It is well known that strong CYP1A2 inhibitors decrease metabolism of tizanidine. In this study we aimed to determine if commonly used mild-moderate CYP1A2 inhibitors would have the same effect on the metabolism of tizanidine by monitoring rates of hypotension.
A list of patient medical records was generated from EPIC, the University of Utah’s electronic medical record system for patients admitted between 10/1/18-10/1/19. The patients selected were administered a mild-moderate CYP1A2 inhibitor and tizanidine within 2 hours from each other. The inhibiting medications that will be included are propranolol, caffeine, butalbital/acetaminophen/caffeine, celecoxib, acyclovir, valacyclovir, verapamil, and allopurinol. A retrospective chart review was performed to determine if a baseline blood pressure was recorded and that all patients meet inclusion/exclusion criteria. Hypotension is defined as SBP < 90mmHg or >20 point mmHg drop in systolic blood pressure from baseline after administration.
Descriptive statistics were used to describe the baseline characteristics of patients included in the study. Categorical variables are reported with numbers and percentages Rates of hypotension were computed using Excel.
A total of 132 doses of a CYP1A2 inhibitor plus tizanidine with baseline blood pressure and post tizanidine blood pressure measurements were included in this study. All CYP1A2 inhibitors that were studied showed some level of blood pressure decrease but all did not meet defined levels of hypotension. Rates of hypotension per CYP1A2 inhibitor defined as <90 systolic blood pressure or >20 mmHg systolic blood pressure decrease were as follows: acyclovir (11.7%; 17.6%), allopurinol (3.7%, 11.1%), verapamil (0%, 20%), valacyclovir (0%,11.1%), celecoxib (4.5%, 11.4%), fioricet (0%, 0%), caffeine (16.7%, 16.7%), propranolol (20%, 40%).
This small study demonstrated that mild to moderate CYP1A2 inhibitors may have a clinically significant effect on tizanidine metabolism. However, the rate of hypotension seen is significantly less than what is seen with strong CYP1A2 inhibitors. Some limitations to note are the patients in this study are all hospitalized with an acute illness, due to this we are unable to attribute the hypotension purely to the drug drug interaction. Additionally, some CYP1A2 inhibitors are antihypertensives so it is unclear if the blood pressure decrease was from the antihypertensives alone or from increased responsiveness with tizanidine in addition to an antihypertensive. This data shows it is possible that hypotension may occur from a mild-moderate CYP1A2 inhibitor used in conjunction with tizanidine. Health care professionals should be aware of this possibility and monitor their patients if administering medications in this combination.Recommend0 recommendationsPublished in