Edoxaban

BRAND NAMES:

Lixiana – It is available in the form of film-coated edoxaban tablets as tosylate with the composition of 60/30mg.

Savaysa – It is also another brand name for Edoxban which is available with the name of Edoxaban 30/60mg, which helps in reducing the stroke and blood clots in the people who have atrial fibrillation.

MECHANISM OF ACTION:

Edoxaban exerts its therapeutic effects by inhibiting factor Xa directly, selectively, and reversibly as a part of its mechanism of action. FXa plays a pivotal role in both the extrinsic and intrinsic pathways of the coagulation cascade. FXa binds with factor Va, creating a complex that facilitates the cleavage of prothrombine into thrombin. Thrombin cleaves fibrinogen into fibrin monomers and creates fibrin meshwork, which adheres to a platelet plug and ultimately forms a clot.

By obstructing the active site of free FXa, thrombin production is inhibited, leading to a reduction in thrombus development. This inhibition occurs independently of the anticoagulant effects of cofactor antithrombin Ⅲ. Edoxaban also functions by inhibiting prothrombinase activity, thereby suppressing thrombin-induced platelet aggregation.

PHARMACOKINETICS:

Absorption: Peak plasma edoxaban concentrations appear approximately 1-2 hours after oral dosing. The absolute bioavailability is 62 percent.

Distribution: Edoxaban has a half-life of 10-14 hours and reaches peak serum concentration levels within 1–2 hours. The study state distribution volume is 107L.

Metabolism: Edoxaban is little metabolized by CYP3A4, resulting in few drug-drug interactions. However, it interacts with drugs that inhibit p-gp, which is important for moving edoxaban across the gut wall. Plasma contains the most stable form of edoxaban. Cyp3A4 hydrolyzes, conjugates, and oxidizes tiny quantities of substrate. When the parent chemical is hydrolyzed, the primary metabolite M-4 is formed. This active, human-specific metabolite exposes healthy people to less than 10% of their original concentration. Other metabolites represent less than 5% of total edoxaban exposure.

Excretion: Urine contains the intact medicine edoxaban, which is mainly eliminated. Renal clearance (11 L/hour) accounts for nearly half of total edoxaban clearance (22 L/hour). Metabolism and biliary/intestinal excretion contribute to the remainder elimination.

PHARMACODYNAMICS:

Edoxaban administration prolongs clotting time tests, including a PTT, PT, and INR (international normalized ratio).

DOSAGE AND ADMINISTRATION:

Edoxaban is available for oral administration. The film-coated pills of edoxaban come in dosages of 15 mg, 30 mg, and 60 mg. Before starting treatment, the patient's creatinine clearance should be evaluated.

CONTRAINDICATIONS: 

Edoxaban is contraindicated in patients with massive or pathological bleeding. Clinicians should avoid prescribing edoxaban for thromboembolism or stroke prevention in patients with a creatinine clearance >95 ml/min. This drug is not indicated for patients with underlying valvular pathologies or those who have mechanical heart valves.

Patients taking edoxaban and undergoing spinal or epidural puncture procedures are at risk of developing a spinal or epidural hematoma. Indwelling catheters should be paused for a minimum of 12 hours after edoxaban therapy, and the initiation of the drug should be delayed by at least 2 hours after catheter removal. Edoxaban use in patients with moderate-to-severe liver dysfunction is not recommended.

DRUG INTERACTIONS:

• Due to probable medication interactions and increased risk of bleeding, Edoxaban should not be taken concurrently with the following agents: 

• Anticoagulants, antiplatelets, thrombolytics, selective serotonin reuptake inhibitors, and serotonin and norepinephrine reuptake inhibitors.

• Taking defibrotide in conjunction with edoxaban may result in cumulative effects and an increased risk of bleeding.

• Combining edoxaban with mifepristone may raise edoxaban levels, raising the risk of serious bleeding.

FOOD INTERACTIONS:

Avoid herbs and supplements with anticoagulant or antiplatelet action. Additive anticoagulant action may raise the risk of bleeding. Examples include garlic, ginger, and bilberry. You can take it with or without food.

ADVERSE EFFECTS:

Edoxaban use is beneficial in preventing thrombotic events; the drug is also associated with a range of potential adverse effects, ranging from severe reactions with profound implications to mild and manageable ones.

The severe adverse effects of edoxaban include epidural hematoma, spinal hematoma, severe bleeding, thrombocytopenia, angioedema, and thrombosis with premature discontinuation. Edoxaban may cause side effects. It includes rash, weakness, dizziness, pale skin, a bloody nose, and heavy non-menstrual vaginal bleeding.

OVERDOSE:

Overdoses of edoxaban may include

- Unusual bleeding

- Black or tarry stools

- Blood in urine

- Coughing up or vomiting blood.

STORAGE:

Keep at ambient temperature, around 68°F to 77°F (20°C to 25°C).