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November 28, 2004

Transdermal fentanyl (Duragesic): respiratory arrest in adolescents

Topics: Clinical Pharmacology

Reported in Canadian Adverse Reaction Newsletter, Volume 14, Issue 4, October 2004:

Health Canada has received 2 case reports of death suspected by the reporters of being associated with the use of Duragesic (transdermal fentanyl system) prescribed off-label to adolescents. In one case, a 15-year-old girl was prescribed Duragesic 25 for chronic headache. She was discovered unresponsive and with respiratory depression 21 hours after the first and only application. She was resuscitated but suffered severe anoxic brain injury and died 2 days later. In the second case, a 14-year-old boy was prescribed Duragesic 25 for throat pain due to infectious mononucleosis. He was found in respiratory arrest 14 hours after the first and only patch was applied. Resuscitative efforts were unsuccessful.

Duragesic has been marketed in Canada since 1992 and is indicated for the management of chronic pain in patients requiring continuous opioid analgesia for pain that is not optimally managed with weak or short-acting opioids.¹ Duragesic is contraindicated for the management of acute or postoperative pain and mild or intermittent pain, and for use in opioid-naive patients. These contraindications and the risk of serious and life-threatening hypoventilation are well labelled in the Canadian product monograph. The use of Duragesic in children under 18 years of age is not recommended in Canada.¹

A thorough understanding of the pharmacokinetics and delivery system of Duragesic is essential to the safe prescribing of this product. The Duragesic transdermal therapeutic system allows the continuous delivery of the opioid analgesic fentanyl for up to 72 hours.¹ It is a transparent patch comprised of a protective peel strip and 4 functional layers. The protective peel strip is removed before use, and the patch is attached to the skin via a silicone-based contact adhesive, which delivers a loading dose of drug upon application. The fentanyl drug reservoir is located behind a rate-control membrane. The drug diffuses through this membrane and the adhesive to reach the skin. A fentanyl depot accumulates in the upper skin layers, diffuses through to the dermis and is then available for uptake into systemic circulation.² In adults, the time from application to minimal effective serum concentrations can range from 1.2 to 40 hours, and the time to reach maximum serum concentrations can range from 12 to 48 hours. When the Duragesic patch is removed, fentanyl continues to be absorbed into the systemic circulation from the cutaneous depot.² The serum fentanyl concentrations decline gradually to about 50% in about 17 (range 13-22) hours.¹

In the 2 cases reported to Health Canada, these opioid-naive adolescents experienced severe respiratory depression 21 and 14 hours after application of Duragesic 25 and died. Prescribers are reminded that this dosage delivery system for fentanyl is not suitable for acute pain management or for opioid-naive patients. Patients and their caregivers must be instructed in how to recognize symptoms of serious opioid-related toxicity such as hypoventilation and cognitive impairment.³

Barbara Raymond, BSc, MD; Iza Morawiecka, BScPhm, Health Canada      

References;      

Duragesic 25 (fentanyl transdermal system) [product monograph]. Toronto: Janssen-Ortho Inc.; 2002.

Grond S, Radbruch L, Lehmann KA. Clinical pharmacokinetics of transdermal opioids: focus on transdermal fentanyl. Clin Pharmacokinet 2000;38(1):59-89.

Kornick CA, Santiago-Palma J, Moryl N, Payne R, Obbens EA. Benefit-risk assessment of transdermal fentanyl for the treatment of chronic pain. Drug Saf 2003;26(13):951-73.

Posted by Hyscience at November 28, 2004 10:21 AM

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