FENTANYL- fentanyl patch, extended release
Actavis Pharma, Inc.
WARNING: ADDICTION, ABUSE, AND MISUSE; LIFE-THREATENING RESPIRATORY DEPRESSION; ACCIDENTAL EXPOSURE; NEONATAL OPIOID WITHDRAWAL SYNDROME; CYTOCHROME P450 3A4 INTERACTION; RISK OF INCREASED FENTANYL ABSORPTION WITH APPLICATION OF EXTERNAL HEAT; and RISKS FROM CONCOMITANT USE WITH BENZODIAZEPINES OR OTHER CNS DEPRESSANTS
Addiction, Abuse, and Misuse
Fentanyl transdermal system exposes patients and other users to the risks of opioid addiction, abuse, and misuse, which can lead to overdose and death. Assess each patient’s risk prior to prescribing fentanyl transdermal system, and monitor all patients regularly for the development of these behaviors and conditions [see Warnings and Precautions ( 5.1 )].
Life-threatening Respiratory Depression
Serious, life-threatening, or fatal respiratory depression may occur with use of fentanyl transdermal system. Monitor for respiratory depression, especially during initiation of fentanyl transdermal system or following a dose increase. Because of the risk of respiratory depression, fentanyl transdermal system is contraindicated for use as an as-needed analgesic, in non-opioid tolerant patients, in acute pain, and in postoperative pain [see Contraindications ( 4 ) and Warnings and Precautions ( 5.2 )].
Accidental exposure to even one dose of fentanyl transdermal system, especially in children, can result in a fatal overdose of fentanyl. Deaths due to an overdose of fentanyl have occurred when children and adults were accidentally exposed to fentanyl transdermal system. Strict adherence to the recommended handling and disposal instructions is of the utmost importance to prevent accidental exposure [see Warnings and Precautions ( 5.3 )].
Neonatal Opioid Withdrawal Syndrome
Prolonged use of fentanyl transdermal system during pregnancy can result in neonatal opioid withdrawal syndrome, which may be life-threatening if not recognized and treated, and requires management according to protocols developed by neonatology experts. If opioid use is required for a prolonged period in a pregnant woman, advise the patient of the risk of neonatal opioid withdrawal syndrome and ensure that appropriate treatment will be available [see Warnings and Precautions ( 5.4 )].
Cytochrome P450 3A4 Interaction
The concomitant use of fentanyl transdermal system with all cytochrome P450 3A4 inhibitors may result in an increase in fentanyl plasma concentrations, which could increase or prolong adverse drug effects and may cause potentially fatal respiratory depression. In addition, discontinuation of a concomitantly used cytochrome P450 3A4 inducer may result in an increase in fentanyl plasma concentration. Monitor patients receiving fentanyl transdermal system and any CYP3A4 inhibitor or inducer [see Warnings and Precautions ( 5.5 ) and Clinical Pharmacology ( 12.3 )].
Risk of Increased Fentanyl Absorption with Application of External Heat
Exposure of the fentanyl transdermal system application site and surrounding area to direct external heat sources, such as heating pads or electric blankets, heat or tanning lamps, sunbathing, hot baths, saunas, hot tubs, and heated water beds may increase fentanyl absorption and has resulted in fatal overdose of fentanyl. Warn patients to avoid exposing the application site and surrounding area to direct external heat sources [see Warnings and Precautions ( 5.6 )].
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 [see Warnings and Precautions ( 5.7 ), Drug Interactions ( 7 )].
- Reserve concomitant prescribing of fentanyl transdermal system and benzodiazepines or other CNS depressants for use in patients for whom alternative treatment options are inadequate.
- Limit treatment to the minimum effective dosages and durations.
- Follow patients for signs and symptoms of respiratory depression and sedation.
Fentanyl transdermal system is indicated for the management of pain in opioid-tolerant patients, severe enough to require daily, around-the-clock, long-term opioid treatment and for which alternative treatment options are inadequate.
Patients considered opioid-tolerant are those who are taking, for one week or longer, at least 60 mg morphine per day, 25 mcg transdermal fentanyl per hour, 30 mg oral oxycodone per day, 8 mg oral hydromorphone per day, 25 mg oral oxymorphone per day, 60 mg oral hydrocodone per day, or an equianalgesic dose of another opioid.
Limitations of Use
● Because of the risks of addiction, abuse, and misuse with opioids, even at recommended doses, and because of the greater risks of overdose and death with extended-release/long-acting opioid formulations [see Warnings and Precautions ( 5.1)] , reserve fentanyl transdermal system for use in patients for whom alternative treatment options (e.g., non-opioid analgesics or immediate-release opioids) are ineffective, not tolerated, or would be otherwise inadequate to provide sufficient management of pain.
● Fentanyl transdermal system is not indicated as an as-needed (prn) analgesic.
Fentanyl transdermal system 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, fentanyl transdermal system is only indicated for use in patients who are already opioid-tolerant. Discontinue or taper all other extended-release opioids when beginning fentanyl transdermal system therapy. As fentanyl transdermal system is only for use in opioid-tolerant patients, do not begin any patient on fentanyl transdermal system 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 to 72 hours of initiating therapy with fentanyl transdermal system when serum concentrations from the initial patch will peak [see Warnings and Precautions ( 5.2)].
Do not initiate treatment with fentanyl transdermal system in opioid nontolerant patients [see Contraindications (4)].
The recommended starting dose when converting from other opioids to fentanyl transdermal system is intended to minimize the potential for overdosing patients with the first dose.
Discontinue all other around-the-clock opioid drugs when fentanyl transdermal system 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 fentanyl transdermal system clinical trial, patients were converted from their prior opioid to fentanyl transdermal system using Table 1 as a guide for the initial fentanyl transdermal system dose.
Each fentanyl transdermal system is worn continuously for up to 72 hours [see Dosage and Administration (2.6)].
When converting patients from oral or parenteral opioids to fentanyl transdermal system, 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 fentanyl transdermal system.
- The tables cannot be used to convert from fentanyl transdermal system 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.
| Current Analgesic|| Daily Dosage (mg/day)|
| Oral morphine|| 60–134|| 135–224|| 225–314|| 315–404|
| Intramuscular orIntravenous morphine|| 10–22|| 23–37|| 38–52|| 53–67|
| Oral oxycodone|| 30–67|| 67.5–112|| 112.5–157|| 157.5–202|
| Oral codeine|| 150–447|||||||
| Oral hydromorphone|| 8–17|| 17.1–28|| 28.1–39|| 39.1–51|
| Intravenous hydromorphone|| 1.5–3.4|| 3.5–5.6|| 5.7–7.9|| 8–10|
| Intramuscular meperidine|| 75–165|| 166–278|| 279–390|| 391–503|
| Oral methadone|| 20–44|| 45–74|| 75–104|| 105–134|
| Recommended FentanylTransdermal System Dose|| 25 mcg/hour|| 50 mcg/hour|| 75 mcg/hour|| 100 mcg/hour|
|1 Table 1 should not be used to convert from fentanyl transdermal system to other therapies because this conversion to fentanyl transdermal system is conservative. Use of Table 1 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 ( 2.8)].|
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 fentanyl transdermal system:
- Calculate the previous 24-hour analgesic requirement.
- Convert this amount to the equianalgesic oral morphine dose using a reliable reference.
- Refer to Table 2 for the range of 24-hour oral morphine doses that are recommended for conversion to each fentanyl transdermal system dose. Use this table to find the calculated 24-hour morphine dose and the corresponding recommended initial fentanyl transdermal system dose.
- Initiate fentanyl transdermal system 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. For patients that require more than 100 mcg/hour, several transdermal systems may be used.
- Do not use Table 2 to convert from fentanyl transdermal system to other therapies because this conversion to fentanyl transdermal system is conservative and will overestimate the dose of the new agent.
| Oral 24-hour Morphine (mg/day)|| Fentanyl Transdermal System Dose (mcg/hour)|
| 60–134|| 25|
| 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|
| NOTE: In clinical trials, these ranges of daily oral morphine doses were used as a basis for conversion to fentanyl transdermal system.|
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