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Indications, posology and method of administration
THERAPEUTIC INDICATIONS
- Prevention of stroke and systemic embolism in adult patients with non-valvular atrial fibrillation with one or more riskfactors, such as congestive heart failure, hypertension, age ≥ 75 years, 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 in adults.
POSOLOGY AND METHOD OF ADMINISTRATION
Posology:
Prevention of VTE in adult patients undergoing elective hip or knee replacement surgery:
The recommended dose is 10 mg rivaroxaban taken orally once daily. The initial dose should be taken 6 to 10 hoursafter surgery, provided that haemostasis has been established.
The duration of treatment depends on the individual risk of the patient for venous thromboembolism which is determinedby the type of orthopaedic surgery.
- For patients undergoing major hip surgery, a treatment duration of 5 weeks is recommended.
- For patients undergoing major knee surgery, a treatment duration of 2 weeks is recommended.
If a dose is missed the patient should take rivaroxaban immediately and then continue the following day with once daily intake as before.
Prevention of stroke and systemic embolism:
The recommended dose is 20 mg once daily, which is also the recommended maximum dose.
Therapy with rivaroxaban should be continued long term provided the benefit of prevention of stroke and systemic embolism outweighs the risk of bleeding.
If a dose is missed 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 DVT, treatment of PE and prevention of recurrent DVT and PE:
The recommended dose for the initial treatment of acute DVT or PE is 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 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.
When extended prevention of recurrent DVT and PE is indicated (following completion of at least 6 months therapy for DVT or PE), the recommended dose is 10 mg once daily. In patients in whom the risk of recurrent DVT or PE isconsidered high, such as those with complicated comorbidities, or who have developed recurrent DVT or PE on extended prevention with rivaroxaban 10 mg once daily, a dose of rivaroxaban 20 mg once daily should be considered.
The duration of therapy and dose selection should be individualised after careful assessment of the treatment benefit against the risk for bleeding.
| |
Time period |
Dosing schedule |
Total daily dose |
| Treatment and prevention of recurrent DVT and PE |
Day 1 – 21 |
15 mg twice daily |
30 mg |
| Day 22 on wards |
20 mg once daily |
20 mg |
| Prevention of recurrent DVT and PE |
Following completion of atleast 6 months therapy for DVT or PE |
10 mg once daily or
20 mg once daily |
10 mg or 20 mg |
If a dose is missed during the 15 mg twice daily treatment phase (day 1 – 21), the patient should take rivaroxaban immediately to ensure intake of 30 mg rivaroxaban per day. In this case two 15 mg tablets may be taken at once. The patient should 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 (day 22 on wards), 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 prevention of stroke and systemic embolism, VKA treatment should be stopped and rivaroxaban therapy should be initiated when the International Normalised Ratio (INR) is ≤ 3.0.
For patients treated for DVT, PE and prevention of recurrence, VKA treatment should be stopped and rivaroxaban therapy should be initiated once the INR is ≤ 2.5.
When converting patients from VKAs to rivaroxaban, International Normalised Ratio (INR) values will be falsely elevated after the intake of rivaroxaban. The INR is not valid to measure the anticoagulant activity of rivaroxaban, and therefore should not be used.
Converting from rivaroxaban to Vitamin K antagonists (VKA):
There is a potential for inadequate anticoagulation during the transition from rivaroxaban to VKA. Continuous adequateanticoagulation should be ensured during any transition to an alternate anticoagulant. It should be noted that rivaroxaban can contribute to an elevated INR.
In patients converting from rivaroxaban to VKA, 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 rivaroxaban and VKA the INR should not be tested earlier than 24 hours after the 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 that the next scheduled administration of the parenteral medicinal product (e.g. low molecularweight 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.
Special populations:
Renal impairment
Limited clinical data for patients with severe renal impairment (creatinine clearance 15 – 29 ml/min) indicate that rivaroxaban plasma concentrations are significantly increased. Therefore, rivaroxaban is to be used with caution in these patients. Use is not recommended in patients with creatinine clearance < 15 ml/min.
In patients with moderate (creatinine clearance 30 – 49 ml/min) or severe (creatinine clearance 15 – 29 ml/min) renal impairment the following dose recommendations apply:
- For the prevention of stroke and systemic embolism in patients with non-valvular atrial fibrillation, the recommended dose is 15 mg once daily.
- For the treatment of DVT, treatment of PE and prevention of recurrent DVT and PE: patients should be treated with 15mg twice daily for the first 3 weeks. Thereafter, when the recommended dose is 20 mg once daily, a reduction of thedose from 20 mg once daily to 15 mg 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 15 mg is based on PK modelling and has not been studied in this clinical setting.
When the recommended dose is 10 mg once daily, no dose adjustment from the recommended dose is necessary.
No dose adjustment is necessary in patients with mild renal impairment (creatinine clearance 50 – 80 ml/min).
Hepatic impairment
Rivaroxaban 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.
Body weight
No dose adjustment.
Gender
No dose adjustment.
Paediatric population
The safety and efficacy of rivaroxaban in children aged 0 to < 18 years have not been established, no data are available. Therefore, it is not recommended for use in children below 18 years of age.
Patients undergoing cardioversion
Rivaroxaban can be initiated or continued in patients who may require cardioversion.
For transesophageal echocardiogram (TEE) 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 15 mg rivaroxaban once daily (or 10 mg rivaroxaban once daily for patients with moderate renal impairment [creatinine clearance 30 – 49 ml/min]) 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 stentplacement.
Method of administration:
- For oral administration.
- For a 10 mg rivaroxaban dose once daily: It may be taken with or without food.
- For a 15 mg or higher rivaroxaban dose daily: Take after food.
- For patients who are unable to swallow whole tablets, the rivaroxaban tablet should be crushed and mixed with water or applesauce immediately prior to oral administration. For the 15 mg rivaroxaban film-coated tablet, food should be taken immediately afterward.
- Crushed rivaroxaban tablets may also be administered via a gastric tube after confirming correct tube placement. The crushed tablet should be mixed with a small amount of water and administered through the gastric tube, followed by additional water. For the 15 mg rivaroxaban film-coated tablet, enteral feeding should be initiated immediately thereafter.
CONTRAINDICATIONS
- Hypersensitivity to the active substance or to any of the excipients.
- 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 neoplasms at high risk of bleeding, recent brain or spinal injury, recentbrain, 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, e.g. unfractionated heparin (UFH), low molecular weight heparins (enoxaparin, dalteparin, etc.), heparin derivatives (fondaparinux, etc.), oral anticoagulants (warfarin, dabigatran etexilate, apixaban, etc.) except under specific circumstances of switching anticoagulant therapy or when 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.
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Contraindications
- Quá mẫn với bất kỳ thành phần nào của thuốc.
- Đang chảy máu nghiêm trọng trên lâm sàng.
- Thương tổn hoặc bệnh lý nếu được xem như là nguy cơ chảy máu nghiêm trọng.
- Điều trị đồng thời với bất kỳ thuốc chống đông máu khác.
- Bệnh gan với bệnh đông máu và nguy cơ chảy máu lâm sàng bao gồm những bệnh nhân xơ gan nhóm B và C theo phân loại Child Pugh.
- Phụ nữ có thai và đang cho con bú.
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Undesirable effects
TÁC DỤNG KHÔNG MONG MUỐN
Thường gặp (1/100 ≤ ADR < 1/10)
- Máu và hệ bạch huyết: Chứng thiếu máu.
- Thần kinh: Chóng mặt, đau đầu.
- Mạch máu: Hạ huyết áp, tụ máu.
- Hô hấp, lồng ngực và trung thất: Chảy máu cam, ho ra máu.
- Tiêu hóa: Chảy máu nướu răng, xuất huyết tiêu hóa buồn nôn, nôn, táo bón, tiêu chảy.
- Da và mô dưới da: Ngứa, xuất huyết da và dưới da.
- Cơ xương khớp và mô liên kết: Đau ở chân tay.
- Thận và tiết niệu: Xuất huyết đường tiết niệu, suy giảm chức năng thận.
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Warnings and precautions
CẢNH BÁO VÀ THẬN TRỌNG KHI DÙNG THUỐC
Khuyến cáo giám sát lâm sàng phù hợp với thực hành chống đông máu trong suốt thời gian điều trị.
Giống như các thuốc chống đông khác, bệnh nhân dùng Rivarelta phải được quan sát cẩn thận các dấu hiệu chảy máu. Khuyến cáo nên sử dụng thận trọng trong những chứng bệnh có gia tăng nguy cơ xuất huyết. Phải ngưng dùng Rivarelta nếu tình trạng xuất huyết nghiêm trọng xảy ra.
Rivaroxaban nên được sử dụng thận trọng ở những bệnh nhân có hệ số thanh thải creatinin 15 – 29 ml/phút. Không dùng rivaroxaban cho những bệnh nhân có hệ số thanh thải creatinin < 15 ml/phút.
Như các thuốc chống huyết khối khác, rivaroxaban không được sử dụng ở những bệnh nhân có nguy cơ tăng chảy máu.
Nếu cần phải can thiệp thủ thuật xâm lấn hoặc phẫu thuật, nên ngừng ngay rivaroxaban ít nhất 24 giờ trước khi tiến hành can thiệp nếu có thể và dựa trên đánh giá lâm sàng của bác sỹ.
Người càng lớn tuổi, nguy cơ xuất huyết càng tăng.
Sản phẩm này có chứa lactose. Bệnh nhân có vấn đề di truyền hiếm gặp không dung nạp galactose, thiếu hụt lactase hoặc kém hấp thụ glucose-galactose không nên dùng thuốc này.
SỬ DỤNG THUỐC CHO PHỤ NỮ CÓ THAI VÀ CHO CON BÚ
Phụ nữ mang thai:
Do độc tính sinh sản, nguy cơ xuất huyết và bằng chứng cho thấy rivaroxaban qua được nhau thai, không dùng rivaroxaban cho phụ nữ có thai.
Phụ nữ nên tránh mang thai khi đang điều trị với rivaroxaban.
Phụ nữ cho con bú:
Chống chỉ định sử dụng rivaroxaban ở phụ nữ đang cho con bú.
ẢNH HƯỞNG CỦA THUỐC LÊN KHẢ NĂNG LÁI XE, VẬN HÀNH MÁY MÓC
Những phản ứng bất lợi như ngất tạm thời và chóng mặt (thường gặp) được ghi nhận. Những bệnh nhân gặp những tác dụng không mong muốn này không nên lái xe hoặc sử dụng máy móc.
TƯƠNG TÁC THUỐC
Chất ức chế CYP3A4 và P-gp
Không khuyến cáo sử dụng rivaroxaban đồng thời với thuốc kháng nấm nhóm azole tác dụng toàn thân hoặc ức chế protease HIV.
Các thuốc chống đông máu
Tăng nguy cơ xuất huyết, cần theo dõi cẩn thận đối với những bệnh nhân dùng đồng thời rivaroxaban với những thuốc chống đông máu khác.
Các NSAID hoặc thuốc ức chế kết tập tiểu cầu
Cần lưu ý đến những bệnh nhân sử dụng đồng thời với các NSAID và chất ức chế kết tập tiểu cầu bởi vì những chất này làm tăng nguy cơ chảy máu.
Những thuốc cảm ứng enzym CYP3A4
Sử dụng đồng thời rivaroxaban với những chất cảm ứng CYP3A4 mạnh có thể cũng dẫn đến giảm nồng độ huyết tương của rivaroxaban.
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