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Co‐Prescription of Strong CYP 1A2 Inhibitors and the Risk of Tizanidine‐Associated Hypotension: A Retrospective Cohort Study
Author(s) -
Chaugai Sandip,
Dickson Alyson L.,
Shuey Megan M.,
Feng QiPing,
Barker Katherine A.,
Wei WeiQi,
Luther James M.,
Stein C. Michael,
Chung Cecilia P.
Publication year - 2019
Publication title -
clinical pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.941
H-Index - 188
eISSN - 1532-6535
pISSN - 0009-9236
DOI - 10.1002/cpt.1233
Subject(s) - tizanidine , medicine , blood pressure , muscle relaxant , anesthesia , odds ratio , pharmacology , spasticity
Tizanidine, a widely used muscle relaxant that can lower blood pressure, is metabolized by the cytochrome P450 1A2 ( CYP 1A2). We studied 1,626 patients prescribed tizanidine and 5,012 prescribed cyclobenzaprine concurrently with a strong CYP 1A2 inhibitor. The primary outcome was severe hypotension, defined as systolic blood pressure ( SBP ) ≤ 70 mmHg during periods of drug co‐exposure. Severe hypotension occurred more often in the tizanidine group (2.03%; n = 33) than the cyclobenzaprine group (1.28%; n = 64); odds ratio ( OR ) = 1.60; P = 0.029. This difference remained statistically significant after adjustment for a log‐transformed propensity score that included age, sex, race, Charlson's comorbidity index, and concurrent use of antihypertensive medications ( OR = 1.57; P = 0.049). A sensitivity analysis that defined hypotension as SBP < 90 mmHg also yielded higher rates of hypotension among patients prescribed tizanidine. In conclusion, CYP 1A2 inhibition increases the risk of hypotensive episodes associated with the use of tizanidine in routine clinical practice.