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Duragesic (Fentanyl Citrate Transdermal) - Indications and Dosage

 
 



INDICATIONS AND USAGE

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 (see DOSAGE AND ADMINISTRATION). 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 result, DURAGESIC® is contraindicated for use on an as needed basis (i.e., prn), for the management of post-operative or acute pain, or in patients who are not opioid-tolerant or who require opioid analgesia for a short period of time (see BOX WARNING and CONTRAINDICATIONS).

An evaluation of the appropriateness and adequacy of treating with immediate-release opioids is advisable prior to initiating therapy with any modified-release opioid. Prescribers should individualize treatment in every case, initiating therapy at the appropriate point along a progression from non-opioid analgesics, such as non-steroidal anti-inflammatory drugs and acetaminophen, to opioids, in a plan of pain management such as outlined by the World Health Organization, the Agency for Health Research and Quality, the Federation of State Medical Boards Model Policy, or the American Pain Society.

Patients should be assessed for their clinical risks for opioid abuse or addiction prior to being prescribed opioids. Patients receiving opioids should be routinely monitored for signs of misuse, abuse, and addiction. 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 at increased risk may still be appropriately treated with modified-release opioid formulations; however these patients will require intensive monitoring for signs of misuse, abuse, or addiction.

DOSAGE AND ADMINISTRATION

Special Precautions

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 ® patches are intended for transdermal use (on intact skin) only. The DURAGESIC ® patch should not be used 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.

Each DURAGESIC® 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 problems with adhesion of the DURAGESIC® patch occur, the edges of the patch may be taped with first aid tape. If problems with adhesion persist, the patch may be overlayed with a transparent adhesive film dressing (e.g., Bioclusive™ or Tegaderm™).

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.

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.

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 BOX WARNING, CLINICAL PHARMACOLOGY – Drug Interactions, WARNINGS, and PRECAUTIONS for further information).

Pediatric patients converting to DURAGESIC® with a 25 mcg/h patch should be opioid-tolerant and receiving at least 60 mg of oral morphine or the equivalent per day. The dose conversion schedule described in Table C, and method of titration described below are recommended in opioid-tolerant pediatric patients over 2 years of age with chronic pain (see PRECAUTIONS - Pediatric Use).


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.


DURAGESIC® 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

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
  • 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 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.)

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).

Prescribers should individualize treatment using a progressive plan of pain management such as outlined by the World Health Organization, the Agency for Health Research and Quality, the Federation of State Medical Boards Model Policy, or the American Pain Society.

With all opioids, the safety of patients using the products is dependent on health care practitioners prescribing them in strict conformity with their approved labeling with respect to patient selection, dosing, and proper conditions for use.

As with all opioids, dosage should be individualized. The most important factor to be considered in determining the appropriate dose is the extent of pre-existing opioid-tolerance (see BOX WARNING and CONTRAINDICATIONS). Initial doses should be reduced in elderly or debilitated patients (see PRECAUTIONS).

DURAGESIC® (fentanyl transdermal system) should be applied to intact, non-irritated, and non-irradiated skin on a flat surface such as the chest, back, flank, or upper arm. In young children and persons with cognitive impairment, adhesion should be monitored and the upper back is the preferred location to minimize the potential of inappropriate patch removal. Hair at the application site should be clipped (not shaved) prior to system application. If the site of DURAGESIC® application must be cleansed prior to application of the patch, do so with clear water. Do not use soaps, oils, lotions, alcohol, or any other agents that might irritate the skin or alter its characteristics. Allow the skin to dry completely prior to patch application.

DURAGESIC® should be applied immediately upon removal from the sealed package. Do not use if the 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.

Thetransdermal 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. If the gel from the drug reservoir accidentally contacts the skin of the patient or caregiver, the skin should be washed with copious amounts of water. Do not use soap, alcohol, or other solvents to remove the gel because they may enhance the drug's ability to penetrate the skin.

DURAGESIC® should be kept out of the reach of children. Used patches should be folded so that the adhesive side of the patch adheres to itself, then the patch should be flushed down the toilet immediately upon removal. Patients should dispose of any patches remaining from a prescription as soon as they are no longer needed. Unused patches should be removed from their pouches, folded so that the adhesive side of the patch adheres to itself, and flushed down the toilet.

Dose Selection

Doses must be individualized based upon the status of each patient and should be assessed at regular intervals after DURAGESIC® application. Reduced doses of DURAGESIC® are suggested for the elderly and other groups discussed in PRECAUTIONS.

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.

In selecting an initial DURAGESIC® dose, attention should be given to 1) the daily dose, potency, and characteristics of the opioid the patient has been taking previously (e.g., whether it is a pure agonist or mixed agonist-antagonist), 2) the reliability of the relative potency estimates used to calculate the DURAGESIC® dose needed (potency estimates may vary with the route of administration), 3) the degree of opioid tolerance and 4) the general condition and medical status of the patient. Each patient should be maintained at the lowest dose providing acceptable pain control.

Initial DURAGESIC® Dose Selection

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.

There has been no systematic evaluation of DURAGESIC® as an initial opioid analgesic in the management of chronic pain, since most patients in the clinical trials were converted to DURAGESIC® from other narcotics. The efficacy of DURAGESIC® 12 mcg/h as an initiating dose has not been determined. In addition, patients who are not opioid-tolerant have experienced hypoventilation and death during use of DURAGESIC®. Therefore, DURAGESIC® should be used only in patients who are opioid-tolerant.

To convert adult and pediatric patients from oral or parenteral opioids to DURAGESIC®, use Table C:

Alternatively, for adult and pediatric patients taking opioids or doses not listed in Table C, use the following methodology:

  • Calculate the previous 24-hour analgesic requirement.
  • Convert this amount to the equianalgesic oral morphine dose using Table D.
  • Table E displays the range of 24-hour oral morphine doses that are recommended for conversion to each DURAGESIC® dose. Use this table to find the calculated 24-hour morphine dose and the corresponding DURAGESIC® dose. Initiate DURAGESIC® 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 analgesic efficacy is attained. The recommended starting dose when converting from other opioids to DURAGESIC® 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.
TABLE C1 DOSE CONVERSION GUIDELINES

1 Table C should not be used to convert from DURAGESIC ® to other therapies because this conversion to DURAGESIC ® is conservative. Use of table C for conversion to other analgesic therapies can overestimate the dose of the new agent. Overdosage of the new analgesic agent is possible (see DOSAGE AND ADMINISTRATION - Discontinuation of DURAGESIC ® ).

Current Analgesic Daily Dosage (mg/d)
Oral morphine 60-134 135-224 225-314 315-404
IM/IV morphine 10-22 23-37 38-52 53-67
Oral oxycodone 30-67 67.5-112 112.5-157 157.5-202
IM/IV oxycodone 15-33 33.1-56 56.1-78 78.1-101
Oral codeine 150-447 448-747 748-1047 1048-1347
Oral hydromorphone 8-17 17.1-28 28.1-39 39.1-51
IV hydromorphone 1.5-3.4 3.5-5.6 5.7-7.9 8-10
IM meperidine 75-165 166-278 279-390 391-503
Oral methadone 20-44 45-74 75-104 105-134
IM methadone 10-22 23-37 38-52 53-67
Recommended
DURAGESIC® Dose
25 mcg/h 50 mcg/h 75 mcg/h 100 mcg/h

Alternatively, for adult and pediatric patients taking opioids or doses not listed in Table C, use the conversion methodology outlined above with Table D.

TABLE D1a EQUIANALGESIC POTENCY CONVERSION

1 Table D should not be used to convert from DURAGESIC ® to other therapies because this conversion to DURAGESIC ® is conservative. Use of Table D for conversion to other analgesic therapies can overestimate the dose of the new agent. Overdosage of the new analgesic agent is possible (see Dosage And Administration - Discontinuation of DURAGESIC ® ).

a All IM and PO doses in this chart are considered equivalent to 10 mg of IM morphine in analgesic effect. IM denotes intramuscular, PO oral, and PR rectal.

b Based on single-dose studies in which an intramuscular dose of each drug listed was compared with morphine to establish the relative potency. Oral doses are those recommended when changing from parenteral to an oral route. Reference: Foley, K.M. (1985) The treatment of cancer pain. NEJM 313(2):84-95.

c Although controlled studies are not available, in clinical practice it is customary to consider the doses of opioid given IM, IV, or subcutaneously to be equivalent. There may be some differences in pharmacokinetic parameters such as Cmax and Tmax.

d The conversion ratio of 10 mg parenteral morphine = 30 mg oral morphine is based on clinical experience in patients with chronic pain. The conversion ratio of 10 mg parenteral morphine = 60 mg oral morphine is based on a potency study in acute pain. Reference: Ashburn and Lipman (1993) Management of pain in the cancer patient. Anesth Analg 76:402-416.

Name Equianalgesic Dose (mg)
IM b,c PO
Morphine 10 60 (30)d
Hydromorphone (Dilaudid®) 1.5 7.5
Methadone (Dolophine®) 10 20
Oxycodone 15 30
Levorphanol (Levo-Dromoran®) 2 4
Oxymorphone (Numorphan®) 1 10 (PR)
Meperidine (Demerol®) 75
Codeine 130 200
TABLE E1 RECOMMENDED INITIAL DURAGESIC® DOSE BASED UPON DAILY ORAL MORPHINE DOSE

NOTE: In clinical trials, these ranges of daily oral morphine doses were used as a basis for conversion to DURAGESIC®.

1 Table E should not be used to convert from DURAGESIC ® to other therapies because this conversion to DURAGESIC ® is conservative. Use of Table E for conversion to other analgesic therapies can overestimate the dose of the new agent. Overdosage of the new analgesic agent is possible (see DOSAGE AND ADMINISTRATION - Discontinuation of DURAGESIC ® ).

Oral 24-hour
Morphine
(mg/day)
DURAGESIC ®
Dose
(mcg/h)
60–13425
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

The majority of patients are adequately maintained with DURAGESIC® 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 DURAGESIC® 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.

Because of the increase in serum fentanyl concentration over the first 24 hours following initial system application, the initial evaluation of the maximum analgesic effect of DURAGESIC® cannot be made before 24 hours of wearing. The initial DURAGESIC® dose may be increased after 3 days (see DOSAGE AND ADMINISTRATION - Dose Titration).

During the initial application of DURAGESIC®, patients should use short-acting analgesics as needed until analgesic efficacy with DURAGESIC® is attained. Thereafter, some patients still may require periodic supplemental doses of other short-acting analgesics for “breakthrough” pain.

Dose Titration

The recommended initial DURAGESIC® dose based upon the daily oral morphine dose is conservative, and 50% of patients are likely to require a dose increase after initial application of DURAGESIC®. The initial DURAGESIC® dose may be increased after 3 days based on the daily dose of supplemental opioid analgesics required by the patient in the second or third day of the initial application.

Physicians are advised that it may take up to 6 days after increasing the dose of DURAGESIC® for the patient to reach equilibrium on the new dose (see graph in CLINICAL PHARMACOLOGY). Therefore, patients should wear a higher dose through two applications before any further increase in dosage is made on the basis of the average daily use of a supplemental analgesic.

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 DURAGESIC® dose. DURAGESIC®-12 delivers 12.5 mcg/h of fentanyl.

Discontinuation of DURAGESIC®

To convert patients to another opioid, remove DURAGESIC® and titrate the dose of the new analgesic based upon the patient's report of pain until adequate analgesia has been attained. Upon system removal, 17 hours or more are required for a 50% decrease in serum fentanyl concentrations. Opioid withdrawal symptoms (such as nausea, vomiting, diarrhea, anxiety, and shivering) are possible in some patients after conversion or dose adjustment. For patients requiring discontinuation of opioids, a gradual downward titration is recommended since it is not known at what dose level the opioid may be discontinued without producing the signs and symptoms of abrupt withdrawal.

Tables C, D, and E should not be used to convert from DURAGESIC ® to other therapies. Because the conversion to DURAGESIC ® is conservative, use of Tables C, D, and E for conversion to other analgesic therapies can overestimate the dose of the new agent. Overdosage of the new analgesic agent is possible.

HOW SUPPLIED

DURAGESIC® (fentanyl transdermal system) is supplied in cartons containing 5 individually packaged systems. See chart for information regarding individual systems.

DURAGESIC ®
Dose
(mcg/h)
System
Size
(cm 2 )
Fentanyl
Content
(mg)
NDC
Number
DURAGESIC®-12 5 1.25 50458-037-05
DURAGESIC®-25 10 2.5 50458-033-05
DURAGESIC®-50 20 5 50458-034-05
DURAGESIC®-75 30 7.5 50458-035-05
DURAGESIC®-100 40 10 50458-036-05

Safety and Handling

DURAGESIC® is supplied in sealed transdermal systems which pose little risk of exposure to health care workers. If the gel from the drug reservoir accidentally contacts the skin, the area should be washed with copious amounts of water. Do not use soap, alcohol, or other solvents to remove the gel because they may enhance the drug's ability to penetrate the skin. 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.

KEEP DURAGESIC ® OUT OF THE REACH OF CHILDREN AND PETS.

Do not store above 77°F (25°C). Apply immediately after removal from individually sealed package. Do not use if the seal is broken. For transdermal use only.

BioclusiveTM is a trademark of Ethicon, Inc.
TegadermTM is a trademark of 3M

A schedule CII narcotic. DEA order form required.

Manufactured by:
ALZA Corporation
Mountain View, CA 94043

Manufactured for::
Janssen, division of Ortho-McNeil-Janssen Pharmaceuticals, Inc.
Titusville, NJ 08560

10459501

February 2008

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