experimental infection and cancer. It is considered that opioid-induced immunosuppression is less relevant in chronic administration than in acute or short-time administration. The immunosuppressive effect of opioids has been linked to µ-receptor agonism: opioids with high affinity for the µ-opioid receptor induce significant immunosuppression while those with κ-receptor of δ-receptor selectivity do not. Antagonists at the µ-opioid receptor tend to enhance the immune system (Budd 2004). The immunosuppressive effects of opioids are independent of their analgesic effects and appear to be a function of molecular structure. The opioids with lack of immunomodulatory capacity are buprenorphine, hydromorphone, oxycodone, oxymorphone, and tramadol all of which have a carbonyl substitution at C6 and a single bond between C7 and C8. An assessment of buprenorphine toxicity in rats indicated that buprenorphine may have a slight stimulatory effect on the immune system although the exact mechanism remains unclear (Van Loveren et al 1994). After 24 hours of administration of fentanyl in mice, key parameters for immune response were reduced including natural killer cell activity, lymphoproliferation, and interleukin-2 and interferon-γ production. By contrast, neither acute nor chronic administration of equianalgesic doses of buprenorphine produced any effect (Martucci et al 2004). Special patient populations Buprenorphine has been used in children in the past mainly in acute pain conditions such as postoperative pain where it proved to be safe and effective irrespective of the administration route (Maunuksela et al 1988a, 1988b; Kamal and Khan 1995; Olkkola et al 1995). Basically, the transdermal formulation is an ideal analgesic device for children as it is completely noninvasive and produces longlasting reliable analgesia. In addition, due to their matrix structure, patches can be cut into halves or quarters to allow for an easy adaptation to smaller dosing needs of younger patients. However, as there are as yet no data available in this patient group, transdermal buprenorphine is not licensed for children and young patients under the age of 18, and therefore cannot be recommended to be used in this group. For the elderly, ie, patients above the age of 65 years, transdermal buprenorphine is an easy-to-use, safe, and effective analgesic device what has also been shown in the clinic (Griessinger et al 2005; Likar et al 2006, pers comm). In particular, buprenorphine’s low potential for drug–drug- Therapeutics and Clinical Risk Management 2006:2(1) Safety of pain management with transdermal buprenorphine interactions (see chapter on Interactions), its beneficial effects on the immune system, and in patients with renal impairment, make it the opioid of choice for pain treatment in elderly patients. Tolerability Gastrointestinal adverse events associated with strong opioid use include nausea, vomiting, and constipation. None of these conditions present a severe medical risk and can normally be dealt with by the clinician. Buprenorphine has a low incidence of adverse events in practice. Following parenteral use, the incidence of nausea is 8.8% and the incidence of vomiting is 7.4% (Harcus et al 1979). Continuous sublingual use in chronic pain has found that the incidence for nausea falls to 6.5% and for vomiting to 3.5% (Bach et al 1991). Constipation is another commonly encountered side effect of opioid use that can significantly affect quality of life, particularly for elderly patients. The incidence of constipation with buprenorphine has been shown to be lower than with morphine use (Bach et al 1991). In a study of sublingual administration of buprenorphine in 51 elderly patients with chronic pain, only one patient reported constipation (Nasar et al 1986). Bypassing the gut µ-opioid receptors through the use of parenteral or transdermal preparations of opioids may offer advantages in this respect. Central nervous system (CNS)-related adverse events including dizziness, drowsiness, and euphoria may occur at the start of opioid treatment or following an increase in dosage. The incidence is directly linked to kidney function. Any opioid that is mainly excreted by the renal route will accumulate in patients with renal impairment and has the potential to cause an increase in the incidence of adverse events. This situation is particularly relevant in the elderly, a group in whom renal function may decline often even unrecognised with increasing age. As only approximately 15% of buprenorphine is excreted by the kidneys the likelihood of accumulation is low in comparison with either morphine or fentanyl, where 75% or more is excreted by the renal route. Buprenorphine has a lower risk of CNS- related adverse effects than other opioids. Interactions A drug–drug interaction occurs when the effect of a particular drug is modified by another drug taken concomitantly. This is a situation that may be of particular concern in the elderly where reduced renal function and multiple drug therapy are often combined. Competition for 121