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Medline ® Abstract for Reference 40

of 'Prevention and management of side effects in patients receiving opioids for chronic pain'

An investigation of the ability of oral naloxone to correct opioid-related constipation in patients with advanced cancer.
Sykes NP
Palliat Med. 1996;10(2):135.
A dose-ranging study of the use of oral naloxone in opioid-related constipation in patients with far-advanced cancer is reported. Naloxone doses were calculated as a percentage of the morphine dose each patient was receiving. Seventeen patients entered the first phase of the study, which had a randomised, double-blind design. Outcome measures were small bowel transit time (SBTT) measured by the lactulose/hydrogen breath test, pain scores and the occurrence of adverse events. One subject was excluded before receiving naloxone. No significant difference between placebo and naloxone occurred in the 14 remaining patients receiving total daily doses of naloxone 10% or less of the 24 h dose of morphine. Two further patients experienced a marked laxative effect with naloxone at 20% of the 24 h dose of morphine. In one of these, SBTT was available and was unchanged from placebo. The other declined to continue with SBTT measurement. Phase two of the study had an open design, in which laxative effects were determined clinically. Naloxone at a maximum dose level of 20% was given to seven patients, up to 40% to two patients and up to 80% to one patient. Four out of the seven patients in the 20% dose level group, and all of the remainder, experienced laxative effects. Two patients experienced symptoms of opioid withdrawal, one of whom also had return of pain. It is concluded that oral naloxone at a daily dose of 20% or more of the prevailing 24 h morphine dose is a potentially valuable therapy foropioid-related constipation. However, opioid withdrawal was observed and it is suggested that initial individual naloxone doses should not exceed 5 mg. Further research is needed into the oral absorption of naloxone, as well as further studies of clinical efficacy and dosing.
University of Leeds, UK.