Table 3.

Benzodiazepine and related drugs (BZD) drug-drug-drug interaction signals of potential clinical concern given statistically significantly increased rates of unintentional traumatic injury, by commonly used BZD and therapeutic category of co-dispensed drug of the base pair.

BZD	Therapeutic class of co-dispensed drug of the base pair	Co-dispensed drug of the base pair	Candidate Interacting Precipitant	Rate ratio, semi-Bayes shrunk and adjusteda	95% confidence interval
ALPRAZOLAM	Cardiovascular	Fenofibrate	Ciprofloxacin	2.15	1.01–4.57
		Amlodipine	Pregabalin	2.02	1.10–3.69
		Diltiazem	Gabapentin	1.94	1.06–3.52
		Carvedilol	Gabapentin	1.69	1.04–2.75
		Lisinopril	Gabapentin	1.42	1.03–1.97
	Central nervous system	Methadone	Ondansetron	2.48	1.16–5.31
		Meloxicam	Fluconazole	2.34	1.13–4.85
		Aripiprazole	Ondansetron	2.25	1.10–4.64
		Gabapentin	Fluconazole	2.22	1.25–3.94
		Quetiapine	Levothyroxine	2.05	1.06–3.95
		Oxycodone	Morphine	1.80	1.09–2.96
		Quetiapine	Omeprazole	1.79	1.00–3.18
		Gabapentin	Quetiapine	1.72	1.02–2.91
		Oxycodone	Levothyroxine	1.72	1.06–2.77
		Hydrocodone	Sulfamethoxazole	1.60	1.02–2.50
		Hydrocodone	Trimethoprim	1.60	1.02–2.49
		Hydrocodone	Gabapentin	1.45	1.07–1.97
		Hydrocodone	Tizanidine	1.42	1.00–2.02**
	Endocrine and metabolic	Alendronate	Fluconazole	2.16	1.04–4.49
		Levothyroxine	Risperidone	1.92	1.03–3.60
		Levothyroxine	Trimethoprim	1.53	1.01–2.30
		Levothyroxine	Sulfamethoxazole	1.51	1.00–2.28
	Gastrointestinal	Ranitidine	Furosemide	2.26	1.20–4.24
		Omeprazole	Propranolol	2.12	1.02–4.41
	Hematological	Clopidogrel	Meloxicam	2.22	1.11–4.45
	Renal and genitourinary	Furosemide	Metolazone	2.00	1.02–3.91
		Furosemide	Sulfamethoxazole	1.80	1.08–3.00
		Furosemide	Trimethoprim	1.80	1.08–2.99
CLONAZEPAM	Cardiovascular	Atorvastatin	Cefuroxime	3.01	1.53–5.94
		Simvastatin	Clindamycin	2.46	1.27–4.77
		Amlodipine	Pantoprazole	2.00	1.16–3.45
		Metoprolol	Duloxetine	1.93	1.13–3.29
	Central nervous system	Meloxicam	Furosemide	2.96	1.54–5.69
		Topiramate	Sumatriptan	2.53	1.28–5.00
		Memantine	Tramadol	2.24	1.15–4.36
		Donepezil	Metoprolol	2.17	1.08–4.33
		Mirtazapine	Promethazine	2.15	1.08–4.30
		Oxycodone	Hydroxyzine	2.12	1.20–3.73
		Meloxicam	Prednisone	2.07	1.19–3.61
		Escitalopram	Metoprolol	2.00	1.06–3.78
		Sertraline	Gabapentin	1.71	1.05–2.77
		Gabapentin	Duloxetine	1.61	1.02–2.54
	Endocrine and metabolic	Metformin	Nitrofurantoin	2.04	1.04–4.00
		Metformin	Clindamycin	2.03	1.02–4.04
		Levothyroxine	Omeprazole	1.54	1.06–2.25
		Levothyroxine	Gabapentin	1.49	1.08–2.04
	Gastrointestinal	Omeprazole	Atorvastatin	1.68	1.02–2.78
		Omeprazole	Gabapentin	1.55	1.09–2.21
	Hematological	Clopidogrel	Furosemide	1.68	1.02–2.78
	Renal and genitourinary	Hydrochlorothiazide	Amlodipine	1.66	1.02–2.70
		Hydrochlorothiazide	Lisinopril	1.58	1.02–2.44
DIAZEPAM	Central nervous system	Fluoxetine	Tramadol	2.05	1.03–4.08
LORAZEPAM	Cardiovascular	Benazepril	Trimethoprim	2.27	1.08–4.75
		Benazepril	Sulfamethoxazole	2.15	1.02–4.55
		Fenofibrate	Hydrocodone	1.90	1.06–3.40
		Amlodipine	Escitalopram	1.84	1.05–3.22
		Digoxin	Hydrocodone	1.77	1.02–3.07
		Metoprolol	Escitalopram	1.75	1.04–2.97
		Amlodipine	Sulfamethoxazole	1.66	1.02–2.72
	Central nervous system	Memantine	Gabapentin	2.15	1.03–4.50
		Venlafaxine	Hydrochlorothiazide	2.06	1.07–3.98
		Escitalopram	Nitrofurantoin	1.93	1.03–3.64
		Citalopram	Sulfamethoxazole	1.87	1.07–3.28
		Citalopram	Trimethoprim	1.77	1.01–3.11
		Hydrocodone	Levothyroxine	1.74	1.05–2.90
	Endocrine and metabolic	Metformin	Escitalopram	2.01	1.02–3.94
		Levothyroxine	Atorvastatin	1.69	1.08–2.64
	Gastrointestinal	Famotidine	Ondansetron	2.54	1.24–5.24
		Omeprazole	Nitrofurantoin	2.09	1.25–3.50
	Renal and genitourinary	Furosemide	Clindamycin	2.27	1.21–4.25
		Hydrochlorothiazide	Escitalopram	1.78	1.01–3.15
ZOLPIDEM	Cardiovascular	Valsartan	Codeine	2.05	1.04–4.04
		Amlodipine	Cyclobenzaprine	2.01	1.21–3.34
		Amlodipine	Omeprazole	1.68	1.05–2.70
	Central nervous system	Amitriptyline	Pantoprazole	2.14	1.02–4.52
	Endocrine and metabolic	Levothyroxine	Meloxicam	1.63	1.01–2.61
	Hematological	Warfarin	Azithromycin	2.15	1.11–4.15
		Clopidogrel	Gabapentin	2.06	1.17–3.64
	Renal and genitourinary	Tamsulosin	Tramadol	1.98	1.14–3.43

**p = 0.049.

^aRate ratio was calculated as outcome rates during candidate precipitant-exposed person-time divided by outcome rates during candidate precipitant-unexposed days, i.e., $\frac{{\mathrm{rate}}_{\mathrm{BZD}\mathrm{base}\mathrm{pair}+\mathrm{candidate}\mathrm{precipitant}}}{{\mathrm{rate}}_{\mathrm{BZD}\mathrm{base}\mathrm{pair}}}$, adjusting for the following time-varying covariates: average daily dose of BZD, follow-up month, and ever having a prior traumatic injury of interest.