The ability to augment the properties of blood coagulation for patients suffering from hypercoagulable states has been one of the most important advances in the history of modern medicine. Clots, DVTs (deep vein thrombosis), and strokes use to spell dire circumstances with an unfavorable prognosis to the individuals affected. Fortunately, in today’s modern world we have implemented the use of blood thinner drugs that effectively prevent fatal outcomes that blood clots present. One medication being used is Savaysa, also known by its generic name, Edoxaban. In this article, we will discuss how Savaysa medication can be used in clinical practice, its mechanism of action as well as detailing various Savaysa dosing regimens, Savaysa side effects, in addition to Savaysa Edoxaban comparison to other blood thinner drugs.
There are many different kinds of anticoagulation medications on the market today, falling into different classes that work at various biochemical locations in the coagulation cascade. Although many do exist, they all have the singular purpose of reducing clot formation within the body during times where the physiology of the body promotes clotting; however, each anticoagulant may display unique characteristics that could be beneficial to the overall health of the individual it’s being used on, such as effect reversibility or ease of use. Dosing of medication is also taken into account, as many variables are in play, from the type of venous thromboembolism to liver and kidney function.
Savaysa Dosing, and Mechanism of Action
Developed in Japan by the Daiichi Sankyo pharmaceutical company, Savaysa was approved for use in the prevention of venous thromboembolism following lower limb orthopedic surgery, a common phenomenon that occurs during the recovery phase of post-surgical procedures. These procedures increase the risk for a condition called Deep Vein Thrombosis (DVT); a blood clot commonly located in the lower limbs. This condition is dangerous as it can potentially travel through the venous arterial system that is connected to the heart, lungs and brain, and can potentially lead to cardiac arrest, pulmonary embolism (PE) or even stroke.
The Savaysa medication works by directly inhibiting factor Xa of the coagulation cascade; a series of coagulation factors that sequentially trigger with the ultimate goal of producing a stable clot, the sole purpose of which is preventing excessive blood loss. However, during circumstances where excessive blood clotting is exemplified, such as after an invasive surgery, these clots can become hazardous, breaking off into the blood stream and wreaking havoc elsewhere.
Factor Xa is the product of Factor X and promotes the enzymatic cleavage of Prothrombin to Thrombin, which in turn converts Fibrinogen to Fibrin; a fibrous protein involved in the clotting of blood. While this is a normal occurring phenomenon, when the body is put under high levels of stress these clots can grow, becoming so large that they can occlude entire vessels. This swelling prevents the circulation of blood called a thrombosis, or in the worst case break off the vessel becoming an emboli with the potential of traveling and getting lodged in vital organs. Savaysa dosing can be implemented to impede this vital step in the coagulation cascade, effectively reducing the risk of venous thromboembolisms and decreasing overall mortality rates.
Savaysa Dosing Treatment
Savaysa dosing has been approved in the United States for use in treating and preventing blood clots in certain patients. Helping to reduce clot formation and effectively decreasing the events of strokes as seen in patients with nonvalvular atrial fibrillation; a condition involving irregular heart rhythms called arrhythmias. This irregular heartbeat causes the heart to beat out of sync, decreasing its efficacy for pushing out blood and causing an abnormal amount of blood to accumulate in the heart and pooling in the heart chambers. This results in the spontaneous activation of the coagulation cascade, leading to clot formation. These clots can then easily travel through the blood vasculature, leading to ischemic infarction of brain tissue, or strokes. With proper anticoagulation, atrial fibrillation patients can reduce their risk of stroke by up to 80% when used properly.
Savaysa dosing is also approved for use in the treatment of deep vein thrombosis and pulmonary embolism. These two clot related conditions often occur one after the other, with pulmonary embolism occurring as a complication of a deep vein thrombosis.
Savaysa Clot Treatment
Beginning in the lower extremity a clot may manifest largely due to three processes, collectively called Virchow’s Triad; Venous stasis (decreased blood flow), hypercoagulability (an individual’s increased tendency to clot), and endothelial injury of blood vessels. Together all three create the ideal environment for clot formation. Once a clot is formed it can either become so large that it occludes the entire vessel leading to symptoms such as pain, swelling, and redness, but the real threat is the clot breaking off becoming an emboli. This newly freely floating clot in the bloodstream now has access to the venous circulation that leads back to the heart and lungs. If a clot were to reach all the way to the lung parenchyma, it can block the important structures for oxygen and carbon dioxide transfer leading the onset of shortness of breath, chest pain, and even sudden death in 15% of cases.
While currently approved by the FDA for use on American citizens, Savaysa Canada Health authorities are still in the process of reviewing the medication for use on Canadians. Savier Canada, a French research-based organization located in Quebec have announced a strategic agreement with the makers of Savaysa to commercialize the oral anticoagulant in Canada once approved by the proper channels, as Savaysa could help the nearly 350,000 Canadians currently affected by nonvalvular atrial fibrillation , with that number expected to rise as the population ages.
Savaysa INR/Edoxaban INR
Being a relatively new drug, many comparisons are drawn between the more widely used and recommended methods for anticoagulation, with many studies done to compare the effectiveness and safety of each in clinical scenarios. One such anticoagulant is Warfarin, a vitamin K inhibitor that achieves a similar level of anticoagulation. Having been used for decades for the treatment and prevention of venous thromboembolism, Warfarin is associated with various adverse effects due to its narrow therapeutic margin and wide variability of dose response in patients. An International Normalized Ratio (INR) is often used to monitor Warfarin which requires blood samples to be taken on a regular basis. This is the measure of how long it will take the blood to clot when using the anticoagulation medication compared to the bodies clotting times without the anticoagulant.
Savaysa INR/Edoxaban INR monitoring is virtually nonexistent, as it is not an accurate method to determine Savaysa INR/Edoxaban INR levels or its effectiveness for anticoagulation. In fact, Savaysa dosing is not required to be monitored at all, owing to the safety of administering fixed doses, and the predictability of anticoagulation activity. However if the circumstance were to arise where the plasma concentration of the specific savaysa dosing administered were to be measured, such as to determine if any clinically relevant anticoagulant effect is present, or to detect if the drug is present in excess, using liquid chromatography-mass spectrometry (LC-MS) or Anti-Xa activity levels can be useful. Generally, physicians take a more practical approach for Savaysa/Edoxaban monitoring, looking for signs and symptoms of bleeding complications, such as bruises, bloody gums, or blood in the stool or urine and making adjustments thereafter.
Savaysa Side Effects/Edoxaban Side Effects
Nearly all prescribed or over the counter medications have some form of undesirable side effect on the user. From rashes to gastrointestinal upset, medications designed to make enahnce our healthtend to have some if not many adverse effects that often make us feel worse, albeit only temporally. When augmenting the body’s natural mechanism for producing clots it is appropriate to assume that the anticoagulant medication being used may, in fact, work too well making the clotting process near impossible to initiate until the effects of the medication wear off. While some may consider this ideal, as stopping clot formation and therefore the potential complication for systemic emboli will efficiently reduce the risk of strokes, however, not being able to clot naturally gives rise to a whole new set problems, and in the case Savaysa side effects/ Edoxaban side effects, excessive bleeding is the most common making patients bruise easier and take longer for cuts and scrapes to stop bleeding. While these types of Savaysa side effects/Edoxaban side effects can be managed by simply adjusting Savaysa dosing or simply stopping the medication until the effects wear off (while still using a bridging anticoagulant to maintain adequate clot prevention), some patients prone to injury and poor wound healing, such as the elderly, may not recover in time. It is often to the discretion of the prescribing physician to weigh the pros and cons of particular medications and to determine whether the benefits are greater than the risks. It is also important as a patient to report any unusual side effect to your physician as soon as possible.
Common Side Effects
• Unusual bleeding/bruising
• Bloody nose
• Pale skin
• Heavy non-menstrual vaginal bleeding
• Trouble breathing with exertion
• Unusual tiredness or weakness
Less Common/Rare Side Effects
-Inability to move arms, legs, or facial muscles
-Nausea and vomiting
Savaysa Dosing Considerations
When comes to prescribing this particular anticoagulant, Savaysa dosing is a once daily oral pill that comes in three formats; 15mg, 30mg, and 60mg. While Savaysa dosing of 60mg is the most commonly prescribed amount given to adults with atrial fibrillation, it depends greatly on kidney function, as the kidneys are the main mode for clearing the drug from the body. It is documented that 50%-60% of Savaysa/Edoxaban is excreted by the kidneys, so patients with normal renal function may, clear more of the drug from the body decreasing the overall benefits of using Savana/Edoxaban.
The FDA has stated that patients with a creatinine clearance (a measure of kidney function) of >95ml/min to not use Savaysa/Edoxaban as it can be less effective for treating venous thromboembolisms due to the decreased levels of the drug in circulation, and therefore not adequate for the prevention of ischemic stroke. It is also important to note that for the treatment of DVT and PE requires 5-10 days of initial therapy with a parental anticoagulant, such as heparin before utilization of Savaysa/Edoxaban can be used.
Renal Dose Adjustments
Non Valvular Atrial Fibrillation Systemic emboli and stroke prevention
• CrCl >95ml/min: not recommended
• CrCl 51-95ml/min: 60mg
• CrCl 15-50ml/min: 30mg
• CrCl <15ml/min: not recommended Deep Vein Thrombosis or Pulmonary embolism Treatment • CrCl >50ml/min: 60mg
• CrCl 15-50ml/min: 30mg
• CrCl <15ml/min: not recommended
Other considerations need to be taken into account before a prescription of Savaysa/Edoxaban can be prescribed. The following some considerations:
Liver Dose Adjustments (according to Child-Pugh Score)
• Mild liver dysfunction: 60mg
• Moderate to severe dysfunction: Not recommended
Patients weighing ≤60kg
• Treatment for DVT or PE: 30mg
Switching from another Anticoagulant to Savaysa/Edoxaban
Gaining the knowledge of newer anticoagulants on the market may prompt you to want to switch from your current blood thinner, but it is important to speak to your physician about the various pros and cons of switching, for your own particular circumstance. It is important to take into consideration the health of your liver and kidneys for the aforementioned reasons, and the potential cost of medication, as newer pharmaceuticals tend to come at a premium. If you do have your heart set on making the switch or have already switched to Sayaysa and want to switch back to your previous warfarin treatment, there are important drug switching regimens that need to take place in order to maintain adequate anticoagulation during the transition phase.
Switching to Savaysa/Edoxaban from another anticoagulant:
• From Warfarin: discontinue Warfarin and start Savaysa/Edoxaban when the INR is 2.5 or less
• From low molecular weight Heparin (LMWH): Discontinue LMWH and start Savaysa/Edoxaban at the time of the next scheduled LMWH dose
• From unfractionated Heparin: Discontinue the infusion and start Savaysa/Edoxaban 4 hours later
Switching from Savaysa/Edoxaban to Warfarin (oral option):
• For patients on 60mg Savaysa/Edoxaban, reduce to 30mg and begin parallel warfarin therapy
• For patients on 30mg Savaysa/Edoxaban, reduce to 15mg and begin parallel warfarin therapy
• Measure INR at least weekly and just prior to the daily dose of Savaysa/Edoxaban, and once INR is stable and measured at 2 or above, discontinue Savaysa/Edoxaban and continue Warfarin therapy as usual.