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11 Articles in Volume 12, Issue #10
An Anti-inflammatory Diet For Pain Patients
Focus on the Foot
How to Use Adrenocorticotropin As a Biomarker in Pain Management
Iatrogenic Nerve Injury Following Dry Needling For Foot Pain: Case Challenge
Methamphetamine Urine Toxicology: An In-depth Review
Musculoskeletal Ultrasound: A Primer for Primary Care
November 2012 Letters to the Editor
Off-label Use of Pain Treatment No Longer Covered by Insurance
Proper Disposal of Fentanyl Patches: What Patients Need to Know
The Next Barriers to Care: Your Local Pharmacy
Why Podiatric Medicine Must Embrace Pain Management

Proper Disposal of Fentanyl Patches: What Patients Need to Know

Recent media reports of adverse events and deaths in young children as a result of accidental exposures to the fentanyl patch highlight the need for patient education when clinicians prescribe these products.

Transdermal drug delivery systems (TDDS), also known as medication patches, are becoming more popular with more than 25 transdermal medications available for a variety of indications.1 Recent media reports of adverse events and death in young children as a result of accidental exposures to the fentanyl patch (Duragesic) highlight the need for patient education when prescribing these products. The following article will discuss the risks and benefits of the fentanyl patch, as well as proper disposal procedures.

The ideal characteristics for a medication to be delivered transdermally include low molecular weight, high lipid solubility, and efficacy at small doses.1,2 The increasing use of TDDS can be attributed to several benefits, such as improved patient compliance, noninvasive administration, reduced gastrointestinal irritation, rate control of absorption leading to steady drug concentrations, and prevention of first-pass metabolism.1-3 However, there are several disadvantages associated with medication patches. These include skin reactions, prolonged time to reach therapeutic effect, the possibility of loss of adhesion, varied absorption, the risk of burns from magnetic resonance imaging if the patch contains metallic backing, and the need for proper disposal.

Safety Concerns With Transdermal Fentanyl
Fentanyl, a schedule II µ opioid receptor agonist, is approximately 80 to 100 times more potent than morphine.4 This high potency, along with fentanyl’s low molecular weight and lipid solubility, make the drug a popular option for the transdermal management of chronic pain. Fentanyl’s high lipid solubility facilitates rapid diffusion into the epidermal tissue with slower movement into the dermal tissue; peak serum concentrations are reached within 20 to 72 hours.5 Variations in peak and steady-state concentrations of fentanyl occur due to differences among patients with regard to skin permeability and hepatic clearance. After the patch is removed, serum fentanyl concentrations gradually decline according to the drug's half-life of approximately 20 to 27 hours.4,5

The Institute for Safe Medication Practices (ISMP) classifies fentanyl as a high-alert medication due to its risk of causing significant patient harm when it is used in error.6 Because of this risk of serious harm when used inappropriately, transdermal fentanyl carries a boxed warning detailing its many safety concerns, which are described below.5

Abuse Potential
Numerous reports in the literature describe fentanyl patch abuse leading to death. Various methods of abuse include: oral ingestion of the patch, intravenous injection of patch contents, inhalation of patch contents, rectal insertion, application of multiple patches, oral ingestion of a “tea” made with patches, and application of patches obtained from unusual sources including dead bodies.7-20

Respiratory Depression and Death
The fentanyl patch should only be prescribed to patients with chronic pain who have demonstrated opioid tolerance, defined as those taking at least 60 mg of oral morphine, 30 mg of oral oxycodone, or 8 mg of oral hydromorphone daily, or an equianalgesic dose of another opioid, for a week or longer.5 The fentanyl patch should not be used in patients who are not opioid tolerant, or for the management of acute or postoperative pain. Cases of fatal respiratory depression due to inappropriate prescribing of the patch to patients who were opioid naïve or experiencing acute pain have been reported.21,22

Drug Interactions
Fentanyl is metabolized into inactive metabolites by cytochrome P450-3A4 (CYP3A4).4,5 Therefore, the concomitant use of fentanyl with CYP3A4 inhibitors (such as amiodarone, clarithromycin, diltiazem, erythromycin, fluconazole, itraconazole, ketoconazole, ritonavir, or verapamil) may increase the risk of adverse effects by decreasing the clearance of fentanyl. It is important to appropriately reduce the dose of fentanyl when it is administered with potent CYP3A4 inhibitors. One case report describes a possible drug interaction with fluconazole and the fentanyl patch, which resulted in death.23 Another case series attributed the death of a 46-year-old woman to a drug interaction with fentanyl and lopinavir/ritonavir.24

Exposure to Heat
Increased systemic fentanyl absorption from the patch can occur with heat exposure and may result in overdose and death. Per the product labeling, pharmacokinetic modeling suggests that serum fentanyl concentrations may increase by about 33% in patients with an increased body temperature of 40°C (104°F).5 Heat sources include heating pads, warming blankets, hot baths, and exposure to outdoor heat.25 Increases in core body temperature due to fever or increased physical activity also may lead to increased absorption. One case report describes fentanyl toxicity redulting from increased physical activity occurring outdoors in a hot environment.25

Accidental Exposure
For most TDDS, drug delivery requires movement of the drug from high to low concentrations down a concentration gradient.2,4 Due to the need for higher drug concentrations in the patch compared to the tissue, a substantial amount of drug still remains in the patch after removal. According to one study, the amount of fentanyl remaining in the patch after 3 days of continuous use ranges from 0.7 to 8.4 mg or 28% to 84.4% of the original content depending on the size of the patch.26 Therefore, patients are advised to strictly adhere to recommended disposal instructions to prevent accidental exposures, which have led to death in both children and adults.5

Unintended Fentanyl Transdermal Exposure
As noted, there have been several cases of adverse effects and death in young children as a result of accidental exposure to the fentanyl patch. In one case, a grandmother wearing a fentanyl patch was napping beside her 8-month-old grandchild and woke up to find the baby unresponsive.27 The patch was suspected to have caused the baby’s symptoms of opioid toxicity through skin-to-skin absorption. These symptoms were reversed by naloxone.

Two additional cases describe caregivers applying their own fentanyl patches to a child to help alleviate the child’s pain.28,29 This resulted in death in one case, while the other child was aroused after naloxone administration. These cases illustrate the need to educate patients about the significant risks associated with fentanyl when it is used in someone who is not opioid tolerant.

In one fatal case, a 1-year-old girl was found to have unintentionally ingested a fentanyl patch that was not disposed of properly.30 The patch was accidentally dropped on the floor and went unnoticed. Another fatal case occurred in a 2-year-old boy who was visiting his great grandmother at a nursing home.31 The boy ingested a patch, which was likely dropped on the floor. Further investigation at this long-term care facility found used medication patches in other patient rooms on the floor and stuck to bed railings. These cases reinforce that the amount of fentanyl remaining in a used patch can be fatal to a child, therefore highlighting the importance of proper disposal.

Table 1. Safety Tips for Fentanyl Patches

Disposal
A single dose of fentanyl can be fatal if accidental exposure occurs in children, or pets, or when the drug is used inappropriately. For this reason, the FDA has included fentanyl patches on a select list of medications that have specific disposal recommendations.32,33 When it is not possible to return the fentanyl patch through a medicine take-back event, proper disposal includes folding the adhesive side together then flushing the patch down the toilet after it is no longer needed. The FDA states that, “any potential risk to people and the environment from flushing this small, select list of medicines is outweighed by the real possibility of life-threatening risks from accidental ingestion of these medicines.”33

FDA Recommendations
The FDA warned the public of the need for appropriate use and disposal of fentanyl patches in 2005 and 2006 after reports of death and life-threatening adverse events resulting from improper disposal.33 Despite the earlier warnings from the FDA, there continued to be reports of accidental exposure to fentanyl patches, which prompted an additional alert. On April 18, 2012, the FDA reminded the public of the importance of appropriate storage, use, application, and disposal of fentanyl patches to prevent harm from accidental exposure. The FDA reported 26 cases of pediatric accidental exposures, of which 10 resulted in death and 12 in hospitalization. More than half of the cases occurred in children younger than 2 years old. Along with emphasizing proper disposal, the FDA described several precautions for fentanyl patch users to reduce the risk of accidental exposure in children34:

  • Keep fentanyl patches in a secure location that is out of reach of children because they may think the patch is a sticker, tattoo, or bandage
  • Consider covering the fentanyl patch with an adhesive film to ensure the patch does not come off
  • Inspect the patch throughout the day to ensure it is still in place

Patient Counseling Points
Healthcare providers should ensure that patients are adequately educated about the use, storage, and disposal of fentanyl patches to minimize the risk of harm or accidental exposure. Additionally, prescribers should ensure that patients are appropriate candidates for the patch prior to prescribing this high-risk medication. The ISMP recently developed a list of safety tips for fentanyl patches that includes important counseling points (Table 1).35 The full patient brochure can be found at http://www.ismp.org/docs/fentanyl-brochure.pdf.

Conclusion
Fentanyl patches are effective for managing chronic pain in patients who are opioid tolerant. However, this medication can be fatal when it is not used appropriately. Patients and providers should be aware of the abuse potential, the risk for respiratory depression and death, the possibility of drug interactions, the dangers of heat exposure, and the risks associated with accidental exposure. Accidental exposures were the subject of a recent FDA alert, which emphasized proper use and disposal. To avoid harm from accidental exposure, fentanyl patches have specific disposal recommendations. Proper disposal includes folding the adhesive side together then flushing the patch down the toilet if it is not possible to return the patch through a medicine take-back event. Health care providers should properly educate patients about the risks associated with transdermal fentanyl to prevent this high-risk medication from causing harm through inappropriate use or accidental exposures.

Last updated on: November 30, 2012
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