REZALTO 10 mg Film-coated tablet Ref.[115242] Active ingredients: Rivaroxaban

Posology

Recommended dose and frequency of administration

The recommend dose is one REZALTO once daily for the prevention of various thromboembolism (VTE) in major orthopaedic surgery.

The initial dose should be taken within 6–10 hours after surgery provided that haemostasis has been established.

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

Duration of treatment

The duration of treatment depends on the type of major orthopaedic surgery.

After major hip surgery patients should be treated for 5 weeks.

After major knee surgery patients should be treated for 2 weeks.

Special populations

Elderly (above 65 years). Gender and body Weight

No dose adjustment is required for these patient populations.

Paediatric population

Children (up to 18 years of age):

The safety and efficacy of REZALTO has not been established in children. No clinical data is available for children.

Patients with impaired liver function

REZALTO is contra-indicated in patients with significant hepatic disease which is associated with coagulopathy leading to clinically relevant bleeding risk (see section 4.3).

No dose adjustment is necessary in patients with other hepatic diseases.

Limited clinical data in patients with moderate hepatic impairment indicate a significant increase in the pharmacological activity. No clinical data are available for patients with severe hepatic impairment.

Patients with impaired renal function

No dose adjustment is required if REZALTO is administered in patients with mild (creatinine clearance 80–50 mL/min) or moderate (creatinine clearance <50–30 mL/min) renal impairment.

Limited clinical data for patient with severe renal impairment (creatinine clearance <30 mL/min) indicated that rivaroxaban plasma levels are significantly increased in this patient population. Therefore REZALTO must be used with caution [on] in these patients (see section 4.4).

Ethnic differences

No dose adjustment is required based on ethnic differences.

Method of administration

REZALTO is for oral use.

The tablets can be taken with or without food (see sections 4.5 and 5.2).

For patients who are unable to swallow whole tablets, REZALTO may be crushed and mixed with water or apple puree immediately prior to use and administered orally.

The crushed REZALTO 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 (see section 5.2).

Cases of overdose up to 600 mg have been reported without bleeding complications or other adverse reactions. Due to limited absorption a ceiling effect with no further increase in average plasma exposure is expected at supratherapeutic doses of 50 mg rivaroxaban or above.

A specific antidote antagonising the pharmacodynamic effect of rivaroxaban is not available. The use of activated charcoal to reduce absorption in case of rivaroxaban overdose may be considered.

Management of bleeding

Should a bleeding complication arise in a patient receiving rivaroxaban, the next rivaroxaban administration should be delayed or treatment should be discontinued as appropriate. Rivaroxaban has a half-life of approximately 5 to 13 hours (see section 5.2). Management should be individualised according to the severity and location of the haemorrhage. Appropriate symptomatic treatment could be used as needed, such as mechanical compression (e.g. for severe epistaxis), surgical haemostasis with bleeding control procedures, fluid replacement and haemodynamic support, blood products (packed red cells or fresh frozen plasma, depending on associated anaemia or coagulopathy) or platelets.

If bleeding cannot be controlled by the above measures, administration of a specific procoagulant reversal agent should be considered, such as prothrombin complex concentrate (PCC), activated prothrombin complex concentrate (APCC) or recombinant factor VIIa (r-FVIIa). However, there is currently very limited clinical experience with the use of these medicinal products in individuals receiving rivaroxaban. The recommendation is also based on limited non-clinical data. Re-dosing of recombinant factor VIIa shall be considered and titrated depending on improvement of bleeding. Depending on local availability, a consultation with a coagulation expert should be considered in case of major bleedings (see section 5.1).

Protamine sulphate and vitamin K are not expected to affect the anticoagulant activity of rivaroxaban. There is limited experience with tranexamic acid and no experience with aminocaproic acid and aprotinin in individuals receiving rivaroxaban. There is neither scientific rationale for benefit nor experience with the use of the systemic haemostatic desmopressin in individuals receiving rivaroxaban. Due to the high plasma protein binding rivaroxaban is not expected to be dialysable.

3 years.

Store at or below 30°C.

Tablets are packed in transparent PVC/Aluminium blister strips of 7 or 10, which are further packed in printed cartons, in pack sizes of 10 or 30 tablets.

Not all pack sizes may be marketed.

Any unused medicinal product or waste material should be disposed of in accordance with local requirements.