Welcome to Lesson 2 of this learning activity titled Medication Review, DOACS vs. Warfarin. The content in this lesson was developed by myself, Kate Malish, and I will also be narrating this lesson. Picking up from Lesson 1, let's look at another diagram of the clotting cascade and see where the direct oral anticoagulants take effect. We learned that Warfarin acts on four different clotting factors. However, our direct oral anticoagulants, or DOACS, act on only one clotting factor. Rivaroxaban, Apixaban, Edoxaban, and the newest Vitrixaban directly inhibit Factor Xa. Dabigatran directly inhibits Factor IIa, which is thrombin. Another direct thrombin inhibitor is the IV medication Argatraban. We will now examine the DOACS individually. Our first DOAC is Rivaroxaban, which was the first approved Factor Xa inhibitor. Brand name Xarelto, this medication is indicated for stable coronary or peripheral artery disease. Non-valvular atrial fibrillation and treatment of DVT and PE. It is also used for venous thromboembolism prophylaxis in acutely ill patients or those having hip or knee replacement. Finally, Rivaroxaban can be given to patients with certain disease states which require indefinite anticoagulation. You will notice that DOACS as a class have a much faster onset of action time compared to Warfarin. They also have a shorter half-life, which as you recall is the time it takes for the medication to be half as potent. Rivaroxaban's onset of action is 2-4 hours and the half-life is 7-13 hours. The dosing regimen is once daily. Although there are no specific foods which affect Rivaroxaban, it does have drug-drug interactions the patient should be aware of. Drugs which can decrease the effectiveness of Rivaroxaban and therefore make the patient more susceptible for a blood clot include rifampin, carbamazepine, phenytoin, phenobarbital, and the herbal St. John's wort. Drugs which may increase the effectiveness of Rivaroxaban and therefore may increase bleeding include ketoconazole, itraconazole, and the HIV medication ritonavir. The dosing of Rivaroxaban is dependent on the indication. While most regimens are once daily, the exception is patients taking it for CAD or PAD. This patient should take 2.5 mg twice daily along with their once daily 81 mg aspirin. Patients with non-valvular atrial fibrillation take 20 mg once daily with their evening meal. Patients with DBT or PE take 15 mg twice daily with food for 21 days, then 20 mg once daily with food. But only doses of 15 mg or more should be taken with food, otherwise patients may take Rivaroxaban without regards to meals. Patients taking this medication to prevent venous thromboembolism take 10 mg once daily for 31 to 39 days, while those undergoing hip or knee replacement take 10 mg once daily at least 6 to 10 hours post-surgery, then for 10 to 14 days after surgery. It is important to note that patients with a BMI greater than 40 or who weigh greater than 120 kg should avoid use of Rivaroxaban as it has been shown to be ineffective. Our next DOAC to review is Apixaban, commonly known by its brand name Eliquis. Apixaban is indicated for post-DVT or PE treatment, as well as prophylaxis for DVT or PE following hip or knee replacement. Finally, it is used to prevent stroke in patients with non-valvular atrial fibrillation. Apixaban has similar pharmacology to Rivaroxaban, with an onset of action of 3 to 4 hours and a half-life of 8 to 15 hours. Apixaban is dosed twice daily for all indications. Similar to Rivaroxaban, Apixaban's effectiveness may decrease when a patient is concomitantly taking rifampin, phenobarbital, or phenytoin. An interesting interaction with Apixaban is grapefruit and grapefruit juice, which can increase the effectiveness of Apixaban and thus put the patient more at risk for bleeding. Apixaban may be taken without regard to food. Dosing for post-DVT or PE is 10 mg twice daily for 7 days, followed by 5 mg twice daily thereafter. Non-valvular atrial fibrillation patients also take 5 mg twice daily. Post-operative surgical patients needing Apixaban for VTE prophylaxis take 2.5 mg twice daily, including 12 to 24 hours post-op. A well-established dose adjustment for Apixaban in patients with non-valvular atrial fibrillation is to lower a 5 mg twice daily dose to 2.5 mg twice daily if the patient has two of the following parameters, age greater than 80 years, body weight less than 60 kg, or serum creatinine greater than or equal to 1.5 mg per deciliter. When a patient has any two of these parameters, the dose should be lowered to 2.5 mg twice daily. Our next DOAC to review is Edoxaban, a slightly lesser-known DOAC than Ribaroxaban and Apixaban. Its brand names are Lixiana and Sevesa. It is indicated for strict prevention in non-valvular atrial fibrillation and for DVT and PE prophylaxis in treatment. It is important to note that Edoxaban is not approved for prevention of venous thromboembolism after hip or knee replacement surgery. The onset of action for Edoxaban is 2-4 hours and the half-life is 10-14 hours. Edoxaban is dosed once daily. Like the other DOACs, Edoxaban's effectiveness may be decreased when patients also take rifampin while those taking ketoconazole or dronetarone may have an increased effect. The dosing for patients with non-valvular atrial fibrillation is 60 mg once daily. Those treating a DVT or PE who weigh greater than 60 kg also take 60 mg once daily while those weighing less than or equal to 60 kg should only take 30 mg once daily. Edoxaban should not be used in atrial fibrillation patients with a creatinine clearance greater than 95 mL per minute. Since Edoxaban is metabolized by the kidneys, a patient with a high creatinine clearance will metabolize the medication at a faster rate, thus making the drug less effective and putting the patient at a higher risk for stroke. Conversely, patients weighing less than 55 kg have increased exposure to Edoxaban by 13% and will therefore require a smaller dose. Our last DOAC is Dabigatran, brand name Pradaxa. Dabigatran has a different mechanism of action, which is to directly inhibit thrombin or factor 2A. Its indications are the same as Edoxaban, which are reduction of stroke in non-valvular AFib patients and treatment or prophylaxis for DVT or PE. Dabigatran is also not indicated for venous thromboembolism prophylaxis after hip or knee replacement. Dabigatran has the shortest onset of action, which is 1 to 2 hours. Its half-life is 12 to 17 hours. The dosing regimen is twice daily. Like other DOACs, patients taking Rifampin may have decreased effect of Dabigatran, while those taking Ketoconazole or Dronetarun may have an increased effect. Dosing for non-valvular atrial fibrillation is 150 mg twice daily, as is the dosing for DVT or PE treatment. Those being treated for DVT or PE should be started on an IV anticoagulant for 5 to 10 days, then begin taking oral Dabigatran. Dabigatran is 80% renally eliminated, therefore patients with renal insufficiency should take a reduced dose or avoid this medication entirely. Here is a nice chart to summarize the major differences between DOACs. As you can see, both Idoxaban and Dabigatran require IV anticoagulation before starting for certain conditions, while Apixaban and Rivaroxaban do not. Rivaroxaban is the only DOAC that must be taken with food when the dose is 15 mg or greater. DOACs are either once daily or twice daily dosing, with certain dose adjustments previously mentioned. All DOACs can be crushed, except for Dabigatran. This is helpful when a patient cannot swallow pills or has a feeding tube. Finally, all DOACs, except for Idoxaban, have a reversal agent, although those agents are not as readily available as those for Warfarin and are very expensive. We will discuss reversal agents in the next lesson when we compare and contrast DOACs with Warfarin. This concludes Lesson 2 of Medication Review, DOACs vs. Warfarin. Thank you for your participation.

DOACs vs. Warfarin

direct oral anticoagulants

Rivaroxaban

Apixaban

Edoxaban