Fentanyl (Page 5 of 12)

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 transdermal fentanyl with all CYP3A4 inhibitors (such as ritonavir, ketoconazole, itraconazole, troleandomycin, clarithromycin, nelfinavir, nefazadone, 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 fentanyl transdermal system 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, PRECAUTIONS, and DOSAGE AND ADMINISTRATION for further information).

PRECAUTIONS

General

Fentanyl transdermal system should not be used to initiate opioid therapy in patients who are not opioid-tolerant. Children converting to fentanyl transdermal system should be opioid-tolerant and 2 years of age or older (see BOX WARNING).

Patients, family members, and caregivers should be instructed to keep patches (new and used) out of the reach of children and others for whom fentanyl transdermal system was not prescribed. A considerable amount of active fentanyl remains in fentanyl transdermal system even after use as directed. Accidental or deliberate application or ingestion by a child or adolescent will cause respiratory depression that could result in death.

Cardiac Disease

Fentanyl may produce bradycardia. Fentanyl should be administered with caution to patients with bradyarrhythmias.

Hepatic or Renal Disease

Insufficient information exists to make recommendations regarding the use of fentanyl transdermal system in patients with impaired renal or hepatic function. If the drug is used in these patients, it should be used with caution because of the hepatic metabolism and renal excretion of fentanyl.

Use in Pancreatic/Biliary Tract Disease

Fentanyl transdermal system may cause spasm of the sphincter of Oddi and should be used with caution in patients with biliary tract disease, including acute pancreatitis. Opioids like fentanyl transdermal system may cause increases in the serum amylase concentration.

Tolerance

Tolerance is a state of adaptation in which exposure to a drug induces changes that result in a diminution of one or more of the drug’s effects over time. Tolerance may occur to both the desired and undesired effects of drugs, and may develop at different rates for different effects.

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 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 Fentanyl Transdermal System).

Ambulatory Patients

Strong opioid analgesics impair the mental or physical abilities required for the performance of potentially dangerous tasks, such as driving a car or operating machinery. Patients who have been given fentanyl transdermal system should not drive or operate dangerous machinery unless they are tolerant to the effects of the drug.

Information for Patients

Patients and their caregivers should be provided with a Medication Guide each time fentanyl transdermal system is dispensed because new information may be available.

Patients receiving fentanyl transdermal system patches should be given the following instructions by the physician:

1. Patients should be advised that fentanyl transdermal system patches contain fentanyl, an opioid pain medicine similar to morphine, hydromorphone, methadone, oxycodone, and oxymorphone.
2. Patients should be advised that each fentanyl transdermal system patch may be worn continuously for 72 hours, and that each patch should be applied to a different skin site after removal of the previous transdermal patch.
3. Patients should be advised that fentanyl transdermal system patches should be applied to intact, non-irritated, and non-irradiated skin on a flat surface such as the chest, back, flank, or upper arm. Additionally, patients should be advised of the following:
   • In young children or persons with cognitive impairment, the patch should be put on the upper back to lower the chances that the patch will be removed and placed in the mouth.
   • Hair at the application site should be clipped (not shaved) prior to patch application.
   • If the site of fentanyl transdermal system 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.
4. Patients should be advised that fentanyl transdermal system should be applied immediately upon removal from the sealed pouch and after removal of the protective liner. Additionally the patient should be advised of the following:
   • The fentanyl transdermal system 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 fentanyl transdermal system 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 fentanyl transdermal system application site and surrounding area to direct external heat sources, such as:
   • heating pads,
   • electric blankets,
   • sunbathing,
   • heat or tanning lamps,
   • saunas,
   • hot tubs or hot baths, and
   • heated water beds, etc.
7. Patients should also be advised of a potential for temperature-dependent increases in fentanyl release from the patch that could result in an overdose of fentanyl; therefore, patients who develop a high fever or increased body temperature due to strenuous exertion while wearing the patch should contact their physician.
8. Patients should be advised that if they experience problems with adhesion of the fentanyl transdermal system patch, they may tape the edges of the patch with first aid tape. If problems with adhesion persist, patients may overlay the patch with a transparent adhesive film dressing (e.g., Bioclusive^TM or Tegaderm^TM).
9. Patients should be advised that if the patch falls off before 72 hours a new patch may be applied to a different skin site.
10. Patients should be advised to fold (so that the adhesive side adheres to itself) and immediately flush down the toilet used fentanyl transdermal system patches after removal from the skin.
11. Patients should be advised that fentanyl transdermal system may impair mental and/or physical ability required for the performance of potentially hazardous tasks (e.g., driving, operating machinery).
12. Patients should be advised to refrain from any potentially dangerous activity when starting on fentanyl transdermal system or when their dose is being adjusted, until it is established that they have not been adversely affected.
13. Patients should be advised that fentanyl transdermal system should not be combined with alcohol or other CNS depressants (e.g. sleep medications, tranquilizers) because dangerous additive effects may occur, resulting in serious injury or death.
14. Patients should be advised to consult their physician or pharmacist if other medications are being or will be used with fentanyl transdermal system.
15. Patients should be advised of the potential for severe constipation.
16. Patients should be advised that if they have been receiving treatment with fentanyl transdermal system and cessation of therapy is indicated, it may be appropriate to taper the fentanyl transdermal system dose, rather than abruptly discontinue it, due to the risk of precipitating withdrawal symptoms.
17. Patients should be advised that fentanyl transdermal system contains fentanyl, a drug with high potential for abuse.
18. Patients, family members, and caregivers should be advised to protect fentanyl transdermal system from theft or misuse in the work or home environment.
19. Patients should be instructed to keep fentanyl transdermal system in a secure place out of the reach of children due to the high risk of fatal respiratory depression.
20. Patients should be advised that fentanyl transdermal system should never be given to anyone other than the individual for whom it was prescribed because of the risk of death or other serious medical problems to that person for whom it was not intended.
21. Patients should be informed that, if the patch dislodges and accidentally sticks to the skin of another person, they should immediately take the patch off, wash the exposed area with water and seek medical attention for the accidentally exposed individual.
22. When fentanyl transdermal system is no longer needed, the 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.
23. Women of childbearing potential who become, or are planning to become pregnant, should be advised to consult a physician prior to initiating or continuing therapy with fentanyl transdermal system.
24. Patients should be informed that accidental exposure or misuse may lead to death or other serious medical problems.