Rivaroxaban 15mg and 20mg oral
- Drugs List
- Therapeutic Indications
- Dosage
- Administration
- Contraindications
- Precautions and Warnings
- Pregnancy and Lactation
- Side Effects
- Monograph
Presentation
Oral formulations of high strength rivaroxaban (15mg and/or 20mg).
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
Recurrent deep vein thrombosis: Extended prevention
Recurrent pulmonary embolism: Extended prevention
Prevention of stroke and systemic embolism in adult patients with non-valvular atrial fibrillation with one or more risk factors, such as congestive heart failure, hypertension, age 75 years and older, diabetes mellitus, prior stroke or transient ischaemic attack.
Treatment of deep vein thrombosis (DVT) and pulmonary embolism (PE), and prevention of recurrent DVT and PE.
Treatment of venous thromboembolism (VTE) and prevention of VTE recurrence in children and adolescents aged less than 18 years and weighing more than 50kg after at least 5 days of initial parenteral anticoagulation treatment.
Dosage
Adults
Prevention of stroke and systemic embolism
The recommended dose is 20mg once daily. Maximum daily dose of 20mg.
Therapy with rivaroxaban should be continued long term provided the benefit of prevention of stroke and systemic embolism outweighs the risk of bleeding.
Treatment of deep vein thrombosis (DVT) and pulmonary embolism (PE) and prevention of recurrent DVT and PE
The initial dose for the treatment of acute DVT or PE is 15mg twice daily for the first three weeks, followed by 20mg once daily for the continued treatment and prevention of recurrent DVT or PE.
Short duration of therapy (at least 3 months) should be considered in patients with DVT or PE provoked by major transient risk factors (i.e recent major surgery or trauma). Longer duration of therapy should be considered in patients with provoked DVT or PE not related to major transient risk factors, unprovoked DVT or PE, or a history of recurrent DVT or PE.
Extended prevention of recurrent DVT and PE (Following completion of at least 6 months therapy for DVT or PE)
The recommended dose is 10mg once daily. In patients whom the risk of recurrent DVT or PE is considered high, such as those with complicated co morbidities, or who have developed recurrent DVT or PE on extended prevention with rivaroxaban 10mg once daily, a dose of rivaroxaban 20mg once daily should be considered.
Children
Treatment of VTE and prevention of VTE recurrence
Initiate treatment following at least 5 days of initial parenteral anticoagulation treatment. Treatment should be continued for at least 3 months and extended to up to 12 months if clinically necessary.
Dose adjustments should be made based on changes in body weight only. Monitor body weight regularly.
Body weight of 50kg or more
20mg once daily. This is the maximum daily dose.
Body weight from 30kg to 50kg
15mg once daily. This is the maximum daily dose.
Patients with Renal Impairment
Adult patients with moderate or severe renal impairment (creatinine clearance 15 to 49ml/minute)
For the prevention of stoke and systemic embolism in patients with non-valvular atrial fibrillation, the recommended dose is 15mg once daily.
For the treatment of DVT and PE, and prevention of recurrent DVT and PE, the recommended dose is 15mg twice daily for the first three weeks. Thereafter, the recommended dose is 20mg once daily. A reduction of the dose from 20mg once daily to 15mg once daily should be considered if the patient's assessed risk for bleeding outweighs the risk for recurrent DVT and PE.
When the recommended dose is 10mg once daily, no dose adjustment from the recommended dose is necessary.
Additional Dosage Information
Missed dose
Prevention of stroke and systemic embolism
If a dose is missed the patient should take rivaroxaban immediately and continue as normal the following day with one tablet once daily. The dose should not be doubled within the same day to make up for a missed dose.
Treatment of deep vein thrombosis (DVT) and pulmonary embolism (PE) and prevention of recurrent DVT and PE in adults
If a dose is missed during the 15mg twice daily treatment stage (day 1 to 21), the patient should take rivaroxaban immediately to ensure intake of 30mg rivaroxaban daily. In this case two 15mg tablets may be taken at once. Patients should continue with the regular 15mg twice daily intake as recommended on the following day.
If a dose is missed during the once daily treatment stage (day 22 onwards), the patient should take rivaroxaban immediately and continue on the following day with the once daily intake as recommended. The dose should not be doubled within the same day to make up for a missed dose.
Treatment of venous thromboembolism (VTE) and prevention of VTE recurrence in children and adolescents aged less than 18 years and weighing more than 50kg
If a dose is missed, the missed dose should be taken as soon as possible after it is noticed, but only on the same day. If this is not possible, the patient should skip the dose and continue with the next dose as prescribed, The patient should not take two doses to make up for the missed dose.
If the patient spits up the dose or vomits within 30 minutes after receiving the dose, a new dose should be given. If the patient vomits more than 30 minutes after the dose, the dose should not be re-administered and the next dose should be taken as scheduled.
Converting from vitamin K antagonists (VKA) to rivaroxaban
For patients treated for prevention of stroke and systemic embolism, VKA treatment should be stopped and rivaroxaban therapy should be initiated when the INR is 3 or less.
For patients treated for DVT and PE, and prevention of recurrent DVT and PE, VKA treatment should be stopped and rivaroxaban therapy should be initiated once the INR is less than or equal to 2.5. When converting patients from VKAs to rivaroxaban, INR values will be falsely elevated after the intake of rivaroxaban, and therefore is not valid to measure the anticoagulant activity of rivaroxaban.
Converting from rivaroxaban to vitamin K antagonists (VKA)
In patients converting from rivaroxaban to VKA, VKA should be given concurrently until the INR is 2 or greater. For the first two days of the conversion period, standard initial dosing of VKA should be used followed by VKA dosing guided by INR testing. While patients are on both rivaroxaban and VKA the INR should not be tested earlier than 24 hours after previous dose but prior to the next dose of rivaroxaban. Once rivaroxaban is discontinued INR testing may be done reliably at least 24 hours after the last dose.
Children converting from rivaroxaban to VKA need to continue rivaroxaban for 48 hours after the first dose of VKA. Following 2 days of co-administration an INR should be obtained prior to the next scheduled dose of rivaroxaban. Co-administration of rivaroxaban and VKA should continue until the INR is 2 or greater. Once rivaroxaban is discontinued INR testing may be done reliably 24 hours after the last dose.
Converting from parenteral anticoagulants to rivaroxaban
For patients currently receiving a parenteral anticoagulant, discontinue the parenteral anticoagulant and start rivaroxaban 0 to 2 hours before the time of the next scheduled administration of the parenteral medicinal product (e.g. low molecular weight heparin) would be due or at the time of discontinuation of a continuously administered parenteral medicinal product (e.g. intravenous unfractionated heparin).
Converting from rivaroxaban to parenteral anticoagulants
Give the first dose of parenteral anticoagulant at the time the next rivaroxaban dose would be taken.
Patients undergoing cardioversion
Rivaroxaban can be initiated or continued in patients who may require cardioversion.
For transoesophageal echocardiogram guided cardioversion in patients not previously treated with anticoagulants, rivaroxaban treatment should be started at least 4 hours before cardioversion to ensure adequate anticoagulation. For all patients, confirmation should be sought prior to cardioversion that the patient has taken rivaroxaban as prescribed. Decisions on initiation and duration of treatment should take established guideline recommendations for anticoagulant treatment in patients undergoing cardioversion into account.
Patients with non-valvular atrial fibrillation who undergo PCI (percutaneous coronary intervention) with stent placement.
There is limited experience of a reduced dose of 15mg rivaroxaban once daily, in addition to a P2Y12 inhibitor for a maximum of 12 months in patients with non-valvular atrial fibrillation who require oral anticoagulation and undergo PCI with stent placement and there is no data available for such patients with a history of stroke or TIA.
Administration
For oral administration with food. For patients unable to swallow whole tablets, rivaroxaban may be crushed and mixed with water or apple puree immediately prior to use and administered orally. The dose should be followed by food immediately.
Children under 18 years
Swallow tablet with liquid and also take with food. Tablets should be taken approximately 24 hours apart. Children who are unable to swallow whole tablets should use the granules for oral suspension.
Contraindications
Children weighing less than 30kg
Haemorrhage
Arteriovenous malformation
Breastfeeding
Coagulopathy due to hepatic disorder
Galactosaemia
Gastrointestinal ulcer
History of gastrointestinal ulceration
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 impairment - creatinine clearance below 15ml/minute
Renal impairment in children under 18 years - GFR <50ml/minute/1.73m sq
Vascular disorder
Precautions and Warnings
Children under 18 years
Predisposition to haemorrhage
Spinal/epidural anaesthesia
Antiphospholipid syndrome
Bronchiectasis
Coagulopathy
Gastrointestinal disorder
Glucose-galactose malabsorption syndrome
Haemorrhagic retinopathy
History of pulmonary haemorrhage
Lactose intolerance
Renal impairment - creatinine clearance 15-49ml/minute
Uncontrolled severe hypertension
Not recommended for anticoagulation with prosthetic heart valves
Reduce dose in patients with moderate renal impairment
Advise ability to drive/operate machinery may be affected by side effects
Not all presentations are licensed for all indications
Contains lactose
Administer at least 6 hours after removal of epidural catheter
Must be taken with food and water
Increased risk of spinal haematoma with post-op insitu epidural catheter
Consider monitoring haemoglobin/haematocrit
Monitor anti-Factor Xa levels in patients at risk of bleeding
Monitor for bleeding during treatment
Monitor patients undergoing spinal or epidural anaesthesia closely
Reversal agent available
Spinal anaesthesia: tell patient-report symptoms of neurological impairment
Discontinue treatment 24 hours prior to surgery
Discontinue if drug-related rash or other hypersensitivity reactions occur
Discontinue if severe haemorrhage occurs
Not licensed for all indications in all age groups
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
Several subgroups are at increased risk of bleeding, they should be monitored for signs and symptoms of bleeding complications and anaemia after initiation of treatment. If an unexplained fall in haemoglobin or blood pressure occurs the patient should be investigated for a bleeding site.
Patients undergoing spinal or epidural anaesthesia or puncture while being treated with rivaroxaban are at risk of developing an epidural or spinal haematoma which could result in long term or permanent paralysis. This risk is increased by the use of indwelling epidural catheters or other drugs affecting haemostasis. Traumatic or repeated epidural or spinal puncture will also increase the risk. Urgent diagnosis and treatment is required if neurological compromise is observed. Prior to neuraxial intervention the potential risks should be weighed against the benefits in patients currently anticoagulated or planned to be anticoagulated for thromboprophylaxis.
To reduce the potential risk of bleeding associated with the concurrent use of rivaroxaban and neuraxial (epidural/spinal) anaesthesia or spinal puncture, consider the pharmacokinetic profile of rivaroxaban. Placement or removal of an epidural catheter or lumbar puncture is best performed when the anticoagulant effect of rivaroxaban is estimated to be low.
At least 18 hours in young patients and 26 hours in elderly patients should elapse after the last administration of rivaroxaban before removal of an epidural catheter. Following removal of the catheter, at least 6 hours should elapse before the next rivaroxaban dose is administered.
If traumatic puncture occurs the administration of rivaroxaban is to be delayed for 24 hours.
Increasing age may increase haemorrhagic risk.
Administration of rivaroxaban must be stopped at least 24 hours before invasive procedure. Rivaroxaban should be restarted after the invasive procedure or surgical intervention as soon as possible provided the clinical situation allows and adequate haemostasis has been established.
Rivaroxaban is not recommended as an alternative to unfractionated heparin in patients with pulmonary embolism who are haemodynamically unstable or may receive thrombolysis or pulmonary embolectomy since the safety and efficacy of rivaroxaban have not been established in these clinical situations.
Serious skin reactions, including Stevens-Johnson syndrome, Toxic Epidermal Necrolysis and DRESS syndrome (Drug rash with eosinophilia and systemic symptoms) have been reported. The highest risk for these reactions occurs early in the course of therapy within the first weeks of treatment. Rivaroxaban should be discontinued at the first appearance of a severe skin rash, or any other sign of hypersensitivity in conjunction with mucosal lesions.
Direct acting Oral Anticoagulants (DOACs) including rivaroxaban 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
Rivaroxaban is contraindicated during pregnancy.
Use of rivaroxaban during pregnancy is contraindicated by the manufacturer. Animal studies have shown reproductive toxicity. Human data is limited and as such a potential risk cannot be ruled out.
Lactation
Rivaroxaban is contraindicated during breastfeeding.
The manufacturer advises that the patient either discontinues rivaroxaban or discontinues breastfeeding. Animal studies show that rivaroxaban is excreted in the breast milk, however presence in human breast milk is unknown. Effects on exposed infants are unknown.
Side Effects
Abdominal pain
Abnormal liver function
Acute renal failure
Allergic dermatitis
Allergic reaction
Anaemia
Anaphylactic reaction
Anaphylactic shock
Angioedema
Asthenia
Blood urea increased
Cerebral haemorrhage
Cholestasis
Compartment syndrome
Conjunctival haemorrhage
Constipation
Contusion
Diarrhoea
Dizziness
Drug rash with eosinophilia and systemic symptoms (DRESS)
Dry mouth
Dyspepsia
Ecchymosis
Elevated amylase levels
Elevated serum lipase
Eosinophilic pneumonia
Epistaxis
Extremity pain
Fatigue
Fever
Gamma glutamyl transferase (GGT) increased
Gastro-intestinal haemorrhage
Genitourinary bleeding
Gingival bleeding
Haemarthrosis
Haematoma
Haematuria
Haemoptysis
Haemorrhage
Headache
Hepatitis
Hypersensitivity reactions
Hypotension
Increase in alkaline phosphatase
Increase of liver transaminases
Increased platelet count
Intracranial bleeding
Jaundice
Malaise
Menorrhagia
Muscle haemorrhage
Nausea
Ocular haemorrhage
Oedema
Peripheral oedema
Post operative wound haemorrhage
Pruritus
Rash
Rectal bleeding
Renal impairment
Serum bilirubin increased
Serum creatinine increased
Stevens-Johnson syndrome
Syncope
Tachycardia
Thrombocythaemia
Thrombocytopenia
Toxic epidermal necrolysis
Urticaria
Vascular pseudoaneurysm
Vomiting
Wound secretion
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: December 2022
Reference Sources
Summary of Product Characteristics: Xarelto 15mg film coated tablets. Bayer Plc. Revised November 2022.
Summary of Product Characteristics: Xarelto 20mg film coated tablets. Bayer Plc. Revised November 2022.
Summary of Product Characteristics: Xarelto 15-20mg Film-Coated Tablets Treatment Initiation Pack. Bayer Plc. Revised November 2022.
HPRA Safety Notices October 2018, May 2019
Available at: https://www.hpra.ie
Last accessed: 06 September 2019
NICE Evidence Services Available at: www.nice.org.uk Last accessed: 08 April 2021
MHRA Drug Safety Update July 2019
Available at: https://www.mhra.gov.uk
Last accessed: 06 September 2019
MHRA Drug Safety Update June 2020
Available at: https://www.mhra.gov.uk
Last accessed: 06 November 2020
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