Table 2.
Object drug (ASO rating) | Precipitant drug | Precipitant drug therapeutic category | RR, semi-Bayes shrunk | Lower bound of 95% CI | Upper bound of 95% CI |
---|---|---|---|---|---|
5-hydroxytryptamine2 receptor antagonist | |||||
Nefazodone (4) | meperidine*,**,*** | CNS | 2.94 | 1.41 | 6.12 |
quetiapine†,‡ | 2.26 | 1.06 | 4.83 | ||
levonorgestrel | Endocrine and metabolic | 3.06 | 1.42 | 6.60 | |
finasteride | Renal and genitourinary | 1.86 | 1.03 | 3.38 | |
cetirizine | Respiratory | 1.55 | 1.07 | 2.25 | |
Trazodone (3) | cefaclor*** | Anti-infective | 1.96 | 1.01 | 3.81 |
hydroxychloroquine* | Biologic and immunologic | 1.38 | 1.06 | 1.80 | |
hydralazine | CV | 1.40 | 1.06 | 1.85 | |
indomethacin†,*** | CNS | 1.45 | 1.05 | 2.00 | |
nabumetone†,*** | 1.34 | 1.03 | 1.75 | ||
donepezil* | 1.18 | 1.01 | 1.38 | ||
lorazepam* | 1.15 | 1.03 | 1.29 | ||
desogestrel | Endocrine and metabolic | 1.75 | 1.16 | 2.64 | |
liothyronine | 1.53 | 1.06 | 2.21 | ||
risedronate | 1.28 | 1.07 | 1.54 | ||
levothyroxine | 1.15 | 1.06 | 1.26 | ||
sodium biphosphate* | GI | 1.78 | 1.04 | 3.06 | |
metoclopramide | 1.34 | 1.09 | 1.65 | ||
multivitamin with iron | Nutrients and nutritional | 2.02 | 1.12 | 3.64 | |
spironolactone | Renal and genitourinary | 1.21 | 1.01 | 1.45 | |
homatropine | Respiratory | 1.60 | 1.05 | 2.44 | |
Dopamine reuptake blocking compound | |||||
Bupropion (1) | nebivolol†,‡ | CV | 1.41 | 1.03 | 1.92 |
valsartan | 1.23 | 1.05 | 1.43 | ||
atorvastatin | 1.10 | 1.01 | 1.19 | ||
rizatriptan | CNS | 1.26 | 1.03 | 1.54 | |
buspirone | 1.23 | 1.04 | 1.45 | ||
pregabalin | 1.23 | 1.01 | 1.49 | ||
cyclobenzaprine*** | 1.21 | 1.10 | 1.32 | ||
glimepiride | Endocrine and metabolic | 1.37 | 1.05 | 1.79 | |
glipizide | 1.31 | 1.02 | 1.69 | ||
allopurinol | 1.27 | 1.00 | 1.60 | ||
lubiprostone | GI | 1.70 | 1.24 | 2.34 | |
metolazone | Renal and genitourinary | 1.76 | 1.08 | 2.89 | |
silodosin | 1.70 | 1.05 | 2.74 | ||
furosemide | 1.21 | 1.07 | 1.36 | ||
sildenafil | 1.17 | 1.00 | 1.36 | ||
cetirizine | Respiratory | 1.15 | 1.01 | 1.32 | |
Noradrenergic antagonist | |||||
Mirtazapine (3) | clarithromycin*** | Anti-infective | 1.94 | 1.21 | 3.09 |
trimethoprim*** | 1.76 | 1.50 | 2.06 | ||
sulfamethoxazole*** | 1.74 | 1.48 | 2.05 | ||
metronidazole | 1.37 | 1.02 | 1.86 | ||
levofloxacin*** | 1.34 | 1.13 | 1.60 | ||
rosuvastatin | CV | 1.57 | 1.13 | 2.16 | |
amiodarone | 1.32 | 1.00 | 1.74 | ||
caffeine | CNS | 1.89 | 1.27 | 2.80 | |
butalbital*** | 1.76 | 1.19 | 2.61 | ||
primidone | 1.62 | 1.02 | 2.57 | ||
lamotrigine | 1.60 | 1.19 | 2.14 | ||
pregabalin | 1.60 | 1.20 | 2.12 | ||
alprazolam* | 1.32 | 1.14 | 1.54 | ||
tramadol*,**,*** | 1.23 | 1.10 | 1.38 | ||
lorazepam* | 1.22 | 1.07 | 1.40 | ||
megestrol | Endocrine and metabolic | 1.24 | 1.04 | 1.49 | |
rabeprazole | GI | 1.74 | 1.05 | 2.89 | |
clopidogrel | Hematological | 1.37 | 1.16 | 1.60 | |
tadalafil | Renal and genitourinary | 2.38 | 1.25 | 4.53 | |
alfuzosin | 2.06 | 1.12 | 3.77 | ||
solifenacin | 1.43 | 1.01 | 2.03 | ||
spironolactone | 1.35 | 1.04 | 1.76 | ||
hydrochlorothiazide | 1.21 | 1.07 | 1.38 | ||
furosemide | 1.12 | 1.01 | 1.23 | ||
Serotonin-norepinephrine reuptake inhibitors | |||||
Desvenlafaxine (0) | erythromycin*** | Anti-infective | 2.08 | 1.04 | 4.14 |
fenofibrate | CV | 1.48 | 1.01 | 2.17 | |
lisinopril | 1.23 | 1.00 | 1.50 | ||
metaxalone*,*** | CNS | 1.53 | 1.07 | 2.18 | |
methylprednisolone | Endocrine and metabolic | 1.44 | 1.02 | 2.03 | |
Duloxetine (0) | famciclovir | Anti-infective | 1.75 | 1.16 | 2.65 |
trimethoprim*** | 1.25 | 1.09 | 1.43 | ||
sulfamethoxazole*** | 1.24 | 1.07 | 1.43 | ||
levofloxacin*** | 1.19 | 1.03 | 1.37 | ||
methotrexate | Antineoplastic | 1.35 | 1.09 | 1.68 | |
hydroxychloroquine | Biologic and immunologic | 1.34 | 1.12 | 1.61 | |
flurazepam | CNS | 2.54 | 1.35 | 4.79 | |
valproic acid | 1.82 | 1.10 | 3.03 | ||
tapentadol*,*** | 1.64 | 1.06 | 2.54 | ||
metaxalone*,‡,*** | 1.25 | 1.04 | 1.51 | ||
gabapentin | 1.07 | 1.00 | 1.15 | ||
liothyronine | Endocrine and metabolic | 1.58 | 1.18 | 2.12 | |
apixaban† | Hematological | 2.62 | 1.62 | 4.26 | |
multivitamin with minerals | Nutrients and nutritional | 1.91 | 1.14 | 3.19 | |
multivitamin prenatal | 1.59 | 1.06 | 2.39 | ||
levocetirizine | Respiratory | 1.38 | 1.07 | 1.79 | |
Venlafaxine (0) | proguanil | Anti-infective | 1.81 | 1.11 | 2.95 |
atovaquone | 1.69 | 1.03 | 2.79 | ||
isosorbide dinitrate | CV | 1.58 | 1.02 | 2.44 | |
ramipril | 1.34 | 1.11 | 1.62 | ||
atorvastatin | 1.09 | 1.01 | 1.17 | ||
oxymorphone*,*** | CNS | 1.67 | 1.04 | 2.66 | |
valdecoxib†,*** | 1.55 | 1.18 | 2.06 | ||
chlordiazepoxide | 1.41 | 1.02 | 1.93 | ||
etodolac†,‡,*** | 1.36 | 1.08 | 1.71 | ||
tizanidine*** | 1.25 | 1.10 | 1.43 | ||
rizatriptan*,** | 1.23 | 1.00 | 1.50 | ||
metaxalone*,**,*** | 1.22 | 1.01 | 1.46 | ||
tramadol*,**,*** | 1.11 | 1.02 | 1.22 | ||
ethynodiol | Endocrine and metabolic | 1.76 | 1.12 | 2.77 | |
liothyronine | 1.33 | 1.04 | 1.70 | ||
methylprednisolone | 1.18 | 1.00 | 1.38 | ||
clidinium | GI | 1.51 | 1.04 | 2.19 | |
methscopolamine | 1.36 | 1.00 | 1.85 | ||
cholecalciferol | Nutrients and nutritional | 1.71 | 1.21 | 2.41 | |
bumetanide | Renal and genitourinary | 1.59 | 1.14 | 2.22 | |
metolazone | 1.44 | 1.03 | 2.02 | ||
Selective serotonin reuptake inhibitors | |||||
Citalopram (0) | mebendazole | Anti-infective | 2.45 | 1.15 | 5.20 |
ampicillin*** | 1.61 | 1.06 | 2.43 | ||
amantadine | 1.55 | 1.12 | 2.15 | ||
sulfamethoxazole*** | 1.45 | 1.33 | 1.57 | ||
trimethoprim*** | 1.43 | 1.32 | 1.55 | ||
losartan | CV | 1.09 | 1.00 | 1.18 | |
valproic acid | CNS | 1.51 | 1.01 | 2.25 | |
pramipexole | 1.37 | 1.15 | 1.63 | ||
haloperidol*,** | 1.34 | 1.06 | 1.69 | ||
modafinil | 1.33 | 1.02 | 1.73 | ||
metaxalone*,‡,*** | 1.25 | 1.04 | 1.49 | ||
lamotrigine | 1.20 | 1.04 | 1.38 | ||
sumatriptan*,** | 1.16 | 1.01 | 1.33 | ||
tramadol*,**,*** | 1.11 | 1.05 | 1.18 | ||
codeine*,*** | 1.11 | 1.01 | 1.23 | ||
cyclobenzaprine*,‡,*** | 1.08 | 1.01 | 1.15 | ||
clonazepam | 1.08 | 1.01 | 1.16 | ||
lorazepam | 1.08 | 1.01 | 1.15 | ||
gabapentin | 1.06 | 1.00 | 1.12 | ||
norgestrel | Endocrine and metabolic | 1.52 | 1.16 | 2.00 | |
mesalamine | GI | 1.29 | 1.02 | 1.62 | |
ticagrelor† | Hematological | 2.25 | 1.35 | 3.74 | |
prasugrel† | 1.50 | 1.02 | 2.20 | ||
multivitamin | Nutrients and nutritional | 1.36 | 1.02 | 1.80 | |
omega-3 polyunsaturated fatty acid | 1.25 | 1.01 | 1.54 | ||
metolazone | Renal and genitourinary | 1.45 | 1.21 | 1.74 | |
bumetanide | 1.36 | 1.11 | 1.68 | ||
Escitalopram (0) | amantadine | Anti-infective | 1.70 | 1.22 | 2.37 |
sulfamethoxazole*** | 1.21 | 1.09 | 1.34 | ||
trimethoprim*** | 1.21 | 1.09 | 1.34 | ||
cyclosporine | Biologic and immunologic | 1.88 | 1.02 | 3.49 | |
aliskiren | CV | 1.46 | 1.02 | 2.09 | |
ranolazine* | 1.41 | 1.00 | 1.99 | ||
terazosin | 1.33 | 1.00 | 1.77 | ||
losartan | 1.15 | 1.03 | 1.27 | ||
pramipexole | CNS | 1.30 | 1.07 | 1.58 | |
aripiprazole* | 1.24 | 1.07 | 1.43 | ||
carisoprodol*** | 1.20 | 1.05 | 1.38 | ||
clonazepam | 1.15 | 1.07 | 1.24 | ||
thyroid desiccated | Endocrine and metabolic | 1.20 | 1.01 | 1.43 | |
glimepiride | 1.19 | 1.01 | 1.40 | ||
rabeprazole | GI | 1.16 | 1.02 | 1.32 | |
omeprazole*,** | 1.07 | 1.01 | 1.14 | ||
dabigatran† | Hematological | 1.56 | 1.01 | 2.39 | |
fesoterodine | Renal and genitourinary | 1.46 | 1.02 | 2.09 | |
tolterodine* | 1.20 | 1.03 | 1.40 | ||
theophylline | Respiratory | 1.49 | 1.03 | 2.16 | |
Fluoxetine (1) | ampicillin*** | Anti-infective | 1.69 | 1.05 | 2.72 |
sulfamethoxazole*,*** | 1.32 | 1.18 | 1.48 | ||
trimethoprim*,*** | 1.32 | 1.18 | 1.47 | ||
nitrofurantoin | 1.22 | 1.06 | 1.41 | ||
azilsartan | CV | 2.28 | 1.07 | 4.83 | |
carvedilol | 1.13 | 1.00 | 1.29 | ||
nabumetone†,‡,*** | CNS | 1.25 | 1.05 | 1.50 | |
divalproex sodium‡ | 1.24 | 1.06 | 1.45 | ||
carisoprodol*** | 1.16 | 1.02 | 1.32 | ||
cyclobenzaprine*,**,*** | 1.10 | 1.03 | 1.19 | ||
budesonide | Endocrine and metabolic | 1.73 | 1.04 | 2.89 | |
desogestrel | 1.25 | 1.02 | 1.53 | ||
levothyroxine | 1.10 | 1.04 | 1.16 | ||
esomeprazole | GI | 1.14 | 1.04 | 1.25 | |
cilostazol†,‡ | Hematological | 1.70 | 1.09 | 2.65 | |
clopidogrel†,‡ | 1.17 | 1.05 | 1.31 | ||
acetazolamide | Renal and genitourinary | 1.74 | 1.16 | 2.62 | |
solifenacin* | 1.20 | 1.00 | 1.44 | ||
Furosemide | 1.08 | 1.01 | 1.16 | ||
Pseudoephedrine | Respiratory | 1.11 | 1.00 | 1.23 | |
Fluvoxamine (1) | Lisinopril | CV | 1.71 | 1.04 | 2.81 |
Ezetimibe | 1.62 | 1.06 | 2.48 | ||
Benztropine | CNS | 2.26 | 1.09 | 4.67 | |
buspirone** | 1.52 | 1.08 | 2.14 | ||
esomeprazole‡ | GI | 1.79 | 1.26 | 2.54 | |
Paroxetine (3) | quinine* | Anti-infective | 1.47 | 1.02 | 2.11 |
terbinafine** | 1.33 | 1.04 | 1.69 | ||
sulfamethoxazole*** | 1.22 | 1.07 | 1.38 | ||
trimethoprim*** | 1.22 | 1.08 | 1.38 | ||
ciprofloxacin*** | 1.16 | 1.03 | 1.30 | ||
Methotrexate | Antineoplastic | 1.33 | 1.02 | 1.72 | |
propafenone* | CV | 1.98 | 1.15 | 3.40 | |
Primidone | CNS | 1.41 | 1.05 | 1.88 | |
prochlorperazine | 1.38 | 1.02 | 1.87 | ||
Eszopiclone | 1.24 | 1.00 | 1.53 | ||
Lorazepam | 1.14 | 1.05 | 1.25 | ||
tramadol*,**,*** | 1.09 | 1.00 | 1.19 | ||
Gabapentin | 1.09 | 1.00 | 1.18 | ||
Hydrocortisone | Endocrine and metabolic | 1.73 | 1.13 | 2.64 | |
Sitagliptin | 1.25 | 1.01 | 1.54 | ||
Omeprazole | GI | 1.11 | 1.04 | 1.19 | |
multivitamin with iron | Nutrients and nutritional | 1.61 | 1.01 | 2.58 | |
Sertraline (0) | Valganciclovir | Anti-infective | 2.44 | 1.20 | 4.98 |
sulfamethoxazole*** | 1.50 | 1.38 | 1.63 | ||
trimethoprim*** | 1.46 | 1.35 | 1.59 | ||
levofloxacin*,*** | 1.12 | 1.02 | 1.23 | ||
Erlotinib | Antineoplastic | 2.37 | 1.19 | 4.74 | |
mycophenolate mofetil | Biologic and immunologic | 1.50 | 1.06 | 2.12 | |
nebivolol† | CV | 1.39 | 1.14 | 1.68 | |
Midodrine | 1.33 | 1.02 | 1.74 | ||
dexmethylphenidate‡ | CNS | 2.07 | 1.24 | 3.44 | |
pyridostigmine | 1.98 | 1.13 | 3.47 | ||
triazolam† | 1.51 | 1.09 | 2.11 | ||
chlordiazepoxide | 1.32 | 1.00 | 1.74 | ||
haloperidol†,‡ | 1.29 | 1.02 | 1.63 | ||
butalbital*** | 1.23 | 1.06 | 1.43 | ||
Caffeine | 1.22 | 1.05 | 1.42 | ||
Diazepam | 1.13 | 1.01 | 1.26 | ||
Temazepam | 1.13 | 1.00 | 1.28 | ||
tramadol†,**,*** | 1.10 | 1.03 | 1.16 | ||
alprazolam* | 1.08 | 1.02 | 1.14 | ||
thyroid desiccated‡ | Endocrine and metabolic | 1.21 | 1.03 | 1.41 | |
Progesterone | 1.20 | 1.03 | 1.40 | ||
Megestrol | 1.18 | 1.01 | 1.39 | ||
dipyridamole† | Hematological | 1.33 | 1.03 | 1.70 | |
clopidogrel† | 1.13 | 1.05 | 1.22 | ||
omega-3 polyunsaturated fatty acid | Nutrients and nutritional | 1.40 | 1.16 | 1.68 | |
Indapamide | Renal and genitourinary | 1.54 | 1.03 | 2.29 | |
Mirabegron | 1.48 | 1.12 | 1.97 | ||
Metolazone | 1.39 | 1.15 | 1.69 | ||
Tricyclic and related antidepressants | |||||
Amitriptyline (9) | sulfamethoxazole*,**,*** | Anti-infective | 1.28 | 1.11 | 1.47 |
trimethoprim*,**,*** | 1.27 | 1.10 | 1.45 | ||
amiodarone** | CV | 1.76 | 1.36 | 2.27 | |
Ramipril | 1.52 | 1.13 | 2.03 | ||
isosorbide mononitrate | 1.30 | 1.05 | 1.62 | ||
risperidone* | CNS | 1.52 | 1.07 | 2.16 | |
Lamotrigine | 1.49 | 1.11 | 2.00 | ||
Lorazepam | 1.17 | 1.01 | 1.34 | ||
Pregabalin | 1.17 | 1.03 | 1.34 | ||
Prednisone | Endocrine and metabolic | 1.13 | 1.02 | 1.26 | |
levothyroxine** | 1.09 | 1.00 | 1.18 | ||
Esomeprazole | GI | 1.12 | 1.00 | 1.26 | |
Clopidogrel | Hematological | 1.15 | 1.02 | 1.31 | |
potassium chloride | Nutrients and nutritional | 1.14 | 1.04 | 1.26 | |
Darifenacin | Renal and genitourinary | 1.68 | 1.13 | 2.48 | |
Metolazone | 1.48 | 1.08 | 2.04 | ||
Desipramine (4) | Atorvastatin | CV | 1.50 | 1.00 | 2.25 |
Methylprednisolone | Endocrine and metabolic | 1.93 | 1.04 | 3.60 | |
Doxepin (9) | sulfamethoxazole*,**,*** | Anti-infective | 1.43 | 1.04 | 1.96 |
trimethoprim*,**,*** | 1.38 | 1.01 | 1.88 | ||
Memantine | CNS | 2.05 | 1.20 | 3.49 | |
Diazepam | 1.56 | 1.09 | 2.21 | ||
Pantoprazole | GI | 1.41 | 1.09 | 1.84 | |
Imipramine (6) | ondansetron*,** | CNS | 2.15 | 1.22 | 3.80 |
Omeprazole | GI | 1.39 | 1.05 | 1.85 | |
Triamterene | Renal and genitourinary | 2.02 | 1.19 | 3.43 | |
Nortriptyline (3) | sulfamethoxazole*,**,*** | Anti-infective | 1.33 | 1.03 | 1.73 |
trimethoprim*,**,*** | 1.33 | 1.03 | 1.73 | ||
ketoprofen†,*** | CNS | 2.96 | 1.48 | 5.91 | |
oxaprozin†,*** | 1.67 | 1.02 | 2.74 | ||
Glipizide | Endocrine and metabolic | 1.65 | 1.05 | 2.60 | |
pioglitazone | 1.65 | 1.07 | 2.53 | ||
estradiol*,** | 1.50 | 1.08 | 2.07 | ||
omeprazole | GI | 1.19 | 1.03 | 1.39 | |
multivitamin with iron | Nutrients and nutritional | 2.55 | 1.14 | 5.67 | |
silodosin | Renal and genitourinary | 2.28 | 1.16 | 4.51 |
ASO = anticholinergic activity, sedation, and orthostasis; CV = cardiovascular; CNS = central nervous system; GI = gastrointestinal; RR = rate ratio
Rate ratios > 2.00 are bolded to highlight N = 22 potential signals that may warrant particular attention in future etiologic work.
Categorization of object drugs by severity of anticholinergic activity, sedation, and orthostasis: Within the Facts & Comparisons eAnswers central nervous system agents therapeutic category, we used the antidepressants monograph to categorize object drugs by severity of anticholinergic activity, sedation, and orthostasis. Our rationale for focusing on these adverse effects was their potential relationships with the unintentional traumatic injury outcomes being examined. For each antidepressant, we calculated a composite score by summing numeric severity ratings (0 = none or very low, 1 = low, 2 = moderate, 3 = high) for each of the three adverse effects. Therefore, each antidepressant was assigned a score of zero through nine, with a nine indicating a drug with high severity for anticholinergic activity, sedation, and orthostasis.
drug interaction with impact on object documented in Micromedex
drug interaction with impact on object documented in Facts & Comparisons eAnswers
finding may be particularly affected by protopathic bias
drug interaction with impact on precipitant documented in Micromedex
drug interaction with impact on precipitant documented in Facts & Comparisons eAnswers