https://interactions.guidetherapeutiquevih.com/en/interaction-details?id=13615
https://interactions.guidetherapeutiquevih.com/en/interaction-details?id=13615
No pharmaceutical opinion available for this interaction.
Cobicistat can inhibit the intestinal P-gp and increase the plasma concentration of Dabigatran.
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Avoid association.
Choose an antiretroviral that does not have this interaction.
Possible increase of adverse effects.
Choose an alternative.
If this combination cannot be avoided, give only after considering increased risk of bleeding: co-administration with antiplatelet (including aspirin or NSAIDs), age > 75 years, weight < 60kg, impaired renal function, systemic corticosteroids,
history or active gastrointestinal bleeding, recent surgery (eyes, brain), thrombocytopenia (eg chemotherapy), HAS-BLED ≥ 3.
Use this combination with caution.
See comments.
Prefer warfarin or low molecular weight heparin (LMWH).
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| Reference number |
|---|
| # patients |
| HIV |
| Dose |
| Frequency |
| Cmax |
| AUC |
| 3341 | 3341 |
|---|---|
| 16 | 16 |
| - | - |
| 150 mg | 150 mg |
| QD | QD |
| 3341 | 3341 |
|---|---|
| 16 | 16 |
| - | - |
| 150 mg * | 150 mg † |
| x 1 * | x 1 † |
| + 99% (2x) | + 127% (2.3x) |
| + 110% (2.1x) | + 127% (2.3x) |
Ref #3341 : * Dabigatran given 2 hours before cobicistat.
† Dabigatran given simultaneously with cobicistat.
Unlike ritonavir, cobicistat significantly increased dabigatran concentrations weither being administered simultaneously or 2 hours after dabigatran. The anticoagulant effect was also increased, with a 46-51% increase in thrombin time (TT) at 24 hours and a 30-33% increase in TT-AUC. Researchers conclude that dabigatran should be co-administered with cobicistat with caution by decreasing dabigratran dosing or by spacing administration with cobicistat by ≥4 hours, in addition with close monitoring of its anticoagulant effect.
The product monograph recommended dose adjustments when used for prevention of venous thrombophlebitis after surgery:
A. With potent P-gp inhibitors (as ketoconazole): Avoid administration.
B. With P-gp inhibitors (amiodarone, quinidine, verapamil°): Consider dose reduction. See product monograph for indications.
C. With P-gp inhibitors (amiodarone, quinidine, vérapamil°) and moderate renal impairment (ClCre 30-50 ml/min) : Consider a greater dose reduction. See product monograph for indications.
D. With other P-gp inhibitors (cyclosporine, itraconazole, posaconazole, nelfinavir, ritonavir, saquinavir) : Exercer un suivi plus étroit.
° For verapamil, it is also recommended to avoid concurrent administration. Give dabigatran 2 hours before verapamil.