1. Rivaroxaban is a drug used as deep vein thrombosis (DVT) prophylaxis for patients who underwent hip or knee replacement surgery. It can also be used as treatment for deep vein thrombosis and/or pulmonary embolism and as prophylaxis in patients who are at risk for venous thromboembolism due to their restricted mobility, or other factors. It is also used in patients who suffer from nonvalvular atrial fibrillation to reduce the risk of stroke and systemic embolism. Patients who take this drug were also noted to have a reduced risk for major cardiovascular events.
2. Rivaroxaban (Brand Name: Xarelto) falls under the class of Anticoagulants, specifically Factor Xa Inhibitors.
3. Rivaroxaban is a Factor Xa inhibitor. The drug works by inhibiting platelet activation through the selective blocking of the Factor Xa active site. This results in the blockage of the common pathway of coagulation from both the intrinsic and extrinsic pathway. In addition, Rivaroxaban also exerts a dose-dependent effect on antifactor Xa, thus further prolonging prothrombin time (PT), activated partial thromboplastin time (aPTT), and HepTest.
4. Rivaroxaban is absorbed rapidly by the stomach, with the maximum plasma concentration noted at around 2-4 hours after intake of the tablet. There is a 29-56% decrease in its bioavailability when the drug is released in the proximal intestine compared to when it is absorbed by the stomach, and a further decrease when it is released in more distal locations of the gastrointestinal tract. For its distribution, about 92-95% of Rivaroxaban is protein-bound, mainly by albumin. It has a volume of distribution of approximately 50 liters (0.62 L/kg) and has low tissue penetration. For its metabolism, about 90% of Rivaroxaban circulates in plasma as unchanged drug, as this drug does not have any major or active metabolites. About 50% of Rivaroxaban taken orally is metabolized by hepatic enzymes: CYP3A4 (18%), CYP2J2 (14%), and CYP-independent hydrolytic cleavage (14%). The drug has a 5-9 hour half-life, or 11-13 hours for the elderly. It is excreted in the urine and feces, both as metabolites and as unchanged drug.
5. For prophylaxis of deep venous thrombosis, patients are prescribed Rivaroxaban 15 mg/tablet 1 tablet to be taken orally twice daily (one tab every 12 hours) for the first 21 days. From days 22-90, the dosage is reduced to Rivaroxaban 20 mg/tablet 1 tablet to be taken orally once daily. After the 90th day or 3 months, patients are required to follow-up with their physician to determine whether or not the drug should still be continued.
6. Rivaroxaban is typically well-tolerated, with predictable pharmacokinetics, not affected by age, gender, body weight, or race. There is maximal inhibition of Factor Xa activity after 3 hours, with the drug’s effects maintained for 12 hours. The drug reaches a steady state concentration in the body after 7 days. Although PT, aPTT, and HepTest were prolonged, there were no clinically significant changes to the bleeding time. The drug also does not accumulate in concentration beyond the steady state.
7. Rivaroxaban should be taken with food as it enhances the bioavailability of the drug. Without food, it is only at 66%, but with food, bioavailability nears 100%. This decrease in absorption is due to the limited aqueous solubility of the drug at doses as high as 20 mg. Taking antacids or Ranitidine does not have an influence on drug absorption. It is also advisable to discontinue Rivaroxaban at least 24 hours prior to any surgical procedure.
8. Side effects are those that are anticipated due to the use of the drug, and it is in line with the drug’s mechanism of action. For Rivaroxaban, it is hematoma formation and major bleeding. <1% of patients taking the drug for DVT prophylaxis are at risk for bleeding events including retroperitoneal hemorrhage, cerebral hemorrhage, subdural hematoma, epidural hematoma, and spinal hematoma. Adverse effects are those effects unrelated to the drug’s mechanism of action. There are several adverse effects of Rivaroxaban which includes back pain, abdominal pain, dizziness, pruritus and hypersensitivity, pain in the extremities, insomnia, anxiety, blister formation, fatigue, muscle spasm, syncope, hepatitis, and depression.
9. Patients with major bleeding may present with symptomss of blood loss such as lightheadedness, fatigue, and pallor. Medical consult should be sought, and the patient may be transfused with blood in severe cases. Patients who have gastrointestinal bleeding may present with non-localizing abdominal or low back pain or dark-colored or bloody stools. Patients presenting with cerebrovascular bleeding or bleeding in the spine may present with mental status changes, weakness, paresthesias, or paralysis, which may be long-term or permanent. Urgent consult at the emergency department is required in these cases.
10. Any pains felt due to Rivaroxaban intake can be managed with analgesics, however these need to be taken with caution if the analgesic also affects hemostasis. Any pruritus/itchiness or hypersensitivity (presenting as rashes and swelling) reactions can be managed with Claritin 10 mg/tablet 1 tablet taken once daily, ideally at night. This drug also induces drowsiness in some, so this can also address insomnia. However, if the hypersensitivity becomes severe and uncontrollable, patients are advised to seek medical consult. Hepatitis, which may present as right-upper quadrant abdominal pain and jaundice, will require consult with a gastroenterologist. Depression, which presents as a feeling of sadness or loss of interest in the patient’s usual activities or hobbies, will require psychiatric consult.
11. Since Rivaroxaban is metabolzed by CYP3A4/5, CYP2J2, and the P-gp and ATP-binding casette G2 (ABCG2) transporters, it is not recommended that Rivaroxaban be taken with ketoconazole, itraconazole, lopinavir/ritonavir, and conivaptan, as it may increase the risk of bleeding. Concomitant use of Rivaroxaban with erythromycin, azithromycin, verapamil, quinidine, ranolazine, dronedarone, amiodarone, felodipine, citalopram, escitalopram, fluoxetine, fluvoxamine, desvenlafexine, and venlafaxine should be done with caution. Concomitant use of Rivaroxaban with carbamazepine, phenytoin, rifampin, and St. John’s wort decrease the systemic effects and efficacy of Rivaroxaban, thus increasing the risk of thromboembolic events. Concomitant use of Rivaroxaban with drugs that impair hemostasis such as aspirin, clopidogrel, and non-steroidal anti-inflammatory drugs may increase the risk of bleeding.
12. Upon follow-up at 90 days, the patient is assessed for any thromboembolic and bleeding events, compliance to the medication, development of side-effects, prescription of other drugs, and modifiable risk factors. Blood may also be drawn to further work-up the patient. It is at this time when the physician will decide whether or not the drug should still be continued.
13. If the patient presents with recurrent or persistent pain, recurrent or persistent allergic reactions, or is scheduled for surgery, the patient should contact his/her physician to seek advise on what to do. The physician may advise a temporary or permanent discontinuation of the drug, or a shift to another drug in the same or different class.
14. Clients should immediately call 911 or proceed to the emergency department if the patient presents with symptoms of gastrointestinal bleeding, such as dark-colored or bloody stools and worsening abdominal or back pain, or if the patient presents with any symptoms of neurological impairment, such as changes in the mental status, weakness, paresthesias or paralysis.