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DURAGESIC ® contains a high concentration of a potent Schedule II opioid agonist, fentanyl. Schedule II opioid substances which include fentanyl, hydromorphone, 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 (DURAGESIC ® ) may be a particular target for abuse and diversion.
DURAGESIC® 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, and
- cannot be managed by other means such as non-steroidal analgesics, opioid combination products, or immediate-release opioids
DURAGESIC ® should ONLY be used in patients who are already receiving opioid therapy, who have demonstrated opioid tolerance, and who require a total daily dose at least equivalent to DURAGESIC ® 25 mcg/h. Patients who are considered opioid-tolerant are those who have been taking, for a week or longer, at least 60 mg of morphine daily, or at least 30 mg of oral oxycodone daily, or at least 8 mg of oral hydromorphone daily or an equianalgesic dose of another opioid.
Because serious or life-threatening hypoventilation could occur, DURAGESIC® (fentanyl transdermal system) is contraindicated:
- in patients who are not opioid-tolerant
- in the management of acute pain or in patients who require opioid analgesia for a short period of time
- in the management of post-operative pain, including use after out-patient or day surgeries (e.g., tonsillectomies)
- in the management of mild pain
- in the management of intermittent pain (e.g., use on an as needed basis [prn])
(See CONTRAINDICATIONS for further information.)
Since the peak fentanyl levels occur between 24 and 72 hours of treatment, prescribers should be aware that serious or life threatening hypoventilation may occur, even in opioid-tolerant patients, during the initial application period.
The concomitant use of DURAGESIC® with all cytochrome P450 3A4 inhibitors (such as ritonavir, ketoconazole, itraconazole, troleandomycin, clarithromycin, nelfinavir, nefazodone, 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. Patients receiving DURAGESIC ® and any CYP3A4 inhibitor 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 and for further information).
The safety of DURAGESIC® has not been established in children under 2 years of age. DURAGESIC® should be administered to children only if they are opioid-tolerant and 2 years of age or older (see PRECAUTIONS - Pediatric Use ).
DURAGESIC® 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 DURAGESIC ® 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 hours of DURAGESIC ® , patients who are thought to have had a serious adverse event, including overdose, will require monitoring and treatment for at least 24 hours.
DURAGESIC ® can be abused in a manner similar to other opioid agonists, legal or illicit. This risk should be considered when administering, prescribing, or dispensing DURAGESIC ® in situations where the healthcare professional is concerned about increased risk of misuse, abuse, or diversion.
Persons at increased risk for opioid abuse include those with a personal or family history of substance abuse (including drug or alcohol abuse or addiction) or mental illness (e.g., major depression). Patients should be assessed for their clinical risks for opioid abuse or addiction prior to being prescribed opioids. All patients receiving opioids should be routinely monitored for signs of misuse, abuse, and addiction. Patients at increased risk of opioid abuse may still be appropriately treated with modified-release opioid formulations; however, these patients will require intensive monitoring for signs of misuse, abuse, or addiction.
DURAGESIC ® patches are intended for transdermal use (on intact skin) only. Do not use a DURAGESIC ® patch if the seal is broken or the patch is cut, damaged or changed in any way. Using a patch that is cut, damaged, or changed in any way can expose the patient or caregiver to the contents of the patch, which can result in an overdose of fentanyl that may be fatal.
Avoid exposing the DURAGESIC ® 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, while wearing the system. Avoid taking hot baths or sunbathing. There is a potential for temperature-dependent increases in fentanyl released from the system resulting in possible overdose and death. Patients wearing DURAGESIC® systems who develop fever or increased core body temperature due to strenuous exertion should be monitored for opioid side effects and the DURAGESIC® dose should be adjusted if necessary.
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NEWS HIGHLIGHTS
Published Studies Related to Duragesic (Fentanyl Transdermal)
Efficacy and long-term tolerability of sublingual fentanyl orally disintegrating tablet in the treatment of breakthrough cancer pain. [2009.10.08]
Abstract Background and objectives: Breakthrough cancer pain (BTcP) represents an important clinical challenge in the care of patients with cancer. This trial evaluated the efficacy and long-term tolerability of a sublingual formulation of the fast-acting opioid fentanyl, for the treatment of BTcP in opioid-tolerant patients with cancer...
Analgesia during abdominal aortic aneurysm endovascular repair: remifentanil vs. fentanyl-midazolam--a randomized controlled trial. [2009.09]
BACKGROUND AND OBJECTIVE: Endovascular repair offers a less surgically invasive procedure for abdominal aortic aneurysms but nevertheless, still requires analgesic sedative cover to ensure an acceptable level of patient comfort and cardiorespiratory stability. The peculiarity of this kind of operation is that painful stimuli are concentrated in specific moments separated by intervals devoid of pain, so the insurgence of pain can be predicted and prevented with a bolus of analgesic, making a continuous infusion not essential, but potentially useful in achieving a better analgesic stability. The primary objective of the study was pain control measured by Visual Analogue Scale; secondary endpoints were cardiorespiratory stability and an acceptable level of sedation... CONCLUSION: Both techniques were shown to be safe and most importantly effective in offering cardiovascular stability and analgesia for American Society of Anaesthesiologists III-IV patients undergoing endovascular abdominal aortic aneurysm repair. However, remifentanil continuous infusion proved to offer significantly more stable pain control compared with the currently used combination fentanyl-midazolam.
Morphine-based cardiac anesthesia provides superior early recovery compared with fentanyl in elective cardiac surgery patients. [2009.08]
BACKGROUND: Experimental and clinical data suggest that morphine possesses unique cardioprotective and antiinflammatory properties. In this clinical investigation, we sought to determine whether the choice of intraoperative opioid (morphine or fentanyl) influences early recovery after cardiac surgery... CONCLUSIONS: In patients undergoing elective cardiac surgery with cardiopulmonary bypass, postoperative quality-of-life measures and pain control during recovery were enhanced when morphine (40 mg) was administered intraoperatively as part of a balanced anesthetic technique compared with fentanyl.
The effects of dexmedetomidine and fentanyl on emergence characteristics after adenoidectomy in children. [2009.07]
This randomised controlled study evaluated the effects of fentanyl and dexmedetomidine on emergence characteristics of children having adenoidectomy and anaesthetised with sevoflurane. Ninety children, two to seven years of age and ASA physical status I, were studied.Further studies of dexmedetomidine safety and its interaction with other anaesthetic agents are required before recommending its routine use during general anaesthesia in children.
Subarachnoid morphine, bupivacaine and fentanyl as part of combined spinal-epidural analgesia for low anterior resection. A prospective, randomised, double-blind clinical trial. [2009.07]
This study was designed to compare the efficacy of subarachnoid morphine alone or in combination with bupivacaine and fentanyl for combined spinal-epidural analgesia in colorectal surgery... The addition of bupivacaine and fentanyl to subarachnoid morphine did not confer any advantage on postoperative visual analogue scale scores and tramadol use, but lowered the need for additional intraoperative intravenous fentanyl and epidural bupivacaine and prolonged the time to first analgesia request.
Clinical Trials Related to Duragesic (Fentanyl Transdermal)
Staccato® Fentanyl Pharmacokinetics in Healthy Volunteers [Completed]
The Phase I clinical trial in approximately 50 healthy volunteers will be conducted at a
single clinical center in two stages. Stage 1 is an open-label, cross-over comparison of a
single dose of Staccato Fentanyl and an equivalent dose of intravenous (IV) fentanyl. Stage 2
is a randomized, doubleblind, placebo-controlled dose escalation of Staccato Fentanyl,
evaluating multiple doses of fentanyl. The three primary aims of the Phase I clinical trial
are to evaluate the pharmacokinetics (PK) and absolute bioavailability for Fentanyl, compare
the Staccato Fentanyl PK profile to the IV fentanyl PK profile, and examine the tolerability
and safety of Staccato Fentanyl in a non-opioid-tolerant, healthy volunteer population.
Study of the Effect of Clinical Procedures on Drug Delivery of Mylan Fentanyl Transdermal System 25 µg/hr and Duragesic® 25 µg/hr [Terminated]
The objective of this study was to investigate the effect of clinical procedures on the drug
delivery of Fentanyl Transdermal Systems, 25 mcg/h manufactured for Mylan Pharmaceuticals
Inc. by Mylan Technologies Inc., and Duragesic, 25 mcg/h manufactured for Janssen
Pharmaceutica by ALZA Corporation.
Analgesic Effect and Plasma Concentration of Epidural Versus Intravenous Fentanyl [Completed]
CONTEXT AND OBJECTIVE: Controversies exist regarding the site of action of Fentanyl after
epidural injection. The objective of this investigation was to compare the analgesic effect
of epidural and intravenous Fentanyl for lower limb orthopedic surgeries.
DESIGN AND SETTING: A randomized and double-blind study was performed in Hospital São Paulo.
METHODS: 29 patients were divided into two groups. During the postoperative period, in the
presence of pain, group 1 (n = 14) patients received 5 mL of a 100 mcg Fentanyl solution in
saline without preservative by the epidural route and 2 mL saline intravenously. Group 2 (n =
15) patients received 5 mL saline by the epidural route and 2 mL (100 mcg) Fentanyl
intravenously. Analgesic supplementation consisted of 40 mg intravenous Tenoxicam and 5 mL
epidural 0. 25% bupivacaine (if pain relief was not achieved with Tenoxicam). Pain intensity
was evaluated by numerical scale and plasma concentrations of Fentanyl were measured
simultaneously.
A Study to Assess the Safety, Dose Conversion, and Dose Individualization of Duragesic® (Fentanyl Transdermal Patch) in the Treatment of Children With Chronic Pain Requiring Narcotic Pain Relief Therapy [Completed]
The objective of this study is to assess the safety of treatment with Duragesic® (a
transdermal patch delivering the narcotic pain-reliever fentanyl) in doses of 12. 5, 25, 50,
75 and 100 micrograms/hour in pediatric subjects requiring narcotic pain relief therapy.
Particular attention is paid to appropriate dose conversion to Duragesic® therapy from the
subject's current narcotic pain relief therapy, and to the parameters for increasing the
Duragesic® dose to achieve analgesic effectiveness. Pharmacokinetics (fentanyl levels in the
bloodstream during treatment) will also be assessed.
Bioequivalence and Wear Study of Mylan Fentanyl Transdermal System 25 µg/h and Mylan Fentanyl Transdermal System [Completed]
The objective of this study was to investigate the effect of three different types of
occlusive overlays on the drug delivery of Fentanyl Transdermal Systems, 25 mcg/h
manufactured for Mylan Pharmaceuticals Inc. by Mylan Technologies Inc., and Duragesic, 25
mcg/h manufactured for Janssen Pharmaceutica by ALZA Corporation. The acute irritation of
each type of overlay worn with each fentanyl treatment was also assessed after patch
removal.
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