Prevention of stroke and systemic embolism

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

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)

Treatment of VTE and prevention of VTE recurrence

Dose adjustments should be made based on changes in body weight only. Monitor body weight regularly.

Body weight of 50kg or more

Body weight from 30kg to 50kg

Adult patients with moderate or severe renal impairment (creatinine clearance 15 to 49ml/minute)

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.

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