Radbruch, L., Sabatowski, R., Loick, G., Kulbe, C., Kasper, M., Grond, S., & Lehmann, K.A. (2000). Constipation and the use of laxatives: A comparison between transdermal fentanyl and oral morphine. Palliative Medicine, 14, 111–119.

To investigate constipation and the use of laxatives in patients with chronic cancer pain treated with oral morphine and transdermal fentanyl.

Patients were switched from long-acting morphine to fentanyl patches. Fentanyl doses were calculated with a conversion table based on a 100:1 dose ratio. If the calculated fentanyl dose was higher than 2.4 mg/day = 100 ug/hour (more than 270 mg/day slow-release morphine), more than one patch was used. Patients were treated with oral slow-release morphine for at least six days (morphine phase) until they reported stable pain intensity scores of 40 or less on a visual analog scale (0 = no pain, 100 = worst pain imaginable) for at least two days. Analgesic therapy then was switched from oral morphine to transdermal fentanyl (fentanyl phase). Fentanyl patches were changed regularly after three days. Fentanyl doses were increased when patients reported inadequate pain relief or had to take more than six rescue medications per day. The study was terminated after 30 days of transdermal therapy. Patients who completed the study until day 17 or longer were included in an intraindividual comparison of laxative intake using the Wilcoxon rank test.

• The study reported on a sample of 46 patients (29 males and 17 females).
• Median patient age was 57.5 years (range 31-83).
• Median patient weight was 62.5 kg, and median height was 172 cm.
• Sites of primary cancer included gastrointestinal, head and neck, genitourinary, respiratory, breast, and hematologic.

• Germany, June 1995 to January 1996
• Unclear if inpatient or outpatient; the researcher was based at the University of Cologne.

This was an open, sequential, multi-center study.

• Patient diary recording of intensity on a 0 to 10 visual analog scale three times daily, frequency of breakthrough pain and use of as-needed medications, use of laxatives, and self-assessment of frequency and consistency of defecation.
• European Organization for Research and Treatment of Cancer Core Quality of Life Questionnaire (EORTC QOL-C30), with 30 items that assesses nine symptoms and six dimensions of quality of life.
• Blood pressure, heart rate, respiratory rate, and skin reaction at the site of fentanyl application were documented by the treating physician on days 0, 6, 12, 18, 24, and 30.

• Forty-six patients were treated with slow-release morphine (7 were excluded in the morphine phase because stable analgesia could not be achieved), and 39 were switched to transdermal fentanyl.
• Twenty-three patients completed the study. Two patients died from basic disease, 12 were excluded for various reasons, and two did not have enough data available for evaluation.
• The frequency of bowel movements did not change significantly, but the use of laxatives was reduced in 23 and increased in 2 of 28 patients on transdermal fentanyl.
• No significant changes in vital signs were noted.
• Mild-to-moderate skin reaction was noted in five patients.
• The EORTC QOL-C30 symptom scores showed a significant decrease for constipation only.

The use of laxatives was reduced significantly with transdermal fentanyl.

• This was an open study, so prejudices from staff or patients may have biased the results.
• The site of primary tumor was situated in the gastrointestinal tract for about 25% of the patients; in those patients, constipation easily may have been caused by tumor growth.
• It may be questioned whether the conversion from morphine to fentanyl really was equianalgesic. Therefore, less constipation may have been the consequence of lower equianalgesic opioid dosage.
• Results may have been influenced by the high number of patients who dropped out of the study.
• Difference in the degree of constipation experienced by patients between the two analgesics regimens should be confirmed in a randomized, double-blind study that takes into account both constipation and use of laxatives.
• Short-acting morphine was used for breakthrough pain in both arms of the study; as a result, the patients on fentanyl also had morphine on board.
• The laxative used was not standardized; whether this influenced the results is unclear.
• The study was supported by a research grant from a pharmaceutical company.