Table 4.
Types of Interaction | Mechanism of Interaction | Interaction Management | |
---|---|---|---|
Lopinavir/Ritonavir or Atazanavir plus Clopidogrel | Pharmacokinetic | Ritonavir and atazanavir might inhibit clopidogrel (a pro-drug) metabolism to its active metabolite so it result in the diminished antiplatelet activity. | Avoid combinations and consider possible alternatives. |
Lopinavir/Ritonavir or Atazanavir plus Ticagrelor | Pharmacokinetic | Strong CYP3A4a inhibitors would enhance the serum concentration of ticagrelor and reduce the serum concentration of its active metabolites. | Avoid a combination of ticagrelor with strong CYP3A4 inhibitors and consider alternatives. |
Lopinavir/Ritonavir or Atazanavir plus Rivaroxaban | Pharmacokinetic | Since rivaroxaban is a substrate for both CYP3A4 isoenzyme and P-gpb, concomitant administration of this drug with strong inhibitors of CYP3A4 and inhibitors of P-gp may enhance the serum concentration of rivaroxaban and risk of major bleeding. | Avoid a combination of rivaroxaban with strong CYP3A4 inhibitors and P-gp inhibitors. |
Lopinavir/Ritonavir or Atazanavir plus Apixaban | Pharmacokinetic | These concomitant administrations might result in inhibition of CYP3A4 mediated metabolism and P-gp induced efflux of apixaban which may cause enhanced serum concentration of apixaban and bleeding complications. | A combination of apixaban with strong CYP3A4 inhibitors and P-gp inhibitors is contraindicated. |
Lopinavir/Ritonavir or Atazanavir plus Edoxaban | Pharmacokinetic | Inhibitors of P-gp/ABCB1c might enhance the Cmaxd, AUCe, and anticoagulant effect of edoxaban. | A combination of edoxaban with P-gp/ABCB1 inhibitors should be avoided or dose adjustment should be considered in patients with venous thromboembolism. No dosage modification is available in patients with non-valvular atrial fibrillation. |
Lopinavir/Ritonavir or Atazanavir plus Dabigatran etexilate | Pharmacokinetic | Inhibitors of P-gp/ABCB1 could enhance the serum concentration of active metabolites of dabigatran etexilate, which is a pro-drug agent. These drug–drug interactions would be significantly precipitated in patients with moderate to severe renal failure. | Avoid combination or consider therapy modification. Dose adjustment may also be considered according to the patients’ renal function, dabigatran etexilate indications, and labeling recommendations. |
Notes: aCytochrome P450 (CYP) 3A4. bP-glycoprotein. cATP-binding cassette sub-family B member 1. dMax serum concentration. eArea under the curve.