Risk of tizanidine-induced adverse events after concomitant exposure to ciprofloxacin: A cohort study in the U.S

Abstract

Background: Tizanidine's potent muscle relaxant properties and short onset of action makes it desirable for pain management. However, concomitant use of tizanidine with ciprofloxacin, a strong inhibitor of the P450-CYP1A2 cytochrome metabolic pathway of tizanidine, can result in increased tizanidine plasma levels and associated adverse outcomes, particularly hypotension. The aim of this study was to assess the risk of hypotension with coadministration of tizanidine and ciprofloxacin.

Methods: An observational nested cohort study of patients 18 years or older on tizanidine was conducted using data from electronic health records from 2000 to 2018 in the US. We estimated the prevalence and risk of hypotension associated with the DDI between tizanidine and ciprofloxacin using multivariable logistic regression models.

Results: Our analysis included 70,110 encounters of patients on tizanidine across 221 hospitals. Most encounters included females (65.7%), whites (82.4%), with an average age of 56 years (SD 14.9) and an Elixhauser comorbidity index mean of 1.6 (SD 2.3). Ciprofloxacin was co-administered with tizanidine in 2487 encounters (3.6%). Compared to patients who did not receive ciprofloxacin, co-administration of tizanidine and ciprofloxacin was associated with an increased likelihood of hypotension (adjusted odds ratio: 1.43, 95% Confidence Intervals:1.25-1.63, p-value<0.001).

Conclusions: Our findings suggest that the concomitant use of tizanidine and ciprofloxacin is associated with an elevated risk of hypotension. The prevalence of co-administration of drugs with a documented interaction highlights the need for continuous education across providers to avoid the incidence of DDI related adverse events and further complications and to improve patient outcomes.

Keywords: Ciprofloxacin; Cytochrome P-450-CYP1A2; Drug interactions; Drug-related side effects and adverse reactions; Hypotension; Tizanidine.