Prevention of venous thromboembolism (VTE) in adults patients undergoing elective hip or knee replacement surgery.

Initially 10mg, 6 to 10 hours after surgery provided that haemostasis has been established, thereafter, 10mg once a day.
The duration of treatment depends on the patient's risk of venous thromboembolism, which is determined by the type of orthopaedic surgery:
Following major hip surgery a treatment duration of 5 weeks is recommended.
Following major knee surgery a treatment duration of 2 weeks is recommended.

 

 

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 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)

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 comorbidities, or who have developed recurrent DVT or PE on extended prevention with rivaroxaban 10mg once daily, a dose of rivaroxaban 20mg once daily

Moderate or severe renal impairment (creatinine clearance 15 to 49ml/minute).

For the treatment of DVT and PE and for the prevention of DVT and PE.

 

In patients with moderate or severe renal impairment: patients should be treated with 15mg twice daily for the first 3 weeks. Thereafter, when 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. The recommendation for the use of 15mg is based on PK modelling and has not been studied in this clinical setting.

When the recommended dose is 10mg once daily, no dose adjustment from the recommended dose is necessary.

Missed doses

 

Prevention of VTE in adult patients undergoing elective hip or knee replacement surgery

If a dose is missed the patient should take rivaroxaban immediately and continue the following day with once daily intake as before.

 

 

Treatment of DVT, treatment of PE and prevention of recurrent DVT and PE.

If a dose is missed during the 15mg twice daily treatment phase (day1 to 21), the patient should take rivaroxaban immediately to ensure intake of 30mg rivaroxaban per day. In this case two 15mg tablets may be taken at once. The 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 phase, 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.

 

 

Converting from vitamin K antagonists (VKA) to rivaroxaban

For patients treated for DVT, PE and prevention of recurrence, VKA treatment should be stopped and rivaroxaban therapy should be initiated once the International Normalized Ratio (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.

 

 

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 heparins) 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.

Administration

For oral administration. 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.

Contraindications

Children under 18 years
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
Vascular disorder

Precautions and Warnings

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 15-29ml/minute
Uncontrolled severe hypertension

Not recommended for anticoagulation with prosthetic heart valves
Advise ability to drive/operate machinery may be affected by side effects
Contains lactose
Administer at least 6 hours after removal of epidural catheter
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
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

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.

An epidural catheter must not be removed earlier than 18 hours after the last rivaroxaban dose. The next rivaroxaban dose is not to be administered earlier than 6 hours after the removal of the catheter.

Administration of rivaroxaban must be delayed 24 hours following traumatic puncture or invasive procedure.

Several subgroups of patients are at increased risk of bleeding, these patients are to be carefully monitored for signs and symptoms of bleeding complications and anaemia after initiation of treatment. In patients receiving rivaroxaban for VTE prevention following hip or knee replacement surgery, this may be done by regular physical examination of the patients, close observation of the surgical wound drainage and periodic measurements of haemoglobin. Any unexplained fall in haemoglobin or blood pressure should lead to a search for a bleeding site.

Rivaroxaban has not been studied in interventional clinical trials in patients undergoing hip fracture surgery to evaluate efficacy and safety.

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.

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.