Sebastiano Mercadante

Opioid plasma concentration during switching from morphine to methadone: preliminary data

Opioid switching is often used to improve the opioid response in cancer patients experiencing poor analgesia or adverse effects. However, no data are available on plasmatic changes of opioids and their metabolites during these phases, and whether there exists a relationship with the clinical events. In a prospective study of 10 consecutive cancer patients on oral morphine but with uncontrolled pain (greater >4 on a numerical scale of 0 to 10) and/or moderate to severe opioid adverse effects (on a level of 2 and 3 of a verbal scale) and not responsive to adjuvant medications, switching to oral methadone was performed using a fixed ratio of 5:1, leaving extra-doses of 1/5 of the daily dose of methadone calculated as needed. Blood samples were obtained at the same hour for four days, before the switching, and then on day 1, 2, and 3. The intensity of pain and the adverse effects were assessed daily to calculate the switching score before and after switching. Completed blood samples were obtained in 9 patients. One patient was separately considered, because of his renal impairment. Significant improvements in pain intensity as well as adverse effects within an average period of 1–2 days were observed. Morphine, morphine-6-glucuronide, and morphine-3-glucuronide were progressively cleared from plasma to almost disappear within three days. Methadone rapidly achieved a stable concentration in 1–2 days. The doses of methadone were changed, but not significantly, and tended to decrease in the following days, according to the clinical situation. The results of this study confirm the need to stop rapidly morphine, and to use a priming dose of methadone, rather than using progressive decrements and increments of morphine and methadone, respectively, during opioid switching. This method allows for a rapid clearance of morphine and its metabolites are rapidly cleared, except in patients with renal failure. Opioid plasma changes substantially overlap the clinical changes observed in these patients, in terms of benefit between analgesia and adverse effects.

Gabapentin for opioid-related myoclonus in cancer patients

Abstract. Chronic opioid medication has been found to cause myoclonus in patients taking it for cancer pain. Gabapentin seemed a likely candidate for the treatment of this myoclonus and has indeed proved useful, as illustrated in this paper by two case histories.

When all else fails: stepwise multiple solutions for a complex cancer pain syndrome

Abstract In the presence of insufficient pain relief and substantial adverse effects, application of alternative routes of administration and a change of opioid are the main methods used to improve the analgesic response. When all else fails, the result may further be optimized using adjuvant drugs by an alternative route, namely the intrathecal route. A stepwise approach with multiple drugs and routes of administration is described. This was implemented to resolve a complex pain syndrome otherwise considered uncontrollable. We found it possible to manage a very difficult pain situation by intrathecal home infusion through the efforts of a well-trained family and GP and a continuous exchange of information and advice with the pain relief team about changes in therapy to adapt to the clinical situation. A stepwise and a meaningful approach to clinical problems with use of advanced techniques and alternative drugs in the patients home may be helpful in the treatment of conditions otherwise considered intractable.