OBJECT DRUGS

• Digoxin (Lanoxin, etc.)

PRECIPITANT DRUGS

P-glycoprotein Inhibitors:

• Amiodarone (Cordarone, etc.)
• Azithromycin (Zithromax, etc.)
• Canagliflozin (Invokana)
• Clarithromycin (Biaxin, etc.)
• Conivaptan (Vaprisol)
• Cyclosporine (Neoral, etc.)
• Daclatasvir (Daklinza)
• Dronedarone (Multaq)
• Eliglustat (Cerdelga)
• Erythromycin (E-Mycin, etc.)
• Ezogabine (Potiga)
• Flibanserin (Addyi)
• Hydroxychloroquine
• Indinavir (Crixivan)
• Itraconazole (Sporanox, etc.)
• Ketoconazole (Nizoral, etc.)
• Lapatinib (Tykerb)
• Lomitapide (Juxtapid)
• Nelfinavir (Viracept)
• Paritaprevir (Technivie)
• Posaconazole (Noxafil)
• Propafenone (Rythmol, etc.)
• Quinidine (Quinidex)
• Ranolazine (Ranexa)
• Ritonavir (Norvir)
• Saquinavir (Invirase)
• Sunitinib (Sutent)
• Tacrolimus (Prograf, etc.)
• Tamoxifen (Nolvadex)
• Telaprevir (Incivek)
• Telithromycin (Ketek)
• Ticagrelor (Brilinta)

Comment:

Inhibitors of P-glycoprotein reduce the renal and nonrenal elimination of digoxin. Digoxin plasma concentrations may increase two- to four-fold but larger increases may occur especially with potent P-glycoprotein inhibitors such as quinidine or amiodarone. Clarithromycin appears to cause greater increases in digoxin plasma concentrations than erythromycin or azithromycin. The mechanism for the substantial increase in digoxin concentrations following concurrent use of hydroxychloroquine is not established. Carvedilol (Coreg) may produce small increases in digoxin plasma concentrations, although larger increases have been reported in children. A metabolite of ezogabine inhibits P-glycoprotein and may increase plasma digoxin, but clinical reports are lacking.

Class 3: Assess Risk & Take Action if Necessary

• Consider Alternative:
• Macrolide Antibiotics: It is not known if dirithromycin* would interact with digoxin. (*not available in US)
• Monitor: Monitor for altered digoxin effect if one of these P-glycoprotein inhibitors is initiated, discontinued or changed in dosage; adjustments of digoxin dosage may be needed. Up to 10 days may be required for digoxin to achieve a new steady-state. If digoxin is initiated in the presence of therapy with one of these agents, consider conservative doses of digoxin.