Important Dosage and Administration Instructions

DURAGESIC should be prescribed only by healthcare professionals who are knowledgeable in the use of potent opioids for the management of chronic pain.

Due to the risk of respiratory depression, DURAGESIC is only indicated for use in patients who are already opioid-tolerant. Discontinue or taper all other extended-release opioids when beginning DURAGESIC therapy. As DURAGESIC is only for use in opioid-tolerant patients, do not begin any patient on DURAGESIC as the first opioid [see Indications and Usage (1)].

• Use the lowest effective dosage for the shortest duration consistent with individual patient treatment goals [see Warnings and Precautions (5)].
• Initiate the dosing regimen for each patient individually, taking into account the patient's severity of pain, patient response, prior analgesic treatment experience, and risk factors for addiction, abuse, and misuse [see Warnings and Precautions (5.1)].
• Monitor patients closely for respiratory depression, especially within the first 24–72 hours of initiating therapy with DURAGESIC when serum concentrations from the initial patch will peak [see Warnings and Precautions (5.3)].

Patient Access to Naloxone for the Emergency Treatment of Opioid Overdose

Discuss the availability of naloxone for the emergency treatment of opioid overdose with the patient and caregiver and assess the potential need for access to naloxone, both when initiating and renewing treatment with DURAGESIC [see Warnings and Precautions (5.3), Patient Counseling Information (17)].

Inform patients and caregivers about the various ways to obtain naloxone as permitted by individual state naloxone dispensing and prescribing requirements or guidelines (e.g., by prescription, directly from a pharmacist, or as part of a community-based program).

Consider prescribing naloxone, based on the patient's risk factors for overdose, such as concomitant use of CNS depressants, a history of opioid use disorder, or prior opioid overdose. However, the presence of risk factors for overdose should not prevent the proper management of pain in any given patient [see Warnings and Precautions (5.1, 5.3, 5.8)].

Consider prescribing naloxone if the patient has household members (including children) or other close contacts at risk for accidental exposure or overdose.

Initial Dosage

Do not initiate treatment with DURAGESIC in opioid nontolerant patients [see Contraindications (4)].

The recommended starting dose when converting from other opioids to DURAGESIC is intended to minimize the potential for overdosing patients with the first dose.

Discontinue all other around-the-clock opioid drugs when DURAGESIC therapy is initiated.

While there are useful tables of opioid equivalents readily available, there is substantial inter-patient variability in the relative potency of different opioid drugs and products. As such, it is preferable to underestimate a patient's 24-hour fentanyl requirements and provide rescue medication (e.g., immediate-release opioid) than to overestimate the 24-hour fentanyl requirements which could result in adverse reactions. In a DURAGESIC clinical trial, patients were converted from their prior opioid to DURAGESIC using Table 1 as a guide for the initial DURAGESIC dose.

Each DURAGESIC transdermal system is worn continuously for up to 72 hours [see Dosage and Administration (2.7)].

When converting patients from oral or parenteral opioids to DURAGESIC, use Table 1 (alternatively use Table 2 for adult and pediatric patients taking opioids or doses not listed in Table 1) and consider the following:

• These are not tables of equianalgesic doses.
• The conversion doses in these tables are only for the conversion from one of the listed oral or parenteral opioid analgesics to DURAGESIC.
• The tables cannot be used to convert from DURAGESIC to another opioid because these conversions will result in an overestimation of the dose of the new opioid (these conversions are conservative) and may result in fatal overdosage.

Alternatively, for adult and pediatric patients taking opioids or doses not listed in Table 1, use the following methodology when converting patients from oral or parenteral opioids to DURAGESIC:

1. Calculate the previous 24-hour analgesic requirement.
2. Convert this amount to the equianalgesic oral morphine dose using a reliable reference.
3. Refer to Table 2 for 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 recommended initial DURAGESIC dose.
4. Initiate DURAGESIC treatment using the recommended dose and titrate patients upwards (no more frequently than 3 days after the initial dose and every 6 days thereafter) until analgesic efficacy is attained. A 37.5 mcg/hour dose may also be used. The 37.5 mcg/hour strength is not available as DURAGESIC. It is available as Fentanyl Transdermal System. For patients that require more than 100 mcg/hour, several transdermal systems may be used.
5. Do not use Table 2 to convert from DURAGESIC to other therapies because this conversion to DURAGESIC is conservative and will overestimate the dose of the new agent.

An additional intermediate strength 37.5 mcg/hour DURAGESIC transdermal system is available and may be considered during conversion from prior opioids or dose titration. For example, the 37.5 mcg/hour system could be used before converting or titrating to a 50 mcg/hour system.

The additional 37.5 mcg/hour system was not used in the clinical studies.

For delivery rates in excess of 100 mcg/hour, multiple systems may be used.

Titration and Maintenance of Therapy

Individually titrate DURAGESIC to a dose that provides adequate analgesia and minimizes adverse reactions. Continually reevaluate patients receiving DURAGESIC to assess the maintenance of pain control and the relative incidence of adverse reactions, as well as monitoring for the development of addiction, abuse, or misuse [see Warnings and Precautions (5.1)]. Frequent communication is important among the prescriber, other members of the healthcare team, the patient, and the caregiver/family during periods of changing analgesic requirements, including initial titration. During chronic therapy, periodically reassess the continued need for opioid analgesics.

Patients who experience breakthrough pain may require a dosage adjustment of DURAGESIC, or may need rescue medication with an appropriate dose of an immediate-release analgesic. If the level of pain increases after dosage stabilization, attempt to identify the source of increased pain before increasing the DURAGESIC dosage.

The dosing interval for DURAGESIC is 72 hours. Do not increase the DURAGESIC dose for the first time until at least 3 days after the initial application. Titrate the dose based on the daily dose of supplemental opioid analgesics required by the patient on the second or third day of the initial application.

It may take up to 6 days for fentanyl levels to reach equilibrium on a new dose [see Clinical Pharmacology (12.3)]. Therefore, evaluate patients for further titration after no less than two 3-day applications before any further increase in dosage is made.

Base dosage increments on the daily dosage of supplementary opioids, using the ratio of 45 mg/24 hours of oral morphine to a 12 mcg/hour increase in DURAGESIC dose.

If unacceptable opioid-related adverse reactions are observed, consider reducing the dosage. Adjust the dose to obtain an appropriate balance between management of pain and opioid-related adverse reactions.

A small proportion of adult patients may not achieve adequate analgesia using a 72-hour dosing interval and may require systems to be applied at 48 hours rather than at 72 hours, only if adequate pain control cannot be achieved using a 72-hour regimen. 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.

Dosage Modifications in Patients with Hepatic Impairment

Avoid the use of DURAGESIC in patients with severe hepatic impairment. In patients with mild to moderate hepatic impairment, start with one half of the usual dosage of DURAGESIC. Closely monitor for signs of respiratory and central nervous system depression, including at each dosage increase [see Warnings and Precautions (5.16), Use in Specific Populations (8.6) and Clinical Pharmacology (12.3)].

Dosage Modifications in Patients with Renal Impairment

Avoid the use of DURAGESIC in patients with severe renal impairment. In patients with mild to moderate renal impairment, start with one half of the usual dosage of DURAGESIC. Closely monitor for signs of respiratory and central nervous system depression, including at each dosage increase [see Warnings and Precautions (5.17), Use in Specific Populations (8.7), and Clinical Pharmacology (12.3)].

Administration of DURAGESIC

DURAGESIC PATCHES ARE FOR TRANSDERMAL USE ONLY.

Proper handling of DURAGESIC is necessary in order to prevent serious adverse outcomes, including death, associated with accidental secondary exposure to DURAGESIC [see Warnings and Precautions (5.4)].

Disposal Instructions

Failure to properly dispose of DURAGESIC has resulted in accidental exposures and deaths, including deaths of children [see Warnings and Precautions (5.4)].

Instruct patients to dispose of used patches immediately upon removal by folding the adhesive side of the patch to itself, then flushing down the toilet.

Instruct patients to remove unused patches from their pouches, remove the release liners, fold the patches so that the adhesive side of the patch adheres to itself, and to immediately flush the patches down the toilet.

Instruct patients to dispose of any patches remaining from a prescription as soon as they are no longer needed.

Safe Reduction or Discontinuation of DURAGESIC

Do not abruptly discontinue DURAGESIC in patients who may be physically dependent on opioids. Rapid discontinuation of opioid analgesics in patients who are physically dependent on opioids has resulted in serious withdrawal symptoms, uncontrolled pain, and suicide. Rapid discontinuation has also been associated with attempts to find other sources of opioid analgesics, which may be confused with drug-seeking for abuse. Patients may also attempt to treat their pain or withdrawal symptoms with illicit opioids, such as heroin, and other substances.

When a decision has been made to decrease the dose or discontinue therapy in an opioid-dependent patient taking DURAGESIC, there are a variety of factors that should be considered, including the dose of DURAGESIC the patient has been taking, the duration of treatment, the type of pain being treated, and the physical and psychological attributes of the patient. It is important to ensure ongoing care of the patient and to agree on an appropriate tapering schedule and follow-up plan so that patient and provider goals and expectations are clear and realistic. When opioid analgesics are being discontinued due to a suspected substance use disorder, evaluate and treat the patient, or refer for evaluation and treatment of the substance use disorder. Treatment should include evidence-based approaches, such as medication assisted treatment of opioid use disorder. Complex patients with comorbid pain and substance use disorders may benefit from referral to a specialist.

There are no standard opioid tapering schedules that are suitable for all patients. Good clinical practice dictates a patient-specific plan to taper the dose of the opioid gradually. For patients on DURAGESIC who are physically opioid-dependent, initiate the taper by a small enough increment (e.g., no greater than 25% of the total daily dose) to avoid withdrawal symptoms, and proceed with dose-lowering at an interval of every 2 to 4 weeks. Patients who have been taking opioids for briefer periods of time may tolerate a more rapid taper.

It may be necessary to provide the patient with a lower dosage strength to accomplish a successful taper. Reassess the patient frequently to manage pain and withdrawal symptoms, should they emerge. Common withdrawal symptoms include restlessness, lacrimation, rhinorrhea, yawning, perspiration, chills, myalgia, and mydriasis. Other signs and symptoms also may develop, including irritability, anxiety, backache, joint pain, weakness, abdominal cramps, insomnia, nausea, anorexia, vomiting, diarrhea, or increased blood pressure, respiratory rate, or heart rate. If withdrawal symptoms arise, it may be necessary to pause the taper for a period of time or raise the dose of the opioid analgesic to the previous dose, and then proceed with a slower taper. In addition, monitor patients for any changes in mood, emergence of suicidal thoughts, or use of other substances.

When managing patients taking opioid analgesics, particularly those who have been treated for a long duration and/or with high doses for chronic pain, ensure that a multimodal approach to pain management, including mental health support (if needed), is in place prior to initiating an opioid analgesic taper. A multimodal approach to pain management may optimize the treatment of chronic pain, as well as assist with the successful tapering of the opioid analgesic [see Warnings and Precautions (5.20), Drug Abuse and Dependence (9.3)].