1 tablet contains edoxaban (in the form of tosylate monohydrate) 15 mg or 30 mg, or 60 mg;
Excipients: mannitol (E 421); pregelatinized starch; crospovidone; hydroxypropylcellulose; magnesium stearate;
shell:
15 mg tablets: Opadry II Orange 32F230000: hypromellose (hydroxypropylmethylcellulose); lactose monohydrate; polyethylene glycol (macrogol); titanium dioxide (E 171); iron oxide yellow (E 172), iron oxide red (E 172);
30 mg tablets: Opadry II Pink 32F240010: hypromellose (hydroxypropylmethylcellulose); lactose monohydrate; polyethylene glycol (macrogol); titanium dioxide (E 171); iron oxide red (E 172);
60 mg tablets: Opadry II Yellow 32F220004: hypromellose (hydroxypropylmethylcellulose); lactose monohydrate; polyethylene glycol (macrogol); titanium dioxide (E 171); iron oxide yellow (E 172).
Dosage form
Film-coated tablets.
Main physicochemical properties:
15 mg tablets: round tablets with a biconvex surface, film-coated from light brown to brown;
30 mg tablets: round tablets with a biconvex surface, film-coated from light pink to pink;
60 mg tablets: round tablets with a biconvex surface, film-coated from light yellow to brownish yellow.
Pharmacotherapeutic group
Antithrombotic agents. Direct inhibitors of factor Xa. Edoxaban. ATC code B01A F03.
Pharmacological properties
Pharmacodynamics.
Mechanism of action
Edoxaban is a highly selective, direct, reversible inhibitor of factor Xa, a serine protease that is the final step in the normal coagulation cascade. Edoxaban inhibits free factor Xa and prothrombinase activity. Inhibition of factor Xa in the coagulation cascade results in reduced thrombin generation, prolonged clotting time, and reduced risk of thrombus formation.
Pharmacodynamic effects
Edoxaban provides a rapid onset of pharmacodynamic effect, within 1–2 hours, corresponding to the maximum plasma concentration (Cmax) of edoxaban. Pharmacodynamic effects, as measured by the anti-factor Xa activity assay, are predictable and correlated with the dose and concentration of edoxaban. As a result of inhibition of factor Xa, edoxaban also prolongs clotting times as measured by prothrombin time (PT) and activated partial thromboplastin time (aPTT). Changes in coagulation parameters observed at therapeutic doses are small and highly variable and are not recommended for monitoring the anticoagulant effect of edoxaban.
Effect of blood coagulation markers when switching from rivaroxaban, dabigatran, or apixaban to edoxaban
It is known that in clinical pharmacology studies, healthy subjects received rivaroxaban 20 mg once daily, dabigatran 150 mg twice daily, or apixaban 5 mg twice daily followed by a single dose of edoxaban 60 mg on day 4. The effect on the PC and other coagulation biomarkers (e.g. anti-factor Xa activity, aPTT) was determined. After switching to edoxaban on day 4, the PC value was equivalent to that observed on day 3 of rivaroxaban and apixaban. aPTT values were higher after edoxaban with prior dabigatran treatment compared to after edoxaban alone. This is thought to be due to a residual effect of dabigatran treatment, but it did not result in a prolongation of bleeding time.
Based on the data provided, when switching from these anticoagulants to edoxaban, the first dose of edoxaban can be administered in place of the next scheduled dose of the previous anticoagulant.
Clinical efficacy and safety
Stroke and systemic embolism prevention
The edoxaban clinical trial in atrial fibrillation was designed to demonstrate the efficacy and safety of two dose groups of edoxaban compared with warfarin for the prevention of stroke and systemic embolism in patients with nonvalvular atrial fibrillation (NAF) and at moderate to high risk of stroke and systemic embolic events. The primary efficacy endpoint was the composite of stroke and systemic embolic events. Secondary efficacy endpoints included: the composite of stroke, systemic embolic events, and cardiovascular death; serious adverse cardiovascular event (SACE), which is the composite of nonfatal myocardial infarction (MI), nonfatal stroke, nonfatal systemic embolic event, and death from cardiovascular causes or bleeding; and the composite of stroke, systemic embolic event, and death from any cause.
The primary safety endpoint was major bleeding.
There was a significant reduction in the risk of major bleeding, intracranial hemorrhage, and other types of bleeding in the edoxaban 60 mg treatment group compared with the warfarin treatment group.
The edoxaban 60 mg treatment group also had a significant reduction in fatal bleeding compared to the warfarin treatment group, mainly due to a reduction in fatal intracranial hemorrhage.
Treatment of deep vein thrombosis (DVT) and pulmonary embolism (PE), as well as prevention of recurrence of DVT and PE [VTE (venous thromboembolism)]
The edoxaban clinical trial program in VTE was designed to demonstrate the efficacy and safety of edoxaban for the treatment of DVT and PE and for the prevention of recurrent DVT and PE.
The study found that edoxaban was non-inferior to warfarin on the primary efficacy endpoint of recurrent VTE.
Efficacy results in pre-specified key subgroups (with dose reductions as appropriate), including age, weight, gender, and renal function status, were consistent with the primary efficacy results in the overall trial population.
The primary safety endpoint was clinically significant bleeding (severe or non-severe but clinically significant).
The edoxaban group showed a significant reduction in the risk of clinically significant bleeding, major bleeding, or clinically significant non-major bleeding compared with warfarin.
Prevention of stroke and systemic embolism in patients with NPF with creatinine clearance (CC) > 100 ml/min
Based on the pooled data in patients with NPF and high creatinine clearance (> 100 mL/min) treated with edoxaban 60 mg, the expected annual rate of ischemic stroke/systemic embolism is ≤ 1%. Increasing the dose of edoxaban (above 60 mg) in patients with NPF and high creatinine clearance (> 100 mL/min) does not provide greater protection against stroke and may be associated with increased adverse events. Therefore, the edoxaban 60 mg once daily regimen is recommended in these patients after careful assessment of the individual thromboembolic and bleeding risk.
Patients undergoing cardioversion
During the studies, a low incidence of major and clinically significant non-major bleeding and thromboembolism was observed among patients undergoing cardioversion.
Children
The European Medicines Agency has deferred the obligation to submit the results of studies with edoxaban in one or more subsets of the paediatric population for the prevention of arterial thromboembolism, treatment of thromboembolism and prevention of thromboembolism (see section 4.2).
Pharmacokinetics.
Absorption. After absorption, peak plasma concentrations of edoxaban are reached within 1–2 hours. Absolute bioavailability is approximately 62%. Food intake increases peak exposure unevenly but has minimal effect on overall potency. Edoxaban has been used in studies with and without food. Edoxaban is poorly soluble at pH levels of 6.0 or higher. Concomitant use of proton pump inhibitors has no significant effect on the potency of edoxaban.
Distribution: Edoxaban has a biphasic distribution. The volume of distribution is on average 107 L (standard deviation 19.9 L).
In vitro plasma protein binding is approximately 55%. There is no clinically significant accumulation of edoxaban (accumulation factor 1.14) with once-daily dosing. Steady-state concentrations are reached within 3 days.
Biotransformation. Edoxaban is predominantly found unchanged in plasma. Edoxaban is metabolized by hydrolysis (mediated by carboxylesterase 1), conjugation, or oxidation by CYP3A4/5 (< 10%). Edoxaban has three active metabolites, the major one (M-4) formed by hydrolysis, is active, and accounts for less than 10% of the parent drug concentration in healthy subjects. The concentrations of the other metabolites are less than 5%. Edoxaban is a substrate for the efflux transporter P-glycoprotein (P-gp), but is not a substrate for uptake transporters such as the polypeptide organic anion transporter OATP1B1, the organic anion transporters OAT1 or OAT3, or the organic cation transporter OCTS2. Its active metabolite is a substrate for OATP1B1.
Elimination: In healthy subjects, the estimated total clearance is 22 (± 3) l/h; 50% of the drug is excreted by the kidneys (11 l/h). Renal clearance accounts for approximately 35% of the administered dose. The remaining clearance is due to metabolism and biliary/intestinal excretion. The half-life of the drug after oral administration is 10–14 hours.
Linearity: Edoxaban exhibits approximately dose-proportional pharmacokinetics over the 15 mg to 60 mg dose range.
Special groups
Elderly patients
A population pharmacokinetic analysis, taking into account renal function and body weight, showed that patient age had no additional clinically significant effect on the pharmacokinetics of edoxaban.
The AUC (area under the concentration-time curve) in patients with mild (CC > 50–80 mL/min), moderate (CC 30–50 mL/min), and severe (CC < 30 mL/min, not on dialysis) renal impairment was increased by 32%, 74%, and 72%, respectively, compared to patients with normal renal function. In patients with renal impairment, the metabolite profile is altered and a greater number of active metabolites are formed.
A linear correlation was observed between edoxaban plasma concentrations and anti-factor Xa activity, independent of renal function.
Patients with end-stage renal disease undergoing peritoneal dialysis had a 93% higher total exposure compared to healthy subjects.
Population pharmacokinetic modeling suggests that exposure is approximately doubled in patients with severe renal impairment compared to patients with normal renal function.
Anti-factor Xa activity depending on the CK index
Treatment with edoxaban does not require regular monitoring - the effect on anticoagulant activity can be assessed using a calibrated quantitative anti-factor Xa assay, which is useful in exceptional situations where information on edoxaban exposure may help in clinical decision-making, such as in cases of overdose and emergency surgery.
After a 4-hour hemodialysis session, a decrease in total edoxaban exposure of less than 9% was observed.
Liver dysfunction
In patients with mild to moderate hepatic impairment, pharmacokinetic and pharmacodynamic profiles were similar to those observed in healthy controls. Edoxaban has not been studied in patients with severe hepatic impairment.
Sex
A population pharmacokinetic analysis found that patient gender had no additional clinically significant effect on the pharmacokinetics of edoxaban.
Ethnic origin
In a population pharmacokinetic analysis, it was found that peak and total exposures were comparable in Asian and non-Asian patients.
Body weight
Population pharmacokinetic analysis showed that in patients with low body weight (55 kg) Cmax and AUC were increased by 40% and 13%, respectively, compared to patients with average body weight (84 kg). In the study (indicated for NPF and VTE), patients with body weight ≤ 60 kg received a 50% reduced dose of edoxaban, while they had similar efficacy and fewer bleeding events compared to warfarin.
Pharmacokinetic/pharmacodynamic relationship
PC, INR (international normalized ratio), aPTT, and anti-factor Xa were linearly correlated with edoxaban concentration.
Indication
For the prevention of stroke and systemic embolism in adult patients with non-valvular atrial fibrillation (NAFLD) and one or more risk factors such as congestive heart failure, hypertension, diabetes mellitus, history of stroke or transient ischemic attack (TIA), aged 75 years and older.
For the treatment of deep vein thrombosis (DVT) and pulmonary embolism (PE), as well as for the prevention of recurrent DVT and PE in adults (see section "Special instructions" for patients with PE who have unstable hemodynamic parameters).
Contraindication
Hypersensitivity to the active substance or to any of the excipients of the medicinal product.
Clinically significant active bleeding.
Liver diseases accompanied by coagulopathy and clinically significant risk of bleeding.
Injuries or conditions associated with a significant risk of bleeding, including current or recent gastrointestinal ulceration, malignancies with a high risk of bleeding, recent brain or spinal cord trauma, recent brain, spinal cord or eye surgery, recent intracranial bleeding, known or suspected esophageal varices, arteriovenous malformations, vascular aneurysms, or significant intraspinal or intracranial vascular anomalies.
Uncontrolled severe arterial hypertension.
Concomitant use of any other anticoagulants, such as unfractionated heparin (UFH), low molecular weight heparins (LMWH) (enoxaparin, dalteparin, etc.), heparin derivatives (fondaparinux, etc.), oral anticoagulants (warfarin, dabigatran, rivaroxaban, apixaban, etc.), except in specific cases of changing anticoagulant therapy (see section "Method of administration and dosage") or administration of UFH in doses necessary to ensure patency of the central venous or arterial catheter.
Pregnancy or breastfeeding (see section "Use during pregnancy or breastfeeding").
Interaction with other medicinal products and other types of interactions
P-gp (P-glycoprotein) inhibitors
Edoxaban is a substrate of the efflux transporter P-gp. In pharmacokinetic studies, concomitant administration of edoxaban with the P-gp inhibitors cyclosporine, dronedarone, erythromycin, ketoconazole, quinidine, or verapamil resulted in increased plasma concentrations of edoxaban.
Concomitant use of edoxaban with cyclosporine, dronedarone, erythromycin, or ketoconazole requires a dose reduction to 30 mg once daily.
Concomitant use of edoxaban with quinidine, verapamil, or amiodarone does not require dose reduction.
The use of edoxaban with other P-gp inhibitors, including HIV protease inhibitors, has not been studied.
Edoxaban 30 mg once daily can be used concomitantly with the following P-gp inhibitors:
– Cyclosporine: Co-administration of a single dose of cyclosporine 500 mg with a single dose of edoxaban 60 mg increased the AUC and Cmax of edoxaban.
– Dronedarone 400 mg twice daily for 7 days with a single concomitant dose of edoxaban 60 mg on day 5 increased edoxaban AUC and Cmax.
– Erythromycin 500 mg 4 times daily for 8 days with a single concomitant dose of edoxaban 60 mg on day 7 increased the AUC and Cmax of edoxaban.
– Ketoconazole 400 mg once daily for 7 days with a single concomitant dose of edoxaban 60 mg on day 4 increased edoxaban AUC and Cmax.
Edoxaban 60 mg once daily can be used concomitantly with the following P-gp inhibitors:
– Quinidine: When quinidine was administered at a dose of 300 mg once daily on days 1 and 4 and 3 times daily on days 2 and 3 simultaneously with a single concomitant dose of edoxaban 60 mg on day 3, an increase in edoxaban AUC was observed throughout the day.
– Verapamil: When verapamil 240 mg once daily was administered for eleven days with a single dose of edoxaban 60 mg on the tenth day, an increase in edoxaban AUC and Cmax of approximately 53% was observed.
– Amiodarone: Co-administration of amiodarone 400 mg once daily with edoxaban 60 mg once daily resulted in an increase in AUC and Cmax. This increase was not considered clinically relevant. It is known that in a study in patients with NPF, efficacy and safety were similar in patients receiving concomitant amiodarone and those not receiving concomitant amiodarone.
P-gp inducers
Concomitant use of edoxaban with the P-gp inducer rifampicin resulted in a decrease in the mean AUC of edoxaban and a shortening of the elimination half-life with possible reduction of pharmacodynamic effects. Concomitant use of edoxaban with other P-gp inducers (e.g. phenytoin, carbamazepine, phenobarbital or St. John's wort) may result in decreased plasma concentrations of edoxaban. Caution should be exercised when edoxaban is used concomitantly with P-gp inducers.
P-gp substrates
Digoxin: When edoxaban 60 mg once daily was administered for 1–14 days with multiple doses of digoxin 0.25 mg twice daily (on days 8 and 9) and 0.25 mg once daily (on days 10 and 11), a 17% increase in edoxaban Cmax was observed without any significant effect on AUC or renal clearance at steady state. In a study of the effect of edoxaban on the pharmacokinetics of digoxin, it was found that the Cmax of digoxin increased by approximately 28% and the AUC by 7%. This increase was not considered clinically relevant. No dose adjustment is necessary when edoxaban is administered concomitantly with digoxin.
Anticoagulants: Concomitant use of edoxaban with other anticoagulants is contraindicated due to an increased risk of bleeding (see section “Contraindications”).
ASA (acetylsalicylic acid): Concomitant use of ASA (100 mg or 325 mg) and edoxaban increases bleeding time. Concomitant use of high doses of ASA (325 mg) resulted in increased steady-state Cmax and AUC of edoxaban. Long-term concomitant use of high doses of ASA and edoxaban is not recommended. Concomitant use of doses of ASA above 100 mg should only be carried out under medical supervision.
The trials allowed concomitant use of ASA (at low doses, ≤ 100 mg/day), other antiplatelet agents, and thienopyridines, which resulted in an approximately two-fold increase in major bleeding compared to monotherapy, with similar increases observed in both the edoxaban and warfarin groups. Concomitant use of low doses of ASA did not affect the maximum or total potency of edoxaban after a single dose.
Edoxaban can be used concomitantly with low doses of ASA.
Platelet aggregation inhibitors: In a trial, concomitant use of thienopyridine monotherapy (e.g. clopidogrel) resulted in an increased incidence of clinically significant bleeding, although the risk was relatively lower with edoxaban than with warfarin.
NSAIDs: Concomitant use of naproxen and edoxaban resulted in prolonged bleeding time compared to monotherapy with the aforementioned drugs. Naproxen did not affect the Cmax and AUC of edoxaban. Concomitant use of NSAIDs has been shown to increase the incidence of clinically significant bleeding in clinical trials. Long-term use of NSAIDs with edoxaban is not recommended.
SSRIs/INRs: As with other anticoagulants, there is an increased risk of bleeding in patients receiving concomitant SSRIs or IRRs due to their effects on platelet function (see section 4.4).
Application features
Edoxaban 15 mg is not indicated as monotherapy as this may result in reduced efficacy. It is only indicated when switching from edoxaban 30 mg [with one or more clinical factors for increased exposure (see Table 1)] to a VKA (vitamin K antagonist) together with the appropriate dose of VKA (see Table 2, Dosage and Administration).
Risk of bleeding
Edoxaban increases the risk of bleeding and may cause severe, potentially life-threatening bleeding. As with other anticoagulants, edoxaban should be used with caution in patients with conditions that put them at increased risk of bleeding. In the event of serious bleeding, the drug should be discontinued.
In clinical trials, mucosal bleeding (e.g., epistaxis, gastrointestinal bleeding, genitourinary bleeding) and anemia were reported to occur more frequently with long-term edoxaban therapy than with VKA. Therefore, in addition to appropriate clinical monitoring, laboratory monitoring of hemoglobin/hematocrit should be considered as appropriate to detect occult bleeding.
Certain categories of patients, as listed below, are at increased risk of bleeding. Such patients should be closely monitored for signs of bleeding complications and anemia after initiation of treatment. Any unexplained decrease in hemoglobin or blood pressure should prompt investigation of the source of bleeding.
The anticoagulant effect of edoxaban cannot be reliably monitored by standard laboratory tests. There is no specific anticoagulant reversal agent for edoxaban.
Hemodialysis does not significantly affect the clearance of edoxaban.
Elderly patients
Concomitant use of edoxaban and ASA in elderly patients requires caution due to an increased risk of bleeding.
Patients with renal impairment
The AUC in plasma was increased in patients with mild (CC > 50–80 mL/min), moderate (CC 30–50 mL/min) and severe (CC < 30 mL/min, not on dialysis) renal impairment compared to patients with normal renal function (see section 4.2).
Edoxaban treatment is not recommended for patients with creatinine clearance < 15 mL/min or patients on dialysis.
Kidney function in NPF
Edoxaban has been shown to have a trend toward decreased efficacy with increasing CK compared with appropriate warfarin use. Therefore, edoxaban should only be used in patients with APF and high CK after careful assessment of the individual risk of thromboembolism and bleeding.
Assessment of renal function: monitoring of CK levels should be performed at the beginning of treatment in all patients and then as clinically indicated.
Patients with hepatic impairment
Edoxaban is not recommended for use in patients with severe hepatic impairment.
Edoxaban should be used with caution in patients with mild or moderate hepatic impairment.
Patients with elevated liver enzymes (alanine aminotransferase/aspartate aminotransferase (ALT/AST) >2 times the upper limit of normal) or total bilirubin >1.5 times the upper limit of normal were excluded from clinical trials. Therefore, edoxaban should be used with caution in this patient population. Liver function tests should be performed prior to initiating treatment with edoxaban. Periodic liver function testing is recommended in patients treated with edoxaban for more than one year.
Treatment discontinuation due to surgical and other interventions
If anticoagulant therapy must be discontinued to reduce the risk of bleeding during surgery or other procedures, edoxaban should be discontinued as early as possible, at least 24 hours before the procedure.
If the procedure cannot be postponed, the increased risk of bleeding and the urgency of the intervention should be assessed. Edoxaban treatment should be resumed after surgical or other interventions as soon as adequate hemostasis has been achieved, taking into account that the anticoagulant effect of edoxaban is manifested 1–2 hours after administration.
If oral medication is not possible during or after surgery, parenteral anticoagulant therapy should be considered, followed by a switch to once-daily oral edoxaban.
Concomitant use of medicinal products that affect blood clotting increases the risk of bleeding. Such medicinal products include ASA, platelet aggregation inhibitors, other antiplatelet agents, fibrinolytics, SSRIs and NSAIDs in long-term use (see section "Interaction with other medicinal products and other types of interactions").
Artificial heart valves and moderate or severe mitral valve stenosis
Edoxaban has not been studied in patients with prosthetic heart valves, in patients within the first 3 months of bioprosthetic heart valve implantation, with or without atrial fibrillation, or in patients with moderate to severe mitral stenosis. Therefore, edoxaban is not recommended for the treatment of these patients.
Patients suffering from PE and are hemodynamically unstable, or patients requiring thrombolysis or pulmonary embolectomy
Edoxaban is not recommended as an alternative to UFH in patients with PE who are hemodynamically unstable or may undergo thrombolysis or pulmonary embolectomy, as the safety and efficacy of edoxaban in these clinical situations have not been established.
Patients with active cancer
The efficacy and safety of edoxaban in the treatment and/or prevention of VTE in patients with active cancer have not been established.
Patients with antiphospholipid syndrome
Direct oral anticoagulants, including edoxaban, are not recommended for patients with a history of thrombosis and a diagnosis of antiphospholipid syndrome. In particular, in patients who have confirmed positive test results for all three antiphospholipid antibodies (lupus anticoagulant, anticardiolipin antibodies, anti-beta-2-glycoprotein I antibodies), treatment with direct oral anticoagulants increases the risk of recurrent thrombotic events compared with VKA therapy.
Laboratory indicators
Although treatment with edoxaban does not require regular monitoring, the effect on anticoagulant activity can be assessed by a calibrated quantitative anti-factor Xa assay, the results of which may assist in clinical decision-making in certain situations, such as overdose or emergency surgery.
Edoxaban prolongs the value of standard coagulation tests such as INR, INR, and aPTT as a result of factor Xa inhibition. However, changes in these coagulation tests when used within the expected therapeutic range are small and due to high variability, are not useful for monitoring the anticoagulant effect of edoxaban.
Excipients
The medicine contains lactose, therefore patients with rare hereditary diseases such as galactose intolerance, lactase deficiency or glucose-galactose malabsorption should not use this medicine.
Use during pregnancy or breastfeeding
Effects on reproductive function: Women of reproductive potential should avoid pregnancy during treatment with edoxaban.
Pregnancy. The efficacy and safety of edoxaban in pregnant women have not been studied. Animal studies have shown reproductive toxicity. Due to the potential for reproductive toxicity, the significant risk of bleeding, and the passage of edoxaban through the placental barrier, Edoxacord is contraindicated during pregnancy (see section "Contraindications").
Breastfeeding. The efficacy and safety of edoxaban in breast-feeding women have not been studied. Animal studies have shown that edoxaban is excreted in breast milk. Therefore, Edoxacord is contraindicated during breast-feeding (see section 4.3). A decision must be made whether to discontinue breast-feeding or to discontinue/abstain from therapy.
Fertility: No specific studies have been conducted to evaluate the effects of edoxaban on human fertility. No effects were observed in a fertility study in male and female rats.
Ability to influence reaction speed when driving vehicles or other mechanisms
The drug Edoxacord has no or little effect on the reaction speed when driving vehicles or using other mechanisms.
Method of administration and doses
Stroke and systemic embolism prevention
The recommended dose is 60 mg edoxaban once daily.
Edoxaban therapy in patients with NPF is carried out over a long period of time.
Treatment of DVT and PE, as well as prevention of recurrence of DVT and PE (VTE)
The duration of treatment for DVT and PE (VTE), as well as for the prevention of recurrent VTE, is determined on an individual basis after careful assessment of the benefit of treatment against the risk of bleeding. Short-term therapy (at least 3 months) is indicated in the presence of temporary risk factors (e.g., recent surgery, trauma, immobilization), while longer therapy is indicated in the presence of permanent risk factors or in the case of idiopathic DVT or PE.
The recommended dose for NPF and VTE is 30 mg edoxaban once daily for patients with one or more of the following clinical factors:
moderate or severe renal failure (CC 15–50 ml/min);
low body weight: ≤ 60 kg;
simultaneous use of the following P-glycoprotein (P-gp) inhibitors: cyclosporine, dronedarone, erythromycin or ketoconazole.
Table 1. Summary of dosing information for NPF and VTE (DVT and PE)
General dosage recommendations
Recommended dose
60 mg edoxaban once daily
Dosage recommendations for patients with one or more of the following clinical factors:
moderate or severe renal insufficiency (creatinine clearance 15–50 ml/min)
If a dose of edoxaban is missed, the dose should be taken as soon as possible and the next day the recommended once-daily dose should be resumed. A double dose should not be taken to make up for a missed dose.
Switching to and from edoxaban
Patients with NFP and VTE should receive continuous anticoagulation therapy. In some situations, a change in anticoagulant therapy may be necessary (Table 2).
Table 2. Replacement of anticoagulant treatment for NFP and VTE (DVT and PE)
Switching to edoxaban
Current medication
Recommendations
Vitamin K antagonist (VKA)
Discontinue VKA and start edoxaban when INR ≤ 2.5
Other oral anticoagulants other than VKA
· dabigatran
· rivaroxaban
· apixaban
Stop dabigatran, rivaroxaban, or apixaban and start edoxaban when the next dose of oral anticoagulant would have been due
Parenteral anticoagulants
These medicines should not be used simultaneously.
Subcutaneous anticoagulants (e.g. LMWH, fondaparinux): subcutaneous anticoagulant should be discontinued and edoxaban should be initiated at the time the next subcutaneous dose of anticoagulant was scheduled.
Intravenous UFH: infusion should be stopped and edoxaban should be started after 4 hours.
Switching from edoxaban
The drug to which they are switching
Recommendations
AVK
There is a potential for inappropriate anticoagulant effect during the transition from edoxaban to VKA. Adequate anticoagulation should be ensured during any transition to an alternative anticoagulant.
Oral administration: Patients receiving the 60 mg dose should be prescribed edoxaban 30 mg once daily with the appropriate dose of VKA.
Patients receiving the 30 mg dose (due to one or more of the following clinical factors: moderate or severe renal impairment, low body weight, or concomitant use with specific P-gp inhibitors) should receive edoxaban at a dose of 15 mg once daily with the appropriate dose of VKA.
Patients should not take a loading dose of VKA with the aim of quickly achieving a stable INR of 2 to 3.
It is recommended to consider
Specifications
Characteristics
Active ingredient
Edoxaban
Country of manufacture
Ukraine
Dosage
60 мг
Form
Film-coated tablets
Method of application
Inside, solid
Primary packaging
blister
Producer
Kyiv Vitamin Plant JSC
Quantity per package
30 pcs
Trade name
Edoxacord
Vacation conditions
By prescription
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