Table 1.

Benzodiazepine drug interaction signals, given statistically significantly increased rates of hospital presentation for unintentional traumatic injury, by pharmacologic category of benzodiazepine, and by magnitude of association within therapeutic class of the co-administered drug

Benzodiazepine	Co-administered drug	Co-administered drug therapeutic class	RR*, semi-Bayes shrunk	Lower bound of 95% CI**	Upper bound of 95% CI
Benzodiazepine receptor agonist, anxiolytic
Alprazolam	Eletriptan	CNS	2.27	1.18	4.37
	Vortioxetinea		1.61	1.03	2.52
	Baclofenc		1.24	1.01	1.50
	Tizanidinec		1.19	1.04	1.36
	Bupropion		1.16	1.01	1.34
	Gabapentinb		1.14	1.04	1.25
	Propranolol	Cardiovascular	2.08	1.60	2.71
	Metolazone	Renal & Genitourinary	1.86	1.33	2.61
	Clarithromycina,b,c	Anti-infective	1.49	1.01	2.19
	Trimethoprimc		1.19	1.02	1.40
	Sulfamethoxazolec		1.18	1.01	1.39
	Apixaban	Hematological	1.36	1.04	1.78
Clonazepam	Tegaserod	Gastrointestinal	2.06	1.04	4.11
	Gemfibrozil	Cardiovascular	1.64	1.06	2.53
	Methylphenidate	CNS	1.44	1.00	2.07
	Amphetamine		1.39	1.04	1.84
	Sumatriptan		1.36	1.04	1.78
	Dextroamphetamine		1.35	1.03	1.78
	Butalbitalb,c,d		1.31	1.01	1.71
	Gabapentinb		1.15	1.04	1.27
	Levothyroxine	Endocrine & Metabolic	1.18	1.04	1.33
	Furosemide	Renal & Genitourinary	1.17	1.03	1.32
Diazepam	Benzonatate	Respiratory	1.70	1.00	2.87
	Pregabalinb	CNS	1.38	1.04	1.82
	Bupropiona		1.31	1.01	1.70
Lorazepam	Sulindacc	CNS	2.50	1.17	5.33
	Bupropion		1.26	1.04	1.54
	Divalproex sodiuma,b		1.23	1.00	1.51
	Sulfamethoxazolec	Anti-infective	1.47	1.24	1.75
	Trimethoprimc		1.47	1.24	1.74
Benzodiazepine receptor agonist, hypnotic
Temazepam	Phenobarbitalb,d	CNS	2.29	1.11	4.73
	Methadonea–e		2.14	1.16	3.94
	Rizatriptan		2.00	1.07	3.73
	Buspirone		1.56	1.09	2.24
	Lovastatin	Cardiovascular	1.47	1.01	2.14
Triazolam	Promethazine	Gastrointestinal	2.09	1.07	4.08
Nonbenzodiazepine GABA agonist hypnotic (Z-drug)
Eszopiclone	Megestrol	Endocrine & Metabolic	2.15	1.11	4.19
	Alendronate		1.69	1.02	2.79
Zaleplon	Metformin	Endocrine & Metabolic	1.83	1.08	3.10
Zolpidem	Minoxidil	Cardiovascular	2.51	1.09	5.80
	Clarithromycina,b,c	Anti-infective	1.63	1.14	2.33
	Trimethoprimc		1.19	1.02	1.38
	Methotrexate	Antineoplastic	1.45	1.00	2.09
	Rabeprazole	Gastrointestinal	1.41	1.00	1.98
	Spironolactone	Renal & Genitourinary	1.22	1.01	1.47
	Montelukast	Respiratory	1.21	1.01	1.46
Nonbenzodiazepine hypnotic, miscellaneous
Ramelteon	Furosemide	Renal & Genitourinary	1.60	1.01	2.52
Suvorexant	Metformin	Endocrine & Metabolic	1.63	1.01	2.64

RR: rate ratio; CI: confidence interval; CNS: central nervous system; GABA: gamma-aminobutyric acid

RRs >2.00 are bolded to highlight 10 potential signals that may warrant particular attention in future etiologic work.

^*Causal contrast is concomitant use of benzodiazepine + co-administered drug vs. use of benzodiazepine alone.

^**p-values <0.05 for lower bounds equal to 1.00 after rounding

^aDrug interaction with impact on benzodiazepine documented in Facts & Comparisons eAnswers.

^bDrug interaction with impact on benzodiazepine documented in Micromedex.

^cFinding may be particularly affected by protopathic bias.

^dDrug interaction with impact on co-administered drug documented in Micromedex.

^eDrug interaction with impact on co-administered drug documented in Facts & Comparisons eAnswers.