Addiction, Abuse, and Misuse; Life-Threatening Depression; Accidental Exposure; Neonatal Opioid Withdarawal Symdrome; Risk Evaluation and Mitigation Strategy (REMS)

High Concentration of Schedule II opioid agonist

• This product contains a high concentration of a potent Schedule II opioid agonist, fentanyl. Schedule II opioid substances (e.g., 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 may a particular target for abuse and diversion.

Indications

• This product is indicated for the 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 (NSAIDs, opioid combination products, or immediate release opioids).

For Use in Opioid Tolerant Patients Only

• Should ONLY be used inpatients who are already receiving opioid thearpy, who have demonstrated opioid tolerance, and who require a total daily dose at least equivalent to fentanyl (Duragesic) 25 mcg/hr.
• 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.
• Transdermal fentanyl 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.

Dose Conversion

• Overestimating the dose when converting patients from another opioid medication can result in a fatal overdose with the first dose.
• Due to the mean elimination half-life of 17 hrs, patients who are thought to have had a serious adverse event,including overdose, will require monitoring and treatment for at least 24 hours.

Serious or Life Threatening Hypoventilation Risk: Fentanyl Transdermal System Contraindicatons

• 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 of after out-patient or day surgeries
• In the management of mild pain
• In the management of intermittent pain (e.g., use on an as needed basis)

Hypoventilation

• Since peak fentanyl levels occur between 24 and 72 hrs of treatment, life-threatening or serious hypoventilation may occur, even in opioid tolerant patients, during the initial application period.

Interactions: CYP450 3A4 Inhibitors

• The concomitant use of this product with all cytochrome CYP450 3A4 inhibitors (ritonavir, ketoconazole, itraconazole, trolenadomycin, 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 fentanyl transdermal and any CYP34A 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).

Pediatrics

• The safety of this product has not been established in children under 2 yrs of age.
• This product should be administered to children only if they are opioid tolerant and 2 yrs or older. (See PRECAUTIONS-Pediatric Use)

Addiction, Abuse and Misuse Potential

• This product can be abused in a manner similar to other opioid agonists, legal or illicit. This risk should be considered when administering, prescribing, or dispensing in situations where the healthcare professional is concerned about increased risk of misuse, abuse, or diversion.
• Persons at increased risk of opioid abuse include those with a personal or family history of substance abuse or mental illness.
• Patients should be assessed for their clinical risks for opioid abuse or addiction prior to prescribing.
• 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
• Patients at increased risk may be prescribed opioids, but use in such patients necessitates intensive counseling about the risks and proper use along with intensive monitoring for signs of addiction, abuse, and misuse. Consider prescribing naloxone for the emergency treatment of opioid overdose. 

Application, Avoidance of Heat Sources

• These patches are intended for transdermal use (on intact skin) only
• Do not use a patch if the seal is broken or the patch is cut, damaged, or changed in any way.
• Using a patch that is damaged, cut 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 patch 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 fentanyl systems who develop fever or increased core body temperature due to strenuous exertion should be monitored for opioid side effects and the dose should be adjusted if necessary

Risks From Concomitant Use With Benzodiazepines Or Other CNS Depressants 
Concomitant use of opioids with benzodiazepines or other central nervous system (CNS) depressants, including alcohol, may result in profound sedation, respiratory depression, coma, and death 

• Reserve concomitant prescribing of opioids and benzodiazepines or other CNS depressants for use in patients for whom alternative treatment options are inadequate.
• Limit dosages and durations to the minimum required.
• Follow patients for signs and symptoms of respiratory depression and sedation.

Life-Threatening Respiratory Depression

• Opioids can cause sleep-related breathing disorders including central sleep apnea (CSA) and sleep-related hypoxemia. Opioid use increases the risk of CSA in a dose-dependent fashion. In patients who present with CSA, consider decreasing the opioid dosage using best practices for opioid taper.

Opioid Analgesic Risk Evaluation and Mitigation Strategy (REMS)

To ensure that the benefits of opioid analgesics outweigh the risks of addiction, abuse, and misuse, the Food and Drug Administration (FDA) has required a REMS for these products. Under the requirements of the REMS, drug companies with approved opioid analgesic products must make REMS-compliant education programs available to healthcare providers. Healthcare providers are strongly encouraged to:

• complete a REMS-compliant education program,
• counsel patients and/or their caregivers, with every prescription, on safe use, serious risks, storage, and disposal of these products,
• emphasize to patients and their caregivers the importance of reading the Medication Guide every time it is provided by their pharmacist, and
• consider other tools to improve patient, household, and community safety.