https://interactions.guidetherapeutiquevih.com/en/interaction-details?id=12295

Ritonavir

Apixaban

Avoid association.

Available pharmaceutical opinion

Document made available to the pharmacist to communicate a drug interaction to the doctor.

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Mechanism

Ritonavir can inhibit the CYP 3A4 and P-gp and increase the plasma concentration of Apixaban.

Ritonavir

Pharmacodynamic effects

–

Recommendations

If possible, consider an alternative.

Alternative solution(s)

Depending on previous virological failures and genotype reports, doravirine or rilpivirine, or even dolutegravir, raltegravir or bictegravir.

Apixaban

Pharmacodynamic effects

Increased risk of severe bleeding including hemorrhage.

Recommendations

The canadian monograph contraindicates this combination.

For patients receiving a 5 or 10 mg BID dose of apixaban, the US Product Monograph suggests a 50% dose reduction when given with potent CYP3A4 or P-gp inhibitors.

This combination, however, should be avoided in patients already taking apixaban 2.5 mg BID or with two or more risk factors for bleeding (elderly ≥ 80 years, low weight ≤ 60 kg, serum creatinine ≥ 133 μmol/L).

Monitor the clinical efficacy and appearance of adverse effects.

See comments for further details.

Alternative solution(s)

Prefer warfarin or low molecular weight heparin (LMWH).

Monitor

Adverse effects of apixaban : nausea, symptoms of bleeding and anemia. We should also follow CBC closely to detect thrombocytopenia and anemia that may result from apixaban administration.

Tests

–

Pharmacokinetic parameters

–

Comment

Ref #2690 : A pharmacokinetic study with a strong CYP3A4 inhibitor, ketoconazole, has shown an increase in apixaban AUC and Cmax of 2-fold and 1.6-fold, respectively. With diltiazem, a moderate CYP3A4 inhibitor, an increase was observed in apixaban AUC and Cmax of 1.3-fold and 1.4-fold, respectively.

Real-world retrospective studies and case reports also report interactions of combined P-gp and CYP 3A4 inhibitors with apixaban.

Currently available data are not sufficient to define a clear recommendation. In addition, we do not have a specific marker to monitor the efficacy of apixaban or antidote.

Thus, the apixaban monograph considers as contraindicated concomitant administration of this drug with agents that inhibit both CYP3A4 and P-gp. Warfarin can be used as an alternative (see warfarin and PI/r).

However, if the association can be avoided, the American monograph recommends lowering the dose to 2.5 mg BID if the patient has no risk factors for bleeding. The association, however, should be avoided in patients already taking apixaban 2.5 mg bid or with two or more risk factors for bleeding (elderly ≥ 80 years, low weight ≤ 60 kg, serum creatinine ≥ 133 μmol/L).

Ref #3695 : This article reports the successful use of reduced dose apixaban to treat and prevent thromboembolic complications in six people living with HIV on ART boosted with ritonavir or cobicistat and may support US recommendations.

Comment
Reference
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