Xelostad 10

Rx

Indications

• Prevention of venous thromboembolism (VTE) in adult patients undergoing elective hip or knee replacement surgery.
• Treatment of deep vein thrombosis (DVT) and pulmonary embolism (PE), and prevention of recurrent DVT and PE in adults.

Dosage

Prevention of venous thromboembolism (VTE):

• 10 mg rivaroxaban, once daily, should be taken 6 – 10 hours after surgery, provided that haemostasis has been established.
• Duration of treatment: 5 weeks (undergoing major hip surgery), 2 weeks (undergoing major knee surgery).
• If a dose is missed the patient should take Xelostad 10 immediately and then continue the following day with once daily intake as before.

Treatment of deep vein thrombosis (DVT) and pulmonary embolism (PE), and prevention of recurrent DVT and PE:

• Treatment: Initiate at 15 mg twice daily for the first three weeks followed by 20 mg 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 provoked by major transient risk factors and longer duration of therapy should be considered in patients with provoked not related to major transient risk factors, unprovoked DVT or PE, or a history of recurrent DVT or PE.
• If a dose is missed during the 15 mg twice daily treatment phase, the patient can take two 15 mg tablets at once immediately, and continue with the regular 15 mg 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.
• Extended prevention of recurrent DVT and PE (following at least 6 months therapy for DVT or PE): 10 mg once daily. In patients in whom the risk of recurrent is considered high, a dose of rivaroxaban 20 mg once daily should be considered. Careful assessment of the treatment benefit against the risk for bleeding

Converting from Vitamin K antagonists (VKA) to Xelostad 10: International Normalized Ratio (INR) values will be falsely elevated and should not be used to measure the anticoagulant activity of Xelostad 10.

Converting from Xelostad 10 to Vitamin K antagonists (VKA):

• Continuous adequate anticoagulation should be ensured during any transition to an alternate anticoagulant. It should be noted that Xelostad 10 can contribute to an elevated INR.
• VKA should be given concurrently until the INR is ≥ 2.0. For the first two days of the conversion period, standard initial dosing of VKA should be used followed by VKA dosing, as guided by INR testing. While patients are on both Xelostad 10 and VKA the INR should not be tested earlier than 24 hours after the previous dose but prior to the next dose of Xelostad 10. Once Xelostad 10 is discontinued INR testing may be done reliably at least 24 hours after the last dose.

Converting from parenteral anticoagulants to Xelostad 10: Discontinue the parenteral anticoagulant and start Xelostad 10 from 0 to 2 hours before the time that 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 Xelostad 10 to parenteral anticoagulants: Give the first dose of parenteral anticoagulant at the time the next Xelostad 10 dose would be taken.

Renal impairment:

• Use is not recommended in patients with creatinine clearance < 15 ml/min, Xelostad 10 is to be used with caution in patients with severe renal impairment (creatinine clearance 15 – 29 ml/min).
• No dose adjustment is necessary in patients with mild renal impairment (creatinine clearance 50 – 80 ml/min) or moderate renal impairment (creatinine clearance 30 – 49 ml/min).

Hepatic impairment: Xelostad 10 is contraindicated in patients with hepatic disease associated with coagulopathy and clinically relevant bleeding risk including cirrhotic patients with Child Pugh B and C.

Elderly population: No dose adjustment.

No dose adjustment according to body weight, gender.

Paediatric population: Not recommended for use in children below 18 years of age.

Usage

• Xelostad 10 is administered orally, with or without food.
• For patients who are unable to swallow whole tablets, Xelostad 10 tablet may be crushed and mixed with water or apple puree immediately prior to use and administered orally.
• The crushed Xelostad 10 tablet may also be given through gastric tubes after confirmation of the correct gastric placement of the tube. The crushed tablet should be administered in a small amount of water via a gastric tube after which it should be flushed with water.

• Hypersensitivity to any of the ingredients.
• Active clinically significant bleeding.
• Lesion or condition, if considered to be a significant risk for major bleeding. This may include current or recent gastrointestinal ulceration, presence of malignant eoplasms at high risk of bleeding, recent brain or spinal injury, recent brain, spinal or ophthalmic surgery, recent intracranial haemorrhage, known or suspected oesophageal varices, arteriovenous malformations, vascular aneurysms or major intraspinal or intracerebral vascular abnormalities.
• Concomitant treatment with any other anticoagulants except under specific circumstances of switching anticoagulant therapy or when unfractionated heparin (UFH) is given at doses necessary to maintain an open central venous or arterial catheter.
• Hepatic disease associated with coagulopathy and clinically relevant bleeding risk including cirrhotic patients with Child Pugh B and C.
• Pregnancy and breast feeding.

Common

• Anaemia (incl. respective laboratory parameters);
• Dizziness, headache;
• Eye haemorrhage (incl. conjunctival haemorrhage);
• Epistaxis, haemoptysis;
• Gingival bleeding, gastrointestinal tract haemorrhage (incl. rectal haemorrhage), gastrointestinal and abdominal pains, dyspepsia, nausea, constipation, diarrhoea, vomiting;
• Pruritus (incl. uncommon cases of generalised pruritus), rash, ecchymosis, cutaneous and subcutaneous haemorrhage;
• Pain in extremity;
• Urogenital tract haemorrhage (incl. haematuria and menorrhagia), renal impairment (incl. blood creatinine increased, blood urea increased);
• Fever, peripheral oedema, decreased general strength and energy (incl. fatigue and asthenia);
• Increase in transaminases;
• Postprocedural haemorrhage (incl. postoperative anaemia, and wound haemorrhage), contusion, wound secretion.

Haemorrhagic risk

• Caution in conditions with increased risk of haemorrhage (congenital or acquired bleeding disorders; uncontrolled severe arterial hypertension; other gastrointestinal disease without active ulceration that can potentially lead to bleeding complications; vascular retinopathy; bronchiectasis or history of pulmonary bleeding). Xelostad 10 administration should be discontinued if severe haemorrhage occurs.

Renal impairment

• Caution in patients with creatinine clearance 15 – 29 ml/min. Use is not recommended in patients with creatinine clearance < 15 ml/min.
• In patients with moderate renal impairment (creatinine clearance 30 – 49 ml/min) concomitantly receiving other medicinal products which increase rivaroxaban plasma concentrations Xelostad 10 is to be used with caution.

Interaction with other medicinal products

• The use of Xelostad 10 is not recommended in patients receiving concomitant systemic treatment with azole-antimycotics or HIV protease inhibitors.
• Care is to be taken if patients are treated concomitantly with medicinal products affecting haemostasis such as nonsteroidal anti-inflammatory medicinal products NSAIDs), acetylsalicylic acid (ASA) and platelet aggregation inhibitors or selective serotonin reuptake inhibitors (SSRIs), and serotonin norepinephrine reuptake inhibitors (SNRIs).

Safety and efficacy of Xelostad 10 have not been studied in patients with prosthetic heart valves. Treatment with Xelostad 10 is not recommended for these patients.

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

Spinal/epidural anaesthesia or puncture

• Prior to neuraxial intervention the physician should consider the potential benefit versus the risk in anticoagulated patients or in patients to be anticoagulated for thromboprophylaxis. Patients are to be frequently monitored for signs and symptoms of neurological impairment (e.g. numbness or weakness of the legs, bowel or bladder dysfunction). If neurological compromise is noted, urgent diagnosis and treatment is necessary.
• At least 18 hours 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.

Dosing recommendations before and after invasive procedures and surgical intervention other than elective hip or knee replacement surgery

• If an invasive procedure or surgical intervention is required, Xelostad 10 should be stopped at least 24 hours before the intervention, if possible and based on the clinical judgement of the physician.
• If the procedure cannot be delayed the increased risk of bleeding should be assessed against the urgency of the intervention.
• Xelostad 10 should be restarted as soon as possible after the invasive procedure or surgical intervention provided the clinical situation allows and adequate haemostasis has been established as determined by the treating physician.

Elderly population: Increasing age may increase haemorrhagic risk.

Dermatological reactions: Rivaroxaban should be discontinued at the first appearance of a severe skin rash (e.g. spreading, intense and/or blistering), or any other sign of hypersensitivity in conjunction with mucosal lesions.

Xelostad 10 contains lactose. Patients with rare hereditary problems of galactose intolerance, total lactase deficiency or glucose-galactose malabsorption should not take this medicine.Patients should be aware of how they react to drug before driving or operating machinery.

Xelostad 10 is contraindicated during pregnancy and lactation.

Patients should be aware of how they react to drug before driving or operating machinery.