Background and Purpose. Skeletal muscle relaxants (SMRs) are commonly co-prescribed with potentially interacting medications that may contribute to increased risk of unintentional traumatic injury (hereafter, injury). While prior research has investigated clinical outcomes for some pairwise drug interactions involving SMRs, drug interactions involving more than two drugs, such as drug triads (3DIs), largely remain unexamined. We sought to identify SMR 3DI signals associated with injury via automated high-throughput pharmacoepidemiologic screening of 2000–2019 healthcare data for members of commercial and Medicare Advantage health plans. Experimental Approach. We performed a self-controlled case series study for each drug triad consisting of an SMR base pair (i.e., concomitant use of an SMR with another medication), and a co-dispensed medication (i.e., candidate interacting precipitant) taken during ongoing use of the base pair. We included patients aged ≥16 years with an injury occurring during base pair-exposed observation time. We used conditional Poisson regression to calculate adjusted rate ratios (RRs) with 95% confidence intervals (CIs) for injury with each SMR base pair + candidate interacting precipitant (i.e., triad) versus the SMR-containing base pair alone. Key Results. Among 58,478 triads, 29 were significantly positively associated with injury; confounder-adjusted RRs ranged from 1.39 (95% CI=1.01–1.91) for tizanidine+omeprazole with gabapentin to 2.23 (95% CI=1.02–4.87) for tizanidine+diclofenac with alprazolam. Most identified 3DI signals are new and have not been formally investigated. Conclusions and Implications. We identified 29 SMR 3DI signals associated with increased rates of injury. Future etiologic studies should confirm or refute these SMR 3DI signals.

Objective: To compare maternal and infant outcomes with different antihypertensive medications in pregnancy Design: Retrospective cohort study Setting: Kaiser Permanente, a large US healthcare system. Population: Women aged 15-49 years with a singleton birth from 2005-2014 treated for hypertension. Methods: We identified medication exposure from automated pharmacy data based on the earliest dispensing after the first prenatal visit. Using logistic regression, we calculated weighted outcome prevalences, adjusted odds ratios (aORs) and 95% confidence intervals, with inverse probability of treatment weighting to address confounding. Main outcome measures: Small for gestational age (SGA), preterm delivery, neonatal and maternal intensive care unit (ICU) admission, preeclampsia, and stillbirth or termination at > 20 weeks. Results: Among 6346 deliveries, 87% with chronic hypertension, the risk of SGA (birthweight < 10th percentile) was lower with methyldopa than labetalol (prevalence 13.6% vs. 16.6%; aOR 0.77, 95% CI 0.63 to 0.92). For birthweight < 3rd percentile the aOR was 0.57 (0.39 to 0.80). Compared with labetalol (26.0%), risk of preterm delivery was similar for methyldopa (26.5%; aOR 1.10 [0.95 to 1.27]) and slightly higher for nifedipine (28.5%; aOR 1.25 [1.06 to 1.46]) and other β-blockers (31.2%; aOR 1.58 [1.07 to 2.23]). NICU admission was more common with nifedipine than labetalol (25.9% vs. 23.3%, aOR 1.21 [1.02 to 1.43]) but not elevated with methyldopa. Risks of other outcomes did not differ by medication. Conclusions: Risk of most outcomes was similar comparing labetalol, methyldopa and nifedipine. SGA risk was substantially lower for methyldopa, suggesting this medication may warrant further consideration.