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. 2021 Apr 7;21:233. doi: 10.1186/s12877-021-02183-0

Table 3.

Most common severe potential drug-drug interactions among home medications and potential severe adverse effects

Category D
N = 902
Potential severe adverse effectsa Number of DDIs (%)

Additive CNS depressant effect (CNS depressant* + Opioidanalgesic or two CNS depressants)

* Including antipsychotics, benzodiazepines, TCAs, musclerelaxants, sedating antihistamines, and sedative-hypnotics.

Hypotension, sedation, respiratory depression 266 (29.5)

Additive QT prolongation effect

Mostly: amiodarone, aripiprazole, citalopram, fluconazole,mirtazapine, and ondansetron.

Torsades de pointes (TdP), death 80 (8.9)

Interactions affecting drug absorption

➢ Sucralfate + digoxin, warfarin, or furosemide

➢ Levothyroxine + minerals, or lanthanum

➢ Quinolones or tetracyclines + minerals

➢ Bile acid sequestrants + hydrochlorothiazide or statins

Variations in systemic drug availability and henceclinical efficacy 80 (8.9)
Antiplatelet agents + oral anticoagulant Increased risk of bleeding, both major and minor 65 (7.2)

Statins + drugs that increase their levels

(Simvastatin + amiodarone, amlodipine, diltiazem, or ranolazine)

(Atorvastatin + diltiazem or verapamil)

Increased risk of muscle toxicity, rhabdomyolysis 56 (6.2)

Drug combination that can cause bradycardia/AV block

Mostly: β-blockers, clonidine, diltiazem verapamil, and centralα2agonists.

Bradycardia, AV block 36 (4)
Esomeprazole/omeprazole + Clopidogrel Increase in incidence of major adverse cardiac events 35 (3.9)
Aspirin + NSAID Increase in incidence of major adverse cardiac events 25 (2.8)
SSRI + SSRI/SNRI/TCA Increased risk of serotonin syndrome/serotonin toxicity 25 (2.8)
NSAID + SSRI Increased risk of bleeding 13 (1.4)
NSAIDs + loop diuretics Reduced diuretic effect, acute kidney injury 12 (1.3)
ACEI + ARB Hyperkalemia, acute kidney injury 11 (1.2)
Oral anticoagulant + estradiol Increased risk of thromboembolism 8 (0.9)
Colchicine + statins Increased risk of muscle toxicity, rhabdomyolysis 7 (0.8)

Category X

N = 178

Nonselective β-blocker (carvidolol, propranolol) + β2 agonist(albuterol, formoterol) Bronchospasm, could be severe 44 (24.7)

Anticholinergic agents# + oral solid potassium dosage forms

# Amitriptyline, benztropine, cyproheptadine, diphenhydramine,olanzapine, oxybutynin, promethazine, quetiapine, or solifenacin.

Increased risk of ulcerative/stenotic lesions 44 (24.7)

Concomitant use of highest risk QTc-prolonging agents& with any other QTc-prolonging agent

& Amiodarone, citalopram, sotalol, dronedarone, quetiapine,ziprasidone

Torsades de pointes (TdP), death 26 (14.6)
Dual anticholinergic agents Confusion, dry mouth, blurred vision, arrhythmia, falls 24 (13.5)
Sucralfate + Vitamin D analogs Increased risk for aluminum accumulation/toxicity 10 (5.6)
Concomitant vitamin D analogs Vitamin D toxicity, hypercalcemia 6 (3.4)
Rivastigmine + β-blocker Bradycardia, syncope 4 (2.2)
Cyclosporine + atorvastatin Myopathy, rhabdomyolysis 2 (1.1)

ACEI Angiotensin-converting-enzyme inhibitor, ARB Angiotensin II receptor blocker, CNS Central nervous system, NSAID Non-steroidal anti-inflammatory drug, SSRI Selective serotonin reuptake inhibitor, SNRI Serotonin norepinephrine reuptake inhibitor, TCA Tricyclic antidepressant

a Reference: Lexicomp®