Based on theoretical considerations darunavir/cobicistat is expected to increase digoxin plasma concentrations (P-glycoprotein inhibition). It is recommended that the lowest possible dose of digoxin should initially be given to patients on darunavir/cobicistat. The digoxin dose should be carefully titrated to obtain the desired clinical effect while assessing the overall clinical state of the subject.

Coadministration is expected to increase digoxin concentrations. When co-administering with digoxin, titrate the digoxin dose and monitor digoxin concentrations.

A case was reported of a 51-year-old man taking digoxin (0.25 mg, once daily) who experienced digoxin toxicity (nausea, vomiting and weight loss) and atrial flutter after being prescribed darunavir (800 mg), ritonavir (100 mg), dolutegravir (50 mg) and rilpivirine (25 mg). After withdrawal of digoxin and changing his ART to efavirenz, abacavir and dolutegravir, his symptoms abated and his ECG was normal. The authors hypothesise a drug-drug interaction occurred via inhibition of P-gp by darunavir and ritonavir.