Fentanyl system
Fentanyl · Patch · Transdermal
Uses
Fentanyl transdermal system is indicated for the management of severe and persistent pain in opioid-tolerant patients, that requires an opioid analgesic and that cannot be adequately treated with alternative options, including immediate-release opioids. 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, misuse, overdose, and death, which can occur at any dosage or duration and persist over the course of therapy [see Warnings and Precautions ( 5.1 ) ], reserve opioid analgesics, including fentanyl transdermal system, for use in patients for whom alternative treatment options 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, an opioid agonist, is indicated for the management of severe and persistent pain in opioid-tolerant patients that requires an opioid analgesic and that cannot be adequately treated with alternative options, including immediate-release opioids. (1) Patients considered opioid-tolerant are those taking, for one week or longer, at least 60 mg oral 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. ( 2.1 ) Limitations of use: Because of the risks of addiction, abuse, misuse, overdose, and death, which can occur at any dosage or duration and persist over the course of therapy, reserve opioid analgesics, including fentanyl transdermal system, for use in patients for whom alternative treatment options are ineffective, not tolerated, or would be otherwise inadequate to provide sufficient management of pain. (1, 5.1) Fentanyl transdermal system is not indicated as an as-needed (prn) analgesic. (1)
Dosage and administration
Fentanyl transdermal system should be prescribed only by healthcare providers who are knowledgeable about the use of extended-release/long-acting opioids and how to mitigate the associated risks. ( 2.1 ) Use the lowest effective dosage for the shortest duration of time consistent with individual patient treatment goals. Reserve titration to higher doses of fentanyl transdermal system for patients in whom lower doses are insufficiently effective and in whom the expected benefits of using a higher dose opioid clearly outweigh the substantial risks. ( 2.1 , 5 ) Initiate the dosing regimen for each patient individually, taking into account the patient's underlying cause and severity of pain, prior analgesic treatment and response, and risk factors for addiction, abuse, and misuse. ( 5.1 ) Respiratory depression can occur at any time during opioid therapy, especially when initiating and following dosage increases with fentanyl transdermal system. Consider this risk when selecting an initial dose and when making dose adjustments. ( 2.1 , 5.2 ) Discuss opioid overdose reversal agents and options for acquiring them with the patient and/or caregiver, both when initiating and renewing treatment with fentanyl transdermal system, especially if the patient has additional risk factors for overdose, or close contacts at risk for exposure and overdose. ( 2.2 , 5.1 , 5.2 , 5.4 ) Initial dose selection: consult conversion instructions. ( 2.3 ) Periodically reassess patients receiving fentanyl transdermal system to evaluate the continued need for opioid analgesics to maintain pain control, for the signs or symptoms of adverse reactions, and for the development of addiction, abuse, or misuse ( 2.4 ) Each transdermal system is intended to be worn continuously for up to 72 hours. ( 2.3 , 2.7) Adhere to instructions concerning administration and disposal of fentanyl transdermal system. ( 2.7 , 2.8 ) Mild to moderate hepatic and renal impairment: Initiate treatment with one half the usual starting dose, titrate slowly, and regularly evaluate for signs of respiratory and central nervous system depression. ( 2.5 , 2.6 ) Do not rapidly reduce or discontinue fentanyl transdermal system in a physically-dependent patient because rapid reduction or abrupt discontinuation of opioid analgesics has resulted in serious withdrawal symptoms, uncontrolled pain, and suicide. ( 2.9 , 5.21 ) 2.1 Important Dosage and Administration Instructions Fentanyl transdermal system should be prescribed only by healthcare professionals who are knowledgeable about the use of extended-release/long-acting opioids and how to mitigate the associated risks. 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 of time consistent with individual patient treatment goals [see Warnings and Precautions ( 5 )] . Because the risk of overdose increases as opioid doses increase, reserve titration to higher doses of fentanyl transdermal system for patients in whom lower doses are insufficiently effective and in whom the expected benefits of using a higher dose opioid clearly outweigh the substantial risks. Initiate the dosing regimen for each patient individually, taking into account the patient's underlying cause and severity of pain, prior analgesic treatment and response, and risk factors for addiction, abuse, and misuse [see Warnings and Precautions ( 5.1 )] . Respiratory depression can occur at any time during opioid therapy, especially when initiating and following dosage increases with fentanyl transdermal system. Consider this risk when selecting an initial dose and when making dose adjustments [see Warnings and Precautions ( 5 )] . Each fentanyl transdermal system is worn continuously for up to 72 hours [see Dosage and Administration (2.7)] . 2.2 Patient Access to an Opioid Overdose Reversal Agent for the Emergency Treatment of Opioid Overdose Inform patients and caregivers about opioid overdose reversal agents (e.g. naloxone, nalmefene). Discuss the importance of having access to an opioid overdose reversal agent, especially if the patient has risk factors for overdose (e.g. concomitant use of CNS depressants, a history of opioid use disorder, or prior opioid overdose) or if there are household members (including children) or other close contacts at risk for accidental ingestion or opioid overdose. The presence of risk factors for overdose should not prevent the management of pain in any patient [see Warnings and Precautions ( 5.1 , 5.2, 5.4) ]. Discuss the options for obtaining an opioid overdose reversal agent (e.g. prescription, over-the-counter, or as part of a community-based program) [see Warnings and Precautions (5.2)]. There are important differences among the opioid overdose reversal agents, such as route of administration, product strength, approved patient age range, and pharmacokinetics. Be familiar with these differences, as outlined in the approved labeling for those products, prior to recommending or prescribing such an agent. 2.3 Initial Dosage It is safer to underestimate a patient's 24-hour fentanyl dosage and provide rescue medication (e.g. immediate-release opioid) than to overestimate the 24-hour fentanyl dosage and manage an adverse reaction to an overdose. While useful tables of opioid equivalents are readily available, there is inter-patient variability in the potency of opioid drugs and opioid formulations. Frequently reevaluate patients for signs and symptoms of opioid withdrawal and for signs of oversedation/toxicity after converting patients to fentanyl transdermal system.
Dosage forms and strengths
Transdermal system: Fentanyl Transdermal System 12 mcg/hour* Transdermal System (system size 4.72 cm 2 ) Fentanyl Transdermal System 25 mcg/hour Transdermal System (system size 9.44 cm 2 ) Fentanyl Transdermal System 50 mcg/hour Transdermal System (system size 18.88 cm 2 ) Fentanyl Transdermal System 75 mcg/hour Transdermal System (system size 28.32 cm 2 ) Fentanyl Transdermal System 100 mcg/hour Transdermal System (system size 37.76 cm 2 ) This lowest strength is designated as 12 mcg/hour (however, the actual strength is 12.5 mcg/hour) to distinguish it from a possible 125 mcg/hour dosage that could be prescribed by using multiple transdermal systems. Transdermal system : 12 mcg/hour, 25 mcg/hour, 50 mcg/hour, 75 mcg/hour, 100 mcg/hour. ( 3 )
Contraindications
Fentanyl transdermal system is contraindicated in: patients who are not opioid-tolerant. the management of acute or intermittent pain, or in patients who require opioid analgesia for a short period of time. the management of post-operative pain, including use after outpatient or day surgeries, (e.g., tonsillectomies). the management of mild pain. patients with significant respiratory depression [see Warnings and Precautions ( 5.12 ) ]. patients with acute or severe bronchial asthma in an unmonitored setting or in the absence of resuscitative equipment [see Warnings and Precautions ( 5.12 ) ]. patients with known or suspected gastrointestinal obstruction, including paralytic ileus [see Warnings and Precautions ( 5.19 ) ]. patients with hypersensitivity to fentanyl (e.g., anaphylaxis) or any components of the transdermal system [see Adverse Reactions ( 6.2 ) ]. Opioid non-tolerant patients. ( 4 ) Acute or intermittent pain, postoperative pain, mild pain. ( 4 ) Significant respiratory depression. ( 4 ) Acute or severe bronchial asthma in an unmonitored setting or in absence of resuscitative equipment. ( 4 ) Known or suspected gastrointestinal obstruction, including paralytic ileus. ( 4 ) Known hypersensitivity to fentanyl or any of the components of the transdermal system. ( 4 )
Warnings and precautions
5 WARNINGS AND PRECAUTIONS . Risk of Increased Fentanyl Absorption with Elevated Body Temperature : Regularly evaluate patients with fever closely for sedation and respiratory depression and reduce the dose if necessary. Warn patients to avoid strenuous exertion that may lead to increased body temperature. ( 5.9 ) Opioid Induced Hyperalgesia (OIH) and Allodynia : Opioid-Induced Hyperalgesia (OIH) occurs when an opioid analgesic paradoxically causes an increase in pain, or an increase in sensitivity to pain. If OIH is suspected, carefully consider appropriately decreasing the dose of the current opioid analgesic, or opioid rotation. ( 5.10 ) Serotonin Syndrome with Concomitant Use of Serotonergic Drugs : Potentially life-threatening condition could result from concomitant serotonergic drug administration. Discontinue fentanyl transdermal system immediately if serotonin syndrome is suspected. ( 5.11 ) Life-Threatening Respiratory Depression in Patients with Chronic Pulmonary Disease or in Elderly, Cachectic, or Debilitated Patients : Regularly evaluate closely, particularly during initiation and titration. ( 5.12 ) Adrenal Insufficiency : If diagnosed, treat with physiologic replacement of corticosteroids, and wean patient off of the opioid. ( 5.13 ) Severe Hypotension : Regularly evaluate during dose initiation and titration. Avoid the use of fentanyl transdermal system in patients with circulatory shock. ( 5.14 ) Risks of Use in Patients with Increased Intracranial Pressure, Brain Tumors, Head Injury or Impaired Consciousness : Monitor for sedation and respiratory depression. Avoid use of fentanyl transdermal system in patients with impaired consciousness or coma. ( 5.15 ) 5.1 Addiction, Abuse, and Misuse Fentanyl transdermal system contains fentanyl, an opioid agonist and a Schedule II controlled substance. As an opioid, fentanyl transdermal system exposes users to the risks of addiction, abuse, and misuse. Although the risk of addiction in any individual is unknown, it can occur in patients appropriately prescribed fentanyl transdermal system. Addiction can occur at recommended doses and if the drug is misused or abused. The risk of opioid-related overdose or overdose-related death is increased with higher opioid doses, and this risk persists over the course of therapy. In postmarketing studies, addiction, abuse, misuse, and fatal and non-fatal opioid overdose were observed in patients with long-term opioid use [see Adverse Reactions (6.2)]. Assess each patient's risk for opioid addiction, abuse, or misuse prior to prescribing fentanyl transdermal system, and reassess all patients receiving fentanyl transdermal system for the development of these behaviors and conditions. Risks are increased in patients with a personal or family history of substance abuse (including drug or alcohol abuse or addiction) or mental illness (e.g., major depression). The potential for these risks should not, however, prevent the proper management of pain in any given patient. Patients at increased risk may be prescribed opioids such as fentanyl transdermal system, but use in such patients necessitates intensive counseling about the risks and proper use of fentanyl transdermal system along with frequent reevaluation for signs of addiction, abuse, and misuse. Consider recommending or prescribing an opioid overdose reversal agent [see Dosage and Administration ( 2.2 ), Warnings and Precautions ( 5.2 ) ]. Abuse or misuse of fentanyl transdermal system by placing it in the mouth, chewing it, swallowing it, or using it in ways other than indicated may cause choking, overdose, and death [see Overdosage ( 10 ) ]. Opioids are sought for nonmedical use and are subject to diversion from legitimate prescribed use. Consider these risks when prescribing or dispensing fentanyl transdermal system. Strategies to reduce these risks include prescribing the drug in the smallest appropriate quantity and advising the patient on careful storage of the drug during the course of treatment and the proper disposal of unused drug. Contact local state professional licensing board or state-controlled substances authority for information on how to prevent and detect abuse or diversion of this product. 5.2 Life-Threatening Respiratory Depression Serious, life-threatening, or fatal respiratory depression has been reported with the use of opioids, even when used as recommended. Respiratory depression, if not immediately recognized and treated, may lead to respiratory arrest and death. Management of respiratory depression may include close observation, supportive measures, and use of opioid overdose reversal agents, depending on the patient's clinical status [see Overdosage ( 10 ) ]. Carbon dioxide (CO 2 ) retention from opioid-induced respiratory depression can exacerbate the sedating effects of opioids. Fentanyl transdermal system is indicated only in opioid tolerant patients because of the risk for respiratory depression and death. While serious, life-threatening, or fatal respiratory depression can occur at any time during the use of fentanyl transdermal system, the risk is greatest during the initiation of therapy or following a dosage increase. To reduce the risk of respiratory depression, proper dosing and titration of fentanyl transdermal system are essential [see Dosage and Administration ( 2 ) ]. Overestimating the fentanyl transdermal system dosage when converting patients from another opioid product can result in fatal overdose with the first dose. Accidental exposure to fentanyl transdermal system, especially in children, can result in respiratory depression and death due to an overdose of fentanyl. Educate patients and caregivers on how to recognize respiratory depression and emphasize the importance of calling 911 or getting emergency medical help right away in the event of a known or suspected overdose [see Patient Counseling Information ( 17 ) ].
Side effects
The following serious adverse reactions are discussed elsewhere in the labeling: Addiction, Abuse, and Misuse [see Warnings and Precautions ( 5.1 )] Life-Threatening Respiratory Depression [see Warnings and Precautions ( 5.2 )] Accidental Exposure [see Warnings and Precautions ( 5.3 )] Interactions with Benzodiazepines or Other Central Nervous System Depressants [see Warnings and Precautions ( 5.4 )] Neonatal Opioid Withdrawal Syndrome [see Warnings and Precautions ( 5.5 )] Opioid-Induced Hyperalgesia and Allodynia [see Warnings and Precautions ( 5.10 )] Serotonin Syndrome [see Warnings and Precautions ( 5.11 )] Adrenal Insufficiency [see Warnings and Precautions ( 5.13 )] Severe Hypotension [see Warnings and Precautions ( 5.14 )] Gastrointestinal Adverse Reactions [see Warnings and Precautions ( 5.19 )] Seizures [see Warnings and Precautions ( 5.20 )] Withdrawal [see Warnings and Precautions ( 5.21 )] Most common adverse reactions (≥5%) are nausea, vomiting, somnolence, dizziness, insomnia, constipation, hyperhidrosis, fatigue, feeling cold, anorexia, headache, and diarrhea. ( 6 ) To report SUSPECTED ADVERSE REACTIONS, call Alvogen, Inc. at 1-866-770-3024 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 6.1 Clinical Trial Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in clinical practice. The safety of fentanyl transdermal system was evaluated in 216 patients who took at least one dose of fentanyl transdermal system in a multicenter, double-blind, randomized, placebo-controlled clinical trial of fentanyl transdermal system. This trial examined patients over 40 years of age with severe pain induced by osteoarthritis of the hip or knee and who were in need of and waiting for joint replacement. The most common adverse reactions (≥5%) in a double-blind, randomized, placebo-controlled clinical trial in patients with severe pain were nausea, vomiting, somnolence, dizziness, insomnia, constipation, hyperhidrosis, fatigue, feeling cold, and anorexia. Other common adverse reactions (≥5%) reported in clinical trials in patients with chronic malignant or nonmalignant pain were headache and diarrhea. Adverse reactions reported for ≥1% of fentanyl transdermal system-treated patients and with an incidence greater than placebo-treated patients are shown in Table 3 . The most common adverse reactions that were associated with discontinuation in patients with pain (causing discontinuation in ≥1% of patients) were depression, dizziness, somnolence, headache, nausea, vomiting, constipation, hyperhidrosis, and fatigue. Table 3: Adverse Reactions Reported by ≥1% of Fentanyl Transdermal System-Treated Patients and With an Incidence Greater Than Placebo-Treated Patients in 1 Double-Blind, Placebo-Controlled Clinical Trial of Fentanyl Transdermal System System/Organ Class Adverse Reaction Fentanyl Transdermal System % (N=216) Placebo % (N=200) Cardiac disorders Palpitations 4 1 Ear and labyrinth disorders Vertigo 2 1 Gastrointestinal disorders Nausea 41 17 Vomiting 26 3 Constipation 9 1 Abdominal pain upper 3 2 Dry mouth 2 0 General disorders and administration site conditions Fatigue 6 3 Feeling cold 6 2 Malaise 4 1 Asthenia 2 0 Edema peripheral 1 1 Metabolism and nutrition disorders Anorexia 5 0 Musculoskeletal and connective tissue disorders Muscle spasms 4 2 Nervous system disorders Somnolence 19 3 Dizziness 10 4 Psychiatric disorders Insomnia 10 7 Depression 1 0 Skin and subcutaneous tissue disorders Hyperhidrosis 6 1 Pruritus 3 2 Rash 2 1 Adverse reactions not reported in Table 3 that were reported by ≥1% of fentanyl transdermal system-treated adult and pediatric patients (N=1854) in 11 controlled and uncontrolled clinical trials of fentanyl transdermal system used for the treatment of chronic malignant or nonmalignant pain are shown in Table 4 . Table 4: Adverse Reactions Reported by ≥1% of Fentanyl Transdermal System-Treated Patients in 11 Clinical Trials of Fentanyl Transdermal System System/Organ Class Adverse Reaction Fentanyl Transdermal System % (N=1854) Gastrointestinal disorders Diarrhea 10 Abdominal pain 3 Immune system disorders Hypersensitivity 1 Nervous system disorders Headache 12 Tremor 3 Paresthesia 2 Psychiatric disorders Anxiety 3 Confusional state 2 Hallucination 1 Renal and urinary disorders Urinary retention 1 Skin and subcutaneous tissue disorders Erythema 1 The following adverse reactions occurred in adult and pediatric patients with an overall frequency of <1% and are listed in descending frequency within each System/Organ Class: Cardiac disorders : cyanosis Eye disorders : miosis Gastrointestinal disorders : subileus General disorders and administration site conditions : application site reaction, influenza-like illness, application site hypersensitivity, drug withdrawal syndrome, application site dermatitis Musculoskeletal and connective tissue disorders : muscle twitching Nervous system disorders : hypoesthesia Psychiatric disorders : disorientation, euphoric mood Reproductive system and breast disorders : erectile dysfunction, sexual dysfunction Respiratory, thoracic and mediastinal disorders : respiratory depression Skin and subcutaneous tissue disorders : eczema, dermatitis allergic, dermatitis contact Pediatrics The safety of fentanyl transdermal system was evaluated in three open-label trials in 289 pediatric patients with chronic pain, 2 years of age through 18 years of age. Adverse reactions reported by ≥1% of fentanyl transdermal system-treated pediatric patients are shown in Table 5 .
Drug interactions
Table 6 includes clinically significant drug interactions with fentanyl transdermal system. Table 6: Clinically Significant Drug Interactions with Fentanyl Transdermal System Inhibitors of CYP3A4 Clinical Impact: The concomitant use of fentanyl transdermal system and CYP3A4 inhibitors can increase the plasma concentration of fentanyl, resulting in increased or prolonged opioid effects particularly when an inhibitor is added after a stable dose of fentanyl transdermal system is achieved [see Warnings and Precautions ( 5.7 ) ]. After stopping a CYP3A4 inhibitor, as the effects of the inhibitor decline, the fentanyl transdermal system plasma concentration will decrease [see Clinical Pharmacology ( 12.3 ) ], resulting in decreased opioid efficacy or a withdrawal syndrome in patients who had developed physical dependence to fentanyl. Intervention: If concomitant use is necessary, consider dosage reduction of fentanyl transdermal system until stable drug effects are achieved. Evaluate patients at frequent intervals for respiratory depression and sedation. If a CYP3A4 inhibitor is discontinued, consider increasing the fentanyl transdermal system dosage until stable drug effects are achieved. Evaluate for signs of opioid withdrawal. Examples: Macrolide antibiotics (e.g., erythromycin), azole-antifungal agents (e.g. ketoconazole), protease inhibitors (e.g., ritonavir), grapefruit juice. CYP3A4 Inducers Clinical Impact: The concomitant use of fentanyl transdermal system and CYP3A4 inducers can decrease the plasma concentration of fentanyl [see Clinical Pharmacology ( 12.3 ) ], resulting in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence to fentanyl [see Warnings and Precautions ( 5.7 ) ]. After stopping a CYP3A4 inducer, as the effects of the inducer decline, the fentanyl plasma concentration will increase [see Clinical Pharmacology ( 12.3 )] , which could increase or prolong both the therapeutic effects and adverse reactions, and may cause serious respiratory depression. Intervention: If concomitant use is necessary, consider increasing the fentanyl transdermal system dosage until stable drug effects are achieved. Evaluate for signs of opioid withdrawal. If a CYP3A4 inducer is discontinued, consider fentanyl transdermal system dosage reduction and evaluate patients at frequent intervals for signs of respiratory depression and sedation. Examples: Rifampin, carbamazepine, phenytoin Benzodiazepines and Other Central Nervous System (CNS) Depressants Clinical Impact: Due to additive pharmacologic effect, the concomitant use of benzodiazepines or other CNS depressants, including alcohol, can increase the risk of hypotension, respiratory depression, profound sedation, coma, and death. Intervention: Reserve concomitant prescribing of these drugs for use in patients for whom alternative treatment options are inadequate. Limit dosages and durations to the minimum required. Inform patients and caregivers of this potential interaction, educate them on the signs and symptoms of respiratory depression (including sedation). If concomitant use is warranted, consider recommending or prescribing an opioid overdose reversal agent [see Dosage and Administration ( 2.2 ), Warnings and Precautions ( 5.1 , 5.2 , 5.4 )] . Examples: Benzodiazepines and other sedatives/hypnotics, anxiolytics, tranquilizers, muscle relaxants, general anesthetics, antipsychotics, gabapentinoids (gabapentin or pregabalin), other opioids, alcohol. Serotonergic Drugs Clinical Impact: The concomitant use of opioids with other drugs that affect the serotonergic neurotransmitter system has resulted in serotonin syndrome [see Warnings and Precautions ( 5.11 ) ]. Intervention: If concomitant use is warranted, frequently evaluate the patient, particularly during treatment initiation and dose adjustment. Discontinue fentanyl transdermal system immediately if serotonin syndrome is suspected. Examples: Selective serotonin reuptake inhibitors (SSRIs), serotonin and norepinephrine reuptake inhibitors (SNRIs), tricyclic antidepressants (TCAs), triptans, 5-HT3 receptor antagonists, drugs that affect the serotonin neurotransmitter system (e.g., mirtazapine, trazodone, tramadol), certain muscle relaxants (i.e., cyclobenzaprine, metaxalone), monoamine oxidase (MAO) inhibitors (those intended to treat psychiatric disorders and also others, such as linezolid and intravenous methylene blue). Monoamine Oxidase Inhibitors (MAOIs) Clinical Impact: MAOI interactions with opioids may manifest as serotonin syndrome [see Warnings and Precautions ( 5.11 ) ] or opioid toxicity (e.g., respiratory depression, coma). Intervention: The use of fentanyl transdermal system is not recommended for patients taking MAOIs or within 14 days of stopping such treatment. Examples: phenelzine, tranylcypromine, linezolid Mixed Agonist/Antagonist and Partial Agonist Opioid Analgesics Clinical Impact: May reduce the analgesic effect of fentanyl transdermal system and/or precipitate withdrawal symptoms. Intervention: Avoid concomitant use. Examples: butorphanol, nalbuphine, pentazocine, buprenorphine Muscle Relaxants Clinical Impact: Fentanyl transdermal system may enhance the neuromuscular blocking action of skeletal muscle relaxants and produce an increased degree of respiratory depression. Intervention: Because respiratory depression may be greater than otherwise expected, decrease the dosage of fentanyl transdermal system and/or the muscle relaxant as necessary. Due to the risk of respiratory depression with concomitant use of skeletal muscle relaxants and opioids, consider prescribing an opioid overdose reversal agent [see Dosage and Administration ( 2.2 ), Warnings and Precautions ( 5.2 , 5.4 )] . Examples: cyclobenzaprine, metaxalone Diuretics Clinical Impact: Opioids can reduce the efficacy of diuretics by inducing the release of antidiuretic hormone.
Use in specific populations
8 USE IN SPECIFIC POPULATIONS . Pregnancy : May cause fetal harm. ( 8.1 ) Lactation : Not recommended. ( 8.2 ) Severe Hepatic and Renal Impairment : Use not recommended. ( 8.6 , 8.7 ) 8.1 Pregnancy . Risk Summary Use of opioid analgesics for an extended period of time during pregnancy may cause neonatal opioid withdrawal syndrome [see Warnings and Precautions ( 5.5 ) ]. Available data with fentanyl transdermal system in pregnant women are insufficient to inform a drug-associated risk for major birth defects and miscarriage. In animal reproduction studies, fentanyl administration to pregnant rats during organogenesis was embryocidal at doses within the range of the human recommended dosing. When administered during gestation through lactation fentanyl administration to pregnant rats resulted in reduced pup survival and developmental delays at doses within the range of the human recommended dosing. No evidence of malformations were noted in animal studies completed to date [see Data ]. The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2-4% and 15-20%, respectively. Clinical Considerations Fetal/Neonatal Adverse Reactions Use of opioid analgesics for an extended period of time during pregnancy for medical or nonmedical purposes can result in physical dependence in the neonate and neonatal opioid withdrawal syndrome shortly after birth. Neonatal opioid withdrawal syndrome presents as irritability, hyperactivity and abnormal sleep pattern, high pitched cry, tremor, vomiting, diarrhea, and failure to gain weight. The onset, duration, and severity of neonatal opioid withdrawal syndrome vary based on the specific opioid used, duration of use, timing and amount of last maternal use, and rate of elimination of the drug by the newborn. Observe newborns for symptoms of neonatal opioid withdrawal syndrome and manage accordingly [see Warnings and Precautions ( 5.5 ) ]. Labor or Delivery Opioids cross the placenta and may produce respiratory depression and psycho-physiologic effects in neonates. An opioid overdose reversal agent, such as naloxone or nalmefene, must be available for reversal of opioid-induced respiratory depression in the neonate. Fentanyl transdermal system is not recommended for use in pregnant women during or immediately prior to labor, when use of shorter-acting analgesics or other analgesic techniques are more appropriate. Opioid analgesics, including fentanyl transdermal system, can prolong labor through actions that temporarily reduce the strength, duration, and frequency of uterine contractions. However, this effect is not consistent and may be offset by an increased rate of cervical dilatation, which tends to shorten labor. Monitor neonates exposed to opioid analgesics during labor for signs of excess sedation and respiratory depression. Data Human Data There are no adequate and well-controlled studies in pregnant women. Fentanyl transdermal system should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. Chronic maternal treatment with fentanyl during pregnancy has been associated with transient respiratory depression, behavioral changes, or seizures characteristic of neonatal abstinence syndrome in newborn infants. Symptoms of neonatal respiratory or neurological depression were no more frequent than expected in most studies of infants born to women treated acutely during labor with intravenous or epidural fentanyl. Transient neonatal muscular rigidity has been observed in infants whose mothers were treated with intravenous fentanyl. Animal Data No evidence of malformations or adverse effects on the fetus was reported in a published study in which pregnant rats were administered fentanyl continuously via subcutaneously implanted osmotic minipumps at doses of 10, 100, or 500 mcg/kg/day starting 2-weeks prior to breeding and throughout pregnancy. The high dose was approximately 2 times the daily human dose administered by a 100 mcg/h patch on a mg/m 2 basis). In contrast, the intravenous administration of fentanyl (0, 0.01, or 0.03 mg/kg) to pregnant rats from Gestation Day 6 to 18 suggested evidence of embryo-toxicity and a slight increase in mean delivery time in the 0.03 mg/kg/day group (0.1 times the human dose administered by a 100 mcg/h patch on a mg/m 2 basis). There was no clear evidence of teratogenicity noted. Pregnant female New Zealand White rabbits were treated with fentanyl (0, 0.025, 0.1, 0.4 mg/kg) via intravenous infusion from day 6 to day 18 of pregnancy. Fentanyl produced a slight decrease in the body weight of the live fetuses at the high dose, which may be attributed to maternal toxicity. Under the conditions of the assay, there was no evidence for fentanyl induced adverse effects on embryo-fetal development at doses up to 0.4 mg/kg (approximately 3 times the daily human dose administered by a 100 mcg/hour patch on a mg/m 2 basis). The potential effects of fentanyl on prenatal and postnatal development were examined in the rat model. Female Wistar rats were treated with 0, 0.025, 0.1, or 0.4 mg/kg/day fentanyl via intravenous infusion from Day 6 of pregnancy through 3 weeks of lactation. Fentanyl treatment (0.4 mg/kg/day) significantly decreased body weight in male and female pups and also decreased survival in pups at Day 4. Both the mid-dose and high-dose of fentanyl animals demonstrated alterations in some physical landmarks of development (delayed incisor eruption and eye opening) and transient behavioral development (decreased locomotor activity at Day 28 which recovered by Day 50). The mid-dose and the high-dose are 0.4 and 1.6 times the daily human dose administered by a 100 mcg/hour patch on a mg/m 2 basis.
Pregnancy
8.1 Pregnancy . Risk Summary Use of opioid analgesics for an extended period of time during pregnancy may cause neonatal opioid withdrawal syndrome [see Warnings and Precautions ( 5.5 ) ]. Available data with fentanyl transdermal system in pregnant women are insufficient to inform a drug-associated risk for major birth defects and miscarriage. In animal reproduction studies, fentanyl administration to pregnant rats during organogenesis was embryocidal at doses within the range of the human recommended dosing. When administered during gestation through lactation fentanyl administration to pregnant rats resulted in reduced pup survival and developmental delays at doses within the range of the human recommended dosing. No evidence of malformations were noted in animal studies completed to date [see Data ]. The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2-4% and 15-20%, respectively. Clinical Considerations Fetal/Neonatal Adverse Reactions Use of opioid analgesics for an extended period of time during pregnancy for medical or nonmedical purposes can result in physical dependence in the neonate and neonatal opioid withdrawal syndrome shortly after birth. Neonatal opioid withdrawal syndrome presents as irritability, hyperactivity and abnormal sleep pattern, high pitched cry, tremor, vomiting, diarrhea, and failure to gain weight. The onset, duration, and severity of neonatal opioid withdrawal syndrome vary based on the specific opioid used, duration of use, timing and amount of last maternal use, and rate of elimination of the drug by the newborn. Observe newborns for symptoms of neonatal opioid withdrawal syndrome and manage accordingly [see Warnings and Precautions ( 5.5 ) ]. Labor or Delivery Opioids cross the placenta and may produce respiratory depression and psycho-physiologic effects in neonates. An opioid overdose reversal agent, such as naloxone or nalmefene, must be available for reversal of opioid-induced respiratory depression in the neonate. Fentanyl transdermal system is not recommended for use in pregnant women during or immediately prior to labor, when use of shorter-acting analgesics or other analgesic techniques are more appropriate. Opioid analgesics, including fentanyl transdermal system, can prolong labor through actions that temporarily reduce the strength, duration, and frequency of uterine contractions. However, this effect is not consistent and may be offset by an increased rate of cervical dilatation, which tends to shorten labor. Monitor neonates exposed to opioid analgesics during labor for signs of excess sedation and respiratory depression. Data Human Data There are no adequate and well-controlled studies in pregnant women. Fentanyl transdermal system should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. Chronic maternal treatment with fentanyl during pregnancy has been associated with transient respiratory depression, behavioral changes, or seizures characteristic of neonatal abstinence syndrome in newborn infants. Symptoms of neonatal respiratory or neurological depression were no more frequent than expected in most studies of infants born to women treated acutely during labor with intravenous or epidural fentanyl. Transient neonatal muscular rigidity has been observed in infants whose mothers were treated with intravenous fentanyl. Animal Data No evidence of malformations or adverse effects on the fetus was reported in a published study in which pregnant rats were administered fentanyl continuously via subcutaneously implanted osmotic minipumps at doses of 10, 100, or 500 mcg/kg/day starting 2-weeks prior to breeding and throughout pregnancy. The high dose was approximately 2 times the daily human dose administered by a 100 mcg/h patch on a mg/m 2 basis). In contrast, the intravenous administration of fentanyl (0, 0.01, or 0.03 mg/kg) to pregnant rats from Gestation Day 6 to 18 suggested evidence of embryo-toxicity and a slight increase in mean delivery time in the 0.03 mg/kg/day group (0.1 times the human dose administered by a 100 mcg/h patch on a mg/m 2 basis). There was no clear evidence of teratogenicity noted. Pregnant female New Zealand White rabbits were treated with fentanyl (0, 0.025, 0.1, 0.4 mg/kg) via intravenous infusion from day 6 to day 18 of pregnancy. Fentanyl produced a slight decrease in the body weight of the live fetuses at the high dose, which may be attributed to maternal toxicity. Under the conditions of the assay, there was no evidence for fentanyl induced adverse effects on embryo-fetal development at doses up to 0.4 mg/kg (approximately 3 times the daily human dose administered by a 100 mcg/hour patch on a mg/m 2 basis). The potential effects of fentanyl on prenatal and postnatal development were examined in the rat model. Female Wistar rats were treated with 0, 0.025, 0.1, or 0.4 mg/kg/day fentanyl via intravenous infusion from Day 6 of pregnancy through 3 weeks of lactation. Fentanyl treatment (0.4 mg/kg/day) significantly decreased body weight in male and female pups and also decreased survival in pups at Day 4. Both the mid-dose and high-dose of fentanyl animals demonstrated alterations in some physical landmarks of development (delayed incisor eruption and eye opening) and transient behavioral development (decreased locomotor activity at Day 28 which recovered by Day 50). The mid-dose and the high-dose are 0.4 and 1.6 times the daily human dose administered by a 100 mcg/hour patch on a mg/m 2 basis.
Pediatric use
8.4 Pediatric Use The safety of fentanyl transdermal system was evaluated in three open-label trials in 289 pediatric patients with chronic pain, 2 years of age through 18 years of age. Starting doses of 25 mcg/h and higher were used by 181 patients who had been on prior daily opioid doses of at least 45 mg/day of oral morphine or an equianalgesic dose of another opioid. Initiation of fentanyl transdermal system therapy in pediatric patients taking less than 60 mg/day of oral morphine or an equianalgesic dose of another opioid has not been evaluated in controlled clinical trials. The safety and effectiveness of fentanyl transdermal system in children under 2 years of age have not been established. To guard against excessive exposure to fentanyl transdermal system by young children, advise caregivers to strictly adhere to recommended fentanyl transdermal system application and disposal instructions [see Dosage and Administration ( 2.7 ), ( 2.8 ) and Warnings and Precautions ( 5.3 ) ].
Geriatric use
8.5 Geriatric Use Clinical studies of fentanyl transdermal system did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. Other reported clinical experience has not identified differences in responses between the elderly and younger patients. In general, use caution when selecting a dosage for an elderly patient, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy. Data from intravenous studies with fentanyl suggest that the elderly patients may have reduced clearance and a prolonged half-life. Moreover, elderly patients may be more sensitive to the active substance than younger patients. A study conducted with the fentanyl transdermal system patch in elderly patients demonstrated that fentanyl pharmacokinetics did not differ significantly from young adult subjects, although peak serum concentrations tended to be lower and mean half-life values were prolonged to approximately 34 hours [see Clinical Pharmacology ( 12.3 ) ]. Respiratory depression is the chief risk for elderly patients treated with opioids, and has occurred after large initial doses were administered to patients who were not opioid-tolerant or when opioids were co-administered with other agents that depress respiration. Titrate the dosage of fentanyl transdermal system slowly in geriatric patients and frequently reevaluate the patient for signs of central nervous system and respiratory depression [see Warnings and Precautions ( 5.12 ) ]. Fentanyl is known to be substantially excreted by the kidney, and the risk of adverse reactions to this drug may be greater in patients with impaired renal function. Because elderly patients are more likely to have decreased renal function, care should be taken in dose selection, and it may be useful to monitor renal function.
Overdosage
10 OVERDOSAGE . Clinical Presentation Acute overdose with fentanyl transdermal system can be manifested by respiratory depression, somnolence progressing to stupor or coma, skeletal muscle flaccidity, cold and clammy skin, constricted pupils, and in some cases, pulmonary edema, bradycardia, hypotension, hypoglycemia, partial or complete airway obstruction, atypical snoring, and death. Marked mydriasis rather than miosis may be seen with hypoxia in overdose situations [see Clinical Pharmacology ( 12.2 ) ]. Toxic leukoencephalopathy has been reported after opioid overdose and can present hours, days, or weeks after apparent recovery from initial intoxication. Treatment of Overdose Give primary attention to the reestablishment of a patent airway and institution of assisted or controlled ventilation, if needed. Employ other supportive measures (including oxygen and vasopressors) in the management of circulatory shock and pulmonary edema as indicated. Cardiac arrest or arrhythmias will require advanced life-support measures. Once stable, examine the patient and ensure that all fentanyl transdermal systems have been removed. For clinically significant respiratory or circulatory depression secondary to opioid overdose, administer an opioid overdose reversal agent such as naloxone or nalmefene. Because the duration of opioid reversal is expected to be less than the duration of action of fentanyl in fentanyl transdermal system, carefully monitor the patient until spontaneous respiration is reliably reestablished. After fentanyl transdermal system removal, serum fentanyl concentrations decline gradually, falling about 50% in approximately 20-27 hours. Therefore, management of an overdose must be monitored accordingly, at least 72 to 96 hours beyond the overdose. In an individual physically dependent on opioids, administration of the recommended usual dosage of the opioid overdose reversal agent will precipitate an acute withdrawal syndrome. The severity of the withdrawal symptoms experienced will depend on the degree of physical dependence and the dose of the reversal agent administered. If a decision is made to treat serious respiratory depression in the physically-dependent patient, administration of the reversal agent should be initiated with care and by titration with smaller than usual doses of the reversal agent.
Description
The system contains fentanyl, an opioid agonist, for transdermal administration. The amount of fentanyl released from each system per hour is proportional to the surface area (25 mcg/hour per 9.44 cm 2 ). The composition per unit area of all transdermal system sizes is identical. * Nominal delivery rate is 12.5 mcg/hour per hour ** Nominal delivery rate per hour Strength (mcg/hour) Size (cm²) Fentanyl Content (mg) 12* 4.72 1.33 25** 9.44 2.66 50** 18.88 5.32 75** 28.32 7.99 100** 37.76 10.65 The molecular weight of fentanyl base is 336.5, and the molecular formula is C 22 H 28 N 2 O. The n-octanol: water partition coefficient is 860:1. The pKa is 8.4. The chemical name is N-Phenyl-N-(1-(2-phenylethyl)-4-piperidinyl) propanamide. The structural formula is: Fentanyl transdermal system is a rectangular translucent system with rounded corners. The product name, “FENTANYL” and dosage strength are printed in green on each system. Each system is comprised of a clear polyethylene terephthalate (PET) release liner and two functional layers. Proceeding from the outer surface toward the surface adhering to skin, these functional layers are: 1) a translucent backing layer of ethylene vinyl acetate/polyethylene terephthalate (EVA/PET) film with green print; 2) a drug-in-adhesive layer containing fentanyl, acrylate copolymer adhesive, and methyl laurate. Before use, a clear PET release liner covering the drug-in-adhesive layer is removed and discarded. Structural Formula Parts of the Fentanyl Transdermal System Patch
Mechanism of action
12.1 Mechanism of Action Fentanyl is an opioid agonist. Fentanyl interacts predominately with the opioid mu-receptor. These mu-binding sites are distributed in the human brain, spinal cord, and other tissues.
How supplied
Fentanyl transdermal system is supplied in cartons containing 5 individually packaged systems. See chart for information regarding individual systems. * This lowest strength is designated as 12 mcg/hour (however, the actual strength is 12.5 mcg/hour) to distinguish it from a 125 mcg/hour strength that could be prescribed by using multiple transdermal systems. Fentanyl Transdermal System Strength (mcg/hour) System Size (cm 2 ) Fentanyl Content (mg) NDC Number Fentanyl transdermal system – 12 * 4.72 1.33 47781-423-47 Fentanyl transdermal system – 25 9.44 2.66 47781-424-47 Fentanyl transdermal system – 50 18.88 5.32 47781-426-47 Fentanyl transdermal system – 75 28.32 7.99 47781-427-47 Fentanyl transdermal system – 100 37.76 10.65 47781-428-47 Store in original unopened pouch. Store up to 25°C (77°F); excursions permitted to 15-30°C (59-86°F) [see USP Controlled Room Temperature]. Store fentanyl transdermal system securely and dispose of properly [see Patient Counseling Information ( 17 ) ].
Label text from the FDA structured product label by ALVOGEN (revised Mar 2, 2026). Long sections are shortened; the complete label is on DailyMed.
Active ingredients
- Fentanyl in 5 products
Fentanyl system NDC products (5)
Fentanyl system recalls
- D-0245-2025 Feb 26, 2025 · Class I · Ongoing
Defective delivery system - patches could be multi-stacked, adhered one on top of the other, in a single product pouch. - D-1277-2019 May 15, 2019 · Class I · Terminated
Product Mix-Up: Customer complaint that their carton labeled as Fentanyl Transdermal Systems, 12 mcg/h contained five patches labeled and containing 50 mcg/h.
Frequently asked questions
What is Fentanyl system used for?
Fentanyl transdermal system is indicated for the management of severe and persistent pain in opioid-tolerant patients, that requires an opioid analgesic and that cannot be adequately treated with alternative options, including immediate-release opioids. Patients considered opioid-tolerant are those who are taking, for one week or longer, at least 60 mg morphine per day, 25 mcg transdermal…
What are the side effects of Fentanyl system?
The following serious adverse reactions are discussed elsewhere in the labeling: Addiction, Abuse, and Misuse [see Warnings and Precautions ( 5.1 )] Life-Threatening Respiratory Depression [see Warnings and Precautions ( 5.2 )] Accidental Exposure [see Warnings and Precautions ( 5.3 )] Interactions with Benzodiazepines or Other Central Nervous System Depressants [see Warnings and Precautions (… See the full label for the complete list.
Who makes Fentanyl system?
Fentanyl system is listed by 1 labeler in the FDA NDC directory, including ALVOGEN.
Has Fentanyl system been recalled?
The FDA enforcement database lists 2 recalls for Fentanyl system, most recently D-0245-2025 (class i): Defective delivery system - patches could be multi-stacked, adhered one on top of the other, in a single product pouch.