The anticoagulant rivaroxaban (Xarelto), which was originally approved last July for postoperative prevention of venous thrombosis and pulmonary embolism after hip- or knee-replacement surgery, has now been approved by the Food and Drug Administration for the prevention of stroke in patients with nonvalvular atrial fibrillation. In clinical trials rivaroxaban was associated with a decrease in the incidence of stroke comparable to that seen with warfarin. As with all anticoagulants, rivaroxaban can induce bleeding, and the bleeding can be serious. Although in clinical trials rivaroxaban carried a risk of serious bleeding similar to that of warfarin, the site of bleeding was different: rivaroxaban caused less bleeding in the brain than warfarin but more in the stomach and intestines.
Rivaroxaban is an inhibitor of clotting factor Xa (the active form of clotting factor X); it blocks the active site of factor Xa, preventing the cascade of events that produces a blood clot. It is taken orally at night with the evening meal (food increases the bioavailability of the drug). Rivaroxaban carries two boxed warnings. The first is that the risk of stroke will increase if the drug is discontinued. If the drug must be discontinued, another anticoagulant should be started. (That isn't the case if the drug is discontinued because of severe bleeding.) The second is that epidural or spinal hematomas can occur if the patient receiving rivaroxaban undergoes spinal puncture or receives neuraxial anesthesia. These hematomas can lead to long-term or even permanent paralysis.
The drug is highly (92% to 95%) protein bound. Metabolism of the drug depends on two isoenzymes in the cytochrome P-450 (CYP) system, CYP3A4 and CYP2J2. About a third of the drug is excreted unchanged in the urine. Patients with mild-to-moderate (Child–Pugh class B or C) hepatic disease or with hepatic disease associated with bleeding disorders shouldn't receive rivaroxaban. Patients with diminished renal function (on measurement of creatinine clearance) will have elevated circulating levels of rivaroxaban, and more anticoagulant effects will be noted. Those with a creatinine clearance between 15 and 50 mL/min should therefore receive a lower dose, and those with a creatinine clearance lower than 15 mL/min shouldn't be prescribed rivaroxaban.
Switching from warfarin to rivaroxaban requires stopping warfarin and starting rivaroxaban as soon as the international normalized ratio is less than 3, in order to prevent thrombus formation. There's no clinical trial information regarding the best method of switching from rivaroxaban to warfarin, although the label suggests starting both a parenteral anticoagulant and warfarin at the time rivaroxaban would next have been administered. If the patient is switching from an anticoagulant other than warfarin, the recommendation is to start rivaroxaban either at the time of the next scheduled evening dose or up to two hours prior to the time of the next scheduled dose of that drug. To move from rivaroxaban to a rapid-onset anticoagulant, rivaroxaban should be stopped and the other anticoagulant started at the time of the next rivaroxaban dose.
Nurses administering rivaroxaban should confirm that hepatic and renal function are adequate for use of the drug. The patient's albumin status should be assessed because of the drug's protein-binding activity. Administering rivaroxaban with other drugs that inhibit the CYP3A4 isoenzyme, such as ketoconazole (Nizoral and others), itraconazole (Sporanox), lopinavir with ritonavir (Kaletra, Aluvia), ritonavir (Norvir), indinavir with ritonavir, and conivaptan (Vaprisol), should be avoided because they can cause significant increases in circulating levels of rivaroxaban. Teach patients to be alert for signs of bleeding, and instruct them to report any signs at once. Also teach them the importance of not discontinuing therapy, which greatly increases the risk of stroke, without direction from the prescriber. For the complete prescribing information, see http://1.usa.gov/uxh6AC.