Antagonistic effects of ondansetron and tramadol? A randomized placebo and active drug controlled study.
Opposing effects of ondansetron and tramadol on the serotonin pathway have been suggested which possibly increase tramadol consumption and emesis when co-administered. In a randomized, double-blinded study, 179 patients received intravenous ondansetron, metoclopramide, or placebo for emesis prophylaxis. Analgesic regimen consisted of tramadol intraoperative loading and subsequent patient-controlled analgesia. Tramadol consumption and response to antiemetic treatment were compared. Additionally, plasma concentrations of ondansetron and (+)O-demethyltramadol and CYP2D6 genetic variants were analyzed as possible confounders influencing analgesic and antiemetic efficacy. Tramadol consumption did not differ between the groups. Response rate to antiemetic prophylaxis was superior in patients receiving ondansetron (85.0%) compared with placebo (66.7%, P = .046), with no difference to metoclopramide (69.5%). Less vomiting was reported in the immediate postoperative hours in the verum groups (ondansetron 5.0%, metoclopramide 5.1%) compared with placebo (18.6%; P = .01). Whereas plasma concentrations of (+)O-demethyltramadol were significantly correlated to CYP2D6 genotype, no influence was detected for ondansetron. Co-administration of ondansetron neither increased tramadol consumption nor frequency of PONV in this postoperative setting.


CONCLUSIONS
Controversial findings were reported for efficacy of tramadol and ondansetron when co-administered due to their opposing serotonergic effects. Co-medication of these drugs neither increased postoperative analgesic consumption nor frequency of emesis in this study enrolling patients recovering from major surgery.
Rauers
Neele I
NI
Department of Anesthesiology and Intensive Care Medicine, University of Bonn, Bonn, Germany.
Stüber
Frank
F
Lee
Eun-Hae
EH
Musshoff
Frank
F
Fimmers
Rolf
R
Barann
Martin
M
Stamer
Ulrike M
UM
D016058:Analgesia, Patient-Controlled; D000701:Analgesics, Opioid / Q000097:blood / Q000627:therapeutic use*; D000932:Antiemetics / Q000097:blood / Q000627:therapeutic use*; D019540:Area Under Curve; D019389:Cytochrome P-450 CYP2D6 / Q000235:genetics; D004311:Double-Blind Method; D004347:Drug Interactions; D005260:Female; D006801:Humans; D008297:Male; D008787:Metoclopramide / Q000627:therapeutic use*; D008875:Middle Aged; D017294:Ondansetron / Q000097:blood / Q000627:therapeutic use*; D020250:Postoperative Nausea and Vomiting / Q000517:prevention & control*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014147:Tramadol / Q000097:blood / Q000627:therapeutic use*
D000701:Analgesics, Opioid; D000932:Antiemetics; D014147:Tramadol; D017294:Ondansetron; D019389:Cytochrome P-450 CYP2D6; D008787:Metoclopramide