Fentanyl Transdermal System Patch
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Questions & Answers
Side Effects & Adverse Reactions
Fentanyl transdermal systems are intended for transdermal use (on intact skin) only. Do not use a fentanyl transdermal system if the pouch seal is broken or the patch is cut, damaged, or changed in any way.
The safety of fentanyl transdermal system has not been established in children under 2 years of age. Fentanyl transdermal system should be administered to children only if they are opioid-tolerant and 2 years of age or older (see PRECAUTIONS, Pediatric Use).
Fentanyl transdermal system 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. Overestimating the fentanyl transdermal system dose when converting patients from another opioid medication can result in fatal overdose with the first dose. The mean half-life is approximately 17 hours. Therefore, patients who have experienced serious adverse events, including overdose, will require monitoring for at least 24 hours after fentanyl transdermal system removal since serum fentanyl concentrations decline gradually and reach an approximate 50% reduction in serum concentrations 17 hours after system removal.
Fentanyl transdermal system should be prescribed only by persons knowledgeable in the continuous administration of potent opioids, in the management of patients receiving potent opioids for treatment of pain, and in the detection and management of hypoventilation including the use of opioid antagonists.
All patients and their caregivers should be advised to avoid exposing 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, saunas, hot tubs, and heated water beds, etc., while wearing the system. Patients should be advised against 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. A clinical pharmacology trial conducted in healthy adult subjects has shown that the application of heat over the fentanyl transdermal system increased mean fentanyl AUC values by 120% and mean Cmax values by 61%.
Based on a pharmacokinetic model, serum fentanyl concentrations could theoretically increase by approximately one-third for patients with a body temperature of 40°C (104°F) due to temperature-dependent increases in fentanyl released from the system and increased skin permeability. Patients wearing fentanyl transdermal systems who develop fever or increased core body temperature due to strenuous exertion should be monitored for opioid side effects and the fentanyl transdermal system dose should be adjusted if necessary.
Death and other serious medical problems have occurred when people were accidentally exposed to fentanyl transdermal system. Examples of accidental exposure include transfer of a fentanyl transdermal system from an adult’s body to a child while hugging, accidental sitting on a patch and possible accidental exposure of a caregiver’s skin to the medication in the patch while the caregiver was applying or removing the patch.
Placing fentanyl transdermal system in the mouth, chewing it, swallowing it, or using it in ways other than indicated may cause choking or overdose that could result in death.
Fentanyl is an opioid agonist of the morphine-type. Such drugs are sought by drug abusers and people with addiction disorders and are subject to criminal diversion.
Fentanyl can be abused in a manner similar to other opioids, legal or illicit. This should be considered when prescribing or dispensing fentanyl transdermal system in situations where the physician or pharmacist is concerned about an increased risk of misuse, abuse or diversion.
Fentanyl transdermal system has been reported as being abused by other methods and routes of administration. These practices will result in uncontrolled delivery of the opioid and pose a significant risk to the abuser that could result in overdose and death (see WARNINGS and DRUG ABUSE AND ADDICTION).
Concerns about abuse, addiction and diversion should not prevent the proper management of pain. However, all patients treated with opioids require careful monitoring for signs of abuse and addiction, since use of opioid analgesic products carries the risk of addiction even under appropriate medical use.
Healthcare professionals should contact their state professional licensing board or state controlled substances authority for information on how to prevent and detect abuse or diversion of this product.
Serious or life-threatening hypoventilation may occur at any time during the use of fentanyl transdermal system especially during the initial 24 to 72 hours following initiation of therapy and following increases in dose.
Because significant amounts of fentanyl continue to be absorbed from the skin for 17 hours or more after the patch is removed, hypoventilation may persist beyond the removal of fentanyl transdermal system. Consequently, patients with hypoventilation should be carefully observed for degree of sedation and their respiratory rate monitored until respiration has stabilized.
The use of concomitant CNS active drugs requires special patient care and observation.
Respiratory depression is the chief hazard of opioid agonists, including fentanyl the active ingredient in fentanyl transdermal system. Respiratory depression is more likely to occur in elderly or debilitated patients, usually following large initial doses in non-tolerant patients, or when opioids are given in conjunction with other drugs that depress respiration.
Respiratory depression from opioids is manifested by a reduced urge to breathe and a decreased rate of respiration, often associated with the “sighing” pattern of breathing (deep breaths separated by abnormally long pauses). Carbon dioxide retention from opioid-induced respiratory depression can exacerbate the sedating effects of opioids. This makes overdoses involving drugs with sedative properties and opioids especially dangerous.
Fentanyl transdermal system should be used with extreme caution in patients with significant chronic obstructive pulmonary disease or cor pulmonale, and in patients having a substantially decreased respiratory reserve, hypoxia, hypercapnia, or pre-existing respiratory depression. In such patients, even usual therapeutic doses of fentanyl transdermal system may decrease respiratory drive to the point of apnea. In these patients, alternative non-opioid analgesics should be considered, and opioids should be employed only under careful medical supervision at the lowest effective dose.
Because potent opioids can cause serious or life-threatening hypoventilation, fentanyl transdermal system should be administered with caution to patients with pre-existing medical conditions predisposing them to hypoventilation. In such patients, normal analgesic doses of opioids may further decrease respiratory drive to the point of respiratory failure.
Fentanyl transdermal system should not be used in patients who may be particularly susceptible to the intracranial effects of CO2 retention such as those with evidence of increased intracranial pressure, impaired consciousness, or coma. Opioids may obscure the clinical course of patients with head injury. Fentanyl transdermal system should be used with caution in patients with brain tumors.
The concomitant use of fentanyl transdermal system with other central nervous system depressants, including but not limited to other opioids, sedatives, hypnotics, tranquilizers (e.g., benzodiazepines), general anesthetics, phenothiazines, skeletal muscle relaxants, and alcohol, may cause respiratory depression, hypotension, and profound sedation or potentially result in coma. When such combined therapy is contemplated, the dose of one or both agents should be significantly reduced.
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.
The concomitant use of transdermal fentanyl with all CYP3A4 inhibitors (such as ritonavir, ketoconazole, itraconazole, troleandomycin, 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 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).
Legal Issues
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Manufacturer Warnings
There is currently no manufacturer warning information available for this drug.
FDA Labeling Changes
There are currently no FDA labeling changes available for this drug.
Uses
Fentanyl transdermal system is indicated for 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 such as non-steroidal analgesics, opioid combination products, or immediate-release opioids.
Fentanyl transdermal system should ONLY be used in patients who are already receiving opioid therapy, who have demonstrated opioid tolerance, and who require a total daily dose at least equivalent to fentanyl transdermal system 25 mcg/hr (see DOSAGE AND ADMINISTRATION). 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.
Because serious or life-threatening hypoventilation could result, fentanyl transdermal system is contraindicated for use on an as needed basis (i.e., prn), for the management of post-operative or acute pain, or in patients who are not opioid-tolerant or who require opioid analgesia for a short period of time (see BOX WARNING and CONTRAINDICATIONS).
An evaluation of the appropriateness and adequacy of treating with immediate-release opioids is advisable prior to initiating therapy with any modified-release opioid. Prescribers should individualize treatment in every case, initiating therapy at the appropriate point along a progression from non-opioid analgesics, such as non-steroidal anti-inflammatory drugs and acetaminophen, to opioids, in a plan of pain management such as outlined by the World Health Organization, the Agency for Health Research and Quality, the Federation of State Medical Boards Model Policy, or the American Pain Society.
Patients should be assessed for their clinical risks for opioid abuse or addiction prior to being prescribed opioids. Patients receiving opioids should be routinely monitored for signs of misuse, abuse, and addiction. Persons at increased risk for opioid abuse include those with a personal or family history of substance abuse (including drug or alcohol abuse or addiction) or mental illness (e.g., major depression). Patients at increased risk may still be appropriately treated with modified-release opioid formulations; however these patients will require intensive monitoring for signs of misuse, abuse, or addiction.
History
There is currently no drug history available for this drug.
Other Information
Fentanyl transdermal system is a transdermal system providing continuous systemic delivery of fentanyl, a potent opioid analgesic, for 72 hours. The chemical name is N-Phenyl-N-(1-(2-phenylethyl)-4-piperidinyl) propanamide. The structural formula is:
The molecular weight of fentanyl base is 336.5, and the molecular formula is C22H28N2O. The n-octanol:water partition coefficient is 860:1. The pKa is 8.4.
The amount of fentanyl released from each system per hour is proportional to the surface area (25 mcg/hr per 7.8 cm2). The composition per unit area of all system sizes is identical.
| * Nominal delivery rate per hour |
||
| Dose* (mcg/hr) |
Size (cm2) |
Fentanyl Content (mg) |
| 25 | 7.8 | 2.75 |
| 50 | 15.6 | 5.50 |
| 75 | 23.4 | 8.25 |
| 100 | 31.2 | 11.0 |
Fentanyl transdermal system is a rectangular transparent unit comprising a protective liner and four functional layers. Proceeding from the outer surface toward the surface adhering to skin, these layers are:
- a backing layer of PET foil;
- a drug containing layer of fentanyl and dipropylene glycol with hydroxypropyl cellulose;
- an ethylene vinyl-acetate copolymer membrane that controls the rate of fentanyl delivery to the skin surface; and
- a silicone adhesive. Before use, a protective liner covering the adhesive layer is removed and discarded.
The active component of the system is fentanyl. The remaining components are pharmacologically inactive: dipropylene glycol, hydroxypropyl cellulose, ethylene vinyl-acetate copolymer, silicone adhesives between polyester backings, silicone fluid.
Sources
Fentanyl Transdermal System Patch Manufacturers
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Rebel Distributors Corp
![Fentanyl Transdermal System Patch, Extended Release [Rebel Distributors Corp]](/wp-content/themes/bootstrap/assets/img/loading2.gif)
Fentanyl Transdermal System Patch | Rebel Distributors Corp
Special PrecautionsFentanyl transdermal system contains a high concentration of a potent Schedule II opioid agonist, fentanyl. Schedule II opioid substances which include 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 (fentanyl transdermal system) may be a particular target for abuse and diversion.
Fentanyl transdermal systems are intended for transdermal use (on intact skin) only. The fentanyl transdermal system should not be used if the pouch seal is broken, or the patch is cut, damaged, or changed in any way.
Each fentanyl transdermal system may be worn continuously for 72 hours. The next patch should be applied to a different skin site after removal of the previous transdermal system.
If problems with adhesion of the fentanyl transdermal system occur, the edges of the patch may be taped with first aid tape. If problems with adhesion persist, the patch may be overlaid with a transparent adhesive film dressing (e.g., Bioclusive™ or Tegaderm™).
If the patch falls off before 72 hours, dispose of it by folding in half and flushing down the toilet. A new patch may be applied to a different skin site.
Fentanyl transdermal system 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. Overestimating the fentanyl transdermal system dose when converting patients from another opioid medication can result in fatal overdose with the first dose. Due to the mean half-life of approximately 17 hours, patients who are thought to have had a serious adverse event, including overdose, will require monitoring and treatment for at least 24 hours.
The concomitant use of fentanyl transdermal system with all cytochrome P450 3A4 inhibitors (such as ritonavir, ketoconazole, itraconazole, troleandomycin, 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 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; WARNINGS and PRECAUTIONS for further information).
Pediatric patients converting to fentanyl transdermal system with a 25 mcg/hr patch should be opioid-tolerant and receiving at least 60 mg of oral morphine or the equivalent per day. The dose conversion schedule described in Table C, and method of titration described below are recommended in opioid-tolerant pediatric patients over 2 years of age with chronic pain (see PRECAUTIONS, Pediatric Use).
Respiratory depression is the chief hazard in elderly or debilitated patients, usually following large initial doses in non-tolerant patients, or when opioids are given in conjunction with other agents that depress respiration.
Fentanyl transdermal system should be used with caution in elderly, cachectic, or debilitated patients as they may have altered pharmacokinetics due to poor fat stores, muscle wasting, or altered clearance (see CLINICAL PHARMACOLOGY, Special Populations, Geriatric Use ).
General PrinciplesFentanyl transdermal system is indicated for management of persistent, moderate to severe chronic pain that:
requires continuous, around-the-clock opioid administration for an extended period of time cannot be managed by other means such as non-steroidal analgesics, opioid combination products, or immediate-release opioids.Fentanyl transdermal system should ONLY be used in patients who are already receiving opioid therapy, who have demonstrated opioid tolerance, and who require a total daily dose at least equivalent to fentanyl transdermal system 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 oral hydromorphone daily, or an equianalgesic dose of another opioid.
Because serious or life-threatening hypoventilation could occur, fentanyl transdermal system is contraindicated:
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 after out-patient or day surgeries (e.g., tonsillectomies) in the management of mild pain in the management of intermittent pain (e.g., use on an as needed basis [prn])(see CONTRAINDICATIONS for further information).
Safety of fentanyl transdermal system has not been established in children under 2 years of age. Fentanyl transdermal system should be administered to children only if they are opioid-tolerant and 2 years of age or older (see PRECAUTIONS, Pediatric Use).
Prescribers should individualize treatment using a progressive plan of pain management such as outlined by the World Health Organization, the Agency for Health Research and Quality, the Federation of State Medical Boards Model Policy, or the American Pain Society.
With all opioids, the safety of patients using the products is dependent on healthcare practitioners prescribing them in strict conformity with their approved labeling with respect to patient selection, dosing, and proper conditions for use.
As with all opioids, dosage should be individualized. The most important factor to be considered in determining the appropriate dose is the extent of pre-existing opioid-tolerance (see BOX WARNING and CONTRAINDICATIONS). Initial doses should be reduced in elderly or debilitated patients (see PRECAUTIONS).
Fentanyl transdermal system should be applied to intact, non-irritated, and non-irradiated skin on a flat surface such as the chest, back, flank, or upper arm. In young children and persons with cognitive impairment, adhesion should be monitored and the upper back is the preferred location to minimize the potential of inappropriate patch removal. Hair at the application site should be clipped (not shaved) prior to system 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.
Fentanyl transdermal system should be applied immediately upon removal from the sealed package. Do not use if the pouch seal is broken. Do not alter the patch (e.g., cut) in any way prior to application and do not use cut or damaged patches.
The transdermal system 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.
Fentanyl transdermal system should be kept out of the reach of children. Used patches should be folded so that the adhesive side of the patch adheres to itself, then the patch should be flushed down the toilet immediately upon removal. Patients should dispose of any patches remaining from a prescription as soon as they are no longer needed. 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.
Dose SelectionDoses must be individualized based upon the status of each patient and should be assessed at regular intervals after fentanyl transdermal system application. Reduced doses of fentanyl transdermal system are suggested for the elderly and other groups discussed in PRECAUTIONS.
Initial Fentanyl Transdermal System Dose Selection
Fentanyl transdermal system 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.
In selecting an initial fentanyl transdermal system dose, attention should be given to 1) the daily dose, potency, and characteristics of the opioid the patient has been taking previously (e.g., whether it is a pure agonist or mixed agonist-antagonist), 2) the reliability of the relative potency estimates used to calculate the fentanyl transdermal system dose needed (potency estimates may vary with the route of administration), 3) the degree of opioid tolerance and 4) the general condition and medical status of the patient. Each patient should be maintained at the lowest dose providing acceptable pain control.Overestimating the fentanyl transdermal system dose when converting patients from another opioid medication can result in fatal overdose with the first dose. Due to the mean half-life of approximately 17 hours, patients who are thought to have had a serious adverse event, including overdose, will require monitoring and treatment for at least 24 hours.
Calculate the previous 24-hour analgesic requirement. Convert this amount to the equianalgesic oral morphine dose using Table D. Table E displays 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 fentanyl transdermal system dose. Initiate fentanyl transdermal system treatment using the recommended dose and titrate patients upwards (no more frequently than every 3 days after the initial dose or than every 6 days thereafter) until analgesic efficacy is attained. The recommended starting dose when converting from other opioids to fentanyl transdermal system is likely too low for 50% of patients. This starting dose is recommended to minimize the potential for overdosing patients with the first dose. For delivery rates in excess of 100 mcg/hr, multiple systems may be used. TABLE C* DOSE CONVERSION GUIDELINES Current Analgesic Daily Dosage (mg/d) Oral morphine 60-134 135-224 225-314 315-404 IM/IV morphine 10-22 23-37 38-52 53-67 Oral oxycodone 30-67 67.5-112 112.5-157 157.5-202 IM/IV oxycodone 15-33 33.1-56 56.1-78 78.1-101 Oral codeine 150-447 448-747 748-1047 1048-1347 Oral hydromorphone 8-17 17.1-28 28.1-39 39.1-51 IV hydromorphone 1.5-3.4 3.5-5.6 5.7-7.9 8-10 IM meperidine 75-165 166-278 279-390 391-503 Oral methadone 20-44 45-74 75-104 105-134 IM methadone 10-22 23-37 38-52 53-67 ⇓ ⇓ ⇓ ⇓ Recommended Fentanyl Transdermal System Dose 25 mcg/hr 50 mcg/hr 75 mcg/hr 100 mcg/hr
There has been no systematic evaluation of fentanyl transdermal system as an initial opioid analgesic in the management of chronic pain, since most patients in the clinical trials were converted to fentanyl transdermal system from other narcotics. The efficacy of fentanyl transdermal system 12 mcg/hr as an initiating dose has not been determined. In addition, patients who are not opioid-tolerant have experienced hypoventilation and death during use of fentanyl transdermal system. Therefore, fentanyl transdermal system should be used only in patients who are opioid-tolerant.
To convert patients from oral or parenteral opioids to fentanyl transdermal system, use Table C:
Alternatively, for adult and pediatric patients taking opioids or doses not listed in Table C, use the following methodology:Alternatively, for adult and pediatric patients taking opioids or doses not listed in Table C, use the conversion methodology outlined above with Table D.
*Table C 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 C 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, Discontinuation of Fentanyl Transdermal System).
TABLE D*,† EQUIANALGESIC POTENCY CONVERSION Dilaudid is a registered trademark of Purdue Pharma L.P
Dolophine is a registered trademark of Roxane Laboratories, Inc.
Levo-Dromoran is a registered trademark of Valeant Pharmaceuticals North America
Numorphan is a registered trademark of Endo Pharmaceuticals, Inc.
Demerol is a registered trademark of Sanofi-Aventis U.S. LLC
*Table D 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 D 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, Discontinuation of Fentanyl Transdermal System).
† All IM and PO doses in this chart are considered equivalent to 10 mg of IM morphine in analgesic effect. IM denotes intramuscular, PO oral, and PR rectal.
‡ Based on single-dose studies in which an intramuscular dose of each drug listed was compared with morphine to establish the relative potency. Oral doses are those recommended when changing from parenteral to an oral route. Reference: Foley, K.M. (1985) The treatment of cancer pain. NEJM 313(2):84-95.
§ Although controlled studies are not available, in clinical practice it is customary to consider the doses of opioid given IM, IV, or subcutaneously to be equivalent. There may be some differences in pharmacokinetic parameters such as Cmax and Tmax.
¶ The conversion ratio of 10 mg parenteral morphine = 30 mg oral morphine is based on clinical experience in patients with chronic pain. The conversion ratio of 10 mg parenteral morphine = 60 mg oral morphine is based on a potency study in acute pain. Reference: Ashburn and Lipman (1993) Management of pain in the cancer patient. Anesth Analg 76:402-416.
Name Equianalgesic Dose (mg) IM‡,§ PO Morphine 10 60 (30)¶ Hydromorphone (Dilaudid®) 1.5 7.5 Methadone (Dolophine®) 10 20 Oxycodone 15 30 Levorphanol (Levo-Dromoran®) 2 4 Oxymorphone (Numorphan®) 1 10 (PR) Meperidine (Demerol®) 75 — Codeine 130 200 TABLE E* RECOMMENDED INITIAL FENTANYL TRANSDERMAL SYSTEM DOSE BASED UPON DAILY ORAL MORPHINE DOSENOTE: In clinical trials, these ranges of daily oral morphine doses were used as a basis for conversion to fentanyl transdermal system.
*Table E 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 E 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, Discontinuation of Fentanyl Transdermal System).
Oral 24-hour
Morphine
(mg/day) Fentanyl Transdermal System
Dose
(mcg/hr) 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 300The majority of patients are adequately maintained with fentanyl transdermal system administered every 72 hours. Some patients may not achieve adequate analgesia using this dosing interval and may require systems to be applied every 48 hours rather than every 72 hours. An increase in the fentanyl transdermal system 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.
Dose Titration
Because of the increase in serum fentanyl concentration over the first 24 hours following initial system application, the initial evaluation of the maximum analgesic effect of fentanyl transdermal system cannot be made before 24 hours of wearing. The initial fentanyl transdermal system dose may be increased after 3 days (see DOSAGE AND ADMINISTRATION, Dose Titration).
During the initial application of fentanyl transdermal system, patients should use short-acting analgesics as needed until analgesic efficacy with fentanyl transdermal system is attained. Thereafter, some patients still may require periodic supplemental doses of other short-acting analgesics for “breakthrough” pain.The recommended initial fentanyl transdermal system dose based upon the daily oral morphine dose is conservative, and 50% of patients are likely to require a dose increase after initial application of fentanyl transdermal system. The initial fentanyl transdermal system dose may be increased after 3 days based on the daily dose of supplemental opioid analgesics required by the patient in the second or third day of the initial application.
Discontinuation of Fentanyl Transdermal System
Physicians are advised that it may take up to 6 days after increasing the dose of fentanyl transdermal system for the patient to reach equilibrium on the new dose (see graph in CLINICAL PHARMACOLOGY). Therefore, patients should wear a higher dose through two applications before any further increase in dosage is made on the basis of the average daily use of a supplemental analgesic.
Appropriate dosage increments should be based on the daily dose of supplementary opioids, using the ratio of 45 mg/24 hours of oral morphine to a 12.5 mcg/hr increase in fentanyl transdermal system dose.To convert patients to another opioid, remove fentanyl transdermal system and titrate the dose of the new analgesic based upon the patient’s report of pain until adequate analgesia has been attained. Upon system removal, 17 hours or more are required for a 50% decrease in serum fentanyl concentrations. Opioid withdrawal symptoms (such as nausea, vomiting, diarrhea, anxiety, and shivering) are possible in some patients after conversion or dose adjustment. For patients requiring discontinuation of opioids, a gradual downward titration is recommended since it is not known at what dose level the opioid may be discontinued without producing the signs and symptoms of abrupt withdrawal.
Tables C, D, and E should not be used to convert from fentanyl transdermal system to other therapies. Because the conversion to fentanyl transdermal system is conservative, use of Tables C, D, and E for conversion to other analgesic therapies can overestimate the dose of the new agent. Overdosage of the new analgesic agent is possible. -
Rebel Distributors Corp.
Fentanyl Transdermal System Patch | Rebel Distributors Corp.
Special PrecautionsFentanyl transdermal system contains a high concentration of a potent Schedule II opioid agonist, fentanyl. Schedule II opioid substances which include 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 (fentanyl transdermal system) may be a particular target for abuse and diversion.
Fentanyl transdermal systems are intended for transdermal use (on intact skin) only. The fentanyl transdermal system should not be used if the pouch seal is broken, or the patch is cut, damaged, or changed in any way.
Each fentanyl transdermal system may be worn continuously for 72 hours. The next patch should be applied to a different skin site after removal of the previous transdermal system.
If problems with adhesion of the fentanyl transdermal system occur, the edges of the patch may be taped with first aid tape. If problems with adhesion persist, the patch may be overlaid with a transparent adhesive film dressing (e.g., Bioclusive™ or Tegaderm™).
If the patch falls off before 72 hours, dispose of it by folding in half and flushing down the toilet. A new patch may be applied to a different skin site.
Fentanyl transdermal system 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. Overestimating the fentanyl transdermal system dose when converting patients from another opioid medication can result in fatal overdose with the first dose. Due to the mean half-life of approximately 17 hours, patients who are thought to have had a serious adverse event, including overdose, will require monitoring and treatment for at least 24 hours.
The concomitant use of fentanyl transdermal system with all cytochrome P450 3A4 inhibitors (such as ritonavir, ketoconazole, itraconazole, troleandomycin, 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 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; WARNINGS and PRECAUTIONS for further information).
Pediatric patients converting to fentanyl transdermal system with a 25 mcg/hr patch should be opioid-tolerant and receiving at least 60 mg of oral morphine or the equivalent per day. The dose conversion schedule described in Table C, and method of titration described below are recommended in opioid-tolerant pediatric patients over 2 years of age with chronic pain (see PRECAUTIONS, Pediatric Use).
Respiratory depression is the chief hazard in elderly or debilitated patients, usually following large initial doses in non-tolerant patients, or when opioids are given in conjunction with other agents that depress respiration.
Fentanyl transdermal system should be used with caution in elderly, cachectic, or debilitated patients as they may have altered pharmacokinetics due to poor fat stores, muscle wasting, or altered clearance (see CLINICAL PHARMACOLOGY, Special Populations, Geriatric Use ).
General PrinciplesFentanyl transdermal system is indicated for management of persistent, moderate to severe chronic pain that:
requires continuous, around-the-clock opioid administration for an extended period of time cannot be managed by other means such as non-steroidal analgesics, opioid combination products, or immediate-release opioids.Fentanyl transdermal system should ONLY be used in patients who are already receiving opioid therapy, who have demonstrated opioid tolerance, and who require a total daily dose at least equivalent to fentanyl transdermal system 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 oral hydromorphone daily, or an equianalgesic dose of another opioid.
Because serious or life-threatening hypoventilation could occur, fentanyl transdermal system is contraindicated:
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 after out-patient or day surgeries (e.g., tonsillectomies) in the management of mild pain in the management of intermittent pain (e.g., use on an as needed basis [prn])(see CONTRAINDICATIONS for further information).
Safety of fentanyl transdermal system has not been established in children under 2 years of age. Fentanyl transdermal system should be administered to children only if they are opioid-tolerant and 2 years of age or older (see PRECAUTIONS, Pediatric Use).
Prescribers should individualize treatment using a progressive plan of pain management such as outlined by the World Health Organization, the Agency for Health Research and Quality, the Federation of State Medical Boards Model Policy, or the American Pain Society.
With all opioids, the safety of patients using the products is dependent on healthcare practitioners prescribing them in strict conformity with their approved labeling with respect to patient selection, dosing, and proper conditions for use.
As with all opioids, dosage should be individualized. The most important factor to be considered in determining the appropriate dose is the extent of pre-existing opioid-tolerance (see BOX WARNING and CONTRAINDICATIONS). Initial doses should be reduced in elderly or debilitated patients (see PRECAUTIONS).
Fentanyl transdermal system should be applied to intact, non-irritated, and non-irradiated skin on a flat surface such as the chest, back, flank, or upper arm. In young children and persons with cognitive impairment, adhesion should be monitored and the upper back is the preferred location to minimize the potential of inappropriate patch removal. Hair at the application site should be clipped (not shaved) prior to system 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.
Fentanyl transdermal system should be applied immediately upon removal from the sealed package. Do not use if the pouch seal is broken. Do not alter the patch (e.g., cut) in any way prior to application and do not use cut or damaged patches.
The transdermal system 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.
Fentanyl transdermal system should be kept out of the reach of children. Used patches should be folded so that the adhesive side of the patch adheres to itself, then the patch should be flushed down the toilet immediately upon removal. Patients should dispose of any patches remaining from a prescription as soon as they are no longer needed. 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.
Dose SelectionDoses must be individualized based upon the status of each patient and should be assessed at regular intervals after fentanyl transdermal system application. Reduced doses of fentanyl transdermal system are suggested for the elderly and other groups discussed in PRECAUTIONS.
Initial Fentanyl Transdermal System Dose Selection
Fentanyl transdermal system 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.
In selecting an initial fentanyl transdermal system dose, attention should be given to 1) the daily dose, potency, and characteristics of the opioid the patient has been taking previously (e.g., whether it is a pure agonist or mixed agonist-antagonist), 2) the reliability of the relative potency estimates used to calculate the fentanyl transdermal system dose needed (potency estimates may vary with the route of administration), 3) the degree of opioid tolerance and 4) the general condition and medical status of the patient. Each patient should be maintained at the lowest dose providing acceptable pain control.Overestimating the fentanyl transdermal system dose when converting patients from another opioid medication can result in fatal overdose with the first dose. Due to the mean half-life of approximately 17 hours, patients who are thought to have had a serious adverse event, including overdose, will require monitoring and treatment for at least 24 hours.
Calculate the previous 24-hour analgesic requirement. Convert this amount to the equianalgesic oral morphine dose using Table D. Table E displays 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 fentanyl transdermal system dose. Initiate fentanyl transdermal system treatment using the recommended dose and titrate patients upwards (no more frequently than every 3 days after the initial dose or than every 6 days thereafter) until analgesic efficacy is attained. The recommended starting dose when converting from other opioids to fentanyl transdermal system is likely too low for 50% of patients. This starting dose is recommended to minimize the potential for overdosing patients with the first dose. For delivery rates in excess of 100 mcg/hr, multiple systems may be used. TABLE C* DOSE CONVERSION GUIDELINES Current Analgesic Daily Dosage (mg/d) Oral morphine 60-134 135-224 225-314 315-404 IM/IV morphine 10-22 23-37 38-52 53-67 Oral oxycodone 30-67 67.5-112 112.5-157 157.5-202 IM/IV oxycodone 15-33 33.1-56 56.1-78 78.1-101 Oral codeine 150-447 448-747 748-1047 1048-1347 Oral hydromorphone 8-17 17.1-28 28.1-39 39.1-51 IV hydromorphone 1.5-3.4 3.5-5.6 5.7-7.9 8-10 IM meperidine 75-165 166-278 279-390 391-503 Oral methadone 20-44 45-74 75-104 105-134 IM methadone 10-22 23-37 38-52 53-67 ⇓ ⇓ ⇓ ⇓ Recommended Fentanyl Transdermal System Dose 25 mcg/hr 50 mcg/hr 75 mcg/hr 100 mcg/hr
There has been no systematic evaluation of fentanyl transdermal system as an initial opioid analgesic in the management of chronic pain, since most patients in the clinical trials were converted to fentanyl transdermal system from other narcotics. The efficacy of fentanyl transdermal system 12 mcg/hr as an initiating dose has not been determined. In addition, patients who are not opioid-tolerant have experienced hypoventilation and death during use of fentanyl transdermal system. Therefore, fentanyl transdermal system should be used only in patients who are opioid-tolerant.
To convert patients from oral or parenteral opioids to fentanyl transdermal system, use Table C:
Alternatively, for adult and pediatric patients taking opioids or doses not listed in Table C, use the following methodology:Alternatively, for adult and pediatric patients taking opioids or doses not listed in Table C, use the conversion methodology outlined above with Table D.
*Table C 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 C 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, Discontinuation of Fentanyl Transdermal System).
TABLE D*,† EQUIANALGESIC POTENCY CONVERSION Dilaudid is a registered trademark of Purdue Pharma L.P
Dolophine is a registered trademark of Roxane Laboratories, Inc.
Levo-Dromoran is a registered trademark of Valeant Pharmaceuticals North America
Numorphan is a registered trademark of Endo Pharmaceuticals, Inc.
Demerol is a registered trademark of Sanofi-Aventis U.S. LLC
*Table D 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 D 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, Discontinuation of Fentanyl Transdermal System).
† All IM and PO doses in this chart are considered equivalent to 10 mg of IM morphine in analgesic effect. IM denotes intramuscular, PO oral, and PR rectal.
‡ Based on single-dose studies in which an intramuscular dose of each drug listed was compared with morphine to establish the relative potency. Oral doses are those recommended when changing from parenteral to an oral route. Reference: Foley, K.M. (1985) The treatment of cancer pain. NEJM 313(2):84-95.
§ Although controlled studies are not available, in clinical practice it is customary to consider the doses of opioid given IM, IV, or subcutaneously to be equivalent. There may be some differences in pharmacokinetic parameters such as Cmax and Tmax.
¶ The conversion ratio of 10 mg parenteral morphine = 30 mg oral morphine is based on clinical experience in patients with chronic pain. The conversion ratio of 10 mg parenteral morphine = 60 mg oral morphine is based on a potency study in acute pain. Reference: Ashburn and Lipman (1993) Management of pain in the cancer patient. Anesth Analg 76:402-416.
Name Equianalgesic Dose (mg) IM‡,§ PO Morphine 10 60 (30)¶ Hydromorphone (Dilaudid®) 1.5 7.5 Methadone (Dolophine®) 10 20 Oxycodone 15 30 Levorphanol (Levo-Dromoran®) 2 4 Oxymorphone (Numorphan®) 1 10 (PR) Meperidine (Demerol®) 75 — Codeine 130 200 TABLE E* RECOMMENDED INITIAL FENTANYL TRANSDERMAL SYSTEM DOSE BASED UPON DAILY ORAL MORPHINE DOSENOTE: In clinical trials, these ranges of daily oral morphine doses were used as a basis for conversion to fentanyl transdermal system.
*Table E 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 E 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, Discontinuation of Fentanyl Transdermal System).
Oral 24-hour
Morphine
(mg/day) Fentanyl Transdermal System
Dose
(mcg/hr) 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 300The majority of patients are adequately maintained with fentanyl transdermal system administered every 72 hours. Some patients may not achieve adequate analgesia using this dosing interval and may require systems to be applied every 48 hours rather than every 72 hours. An increase in the fentanyl transdermal system 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.
Dose Titration
Because of the increase in serum fentanyl concentration over the first 24 hours following initial system application, the initial evaluation of the maximum analgesic effect of fentanyl transdermal system cannot be made before 24 hours of wearing. The initial fentanyl transdermal system dose may be increased after 3 days (see DOSAGE AND ADMINISTRATION, Dose Titration).
During the initial application of fentanyl transdermal system, patients should use short-acting analgesics as needed until analgesic efficacy with fentanyl transdermal system is attained. Thereafter, some patients still may require periodic supplemental doses of other short-acting analgesics for “breakthrough” pain.The recommended initial fentanyl transdermal system dose based upon the daily oral morphine dose is conservative, and 50% of patients are likely to require a dose increase after initial application of fentanyl transdermal system. The initial fentanyl transdermal system dose may be increased after 3 days based on the daily dose of supplemental opioid analgesics required by the patient in the second or third day of the initial application.
Discontinuation of Fentanyl Transdermal System
Physicians are advised that it may take up to 6 days after increasing the dose of fentanyl transdermal system for the patient to reach equilibrium on the new dose (see graph in CLINICAL PHARMACOLOGY). Therefore, patients should wear a higher dose through two applications before any further increase in dosage is made on the basis of the average daily use of a supplemental analgesic.
Appropriate dosage increments should be based on the daily dose of supplementary opioids, using the ratio of 45 mg/24 hours of oral morphine to a 12.5 mcg/hr increase in fentanyl transdermal system dose.To convert patients to another opioid, remove fentanyl transdermal system and titrate the dose of the new analgesic based upon the patient’s report of pain until adequate analgesia has been attained. Upon system removal, 17 hours or more are required for a 50% decrease in serum fentanyl concentrations. Opioid withdrawal symptoms (such as nausea, vomiting, diarrhea, anxiety, and shivering) are possible in some patients after conversion or dose adjustment. For patients requiring discontinuation of opioids, a gradual downward titration is recommended since it is not known at what dose level the opioid may be discontinued without producing the signs and symptoms of abrupt withdrawal.
Tables C, D, and E should not be used to convert from fentanyl transdermal system to other therapies. Because the conversion to fentanyl transdermal system is conservative, use of Tables C, D, and E for conversion to other analgesic therapies can overestimate the dose of the new agent. Overdosage of the new analgesic agent is possible. -
Bryant Ranch Prepack
Fentanyl Transdermal System Patch | Bryant Ranch Prepack
2.1 Proper Patient SelectionAbuse Potential
Assess patients for their clinical risks for opioid abuse or addiction prior to being prescribing fentanyl transdermal system [see Warnings and Precautions (5.1)].
Opioid Tolerance
Opioid tolerance to an opioid of comparable potency must be established before prescribing fentanyl transdermal system [see Warnings and Precautions (5.2)].
Patients considered opioid-tolerant are those who are taking 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 for a week or longer.
2.2 DosingConversion to Fentanyl Transdermal System in Opioid-Tolerant Patients
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. Monitor patients closely for respiratory depression, especially within the first 24 to 72 hours of initiating therapy with fentanyl transdermal system [see Warnings and Precautions (5.2)].
In selecting an initial fentanyl transdermal system dose, take the following factors into account:
1. the daily dose, potency, and characteristics of the opioid the patient has been taking previously (e.g., whether it is a pure agonist or mixed agonist-antagonist);
2. the reliability of the relative potency estimates used to calculate the fentanyl transdermal system dose needed (potency estimates may vary with the route of administration);
3. the degree of opioid tolerance;
4. the general condition and medical status of the patient.
To convert adult and pediatric patients from oral or parenteral opioids to fentanyl transdermal system, use Table 1. Do not use Table 1 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.
TABLE 1*: DOSE CONVERSION GUIDELINES
Current Analgesic
Daily Dosage (mg/day)
Oral morphine
60-134
135-224
225-314
315-404
Intramuscular or Intravenous morphine
10-22
23-37
38-52
53-67
Oral oxycodone
30-67
67.5-112
112.5-157
157.5-202
Intramuscular or Intravenous oxycodone
15-33
33.1-56
56.1-78
78.1-101
Oral codeine
150-447
448-747
748-1047
1048-1347
Oral hydromorphone
8-17
17.1-28
28.1-39
39.1-51
Intravenous hydromorphone 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
Intramuscular methadone
10-22
23-37
38-52
53-67
Recommended Fentanyl Transdermal System Dose
25 mcg/hour
50 mcg/hour
75 mcg/hour
100 mcg/hour
Alternatively, for adult and pediatric patients taking opioids or doses not listed in Table 1, use the conversion methodology outlined above with Table 2.
* 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 (2.3)].
Alternatively, for adult and pediatric patients taking opioids or doses not listed in Table 1, use the following methodology:
1. Calculate the previous 24-hour analgesic requirement.
2. 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 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.
3. 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.
TABLE 2*: RECOMMENDED INITIAL FENTANYL TRANSDERMAL SYSTEM DOSE BASED UPON DAILY ORAL MORPHINE DOSE
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.
* Table 2 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 2 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 (2.3)].
For delivery rates in excess of 100 mcg/hour, multiple systems may be used.
Hepatic Impairment
Avoid the use of fentanyl transdermal system in patients with severe hepatic impairment. In patients with mild to moderate hepatic impairment, start with one half of the usual dosage of fentanyl transdermal system. Closely monitor for signs of sedation and respiratory depression, including at each dosage increase [see Warnings and Precautions (5.12), Use in Specific Populations (8.6) and Clinical Pharmacology (12.3)].
Renal Impairment
Avoid the use of fentanyl transdermal system in patients with severe renal impairment. In patients with mild to moderate renal impairment, start with one half of the usual dosage of fentanyl transdermal system. Closely monitor for signs of sedation and respiratory depression, including at each dosage increase [see Warnings and Precautions (5.13), Use in Specific Populations (8.7) and Clinical Pharmacology (12.3)].
2.3 Titration and Maintenance of TherapyOnce therapy is initiated, assess pain intensity and opioid adverse reactions frequently, especially respiratory depression [see Warnings and Precautions (5.2)]. Routinely monitor all patients for signs of misuse, abuse and addiction [see Warnings and Precautions (5.1)].
The initial fentanyl transdermal system dose may be increased after 3 days 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 fentanyl transdermal system dose.
The majority of patients are adequately maintained with fentanyl transdermal system administered every 72 hours. Some patients may not achieve adequate analgesia using this 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 fentanyl transdermal system 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.
Discontinuation of Fentanyl Transdermal System
To convert patients to another opioid, remove fentanyl transdermal system and titrate the dose of the new analgesic based upon the patient’s report of pain until adequate analgesia has been attained. Upon system removal, 17 hours or more are required for a 50% decrease in serum fentanyl concentrations. Withdrawal symptoms are possible in some patients after conversion or dose adjustment [see Warnings and Precautions (5.15)].
Do not use Tables 1 and 2 to convert from fentanyl transdermal system to other therapies to avoid overestimating the dose of the new agent potentially resulting in overdose of the new analgesic and death.
When discontinuing fentanyl transdermal system and not converting to another opioid, use a gradual downward titration, such as halving the dose every 6 days, in order to reduce the possibility of withdrawal symptoms [see Warnings and Precautions (5.15)]. It is not known at what dose level fentanyl transdermal system may be discontinued without producing the signs and symptoms of opioid withdrawal.
2.4 Administration of Fentanyl Transdermal SystemFentanyl transdermal system is for transdermal use, only.
Proper handling of fentanyl transdermal system is advised in order to prevent adverse reactions, including death, associated with accidental secondary exposure to fentanyl transdermal system [see Warnings and Precautions (5.3)].
Application and Handling Instructions
Patients should apply fentanyl transdermal system to intact, non‑irritated, and non-irradiated skin on a flat surface such as the chest, back, flank, or upper arm. In young children and persons with cognitive impairment, adhesion should be monitored and the upper back is the preferred location to minimize the potential of inappropriate patch removal. Hair at the application site may be clipped (not shaved) prior to system 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. Patients should apply fentanyl transdermal system immediately upon removal from the sealed package. The patch must not be altered (e.g., cut) in any way prior to application. Fentanyl transdermal system should not be used if the pouch seal is broken or if the patch is cut or damaged. The transdermal system is pressed firmly in place with the palm of the hand for 30 seconds, making sure the contact is complete, especially around the edges. Each fentanyl transdermal system may be worn continuously for 72 hours. The next patch is applied to a different skin site after removal of the previous transdermal system. If problems with adhesion of the fentanyl transdermal system occur, the edges of the patch may be taped with first aid tape. If problems with adhesion persist, the patch may be overlayed with a transparent adhesive film dressing. If the patch falls off before 72 hours, dispose of it by folding in half and flushing down the toilet. A new patch may be applied to a different skin site. Patients (or caregivers who apply fentanyl transdermal system) should wash their hands immediately with soap and water after applying fentanyl transdermal system. Contact with unwashed or unclothed application sites can result in secondary exposure to fentanyl transdermal system and should be avoided. Examples of accidental exposure include transfer of a fentanyl transdermal system from an adult’s body to a child while hugging, sharing the same bed as the patient, accidental sitting on a patch and possible accidental exposure of a caregiver’s skin to the medication in the patch while applying or removing the patch. Instruct patients, family members, and caregivers to keep patches in a secure location out of the reach of children and of others for whom fentanyl transdermal system was not prescribed.Avoidance of Heat
Instruct patients to avoid exposing 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, while wearing the system [see Warnings and Precautions (5.9)].
2.5 Disposal InstructionsProper disposal of fentanyl transdermal system is advised in order to prevent adverse reactions, including death, associated with accidental secondary exposure to fentanyl transdermal system [see Warnings and Precautions (5.3)].
Patients should dispose of used patches by folding the adhesive side of the patch to itself, then flush the patch down the toilet immediately upon removal.
Patients should dispose of any patches remaining from a prescription as soon as they are no longer needed. Unused patches should be removed from their pouches, fold so that the adhesive side of the patch adheres to itself, and flush down the toilet.
2.1 Proper Patient SelectionAbuse Potential
Assess patients for their clinical risks for opioid abuse or addiction prior to being prescribing fentanyl transdermal system [see Warnings and Precautions (5.1)].
Opioid Tolerance
Opioid tolerance to an opioid of comparable potency must be established before prescribing fentanyl transdermal system [see Warnings and Precautions (5.2)].
Patients considered opioid-tolerant are those who are taking 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 for a week or longer.
2.2 DosingConversion to Fentanyl Transdermal System in Opioid-Tolerant Patients
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. Monitor patients closely for respiratory depression, especially within the first 24 to 72 hours of initiating therapy with fentanyl transdermal system [see Warnings and Precautions (5.2)].
In selecting an initial fentanyl transdermal system dose, take the following factors into account:
1. the daily dose, potency, and characteristics of the opioid the patient has been taking previously (e.g., whether it is a pure agonist or mixed agonist-antagonist);
2. the reliability of the relative potency estimates used to calculate the fentanyl transdermal system dose needed (potency estimates may vary with the route of administration);
3. the degree of opioid tolerance;
4. the general condition and medical status of the patient.
To convert adult and pediatric patients from oral or parenteral opioids to fentanyl transdermal system, use Table 1. Do not use Table 1 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.
TABLE 1*: DOSE CONVERSION GUIDELINES
Current Analgesic
Daily Dosage (mg/day)
Oral morphine
60-134
135-224
225-314
315-404
Intramuscular or Intravenous morphine
10-22
23-37
38-52
53-67
Oral oxycodone
30-67
67.5-112
112.5-157
157.5-202
Intramuscular or Intravenous oxycodone
15-33
33.1-56
56.1-78
78.1-101
Oral codeine
150-447
448-747
748-1047
1048-1347
Oral hydromorphone
8-17
17.1-28
28.1-39
39.1-51
Intravenous hydromorphone 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
Intramuscular methadone
10-22
23-37
38-52
53-67
Recommended Fentanyl Transdermal System Dose
25 mcg/hour
50 mcg/hour
75 mcg/hour
100 mcg/hour
Alternatively, for adult and pediatric patients taking opioids or doses not listed in Table 1, use the conversion methodology outlined above with Table 2.
* 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 (2.3)].
Alternatively, for adult and pediatric patients taking opioids or doses not listed in Table 1, use the following methodology:
1. Calculate the previous 24-hour analgesic requirement.
2. 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 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.
3. 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.
TABLE 2*: RECOMMENDED INITIAL FENTANYL TRANSDERMAL SYSTEM DOSE BASED UPON DAILY ORAL MORPHINE DOSE
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.
* Table 2 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 2 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 (2.3)].
For delivery rates in excess of 100 mcg/hour, multiple systems may be used.
Hepatic Impairment
Avoid the use of fentanyl transdermal system in patients with severe hepatic impairment. In patients with mild to moderate hepatic impairment, start with one half of the usual dosage of fentanyl transdermal system. Closely monitor for signs of sedation and respiratory depression, including at each dosage increase [see Warnings and Precautions (5.12), Use in Specific Populations (8.6) and Clinical Pharmacology (12.3)].
Renal Impairment
Avoid the use of fentanyl transdermal system in patients with severe renal impairment. In patients with mild to moderate renal impairment, start with one half of the usual dosage of fentanyl transdermal system. Closely monitor for signs of sedation and respiratory depression, including at each dosage increase [see Warnings and Precautions (5.13), Use in Specific Populations (8.7) and Clinical Pharmacology (12.3)].
2.3 Titration and Maintenance of TherapyOnce therapy is initiated, assess pain intensity and opioid adverse reactions frequently, especially respiratory depression [see Warnings and Precautions (5.2)]. Routinely monitor all patients for signs of misuse, abuse and addiction [see Warnings and Precautions (5.1)].
The initial fentanyl transdermal system dose may be increased after 3 days 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 fentanyl transdermal system dose.
The majority of patients are adequately maintained with fentanyl transdermal system administered every 72 hours. Some patients may not achieve adequate analgesia using this 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 fentanyl transdermal system 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.
Discontinuation of Fentanyl Transdermal System
To convert patients to another opioid, remove fentanyl transdermal system and titrate the dose of the new analgesic based upon the patient’s report of pain until adequate analgesia has been attained. Upon system removal, 17 hours or more are required for a 50% decrease in serum fentanyl concentrations. Withdrawal symptoms are possible in some patients after conversion or dose adjustment [see Warnings and Precautions (5.15)].
Do not use Tables 1 and 2 to convert from fentanyl transdermal system to other therapies to avoid overestimating the dose of the new agent potentially resulting in overdose of the new analgesic and death.
When discontinuing fentanyl transdermal system and not converting to another opioid, use a gradual downward titration, such as halving the dose every 6 days, in order to reduce the possibility of withdrawal symptoms [see Warnings and Precautions (5.15)]. It is not known at what dose level fentanyl transdermal system may be discontinued without producing the signs and symptoms of opioid withdrawal.
2.4 Administration of Fentanyl Transdermal SystemFentanyl transdermal system is for transdermal use, only.
Proper handling of fentanyl transdermal system is advised in order to prevent adverse reactions, including death, associated with accidental secondary exposure to fentanyl transdermal system [see Warnings and Precautions (5.3)].
Application and Handling Instructions
Patients should apply fentanyl transdermal system to intact, non‑irritated, and non-irradiated skin on a flat surface such as the chest, back, flank, or upper arm. In young children and persons with cognitive impairment, adhesion should be monitored and the upper back is the preferred location to minimize the potential of inappropriate patch removal. Hair at the application site may be clipped (not shaved) prior to system 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. Patients should apply fentanyl transdermal system immediately upon removal from the sealed package. The patch must not be altered (e.g., cut) in any way prior to application. Fentanyl transdermal system should not be used if the pouch seal is broken or if the patch is cut or damaged. The transdermal system is pressed firmly in place with the palm of the hand for 30 seconds, making sure the contact is complete, especially around the edges. Each fentanyl transdermal system may be worn continuously for 72 hours. The next patch is applied to a different skin site after removal of the previous transdermal system. If problems with adhesion of the fentanyl transdermal system occur, the edges of the patch may be taped with first aid tape. If problems with adhesion persist, the patch may be overlayed with a transparent adhesive film dressing. If the patch falls off before 72 hours, dispose of it by folding in half and flushing down the toilet. A new patch may be applied to a different skin site. Patients (or caregivers who apply fentanyl transdermal system) should wash their hands immediately with soap and water after applying fentanyl transdermal system. Contact with unwashed or unclothed application sites can result in secondary exposure to fentanyl transdermal system and should be avoided. Examples of accidental exposure include transfer of a fentanyl transdermal system from an adult’s body to a child while hugging, sharing the same bed as the patient, accidental sitting on a patch and possible accidental exposure of a caregiver’s skin to the medication in the patch while applying or removing the patch. Instruct patients, family members, and caregivers to keep patches in a secure location out of the reach of children and of others for whom fentanyl transdermal system was not prescribed.Avoidance of Heat
Instruct patients to avoid exposing 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, while wearing the system [see Warnings and Precautions (5.9)].
2.5 Disposal InstructionsProper disposal of fentanyl transdermal system is advised in order to prevent adverse reactions, including death, associated with accidental secondary exposure to fentanyl transdermal system [see Warnings and Precautions (5.3)].
Patients should dispose of used patches by folding the adhesive side of the patch to itself, then flush the patch down the toilet immediately upon removal.
Patients should dispose of any patches remaining from a prescription as soon as they are no longer needed. Unused patches should be removed from their pouches, fold so that the adhesive side of the patch adheres to itself, and flush down the toilet.
-
Bryant Ranch Prepack
Fentanyl Transdermal System Patch | Bryant Ranch Prepack
2.1 Proper Patient SelectionAbuse Potential
Assess patients for their clinical risks for opioid abuse or addiction prior to being prescribing fentanyl transdermal system [see Warnings and Precautions (5.1)].
Opioid Tolerance
Opioid tolerance to an opioid of comparable potency must be established before prescribing fentanyl transdermal system [see Warnings and Precautions (5.2)].
Patients considered opioid-tolerant are those who are taking 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 for a week or longer.
2.2 DosingConversion to Fentanyl Transdermal System in Opioid-Tolerant Patients
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. Monitor patients closely for respiratory depression, especially within the first 24 to 72 hours of initiating therapy with fentanyl transdermal system [see Warnings and Precautions (5.2)].
In selecting an initial fentanyl transdermal system dose, take the following factors into account:
1. the daily dose, potency, and characteristics of the opioid the patient has been taking previously (e.g., whether it is a pure agonist or mixed agonist-antagonist);
2. the reliability of the relative potency estimates used to calculate the fentanyl transdermal system dose needed (potency estimates may vary with the route of administration);
3. the degree of opioid tolerance;
4. the general condition and medical status of the patient.
To convert adult and pediatric patients from oral or parenteral opioids to fentanyl transdermal system, use Table 1. Do not use Table 1 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.
TABLE 1*: DOSE CONVERSION GUIDELINES
Current Analgesic
Daily Dosage (mg/day)
Oral morphine
60-134
135-224
225-314
315-404
Intramuscular or Intravenous morphine
10-22
23-37
38-52
53-67
Oral oxycodone
30-67
67.5-112
112.5-157
157.5-202
Intramuscular or Intravenous oxycodone
15-33
33.1-56
56.1-78
78.1-101
Oral codeine
150-447
448-747
748-1047
1048-1347
Oral hydromorphone
8-17
17.1-28
28.1-39
39.1-51
Intravenous hydromorphone 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
Intramuscular methadone
10-22
23-37
38-52
53-67
Recommended Fentanyl Transdermal System Dose
25 mcg/hour
50 mcg/hour
75 mcg/hour
100 mcg/hour
Alternatively, for adult and pediatric patients taking opioids or doses not listed in Table 1, use the conversion methodology outlined above with Table 2.
* 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 (2.3)].
Alternatively, for adult and pediatric patients taking opioids or doses not listed in Table 1, use the following methodology:
1. Calculate the previous 24-hour analgesic requirement.
2. 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 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.
3. 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.
TABLE 2*: RECOMMENDED INITIAL FENTANYL TRANSDERMAL SYSTEM DOSE BASED UPON DAILY ORAL MORPHINE DOSE
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.
* Table 2 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 2 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 (2.3)].
For delivery rates in excess of 100 mcg/hour, multiple systems may be used.
Hepatic Impairment
Avoid the use of fentanyl transdermal system in patients with severe hepatic impairment. In patients with mild to moderate hepatic impairment, start with one half of the usual dosage of fentanyl transdermal system. Closely monitor for signs of sedation and respiratory depression, including at each dosage increase [see Warnings and Precautions (5.12), Use in Specific Populations (8.6) and Clinical Pharmacology (12.3)].
Renal Impairment
Avoid the use of fentanyl transdermal system in patients with severe renal impairment. In patients with mild to moderate renal impairment, start with one half of the usual dosage of fentanyl transdermal system. Closely monitor for signs of sedation and respiratory depression, including at each dosage increase [see Warnings and Precautions (5.13), Use in Specific Populations (8.7) and Clinical Pharmacology (12.3)].
2.3 Titration and Maintenance of TherapyOnce therapy is initiated, assess pain intensity and opioid adverse reactions frequently, especially respiratory depression [see Warnings and Precautions (5.2)]. Routinely monitor all patients for signs of misuse, abuse and addiction [see Warnings and Precautions (5.1)].
The initial fentanyl transdermal system dose may be increased after 3 days 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 fentanyl transdermal system dose.
The majority of patients are adequately maintained with fentanyl transdermal system administered every 72 hours. Some patients may not achieve adequate analgesia using this 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 fentanyl transdermal system 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.
Discontinuation of Fentanyl Transdermal System
To convert patients to another opioid, remove fentanyl transdermal system and titrate the dose of the new analgesic based upon the patient’s report of pain until adequate analgesia has been attained. Upon system removal, 17 hours or more are required for a 50% decrease in serum fentanyl concentrations. Withdrawal symptoms are possible in some patients after conversion or dose adjustment [see Warnings and Precautions (5.15)].
Do not use Tables 1 and 2 to convert from fentanyl transdermal system to other therapies to avoid overestimating the dose of the new agent potentially resulting in overdose of the new analgesic and death.
When discontinuing fentanyl transdermal system and not converting to another opioid, use a gradual downward titration, such as halving the dose every 6 days, in order to reduce the possibility of withdrawal symptoms [see Warnings and Precautions (5.15)]. It is not known at what dose level fentanyl transdermal system may be discontinued without producing the signs and symptoms of opioid withdrawal.
2.4 Administration of Fentanyl Transdermal SystemFentanyl transdermal system is for transdermal use, only.
Proper handling of fentanyl transdermal system is advised in order to prevent adverse reactions, including death, associated with accidental secondary exposure to fentanyl transdermal system [see Warnings and Precautions (5.3)].
Application and Handling Instructions
Patients should apply fentanyl transdermal system to intact, non‑irritated, and non-irradiated skin on a flat surface such as the chest, back, flank, or upper arm. In young children and persons with cognitive impairment, adhesion should be monitored and the upper back is the preferred location to minimize the potential of inappropriate patch removal. Hair at the application site may be clipped (not shaved) prior to system 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. Patients should apply fentanyl transdermal system immediately upon removal from the sealed package. The patch must not be altered (e.g., cut) in any way prior to application. Fentanyl transdermal system should not be used if the pouch seal is broken or if the patch is cut or damaged. The transdermal system is pressed firmly in place with the palm of the hand for 30 seconds, making sure the contact is complete, especially around the edges. Each fentanyl transdermal system may be worn continuously for 72 hours. The next patch is applied to a different skin site after removal of the previous transdermal system. If problems with adhesion of the fentanyl transdermal system occur, the edges of the patch may be taped with first aid tape. If problems with adhesion persist, the patch may be overlayed with a transparent adhesive film dressing. If the patch falls off before 72 hours, dispose of it by folding in half and flushing down the toilet. A new patch may be applied to a different skin site. Patients (or caregivers who apply fentanyl transdermal system) should wash their hands immediately with soap and water after applying fentanyl transdermal system. Contact with unwashed or unclothed application sites can result in secondary exposure to fentanyl transdermal system and should be avoided. Examples of accidental exposure include transfer of a fentanyl transdermal system from an adult’s body to a child while hugging, sharing the same bed as the patient, accidental sitting on a patch and possible accidental exposure of a caregiver’s skin to the medication in the patch while applying or removing the patch. Instruct patients, family members, and caregivers to keep patches in a secure location out of the reach of children and of others for whom fentanyl transdermal system was not prescribed.Avoidance of Heat
Instruct patients to avoid exposing 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, while wearing the system [see Warnings and Precautions (5.9)].
2.5 Disposal InstructionsProper disposal of fentanyl transdermal system is advised in order to prevent adverse reactions, including death, associated with accidental secondary exposure to fentanyl transdermal system [see Warnings and Precautions (5.3)].
Patients should dispose of used patches by folding the adhesive side of the patch to itself, then flush the patch down the toilet immediately upon removal.
Patients should dispose of any patches remaining from a prescription as soon as they are no longer needed. Unused patches should be removed from their pouches, fold so that the adhesive side of the patch adheres to itself, and flush down the toilet.
2.1 Proper Patient SelectionAbuse Potential
Assess patients for their clinical risks for opioid abuse or addiction prior to being prescribing fentanyl transdermal system [see Warnings and Precautions (5.1)].
Opioid Tolerance
Opioid tolerance to an opioid of comparable potency must be established before prescribing fentanyl transdermal system [see Warnings and Precautions (5.2)].
Patients considered opioid-tolerant are those who are taking 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 for a week or longer.
2.2 DosingConversion to Fentanyl Transdermal System in Opioid-Tolerant Patients
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. Monitor patients closely for respiratory depression, especially within the first 24 to 72 hours of initiating therapy with fentanyl transdermal system [see Warnings and Precautions (5.2)].
In selecting an initial fentanyl transdermal system dose, take the following factors into account:
1. the daily dose, potency, and characteristics of the opioid the patient has been taking previously (e.g., whether it is a pure agonist or mixed agonist-antagonist);
2. the reliability of the relative potency estimates used to calculate the fentanyl transdermal system dose needed (potency estimates may vary with the route of administration);
3. the degree of opioid tolerance;
4. the general condition and medical status of the patient.
To convert adult and pediatric patients from oral or parenteral opioids to fentanyl transdermal system, use Table 1. Do not use Table 1 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.
TABLE 1*: DOSE CONVERSION GUIDELINES
Current Analgesic
Daily Dosage (mg/day)
Oral morphine
60-134
135-224
225-314
315-404
Intramuscular or Intravenous morphine
10-22
23-37
38-52
53-67
Oral oxycodone
30-67
67.5-112
112.5-157
157.5-202
Intramuscular or Intravenous oxycodone
15-33
33.1-56
56.1-78
78.1-101
Oral codeine
150-447
448-747
748-1047
1048-1347
Oral hydromorphone
8-17
17.1-28
28.1-39
39.1-51
Intravenous hydromorphone 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
Intramuscular methadone
10-22
23-37
38-52
53-67
Recommended Fentanyl Transdermal System Dose
25 mcg/hour
50 mcg/hour
75 mcg/hour
100 mcg/hour
Alternatively, for adult and pediatric patients taking opioids or doses not listed in Table 1, use the conversion methodology outlined above with Table 2.
* 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 (2.3)].
Alternatively, for adult and pediatric patients taking opioids or doses not listed in Table 1, use the following methodology:
1. Calculate the previous 24-hour analgesic requirement.
2. 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 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.
3. 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.
TABLE 2*: RECOMMENDED INITIAL FENTANYL TRANSDERMAL SYSTEM DOSE BASED UPON DAILY ORAL MORPHINE DOSE
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.
* Table 2 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 2 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 (2.3)].
For delivery rates in excess of 100 mcg/hour, multiple systems may be used.
Hepatic Impairment
Avoid the use of fentanyl transdermal system in patients with severe hepatic impairment. In patients with mild to moderate hepatic impairment, start with one half of the usual dosage of fentanyl transdermal system. Closely monitor for signs of sedation and respiratory depression, including at each dosage increase [see Warnings and Precautions (5.12), Use in Specific Populations (8.6) and Clinical Pharmacology (12.3)].
Renal Impairment
Avoid the use of fentanyl transdermal system in patients with severe renal impairment. In patients with mild to moderate renal impairment, start with one half of the usual dosage of fentanyl transdermal system. Closely monitor for signs of sedation and respiratory depression, including at each dosage increase [see Warnings and Precautions (5.13), Use in Specific Populations (8.7) and Clinical Pharmacology (12.3)].
2.3 Titration and Maintenance of TherapyOnce therapy is initiated, assess pain intensity and opioid adverse reactions frequently, especially respiratory depression [see Warnings and Precautions (5.2)]. Routinely monitor all patients for signs of misuse, abuse and addiction [see Warnings and Precautions (5.1)].
The initial fentanyl transdermal system dose may be increased after 3 days 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 fentanyl transdermal system dose.
The majority of patients are adequately maintained with fentanyl transdermal system administered every 72 hours. Some patients may not achieve adequate analgesia using this 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 fentanyl transdermal system 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.
Discontinuation of Fentanyl Transdermal System
To convert patients to another opioid, remove fentanyl transdermal system and titrate the dose of the new analgesic based upon the patient’s report of pain until adequate analgesia has been attained. Upon system removal, 17 hours or more are required for a 50% decrease in serum fentanyl concentrations. Withdrawal symptoms are possible in some patients after conversion or dose adjustment [see Warnings and Precautions (5.15)].
Do not use Tables 1 and 2 to convert from fentanyl transdermal system to other therapies to avoid overestimating the dose of the new agent potentially resulting in overdose of the new analgesic and death.
When discontinuing fentanyl transdermal system and not converting to another opioid, use a gradual downward titration, such as halving the dose every 6 days, in order to reduce the possibility of withdrawal symptoms [see Warnings and Precautions (5.15)]. It is not known at what dose level fentanyl transdermal system may be discontinued without producing the signs and symptoms of opioid withdrawal.
2.4 Administration of Fentanyl Transdermal SystemFentanyl transdermal system is for transdermal use, only.
Proper handling of fentanyl transdermal system is advised in order to prevent adverse reactions, including death, associated with accidental secondary exposure to fentanyl transdermal system [see Warnings and Precautions (5.3)].
Application and Handling Instructions
Patients should apply fentanyl transdermal system to intact, non‑irritated, and non-irradiated skin on a flat surface such as the chest, back, flank, or upper arm. In young children and persons with cognitive impairment, adhesion should be monitored and the upper back is the preferred location to minimize the potential of inappropriate patch removal. Hair at the application site may be clipped (not shaved) prior to system 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. Patients should apply fentanyl transdermal system immediately upon removal from the sealed package. The patch must not be altered (e.g., cut) in any way prior to application. Fentanyl transdermal system should not be used if the pouch seal is broken or if the patch is cut or damaged. The transdermal system is pressed firmly in place with the palm of the hand for 30 seconds, making sure the contact is complete, especially around the edges. Each fentanyl transdermal system may be worn continuously for 72 hours. The next patch is applied to a different skin site after removal of the previous transdermal system. If problems with adhesion of the fentanyl transdermal system occur, the edges of the patch may be taped with first aid tape. If problems with adhesion persist, the patch may be overlayed with a transparent adhesive film dressing. If the patch falls off before 72 hours, dispose of it by folding in half and flushing down the toilet. A new patch may be applied to a different skin site. Patients (or caregivers who apply fentanyl transdermal system) should wash their hands immediately with soap and water after applying fentanyl transdermal system. Contact with unwashed or unclothed application sites can result in secondary exposure to fentanyl transdermal system and should be avoided. Examples of accidental exposure include transfer of a fentanyl transdermal system from an adult’s body to a child while hugging, sharing the same bed as the patient, accidental sitting on a patch and possible accidental exposure of a caregiver’s skin to the medication in the patch while applying or removing the patch. Instruct patients, family members, and caregivers to keep patches in a secure location out of the reach of children and of others for whom fentanyl transdermal system was not prescribed.Avoidance of Heat
Instruct patients to avoid exposing 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, while wearing the system [see Warnings and Precautions (5.9)].
2.5 Disposal InstructionsProper disposal of fentanyl transdermal system is advised in order to prevent adverse reactions, including death, associated with accidental secondary exposure to fentanyl transdermal system [see Warnings and Precautions (5.3)].
Patients should dispose of used patches by folding the adhesive side of the patch to itself, then flush the patch down the toilet immediately upon removal.
Patients should dispose of any patches remaining from a prescription as soon as they are no longer needed. Unused patches should be removed from their pouches, fold so that the adhesive side of the patch adheres to itself, and flush down the toilet.
-
Bryant Ranch Prepack
Fentanyl Transdermal System Patch | Bryant Ranch Prepack
2.1 Proper Patient SelectionAbuse Potential
Assess patients for their clinical risks for opioid abuse or addiction prior to being prescribing fentanyl transdermal system [see Warnings and Precautions (5.1)].
Opioid Tolerance
Opioid tolerance to an opioid of comparable potency must be established before prescribing fentanyl transdermal system [see Warnings and Precautions (5.2)].
Patients considered opioid-tolerant are those who are taking 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 for a week or longer.
2.2 DosingConversion to Fentanyl Transdermal System in Opioid-Tolerant Patients
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. Monitor patients closely for respiratory depression, especially within the first 24 to 72 hours of initiating therapy with fentanyl transdermal system [see Warnings and Precautions (5.2)].
In selecting an initial fentanyl transdermal system dose, take the following factors into account:
1. the daily dose, potency, and characteristics of the opioid the patient has been taking previously (e.g., whether it is a pure agonist or mixed agonist-antagonist);
2. the reliability of the relative potency estimates used to calculate the fentanyl transdermal system dose needed (potency estimates may vary with the route of administration);
3. the degree of opioid tolerance;
4. the general condition and medical status of the patient.
To convert adult and pediatric patients from oral or parenteral opioids to fentanyl transdermal system, use Table 1. Do not use Table 1 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.
TABLE 1*: DOSE CONVERSION GUIDELINES
Current Analgesic
Daily Dosage (mg/day)
Oral morphine
60-134
135-224
225-314
315-404
Intramuscular or Intravenous morphine
10-22
23-37
38-52
53-67
Oral oxycodone
30-67
67.5-112
112.5-157
157.5-202
Intramuscular or Intravenous oxycodone
15-33
33.1-56
56.1-78
78.1-101
Oral codeine
150-447
448-747
748-1047
1048-1347
Oral hydromorphone
8-17
17.1-28
28.1-39
39.1-51
Intravenous hydromorphone 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
Intramuscular methadone
10-22
23-37
38-52
53-67
Recommended Fentanyl Transdermal System Dose
25 mcg/hour
50 mcg/hour
75 mcg/hour
100 mcg/hour
Alternatively, for adult and pediatric patients taking opioids or doses not listed in Table 1, use the conversion methodology outlined above with Table 2.
* 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 (2.3)].
Alternatively, for adult and pediatric patients taking opioids or doses not listed in Table 1, use the following methodology:
1. Calculate the previous 24-hour analgesic requirement.
2. 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 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.
3. 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.
TABLE 2*: RECOMMENDED INITIAL FENTANYL TRANSDERMAL SYSTEM DOSE BASED UPON DAILY ORAL MORPHINE DOSE
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.
* Table 2 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 2 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 (2.3)].
For delivery rates in excess of 100 mcg/hour, multiple systems may be used.
Hepatic Impairment
Avoid the use of fentanyl transdermal system in patients with severe hepatic impairment. In patients with mild to moderate hepatic impairment, start with one half of the usual dosage of fentanyl transdermal system. Closely monitor for signs of sedation and respiratory depression, including at each dosage increase [see Warnings and Precautions (5.12), Use in Specific Populations (8.6) and Clinical Pharmacology (12.3)].
Renal Impairment
Avoid the use of fentanyl transdermal system in patients with severe renal impairment. In patients with mild to moderate renal impairment, start with one half of the usual dosage of fentanyl transdermal system. Closely monitor for signs of sedation and respiratory depression, including at each dosage increase [see Warnings and Precautions (5.13), Use in Specific Populations (8.7) and Clinical Pharmacology (12.3)].
2.3 Titration and Maintenance of TherapyOnce therapy is initiated, assess pain intensity and opioid adverse reactions frequently, especially respiratory depression [see Warnings and Precautions (5.2)]. Routinely monitor all patients for signs of misuse, abuse and addiction [see Warnings and Precautions (5.1)].
The initial fentanyl transdermal system dose may be increased after 3 days 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 fentanyl transdermal system dose.
The majority of patients are adequately maintained with fentanyl transdermal system administered every 72 hours. Some patients may not achieve adequate analgesia using this 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 fentanyl transdermal system 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.
Discontinuation of Fentanyl Transdermal System
To convert patients to another opioid, remove fentanyl transdermal system and titrate the dose of the new analgesic based upon the patient’s report of pain until adequate analgesia has been attained. Upon system removal, 17 hours or more are required for a 50% decrease in serum fentanyl concentrations. Withdrawal symptoms are possible in some patients after conversion or dose adjustment [see Warnings and Precautions (5.15)].
Do not use Tables 1 and 2 to convert from fentanyl transdermal system to other therapies to avoid overestimating the dose of the new agent potentially resulting in overdose of the new analgesic and death.
When discontinuing fentanyl transdermal system and not converting to another opioid, use a gradual downward titration, such as halving the dose every 6 days, in order to reduce the possibility of withdrawal symptoms [see Warnings and Precautions (5.15)]. It is not known at what dose level fentanyl transdermal system may be discontinued without producing the signs and symptoms of opioid withdrawal.
2.4 Administration of Fentanyl Transdermal SystemFentanyl transdermal system is for transdermal use, only.
Proper handling of fentanyl transdermal system is advised in order to prevent adverse reactions, including death, associated with accidental secondary exposure to fentanyl transdermal system [see Warnings and Precautions (5.3)].
Application and Handling Instructions
Patients should apply fentanyl transdermal system to intact, non‑irritated, and non-irradiated skin on a flat surface such as the chest, back, flank, or upper arm. In young children and persons with cognitive impairment, adhesion should be monitored and the upper back is the preferred location to minimize the potential of inappropriate patch removal. Hair at the application site may be clipped (not shaved) prior to system 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. Patients should apply fentanyl transdermal system immediately upon removal from the sealed package. The patch must not be altered (e.g., cut) in any way prior to application. Fentanyl transdermal system should not be used if the pouch seal is broken or if the patch is cut or damaged. The transdermal system is pressed firmly in place with the palm of the hand for 30 seconds, making sure the contact is complete, especially around the edges. Each fentanyl transdermal system may be worn continuously for 72 hours. The next patch is applied to a different skin site after removal of the previous transdermal system. If problems with adhesion of the fentanyl transdermal system occur, the edges of the patch may be taped with first aid tape. If problems with adhesion persist, the patch may be overlayed with a transparent adhesive film dressing. If the patch falls off before 72 hours, dispose of it by folding in half and flushing down the toilet. A new patch may be applied to a different skin site. Patients (or caregivers who apply fentanyl transdermal system) should wash their hands immediately with soap and water after applying fentanyl transdermal system. Contact with unwashed or unclothed application sites can result in secondary exposure to fentanyl transdermal system and should be avoided. Examples of accidental exposure include transfer of a fentanyl transdermal system from an adult’s body to a child while hugging, sharing the same bed as the patient, accidental sitting on a patch and possible accidental exposure of a caregiver’s skin to the medication in the patch while applying or removing the patch. Instruct patients, family members, and caregivers to keep patches in a secure location out of the reach of children and of others for whom fentanyl transdermal system was not prescribed.Avoidance of Heat
Instruct patients to avoid exposing 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, while wearing the system [see Warnings and Precautions (5.9)].
2.5 Disposal InstructionsProper disposal of fentanyl transdermal system is advised in order to prevent adverse reactions, including death, associated with accidental secondary exposure to fentanyl transdermal system [see Warnings and Precautions (5.3)].
Patients should dispose of used patches by folding the adhesive side of the patch to itself, then flush the patch down the toilet immediately upon removal.
Patients should dispose of any patches remaining from a prescription as soon as they are no longer needed. Unused patches should be removed from their pouches, fold so that the adhesive side of the patch adheres to itself, and flush down the toilet.
2.1 Proper Patient SelectionAbuse Potential
Assess patients for their clinical risks for opioid abuse or addiction prior to being prescribing fentanyl transdermal system [see Warnings and Precautions (5.1)].
Opioid Tolerance
Opioid tolerance to an opioid of comparable potency must be established before prescribing fentanyl transdermal system [see Warnings and Precautions (5.2)].
Patients considered opioid-tolerant are those who are taking 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 for a week or longer.
2.2 DosingConversion to Fentanyl Transdermal System in Opioid-Tolerant Patients
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. Monitor patients closely for respiratory depression, especially within the first 24 to 72 hours of initiating therapy with fentanyl transdermal system [see Warnings and Precautions (5.2)].
In selecting an initial fentanyl transdermal system dose, take the following factors into account:
1. the daily dose, potency, and characteristics of the opioid the patient has been taking previously (e.g., whether it is a pure agonist or mixed agonist-antagonist);
2. the reliability of the relative potency estimates used to calculate the fentanyl transdermal system dose needed (potency estimates may vary with the route of administration);
3. the degree of opioid tolerance;
4. the general condition and medical status of the patient.
To convert adult and pediatric patients from oral or parenteral opioids to fentanyl transdermal system, use Table 1. Do not use Table 1 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.
TABLE 1*: DOSE CONVERSION GUIDELINES
Current Analgesic
Daily Dosage (mg/day)
Oral morphine
60-134
135-224
225-314
315-404
Intramuscular or Intravenous morphine
10-22
23-37
38-52
53-67
Oral oxycodone
30-67
67.5-112
112.5-157
157.5-202
Intramuscular or Intravenous oxycodone
15-33
33.1-56
56.1-78
78.1-101
Oral codeine
150-447
448-747
748-1047
1048-1347
Oral hydromorphone
8-17
17.1-28
28.1-39
39.1-51
Intravenous hydromorphone 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
Intramuscular methadone
10-22
23-37
38-52
53-67
Recommended Fentanyl Transdermal System Dose
25 mcg/hour
50 mcg/hour
75 mcg/hour
100 mcg/hour
Alternatively, for adult and pediatric patients taking opioids or doses not listed in Table 1, use the conversion methodology outlined above with Table 2.
* 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 (2.3)].
Alternatively, for adult and pediatric patients taking opioids or doses not listed in Table 1, use the following methodology:
1. Calculate the previous 24-hour analgesic requirement.
2. 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 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.
3. 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.
TABLE 2*: RECOMMENDED INITIAL FENTANYL TRANSDERMAL SYSTEM DOSE BASED UPON DAILY ORAL MORPHINE DOSE
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.
* Table 2 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 2 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 (2.3)].
For delivery rates in excess of 100 mcg/hour, multiple systems may be used.
Hepatic Impairment
Avoid the use of fentanyl transdermal system in patients with severe hepatic impairment. In patients with mild to moderate hepatic impairment, start with one half of the usual dosage of fentanyl transdermal system. Closely monitor for signs of sedation and respiratory depression, including at each dosage increase [see Warnings and Precautions (5.12), Use in Specific Populations (8.6) and Clinical Pharmacology (12.3)].
Renal Impairment
Avoid the use of fentanyl transdermal system in patients with severe renal impairment. In patients with mild to moderate renal impairment, start with one half of the usual dosage of fentanyl transdermal system. Closely monitor for signs of sedation and respiratory depression, including at each dosage increase [see Warnings and Precautions (5.13), Use in Specific Populations (8.7) and Clinical Pharmacology (12.3)].
2.3 Titration and Maintenance of TherapyOnce therapy is initiated, assess pain intensity and opioid adverse reactions frequently, especially respiratory depression [see Warnings and Precautions (5.2)]. Routinely monitor all patients for signs of misuse, abuse and addiction [see Warnings and Precautions (5.1)].
The initial fentanyl transdermal system dose may be increased after 3 days 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 fentanyl transdermal system dose.
The majority of patients are adequately maintained with fentanyl transdermal system administered every 72 hours. Some patients may not achieve adequate analgesia using this 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 fentanyl transdermal system 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.
Discontinuation of Fentanyl Transdermal System
To convert patients to another opioid, remove fentanyl transdermal system and titrate the dose of the new analgesic based upon the patient’s report of pain until adequate analgesia has been attained. Upon system removal, 17 hours or more are required for a 50% decrease in serum fentanyl concentrations. Withdrawal symptoms are possible in some patients after conversion or dose adjustment [see Warnings and Precautions (5.15)].
Do not use Tables 1 and 2 to convert from fentanyl transdermal system to other therapies to avoid overestimating the dose of the new agent potentially resulting in overdose of the new analgesic and death.
When discontinuing fentanyl transdermal system and not converting to another opioid, use a gradual downward titration, such as halving the dose every 6 days, in order to reduce the possibility of withdrawal symptoms [see Warnings and Precautions (5.15)]. It is not known at what dose level fentanyl transdermal system may be discontinued without producing the signs and symptoms of opioid withdrawal.
2.4 Administration of Fentanyl Transdermal SystemFentanyl transdermal system is for transdermal use, only.
Proper handling of fentanyl transdermal system is advised in order to prevent adverse reactions, including death, associated with accidental secondary exposure to fentanyl transdermal system [see Warnings and Precautions (5.3)].
Application and Handling Instructions
Patients should apply fentanyl transdermal system to intact, non‑irritated, and non-irradiated skin on a flat surface such as the chest, back, flank, or upper arm. In young children and persons with cognitive impairment, adhesion should be monitored and the upper back is the preferred location to minimize the potential of inappropriate patch removal. Hair at the application site may be clipped (not shaved) prior to system 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. Patients should apply fentanyl transdermal system immediately upon removal from the sealed package. The patch must not be altered (e.g., cut) in any way prior to application. Fentanyl transdermal system should not be used if the pouch seal is broken or if the patch is cut or damaged. The transdermal system is pressed firmly in place with the palm of the hand for 30 seconds, making sure the contact is complete, especially around the edges. Each fentanyl transdermal system may be worn continuously for 72 hours. The next patch is applied to a different skin site after removal of the previous transdermal system. If problems with adhesion of the fentanyl transdermal system occur, the edges of the patch may be taped with first aid tape. If problems with adhesion persist, the patch may be overlayed with a transparent adhesive film dressing. If the patch falls off before 72 hours, dispose of it by folding in half and flushing down the toilet. A new patch may be applied to a different skin site. Patients (or caregivers who apply fentanyl transdermal system) should wash their hands immediately with soap and water after applying fentanyl transdermal system. Contact with unwashed or unclothed application sites can result in secondary exposure to fentanyl transdermal system and should be avoided. Examples of accidental exposure include transfer of a fentanyl transdermal system from an adult’s body to a child while hugging, sharing the same bed as the patient, accidental sitting on a patch and possible accidental exposure of a caregiver’s skin to the medication in the patch while applying or removing the patch. Instruct patients, family members, and caregivers to keep patches in a secure location out of the reach of children and of others for whom fentanyl transdermal system was not prescribed.Avoidance of Heat
Instruct patients to avoid exposing 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, while wearing the system [see Warnings and Precautions (5.9)].
2.5 Disposal InstructionsProper disposal of fentanyl transdermal system is advised in order to prevent adverse reactions, including death, associated with accidental secondary exposure to fentanyl transdermal system [see Warnings and Precautions (5.3)].
Patients should dispose of used patches by folding the adhesive side of the patch to itself, then flush the patch down the toilet immediately upon removal.
Patients should dispose of any patches remaining from a prescription as soon as they are no longer needed. Unused patches should be removed from their pouches, fold so that the adhesive side of the patch adheres to itself, and flush down the toilet.
-
Lake Erie Medical Dba Quality Care Products Llc
Fentanyl Transdermal System Patch | Lake Erie Medical Dba Quality Care Products Llc
2.1 Proper Patient SelectionAbuse Potential
Assess patients for their clinical risks for opioid abuse or addiction prior to being prescribing fentanyl transdermal system [see Warnings and Precautions (5.1)].
Opioid Tolerance
Opioid tolerance to an opioid of comparable potency must be established before prescribing fentanyl transdermal system [see Warnings and Precautions (5.2)].
Patients considered opioid-tolerant are those who are taking 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 for a week or longer.
2.2 DosingConversion to Fentanyl Transdermal System in Opioid-Tolerant Patients
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. Monitor patients closely for respiratory depression, especially within the first 24 to 72 hours of initiating therapy with fentanyl transdermal system [see Warnings and Precautions (5.2)].
In selecting an initial fentanyl transdermal system dose, take the following factors into account:
1. the daily dose, potency, and characteristics of the opioid the patient has been taking previously (e.g., whether it is a pure agonist or mixed agonist-antagonist);
2. the reliability of the relative potency estimates used to calculate the fentanyl transdermal system dose needed (potency estimates may vary with the route of administration);
3. the degree of opioid tolerance;
4. the general condition and medical status of the patient.
To convert adult and pediatric patients from oral or parenteral opioids to fentanyl transdermal system, use Table 1. Do not use Table 1 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.
TABLE 1*: DOSE CONVERSION GUIDELINES
Current Analgesic
Daily Dosage (mg/day)
Oral morphine
60-134
135-224
225-314
315-404
Intramuscular or Intravenous morphine
10-22
23-37
38-52
53-67
Oral oxycodone
30-67
67.5-112
112.5-157
157.5-202
Intramuscular or Intravenous oxycodone
15-33
33.1-56
56.1-78
78.1-101
Oral codeine
150-447
448-747
748-1047
1048-1347
Oral hydromorphone
8-17
17.1-28
28.1-39
39.1-51
Intravenous hydromorphone 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
Intramuscular methadone
10-22
23-37
38-52
53-67
Recommended Fentanyl Transdermal System Dose
25 mcg/hour
50 mcg/hour
75 mcg/hour
100 mcg/hour
Alternatively, for adult and pediatric patients taking opioids or doses not listed in Table 1, use the conversion methodology outlined above with Table 2.
*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 (2.3)].
Alternatively, for adult and pediatric patients taking opioids or doses not listed in Table 1, use the following methodology:
1. Calculate the previous 24-hour analgesic requirement.
2. 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 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.
3. 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.
TABLE 2*: RECOMMENDED INITIAL FENTANYL TRANSDERMAL SYSTEM DOSE BASED UPON DAILY ORAL MORPHINE DOSE
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.
*Table 2 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 2 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 (2.3)].
For delivery rates in excess of 100 mcg/hour, multiple systems may be used.
Hepatic Impairment
Avoid the use of fentanyl transdermal system in patients with severe hepatic impairment. In patients with mild to moderate hepatic impairment, start with one half of the usual dosage of fentanyl transdermal system. Closely monitor for signs of sedation and respiratory depression, including at each dosage increase [see Warnings and Precautions (5.12), Use in Specific Populations (8.6) and Clinical Pharmacology (12.3)].
Renal Impairment
Avoid the use of fentanyl transdermal system in patients with severe renal impairment. In patients with mild to moderate renal impairment, start with one half of the usual dosage of fentanyl transdermal system. Closely monitor for signs of sedation and respiratory depression, including at each dosage increase [see Warnings and Precautions (5.13), Use in Specific Populations (8.7) and Clinical Pharmacology (12.3)].
2.3 Titration and Maintenance of TherapyOnce therapy is initiated, assess pain intensity and opioid adverse reactions frequently, especially respiratory depression [see Warnings and Precautions (5.2)]. Routinely monitor all patients for signs of misuse, abuse and addiction [see Warnings and Precautions (5.1)].
The initial fentanyl transdermal system dose may be increased after 3 days 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 fentanyl transdermal system dose.
The majority of patients are adequately maintained with fentanyl transdermal system administered every 72 hours. Some patients may not achieve adequate analgesia using this 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 fentanyl transdermal system 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.
Discontinuation of Fentanyl Transdermal System
To convert patients to another opioid, remove fentanyl transdermal system and titrate the dose of the new analgesic based upon the patient’s report of pain until adequate analgesia has been attained. Upon system removal, 17 hours or more are required for a 50% decrease in serum fentanyl concentrations. Withdrawal symptoms are possible in some patients after conversion or dose adjustment [see Warnings and Precautions (5.15)].
Do not use Tables1 and2 to convert from fentanyl transdermal system to other therapies to avoid overestimating the dose of the new agent potentially resulting in overdose of the new analgesic and death.
When discontinuing fentanyl transdermal system and not converting to another opioid, use a gradual downward titration, such as halving the dose every 6 days, in order to reduce the possibility of withdrawal symptoms [see Warnings and Precautions (5.15)]. It is not known at what dose level fentanyl transdermal system may be discontinued without producing the signs and symptoms of opioid withdrawal.
2.4 Administration of Fentanyl Transdermal SystemFentanyl transdermal system is for transdermal use, only.
Proper handling of fentanyl transdermal system is advised in order to prevent adverse reactions, including death, associated with accidental secondary exposure to fentanyl transdermal system [see Warnings and Precautions (5.3)].
Application and Handling Instructions
Patients should apply fentanyl transdermal system to intact, non‑irritated, and non-irradiated skin on a flat surface such as the chest, back, flank, or upper arm. In young children and persons with cognitive impairment, adhesion should be monitored and the upper back is the preferred location to minimize the potential of inappropriate patch removal. Hair at the application site may be clipped (not shaved) prior to system 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. Patients should apply fentanyl transdermal system immediately upon removal from the sealed package. The patch must not be altered (e.g., cut) in any way prior to application. Fentanyl transdermal system should not be used if the pouch seal is broken or if the patch is cut or damaged. The transdermal system is pressed firmly in place with the palm of the hand for 30 seconds, making sure the contact is complete, especially around the edges. Each fentanyl transdermal system may be worn continuously for 72 hours. The next patch is applied to a different skin site after removal of the previous transdermal system. If problems with adhesion of the fentanyl transdermal system occur, the edges of the patch may be taped with first aid tape. If problems with adhesion persist, the patch may be overlayed with a transparent adhesive film dressing. If the patch falls off before 72 hours, dispose of it by folding in half and flushing down the toilet. A new patch may be applied to a different skin site. Patients (or caregivers who apply fentanyl transdermal system) should wash their hands immediately with soap and water after applying fentanyl transdermal system. Contact with unwashed or unclothed application sites can result in secondary exposure to fentanyl transdermal system and should be avoided. Examples of accidental exposure include transfer of a fentanyl transdermal system from an adult’s body to a child while hugging, sharing the same bed as the patient, accidental sitting on a patch and possible accidental exposure of a caregiver’s skin to the medication in the patch while applying or removing the patch. Instruct patients, family members, and caregivers to keep patches in a secure location out of the reach of children and of others for whom fentanyl transdermal system was not prescribed.Avoidance of Heat
Instruct patients to avoid exposing 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, while wearing the system [see Warnings and Precautions (5.9)].
2.5 Disposal InstructionsProper disposal of fentanyl transdermal system is advised in order to prevent adverse reactions, including death, associated with accidental secondary exposure to fentanyl transdermal system [see Warnings and Precautions (5.3)].
Patients should dispose of used patches by folding the adhesive side of the patch to itself, then flush the patch down the toilet immediately upon removal.
Patients should dispose of any patches remaining from a prescription as soon as they are no longer needed. Unused patches should be removed from their pouches, fold so that the adhesive side of the patch adheres to itself, and flush down the toilet.
2.1 Proper Patient SelectionAbuse Potential
Assess patients for their clinical risks for opioid abuse or addiction prior to being prescribing fentanyl transdermal system [see Warnings and Precautions (5.1)].
Opioid Tolerance
Opioid tolerance to an opioid of comparable potency must be established before prescribing fentanyl transdermal system [see Warnings and Precautions (5.2)].
Patients considered opioid-tolerant are those who are taking 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 for a week or longer.
2.2 DosingConversion to Fentanyl Transdermal System in Opioid-Tolerant Patients
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. Monitor patients closely for respiratory depression, especially within the first 24 to 72 hours of initiating therapy with fentanyl transdermal system [see Warnings and Precautions (5.2)].
In selecting an initial fentanyl transdermal system dose, take the following factors into account:
1. the daily dose, potency, and characteristics of the opioid the patient has been taking previously (e.g., whether it is a pure agonist or mixed agonist-antagonist);
2. the reliability of the relative potency estimates used to calculate the fentanyl transdermal system dose needed (potency estimates may vary with the route of administration);
3. the degree of opioid tolerance;
4. the general condition and medical status of the patient.
To convert adult and pediatric patients from oral or parenteral opioids to fentanyl transdermal system, use Table 1. Do not use Table 1 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.
TABLE 1*: DOSE CONVERSION GUIDELINES
Current Analgesic
Daily Dosage (mg/day)
Oral morphine
60-134
135-224
225-314
315-404
Intramuscular or Intravenous morphine
10-22
23-37
38-52
53-67
Oral oxycodone
30-67
67.5-112
112.5-157
157.5-202
Intramuscular or Intravenous oxycodone
15-33
33.1-56
56.1-78
78.1-101
Oral codeine
150-447
448-747
748-1047
1048-1347
Oral hydromorphone
8-17
17.1-28
28.1-39
39.1-51
Intravenous hydromorphone 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
Intramuscular methadone
10-22
23-37
38-52
53-67
Recommended Fentanyl Transdermal System Dose
25 mcg/hour
50 mcg/hour
75 mcg/hour
100 mcg/hour
Alternatively, for adult and pediatric patients taking opioids or doses not listed in Table 1, use the conversion methodology outlined above with Table 2.
*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 (2.3)].
Alternatively, for adult and pediatric patients taking opioids or doses not listed in Table 1, use the following methodology:
1. Calculate the previous 24-hour analgesic requirement.
2. 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 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.
3. 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.
TABLE 2*: RECOMMENDED INITIAL FENTANYL TRANSDERMAL SYSTEM DOSE BASED UPON DAILY ORAL MORPHINE DOSE
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.
*Table 2 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 2 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 (2.3)].
For delivery rates in excess of 100 mcg/hour, multiple systems may be used.
Hepatic Impairment
Avoid the use of fentanyl transdermal system in patients with severe hepatic impairment. In patients with mild to moderate hepatic impairment, start with one half of the usual dosage of fentanyl transdermal system. Closely monitor for signs of sedation and respiratory depression, including at each dosage increase [see Warnings and Precautions (5.12), Use in Specific Populations (8.6) and Clinical Pharmacology (12.3)].
Renal Impairment
Avoid the use of fentanyl transdermal system in patients with severe renal impairment. In patients with mild to moderate renal impairment, start with one half of the usual dosage of fentanyl transdermal system. Closely monitor for signs of sedation and respiratory depression, including at each dosage increase [see Warnings and Precautions (5.13), Use in Specific Populations (8.7) and Clinical Pharmacology (12.3)].
2.3 Titration and Maintenance of TherapyOnce therapy is initiated, assess pain intensity and opioid adverse reactions frequently, especially respiratory depression [see Warnings and Precautions (5.2)]. Routinely monitor all patients for signs of misuse, abuse and addiction [see Warnings and Precautions (5.1)].
The initial fentanyl transdermal system dose may be increased after 3 days 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 fentanyl transdermal system dose.
The majority of patients are adequately maintained with fentanyl transdermal system administered every 72 hours. Some patients may not achieve adequate analgesia using this 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 fentanyl transdermal system 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.
Discontinuation of Fentanyl Transdermal System
To convert patients to another opioid, remove fentanyl transdermal system and titrate the dose of the new analgesic based upon the patient’s report of pain until adequate analgesia has been attained. Upon system removal, 17 hours or more are required for a 50% decrease in serum fentanyl concentrations. Withdrawal symptoms are possible in some patients after conversion or dose adjustment [see Warnings and Precautions (5.15)].
Do not use Tables1 and2 to convert from fentanyl transdermal system to other therapies to avoid overestimating the dose of the new agent potentially resulting in overdose of the new analgesic and death.
When discontinuing fentanyl transdermal system and not converting to another opioid, use a gradual downward titration, such as halving the dose every 6 days, in order to reduce the possibility of withdrawal symptoms [see Warnings and Precautions (5.15)]. It is not known at what dose level fentanyl transdermal system may be discontinued without producing the signs and symptoms of opioid withdrawal.
2.4 Administration of Fentanyl Transdermal SystemFentanyl transdermal system is for transdermal use, only.
Proper handling of fentanyl transdermal system is advised in order to prevent adverse reactions, including death, associated with accidental secondary exposure to fentanyl transdermal system [see Warnings and Precautions (5.3)].
Application and Handling Instructions
Patients should apply fentanyl transdermal system to intact, non‑irritated, and non-irradiated skin on a flat surface such as the chest, back, flank, or upper arm. In young children and persons with cognitive impairment, adhesion should be monitored and the upper back is the preferred location to minimize the potential of inappropriate patch removal. Hair at the application site may be clipped (not shaved) prior to system 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. Patients should apply fentanyl transdermal system immediately upon removal from the sealed package. The patch must not be altered (e.g., cut) in any way prior to application. Fentanyl transdermal system should not be used if the pouch seal is broken or if the patch is cut or damaged. The transdermal system is pressed firmly in place with the palm of the hand for 30 seconds, making sure the contact is complete, especially around the edges. Each fentanyl transdermal system may be worn continuously for 72 hours. The next patch is applied to a different skin site after removal of the previous transdermal system. If problems with adhesion of the fentanyl transdermal system occur, the edges of the patch may be taped with first aid tape. If problems with adhesion persist, the patch may be overlayed with a transparent adhesive film dressing. If the patch falls off before 72 hours, dispose of it by folding in half and flushing down the toilet. A new patch may be applied to a different skin site. Patients (or caregivers who apply fentanyl transdermal system) should wash their hands immediately with soap and water after applying fentanyl transdermal system. Contact with unwashed or unclothed application sites can result in secondary exposure to fentanyl transdermal system and should be avoided. Examples of accidental exposure include transfer of a fentanyl transdermal system from an adult’s body to a child while hugging, sharing the same bed as the patient, accidental sitting on a patch and possible accidental exposure of a caregiver’s skin to the medication in the patch while applying or removing the patch. Instruct patients, family members, and caregivers to keep patches in a secure location out of the reach of children and of others for whom fentanyl transdermal system was not prescribed.Avoidance of Heat
Instruct patients to avoid exposing 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, while wearing the system [see Warnings and Precautions (5.9)].
2.5 Disposal InstructionsProper disposal of fentanyl transdermal system is advised in order to prevent adverse reactions, including death, associated with accidental secondary exposure to fentanyl transdermal system [see Warnings and Precautions (5.3)].
Patients should dispose of used patches by folding the adhesive side of the patch to itself, then flush the patch down the toilet immediately upon removal.
Patients should dispose of any patches remaining from a prescription as soon as they are no longer needed. Unused patches should be removed from their pouches, fold so that the adhesive side of the patch adheres to itself, and flush down the toilet.
-
Mallinckrodt, Inc.
Fentanyl Transdermal System Patch | Mallinckrodt, Inc.
2.1 Initial DosingFentanyl 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.
Patients considered opioid-tolerant are those who are taking 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 for a week or longer.
Initiate the dosing regimen for each patient individually, taking into account the patient's 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)].
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.
Consider the following when using the information in Table 1:
This is not a table of equianalgesic doses. The conversion doses in this table are only for the conversion from one of the listed oral or parenteral opioid analgesics to fentanyl transdermal system. The table cannot be used to convert from fentanyl transdermal system to another opioid. Doing so will result in an overestimation of the dose of the new opioid and may result in fatal overdose.To convert patients from oral or parenteral opioids to fentanyl transdermal system, use Table 1. Do not use Table 1 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.
Table 1*. Dose Conversion to Fentanyl Transdermal System
Current Analgesic
Daily Dosage (mg/day)
Oral morphine
60-134
135-224
225-314
315-404
Intramuscular or
Intravenous morphine10-22
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 Fentanyl Transdermal System Dose
25 mcg/hour
50 mcg/hour
75 mcg/hour
100 mcg/hour
Alternatively, for adult and pediatric patients taking opioids or doses not listed in Table 1, use the conversion methodology outlined above with Table 2.
* 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 (2.3)].
Alternatively, for adult and pediatric patients taking opioids or doses not listed in Table 1, use the following methodology:
1. Calculate the previous 24-hour analgesic requirement.
2. 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 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.
3. 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.
Table 2*. Recommended Initial Fentanyl Transdermal System Dose Based Upon Daily Oral Morphine Dose
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.
* Table 2 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 2 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 (2.5)].
For delivery rates in excess of 100 mcg/hour, multiple systems may be used.
Hepatic Impairment
Avoid the use of fentanyl transdermal system in patients with severe hepatic impairment. In patients with mild to moderate hepatic impairment, start with one half of the usual dosage of fentanyl transdermal system. Closely monitor for signs of sedation and respiratory depression, including at each dosage increase [see Warnings and Precautions (5.14), Use in Specific Populations (8.6) and Clinical Pharmacology (12.3)].
Renal Impairment
Avoid the use of fentanyl transdermal system in patients with severe renal impairment. In patients with mild to moderate renal impairment, start with one half of the usual dosage of fentanyl transdermal system. Closely monitor for signs of sedation and respiratory depression, including at each dosage increase [see Warnings and Precautions (5.15), Use in Specific Populations (8.7) and Clinical Pharmacology (12.3)].
2.2 Titration and Maintenance of TherapyIndividually titrate fentanyl transdermal system to a dose that provides adequate analgesia and minimizes adverse reactions. Continually reevaluate patients receiving fentanyl transdermal system 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. 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.
The dosing interval for fentanyl transdermal system is 72 hours. Do not increase the fentanyl transdermal system 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 fentanyl transdermal system dose.
If unacceptable opioid-related adverse reactions are observed, the subsequent doses may be reduced. 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 fentanyl transdermal system 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.
2.3 Administration of Fentanyl Transdermal SystemFentanyl transdermal systems are for transdermal use, only.
Proper handling of fentanyl transdermal system is necessary in order to prevent serious adverse outcomes, including death, associated with accidental secondary exposure to fentanyl transdermal system [see Warnings and Precautions (5.3)].
Application and Handling Instructions
Patients should apply fentanyl transdermal system to intact, non-irritated, and non-irradiated skin on a flat surface such as the chest, back, flank, or upper arm. In young children and persons with cognitive impairment, adhesion should be monitored and the upper back is the preferred location to minimize the potential of inappropriate patch removal. Hair at the application site may be clipped (not shaved) prior to system 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. Patients should apply fentanyl transdermal system immediately upon removal from the sealed package. The patch must not be altered (e.g., cut) in any way prior to application. Fentanyl transdermal system should not be used if the pouch seal is broken or if the patch is cut or damaged. The transdermal system is pressed firmly in place with the palm of the hand for 30 seconds, making sure the contact is complete, especially around the edges. Each fentanyl transdermal system may be worn continuously for 72 hours. The next patch is applied to a different skin site after removal of the previous transdermal system. If problems with adhesion of the fentanyl transdermal system occur, the edges of the patch may be taped with first aid tape. If problems with adhesion persist, the patch may be overlayed with a transparent adhesive film dressing. If the patch falls off before 72 hours, dispose of it by folding in half and flushing down the toilet. A new patch may be applied to a different skin site. Patients (or caregivers who apply fentanyl transdermal system) should wash their hands immediately with soap and water after applying fentanyl transdermal system. Contact with unwashed or unclothed application sites can result in secondary exposure to fentanyl transdermal system and should be avoided. Examples of accidental exposure include transfer of a fentanyl transdermal system from an adult’s body to a child while hugging, sharing the same bed as the patient, accidental sitting on a patch and possible accidental exposure of a caregiver’s skin to the medication in the patch while applying or removing the patch. Instruct patients, family members, and caregivers to keep patches in a secure location out of the reach of children and of others for whom fentanyl transdermal system was not prescribed.Avoidance of Heat
Instruct patients to avoid exposing 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, while wearing the system [see Warnings and Precautions (5. 11)].
2.4 Disposal InstructionsFailure to properly dispose of fentanyl transdermal system has resulted in accidental exposures and deaths [see Warnings and Precautions (5.3)].
Patients should dispose of used patches immediately upon removal by folding the adhesive side of the patch to itself, then flushing down the toilet.
Unused patches should be removed from their pouches, the protective liners removed, the patches folded so that the adhesive side of the patch adheres to itself, and immediately flushed down the toilet.
Patients should dispose of any patches remaining from a prescription as soon as they are no longer needed.
2.5 Discontinuation of Fentanyl Transdermal SystemSignificant amounts of fentanyl continue to be absorbed from the skin for 24 hours or more after the patch is removed [see Clinical Pharmacology (12.3)].
To convert patients to another opioid, remove fentanyl transdermal system and titrate the dose of the new analgesic based upon the patient’s report of pain until adequate analgesia has been attained. Upon system removal, 17 hours or more are required for a 50% decrease in serum fentanyl concentrations. Withdrawal symptoms are possible in some patients after conversion or dose adjustment [see Warnings and Precautions (5.17)].
Do not use Tables 1 and 2 to convert from fentanyl transdermal system to other therapies to avoid overestimating the dose of the new agent resulting in overdose of the new analgesic and possibly death.
When discontinuing fentanyl transdermal system and not converting to another opioid, use a gradual downward titration, such as halving the dose every 6 days, in order to reduce the possibility of withdrawal symptoms [see Warnings and Precautions (5.17)]. It is not known at what dose level fentanyl transdermal system may be discontinued without producing the signs and symptoms of opioid withdrawal.
2.1 Initial DosingFentanyl 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.
Patients considered opioid-tolerant are those who are taking 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 for a week or longer.
Initiate the dosing regimen for each patient individually, taking into account the patient's 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)].
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.
Consider the following when using the information in Table 1:
This is not a table of equianalgesic doses. The conversion doses in this table are only for the conversion from one of the listed oral or parenteral opioid analgesics to fentanyl transdermal system. The table cannot be used to convert from fentanyl transdermal system to another opioid. Doing so will result in an overestimation of the dose of the new opioid and may result in fatal overdose.To convert patients from oral or parenteral opioids to fentanyl transdermal system, use Table 1. Do not use Table 1 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.
Table 1*. Dose Conversion to Fentanyl Transdermal System
Current Analgesic
Daily Dosage (mg/day)
Oral morphine
60-134
135-224
225-314
315-404
Intramuscular or
Intravenous morphine10-22
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 Fentanyl Transdermal System Dose
25 mcg/hour
50 mcg/hour
75 mcg/hour
100 mcg/hour
Alternatively, for adult and pediatric patients taking opioids or doses not listed in Table 1, use the conversion methodology outlined above with Table 2.
* 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 (2.3)].
Alternatively, for adult and pediatric patients taking opioids or doses not listed in Table 1, use the following methodology:
1. Calculate the previous 24-hour analgesic requirement.
2. 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 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.
3. 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.
Table 2*. Recommended Initial Fentanyl Transdermal System Dose Based Upon Daily Oral Morphine Dose
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.
* Table 2 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 2 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 (2.5)].
For delivery rates in excess of 100 mcg/hour, multiple systems may be used.
Hepatic Impairment
Avoid the use of fentanyl transdermal system in patients with severe hepatic impairment. In patients with mild to moderate hepatic impairment, start with one half of the usual dosage of fentanyl transdermal system. Closely monitor for signs of sedation and respiratory depression, including at each dosage increase [see Warnings and Precautions (5.14), Use in Specific Populations (8.6) and Clinical Pharmacology (12.3)].
Renal Impairment
Avoid the use of fentanyl transdermal system in patients with severe renal impairment. In patients with mild to moderate renal impairment, start with one half of the usual dosage of fentanyl transdermal system. Closely monitor for signs of sedation and respiratory depression, including at each dosage increase [see Warnings and Precautions (5.15), Use in Specific Populations (8.7) and Clinical Pharmacology (12.3)].
2.2 Titration and Maintenance of TherapyIndividually titrate fentanyl transdermal system to a dose that provides adequate analgesia and minimizes adverse reactions. Continually reevaluate patients receiving fentanyl transdermal system 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. 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.
The dosing interval for fentanyl transdermal system is 72 hours. Do not increase the fentanyl transdermal system 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 fentanyl transdermal system dose.
If unacceptable opioid-related adverse reactions are observed, the subsequent doses may be reduced. 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 fentanyl transdermal system 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.
2.3 Administration of Fentanyl Transdermal SystemFentanyl transdermal systems are for transdermal use, only.
Proper handling of fentanyl transdermal system is necessary in order to prevent serious adverse outcomes, including death, associated with accidental secondary exposure to fentanyl transdermal system [see Warnings and Precautions (5.3)].
Application and Handling Instructions
Patients should apply fentanyl transdermal system to intact, non-irritated, and non-irradiated skin on a flat surface such as the chest, back, flank, or upper arm. In young children and persons with cognitive impairment, adhesion should be monitored and the upper back is the preferred location to minimize the potential of inappropriate patch removal. Hair at the application site may be clipped (not shaved) prior to system 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. Patients should apply fentanyl transdermal system immediately upon removal from the sealed package. The patch must not be altered (e.g., cut) in any way prior to application. Fentanyl transdermal system should not be used if the pouch seal is broken or if the patch is cut or damaged. The transdermal system is pressed firmly in place with the palm of the hand for 30 seconds, making sure the contact is complete, especially around the edges. Each fentanyl transdermal system may be worn continuously for 72 hours. The next patch is applied to a different skin site after removal of the previous transdermal system. If problems with adhesion of the fentanyl transdermal system occur, the edges of the patch may be taped with first aid tape. If problems with adhesion persist, the patch may be overlayed with a transparent adhesive film dressing. If the patch falls off before 72 hours, dispose of it by folding in half and flushing down the toilet. A new patch may be applied to a different skin site. Patients (or caregivers who apply fentanyl transdermal system) should wash their hands immediately with soap and water after applying fentanyl transdermal system. Contact with unwashed or unclothed application sites can result in secondary exposure to fentanyl transdermal system and should be avoided. Examples of accidental exposure include transfer of a fentanyl transdermal system from an adult’s body to a child while hugging, sharing the same bed as the patient, accidental sitting on a patch and possible accidental exposure of a caregiver’s skin to the medication in the patch while applying or removing the patch. Instruct patients, family members, and caregivers to keep patches in a secure location out of the reach of children and of others for whom fentanyl transdermal system was not prescribed.Avoidance of Heat
Instruct patients to avoid exposing 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, while wearing the system [see Warnings and Precautions (5. 11)].
2.4 Disposal InstructionsFailure to properly dispose of fentanyl transdermal system has resulted in accidental exposures and deaths [see Warnings and Precautions (5.3)].
Patients should dispose of used patches immediately upon removal by folding the adhesive side of the patch to itself, then flushing down the toilet.
Unused patches should be removed from their pouches, the protective liners removed, the patches folded so that the adhesive side of the patch adheres to itself, and immediately flushed down the toilet.
Patients should dispose of any patches remaining from a prescription as soon as they are no longer needed.
2.5 Discontinuation of Fentanyl Transdermal SystemSignificant amounts of fentanyl continue to be absorbed from the skin for 24 hours or more after the patch is removed [see Clinical Pharmacology (12.3)].
To convert patients to another opioid, remove fentanyl transdermal system and titrate the dose of the new analgesic based upon the patient’s report of pain until adequate analgesia has been attained. Upon system removal, 17 hours or more are required for a 50% decrease in serum fentanyl concentrations. Withdrawal symptoms are possible in some patients after conversion or dose adjustment [see Warnings and Precautions (5.17)].
Do not use Tables 1 and 2 to convert from fentanyl transdermal system to other therapies to avoid overestimating the dose of the new agent resulting in overdose of the new analgesic and possibly death.
When discontinuing fentanyl transdermal system and not converting to another opioid, use a gradual downward titration, such as halving the dose every 6 days, in order to reduce the possibility of withdrawal symptoms [see Warnings and Precautions (5.17)]. It is not known at what dose level fentanyl transdermal system may be discontinued without producing the signs and symptoms of opioid withdrawal.
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