Benefit-Risk Assessment of Transdermal Fentanyl for the Treatment of Chronic Pain

Abstract

Transdermal fentanyl is effective and well tolerated for the treatment of chronic pain caused by malignancy and non-malignant conditions when administered according to the manufacturer's recommendations. Compared with oral opioids, the advantages of transdermal fentanyl include a lower incidence and impact of adverse effects (constipation, nausea and vomiting, and daytime drowsiness), a higher degree of patient satisfaction, improved quality of life, improved convenience and compliance resulting from administration every 72 hours, and decreased use of rescue medication. Transdermal fentanyl is a useful analgesic for cancer patients who are unable to swallow or have gastrointestinal problems. Transdermal fentanyl forms a depot within the upper skin layers before entering the microcirculation. Therapeutic blood levels are attained 12-16 hours after patch application and decrease slowly with a half-life of 16-22 hours following removal. Patients with chronic pain should be titrated to adequate relief with short-acting oral or parenteral opioids prior to the initiation of transdermal fentanyl in order to prevent exacerbations of pain or opioid-related adverse effects. Transdermal fentanyl can then be initiated based on the 24-hour opioid requirement once adequate analgesia has been achieved. The prolonged elimination of transdermal fentanyl can become problematic if patients develop opioid-related adverse effects, especially hypoventilation. Adverse effects do not improve immediately after patch removal and may take many hours to resolve. Patients who experience opioid-related toxicity associated with respiratory depression should be treated immediately with an opioid antagonist such as naloxone and closely monitored for at least 24 hours. Because of the short half-life of naloxone, sequential doses or a continuous infusion of the opioid antagonist may be necessary. Transdermal fentanyl should be administered cautiously to patients with pre-existing conditions such as emphysema that may predispose them to the development of hypoventilation. Transdermal fentanyl is indicated only for patients who require continuous opioid administration for the treatment of chronic pain that cannot be managed with other medications. It is contraindicated in the management of acute and postoperative pain, as pain may decrease more rapidly in these circumstances than fentanyl blood levels can be adjusted, leading to the development of life-threatening hypoventilation. Cognitive and physical impairments such as confusion and abnormal co-ordination can occur with transdermal fentanyl. Therefore, patients should be instructed to refrain from driving or operating machinery immediately following the initiation of transdermal fentanyl, or after any dosage increase. Patients may resume such activities once the absence of these potential adverse effects is documented.

Dermal and Transdermal Drug Delivery Systems: Current and Future Prospects

“…Passive methods of skin delivery are incapable of enhancing permeation of such large solutes, which has led to studies involving alternative strategies referred to as active methods. These methods of • The avoidance of first pass metabolism and other variables associated with the GI tract such as pH, gastric emptying time (Cleary 1993;Henzel and Loomba 2003;Kormic et al 2003). …”

“…• Reduction in side effects associated with systemic toxicity i.e., minimization of peaks and troughs in blood-drug concentration (Cramer and Saks 1994;Kormic et al 2003). …”

“…• Provides an alternative in circumstances where oral dosing is not possible (in unconscious or nauseated patients) (Kormic et al 2003). …”

Current treatment options in the management of severe pain

“…These release a lipid-soluble opioid through the skin into the subcutaneous fat from where it is absorbed into the systemic circulation. 17 These preparations are ver y potent but plasma levels take 6-12 hours to become therapeutic. Likewise when the patch is removed, a depot of the drug remains in subcutaneous fat continuing to have an effect for a further 12-24 hours.…”

Elderly Dementia Patient with Recurrent Respiratory Failure due to the Abuse of a Fentanyl Patch: A Case Report

“…Opioids have been recently used in patients with moderate-to-severe chronic non-cancer pain and in those with cancer pain in palliative care [1]. A transdermal fentanyl patch has been reported effective for the treatment of chronic cancer and non-cancer pain [2]. However, previous reports showed the life-threatening toxicity of respiratory repression from the use of a fentanyl patch.…”