New Oral Anticoagulants in the Treatment of Pulmonary Embolism: Efficacy, Bleeding Risk, and Monitoring

Table 2

Selected P-glycoprotein and Cytochrome P450 3A4 drug interactions with NOAC based on current FDA-approved indications [18, 21, 31, 32].

Medications^+	Mechanism of Interaction	Dabigatran^#; (Pradaxa)	Rivaroxaban^∧; (Xarelto)	Apixaban; (Eliquis)
Rifampin	P-glycoprotein inducer	Avoid combination	Avoid	Avoid
Carbamazepine, phenytoin,; St. John’s wort	P-glycoprotein inducers and; Strong 3A4 inducers	Avoid	Avoid	Avoid
Dronedarone	P-glycoprotein inhibitors	For CrCl 30–50 mL/min: Dose reduction suggested in dosing for Atrial Fibrillation; For CrCl < 30 mL/min: Aviod	Not addressed in Package Insert	Not addressed
Systemic ketoconazole Itraconazole	P-glycoprotein inhibitors and; Strong 3A4 inhibitors	For CrCl 30–50 mL/min: Dose reduction suggested in dosing for Atrial Fibrillation	Avoid	Reduce dose in 1/2 for those starting on the full dose of 5 mg BID^%
lopinavir/ritonavir, ritonavir,; indinavir/ritonavir, conivaptan	P-glycoprotein inhibitors and; Strong 3A4 inhibitor	Not addressed in Package Insert	Avoid	Reduce dose in 1/2 for those starting on the full dose of 5 mg BID^%
Verapamil, amiodarone, quinidine,	P-glycoprotein inhibitors	For CrCl 30–50 mL/min: No dose adjustment needed, monitor clinical course; For CrCl < 30 mL/min: Aviod	Not addressed in Package Insert	Reduce dose in 1/2 for those starting on the full dose of 5 mg BID^%
Clarithromycin	P-glycoprotein inducers and strong 3A4 inducers	For CrCl < 30 mL/min; Avoid; For CrCl 30–50 mL/min: No dose adjustment needed, monitor clinical course	Unclear: refer to package insert.	Reduce dose in 1/2 for those starting on the full dose of 5 mg BID^%

CrCl: creatinine clearance as determined by Crockcoft-Gault equation.
^#Dabigatran etexilate (prodrug) uses the p-glycoprotein transport system. It is not a substrate, inducer, or inhibitor of the cytochrome p450 system.
^∧Rivaroxaban is a substrate for cytochrome p450 as well as p-glycoprotein.
⁺Listed medications are representatives of potent 3A4 inhibitors and may not be comprehensive.
^%Those patients who need to start at 2.5 mg BID should avoid this combination.