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. 2023 Sep;23(3):289-296.
doi: 10.1007/s40268-023-00436-4. Epub 2023 Jul 28.

Risk of Hyponatremia after Tramadol/Acetaminophen Single-Pill Combination Therapy: A Real-World Study Based on the OMOP-CDM Database

Yu Jeong Lee  1 , Jinmi Kim  2 , Youngmi Han  3 , Kyuhyun Hwang  4 , Byungkwan Choi  5 , Tae Ryom Oh  6 , Il Young Kim  7 , Harin Rhee  8   9
Affiliations

Risk of Hyponatremia after Tramadol/Acetaminophen Single-Pill Combination Therapy: A Real-World Study Based on the OMOP-CDM Database

Yu Jeong Lee et al. Drugs R D. 2023 Sep.

Abstract

Background and objective: Tramadol has been reported to cause hyponatremia but the evidence is conflicting. The risk of hyponatremia resulting from combination oral tramadol/acetaminophen (TA) therapy is thus unknown. This study examined whether, compared with acetaminophen (AA), TA use is associated with an increased risk of hyponatremia.

Methods: Hospital data compatible with the Observational Medical Outcomes Partnership-Common Data Model (OMOP-CDM; version 5.3) for 30,999 patients taking TA or AA from 2011 through 2020 were analyzed. New-onset hyponatremia was defined as a serum sodium level < 135 mEq/L within 10 days after drug initiation. The incidence rate ratio was calculated based on crude and 1:1 propensity-score-matched models. Subgroup analyses compared patients taking TA extended-release (TA-ER) and TA immediate-release (TA-IR) formulations.

Results: Among the 30,999 patients, 12,122 (39.1%) were aged > 65 years and 16,654 (53.7%) were male. Hyponatremia within 10 days developed in 1613 (8.4%) of the 19,149 patients in the TA group; the incidence rate was higher than in the AA group (4.2%; 493 out of 11,850 cases). In the propensity-score-matched model, the incidence rate of hyponatremia in the TA group was 6.8 per 1000 person-days (PD), which was 1.57-fold (1.31, 1.89) higher than that in the AA group (4.3 per 1000 PD). In both the crude and propensity-score-matched models, the incidence rate of hyponatremia was significantly higher in the TA-ER than TA-IR subgroup.

Conclusion: In this real-world study, hyponatremia was more frequently observed in the TA than AA group, and in the TA-ER than TA-IR subgroup. Therefore, it is imperative to prescribe tramadol cautiously and closely monitor electrolyte levels.

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Conflict of interest statement

The authors have no conflicts of interest to declare.

Figures

Fig. 1
Fig. 1
Diagram of cohort construction. TA tramadol/acetaminophen, AA acetaminophen
Fig. 2
Fig. 2
Forest plot comparing the risk of incident hyponatremia between the TA and AA, and TA–ER and TA–IR groups. TA tramadol/acetaminophen, AA acetaminophen, TA–ER tramadol/acetaminophen extended-release formulation, TA–IR tramadol/acetaminophen immediate-release formulation
See this image and copyright information in PMC

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