Edoxaban oral
- Drugs List
- Therapeutic Indications
- Dosage
- Administration
- Contraindications
- Precautions and Warnings
- Pregnancy and Lactation
- Side Effects
- Monograph
Presentation
Oral formulations of edoxaban.
Drugs List
Therapeutic Indications
Uses
Deep vein thrombosis - prophylaxis
Deep vein thrombosis - treatment
Nonvalvular atrial fibrillation; prevention of stroke and systemic embolism
Pulmonary embolism - prophylaxis
Pulmonary embolism - treatment
Prevention of stroke and systemic embolism in patients with non-valvular atrial fibrillation (NVAF), with one or more risk factors, such as congestive heart failure, hypertension; age equal to or greater than 75 years, diabetes mellitus, prior stroke or transient ischaemic attack (TIA).
Treatment and prevention of recurrent deep vein thrombosis (DVT).
Treatment and prevention of recurrent pulmonary embolism (PE).
Dosage
Adults
Prevention of stroke and systemic embolism in patients with non-valvular atrial fibrillation
The recommended dose is 60mg once daily.
Therapy with edoxaban in patients with NVAF should be continued long term.
Treatment of deep vein thrombosis (DVT) and pulmonary embolism (PE), and prevention of recurrent DVT and PE
The recommended dose is 60mg once daily following an initial use of parenteral anticoagulant for at least 5 days.
Edoxaban and initial parenteral anticoagulant should not be administered simultaneously.
The duration of therapy for the treatment of DVT and PE and prevention of recurrent VTE should be individualised after careful assessment of the treatment benefit against the risk for bleeding. Short duration therapy (at least 3 months) should be based on transient risk factor and longer durations should be based on permanent risk factors or idiopathic DVT or PE.
Patients with Renal Impairment
Mild renal impairment (creatinine clearance greater than 50 to 80ml/minute)
The recommended dose is 60mg once daily.
Moderate or severe renal impairment (creatinine clearance 15 to 50ml/minute)
The recommended dose is 30mg once daily.
Additional Dosage Information
Dose reduction in patients with low body weight
For all indications the recommended dose is 30mg once daily in patients with a body weight less than or equal to 60kg.
Missed dose
If a dose of edoxaban is missed, the dose should be taken immediately and then be continued the following day with the once daily intake as recommended. The patient should not take double the prescribed dose on the same day to make up for a missed dose.
Switching from Vitamin K Antagonist (VKA) to edoxaban
Discontinue the VKA and start edoxaban when the international normalised ratio (INR) is less than or equal to 2.5.
Switching from oral anticoagulants other than VKA to edoxaban
Discontinue oral anticoagulant and start edoxaban at the time of the next dose of the oral anticoagulant.
Switching from parenteral anticoagulants to edoxaban
Parenteral anticoagulants should not be administered simultaneously with edoxaban.
From subcutaneous anticoagulants
Discontinue subcutaneous anticoagulant and start edoxaban at the time of the next scheduled subcutaneous anticoagulant dose.
From intravenous unfractionated heparin (UFH)
Discontinue the UFH infusion and start edoxaban 4 hours later.
Switching from edoxaban to VKA
There is a potential for inadequate anticoagulation during the transition from edoxaban to VKA. Continuous adequate anticoagulation should be ensured during any transition to an alternate anticoagulant.
Using oral VKA
For patients currently on a 60mg dose, administer 30mg edoxaban once daily together with an appropriate VKA dose.
For patients currently on a 30mg dose, administer 15mg edoxaban once daily together with an appropriate VKA dose.
Patients should not take a loading dose of VKA in order to promptly achieve a stable INR between 2 and 3. Take into account the maintenance dose of VKA and if the patient was previously taking a VKA or to use valid INR driven VKA treatment algorithm.
Once an INR greater than or equal to 2 is achieved, edoxaban should be discontinued. Most patients should be able to achieve an INR of greater than or equal to 2 within 14 days of concomitant administration of edoxaban and VKA. After 14 days it is recommended that edoxaban is discontinued and the VKA continued to be titrated to achieve an INR between 2 and 3.
Concomitant edoxaban and VKA can increase the INR post edoxaban dose, it is recommended that during the first 14 days of concomitant therapy the INR is measured at least 3 times just prior to taking the daily dose of edoxaban to minimise the influence of edoxaban on INR measurements.
Using a parenteral anticoagulant and oral VKA
Discontinue edoxaban and administer a parenteral anticoagulant and VKA at the time of the next scheduled edoxaban dose. Once a stable INR of greater than or equal to 2 is achieved, the parenteral anticoagulant should be discontinued and the VKA continued.
Switching from edoxaban to oral anticoagulants other than VKA
Discontinue edoxaban and start the non-VKA anticoagulant at the time of the next scheduled dose of edoxaban.
Switching from edoxaban to parenteral anticoagulants
These agents should not be administered simultaneously.
Discontinue edoxaban and start the parenteral anticoagulant at the time of the next scheduled dose of edoxaban.
Patients undergoing cardioversion
Edoxaban can be initiated or continued in patients who may require cardioversion.
Transoesophageal echocardiogram (TEE) guided cardioversion in patients not previously treated with anticoagulants, edoxaban should be started at least 2 hours before cardioversion to ensure adequate anticoagulation.
Cardioversion should be performed no later than 12 hours after the dose of edoxaban. Confirmation should be sought prior to cardioversion that the patient has taken edoxaban as prescribed.
Administration
For patients unable to swallow whole tablets, edoxaban tablets may be crushed and mixed with water or apple puree immediately prior to use and administered orally.
Contraindications
Children under 18 years
Haemorrhage
Arteriovenous malformation
Breastfeeding
Coagulopathy due to hepatic disorder
Gastrointestinal ulcer
History of gastrointestinal ulceration
Moderate mitral stenosis
Neoplasm with increased bleeding risk
Oesophageal varices
Pregnancy
Prosthetic heart valve
Recent central nervous system surgery
Recent central nervous system trauma
Recent intracranial haemorrhage
Recent ocular surgery
Renal dialysis
Renal impairment - creatinine clearance below 15ml/minute
Severe hepatic impairment
Uncontrolled severe hypertension
Vascular disorder
Precautions and Warnings
Elderly
Females of childbearing potential
Risk of haemorrhage
Weight below 61kg
Antiphospholipid syndrome
Elevated serum transaminases - greater than twice the upper limit of normal
Haemodynamic instability
Hepatic impairment
Renal impairment - creatinine clearance 15-50ml/minute
Serum bilirubin above 1.5 times upper limit of normal
Reduce dose in patients with creatinine clearance of 15 - 50ml/min
Anticoagulant effect cannot be reliably monitored with standard tests
Evaluate renal function before and during treatment
Perform liver function tests before commencing therapy
Monitor for bleeding during treatment
Monitor for unexplained fall in blood pressure or haematocrit
Monitor liver function on prolonged therapy
Reduce dose in patients who weigh less than 61kg
Discontinue if severe haemorrhage occurs
Discontinue prior to surgery
Advise patient not to take NSAIDs unless advised by clinician
Advise patient not to take St John's wort concurrently
Female: Ensure adequate contraception during treatment
Advise patient of risk of bleeding
Remind patient of importance of carrying Alert Card with them at all times
Haemorrhagic risk
Mucosal bleedings and anaemia have been seen more frequently during long term edoxaban treatment compared with VKA treatment.
Discontinuation for surgery and other interventions
If the need for a procedure is identified less than 24 hours after the last dose of edoxaban the risk of bleeding should be weighed against the urgency of treatment. Following the procedure, edoxaban should be restarted once adequate haemostasis is established.
If oral medication cannot be taken following a procedure then consider using a parenteral anticoagulant then switching to edoxaban when the oral route is available.
Prosthetic heart valves and moderate to severe mitral stenosis
Edoxaban is not recommended in patients with mechanical heart valves, during the first 3 months after implantation of bioprosthetic heart valves or in patients with moderate to severe mitral stenosis.
Haemodynamically unstable PE patients or those who require thrombolysis or pulmonary embolectomy
Edoxaban is not recommended as an alternative to unfractionated heparin in patients with PE who are either haemodynamically unstable or may receive thrombolysis or pulmonary embolectomy.
Patients with active cancer
Efficacy and safety of edoxaban in the treatment and/or prevention of VTE in patients with active cancer has not been established.
Antiphospholipid syndrome
Direct acting Oral Anticoagulants (DOACs) including edoxaban are not recommended for patients with a history of thrombosis who are diagnosed with antiphospholipid syndrome. In particular for patients that are triple positive (for lupus anticoagulant, anticardiolipin antibodies, and anti-beta 2-glycoprotein 1 antibodies), treatment with DOACs could be associated with increased rates of recurrent thrombotic events compared with vitamin K antagonist therapy.
Pregnancy and Lactation
Pregnancy
Edoxaban is contraindicated during pregnancy.
Use of edoxaban during pregnancy is contraindicated by the manufacturer. There is limited published experience concerning the use of edoxaban during pregnancy. Animal studies have shown reproductive toxicity. Edoxaban is known to cross the placenta. The potential risk to the foetus is unknown.
Lactation
Edoxaban is contraindicated during breastfeeding.
The manufacturer advises that the patient either discontinues edoxaban or discontinues breastfeeding. There is limited published experience concerning the use of edoxaban during breastfeeding. Animal studies haven shown the excretion of edoxaban in breast milk, however the presence in human breast milk and the effects in exposed infants are unknown.
Side Effects
Abdominal pain
Abnormal liver function tests
Anaemia
Anaphylactic reaction
Angioedema
Aspartate aminotransferase increased
Bleeding (surgical site)
Cerebral haemorrhage
Conjunctival haemorrhage
Dizziness
Epistaxis
Gamma glutamyl transferase (GGT) increased
Gastro-intestinal haemorrhage
Haematoma (injection site)
Haemoptysis
Haemorrhage
Headache
Hypersensitivity reactions
Increase in alkaline phosphatase
Increase in serum transaminases
Intracranial bleeding
Joint/bone haemorrhage
Macroscopic haematuria
Menstrual bleeding increased
Muscle haemorrhage
Nausea
Ocular haemorrhage
Pericardial haemorrhage
Pharyngeal haemorrhage
Pruritus
Rash
Retroperitoneal bleeding
Serum bilirubin increased
Skin/soft tissue haemorrhage
Subdural haematoma
Thrombocytopenia
Urethral bleeding
Urticaria
Vaginal haemorrhage
Overdosage
It is strongly recommended that the UK National Poisons Information Service be consulted on cases of suspected or actual overdose where there is doubt over the degree of risk or about appropriate management.
The following number will direct the caller to the relevant local centre (0844) 892 0111
Information may be obtained if you have access to ToxBase the primary clinical toxicology database of the National Poisons Information Service. This is available via password on the internet ( www.toxbase.org ) or if this is unavailable at the backup site ( www.toxbasebackup.org ).
Further Information
Last Full Review Date: May 2019.
Reference Sources
Summary of Product Characteristics: Lixiana 15mg tablets. Daiichi Sankyo UK Ltd. Revised November 2020.
Summary of Product Characteristics: Lixiana 30mg tablets. Daiichi Sankyo UK Ltd. Revised November 2020.
Summary of Product Characteristics: Lixiana 60mg tablets. Daiichi Sankyo UK Ltd. Revised November 2020.
HPRA Safety Notices May 2019.
Available at: https://www.hpra.ie
Last accessed: 07 June 2019.
MHRA Drug Safety Update June 2020
Available at: https://www.mhra.gov.uk
Last accessed: 06 November 2020
Medscape UK | Univadis prescription drug monographs & interactions are based on FDB Multilex Content
FDB Disclaimer : FDB Multilex is intended for the use of healthcare professionals and is provided on the basis that the healthcare professionals will retain FULL and SOLE responsibility for deciding what treatment to prescribe or dispense for any particular patient or circumstance.