Generic Name: fentanyl transmucosal

Brand Names: Abstral, Actiq, Sublimaze

Uses

Pain (Acute)

Preoperatively, during surgery, and in the immediate postoperative period parenterally for its strong analgesic action.

Parenterally for pain that likely will be of short duration (e.g., that associated with diagnostic procedures, orthopedic manipulation) and can be controlled with a short-acting opiate agonist such as fentanyl.

Parenterally for severe but intermittent pain (e.g., renal colic) that can be treated with short-duration opiate analgesia.

IM to alleviate postoperative pain and discomfort. However, the IV route (including patient-controlled analgesia) is preferred for administration of opiate agonists after major surgery since repeated IM injections may cause pain and trauma.

Around-the-clock dosing of analgesics may be considered in the initial stages of acute pain to avoid wide swings in pain and sedation often associated with as-needed dosing regimens.

Because of the risk of life-threatening respiratory depression (e.g., hypoventilation), transdermal systems and buccal preparations are contraindicated in the management of acute or postoperative pain.

Malignant (Cancer) Pain

Transdermally for the management of persistent, moderate to severe chronic pain (e.g., associated with cancer) when continuous around-the-clock, strong opiate analgesia is indicated for an extended period of time. Use only in patients who are opiate tolerant. (See Transdermal Systems in Boxed Warning.)

Intrabuccally (transmucosally) for the management of breakthrough cancer pain only in patients who are already being treated with, and are tolerant of, opiates used around-the-clock for chronic cancer pain. (See Buccal [Transmucosal] Tablets and Lozenges in Boxed Warning.)

Do not use transdermally or intrabuccally in patients who are not opiate tolerant.

In the management of severe, chronic pain associated with a terminal illness such as cancer, the principal goal of analgesic therapy is to make the patient relatively pain-free while maintaining as good a quality of life as possible.

Analgesic therapy must be individualized and titrated according to patient response and tolerance.

Although consideration of the dependence potential of opiate agonists has often limited their effective use by many clinicians in terminally ill patients with severe, chronic pain, such consideration is irrelevant in the context of terminal illness.

Other Chronic Pain

Transdermally for the management of persistent, moderate to severe chronic pain in patients requiring continuous around-the-clock, strong opiate analgesia for an extended period of time. Use only in patients who are opiate tolerant. (See Transdermal Systems in Boxed Warning.)

Do not use transdermally for the management of mild or intermittent chronic pain that can be managed with less intensive analgesic therapy (e.g., acetaminophen/opiateCombinations, NSAIAs, intermittent dosing with short-acting opiates) or on an as-needed (“prn”) basis because of the risk of life-threatening respiratory depression.

Treatment of continuous or frequently recurring pain is best accomplished by the use of around-the-clock dosing regimens designed to prevent pain and minimize fluctuations in serum analgesicConcentrations.

As tolerance to initial dosage develops, larger doses may be given as necessary.

Alternative analgesic adjuncts such as tricyclic antidepressants or anticonvulsants also should be considered in the treatment of chronic nonmalignant pain (e.g., neurogenic pain).

During prolonged use, especially when opiate agonists are self-administered, precautions should be taken to prevent unnecessary increases in dosage.

Anesthesia

A supplement to general or regional anesthesia, including neuroleptanalgesia in which it often is used in combination with droperidol.

For induction and maintenance of anesthesia to provide preinduction sedation and analgesia, provide analgesia for additional vascular line placement, blunt hemodynamic and stress response to laryngoscopy and intubation, reduce requirements for other anesthetics, promote perioperative hemodynamic stability, and provide postoperative analgesia.

As the opiateComponent of balanced anesthesia or total IV anesthesia (balanced anesthesia in which the IV anestheticCompletely replaces the inhalation anesthetic).

May be especially useful preoperatively before surgery of short duration or minor surgery in outpatients and in diagnostic procedures or treatments that require the patient to be awake or very lightly anesthetized.

When attenuation of the response to surgical stress is especially important, may be administered with oxygen and a skeletal muscle relaxant to provide anesthesia without the use of additional anesthetic agents.

Tachypnea and Delirium (Postoperative)

To prevent or relieve tachypnea and postoperative emergence delirium.

Conscious Sedation

Previously was available for restricted use as an intrabuccal (transmucosal) premedicant (Fentanyl Oralet^®) prior to anesthesia or for inducing conscious sedation prior to diagnostic or therapeutic procedures in a monitored anesthesia setting. However, this preparation no longer is commercially available for such use in the US and the currently available buccal preparations (Actiq^® lozenge, Fentora^® tablet, generic oral transmucosal fentanyl citrate lozenge) are labeled only for management of breakthrough pain in opiate-tolerant patients with chronic cancer pain.

Dosage and Administration

Administration

Administer by IM or IV injection or by IV infusion.

Administer intrabuccally (transmucosally) as a lozenge or buccal tablet.

Administer percutaneously by topical application of a transdermal system.

Preservative-free injections have been administered epidurally†.

Intrabuccal (Transmucosal) Administration

Carefully instruct patients in the proper use and disposal of the buccal (transmucosal) lozenges and buccal tablets. (See Buccal Tablets and Lozenges under Advice to Patients.)

If signs of excessive opiate effects develop before the lozenge or buccal tablet is consumed completely, remove the remaining portion from the patient’s mouth immediately and decrease future doses.

Buccal Lozenges

Cut lozenge package open with scissors just prior to administration.

Place the lozenge in the patient’s mouth (between the cheek and the lower gum) using the handle, and instruct the patient to suck, and not bite or chew, the lozenge; efficacy may be reduced if the lozenge is chewed and swallowed rather than being administered as directed. The lozenge occasionally may be moved from one side to the other using the handle.

Usually consume lozenges over a period of 15 minutes; longer or shorter consumption times may result in reduced efficacy.

Buccal Tablets

Bend and tear along the blister card perforations to separate a single blister unit. Just prior to administration, bend along the indicated line on a single blister unit and peel the backing to remove the buccal tablet; do not attempt to push the buccal tablet through the blister.

Do not split buccal tablets.

Place the buccal tablet in the patient’s mouth (above a rear molar, between the upper cheek and gum) and instruct the patient not to suck, chew, or swallow the buccal tablet; efficacy may be reduced if the buccal tablet is sucked, chewed, or swallowed rather than being administered as directed. Alternate sides of the mouth with each dose.

If the buccal tablet has not completely disintegrated after 30 minutes, the remnants may be swallowed with a glass of water. Disintegration time does not appear to affect early systemic exposure to the drug.

IV Administration

For solution and drug compatibility information, see Compatibility under Stability.

Opiate antagonist and facilities for administration of oxygen and controlled respiration should be available during and immediately following IV administration of the drug.

Administer by direct IV injection, IV infusion, or IV via a controlled-delivery device for patient-controlled analgesia (PCA).

Dilution

May give undiluted as direct IV injection.

May dilute in a compatible IV solution for infusion. (See Solution Compatibility under Stability.)

Rate of Administration

Direct IV injection: Usually, slowly over several (e.g., 1–2) minutes. Occasionally, over <1 minute (e.g., for high-dose opiate anesthesia).

IV injection for PCA: Self-administered intermittently as needed (“prn”) via controlled-delivery device, with usual lockout intervals (minimum time between self-administered doses programmed into device) of 6–12 minutes.

IV infusion: Usually, slowly but occasionally rapidly (e.g., for high-dose opiate anesthesia).

IV infusion, maintenance doses in anesthesia: Usually, 2–10 mcg/kg per hour.

Risk of muscular rigidity (particularly of the respiratory muscles) is related to the dose and speed of IV administration; if administered IV rapidly (particularly large doses) or even slowly by IV infusion for anesthesia, administration of a neuromuscular blocking agent prior to or simultaneously with anesthetic fentanyl therapy can reduce the risk.

IM Injection

Administer by IM injection.

Transdermal (Percutaneous) Administration

Carefully instruct patients in the proper use and disposal of the transdermal system. (See Transdermal Systems under Advice to Patients.)

To expose the adhesive surface of the system, peel off and discard the protective-liner covering just prior to application.

Apply the transdermal system to a dry, intact, nonirritated, nonirradiated flat surface on the chest, back, flank, or upper arm by firmly pressing the system by hand for 30 seconds with the adhesive side touching the skin and ensuring that contact is complete, particularly around the edges. Do not fold the transdermal system so that only part of the system is exposed to the skin. When applied to young children or to individuals with cognitive impairment, place transdermal system on the upper back to reduce the risk that the system could be removed and placed in the mouth.

Clip, not shave, hair at the application site prior to application; shaving may be irritating, which could alter percutaneous drug absorption.

Only clear water should be used if the site needs cleaning before transdermal application; do not use soaps, oils, lotions, alcohol, or any other agents that could irritate the skin or alter its characteristics.

Do not use transdermal system if the seal of the package is broken or if the system is altered in any way (e.g., cut, damaged), since use of altered systems may expose the patient or caregiver to the contents of the system and result in rapid release of fentanyl and absorption of a potentially lethal dose of the drug.

Each transdermal system may be worn continuously for 72 hours; apply subsequent systems to a different site after removal of the previous system.

If a system should inadvertently come off during the period of use, apply a new system to a different skin site and leave in place for 72 hours. The edges of the system may be taped in place with first-aid tape if the patient experiences difficulty with system adhesion. If adhesion problems persist, an adhesive film dressing (e.g., Bioclusive^®, Tegaderm^®) may be applied over the system.

Patients may bathe, shower, or swim while wearing transdermal systems.

Epidural Administration

Preservative-free injections have been injected or infused epidurally†; specialized techniques are required for administration by this route, and such administration should be performed only by qualified individuals familiar with the techniques of administration, dosages, and special patient management problems.

Dosage

Available as fentanyl and fentanyl citrate; dosage expressed in terms of fentanyl.

Give the smallest effective dose and as infrequently as possible to minimize the development of tolerance and physical dependence.

Reduced dosage is indicated initially in poor-risk patients, in geriatric patients, and in patients receiving other CNS depressants. (See Geriatric Patients under Dosage and Administration and also see Specific Drugs and Foods under Interactions.)

Individualize dosage of fentanyl according to the clinical status of the patient, desired therapeutic effect, and age and weight. The most important factor in determining the appropriate dose of transdermal fentanyl is the degree of existing opiate tolerance.

Pediatric Patients

Anesthesia and Analgesia

IV or IM

Neonates and infants, anesthesia and analgesia: 1–4 mcg/kg per dose IV, repeated every 2–4 hours as needed, or continuous IV infusion of 0.5–5 mcg/kg per hour.

Children 2–12 years of age, anesthesia induction and maintenance phase: Usually, 1.7–3.3 mcg/kg IV or IM.

Children 2–12 years of age, analgesia: Usually, 1–3 mcg/kg IV or IM, repeated every 30–60 minutes as needed, or continuous IV infusion of 1–5 mcg/kg per hour.

Children >12 years of age, analgesia: 0.5–1 mcg/kg IV or IM, repeated every 30–60 minutes as needed.

PCA (usually IV) via controlled-delivery device: Loading doses of 0.05–2 mcg/kg, preferably titrated by clinician or nurse at bedside, up to 0.5–4 mcg/kg total.

PCA (usually IV) via controlled-delivery device: Maintenance doses (administered intermittently by patient) of 0.25–0.5 mcg/kg, usually no more frequently than every 6–12 minutes as a device-programmed lockout period.

Chronic Malignant (Cancer) Pain and Other Chronic Pain

Initial Dose Selection in Patients Being Switched to Transdermal Fentanyl Therapy

Transdermal

Use transdermal system only in children ≥2 years of age who are opiate tolerant. Risk of fatal respiratory depression when administered to patients not already opiate tolerant. (See Transdermal Systems in Boxed Warning.)

When selecting the initial transdermal dose, consider the daily dose, potency, and characteristics (e.g., pure or partial agonist activity) of the opiate the patient has been receiving and the reliability of potency estimates, which may vary by route, used to calculate an equivalent transdermal dose. Fatal overdose possible with the first transdermal dose if the dose is overestimated.

The manufacturers provide specific dosage recommendations for switching opiate-tolerant children ≥2 years of age from certain oral or parenteral opiates to transdermal fentanyl (see Table 2 and Table 3); the manufacturers consider these initial dosages of transdermal fentanyl to be conservative estimates. Do not use the dosage conversion guidelines in Tables 2 and 3 to convert patients from transdermal fentanyl to oral or parenteral opiates, since dosage of oral or parenteral opiates may be overestimated.

Alternatively, to convert children ≥2 years of age who currently are receiving other opiate therapy or dosages that are not listed in Table 2 or 3, calculate the opiate analgesic requirements during the previous 24 hours. Then calculate an equianalgesic 24-hour dosage of oral morphine sulfate using Table 4. Finally, calculate the equivalent dose of transdermal fentanyl using Table 5. The manufacturers state that this calculated initial dose of transdermal fentanyl may underestimate dosage requirements in about 50% of patients. However, this conservative initial dosage is recommended to reduce the risk of overdosage with the first dose.

Use the lowest possible dose providing acceptable analgesia.

For transdermal doses >100 mcg/hour, apply multiple systems at different sites simultaneously.

If severe adverse effects (including overdosage) occur, monitor and treat patient for ≥24 hours because of long elimination half-life (17 hours).

Dosing intervals <72 hours have not been evaluated in children and adolescents and cannot be recommended in this population.

Postpone the initial evaluation of maximum analgesia for ≥24 hours after initiation of therapy because of gradual percutaneous absorption from the initially applied system.

Many patients are likely to require upward dosage titration. If analgesia is inadequate, dosage may be titrated upward after 3 days.

Give supplemental doses of a short-acting opiate as needed during the initial application period and subsequently thereafter as necessary to relieve breakthrough pain.

Dosage Adjustment to Achieve Adequate Analgesia

Transdermal

If analgesia is inadequate after initial application of a transdermal system, dosage may be titrated upward after 3 days. Initial transdermal dose may be increased after 3 days based on the daily dose of supplemental opiates during the second and third day after initial application.

Because subsequent equilibrium with an increased dose may require up to 6 days to achieve, make further upward dose titration based on supplemental opiate requirements no more frequently than every 6 days (i.e., after two 72-hour application periods with a given dose).

Conversion of supplemental opiate requirements to transdermal dose should be based on a ratio of 45 mg of oral morphine sulfate (during a 24-hour period) to each 12.5-mcg/hour delivery from the fentanyl transdermal system.

Discontinuance of Transdermal Fentanyl Therapy

Transdermal

To convert to another opiate, remove the transdermal system and titrate the dosage of the other opiate according to patient toleration and response.

It generally takes ≥17 hours for serum fentanyl concentrations to decline by 50% following removal of the system. Symptoms of withdrawal (e.g., nausea, vomiting, diarrhea, anxiety, shivering) may occur in some patients following conversion to another opiate agonist or discontinuance of the fentanyl transdermal system.

Adults

Analgesia

IM or IV

Preoperatively: 50–100 mcg IM 30–60 minutes prior to surgery.

Postoperatively: 50–100 mcg IM every 1–2 hours in the recovery room as needed.

Alternatively for analgesia: 0.5–1 mcg/kg IM or IV, repeated every 30–60 minutes as needed.

PCA (usually IV) via controlled-delivery device: Loading doses of 25–50 mcg every 5 minutes, preferably titrated by clinician or nurse at bedside, up to 50–300 mcg total.

PCA (usually IV) via controlled-delivery device: Maintenance doses (self-administered intermittently by patient) of 10–30 mcg, usually no more frequently than every 6–12 minutes as a device-programmed lockout period.

Anesthesia

Adjunct to General Anesthesia

IV or IM

May be given in low-dose, moderate-dose, or high-dose regimens.

Low-dose, used for minor but painful surgical procedures: Usually, 2 mcg/kg IV; additional doses usually not necessary.

Moderate-dose, used in more major surgical procedures: Initially, 2–20 mcg/kg IV; additional doses of 25–100 mcg IV or IM as necessary.

High-dose, used during open heart surgery or certain complicated neurosurgical or orthopedic procedures where surgery is more prolonged: Initially, 20–50 mcg/kg IV; additional doses ranging from 25 mcg to one-half the initial dose IV as necessary.

IV Infusion

Initial loading dose: Usually, 4–20 mcg/kg titrated to effect over several minutes.

Maintenance dose: Usually, 2–10 mcg/kg per hour; additional supplemental IV doses of 25–100 mcg as needed.

Maintenance dose: Alternatively after usual loading dose, variable-rate infusion titrated to maintain targeted plasma and effect site fentanyl concentrations:

Supplemental IV doses also can be used as needed with the alternative maintenance dose.

General Anesthesia without Additional Anesthetic Agent

IV

Attenuation of the response to surgical stress: 50–100 mcg/kg in conjunction with oxygen and a skeletal muscle relaxant; doses up to 150 mcg/kg may be required.

Adjunct to Regional Anesthesia

IV or IM

50–100 mcg IM or by slow IV injection over 1–2 minutes when additional analgesia is required.

Postoperative Pain, Restlessness, Tachypnea, and Emergence Delirium

IM

Postoperatively: 50–100 mcg every 1–2 hours in the recovery room as needed.

Breakthrough Malignant (Cancer) Pain

Intrabuccal (Lozenges [Actiq^®, generic oral transmucosal fentanyl citrate lozenges])

Adults who are already being treated with, and are tolerant of, opiates: Initially, 200 mcg for breakthrough episode.

Prescribe 6 lozenges initially, all of which should be used for various breakthrough episodes before the dose is increased.

May be necessary to use >1 lozenge per episode of breakthrough cancer pain until the appropriate dose is attained; an additional lozenge may be administered 15 minutes after the previous lozenge has been consumed (i.e., 30 minutes after the first lozenge initially was placed in the mouth).

Maximum of 2 lozenges per breakthrough pain episode may be given, if necessary, during dosage titration phase.

Increase dose to the next higher available strength after several consecutive breakthrough cancer pain episodes require the use of >1 lozenge per episode; again, prescribe only 6 lozenges of the new strength.

During titration phase, evaluate each new dose over several breakthrough cancer pain episodes (generally 1–2 days) to determine efficacy and tolerability of the drug.

Once titrated to an adequate dose (average breakthrough pain episode is treated with a single lozenge), the patient should limit consumption to a maximum of 4 lozenges daily.

If patient requires >4 lozenges daily, reevaluate dosage of opiates used around the clock for chronic cancer pain.

Discontinuance of opiates: Gradually taper the dose of the opiate to avoid manifestations associated with abrupt withdrawal.

Intrabuccal (Buccal tablets [Fentora^®])

Consider the increased bioavailability of the buccal tablets when transferring opiate-tolerant patients from fentanyl citrate buccal lozenges (e.g., Actiq^®) to fentanyl citrate buccal tablets. (See Bioavailability under Pharmacokinetics.) Fatal overdosage may occur if the buccal tablets are substituted on a mcg-per-mcg basis for the buccal lozenges or for any other fentanyl preparation.

Instruct patients being transferred from the buccal lozenges to the buccal tablets to discontinue use of the buccal lozenges and to dispose of any remaining lozenges.

Dosage conversion recommendations are available for opiate-tolerant patients being transferred from fentanyl citrate buccal lozenges to fentanyl citrate buccal tablets (see Table 1).

Safe conversion regimens for opiate-tolerant patients being transferred from other fentanyl preparations (i.e., transdermal, parenteral, other oral formulations) have not been established. For all opiate-tolerant patients other than those being transferred from fentanyl citrate buccal lozenges, the initial recommended dose of the buccal tablets is 100 mcg for breakthrough episode.

If breakthrough pain is not relieved within 30 minutes after the initial buccal tablet dose, the patient may take only 1 additional dose of the same strength during that episode of breakthrough pain. After treating 1 episode of breakthrough pain with the buccal tablets, the patient must wait ≥4 hours before treating a subsequent episode of breakthrough pain with the buccal tablets.

Titrate dosage with close monitoring to a level that provides adequate analgesia with minimal adverse effects.

Instruct patients to record use of buccal tablets over several episodes of breakthrough pain and to discuss their experience with their clinician to decide whether dosage adjustment is warranted.

During dosage titration, 1 dose may include administration of 1–4 tablets of the same strength. Administer no more than 4 tablets simultaneously. Manufacturer states that the only time patients should take >1 tablet as a single dose (e.g., two 100-mcg tablets for a single 200-mcg dose) is during dosage titration.

Patients receiving an initial dose of 100 mcg who require titration to a higher dosage level may increase buccal tablet dosage to 200 mcg (two 100-mcg tablets, with one tablet placed on each side of the mouth in the buccal cavity) with the next episode of breakthrough pain. Those who require a further increase in dosage may place two 100-mcg tablets on each side of the mouth in the buccal cavity (total of four 100-mcg tablets). If dosages >400 mcg (i.e., dosages of 600 or 800 mcg) are required, titrate dosage using multiples of 200-mcg tablets.

In patients who initiated buccal tablet therapy with the 200-mcg tablets (i.e., those who were transferred from fentanyl citrate buccal lozenge dosages of ≥600 mcg [see Table 1]), titrate buccal tablet dosage using multiples of 200-mcg tablets.

During dosage titration period, if breakthrough pain is not relieved within 30 minutes after the initial dose of buccal tablets, the patient may take only 1 additional dose of the same strength during that episode of breakthrough pain. Manufacturer states that no more than 2 doses may be given during a single episode of breakthrough pain, even if the patient continues to experience pain after the second dose is administered.

To reduce the risk of overdosage during titration, strongly advise patients to use or discard all the buccal tablets of one strength prior to obtaining tablets of a different strength.

During titration phase, evaluate each new dose over several breakthrough cancer pain episodes to determine efficacy and tolerability of the drug.

Once titrated to an adequate dosage, breakthrough pain episodes generally should be treated effectively with 1 buccal tablet. On occasion during maintenance therapy, when a breakthrough pain episode is not relieved within 30 minutes after the first buccal dose, the patient may take only 1 additional dose of the same strength during that episode of breakthrough pain.

Some patients may require adjustment of the intrabuccal fentanyl dosage to maintain effective analgesia for breakthrough pain episodes; however, dosage generally should be increased only if several consecutive episodes require administration of >1 intrabuccal dose for pain relief.

After treating 1 episode of breakthrough pain with fentanyl citrate buccal tablets, patient must wait ≥4 hours before taking an additional dose of buccal tablets to treat a subsequent episode of breakthrough cancer pain.

If patient experiences >4 breakthrough pain episodes daily, reevaluate dosage of opiates used around the clock for chronic cancer pain.

Dosage adjustment does not appear to be necessary in patients with grade 1 mucositis; safety and efficacy in patients with grade 2 or greater mucositis not established.

Discontinuance of opiates: Gradually taper the dose of the opiate to avoid manifestations associated with abrupt withdrawal.

Chronic Malignant (Cancer) Pain and Other Chronic Pain

Initial Dose Selection in Patients Being Switched to Transdermal Fentanyl Therapy

Transdermal

Use transdermal system only in patients who are opiate tolerant. Risk of fatal respiratory depression when administered to patients not already opiate tolerant. (See Transdermal Systems in Boxed Warning.)

When selecting the initial transdermal dose, consider the daily dose, potency, and characteristics (e.g., pure or partial agonist activity) of the opiate the patient has been receiving and the reliability of potency estimates, which may vary by route, used to calculate an equivalent transdermal dose. Fatal overdose possible with the first transdermal dose if the dose is overestimated.

The manufacturers provide specific dosage recommendations for switching opiate-tolerant patients from certain oral or parenteral opiates to transdermal fentanyl (see Table 2 and Table 3); the manufacturers consider these initial dosages of transdermal fentanyl to be conservative estimates. Do not use the dosage conversion guidelines in Tables 2 and 3 to convert patients from transdermal fentanyl to oral or parenteral opiates, since dosage of oral or parenteral opiates may be overestimated.

Alternatively, to convert patients who currently are receiving other opiate therapy or dosages that are not listed in Table 2 or 3, calculate the opiate analgesic requirements during the previous 24 hours. Then calculate an equianalgesic 24-hour dosage of oral morphine sulfate using Table 4. Finally, calculate the equivalent dose of transdermal fentanyl using Table 5. The manufacturers state that this calculated initial dose of transdermal fentanyl may underestimate dosage requirements in about 50% of patients. However, this conservative initial dosage is recommended to reduce the risk of overdosage with the first dose.

Use the lowest possible dose providing acceptable analgesia.

For transdermal doses >100 mcg/hour, apply multiple systems at different sites simultaneously.

If severe adverse effects (including overdosage) occur, monitor and treat patient for ≥24 hours because of long elimination half-life (17 hours).

Doses in Table 4 are considered equivalent to 10 mg of IM morphine sulfate.

Equivalencies were based on single-dose studies comparing IM doses of these drugs, and oral doses are those recommended when changing from IM to oral therapy with each drug.

Postpone the initial evaluation of maximum analgesia for ≥24 hours because of gradual percutaneous absorption from the initially applied system.

Many patients are likely to require upward dosage titration. If analgesia is inadequate, dosage may be titrated upward after 3 days.

Give supplemental doses of a short-acting opiate as needed during the initial application period and subsequently thereafter as necessary to relieve breakthrough pain.

Dosage Adjustment to Achieve Adequate Analgesia

Transdermal

If analgesia is inadequate after initial application of a transdermal system, dosage may be titrated upward after 3 days. Initial transdermal dose may be increased after 3 days based on the daily dose of supplemental opiates during the second and third day after initial application.

Because subsequent equilibrium with an increased dose may require up to 6 days to achieve, make further upward dose titration based on supplemental opiate requirements no more frequently than every 6 days (i.e., after two 72-hour application periods with a given dose).

Conversion of supplemental opiate requirements to transdermal dose should be based on a ratio of 45 mg of oral morphine sulfate (during a 24-hour period) to each 12.5-mcg/hour delivery from the fentanyl transdermal system.

Most patients are maintained adequately with transdermal systems applied at 72-hour intervals; however, some may require application of the systems at 48-hour intervals to maintain adequate analgesia. Before shortening the dosing interval for inadequate response to a given dose, evaluate a dose increase so that patients can be maintained on a 72-hour regimen if possible.

Discontinuance of Transdermal Fentanyl Therapy

Transdermal

To convert to another opiate, remove the transdermal system and titrate the dosage of the other opiate according to patient toleration and response.

It generally takes ≥17 hours for serum fentanyl concentrations to decline by 50% following removal of the system. Symptoms of withdrawal (e.g., nausea, vomiting, diarrhea, anxiety, shivering) may occur in some patients following conversion to another opiate agonist or discontinuance of the fentanyl transdermal system.

Special Populations

Hepatic Impairment

Exercise caution. Use lowest possible dosage.

Reduce initial parenteral dosage.

Insufficient information available to support recommendations regarding use of transdermal or buccal preparations. If used, caution advised.

Renal Impairment

Exercise caution. Use lowest possible dosage.

Reduce initial parenteral dosage.

Insufficient information available to support recommendations regarding use of transdermal or buccal preparations. If used, caution advised.

Geriatric Patients

Reduce initial parenteral and transdermal doses; response to initial dosing should be considered in determining subsequent incremental doses.

Doses of buccal lozenges in patients >65 years of age generally are about 200 mcg lower than those required in younger patients; doses of buccal tablets are slightly lower than those required in younger patients. Exercise caution during dosage titration.

Cautions

Contraindications

• Patients receiving MAO inhibitors.
• Known hypersensitivity to fentanyl or any ingredient or component (e.g., the adhesive in transdermal systems) of the respective formulation.
• Intrabuccal (transmucosal) preparations contraindicated in the management of acute pain (e.g., painful injuries, migraine or other headaches) or postoperative pain and in non-opiate-tolerant patients because of the risk of life-threatening respiratory depression. (See Buccal [Transmucosal] Tablets and Lozenges in Boxed Warning.)
• Transdermal preparations contraindicated in acute or postoperative pain, in chronic pain that is mild or intermittent and manageable with less potent analgesics, and in patients not already receiving and tolerant of opiates because of the prolonged duration of effects and risk of serious or life-threatening respiratory depression. (See Transdermal Systems in Boxed Warning.)
• Transdermal preparations also contraindicated in patients with substantial respiratory depression, especially in settings where equipment for monitoring and resuscitation is not available; in patients with acute or severe bronchial asthma; and in those with known or suspected paralytic ileus.

Warnings/Precautions

Warnings

Fentanyl shares the toxic potentials of the opiate agonists; observe the usual precautions of opiate agonist therapy.

Supervised Administration

Administer only under the supervision of qualified clinicians who are experienced in the use of opiates for anesthesia or the management of pain, depending on use, and in the management of respiratory effects of potent opiates.

Opiate antagonist and facilities for administration of oxygen and controlled respiration should be available during and immediately following IV administration.

Use intrabuccally only under the supervision of qualified clinicians who are experienced in the use of opiates for the management of cancer pain.

Use transdermally only under the supervision of clinicians who are experienced in continuous administration of potent opiates for management of pain and in the detection and management of hypoventilation.

Respiratory Depression

The major toxicity associated with fentanyl.

Occurs most frequently in geriatric and debilitated patients, usually following large initial doses in nontolerant patients, or when given concomitantly with drugs that depress respiration.

The respiratory depressant effect may persist longer than the analgesic effect.

Observe patients who develop serious adverse effects with transdermal therapy closely for ≥24 hours after removal of the transdermal system since serum concentrations decline gradually and reach an approximate 50% reduction 17 hours after system removal.

Patients who develop hypoventilation (respiratory depression) during transdermal therapy must be observed carefully; observe the degree of sedation and monitor the respiratory rate until respiration has stabilized.

Use of transdermal systems or buccal tablets or lozenges in non-opiate-tolerant patients may result in fatal respiratory depression and is contraindicated. (See Boxed Warning.)

Use of cut, damaged, or altered transdermal systems may expose the patient or caregiver to the contents of the system and result in rapid release of fentanyl and absorption of a potentially lethal dose of the drug.

Death and life-threatening adverse effects reported in patients receiving fentanyl transdermally; attributed to inappropriate prescribing (e.g., use of transdermal fentanyl for postoperative pain, occasional or mild pain, or headaches) and incorrect use by patients (application of too many systems, application of heat to the system, replacement of systems too frequently). Use only for chronic pain in carefully selected patients who are opiate tolerant and are appropriately monitored.

Death and life-threatening adverse effects reported in patients receiving the buccal tablets; attributed to improper patient selection (e.g., use of this formulation in patients who were not opiate tolerant), improper dosage, and/or improper substitution of the buccal tablets for other fentanyl formulations. (See Buccal [Transmucosal] Tablets and Lozenges in Boxed Warning.) Safe dosage conversion ratios established only for patients being transferred from fentanyl buccal lozenges to the buccal tablets; for opiate-tolerant patients being transferred from any other fentanyl preparation, initial dose of the buccal tablets should be 100 mcg. (See Dosage: Breakthrough Malignant [Cancer] Pain under Dosage and Administration.)

Use fentanyl with extreme caution in patients with COPD or cor pulmonale, and in those with substantially decreased respiratory reserve, hypoxia, hypercapnia, or preexisting respiratory depression. Further decreased respiratory drive and increased airway resistance may occur. During anesthesia, this can be managed with assisted or controlled respiration.

Interactions with Other CNS Depressants

Additive depressant effects may occur with concomitant use of other CNS depressants including other opiates, sedatives or hypnotics, general anesthetics, phenothiazines, tranquilizers, skeletal muscle relaxants, sedating antihistamines, and alcohol.

Hypoventilation, hypotension, and profound sedation or coma may occur.

When such combined therapy is contemplated, the dose of one or both agents should be reduced substantially. (See Specific Drugs and Foods under Interactions.)

Interactions with CYP3A4 Inhibitors

Concomitant use of transdermal fentanyl with any CYP3A4 inhibitor and of fentanyl citrate buccal tablets or lozenges with potent or moderately potent CYP3A4 inhibitors may increase plasma fentanyl concentrations, increasing or prolonging opiate effects and potentially resulting in fatal respiratory depression. (See Interactions.)

Interactions with MAO Inhibitors

Severe and unpredictable potentiation by MAO inhibitor may occur. Do not use in patients who have received MAO inhibitors within 14 days.

Dependence and Abuse

Physical and psychic dependence and tolerance may develop with repeated administration, and abuse potential exists; use with caution. (See Boxed Warning.)

Abrupt cessation of therapy or sudden reduction in dosage after prolonged use may result in withdrawal symptoms. After prolonged exposure to opiate analgesics, if withdrawal is necessary, it must be undertaken gradually.

Patients with Fever or Exposure to High Temperatures

Closely observe patients who develop a fever during transdermal fentanyl therapy or whose core body temperature increases following strenuous exercise for manifestations of opiate toxicity and adjust dosage accordingly; drug absorption from fentanyl transdermal systems depends in part on the temperature of the skin and increases with increasing temperature. Serum fentanyl concentrations theoretically could increase by approximately one-third when body temperature increases to 40°C.

Percutaneous absorption of fentanyl from the transdermal system may be increased if the application site or surrounding area is exposed to direct external heat sources (e.g., heating pads, electric blankets, heat or tanning lamps, saunas, hot tubs, hot baths, heated water beds, sunbathing) while the transdermal system is being worn; avoid such exposure.

Accidental Exposure

Risk of serious or fatal adverse effects following accidental exposure to fentanyl transdermal systems (e.g., transfer of a transdermal system from an adult to a child while hugging, inadvertently sitting on a transdermal system, exposure of the caregiver’s skin to the drug during application or removal of the transdermal system). If accidental exposure occurs, remove system and wash area of contact with water. The accidentally exposed individual should seek medical attention immediately.

Risk of choking or potentially fatal overdosage of fentanyl if transdermal system is placed in the mouth, chewed or swallowed, or used in other unintended ways.

Head Injury and Increased Intracranial Pressure

May interfere with evaluation of CNS function, and respiratory depression produced by the drug may produce cerebral hypoxia and elevated CSF pressure not caused by the injury itself.

Use with extreme caution, if at all, in patients with severe CNS depression, anoxia, hypercapnia, respiratory depression, or in those susceptible to the intracranial effects of CO₂ retention or who are especially prone to respiratory depression such as comatose patients or those with head injury, brain tumor, or elevated CSF pressure.

Major Toxicities

Musculoskeletal Effects

Muscle rigidity, particularly involving the respiratory muscles. Concomitant neuromuscular blocking agents before or simultaneous with anesthetic use of fentanyl can reduce the risk.

Dental Decay

Dental decay, including caries, tooth loss, and gum line erosion, has occurred in patients receiving fentanyl citrate buccal lozenges, despite routine oral hygiene in some patients. (See Buccal Tablets and Lozenges under Advice to Patients.) Each fentanyl citrate buccal lozenge contains 2 g of sugar.

General Precautions

Care should be exercised and the initial dosage of the opiate agonist should be reduced in patients with toxic psychosis and in neonates and geriatric or debilitated patients.

CNS Effects

May impair mental alertness and/or physical coordination needed to perform potentially hazardous activities such as driving or operating machinery; warn patient about possible adverse CNS effects of opiate agonists.

Cardiac Arrhythmia

Because of cholinergic effects, may cause bradycardia. Caution in patients with cardiac bradyarrhythmias.

Hypothyroidism

Use with caution and in reduced dosage in patients with hypothyroidism.

Addison’s Disease

Use with caution and in reduced dosage in patients with Addison’s disease.

Pancreatic and Biliary Disease

May cause spasm of the sphincter of Oddi. Use with caution in patients with biliary tract disease, including acute pancreatitis. Opiates may increase serum amylase concentrations.

Diabetes Mellitus

Each buccal lozenge contains 2 g of sugar.

Cachectic or Debilitated Patients

Use transdermal fentanyl with caution, since clearance of the drug may be decreased and reduced fat stores or muscle wasting may alter the drug’s pharmacokinetics.

Local (Oral Mucosal) Reactions

Application site reactions (e.g., paresthesia, pain, ulceration, irritation, bleeding) reported in patients receiving fentanyl citrate buccal tablets; tend to occur early during treatment and generally are self-limited.

Specific Populations

Pregnancy

Category C.

Lactation

Distributed into milk. Discontinue nursing or the drug because of potential risk (sedation, respiratory depression) to nursing infants.

Pediatric Use

Safety and efficacy of parenteral and transdermal therapy not established in children <2 years of age. Administer transdermal systems to children only if they are opiate tolerant and ≥2 years of age.

Safety and efficacy of buccal (transmucosal) lozenges not established in children <16 years of age.

Safety and efficacy of buccal tablets not established in children <18 years of age.

To reduce potential for accidental ingestion, carefully select application site in young children receiving transdermal fentanyl therapy and monitor the system for proper adhesion over the period of application.

Transdermal systems and buccal lozenges and tablets contain fentanyl in amounts that can be fatal to a child. Fatal respiratory depression can occur if a transdermal system is accidentally or deliberately applied or ingested by a child or adolescent. If a child is accidentally exposed to a fentanyl transdermal system or accidentally ingests the buccal tablets or lozenges, parents or caregivers should seek immediate medical treatment for the child.

Strongly warn patients and/or their caregivers to keep new and used transdermal systems and new and partially used buccal preparations in a secure location out of the reach of children. Specifically question patients and/or their caregivers about the presence of children in the patient’s home.

Geriatric Use

Respiratory depression is the major toxicity of fentanyl in geriatric or debilitated patients, especially after large initial doses in non-opiate-tolerant patients or when given in conjunction with other drugs that depress respiration.

Clearance of IV fentanyl may be reduced substantially in individuals ≥60 years of age. Geriatric patients may be more sensitive to effects of IV fentanyl.

Use transdermal fentanyl with caution, since clearance of the drug may be decreased and reduced fat stores or muscle wasting may alter the drug’s pharmacokinetics.

Increased frequency of certain adverse effects (e.g., vomiting, constipation, abdominal pain) reported in geriatric patients compared with younger patients receiving fentanyl citrate buccal tablets. Safety profile of the buccal lozenges in geriatric patients appears similar to that in younger patients; however, caution is advised because of greater sensitivity observed in geriatric patients receiving IV fentanyl.

Caution when selecting and titrating dosage. (See Geriatric Patients under Dosage and Administration.)

Hepatic Impairment

May have a prolonged duration and cumulative effect in patients with hepatic dysfunction.

Exercise caution and reduce initial parenteral dosage. Insufficient information available to support recommendations regarding use of transdermal or buccal preparations; if used, caution advised.

Renal Impairment

May have a prolonged duration and cumulative effect in patients with renal dysfunction.

Exercise caution and reduce initial parenteral dosage. Insufficient information available to support recommendations regarding use of transdermal or buccal preparations; if used, caution advised.

Common Adverse Effects

Abdominal pain, headache, bradyarrhythmia, chest pain, nausea, vomiting, constipation, somnolence, confusion, asthenia, fatigue, dizziness, nervousness, hallucinations, anxiety, depression, euphoria, respiratory depression (hypoventilation, dyspnea, apnea), sweating, pruritus, urinary retention.

IV administration: Skeletal and thoracic muscle rigidity also occur frequently.

Transdermal system: Erythema (may persist for ≥6 hours after removal of the system), papules, pruritus, and edema at the site of application also occur frequently.

Buccal tablets: Application site reactions (e.g., paresthesia, pain, bleeding, ulceration, irritation) also occur frequently.

Interactions

Metabolized by CYP3A4.

Drugs Affecting Hepatic Microsomal Enzymes

CYP3A4 inhibitors: Concomitant use with drugs that inhibit CYP3A4 activity may cause decreased clearance of fentanyl resulting in increased or prolonged opiate effects; exercise caution during concomitant use and adjust dosage as necessary. If potent or moderately potent CYP3A4 inhibitors are used concomitantly with intrabuccal fentanyl therapy, monitor patients for an extended period of time; increases in fentanyl dosage should be conservative. Use of any CYP3A4 inhibitor concomitantly with transdermal fentanyl results in increased plasma fentanyl concentrations and may potentially cause fatal respiratory depression; monitor patients receiving such concomitant therapy for an extended period of time and adjust dosage if needed.

CYP3A4 inducers: Induce metabolism and may cause increased clearance of fentanyl resulting in decreased opiate effects; exercise caution during concomitant use and adjust dosage as necessary.

Specific Drugs and Foods

Pharmacokinetics

Absorption

Bioavailability

Well absorbed percutaneously following topical application of a transdermal system and transmucosally following intrabuccal administration via sucking of a lozenge matrix or administration of a buccal tablet.

When administered as a buccal tablet rather than a buccal lozenge, a larger fraction of the administered dose is absorbed transmucosally (48% versus 22%), peak plasma concentration is achieved earlier (47 versus 91 minutes), and systemic exposure to the drug is approximately 30–50% greater.

Buccal lozenge: Bioavailability averages about 50%. Generally, approximately 25% absorbed rapidly from the buccal mucosa and the remaining portion is swallowed with saliva and then absorbed slowly from the GI tract.

Buccal tablet: Bioavailability averages about 65%. Generally, approximately 50% absorbed rapidly from the buccal mucosa and the remaining portion is swallowed with saliva and then absorbed slowly from the GI tract. The time required for the buccal tablet to fully disintegrate does not appear to affect early systemic exposure to the drug.

Transdermal systems are designed to deliver fentanyl at a nearly constant rate of 25 mcg/hour per 10 cm² (Duragesic^®, Actavis, Sandoz, and Watson transdermal systems) or 25 mcg/hour per 6.25 cm² (Mylan transdermal system); however, actual amount of drug delivered to the skin exhibits interindividual variation. Mylan transdermal systems labeled as delivering 12.5, 25, 50, 75, or 100 mcg of fentanyl per hour are bioequivalent to the respectively labeled delivery concentrations of Duragesic^®.

Transdermal system: Peak concentration attained within 24–72 hours after initial application. With sequential, continuous use, serum concentrations continue to increase with the first few transdermal system applications.

Serum concentrations of transdermally administered fentanyl theoretically could increase by approximately one-third when body temperature increases to 40°C.

Application of a polyurethane film dressing (Bioclusive^®) over a Duragesic^® 100-mcg/hour transdermal system did not alter the pharmacokinetics of the drug.

Following use of transdermal systems in non-opiate-tolerant children 1.5–5 years of age, plasma fentanyl concentrations were about twice the concentrations achieved in adults; however, pharmacokinetic parameters in older children were similar to those in adults.

Onset

IV administration: Rapid, with peak analgesia occurring within several minutes.

IM administration: About 7–15 minutes.

Intrabuccal administration (lozenge): About 5–15 minutes; peaks within 20–50 minutes.

Intrabuccal administration (tablet): About 10 minutes.

Duration

IV administration, analgesia: 0.5–1 hours.

IM administration, analgesia: 1–2 hours.

Respiratory depressant effects may persist longer than analgesia.

Special Populations

Following administration of single 200-mcg buccal tablet, systemic exposure to fentanyl in patients with grade 1 mucositis appears to be similar to that in patients without mucositis.

Distribution

Extent

IV administration: Distributes rapidly from blood into the lungs and skeletal muscle and more slowly into deeper fat compartments; then redistributes slowly from these tissues into systemic circulation.

Large single or repeated doses can result in substantial accumulation, potentially resulting in an extended duration of effect.

Fentanyl crosses the placenta and is distributed into breast milk.

Plasma Protein Binding

80–85% bound, principally to α₁-acid glycoprotein but also to albumin and lipoproteins.

Elimination

Metabolism

Metabolized extensively in the liver and the intestinal mucosa via CYP3A4; also undergoes hydrolysis.

Transdermally administered fentanyl does not appear to be metabolized in the skin.

Elimination Route

Principally in the urine, as inactive metabolites and to a lesser extent (<10%) as unchanged drug.

Half-life

IV: About 7.1 hours.

Oral: About 7.8 hours.

Buccal: 2.6–11.7 hours.

Transdermal: About 17 hours.

Stability

Storage

Buccal (Transmucosal)

Tablets and Lozenges

20–25°C (may be exposed to 15–30°C) in a secure place away from children. Protect from freezing and moisture. Once buccal tablet has been removed from the blister package, do not store for use at a later time since tablet integrity may be compromised or accidental exposure may occur.

Parenteral

Injection

15–30°C (may be exposed to up to 40°C); protect from light.

Topical

Transdermal Systems

≤25°C in a secure place away from children and pets. Apply the system to the skin immediately after removal from the individually sealed package; discard if the seal was previously broken.

Discard cut, damaged, or altered transdermal systems since proper controlled release of the drug cannot be ensured. (See Transdermal Systems in Boxed Warning.)

Compatibility

For information on systemic interactions resulting from concomitant use, see Interactions.

Parenteral

Hydrolyzed in acidic solutions.

Solution Compatibility

Drug Compatibility

Actions

• A potent analgesic; shares the actions of the opiate agonists.
• Opiate agonists alter perception of and emotional response to pain.
• Precise mechanism of action has not been fully elucidated; opiate agonists act at several CNS sites, involving several neurotransmitter systems to produce analgesia.
• Pain perception is altered in the spinal cord and higher CNS levels (e.g., substantia gelatinosa, spinal trigeminal nucleus, periaqueductal gray, periventricular gray, medullary raphe nuclei, hypothalamus).
• Opiate agonists do not alter the threshold or responsiveness of afferent nerve endings to noxious stimuli, nor peripheral nerve impulse conduction.
• Opiate agonists act at specific receptor binding sites in the CNS and other tissues; opiate receptors are concentrated in the limbic system, thalamus, striatum, hypothalamus, midbrain, and spinal cord.
• Agonist activity at the opiate μ- or κ-receptor can result in analgesia, miosis, and/or decreased body temperature.
• Agonist activity at the μ-receptor can also result in suppression of opiate withdrawal (and antagonist activity can result in precipitation of withdrawal).
• Respiratory depression may be mediated by μ-receptors, possibly μ₂-receptors (which may be distinct from μ₁-receptors involved in analgesia); κ- and δ-receptors may also be involved in respiratory depression.
• In equivalent analgesic doses, fentanyl is similar to morphine and meperidine in its respiratory effects except that respiration of healthy individuals returns to normal more quickly after fentanyl than after either of the other drugs.
• Exhibits little hypnotic activity, and histamine release rarely occurs.

Advice to Patients

• Provide manufacturer’s patient information (e.g., medication guide) to the patient each time fentanyl transdermal system or fentanyl citrate buccal tablets or lozenges are dispensed.
• Importance of informing patients that fentanyl is a drug of abuse. Instruct patients to keep the transdermal systems and buccal tablets and lozenges in a secure place to prevent theft or misuse in the home or workplace. Risk of severe or fatal respiratory depression if misused or used in individuals for whom the drug was not prescribed.
• Importance of informing patients that fentanyl may impair mental and/or physical ability required for performance of potentially hazardous tasks; avoid driving or operating heavy machinery until effects on individual are known.
• Importance of informing patients that fentanyl should not be combined with alcohol or other CNS depressants (e.g., sleep medications, tranquilizers).
• Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs, as well as any concomitant illnesses.
• Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.
• Importance of seeking immediate medical attention if signs or symptoms of overdosage (e.g., difficulty breathing; slow, shallow breathing; slow heart rate; extreme drowsiness with slowed breathing; cold, clammy skin; seizures or hallucinations; feelings of faintness, dizziness, or confusion) occur.
• Potential for severe constipation to occur.
• Importance of not abruptly discontinuing fentanyl following prolonged opiate therapy.
• Importance of informing patients of other important precautionary information.(See Cautions.)

Buccal Tablets and Lozenges
• Importance of using buccal tablets and lozenges exactly as prescribed and only if opiate tolerant. Do not substitute buccal tablets for buccal lozenges, or buccal tablets or lozenges for other fentanyl preparations, without consulting clinician.
• Importance of adhering to prescribed dosage and instructions for administration.
• Importance of using or discarding all the buccal tablets of one strength prior to obtaining buccal tablets of a different strength.
• Instruct patients to inform their dentist that they are receiving fentanyl citrate buccal lozenges, so that appropriate dental care is provided.
• Importance of questioning patients and/or their caregivers about the presence of children in the patient’s home, since the buccal tablets and lozenges contain sufficient amounts of fentanyl to be fatal to a child.
• Importance of warning patients and/or their caregivers to keep the buccal tablets and lozenges out of the reach of children and to safely dispose of partially used units.
• Proper disposal of partially consumed buccal lozenges involves dissolving any remaining lozenge under hot running tap water until the matrix is gone and then discarding the handle in a trash receptacle that is out of reach of children.
• Proper disposal of remaining unused buccal lozenges involves cutting open the package with scissors, holding the lozenge by its handle over a toilet bowl and cutting the drug matrix off the handle with wire-cutting pliers, flushing the toilet twice after up to 5 units have been cut and deposited in the toilet, and then discarding the handle in a trash receptacle that is out of reach of children.
• Proper disposal of remaining unused buccal tablets involves removing the buccal tablets from their blister packages and flushing the tablets down the toilet.
• Handles, blister packages, and cartons should not be flushed down the toilet, but disposed of according to instructions provided by the manufacturer.
• If patients and/or their caregivers need additional assistance with disposal of unused lozenges or buccal tablets, contact the manufacturer at 800-896-5855 or, alternatively, the local office of the DEA.

Transdermal Systems
• Importance of using transdermal systems exactly as prescribed and only if opiate tolerant.
• Importance of adhering to prescribed dosage and instructions for administration.
• Risk of serious or fatal adverse effects following accidental exposure to fentanyl transdermal systems. (See Accidental Exposure under Cautions.)
• Importance of questioning patients and/or their caregivers about the presence of children in the patient’s home, since the transdermal systems contain sufficient amounts of fentanyl to be fatal to a child.
• Importance of warning patients and/or their caregivers to keep the transdermal systems out of the reach of children and pets and to safely dispose of used units.
• Importance of not using transdermal systems that have been altered in any way (e.g., cut, damaged, folded so that only part of the system is exposed).
• Instruct patients to carefully fold used transdermal systems immediately following removal so that the adhesive side adheres to itself and then flush them down the toilet.
• Instruct patients who have completed their course of transdermal therapy to discard any remaining unused systems by removing them from their packaging, folding them so that the adhesive side adheres to itself, and flushing them down the toilet.
• If gel from the drug reservoir of the transdermal system accidentally contacts the skin, the area should be washed with copious amounts of water. Do not use soap, alcohol, or other solvents since percutaneous absorption of the drug may be enhanced.
• Advise patients to avoid exposing the application site or surrounding area to direct external heat sources (e.g., heating pads, electric blankets, heat or tanning lamps, saunas, hot tubs, hot baths, heated water beds, sunbathing) while wearing the transdermal system since temperature-dependent increases in percutaneous absorption of fentanyl from the system are possible under such conditions. Importance of contacting clinician if a high fever occurs or if body temperature increases following strenuous exercise during transdermal fentanyl therapy.

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Subject to control under the Federal Controlled Substances Act of 1970 as schedule II (C-II) drugs.

Comparative Pricing

This pricing information is subject to change at the sole discretion of DS Pharmacy. This pricing information was updated 09/2009. For the most current and up-to-date pricing information, please visit www.drugstore.com. Actual costs to patients will vary depending on the use of specific retail or mail-order locations and health insurance copays.

AHFS Drug Information. © Copyright, 1959-2009, Selected Revisions August 2009. American Society of Health-System Pharmacists, Inc., 7272 Wisconsin Avenue, Bethesda, Maryland 20814.

† Use is not currently included in the labeling approved by the US Food and Drug Administration.

Remember, keep this and all other medicines out of the reach of children, never share your medicines with others, and use this medication only for the indication prescribed.