Postoperative Bleeding After Administration of a Single Dose of Rivaroxaban to a Patient Receiving Antiretroviral Therapy.

Article Details

Citation

Corallo CE, Grannell L, Tran H

Postoperative Bleeding After Administration of a Single Dose of Rivaroxaban to a Patient Receiving Antiretroviral Therapy.

Drug Saf Case Rep. 2015 Dec;2(1):11. doi: 10.1007/s40800-015-0014-4.

PubMed ID
27747723 [ View in PubMed
]
Abstract

A 62-year-old man was admitted to hospital for elective revision of a left total hip arthroplasty. His history was significant for human immunodeficiency virus (HIV) infection for which he was taking the following antiretroviral agents (ARVs): etravirine, ritonavir, darunavir, raltegravir and tenofovir/emtricitabine. Rivaroxaban 10 mg daily was commenced on the second postoperative day for venous thromboembolism (VTE) prophylaxis. Approximately 24 h later, the patient developed hypotension and anaemia, accompanied by thigh swelling due to bleeding at the surgical site. Fluid resuscitation was commenced with red cell transfusion. The prothrombin time (PT) was prolonged at 24.3 (10.6-15.3) s, and a rivaroxaban level taken 24 h after administration was 75 ng/mL. Rivaroxaban was ceased, the PT normalised within 24 h of stopping the drug, and the patient made an uneventful recovery. None of the other coadministered drugs are known to interact with rivaroxaban, or are likely to, based on their metabolic pathways. Rivaroxaban, a substrate for cytochrome P450 (CYP) 3A4 and P-glycoprotein (P-gp), is contraindicated in patients concomitantly treated with strong inhibitors of both these systems, e.g. protease inhibitors (PIs) such as ritonavir (based on in vitro data and a pharmacokinetic study in healthy volunteers). No published data are available on the PI darunavir, a moderate inhibitor; however, concomitant use with rivaroxaban should also be avoided. A prolonged PT and a rivaroxaban trough level greater than eight times that predicted from pharmacokinetic modelling suggests that bleeding was due to increased exposure to rivaroxaban, probably due to an interaction with ritonavir and darunavir. This is supported by a Drug Interaction Probability Scale (DIPS) score of 8. An interaction between a single dose of rivaroxaban and ARVs may be clinically significant; therefore, the patient's medication history should be extensively evaluated to identify any potential interactions.

DrugBank Data that Cites this Article

Drug Transporters
DrugTransporterKindOrganismPharmacological ActionActions
RitonavirP-glycoprotein 1ProteinHumans
Unknown
Substrate
Inhibitor
Inducer
Details
Drug Interactions
DrugsInteraction
Abemaciclib
Bortezomib
The serum concentration of Abemaciclib can be increased when it is combined with Bortezomib.
Abemaciclib
Morphine
The serum concentration of Abemaciclib can be increased when it is combined with Morphine.
Abemaciclib
Tenofovir disoproxil
The serum concentration of Abemaciclib can be increased when it is combined with Tenofovir disoproxil.
Abemaciclib
Digoxin
The serum concentration of Abemaciclib can be increased when it is combined with Digoxin.
Abemaciclib
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The serum concentration of Abemaciclib can be increased when it is combined with Gemcitabine.
Abemaciclib
Bisoprolol
The serum concentration of Abemaciclib can be increased when it is combined with Bisoprolol.
Abemaciclib
Mannitol
The serum concentration of Abemaciclib can be increased when it is combined with Mannitol.
Abemaciclib
Sirolimus
The serum concentration of Abemaciclib can be increased when it is combined with Sirolimus.
Abemaciclib
Clomifene
The serum concentration of Abemaciclib can be increased when it is combined with Clomifene.
Abemaciclib
Fexofenadine
The serum concentration of Abemaciclib can be increased when it is combined with Fexofenadine.
Interactions
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