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Efficacy of Tramadol for Pain Management in Patients Receiving Strong Cytochrome P450 2D6 Inhibitors
Author(s) -
Frost Derek A.,
Soric Mate M.,
Kaiser Ricky,
Neugebauer Rachel E.
Publication year - 2019
Publication title -
pharmacotherapy: the journal of human pharmacology and drug therapy
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.227
H-Index - 109
eISSN - 1875-9114
pISSN - 0277-0008
DOI - 10.1002/phar.2269
Subject(s) - tramadol , medicine , discontinuation , analgesic , cyp2d6 , morphine , anesthesia , opioid , pain ladder , opiate , dosing , retrospective cohort study , pharmacology , cytochrome p450 , metabolism , receptor
Study Objective Tramadol is metabolized by cytochrome P450 ( CYP ) 2D6 to form an active metabolite that exhibits its analgesic effect. Medications that inhibit this enzyme are used often in practice, yet the clinical impact of this interaction on the analgesic effects of tramadol has yet to be fully described. The objective was to determine whether a clinically relevant decrease in pain control is observed in patients taking scheduled tramadol concomitantly with a strong CYP 2D6 inhibitor. Design Retrospective cohort study. Setting Large health care system. Patients One hundred fifty‐two adult inpatients who received scheduled tramadol for at least 24 hours with (76 patients) or without (76 patients) a strong CYP 2D6 inhibitor between January 1, 2012, and February 28, 2017, were included in the analysis. Patients hospitalized for opioid use disorder or those receiving substandard dosing of tramadol were excluded. Measurements and Main Results The primary outcome was mean breakthrough opiate consumption in the presence and absence of CYP 2D6 inhibitors. Secondary outcomes included mean pain scores, length of hospital stay, tramadol discontinuation rates, and prespecified subgroup analyses based on patient sex, race, and specific CYP 2D6 inhibitor administered. Patients receiving concurrent CYP 2D6 inhibitors required significantly more breakthrough morphine milligram equivalents per day compared with patients receiving scheduled tramadol without CYP 2D6 inhibitors (geometric mean ± SD 18.2 ± 6.3 vs 5.7 ± 6.7 mg morphine milligram equivalents , p<0.001). No significant differences existed between cohorts for mean pain score, length of hospital stay, or tramadol discontinuation rate. Conclusion This study demonstrated a clinically relevant decrease in the efficacy of tramadol when used for pain control in patients receiving a strong CYP 2D6 inhibitor. These results should encourage clinicians to review medication lists for this interaction and adjust regimens accordingly to ensure adequate pain control.