
3. Table E displays the range of 24-hour oral morphine doses that are
recommended for conversion to each DUROGESIC® dose. Use this table to find
the calculated 24-hour morphine dose and the corresponding DUROGESIC®
dose. Initiate DUROGESIC® treatment using the recommended dose and titrate
patients upwards (no more frequently than every 3 days after the initial dose or
than every 6 days thereafter) until a balance between analgesic efficacy and
tolerability analgesic efficacy is attained. The recommended starting dose when
converting from other opioids to DUROGESIC® is likely too low for 50% of
patients. This starting dose is recommended to minimize the potential for
overdosing patients with the first dose. For delivery rates in excess of 100
mcg/h, multiple systems may be used.
…………………
The majority of patients are adequately maintained with DUROGESIC® administered every
72 hours. Some patients may not achieve adequate analgesia using this dosing interval and
may require systems to be applied every 48 hours rather than every 72 hours. An increase in
the DUROGESIC® dose should be evaluated before changing dosing intervals in order to
maintain patients on a 72-hour regimen. Dosing intervals less than every 72 hours were not
studied in children and adolescents and are not recommended
Early in therapy, some patients may not achieve adequate analgesia during the third day
using this dosing interval and may require DUROGESIC® patch to be applied at 48 hours
rather than at 72 hours. Reducing the duration of system application by replacing the system
before the 72 hours may result in increased serum concentrations of fentanyl.
………
Dose Titration
................
A 12mcg/h strength is available for dose titration.
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 dose of
DUROGESIC® depending on response and supplementary analgesic requirements.
…………………
Appropriate dosage increments should be based on the daily dose of supplementary opioids,
using the ratio of 45 mg/24 hours of oral morphine to a 12.5 mcg/h increase in DUROGESIC®
03
‫‪J-C Health Care Ltd.‬‬
‫‪Kibbutz Shefayim 60990, ISRAEL‬‬
‫‪tel +972-9-959-1111‬‬
‫‪fax +972-9-958-3636‬‬
‫‪dose. DUROGESIC® -12 delivers 12.5 mcg/h of fentanyl.‬‬
‫‪Safety and Handling‬‬
‫‪Patches should be inspected prior to use. Patches that are cut, divided, or damaged in any way‬‬
‫‪should not be used. Do not cut or damage DUROGESIC®.‬‬
‫‪DURAGESIC® is supplied in sealed transdermal systems which pose little risk of exposure to‬‬
‫‪health‬‬
‫‪care workers.‬‬
‫®‬
‫‪Do not use a DUROGESIC patch if the pouch seal is broken or the patch is cut, damaged, or‬‬
‫‪changed in any way.‬‬
‫שינויים בעלון לצרכן‪:‬‬
‫אין להשתמש בתרופה מבלי להיוועץ ברופא לפני התחלת הטיפול‬
‫(‪ )X‬אם הנך מעל גיל ‪00‬‬
‫איך תשפיע התרופה על חיי היום יום שלך ?‬
‫אין לשתות יינות או משקאות חריפים בתקופת הטיפול עם התרופה מאחר והשילוב ביניהם יכול לגרום‬
‫לישנוניות‪.‬‬
‫אזהרות ‪:‬‬
‫במידה והמדבקה נפלה מאליה יש לזרוק אותה להדביק מדבקה חדשה מיד כאשר הבחנת‪/‬ה בכך‪ .‬את‬
‫המדבקה החדשה יש להדביק באיזור אחר על העור‪.‬‬
‫ יידע את הרופא במידה ואתה או מישהו אחר במשפחתך פיתח בעבר תלות או שימוש לרעה באכוהול‪,‬‬‫תרופות מרשם או סמים‪.‬‬
‫תגובות בין תרופתיות‬
‫אם הינך נוטל‪/‬ת תרופה נוספת‪ ,‬כולל תרופות הנמכרות ללא מרשם ותוספי תזונה או אם גמרת זה עתה הטיפול‬
‫בתרופה אחרת עליך לדווח לרופא המטפל כדי למנוע סיכונים או אי‪-‬יעילות הנובעים מתגובות בין תרופתיות‪)X( .‬‬
‫במיוחד‪ ,‬לגבי תרופות מהקבוצות הבאות‪:‬‬
‫(‪) X‬תרופות מסויימות לטיפול בזיהומים פטרייתיים (כגון קטוקונזול‪ ,‬פלוקונזול ואינטרקונזול)‬
‫(‪X‬תרופות מסוימות לטיפול באיידס (כגון תרופות המכילות ריטונוויר‪ ,‬אמפנוויר‪ ,‬פוסאמפנוויר ונלפינוויר)‪.‬‬
‫(‪ ) X‬אפרפיטנט (נגד הקאות)‬
‫(‪ )X‬תרופות המכילות קטוקונזול (לטיפול בפטרת וסבוראה) תרופות מסויימות לטיפול בזיהומים פטרייתיים‬
‫(כגון קטוקונזול ואינטרקונזול)‬
‫(‪ )X‬תרופות המכילות איטרקונזול (לטיפול בפטרת)‬
‫(‪X‬תרופות מסוימות לטיפול באיידס (כגון תרופות המכילות ריטונוויר ונלפינוויר)‪.‬‬
‫(‪ )X‬תרופות מסויימות לטיפול בדיכאון (כגון תרופות המכילות נפאזודון )(לטיפול בדכאון)‬
‫(‪ )X‬תרופות מסויימות הפועלות על הלב וכלי הדם (כגון חוסמי תעלות סידן מסויימים כמו דילטיאזם ווורפמיל)‬
‫(לטיפול בלחץ דם גבוה ותעוקת לב)‬
‫(‪ )X‬תרופות מסויימות לטיפול באי סדירות קצב הלב (כגון אמיודארון) (לטיפול באי סדירות קצב הלב)‬
‫תופעות לוואי‬
‫בנוסף לפעילות הרצויה של התרופה‪ ,‬בזמן השימוש בה עלולות להופיע השפעות לוואי (‪ )X‬כגון ‪:‬‬
‫תופעות לוואי שכיחות מאוד (דווחו לפחות במשתמש אחד מתוך ‪ 01‬משתמשים)‪:‬‬
‫כאבי ראש‪ ,‬סחרחורות ‪ ,‬ישנוניות‪ ,‬בחילות‪ ,‬הקאות‪ ,‬הפרעה בתנועתיות המעיים‪.‬‬
‫תופעות לוואי שכיחות (דווחו לפחות במשתמש אחד מתוך ‪ 011‬משתמשים)‪:‬‬
‫איבוד תאבון ;בילבול; ראייה‪ ,‬שמיעה‪ ,‬הרחה‪ ,‬תחושה‪ ,‬טעימה של דברים אשר אינים קיימים;‬
‫חרדה; הרגשת עצב רב או דיכאון ; קושי להירדם או להישאר יישן; רעד; תחושת דקירות; מודעות לדפיקות‬
‫הלב; דפיקות לב מהירות; לחץ דם גבוה; יובש בפה ; קשיי עיכול; בטן רגיזה;כאב בטן; שילשולים ; גרד‬
‫בעור; אדמומיות בעור ;פריחה בעור; הזעה מוגברת ; תגובה אלרגית הכוללת תגובה עורית (חרלת); תנועות‬
‫שרירים בלתי רצוניות כולל התכווצות שרירים; עייפות ; חולשה; תחושה של אי נוחות כללית ; תחושת קור;‬
‫התנפחות רגליים‪ ,‬קרסוליים וידיים; חוסר יכולת להטיל שתן ; קוצר נשימה‪.‬‬
‫‪04‬‬
‫‪J-C Health Care Ltd.‬‬
‫‪Kibbutz Shefayim 60990, ISRAEL‬‬
‫‪tel +972-9-959-1111‬‬
‫‪fax +972-9-958-3636‬‬
‫תופעות לוואי לא שכיחות (דווחו לפחות במשתמש אחד מתוך ‪ 0111‬משתמשים)‪:‬‬
‫תחושת שימחה עלאית (אופוריה) ; חרדה; נימול ; איבוד זיכרון; התכווצויות; קצב לב איטי; גוון כחול לעור;‬
‫לחץ דם נמוך; קושי או קושי חמור בנשימה; חסימת מעיים; דלקת של העור או אלרגיה של העור כתוצאה‬
‫ממגע עם משהו אליו המשתמש אלרגי; קושי במהלך כל אחד משלבי התגובה המינית הנורמליים (תשוקה‪,‬‬
‫גירוי או אורגזמה) ; חוסר יכולת להשיג או לשמור על זיקפה; תגובות באתר ההדבקה על העור (כולל תגובה‬
‫אלרגית) ; תחושת קור או חום; חולי דמוי שפעת; תסמינים לא נעימים המתרכשים לאחר הפסקת התרופה‬
‫או הורדת המינון‪.‬‬
‫תופעות לוואי נדירות ( דווחו לפחות במשתמש אחד מתוך ‪ 01111‬משתמשים)‪:‬‬
‫התכווצות אישונים; חוסר יכולת לנשום; כניסת אוויר מועט מדיי לריאות‪.‬‬
‫תופעות לוואי מאוד נדירות (דווחו בפחות ממשתמש אחד מתוך ‪ 01111‬משתמשים)‪:‬‬
‫תגובה אלרגית חריפה מספיק הגורמת לציפצופים‪ ,‬קושי בנשימה ולחץ דם נמוך מאוד אשר יכול להיות חמור‬
‫או מסכן חיים; קצב נשימה איטי מאוד‪.‬‬
‫(‪ )X‬יובש בפה (‪ )X‬עצירות (‪ )X‬שלשול ( ) טישטוש ראיה (‪ )X‬בחילה (‪ )X‬הקאות (‪ )X‬ישנוניות (‪ )X‬עייפות (‪)X‬‬
‫גרד‬
‫(‪ )X‬כאבי ראש (‪ )X‬עצבנות (‪ )X‬תסמינים דמויי מחלת השפעת (‪ )X‬סיכוי מוגבר לפציעות (‪ )X‬הזעה מוגברת (‪)X‬‬
‫סחרחורת (‪ )X‬תשישות (‪ )X‬כאב בטן (‪ )X‬הפרעות בעיכול (‪ )X‬אובדן תאבון (‪ )X‬דלקת בלוע‬
‫(‪ )X‬שיהוקים (‪ )X‬בלבול (‪ )X‬דיכאון (‪ )X‬ראיה מעורפלת‬
‫אדמומיות במקום ההדבקה עלולים לקרות לעיתים רחוקות‬
‫(‪ )X‬קשיי נשימה (נשימה איטית מאד או חלשה מדי)‪ )X( ,‬קוצר נשימה (‪ )X‬דום נשימה‪ ,‬הסר את המדבקה ופנה‬
‫לעזרה רפואית מידית‪ .‬שים לב כי המטופל לא ירדם ע"י דיבור איתו ואף ניעורו קלות מפעם לפעם‪.‬‬
‫(‪ )X‬מחשבות לא רגילות‪ ,‬קצב לב איטי‪ )X( ,‬קצב לב מהיר‪ ,‬כאב בחזה ‪,‬שינויים בלחץ הדם‪ ,‬יריקת דם ‪,‬הזיות‪,‬‬
‫תחושת שימחה ועליזות בלתי טבעית (אופוריה)‪ ,‬קשיים בהטלת שתן‪:‬פנה‪/‬י לרופא‪.‬‬
‫תופעות בעור במקום ההדבקה (נדיר) ‪ :‬המשך בטיפול ופנה לרופא‬
‫מינון מקובל בהעדר הוראה אחרת הרופא ‪:‬‬
‫מינון יקבע ע"י הרופא בלבד בהתחשב בעוצמת הכאב‪ ,‬מצבך הכללי גילך וכן הטיפול האופיאטי הקודם בו‬
‫השתמשת‪ .‬אין לשנות את המינון ללא התייעצות עם הרופא‪.‬‬
‫אופן השימוש ‪:‬‬
‫(‪ )X‬יש להדביק את מדבקת הדורוג'סיק מיד עם הוצאתה משקית האלומיניום על פי ההוראות הבאות‪:‬‬
‫(‪ )X‬יש להדביק את מדבקת דורוג'סיק על קטע עור חסר שיער בחלק העליון של הזרוע או על החזה או הגב‪.‬‬
‫אסור להדביק את המדבקה על עור שיש בו פצעים קטנים‪ ,‬חתכים‪ ,‬כוויות‪ ,‬אדמומיות או על עור שעבר הקרנות‪.‬‬
‫במטופלים המוגבלים ביכולתם השכלית‪/‬קוגניטיבית ובילדים יש עדיפות להדבקה על הגב העליון על מנת‬
‫להקטין את הסיכוי שיורידו את המדבקה וייכניסו אותה לפה‪.‬‬
‫הכנת העור‬
‫(‪ )X‬הסר‪/‬י את עודפי השיער מהעור באמצעות מספרים בלבד (אל תגלח‪/‬י על מנת לא לפצוע את העור)‪ ,‬רחץ‪/‬י את‬
‫העור (אם יש צורך בכך) במים נקיים בלבד (ללא סבון !) ויבש‪/‬י היטב ובעדינות‪.‬אין להשתמש בסבון‪ ,‬תחליב‪,‬‬
‫שמנים או אלכוהול לפני הדבקת המדבקה החדשה על העור‪ .‬אל תדביק‪/‬י את המדבקה מיד לאחר מקלחת חמה‬
‫או אמבטיה חמה – המתן‪/‬י עד שהעור יתייבש ויתקרר לחלוטין‪.‬‬
‫‪ .2‬לפתיחת שקית האלומיניום‪ ,‬קפל‪/‬י לאורך החריץ‪ .‬לאחר מכן קרע‪/‬י בעדינות את קצה שקית האלומיניום‪ ,‬אחוז‪/‬י‬
‫בשני הצדדים של שקית האלומיניום הפתוחה‪ ,‬והפרד‪/‬י ביניהם כך ששקית האלומיניום תיפתח כמו ספר ‪ .‬בדוק‬
‫את המדבקה וודא שאינה נראית פגומה‪ .‬אל תשתמש במדבקה הנראית פגומה‪ ,‬או במדבקה שנחתכה או חולקה‪.‬‬
‫(‪ )X‬במידה והמדבקה נפלה מאליה יש לזרוק אותה להדביק מדבקה חדשה מיד כאשר הבחנת‪/‬ה בכך‪ .‬את‬
‫המדבקה החדשה יש להדביק באיזור אחר על העור‪ .‬יידע את הרופא כי המדבקה נפלה‪ ,‬את המדבקה‬
‫החדשה יש להחליפ לאחר ‪ 3‬יממות (‪ 27‬שעות) או ע"פ מה שהורה לך הרופא‪.‬‬
‫אחסנה ‪:‬‬
‫במקום קריר ‪(15-25 C‬‬
‫‪05‬‬

Durogesic 12,25,50,75100MCG/H Durogesic 12,25,50

Transcription

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