HSA would like to update healthcare professionals on the overseas cases of life-threatening and fatal adverse events reported with the use of fentanyl transdermal patch.
Fentanyl is a potent opioid analgesic which should be used only in patients who have previously tolerated opioids as there is a risk of significant respiratory depression in opioid-naïve patients. In Singapore, fentanyl transdermal patch (Durogesic®, Janssen-Cilag) is licensed as a controlled drug for the management of chronic and intractable pain requiring opioid analgesia that involves continuous opioid administration for an extended period of time. It is only licensed for use in adults and in opioid-tolerant children aged 2 years and above.
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Reports received by UK MHRA
Recently, reports of life-threatening adverse reactions and death have been received by the UK Medicines and Health products Regulatory Agency (MHRA) from healthcare professionals, patients and carergivers of patients who were using fentanyl patches for malignant and non-malignant pain control. These were found to be possibly related to unintentional overdose such as dosing errors, accidental exposure (in children) and exposure of the patch to a heat source, potentially resulting in an increase in fentanyl absorption. Some of the reports also reflected the use of fentanyl patches for unlicensed indications and in opioid-naïve patients. In the UK, fentanyl products include Durogesic® Dtrans®, Durogesic®, Matrifen® and Tilofyl®.
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Reports received by Health Canada
Similarly, Health Canada received 105 adverse reactions suspected to be associated with fentanyl transdermal patches between January 1992 to December 2007 where a fatal outcome was reported. In 33 of the 105 reports, the cause of death was reported to be unrelated to the fentanyl patches and in 20 cases, insufficient information was provided in the reports. Among the remaining 52 reports, intentional drug abuse accounted for almost half the cases. The other factors related to the fatal adverse reactions included inappropriate dose initiation and titration including use in opioid-naïve patients, inappropriate application of patches by patients (applying more than prescribed) or healthcare professionals, accidental overdose, intentional overdose or suicide, drug interactions withCYP 3A4 inhibitors (eg. grapefruit juice, ketoconazole, erythromycin, diltiazem) and the sharing of the patch with another patient who was not prescribed the treatment.
Fentanyl transdermal products available in Canada include Duragesic®, Ratio-Fentanyl® and Ran-Fentanyl®. The Health Canada had in earlier warnings issued in 2004 and 2005 described fatal outcomes in opioid-naïve adolescents and when fentanyl patches were abused by adolescents, leading the agency to revise the Canadian product monograph for Duragesic® to emphasize the safe and appropriate use of the patch.
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Reports received by US FDA
In December 2007, the US Food and Drug Administration (FDA) issued a public health advisory to alert patients, caregivers and healthcare professionals to adverse reactions arising from the prescribing of the fentanyl patch to patients for inappropriate indications such as acute pain following surgery, for headaches and occasional mild pain. The agency also received reports on patients who replaced the patch more frequently than was directed in the product label, applying more patches than prescribed, or applying a heat source to the patch, all of which may lead to exceedingly high fentanyl levels in the blood. Both Durogesic® and generic versions of the product are marketed in the US.
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Local situation
To date, no adverse reaction of the nature described above has been reported to the Pharmacovigilance branch of HSA. However, due to the seriousness and occurrence of fatalities associated with the inappropriate use and abuse of the patch reported overseas, healthcare professionals are advised to be aware of the potential serious and fatal adverse effects associated with the use of fentanyl patches. They are also advised to instruct patients and caregivers on the appropriate and safe use of fentanyl patches as well as educate them on the signs and symptoms of fentanyl overdose (see table 1 for list of symptoms).
Healthcare professionals are also encouraged to report all adverse events suspected to be associated with fentanyl patches to the Pharmacovigilance Branch of HSA.
Table 1: Some signs and symptoms of fentanyl overdose
Troubled breathing or shallow breathing Slow heartbeat Cold, clammy skin Tiredness Extreme sleepiness or sedation Inability to think, walk or talk normally Feeling faint, dizzy or confused |
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References
- Drug Safety Update Vol. 2 Issue 2 September 2008 from MHRA and CHM
- Canadian Adverse Reaction Newsletter Vol. 18, Issue 3, July 2008
- Dear Healthcare Professional Letter issued by Health Canada on Duragesic®, September 13, 2005.
- Canadian Adverse Reaction Newsletter Vol. 15, Issue 3, July 2005
- Canadian Adverse Reaction Newsletter Vol. 14, Issue 4, Oct 2004
- http://www.fda.gov/cder/drug/infopage/fentanyl/default.htm
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