edoxaban

Edoxaban is a medication used to prevent blood clot blocks (thromboembolisms) in patients with nonvalvular atrial fibrillation or thromboembolic conditions such as deep vein thrombosis or pulmonary embolism.

Edoxaban is an oral anticoagulant drug that works by inhibiting coagulation factor Xa, a proenzyme (zymogen) that plays a role in the coagulation process. Coagulation factors are specialized proteins in the plasma that regulate blood clotting and clot dissolution processes.

Factor Xa activates prothrombin, a coagulation factor that is produced by the liver. Activation by factor Xa transforms prothrombin into its active form, thrombin. Thrombin, in turn, converts fibrinogen, a fibrous protein in the plasma, into fibrin, an insoluble protein that forms a mesh around aggregated platelets to form a clot. By selectively and reversibly blocking factor Xa, edoxaban prevents this coagulation cascade.

What is edoxaban prescribed for?

Uses of edoxaban include:

• To reduce the risk of stroke and systemic embolism associated with nonvalvular atrial fibrillation (NVAF), a heart condition with irregular heart rhythm
• Treatment of deep vein thrombosis (DVT) and pulmonary embolism (PE) in patients who have been initially treated with an (intravenous) parenteral anticoagulant for 5-10 days

• Do not use edoxaban in patients with active pathological bleeding.
• Do not use edoxaban in patients with NVAF with creatinine clearance higher than 95 mL/minute. Efficacy of drug is lower and it may increase the risk of stroke due to reduced blood flow (ischemia). Use an alternative anticoagulant. 
• Premature discontinuation of edoxaban without adequate alternative anticoagulation therapy can increase the risk for ischemic events. If edoxaban is discontinued for any reason other than active pathological bleeding or completion of therapy, use an alternative coagulation therapy as per the transition dosing guidance.
• Spinal/epidural (neuraxial) anesthesia or spinal puncture in patients receiving edoxaban can result in epidural or spinal hematomas, which can cause long-term or permanent paralysis. Monitor such patients for neurological impairment and promptly initiate appropriate treatment if neurological compromise is observed.
• Assess the risks before scheduling spinal procedures for patients receiving edoxaban treatment. Optimal timing between edoxaban administration and spinal procedures is not established. Risk factors for epidural or spinal hematomas in these patients include:
  • Use of indwelling epidural catheters
  • Concurrent use of other drugs that affect the control of bleeding (hemostasis), such as NSAIDs, platelet inhibitors, other anticoagulants, antithrombotic agents, fibrinolytic therapy, norepinephrine reuptake inhibitors
  • History of spinal deformity or surgery
  • History of traumatic or repeated epidural or spinal punctures
• Edoxaban can increase the risk of bleeding that can be serious or even fatal. Monitor patients for symptoms of blood loss, evaluate and discontinue edoxaban in patients with active pathological bleeding. Concurrent use with other drugs that affect hemostasis can increase the risk of bleeding.
• Do not use edoxaban in patients with mechanical heart valves or moderate to severe narrowing (stenosis) of mitral valve. Safety and efficacy of edoxaban in such patients have not been studied.
• Avoid concurrent use with P-glycoprotein (P-gp) inducer medications such as rifampin. It can reduce the serum concentration of edoxaban. Dose reduction of edoxaban is recommended when co-administered with P-gp inhibitor drugs in the treatment of DVT and PE but not for NVAF.

Common side effects of edoxaban include:

• Minor bleeding (hemorrhage)
• Major hemorrhage
• Oral hemorrhage
• Puncture site bleeding
• Anemia
• Gastrointestinal hemorrhage
• Nasal bleeding (epistaxis)
• Bleeding in the throat (pharyngeal bleeding)
• Vaginal hemorrhage
• Urethral bleeding
• Blood in the urine (hematuria)
• Intracranial hemorrhage
• Dermal hemorrhage
• Skin rash
• Abnormal liver function test results
• Disorders that scar the lung tissue (interstitial pulmonary disease)

Less common side effects of edoxaban include:

• Reduced blood flow to the tissues (ischemia), with premature discontinuation
• In patients receiving neuraxial anesthesia or undergoing spinal puncture:
  • Spinal hematoma
  • Epidural intracranial hemorrhage
• Hives (urticaria)
• Headache
• Dizziness
• Abdominal pain
• Low platelet count (thrombocytopenia)
• Hypersensitivity reactions
• Swelling under the skin and mucous membranes (angioedema)

Call your doctor immediately if you experience any of the following symptoms or serious side effects while using this drug:

• Serious heart symptoms include fast or pounding heartbeats, fluttering in your chest, shortness of breath, and sudden dizziness;
• Severe headache, confusion, slurred speech, severe weakness, vomiting, loss of coordination, feeling unsteady;
• Severe nervous system reaction with very stiff muscles, high fever, sweating, confusion, fast or uneven heartbeats, tremors, and feeling like you might pass out; or
• Serious eye symptoms include blurred vision, tunnel vision, eye pain or swelling, or seeing halos around lights.

This is not a complete list of all side effects or adverse reactions that may occur from the use of this drug. Call your doctor for medical advice about serious side effects or adverse reactions. You may also report side effects or health problems to the FDA at 1-800-FDA-1088.

Tablet

• 15 mg
• 30 mg
• 60 mg

Adult:

Stroke Prophylaxis with Atrial Fibrillation

• 60 mg orally once daily

Limitation of use

Creatinine clearance (CrCl) above 95 mL/minute: Do not use; increased risk of ischemic stroke compared with warfarin in NVAF trial

DVT or PE Treatment

• Adults above 60 kg: 60 mg orally once daily
• Adults 60 kg and below: 30 mg orally once daily

Dosage Modifications

Coadministration with P-gp inhibitors

• Treatment of DVT/PE: Decrease dose to 30 mg orally once daily when co-administered with certain P-gp inhibitors

Renal impairment (NVAF)

• CrCl above 95 mL/min: Do not use; increased ischemic stroke compared with warfarin
• CrCl above 50 to 95 mL/min: No dosage adjustment required
• CrCl 15-50 mL/min: 30 mg orally once daily
• CrCl below 15 mL/min or dialysis: Insufficient data; not recommended (AHA/ACC/HRS guidelines for atrial fibrillation; Circulation July 9, 2019)

Renal impairment (DVT/PE)

• CrCl above 50 mL/min: No dosage adjustment required
• CrCl 15-50 mL/min: 30 mg orally once daily

Hepatic impairment

• Mild (Child-Pugh A): No dose adjustment required
• Moderate-to-severe (Child-Pugh B/C): Not recommended; these patients have intrinsic coagulation abnormalities

Transition dosing to or from edoxaban

Transition to edoxaban

• From warfarin or other vitamin K antagonists (VKAs): Discontinue warfarin and start edoxaban when INR is 2.5 or lower
• From oral anticoagulants other than warfarin or other VKAs: Discontinue current oral anticoagulant and initiate edoxaban at the time of the next scheduled dose of the previous oral anticoagulant
• From low molecular weight heparin (LMWH): Discontinue LMWH and initiate edoxaban at the time of the next scheduled administration of LMWH
• From unfractionated heparin: Discontinue heparin infusion and initiate edoxaban 4 hours later

Transition from edoxaban

• To non-vitamin-K-dependent oral anticoagulants: Discontinue edoxaban and start the other oral anticoagulant at the time of the next dose of edoxaban
• To parenteral anticoagulants: Discontinue edoxaban and start the parenteral anticoagulant at the time of the next dose of edoxaban
• To warfarin (oral option)
  • If taking edoxaban 60 mg/day, reduce dose to 30 mg/day and begin warfarin concomitantly
  • If taking edoxaban 30 mg/day, reduce dose to 15 mg/day and begin warfarin concomitantly
  • INR must be measured at least weekly and just prior to the daily dose of edoxaban to minimize the influence on INR measurements
  • Once a stable INR of 2.0 or more is achieved, discontinue edoxaban and continue warfarin
• To warfarin (parenteral option)
  • Discontinue edoxaban and administer a parenteral anticoagulant and warfarin at the time of the next scheduled edoxaban dose
  • Once a stable INR 2.0 or more is achieved, discontinue the parenteral anticoagulant and continue warfarin

Pediatric:

Safety and efficacy not established

Overdose

• Overdose of edoxaban can increase the risk for major bleeding including intracranial and gastrointestinal hemorrhage.
• There is no specific antidote for edoxaban. Overdose and bleeding may be treated with discontinuation of the drug and appropriate symptomatic and supportive therapy.

Inform your doctor of all medications you are currently taking, who can advise you on any possible drug interactions. Never begin taking, suddenly discontinue, or change the dosage of any medication without your doctor’s recommendation.

• Severe interactions of edoxaban include:
  • defibrotide
• Edoxaban has serious interactions with at least 82 different drugs.
• Edoxaban has moderate interactions with at least 54 different drugs.
• Edoxaban has no known mild interactions with other drugs.

The drug interactions listed above are not all of the possible interactions or adverse effects. For more information on drug interactions, visit the RxList Drug Interaction Checker.

It is important to always tell your doctor, pharmacist, or health care provider of all prescription and over-the-counter medications you use, as well as the dosage for each, and keep a list of the information. Check with your doctor or health care provider if you have any questions about the medication.

• There are no adequate and well-controlled studies on the use of edoxaban in pregnant women. Edoxaban should be used during pregnancy only if clearly needed and maternal benefits outweigh potential fetal risks.
• Edoxaban use during pregnancy can increase the risk of maternal bleeding as well as fetal or placental bleeding, increasing the risk for miscarriage, preterm delivery, fetal compromise, newborn bleeding, and stillbirth.
• Pregnancy increases the risk of thromboembolism in women with underlying thromboembolic disease and certain high-risk pregnancy conditions. If anticoagulant therapy is administered during pregnancy, monitor fetus for bleeding and preterm delivery, and the newborn for bleeding.
• Women of pregnancy potential should use effective contraception while on edoxaban therapy, because there is limited information on the use of direct-acting oral anticoagulants, including edoxaban, during pregnancy. Patients wishing to become pregnant should be switched to an alternate anticoagulant therapy before conception.
• There is no information on the presence of edoxaban in breastmilk, and its effects on milk production or on the breastfed infant, however, edoxaban was excreted in animal milk. Many drugs are excreted in breastmilk, and because of the potential for serious bleeding risk in the breastfed infant, nursing or edoxaban should be discontinued, depending on the importance of the treatment to the mother.

• Take edoxaban exactly as prescribed.
• Take care to avoid injury, you may or bruise or bleed easily, and for a longer period than normal. Notify your physician immediately if you notice any unusual bleeding or bruising.
• If you have a spinal or epidural procedure, be alert for symptoms of spinal/epidural hematoma such as back pain, tingling, numbness (especially in the lower limbs), muscle weakness, and stool or urine incontinence. Inform your physician immediately if you develop any of these symptoms.
• Store safely out of reach of children.
• In case of overdose, seek medical help or contact Poison Control.