is one of the most promising opioids for the treatment of neuropathic pain. The equipotency ratio of transdermal fentanyl to oral morphine has been established as 1:100 (Donner et al 1996). The comparable ratio for transdermal buprenorphine to oral morphine has been proposed to be 1:75, although clinical experience including data from postmarketing-surveys (Griessinger et al 2005; Muriel et al 2004) suggested that buprenorphine TDS may be more potent than initially suggested. A retrospective analysis in patients with both cancer and non-cancer pain has compared calculated equipotent oral morphine doses of transdermal fentanyl with equipotent morphine doses of buprenorphine prescribed in clinical practice and suggested that an equipotency ratio of 1:110 to 1:115, morphine to transdermal buprenorphine, may be more appropriate (Sittl, Likar, et al 2005). Switching and combining with other opioids The goal of pain management with opioids is to provide optimal analgesia with a minimum of adverse events. WHO guidelines on cancer pain recommend a switch of opioid if the current treatment is no longer of sufficient efficacy or if intolerable adverse events occur. Switching therapy to and from buprenorphine to or from other opioids does not present major problems. It has been suggested that buprenorphine being a partial agonist at the same receptor site as morphine might block the effects of morphine if a patient was switched to morphine. Clinical studies have shown this not to be the case and in the analgesic dose range, a switch between buprenorphine sublingual (SL) and an equianalgesic dose of oral morphine sulphate was carried out without problems for the patient (Atkinson et al 1990). More recent animal studies involving combined use of buprenorphine and other opioids have indicated that a moderate antagonistic effect attributed to the partial µ-agonistic properties of bupren- orphine was only seen when doses exceeded the therapeutic dose range, otherwise both morphine and fentanyl showed full efficacy (Koegel et al 2005). Although morphine is considered to be the gold standard drug in pain management according to step III of the WHO analgesic ladder and may provide adequate analgesia for many patients, there are some who suffer from intolerable side effects and/or inadequate pain relief with morphine. Therefore a change also of formulation could be beneficial. As a subanalysis of a large postmarketing survey on buprenorphine TDS found, patients who had been switched Therapeutics and Clinical Risk Management 2006:2(1) Safety of pain management with transdermal buprenorphine from high daily doses of morphine (> 120 mg) to at least 52.5 µg/h transdermal buprenorphine, benefited from an average 50% reduction in pain after the switch (Gruenenthal, data on file, publication in preparation). In 70% of the patients this was achieved without the additional use of other opioid medication. Concerns with long-term therapy Tolerance development Long-term use of opioids may lead to the development of tolerance requiring higher doses to be administered in order to produce a given level of response. Tolerance to analgesia may not be accompanied by tolerance to opioid-induced adverse effects so that dose escalation can often result in a negative impact on the adverse events profile. The development of tolerance to opioids may be brought about by desensitization and down-regulation in µ-opioid receptors in response to agonist treatment. Both fentanyl and morphine have been shown to induce a loss of surface receptors, while buprenorphine was found to cause an increase (Zaki et al 2000). Although tolerance to bupren- orphine may develop to many of its other effects as indicated in animal models, tolerance to its analgesic effects in chronic pain patients has not been shown (Robinson 2002). A study of long-term management of chronic cancer and non-cancer pain showed that the proportion of patients needing 1 mg of sublingual buprenorphine daily in addition to the 35 µg/h patch remained essentially stable throughout the first 6 months of the study, which points to the dose stability of buprenorphine. In addition, 31% of patients were able to control their pain by using only one of the lowest dose patches throughout (Likar et al 2005). When treatment with transdermal fentanyl and buprenorphine TDS for at least 3 months was compared in a retrospective study study on cancer and non-cancer patients, a significantly higher increase in mean daily doses of fentanyl compared with buprenorphine was found (Sittl, Nuitjen, et al 2005). Safety Respiratory depression Respiratory depression caused by opioids can be potentially life-threatening, but is much less of a problem with buprenorphine than with many other opioids including morphine, hydromorphone, methadone, oxycodone, and transdermal fentanyl (Dertwinkel et al 1998). Buprenorphine has a ceiling effect associated with a bell- shaped dose response curve with regard to respiratory 119