SUMMARY  

• No clinical studies designed to investigate the potential for a drug-drug interaction between XARELTO and chloroquine or hydroxychloroquine have been conducted.
• Information relevant to drug interactions has been summarized from the respective pharmacological profiles of these agents.  
• Until further data regarding interactions between XARELTO and chloroquine or hydroxychloroquine are developed and published, careful monitoring of patients receiving these concomitant agents is advised.

PRODUCT LABELING

Please refer to the following sections of the enclosed Full Prescribing Information that are relevant to your inquiry: DRUG INTERACTIONS and CLINICAL PHARMACOLOGY.

Drug Interactions

Rivaroxaban is a substrate of cytochrome P450 (CYP) 3A4/5, CYP2J2, and the P-glycoprotein (P-gp) and ATP-binding cassette G2 (ABCG2) transporters.¹ Combined P-gp and strong CYP3A inhibitors increase exposure to rivaroxaban and may increase the risk of bleeding. Thus, it is recommended to avoid concomitant administration of XARELTO with known combined P-gp and strong CYP3A inhibitors. Combined P-gp and strong CYP3A inducers decrease exposure to rivaroxaban and may increase the risk of thromboembolic events. Thus, it is recommended to avoid concomitant use of XARELTO with drugs that are combined P-gp and strong CYP3A inducers.

QT/QTc Prolongation

In a thorough QT study in healthy men and women aged 50 years and older, no QTc prolonging effects were observed for XARELTO (15 mg and 45 mg, single-dose).¹

in vitro data

No clinical studies designed to investigate the potential for a drug-drug interaction between XARELTO and chloroquine or hydroxychloroquine have been conducted. In the absence of clinical data, relevant information from the respective pharmacological profiles of XARELTO, chloroquine, and hydroxychloroquine has been summarized.  

The respective XARELTO, chloroquine, and hydroxychloroquine product labels do not specifically specify a drug interaction.^1-3 In humans, chloroquine is metabolized into one major metabolite, N-desethylchloroquine (DCQ).^2,4 Using human liver microsomes and recombinant human CYP, Projean et al (2003) conducted in vitro studies to identify the CYP isoform(s) involved in the N-desethylation of chloroquine.⁴ Only DCQ could be detected in human liver microsomes incubated with chloroquine. At therapeutically relevant concentrations, CYP2C8, CYP3A4, and, to a much lesser extent, CYP2D6, were found to account for the majority of chloroquine N-desethylation. As mentioned above, rivaroxaban is a substrate of CYP3A4/5.¹ As both XARELTO and chloroquine are metabolized by the same CYP enzyme, the possibility of drug interaction cannot be ruled out.

Hydroxychloroquine, an analog of chloroquine, is metabolized into DCQ, as well as other active metabolites.^3,5 Thus, the possibility of drug interaction between XARELTO and hydroxychloroquine cannot be ruled out.

CARDIAC EFFECTS

Hydroxychloroquine sulfate tablets prolong the QT interval.³ Ventricular arrhythmias and torsades de pointes have been reported in patients taking hydroxychloroquine sulfate tablets. Hydroxychloroquine sulfate should not be administered with other drugs that prolong the QT interval and have the potential to induce cardiac arrhythmias. QT interval prolongation, torsades de pointes, and ventricular arrhythmias have also been reported with chloroquine.² Chloroquine should be used with caution in patients with cardiac disease, a history of ventricular arrhythmias, uncorrected hypokalemia and/or hypomagnesemia, or bradycardia, as well as during concomitant administration with QT interval prolonging agents, due to potential for QT interval prolongation. As mentioned above, no QTc prolonging effects were observed for XARELTO in a QT study conducted in healthy men and women ≥50 years of age.¹

Until further data regarding interactions between XARELTO and chloroquine or hydroxychloroquine are developed and published, careful monitoring of patients receiving concomitant XARELTO and chloroquine or hydroxychloroquine is advised.

Literature Search

A literature search of MEDLINE^®, EMBASE^®, BIOSIS Previews^®, DERWENT^® (and/or other resources, including internal/external databases) was conducted on 07 February 2025.