Discussion
postherpetic neuralgia, cancer pain, knee osteoarthritis, pain
POSTHERPETIC NEURALGIA, KNEE OSTEOARTHRITIS
Our aim was to investigate the non-inferiority of a bilayer tablet formulation of tramadol, comprising IR and SR layers, versus an IR capsule formulation in terms of managing cancer pain. The two treatments achieved similar improvements in the VAS for pain at rest, satisfying the criterion for non-inferiority, which was confirmed in the PPS analysis. Additionally, the changes in VAS for pain at rest and during movement on each study day, percentages of patients who slept well or moderately well, use of rescue medication, and EQ-5D-5L QOL scores were highly comparable, indicating highly similar effects of both formulations on pain control. The improvement in pain was rapid, from within 2 days of starting administration, and showed good stability throughout the study in both groups. Overall, these findings indicate that twice-daily administration of the bilayer tablets is as effective as four-times-daily IR tramadol for managing cancer pain.Opioids are frequently used to manage cancer pain [We also investigated the safety of both study drugs in terms of AEs/ADRs during the 14-day treatment period and 7-day follow-up period. During the treatment period, AEs were reported for 77.0% and 80.8% of patients in the bilayer tablet and IR capsule groups, respectively, while ADRs were reported for 58.7% and 53.6%, respectively. These values seem reasonable when we consider the frequencies of AEs reported in the initial open-label treatment escalation periods (80.6% and 78.7% in the knee osteoarthritis and postherpetic neuralgia studies, respectively) of two previous dose-withdrawal studies using the bilayer tablet formulation [Clinical guidelines position opioids, including tramadol, as options for managing cancer pain [Several preparations of tramadol, including IR and SR formulations, have been developed and are used to manage cancer pain. However, there are some potential disadvantages of the available formulations related to their pharmacokinetic properties. In particular, the pharmacokinetics of once-daily SR formulations may not be sufficient to maintain effective pain relief over the 24-h period between each dose [