Criteria for Use

Fentanyl Transdermal Systems

VHA Pharmacy Benefits Management Service and the Medical Advisory Panel

These criteria were based on the best clinical evidence currently
available. The recommendations in this document are dynamic, and will be
revised as new clinical information becomes available. This guidance is
intended to assist practitioners in providing consistent, high-quality,
cost-effective drug therapy. These criteria are not intended to
interfere with clinical judgment; the clinician must ultimately decide
the course of therapy based on individual patient situations.

+---+-------------------------------------------------------------------+
|   | **Exclusion Criteria**                                            |
+---+-------------------------------------------------------------------+
|   | *Patient should NOT receive transdermal fentanyl if any of the    |
|   | following criteria are met.*                                      |
+---+-------------------------------------------------------------------+
|   | Use of transdermal fentanyl is for any of the following: (1) mild |
|   | pain; (2) breakthrough or intermittent pain (i.e., for as-needed  |
|   | / p.r.n. analgesia situations); (3) postoperative pain, including |
|   | outpatient or day surgeries; and (4) pain due to acute clinical   |
|   | conditions / situations (e.g., acute trauma, new onset herpes     |
|   | zoster / shingles).                                               |
+---+-------------------------------------------------------------------+
|   | Patient is not opioid-tolerant, defined as taking less than or    |
|   | equal to 60 mg of oral morphine daily, 20 mg of oral methadone    |
|   | daily, 30 mg of oral oxycodone daily, 8 mg of oral hydromorphone  |
|   | daily, or an equianalgesic dose of another opioid, for less than  |
|   | one week.                                                         |
+---+-------------------------------------------------------------------+
|   | Hypersensitivity to fentanyl or local hypersensitivity reaction   |
|   | to any components of the patch that is not adequately controlled  |
|   | with topical medications (e.g., corticosteroids).                 |
+---+-------------------------------------------------------------------+
|   | Patient has a contraindication to opioids (e.g., significant      |
|   | respiratory depression, acute or severe bronchial asthma or       |
|   | hypercarbia, or known or suspected paralytic ileus).              |
+---+-------------------------------------------------------------------+
|   | **Inclusion Criteria**                                            |
+---+-------------------------------------------------------------------+
|   | *Patient must meet all of criteria A--D to use transdermal        |
|   | fentanyl patches. These criteria apply to new starts only;        |
|   | patients stable on transdermal fentanyl should not be required to |
|   | discontinue it or switch to another opioid unless there is a      |
|   | clinical reason for doing so.*                                    |
+---+-------------------------------------------------------------------+
|   | A. Patient requires around-the-clock analgesia for moderate to    |
|   | severe, *persistent* chronic pain                                 |
+---+-------------------------------------------------------------------+
|   | B. Patient is followed by a VA or VA-contracted provider for      |
|   | management of transdermal fentanyl therapy.                       |
+---+-------------------------------------------------------------------+
|   | C. Transdermal fentanyl is *initially* prescribed and titrated by |
|   | a VA or VA-contracted provider who has experience in dosing       |
|   | transdermal fentanyl or is in consultation with a VA or           |
|   | VA-contracted organized pain clinic or local pain management      |
|   | expert with experience in dosing transdermal fentanyl.            |
+---+-------------------------------------------------------------------+
|   | D. Patient meets at least one of the following conditions:        |
|   |                                                                   |
|   | --- is unable to swallow, tolerate, or absorb oral preparations   |
|   |                                                                   |
|   | -   is unable to adhere to an oral opioid regimen because of      |
|   |     cognitive or psychiatric impairment                           |
|   |                                                                   |
|   | ```{=html}                                                        |
|   | <!-- -->                                                          |
|   | ```                                                               |
|   | -   requires *chronic and relatively stable* pain management as   |
|   |     part of end-of-life care, and twice daily or more frequent    |
|   |     oral administration of opioids is likely to be problematic    |
|   |     for the patient or caregiver                                  |
|   |                                                                   |
|   | -   has a documented current or past history of intolerable       |
|   |     adverse effects to long-acting morphine and methadone OR to   |
|   |     only long-acting morphine, if methadone is not acceptable     |
|   |     because an organized pain clinic or local pain management     |
|   |     expert with experience in dosing methadone is not readily     |
|   |     available for referral or consultation                        |
|   |                                                                   |
|   | *Intolerable adverse effects are those that persist despite       |
|   | aggressive measures to alleviate them and that prevent upward     |
|   | titration of dosage to achieve a satisfactory level of analgesia  |
|   | (e.g., constipation unresponsive to aggressive use of laxatives;  |
|   | or nausea inadequately controlled by antiemetics or gradual dose  |
|   | titration).*                                                      |
+---+-------------------------------------------------------------------+

+---+---------------------------------------------------------------------+
|   | **Additional Safety Precautions**                                   |
+---+---------------------------------------------------------------------+
|   | **Verify doses.** For patients who are admitted to the hospital and |
|   | using fentanyl patches at home, the dose should be verified during  |
|   | medication reconciliation.                                          |
+---+---------------------------------------------------------------------+
|   | **Use extra caution with orders for "125-mcg/h" patches.**          |
|   | Healthcare providers should remain cautious about orders for a 125  |
|   | mcg/hour strength because the decimal point has been overlooked at  |
|   | times with orders for 12.5 mcg/h patches. When ordering 12.5-mcg/h  |
|   | patches, get into the habit of writing "12" or twelve mcg/h to      |
|   | avoid decimal point confusion. For CPRS orders, consider a pop-up   |
|   | reminder asking, "Did you really mean one hundred twenty-five       |
|   | mcg/h?"                                                             |
+---+---------------------------------------------------------------------+
|   | **Assess concomitant use of opioids.** To reduce the risk of an     |
|   | overdose, take into consideration any other opioids prescribed for  |
|   | the patient when evaluating the appropriateness of the patient's    |
|   | dose.                                                               |
+---+---------------------------------------------------------------------+
|   | **Do not cut, damage, or alter fentanyl patches prior to            |
|   | application.**                                                      |
|   |                                                                     |
|   | 1.  Do not process orders that require cutting fentanyl patches     |
|   | prior to application.  The prescriber must be notified of the       |
|   | hazard as soon as possible.                                         |
|   |                                                                     |
|   | 2.  Advise patients receiving fentanyl patches not to cut, damage,  |
|   | or alter the transdermal system before use.                         |
|   |                                                                     |
|   | 3.  Use an alternate opioid therapy when a patient requires         |
|   | transdermal fentanyl in fractions of the patch sizes available.     |
|   |                                                                     |
|   | 4\. Repeated requests for cutting fentanyl patches prior to         |
|   | application should be referred to the Pharmacy Manager for review   |
|   | by the facility Medication Use or Pharmacy and Therapeutics         |
|   | Committee.                                                          |
+---+---------------------------------------------------------------------+
|   | **Remove previous patches before applying the next dose.** This is  |
|   | especially important in inpatient settings. Check the patient       |
|   | carefully, including in skin folds, and remove old fentanyl patches |
|   | before applying a new patch. Providers may encourage patients to    |
|   | place patches in view on the front torso or upper arms so they can  |
|   | be seen when looking in the mirror.                                 |
+---+---------------------------------------------------------------------+
|   | **Avoid external heat on patch application site.** All patients and |
|   | their caregivers should be advised to avoid exposing the fentanyl   |
|   | patch application site to direct external heat sources, such as     |
|   | heating pads or electric blankets, heat lamps, saunas, hot tubs,    |
|   | and heated water beds, etc., while wearing the system. Avoid taking |
|   | hot baths and sunbathing. Patients who develop fever or increased   |
|   | core body temperature (e.g., from strenuous exertion) should be     |
|   | monitored for opioid toxicity. There is a potential for             |
|   | temperature-dependent increases in fentanyl released from the       |
|   | system resulting in possible overdose and death.                    |
+---+---------------------------------------------------------------------+
|   | **Remove fentanyl transdermal patches prior to MRI.** Advise        |
|   | patients to remove the patch temporarily during MRI and replace     |
|   | with a new one after the procedure (ISMP Medication Safety Alert,   |
|   | April 8^th^, 2004; [http://www.ismp.org/                            |
|   | Newsletters/acutecare/articles/20040408.asp]                        |
|   | (http://www.ismp.org/ Newsletters/acutecare/articles/20040408.asp)) |
+---+---------------------------------------------------------------------+
|   | **Reduce the dose of fentanyl or CNS depressants when used          |
|   | concomitantly.** The concomitant use of 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, and alcohol, may cause respiratory       |
|   | depression, hypotension, and profound sedation or potentially       |
|   | result in coma. When such combined therapy is contemplated, the     |
|   | dose of one or both agents should be significantly reduced.         |
+---+---------------------------------------------------------------------+
|   | **Use caution with concomitant CYP3A4 inhibitors.** Patients        |
|   | receiving transdermal fentanyl and potent CYP3A4 inhibitors (e.g.,  |
|   | clarithromycin, itraconazole, ketoconazole, nefazodone, ritonavir,  |
|   | troleandomycin) should be carefully monitored for an extended       |
|   | period of time and dosage adjustments should be made if warranted,  |
|   | particularly when CYP3A4 inhibitors are added to existing           |
|   | transdermal fentanyl therapy or when the dose of a CYP3A4 inhibitor |
|   | is increased.                                                       |
+---+---------------------------------------------------------------------+
|   | **Use extra caution when converting to or from fentanyl patches.**  |
|   | Overestimating the transdermal fentanyl dose when converting        |
|   | patients from another opioid medication to transdermal fentanyl     |
|   | patches can result in fatal overdose with the first dose. *The      |
|   | conversion table in the Package Insert is unidirectional (i.e.,     |
|   | from other opioids TO transdermal fentanyl).* *Do not use the       |
|   | conversion table in the Package Insert to convert patients FROM     |
|   | transdermal fentanyl to other opioids because the dosing table is   |
|   | conservative and may result in opioid toxicity if used in this      |
|   | manner.*                                                            |
+---+---------------------------------------------------------------------+
|   | **Provide and document mandatory patient education.** Educate       |
|   | patient and / or caregiver on how to use the transdermal fentanyl   |
|   | patch; provide and review the patient *Medication Guide,*[^1] and   |
|   | document this mandatory education in the patient's medical record.  |
|   | Also provide and view the *Patient Instructions for Use.*^1^ In     |
|   | inpatient and outpatient settings, the discussion should include,   |
|   | at the minimum, indications; high potency; dose; safety precautions |
|   | (e.g., avoid heating pads or hot tubs, remove old patch before      |
|   | application of a new patch); application, removal, and disposal     |
|   | processes; and signs of fentanyl toxicity. Emphasize the need to    |
|   | store medication in a **locked secure place** at work and home, out |
|   | of the reach of children (and pets); the potential for fatal        |
|   | respiratory depression from fentanyl that still remains in used     |
|   | patches; and the suggestion to avoid application of the patch in    |
|   | front of children since children sometimes imitate adults.          |
|   | Pharmacists could use this counseling opportunity to verify that    |
|   | the patient is opioid-tolerant and being treated for chronic pain.  |
+---+---------------------------------------------------------------------+
|   | **Allow adequate time for recovery from any fentanyl toxicity.**    |
|   | Because the mean elimination half-life of transdermal fentanyl is   |
|   | 17 hours, patients who are thought to have had a serious adverse    |
|   | event, including overdose, will require monitoring and treatment    |
|   | for at least 24 hours after removal of patch(es).                   |
+---+---------------------------------------------------------------------+
|   | **Inform pregnant and lactating women that fentanyl may be harmful  |
|   | to babies.** There are no adequate and well-controlled studies in   |
|   | pregnant women (Pregnancy Category C). Use fentanyl during          |
|   | pregnancy only if the potential benefit justifies the potential     |
|   | risk to the fetus. Fentanyl is not recommended for analgesia during |
|   | labor and delivery. Fentanyl is not recommended for use in nursing  |
|   | women because of potential risks to their infants. Consult Product  |
|   | Information for further information.                                |
+---+---------------------------------------------------------------------+

+---+--------------------------------------------------------------------+
|   | **DOSING AND ADMINISTRATION**                                      |
+---+--------------------------------------------------------------------+
|   | Additional dosing information can be found in the *Fentanyl        |
|   | Transdermal Patch Dosing and Safety Information Paper* available   |
|   | at the VHA Pain Management Web site:                               |
|   | <http://www1.va.gov/Pain_Management/>.                             |
+---+--------------------------------------------------------------------+
|   | **Initial Dose**                                                   |
+---+--------------------------------------------------------------------+
|   | -   **Transdermal fentanyl should NOT be used in opioid-naïve      |
|   |     persons. It should only be started in patients who are         |
|   |     opioid-tolerant; therefore, the initial dose is actually an    |
|   |     initial *conversion dose*. See table for initial conversion    |
|   |     doses below.**                                                 |
|   |                                                                    |
|   | -   Initial conversion doses should be individualized. Conversion  |
|   |     dosage requirements can vary widely between individuals and    |
|   |     therefore it is difficult to recommend a fixed method for      |
|   |     conversion. The patient's medical condition, the potency,      |
|   |     dose, and type of previous opioid, the patient's degree of     |
|   |     opioid exposure and tolerance, the patient's past analgesic    |
|   |     response and adverse experiences, and the accuracy and         |
|   |     reliability of opioid conversion factors may all influence the |
|   |     choice of starting dose.                                       |
|   |                                                                    |
|   | -   *Overestimating the transdermal fentanyl dose when converting  |
|   |     patients from another opioid can result in fatal overdose with |
|   |     the first dose.*                                               |
|   |                                                                    |
|   | -   *Use caution in elderly, cachectic or debilitated patients as  |
|   |     they may have altered pharmacokinetics due to poor fat stores, |
|   |     muscle wasting, or altered clearance*                          |
|   |                                                                    |
|   | -   Since there is a delay in analgesic effects after the initial  |
|   |     patch application, providers should consider providing the     |
|   |     patient with short-acting analgesics to take on an as-needed   |
|   |     basis until the patient achieves sufficient analgesic effects  |
|   |     from the fentanyl patch (1 to 2 days)                          |
+---+--------------------------------------------------------------------+
|   | **Conversion of an oral opioid medication TO transdermal           |
|   | fentanyl**                                                         |
+---+--------------------------------------------------------------------+
|   | -   *Table 1 conversions are unidirectional. Use Table 1 to        |
|   |     convert patients from other opioids TO transdermal fentanyl    |
|   |     only. Do not use this table to convert patients from           |
|   |     transdermal fentanyl to other opioids; doing so may result in  |
|   |     fentanyl overdose and toxicity.*                               |
|   |                                                                    |
|   | **Table 1 INITIAL CONVERSION DOSE OF TRANSDERMAL FENTANYL PATCH    |
|   | BASED UPON DAILY DOSE OF CURRENT OPIOID**                          |
|   |                                                                    |
|   | +----------------------+--------+--------+---------+---------+     |
|   | | **Current Oral       | *      |        |         |         |     |
|   | | Opioid**             | *Daily |        |         |         |     |
|   | |                      | Dose   |        |         |         |     |
|   | |                      | (m     |        |         |         |     |
|   | |                      | g/d)** |        |         |         |     |
|   | +----------------------+--------+--------+---------+---------+     |
|   | | Codeine p.o.         | 15     | 44     | 74      | 104     |     |
|   | |                      | 0--447 | 8--747 | 8--1047 | 8--1347 |     |
|   | +----------------------+--------+--------+---------+---------+     |
|   | | Hydrocodone p.o.     | 60     | ------ | ------  | ------  |     |
|   | +----------------------+--------+--------+---------+---------+     |
|   | | Hydromorphone p.o.   | 8--17  | 17     | 2       | 3       |     |
|   | |                      |        | .1--28 | 8.1--39 | 9.1--51 |     |
|   | +----------------------+--------+--------+---------+---------+     |
|   | | Levorphanol p.o.     | 8--17  | 17     | 2       | 3       |     |
|   | |                      |        | .1--28 | 8.1--39 | 9.1--51 |     |
|   | +----------------------+--------+--------+---------+---------+     |
|   | | Methadone p.o.       | 20--44 | 45--74 | 75--104 | 1       |     |
|   | |                      |        |        |         | 05--134 |     |
|   | +----------------------+--------+--------+---------+---------+     |
|   | | Morphine p.o.        | 6      | 13     | 2       | 3       |     |
|   | |                      | 0--134 | 5--224 | 25--314 | 15--404 |     |
|   | +----------------------+--------+--------+---------+---------+     |
|   | | Oxycodone p.o.       | 30--67 | 67.    | 112     | 157     |     |
|   | |                      |        | 5--112 | .5--157 | .5--202 |     |
|   | +----------------------+--------+--------+---------+---------+     |
|   | | Oxymorphone p.o.     | 20--44 | 45--74 | 75--104 | 1       |     |
|   | |                      |        |        |         | 05--134 |     |
|   | +----------------------+--------+--------+---------+---------+     |
|   | |                      | *      | *      | **↓↓↓** | **↓↓↓** |     |
|   | |                      | *↓↓↓** | *↓↓↓** |         |         |     |
|   | +----------------------+--------+--------+---------+---------+     |
|   | | **Recommended Dose   | **25\  | **50\  | **75**  | **100\  |     |
|   | | of\                  | m      | m      |         | mcg/h** |     |
|   | | Transdermal Fentanyl | cg/h** | cg/h** | **      |         |     |
|   | | Patch**              |        |        | mcg/h** |         |     |
|   | +----------------------+--------+--------+---------+---------+     |
|   | | Source: Duragesic    |        |        |         |         |     |
|   | | Product Information, |        |        |         |         |     |
|   | | 2/08; Opana          |        |        |         |         |     |
|   | | (oxymorphone ER)     |        |        |         |         |     |
|   | | Product Information, |        |        |         |         |     |
|   | | 2/08                 |        |        |         |         |     |
|   | +----------------------+--------+--------+---------+---------+     |
|   | | *According to this   |        |        |         |         |     |
|   | | conversion table,    |        |        |         |         |     |
|   | | every 90 mg/d(range, |        |        |         |         |     |
|   | | 60--134 mg/d) of     |        |        |         |         |     |
|   | | oral morphine or     |        |        |         |         |     |
|   | | equivalent converts  |        |        |         |         |     |
|   | | to approximately 25  |        |        |         |         |     |
|   | | mcg/h of transdermal |        |        |         |         |     |
|   | | fentanyl (but not    |        |        |         |         |     |
|   | | necessarily vice     |        |        |         |         |     |
|   | | versa). Dosage       |        |        |         |         |     |
|   | | conversions are only |        |        |         |         |     |
|   | | approximate. Refer   |        |        |         |         |     |
|   | | to Package Insert or |        |        |         |         |     |
|   | | other appropriate    |        |        |         |         |     |
|   | | references for       |        |        |         |         |     |
|   | | alternative dose     |        |        |         |         |     |
|   | | conversion methods.  |        |        |         |         |     |
|   | | Refer to product     |        |        |         |         |     |
|   | | information on       |        |        |         |         |     |
|   | | transdermal fentanyl |        |        |         |         |     |
|   | | for converting from  |        |        |         |         |     |
|   | | non-oral opioids to  |        |        |         |         |     |
|   | | transdermal          |        |        |         |         |     |
|   | | fentanyl.*           |        |        |         |         |     |
|   | +----------------------+--------+--------+---------+---------+     |
+---+--------------------------------------------------------------------+
|   |                                                                    |
+---+--------------------------------------------------------------------+
|   | **Conversion FROM transdermal fentanyl to another opioid**         |
+---+--------------------------------------------------------------------+
|   | -   There is a lack of evidence-based guidance on switching        |
|   |     patients from transdermal fentanyl to other opioids.           |
|   |                                                                    |
|   | -   The Product Information for oxycodone CR (OxyContin^®^, 2007)  |
|   |     suggests starting oxycodone CR 18 hours after removal of the   |
|   |     transdermal fentanyl patch, using a conservative oxycodone     |
|   |     dose of approximately 10 mg q12h of oxycodone CR for each      |
|   |     25 mcg/h transdermal fentanyl patch.                           |
|   |                                                                    |
|   | ```{=html}                                                         |
|   | <!-- -->                                                           |
|   | ```                                                                |
|   | -   After discontinuing the fentanyl patch, carefully titrate the  |
|   |     new opioid according to the patient's clinical response, using |
|   |     conservative initial doses and dosage conversion ratios, and   |
|   |     taking into consideration that serum fentanyl concentrations   |
|   |     derived from the patch decrease by 50% every 17 hours (range,  |
|   |     13--22 hours). As suggested for oxycodone CR, one approach is  |
|   |     to start the new opioid about 18 hours after the fentanyl      |
|   |     patch has been removed.                                        |
|   |                                                                    |
|   | -   Providers inexperienced in converting patients from            |
|   |     transdermal fentanyl to another opioid should consult a        |
|   |     clinician who has experience in dosing transdermal fentanyl    |
+---+--------------------------------------------------------------------+

+---+--------------------------------------------------------------------+
|   | **Dose Titration**                                                 |
+---+--------------------------------------------------------------------+
|   | -   The initial conversion doses shown in Table 1 above are        |
|   |     conservative and large interpatient variability in the         |
|   |     conversion dose exists. Further dose adjustment may be needed. |
|   |                                                                    |
|   | -   Short-acting analgesics should also be considered for          |
|   |     predictable, incident breakthrough pain.                       |
|   |                                                                    |
|   | -   Individualize dosing frequency and assess dosage modifications |
|   |     on a regular basis. **The dose of transdermal fentanyl may be  |
|   |     increased on the basis of average daily use of supplemental    |
|   |     opioid analgesic but dosage increases should generally not be  |
|   |     increased sooner than 3 days after the initial dose or more    |
|   |     frequently than every 6 days (i.e., after 2 patch              |
|   |     applications) thereafter.** Some patients require patches to   |
|   |     be applied every 2 days (48 hours) instead of every 3 days     |
|   |     (72 hours) to achieve adequate analgesia. An increase in the   |
|   |     transdermal fentanyl dose should be evaluated before changing  |
|   |     dosing intervals in order to maintain patients on a 72-hour    |
|   |     regimen.                                                       |
|   |                                                                    |
|   | -   Appropriate dosage increments should be based on the daily use |
|   |     of supplemental opioids with the equivalency of morphine 45    |
|   |     mg/d orally to a 12 mcg/h increase in the transdermal fentanyl |
|   |     dose. Transdermal fentanyl-12 delivers 12.5 mcg/h of fentanyl. |
+---+--------------------------------------------------------------------+
|   | **Guidance on High-dose Transdermal Fentanyl**                     |
+---+--------------------------------------------------------------------+
|   | -   Patients requiring transdermal fentanyl doses greater than     |
|   |     200 mcg/h should be evaluated by a specialist in pain          |
|   |     management, anesthesiology, palliative care, or                |
|   |     hematology/oncology                                            |
+---+--------------------------------------------------------------------+
|   |                                                                    |
+---+--------------------------------------------------------------------+
| * |                                                                    |
| * |                                                                    |
| S |                                                                    |
| u |                                                                    |
| g |                                                                    |
| g |                                                                    |
| e |                                                                    |
| s |                                                                    |
| t |                                                                    |
| i |                                                                    |
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| s |                                                                    |
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| P |                                                                    |
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| r |                                                                    |
| i |                                                                    |
| o |                                                                    |
| p |                                                                    |
| e |                                                                    |
| r |                                                                    |
| a |                                                                    |
| t |                                                                    |
| i |                                                                    |
| v |                                                                    |
| e |                                                                    |
| U |                                                                    |
| s |                                                                    |
| e |                                                                    |
| * |                                                                    |
| * |                                                                    |
+---+--------------------------------------------------------------------+
|   | -   Pain experts suggest continuing transdermal fentanyl           |
|   |     throughout the perioperative period (e.g., for inpatient and   |
|   |     outpatient post-operative pain). Abrupt discontinuation of the |
|   |     patch in the peri-operaive period may lead to opioid           |
|   |     withdrawal or uncontrolled post-operative pain.                |
+---+--------------------------------------------------------------------+

Prepared July 2008. Contact: Francine Goodman, PharmD, BCPS, Clinical
Pharmacy Specialist, PBM Services (119D)

[^1]: Duragesic *Medication Guide* and *Patient Instructions for Use:*
    <http://www.duragesic.com/duragesic/potential_patient_information.html>.
    Mylan's generic fentanyl TD *Patient Application Instructions:
    <http://www.mylanpharms.com/pdfs/Fentanyl_application.pdf>.*