Apixaban is an oral anticoagulant. It belongs to the drug class: Direct Oral Anticoagulant (DOAC).
DOACs were introduced in 2010 as an alternative to warfarin. They address alot of the complexities associated with the use of warfarin.
Warfarin is effective within a very narrow therapeutic range. This window of efficacy is easily disrupted by many drug interactions, food interactions and acute illness.
Because of this, warfarin requires regular and often frequent monitoring of blood levels to ensure that patients are anticoagulated enough to prevent thrombosis but not too much that they are high risk for a major bleed. The study unit on WARFARIN provides an in depth analysis of the drug.
In comparison DOAC including apixaban have a better safety and efficacy profile with a more rapid and predictable onset compared to warfarin.
They do not require frequent blood monitoring and there are very few drug and food interactions.
There are 2 subcategories of DOAC based on the mechanism of action: direct thrombin inhibitors and Xa inhibitor. Apixaban is a Xa inhibitor.
Mechanism of Action
Apixaban is a factor Xa inhibitor. It inhibits clotting factor Xa, the first factor activated in the common pathway of the coagulation cascade.
The mechanism of action of apixaban cannot be understood without knowledge of the coagulation cascade. The unit What You Need to Know: Hemostasis covers the coagulation cascade in detail.
The diagram below illustrates where in the coagulation cascade apixaban works.
Indications
Apixaban also has a growing list of indications that include:
- atrial fibrillation
- heparin induced thrombocytopenia
- treatment and prevention of DVT and PE
- prophylaxis against DVT/PE post hip/knee surgery
Subscribe for Access to Exclusive Content
The Aristotle Trial
The Aristotle trial compared apixaban to warfarin in patients with atrial fibrillation in need of anticoagulation.
Efficacy was determined by the occurrence of stroke and systemic embolism in each group.
Safety was determined by the rate of major bleed in each group.
Apixaban was found to be superior to warfarin in preventing stroke or systemic embolism and caused less bleeding.
Availability & Administration
Apixaban is available as oral tablets. It can be given without regard to meals. If the patient is unable to swallow whole tablets, they can be crushed and suspended in 60cc of water, D5W, apple juice or mixed with applesauce. The preparation should be administered immediately but is stable for up to 4 hours.
Missed Doses
If a dose is missed, the dose should be taken as soon as possible on the same day and twice daily administration should be resumed. The dose should not be doubled to make up for a missed dose.
Dosing
The standard dosing of apixaban is 5mg twice daily. Higher dosing is required in the initial treatment of DVT and PE.
Renal dosing of apixaban is unique in that it is based on 3 patient characteristics: age, body weight and serum creatinine. A dose reduction to 2.5mg is recommended if a the patient meets any 2 of these criteria.
serum creatinine > 1.5mg/dL + (>80 yo OR <60kg) = 2.5mg BID
serum creatinine <1.5mg/dL = (> 80yo AND <60kg) = 2.5mg BID
Drug Interactions
Strong dual inhibitors of CYP3A4 and P-gp increase blood levels of apixaban. The recommendation is to reduce apixaban dose to 2.5 mg or avoid concomitant use. Clinically relevant inhibitors include cobicistat, itraconazole, ketoconazole, ritonavir and posaconazole.
Simultaneous use of strong inducers of CYP3A4 and P-gp reduces blood levels of apixaban. For inducers, the recommendation is to avoid concomitant use. Clinically relevant inducers include carbamezapine, fosphenytoin, phenytoin and rifampin.
If you’ve found this unit helpful, I would love to hear from you! Leave a question or comment below.
Subscribe
Subscribe to get the latest study unit in your inbox.
The information on this website is intended to be used solely for educational and informational purposes. While the content may be about specific medical and health care issues, it is not a substitute for or replacement of personalized medical advice and is not intended to be used as the sole basis for making individualized medical or health-related decisions.