Co-Administration of Ondansetron Decreases the Analgesic Efficacy of Tramadol in Humans

Abstract

Tramadol, a central analgesic acting on serotonin neurotransmission, is often co-used with ondansetron, a 5-HT₃ antagonist, for the management of postoperative pain to decrease nausea and vomiting. The aim of the study is to test the hypothesis that this drug combination raises tramadol requirement by patient-controlled analgesia (PCA). Forty patients undergoing hernioplasty or thyroidectomy were enrolled in a randomized, controlled study and allocated to receive ondansetron 4 mg i.v. (n = 20) or saline (n = 20). At 0, 1, 2, 4 and 24 h of PCA, tramadol consumption was evaluated. Tramadol consumption (mg × kg^–1 × h^–1) was higher in the ondansetron group at the 2-hour time point compared to the control group (0.24 ± 0.1 vs. 0.17 ± 0.16; p = 0.01). Our study suggests that ondansetron acutely reduces the analgesic efficacy of tramadol.

The effect of ondansetron on the efficacy of postoperative tramadol: a systematic review and meta-analysis of a drug interaction

“…We were unable to perform any meaningful meta-analysis of nausea or vomiting for this study as the outcome was reported inconsistently with different measures and at different time points. Although some studies [4,6] supported the suggestion of an increased incidence of nausea when ondansetron was co-administered with tramadol, the finding was not confirmed among the remainder [5,[7][8][9]11]. Whether or not the co-administration of ondansetron and tramadol results in a higher incidence of nausea and/or vomiting, and if so, whether this is due to a direct effect on the efficacy of ondansetron or secondary to increased tramadol consumption, remains unclear.…”

“…Where numerical values of mean and SD results of cumulative tramadol consumption were not supplied within published papers, the author, where available, was contacted by email. Where the information was still not obtained [7][8][9], enlarged-scale visual estimation of the data was undertaken using the figures in the published studies.…”

“…Tramadol acts as a weak agonist at l-opioid receptors and inhibits the re-uptake of both serotonin and noradrenaline, thereby increasing their concentration and activity in descending inhibitory pathways involved in antinociception [2]. Several clinical studies [4][5][6][7][8][9] as well as one animal study [10] have observed an interaction between tramadol and ondansetron that led to significantly greater tramadol requirements, although other studies have found no effect of ondansetron [11,12]. Also, within those studies that did find evidence of an interaction, results were inconsistent regarding its onset and duration.…”

The Effect of Dexamethasone in Tramadol Induced Nausea and Vomiting

“…However, it has been reported that the nausea and vomiting associated with the use of tramadol has high incidence [6,7]. The low dose naloxone infusion, transcutaneous electrical acupuncture point stimulation, ondansetron were preferred until today in the treatment of tramadol induced nausea and vomiting (TINV) [8][9][10]. However, there are publications suggest to that ondansetron may reduce the analgesic effect of tramadol.…”

Eficácia da ondansetrona no tratamento de dependentes de álcool

“…A ondansetrona tem sido identificada como causa de significante redução da ação de ciclofosfamida e cisplatina. Estudos mais recentes mostram que o uso concomitante do antagonista serotoninérgico com os analgésicos opióides pode reduzir o controle álgico, explicado pelo fato de a parcela da ação dos opióides sobre a dor ocorrer via receptor 5-HT (Vale et al, 2011).…”