Fentanyl Patch Well Tolerated in Opioid-Naïve Pain Patients

AMSTERDAM—A Dutch study suggests that physicians can safely skip step 2 of the World Health Organization (WHO) 3-step analgesic ladder and start opioid-naïve patients directly on transdermal fentanyl (Duragesic), a so-called strong opioid.

The ladder begins in step 1 with nonopioid analgesics, including nonsteroidal anti-inflammatory drugs (NSAIDs) and acetaminophen. Step 2 allows addition of a “weak” opioid (often codeine), while “strong” opioids are not introduced until step 3.

This open-label pilot study tested use of the fentanyl patch in 30 patients whose severe chronic cancer pain was inadequately controlled with acetaminophen (step 1) or codeine (step 2).

Because transdermal fentanyl has not previously been evaluated as the initial strong opioid in the treatment of chronic pain, the researchers started with the lowest delivery rate (25 µg/h). Immediate-release oral morphine was available as “rescue” medication.

The researchers reported on 28 patients, 14 in each arm (opioid-naïve and codeine-using). Nineteen patients needed a transdermal fentanyl dose increase from the initial 25 µg/h, and four of these later asked for a dose reduction. In both patient groups, the median fentanyl dose at the end of the study was 50 µg/h.

In the 14 opioid-naïve patients, 10 rated the transdermal fentanyl treatment as good or excellent, as did 9 of the 14 codeine-using patients. “Thus, of the total 28 patients, 19 (68%) rated pain relief at trial termination or, in the case of drop-outs, just before discontinuing participation in the trial, as good to excellent,” the authors said (J Pain Symptom Manage 19:185-192, 2000).

No Respiratory Depression

Four patients dropped out of the study because of adverse events, including 1 (7%) in the opioid-naïve group and 3 (21%) in the codeine-using group. Transdermal fentanyl was well tolerated with no cases of clinically relevant respiratory depression and only three patients (11%) reporting constipation. Other common side effects of opioids experienced by the study participants included nausea (14 patients), vomiting (6 patients), and dizziness (2 patients).

“Although serious adverse events were reported frequently by this group of severely ill patients (13 patients or 46%), most were unlikely to be due to transdermal fentanyl,” the authors said. Only two were thought to be possibly linked to fentanyl (both nausea), but either could have been due to chemotherapy or the cancer process.

16 Patients Ask to Continue

Sixteen of the 17 patients who completed all 4 weeks of the trial requested continued use of transdermal fentanyl at the end of the study.

The authors concluded that randomized trials to evaluate the value of WHO step 2 are warranted.

Authors of the study were Ans P.E. Vielvoye-Kerkmeer, MD, PhD, and Carlien Mattern, MD, of the Department of Medical Oncology/Pain Team, the Netherlands Cancer Institute, Amster-dam; and Martin P. Uitendaal, PhD, of the Department of Clinical Research, Janssen-Cilag BV, Tilburg, the Netherlands.