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

Area of Science:

• Pharmacovigilance
• Clinical Pharmacology
• Internal Medicine

Background:

• Tramadol is associated with hyponatremia, but evidence is conflicting.
• The risk of hyponatremia with tramadol/acetaminophen (TA) combination therapy is unknown.
• This study investigated the association between TA use and hyponatremia risk.

Purpose of the Study:

• To determine if tramadol/acetaminophen (TA) therapy increases the risk of hyponatremia compared to acetaminophen (AA) alone.
• To compare the risk of hyponatremia between extended-release (TA-ER) and immediate-release (TA-IR) tramadol formulations.

Main Methods:

• Analysis of hospital data (OMOP-CDM) for 30,999 patients from 2011-2020.
• Defined new-onset hyponatremia as serum sodium < 135 mEq/L within 10 days of drug initiation.
• Utilized crude and 1:1 propensity-score-matched models to calculate incidence rate ratios.

Main Results:

• Hyponatremia occurred in 8.4% of the TA group versus 4.2% of the AA group.
• The propensity-score-matched model showed a 1.57-fold higher incidence rate of hyponatremia in the TA group (6.8 per 1000 PD) compared to the AA group (4.3 per 1000 PD).
• Both crude and matched models indicated a significantly higher incidence rate of hyponatremia in the TA-ER subgroup compared to the TA-IR subgroup.

Conclusions:

• Tramadol/acetaminophen (TA) therapy is associated with a higher frequency of hyponatremia than acetaminophen (AA) alone.
• Extended-release tramadol/acetaminophen (TA-ER) carries a greater risk of hyponatremia than immediate-release (TA-IR).
• Cautious prescription of tramadol and close monitoring of electrolyte levels are essential.