Current Concepts in Pain Control

Duragesic (Transdermal Fentanyl) in Hospice Care

by
Steven J Baumrucker, MD
Medical Director
Housecall Hospice of East Tennessee
Clinical Assistant Professor
ETSU College of Medicine
(appeared in the American Journal of Hospice and Palliative Care)

The transdermal fentanyl patch (Duragesic, Janssen Pharmaceutica, Titusville, NJ) is a relatively new device that has practically revolutionized pain control in terminal patients. Since its release, the use of morphine pumps has declined significantly in our hospice, and across the country (this may not necessarily be a good thing--see below). The patch boasts ease of use, portability, flexible dosing, and efficacy. Side effects are generally minimal, or easily managed. The use of this device should be in the pain control lexicon of all practitioners who deal with severe pain in the terminal setting.
Duragesic is indicated for chronic pain in patients with severe pain, requiring constant analgesia. The active ingredient, Fentanyl citrate, is approximately 75 times more potent than morphine while producing fewer histaminic side effects. Patches are available in strengths of 25, 50, 75, and 100 mcg per hour. These can be combined to deliver a variety of strengths, and doses up to and beyond 450 mcg/hr have been studied.
Although most people with cancer pain can be treated with oral analgesics, most will probably require parenteral or topical opioids before death. PCA pumps are certainly an option, but are bulky, and occasionally intimidating to the patient and family. Also, not all homes are appropriate for PCA pumps or other parenteral modalities (e.g., concurrent IV drug abuse in live-in family members.) Transdermal analgesics, if effective, would answer these problems, especially if they were long acting. Infrequent dosing allows the patient to attend to matters other than pain control; fewer dosing units in the house removes much of the problem of co-habitant abuse, (when this is an issue.) Fortunately, transdermal fentanyl fulfills these criteria, being both extremely efficacious, and requiring patch changes only every 72 hours.
The choice of initial dose is probably the most difficult aspect of prescribing Duragesic. Most patients in the clinical trials were converted to Duragesic from other narcotics, so very little data is available for its use as an initial drug.1 Therefore, use the smallest dose (25 micrograms/hr) patch for patients not already tolerant to opioids.
For patients already on narcotics, the package insert gives the currently recommended method of conversion, which was used in most of the pre-release studies. First, calculate the previous analgesic requirement. Then, using table 1, convert to the equivalent oral morphine dose. Then, using table 2, find the appropriate starting dose of Duragesic. For example, Patient A is currently taking 6mg of Dilaudid orally six times a day for complete relief. Calculating 36mg of Dilaudid per 24 hours, multiply this times 30/7.5 (the conversion factor for oral morphine, divided by the conversion factor for Dilaudid, from table 1). The result is 144 mg/day of oral morphine which converts (per table 2) to 50 mcg/hr of transdermal fentanyl.
Titration can be done every 72 hours after the first patch (and every six days thereafter), with oral analgesics filling-in for breakthru pain. The Slover study indicated that these calculated doses may be low; at the end of the study, all patients were on three times the initial dose.3 One might draw the conclusion that the recommended doses are too low for practical use; however, the risk of significant respiratory depression has mandated this cautious approach by the manufacturer and the FDA.
Titrate by the patient's symptoms and supplemental analgesic intake: increase the dose by 25 mcg for every 90 mg of oral morphine equivalent. In rare situations of severe unremitting pain, coupled with the inability to take oral or parenteral drugs, experience has shown that the practitioner can be more aggressive than the package insert recommends. This is, of course, a decision to be made with the patient, family, and hospice staff, backed with the weight of experience with this modality. In our hospice, we have found that careful titration can be undertaken more rapidly than the company suggests (by adding additional 25mcg/hr patches at appropriate intervals) with very few adverse effects. One must be aware, however that equilibrium may not be reached for up to six days after increasing the dose.1 Therefore, an overdose may not be apparent until almost one week after the increase was made.
Duragesic is efficacious; the TTS-Fentanyl Multicentre Study showed a reduction in nausea, vomiting, and constipation after conversion from oral narcotics, and breakthru morphine dosing declined. For patients who cannot take oral medications, the advantage of a topical drug is obvious.
Duragesic's disadvantages include a lag period of 24-72 hours before peak levels are achieved, and a similar persistence interval after the patch is removed (50% decline in 17 hours).1 Also, typical opioid negative effects can be seen. Treatment of overdose consists of removing the patch and administering a naloxone bolus followed by a carefully monitored naloxone drip. Obviously, this sort of intervention is best avoided altogether; proper and careful dosing and titration is the key.
Case Report 1 A 62 year old man was taking sustained-release morphine 60mg q 8 hr and oxycodone 5mg q 6 hr for chronic cancer pain associated with bronchogenic carcinoma with localized chest wall metastases. He was ambulatory, but complained of periodic inefficacy, severe constipation, nausea, and decreased daytime vigilance. He was placed on transdermal fentanyl (Duragesic) 50mcg/hr. Oxycodone was continued for breakthru pain.
After 72 hours, he reported decreased somnolence, but incomplete pain relief. Duragesic was increased to 75 mcg/hr with good results. Oxycodone use declined. Constipation was easily treated with milk of magnesia, and he reported decreased nausea.
After two weeks, his pain recurred, and his patch was increased to 100 mcg/hr again with good results. He is currently still ambulatory, and satisfied with his pain regimen.
Case Report 2 An 89 year old woman was taking hydromorphone 4mg q 6 hr with good results for chronic abdominal pain associated with pancreatic carcinoma. She became jaundiced after her ampullar stent failed. Her pain worsened, and she was also unable to take oral medications due to emesis. Hydromorphone was discontinued and transdermal fentanyl started at 25 mcg/hr. Once oral narcotics were discontinued, her emesis improved significantly. She was comfortable at her demise, approximately 10 days later.
Conclusions Transdermal fentanyl is an efficacious therapy for chronic cancer pain, especially in the terminal setting. Its benefits include portability, infrequent dosing, manageable side effects, non-oral ingestion, and efficacy comparable to morphine. Negatives include cost, the possibility of typical opioid adverse affects, and slow peak and wash-out times. Its ease of use, and patient satisfaction with this modality, should encourage all practitioners dealing with severe chronic pain to familiarize themselves with its use.
References:
  • DURAGESIC Package Insert. Janssen Pharmaceutica; June 1994.
  • Rosow CE, et al. Histamine release during morphine and fentanyl anesthesia. Anesthesiology 1982;56:93-96.
  • Slover R, Transdermal Fentanyl: Clinical Trial at the University of Colorado.
  • Bruera E, et al. Palliative care in a cancer center: results in 1984 vs 1987. J Pain Symptom Mgt 1990;5:1-5.
  • Hanks G, et al. Transdermal fentanyl in cancer pain. J Drug Dev 1994;6(3):99-97.
  • Eisele DW, et al. Transdermal Fentanyl. Otolaryngol Head Neck Surg 1994;111:680-3.