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

Pre-Marketing Clinical Trial Experience

Although DURAGESIC® (fentanyl transdermal) use in post-operative or acute pain and in patients who are not opioid-tolerant is CONTRAINDICATED, the safety of DURAGESIC® (fentanyl transdermal) was originally evaluated in 357 post-operative adult patients for 1 to 3 days and 153 cancer patients for a total of 510 patients. The duration of DURAGESIC® (fentanyl transdermal) use varied in cancer patients; 56% of patients used DURAGESIC® (fentanyl transdermal) for over 30 days, 28% continued treatment for more than 4 months, and 10% used DURAGESIC® (fentanyl transdermal) 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 DURAGESIC® (fentanyl transdermal) was not always determined. The frequencies presented here reflect the actual frequency of each adverse effect in patients who received DURAGESIC® (fentanyl transdermal) . 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.

Adverse reactions reported in 153 cancer patients at a frequency of 1% or greater are presented in Table 1; similar reactions were seen in the 357 post-operative patients.

In the pediatric population, the safety of DURAGESIC® (fentanyl transdermal) has been evaluated in 291 patients with chronic pain 2-18 years of age. The duration of DURAGESIC® (fentanyl transdermal) use varied; 20% of pediatric patients were treated for ≤ 15 days; 46% for 16-30 days; 16% for 31-60 days; and 17% for at least 61 days. Twenty-five patients were treated with DURAGESIC® (fentanyl transdermal) for at least 4 months and 9 patients for more than 9 months.

There was no apparent pediatric-specific risk associated with DURAGESIC® (fentanyl transdermal) use in children as young as 2 years old when used as directed. The most common adverse events were fever (35%), vomiting (33%), and nausea (24%).

Adverse events reported in pediatric patients at a rate of ≥ 1% are presented in Table 1.

TABLE 1: ADVERSE EVENTS (at rate of ≥ 1%) Adult (N=380) and Pediatric (N=291) Clinical Trial Experience

The following adverse effects have been reported in less than 1% of the 510 adult post-operative and cancer patients studied:

Cardiovascular: bradycardia

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

Post-Marketing Experience - Adults

The following adverse reactions have been reported in association with the use of DURAGESIC® (fentanyl transdermal) and not reported in the pre-marketing adverse reactions section above:

Body as a Whole: edema

Cardiovascular: tachycardia

Metabolic and Nutritional: weight loss

Special Senses: blurred vision

Urogenital: decreased libido, anorgasmia, ejaculatory difficulty

Drug Abuse And Addiction

DURAGESIC® contains a high concentration of fentanyl, a potent Schedule II opioid agonist. Schedule II opioid substances, which include hydromorphone, methadone, morphine, oxycodone, and oxymorphone, have the highest potential for abuse and risk of fatal overdose due to respiratory depression. Fentanyl, like morphine and other opioids used in analgesia, can be abused and is subject to criminal diversion.

The high content of fentanyl in the patches (DURAGESIC® (fentanyl transdermal) ) may be a particular target for abuse and diversion.

Addiction is a primary, chronic, neurobiologic disease, with genetic, psychosocial, and environmental factors influencing its development and manifestations. It is characterized by behaviors that include one or more of the following: impaired control over drug use, compulsive use, continued use despite harm, and craving. Drug addiction is a treatable disease, utilizing a multidisciplinary approach, but relapse is common.

“Drug seeking” behavior is very common in addicts and drug abusers. Drug-seeking tactics include emergency calls or visits near the end of office hours, refusal to undergo appropriate examination, testing or referral, repeated “loss” of prescriptions, tampering with prescriptions and reluctance to provide prior medical records or contact information for other treating physician(s). “Doctor shopping” to obtain additional prescriptions is common among drug abusers and people suffering from untreated addiction.

Abuse and addiction are separate and distinct from physical dependence and tolerance. Physicians should be aware that addiction may be accompanied by concurrent tolerance and symptoms of physical dependence. In addition, abuse of opioids can occur in the absence of true addiction and is characterized by misuse for non-medical purposes, often in combination with other psychoactive substances. Since DURAGESIC® (fentanyl transdermal) may be diverted for non-medical use, careful record keeping of prescribing information, including quantity, frequency, and renewal requests is strongly advised.

Proper assessment of the patient, proper prescribing practices, periodic re-evaluation of therapy, and proper dispensing and storage are appropriate measures that help to limit abuse of opioid drugs.

DURAGESIC® (fentanyl transdermal) patches are intended for transdermal use (to be applied on the skin) only. Do not use a DURAGESIC® (fentanyl transdermal) patch if the pouch seal is broken or the patch is cut, damaged, or changed in any way.

Agents Affecting Cytochrome P450 3A4 Isoenzyme System

Fentanyl is metabolized mainly via the human cytochrome P450 3A4 isoenzyme system (CYP3A4), therefore potential interactions may occur when DURAGESIC® (fentanyl transdermal) is given concurrently with agents that affect CYP3A4 activity. Coadminstration with agents that induce CYP3A4 activity may reduce the efficacy of DURAGESIC®. The concomitant use of transdermal fentanyl with all CYP3A4 inhibitors (such as ritonavir, ketoconazole, itraconazole, troleandomycin, clarithromycin, nelfanivir, nefazadone, 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 fatal respiratory depression. Patients receiving DURAGESIC® (fentanyl transdermal) 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 DOSAGE AND ADMINISTRATION for further information).

Central Nervous System Depressants

The concomitant use of DURAGESIC® (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 or death. When such combined therapy is contemplated, the dose of one or both agents should be significantly reduced.

MAO Inhibitors

DURAGESIC® (fentanyl transdermal) is not recommended for use in patients who have received MAOI within 14 days because severe and unpredictable potentiation by MAO inhibitors has been reported with opioid analgesics.

Last reviewed on RxList: 10/7/2010
This monograph has been modified to include the generic and brand name in many instances.