DURAGESIC

Generic Name: fentanyl topical (FEN ta nill)
Brand Names: Duragesic

What is the most important information I should know about fentanyl topical?

ï	Fentanyl topical should not be used to treat acute or post-operative pain. Fentanyl topical is used to treat chronic pain.

ï	Use caution when driving, operating machinery, or performing other hazardous activities. Fentanyl may cause drowsiness or fatigue. If you experience drowsiness or fatigue, avoid these activities.

ï	Also avoid alcohol, sleeping pills, tranquilizers, sedatives, and antihistamines. These medications also may cause dangerous sedation.

ï	Fentanyl topical can also cause constipation. Drink plenty of water (six to eight full glasses a day) to lessen this side effect. Increasing the amount of fiber in your diet can also help to alleviate constipation.

ï	Never use more fentanyl than is prescribed for you. If your pain is not being adequately treated, talk to your doctor.

What is fentanyl topical?

ï	Fentanyl is in a class of drugs called narcotic analgesics. It relieves pain.

ï	Fentanyl topical patches are used to treat chronic pain that cannot be controlled by less potent pain relievers.

ï	Fentanyl topical may also be used for purposes other than those listed in this medication guide.

What should I discuss with my healthcare provider before using fentanyl topical?

ï	Fentanyl topical should not be used to treat acute or post-operative pain. Fentanyl topical is used to treat chronic pain.

ï	Fentanyl is habit forming and should be used under close medical supervision.

ï	Before using this medication, tell your doctor if you have

…	kidney disease;

…	liver disease;

…

asthma;

…	urinary retention;

…	an enlarged prostate;

…	hypothyroidism;

…	seizures or epilepsy;

…	gallbladder disease;

…	a head injury; or

…	Addison's disease.

ï	You may not be able to use fentanyl topical, or you may require a lower dose or special monitoring during treatment if you have any of the conditions listed above.

ï	Fentanyl is in the FDA pregnancy category C. This means that it is not known whether fentanyl will harm an unborn baby. This medication may cause addiction and withdrawal symptoms in an unborn baby. Do not use fentanyl topical without first talking to your doctor if you are pregnant.

ï	Fentanyl may also cause addiction and withdrawal symptoms in a nursing infant. Do not use fentanyl topical without first talking to your doctor if you are breast-feeding a baby.

ï	Fentanyl topical patches are not approved for use by children younger than 12 years of age or by children younger than 18 years of age who weigh less than 50 kg (110 lbs).

ï	If you are older than 60 years of age, you may be more likely to experience side effects from fentanyl therapy. A lower dose or special monitoring may be necessary.

How should I use fentanyl topical?

ï	Use fentanyl topical exactly as directed by your doctor. If you do not understand these directions, ask your pharmacist, nurse, or doctor to explain them to you.

ï	Apply the patch to a flat, dry, area such as the chest, back, side, or upper arm. Any hair on the application site should be clipped short but not shaved. Avoid areas that are irritated or otherwise damaged.

ï

If the application site must be washed before the patch is applied, use clear water only. Do not use soaps, oils, lotions, alcohol, or other chemicals. Washing with these substances could change how much of the drug gets absorbed through the skin, which could be dangerous. Allow the skin to dry completely before applying the patch.

ï	Apply the patch as directed. Press the patch firmly with the palm of your hand for 30 seconds making sure that the patch is sticking, especially around the edges. Each patch is worn for 72 hours.

ï	After removing the patch, press the sticky side to itself and dispose of the system in the toilet. If another patch is required, apply it to a different skin site.

ï	Do not cut or otherwise damage the patch, and do not apply any patch that has been cut or damaged.

ï	Never use more of this medication than is prescribed for you. Too much fentanyl could be very harmful.

ï	Increase the amount of fiber and water in your diet to prevent constipation.

ï	Do not share this medication with anyone else. Keep it out of the reach of children and pets.

ï	Store fentanyl topical at room temperature away from moisture and heat.

What happens if I miss a dose?

ï	Apply the missed dose as soon as you remember. Do not use a double dose of this medication. Wait the prescribed amount of time before applying your next patch.

What happens if I overdose?

ï	Seek emergency medical attention.

ï	Symptoms of a fentanyl overdose include slow breathing, seizures, dizziness, weakness, loss of consciousness or coma, confusion, tiredness, cold and clammy skin, and small pupils.

What should I avoid while using fentanyl topical?

ï	Use caution when driving, operating machinery, or performing other hazardous activities. Fentanyl may cause drowsiness or fatigue. If you experience drowsiness or fatigue, avoid these activities.

ï	Avoid alcohol while using fentanyl topical. Alcohol will greatly increase the drowsiness and dizziness caused by fentanyl and could be dangerous.

ï	Also avoid sleeping pills, tranquilizers, sedatives, and antihistamines. These medications also may cause dangerous sedation.

ï	Avoid becoming overheated or applying direct heat such as a heating pad to the area where you have a patch. Increased temperature can increase the amount of drug you absorb through your skin and may cause harmful effects.

What are the possible side effects of fentanyl topical?

ï	If you experience any of the following serious side effects, stop using fentanyl topical and seek emergency medical attention:

…	an allergic reaction (difficulty breathing; closing of your throat; swelling of your lips, tongue, or face; or hives);

…	slow, weak breathing;

…

seizures;

…	cold, clammy skin;

…	severe weakness or dizziness; or

…	unconsciousness.

ï	Other, less serious side effects may be more likely to occur. Continue to use fentanyl topical and talk to your doctor if you experience

…	constipation;

…	dry mouth, nausea, vomiting, or decreased appetite;

…	dizziness or lightheadedness;

…	drowsiness or fatigue;

…	muscle twitches;

…

sweating;

…

itching;

…	decreased urination; or

…	decreased sex drive.

ï	Fentanyl is habit forming. Do not stop using it suddenly.

ï	Side effects other than those listed here may also occur. Talk to your doctor about any side effect that seems unusual or that is especially bothersome.

What other drugs will affect fentanyl topical?

ï

Fentanyl topical may increase the effects of other drugs that cause drowsiness, including antidepressants, alcohol, antihistamines, sedatives (used to treat insomnia), other pain relievers, anxiety medicines, and muscle relaxants. Tell your doctor about all medicines that you are taking, and do not take any medicine unless your doctor approves.

ï	Drugs other than those listed here may also interact with fentanyl topical. Talk to your doctor and pharmacist before taking any prescription or over-the-counter medicines.

Where can I get more information?

ï	Your pharmacist has additional information about fentanyl topical written for health professionals that you may read.

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ï	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.

ï

Every effort has been made to ensure that the information provided by Cerner Multum, Inc. ('Multum') is accurate, up-to-date, and complete, but no guarantee is made to that effect. Drug information contained herein may be time sensitive. Multum information has been compiled for use by healthcare practitioners and consumers in the United States and therefore Multum does not warrant that uses outside of the United States are appropriate, unless specifically indicated otherwise. Multum's drug information does not endorse drugs, diagnose patients or recommend therapy. Multum's drug information is an informational resource designed to assist licensed healthcare practitioners in caring for their patients and/ or to serve consumers viewing this service as a supplement to, and not a substitute for, the expertise, skill, knowledge and judgment of healthcare practitioners. The absence of a warning for a given drug or drug combination in no way should be construed to indicate that the drug or drug combination is safe, effective or appropriate for any given patient. Multum does not assume any responsibility for any aspect of healthcare administered with the aid of information Multum provides. The information contained herein is not intended to cover all possible uses, directions, precautions, warnings, drug interactions, allergic reactions, or adverse effects. If you have questions about the drugs you are taking, check with your doctor, nurse or pharmacist.

DURAGESIC^Æ (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-piperidyl) propanamide.

ADVERSE REACTIONS

In post-marketing experience, deaths from hypoventilation due to inappropriate use of DURAGESICÆ (fentanyl transdermal system) have been reported. (See BOX WARNING and CONTRAINDICATIONS.)

Pre-marketing Clinical Trial Experience

The safety of DURAGESICÆ has been evaluated in 357 postoperative patients and 153 cancer patients for a total of 510 patients. Patients with acute pain used DURAGESICÆ for 1 to 3 days. The duration of DURAGESICÆ use varied in cancer patients; 56% of patients used DURAGESICÆ for over 30 days, 28% continued treatment for more than 4 months, and 10% used DURAGESICÆ for more than 1 year.

Hypoventilation was the most serious adverse reaction observed in 13 (4%) postoperative patients and in 3 (2%) of the cancer patients. Hypotension and hypertension were observed in 11 (3%) and 4 (1%) of the opioid-naive patients.Various adverse events were reported; a causal relationship to DURAGESICÆ was not always determined. The frequencies presented here reflect the actual frequency of each adverse effect in patients who received DURAGESICÆ. There has been no attempt to correct for a placebo effect, concomitant use of other opioids, or to subtract the frequencies reported by placebo-treated patients in controlled trials.

The following adverse reactions were reported in 153 cancer patients at a frequency of 1% or greater; similar reactions were seen in the 357 postoperative patients studied.

Body as a Whole: abdominal pain*, headache*

Cardiovascular: arrhythmia, chest pain

Digestive: nausea**, vomiting**, constipation**, dry mouth**, anorexia*, diarrhea*, dyspepsia*, flatulence

Nervous: somnolence**, confusion**, asthenia**, dizziness*, nervousness*, hallucinations*, anxiety*, depression*, euphoria*, tremor, abnormal coordination, speech disorder, abnormal thinking, abnormal gait, abnormal dreams, agitation, paresthesia, amnesia, syncope, paranoid reactionRespiratory: dyspnea*, hypoventilation*, apnea*, hemoptysis, pharyngitis, hiccups

Skin and Appendages: sweating**, pruritus*, rash, application site reaction - erythema, papules, itching, edema

Urogenital: urinary retention*

* Reactions occurring in 3% - 10% of DURAGESICÆ patients ** Reactions occurring in 10% or more of DURAGESICÆ patients

The following adverse effects have been reported in less than 1% of the 510 postoperative and cancer patients studied; the association between these events and DURAGESICÆ administration is unknown. This information is listed to serve as alerting information for the physician.

Digestive: abdominal distention

Nervous: aphasia, hypertonia, vertigo, stupor, hypotonia, depersonalization, hostility

Respiratory: stertorous breathing, asthma, respiratory disorder

Skin and Appendages, General: exfoliative dermatitis, pustules

Special Senses: amblyopia

Urogenital: bladder pain, oliguria, urinary frequency

DRUG ABUSE AND DEPENDENCE

Fentanyl is a Schedule II controlled substance and can produce drug dependence similar to that produced by morphine. DURAGESICÆ (fentanyl transdermal system) therefore has the potential for abuse. Tolerance, physical and psychological dependence may develop upon repeated administration of opioids. Iatrogenic addiction following opioid administration is relatively rare. Physicians should not let concerns of physical dependence deter them from using adequate amounts of opioids in the management of severe pain when such use is indicated.

DRUG INTERACTIONS

No information provided.

WARNINGS

BECAUSE SERIOUS OR LIFE-THREATENING HYPOVENTILATION COULD OCCUR, DURAGESIC^Æ (FENTANYL TRANSDERMAL SYSTEM) IS CONTRAINDICATED:

ï In the management of acute or post-operative pain, including use in out-patient surgeries

ï In the management of mild or intermittent pain responsive to PRN or non-opioid therapy

ï In doses exceeding 25 µg/h at the initiation of opioid therapy (See CONTRAINDICATIONS for further information.)

DURAGESIC^Æ SHOULD NOT BE ADMINISTERED TO CHILDREN UNDER 12 YEARS OF AGE OR PATIENTS UNDER 18 YEARS OF AGE WHO WEIGH LESS THAN 50 KG (110 LBS) EXCEPT IN AN AUTHORIZED INVESTIGATIONAL RESEARCH SETTING. (See PRECAUTIONS - Pediatric Use.)

DURAGESIC^Æ is indicated for treatment of chronic pain (such as that of malignancy) that:

ï Cannot be managed by lesser means such as acetaminophen-opioid combinations, non-steroidal analgesics, or PRN dosing with short-acting opioids and

ï Requires continuous opioid administration.The 50, 75, and 100 µg/h dosages should ONLY be used in patients who are already on and are tolerant to opioid therapy.

DURAGESIC^Æ (FENTANYL TRANSDERMAL SYSTEM) SHOULD NOT BE ADMINISTERED TO CHILDREN UNDER 12 YEARS OF AGE OR PATIENTS UNDER 18 YEARS OF AGE WHO WEIGH LESS T.A. 50 KG (110 LBS) EXCEPT IN AN AUTHORIZED INVESTIGATIONAL RESEARCH SETTING. (See PRECAUTIONS-Pediatric Use.)

PATIENTS WHO HAVE EXPERIENCED ADVERSE EVENTS SHOULD BE MONITORED FOR AT LEAST 12 HOURS AFTER DURAGESIC^Æ REMOVAL SINCE SERUM FENTANYL CONCENTRATIONS DECLINE GRADUALLY AND REACH AN APPROXIMATE 50% REDUCTION IN SERUM CONCENTRATIONS 17 HOURS AFTER SYSTEM REMOVAL.

DURAGESIC^Æ 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.THE CONCOMITANT USE OF OTHER CENTRAL NERVOUS SYSTEM DEPRESSANTS, INCLUDING OTHER OPIOIDS, SEDATIVES OR HYPNOTICS, GENERAL ANESTHETICS, PHENOTHIAZINES, TRANQUILIZERS, SKELETAL MUSCLE RELAXANTS, SEDATING ANTIHISTAMINES, AND ALCOHOLIC BEVERAGES MAY PRODUCE ADDITIVE DEPRESSANT EFFECTS. HYPOVENTILATION, HYPOTENSION AND PROFOUND SEDATION OR C.M. MAY OCCUR. WHEN SUCH COMBINED THERAPY IS CONTEMPLATED, THE DOSE OF ONE OR BOTH AGENTS SHOULD BE REDUCED BY AT LEAST 50%.

ALL PATIENTS SHOULD BE ADVISED TO AVOID EXPOSING THE DURAGESIC^Æ APPLICATION SITE TO DIRECT EXTERNAL HEAT SOURCES, SUCH AS HEATING PADS OR ELECTRIC BLANKETS, HEAT LAMPS, SAUNAS, HOT TUBS, AND HEATED WATER BEDS, ETC., WHILE WEARING THE SYSTEM. THERE IS A POTENTIAL FOR TEMPERATURE-DEPENDENT INCREASES IN FENTANYL RELEASE FROM THE SYSTEM. (See PRECAUTIONS - Patients with Fever/External Heat.)

PRECAUTIONS

General

DURAGESIC^Æ (fentanyl transdermal system) doses greater than 25 µg/h are too high for initiation of therapy in non-opioid-tolerant patients and should not be used to begin DURAGESIC^Æ therapy in these patients. (See BOX WARNING.)

DURAGESIC^Æ may impair mental and/or physical ability required for the performance of potentially hazardous tasks (eg, driving, operating machinery). Patients who have been given DURAGESIC^Æ should not drive or operate dangerous machinery unless they are tolerant to the side effects of the drug.

Patients should be instructed to keep both used and unused systems out of the reach of children. Used systems should be folded so that the adhesive side of the system adheres to itself and flushed down the toilet immediately upon removal. Patients should be advised to dispose of any systems remaining from a prescription as soon as they are no longer needed. Unused systems should be removed from their pouch and flushed down the toilet.

Hypoventilation (Respiratory Depression)
Hypoventilation may occur at any time during the use of DURAGESIC^Æ.

Because significant amounts of fentanyl are absorbed from the skin for 17 hours or more after the system is removed, hypoventilation may persist beyond the removal of DURAGESIC^Æ. 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. (See WARNINGS.)

Chronic Pulmonary Disease
Because potent opioids can cause hypoventilation, DURAGESIC^Æ (fentanyl transdermal system) should be administered with caution to patients with preexisting 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.

Head Injuries and Increased Intracranial Pressure
DURAGESIC^Æ 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. DURAGESIC^Æ should be used with caution in patients with brain tumors.

Cardiac Disease
Intravenous fentanyl may produce bradycardia. Fentanyl should be administered with caution to patients with bradyarrhythmias.

Hepatic or Renal Disease
At the present time insufficient information exists to make recommendations regarding the use of DURAGESIC^Æ in patients with impaired renal or hepatic function. If the drug is used in these patients, it should be used with caution because of the hepatic metabolism and renal excretion of fentanyl.

Patients with Fever/External Heat
Based on a pharmacokinetic model, serum fentanyl concentrations could theoretically increase by approximately one third for patients with a body temperature of 40ƒC (104ƒF) due to temperature-dependent increases in fentanyl release from the system and increased skin permeability. Therefore, patients wearing DURAGESIC^Æ systems who develop fever should be monitored for opioid side effects and the DURAGESIC^Æ dose should be adjusted if necessary.

All patients should be advised to avoid exposing the DURAGESIC^Æ application site to direct external heat sources, such as heating pads or electric blankets, heat lamps, saunas , hot tubs, and heated water beds, etc., while wearing the system. There is a potential for temperature-dependent increases in fentanyl release from the system.

Central Nervous System Depressants
When patients are receiving DURAGESIC^Æ, the dose of additional opioids or other CNS depressant drugs (including benzodiazepines) should be reduced by at least 50%. With the concomitant use of CNS depressants, hypotension may occur.

Drug or Alcohol Dependence
Use of DURAGESIC^Æ in combination with alcoholic beverages and/or other CNS depressants can result in increased risk to the patient. DURAGESIC^Æ should be used with caution in individuals who have a history of drug or alcohol abuse, especially if they are outside a medically controlled environment.

Ambulatory Patients
Strong opioid analgesics impair the mental or physical abilities required for the performance of potentially dangerous tasks such as driving a car or operating machinery. Patients who have been given DURAGESIC^Æ should not drive or operate dangerous machinery unless they are tolerant to the effects of the drug.

Carcinogenesis, Mutagenesis, and Impairment of Fertility

Because long-term animal studies have not been conducted, the potential carcinogenic effects of DURAGESIC^Æ are unknown. There was no evidence of mutagenicity in the Ames Salmonella typhimurium mutagenicity assay, the primary rat hepatocyte unscheduled DNA synthesis assay, the BALB/c-3T3 transformation test, the mouse lymphoma assay, the human lymphocyte and CHO chromosomal aberration in-vitro assays, or the in-vivo micronucleus test.

Pregnancy

Pregnancy Category C: Fentanyl has been shown to impair fertility and to have an embryocidal effect in rats when given in intravenous doses 0.3 times the human dose for a period of 12 days. No evidence of teratogenic effects has been observed after administration of fentanyl to rats. There are no adequate and well-controlled studies in pregnant women. DURAGESIC^Æ should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

Labor and Delivery

DURAGESIC^Æ is not recommended for analgesia during labor and delivery.

Nursing Mothers

Fentanyl is excreted in human milk; therefore DURAGESIC^Æ is not recommended for use in nursing women because of the possibility of effects in their infants.

Pediatric Use

The safety and efficacy of DURAGESIC^Æ in pediatric patients have not been established. (See BOX WARNING and CONTRAINDICATIONS.)

DURAGESIC^Æ SHOULD NOT BE ADMINISTERED TO CHILDREN UNDER 12 YEARS OF AGE OR PATIENTS UNDER 18 YEARS OF AGE WHO WEIGH LESS THAN 50 KG (110 LBS) EXCEPT IN AN AUTHORIZED INVESTIGATIONAL RESEARCH SETTING.

Geriatric Use

Information from a pilot study of the pharmacokinetics of IV fentanyl in geriatric patients indicates that the clearance of fentanyl may be greatly decreased in the population above the age of 60. The relevance of these findings to transdermal fentanyl is unknown at this time.Since elderly, cachectic, or debilitated patients may have altered pharmacokinetics due to p.o. fat stores, muscle wasting, or altered clearance, they should not be started on DURAGESIC^Æ doses higher than 25 µg/h unless they are already taking more than 135 mg of oral morphine a day or an equivalent dose of another opioid (see DOSAGE AND ADMINISTRATION).

Information for Patients

A patient instruction sheet is included in the package of DURAGESICÆ systems dispensed to the patient.

Disposal of DURAGESICÆ DURAGESICÆ should be kept out of the reach of children. DURAGESICÆ systems should be folded so that the adhesive side of the system adheres to itself, then the system should be flushed down the toilet immediately upon removal. Patients should dispose of any systems remaining from a prescription as soon as they are no longer needed. Unused systems should be removed from their pouch and taken back to your prescribing physician to inspect and count before renewing your prescription.

If the gel from the drug reservoir accidentally contacts the skin, the area should be washed with clear water.