Posology : מינונים

4.2       Posology and method of administration

Restricted to hospital use only.
Posology
Andexanet alfa is administered as an intravenous bolus at a target rate of approximately 30 mg/min over 15 minutes (low dose) or 30 minutes (high dose), followed by administration of a continuous infusion of 4 mg/min (low dose) or 8 mg/min (high dose) for 120 minutes (see table 1).


Table 1: Dosing regimens

Initial                       Continuous              Total number intravenous                      intravenous               of 200 mg bolus                          infusion               vials needed
Low dose           400 mg at a target rate of      4 mg/min for 120 minutes              5 30 mg/min                        (480 mg)
High dose          800 mg at a target rate of      8 mg/min for 120 minutes              9 30 mg/min                        (960 mg)

Reversal of apixaban
The recommended dose regimen of Ondexxya is based on the dose of apixaban the patient is taking at the time of anticoagulation reversal, as well as on the time since the patient’s last dose of apixaban (see table 2). Measurement of baseline anti-FXa-level should support the clinical decision of starting treatment (if level is available in an acceptable timely frame).

Table 2: Summary of dosing for reversal of apixaban

Timing of last dose before
Ondexxya initiation
FXa inhibitor          Last dose
< 8 hours or unknown                      ≥ 8 hours
≤ 5 mg                     Low dose

Apixaban             > 5 mg/                     High dose                         Low dose Unknown


Reversal of rivaroxaban
The recommended dose regimen of Ondexxya is based on the dose of rivaroxaban the patient is taking at the time of anticoagulation reversal, as well as on the time since the patient’s last dose of rivaroxaban (see table 3). Measurement of baseline anti-FXa-level should support the clinical decision of starting treatment (if level is available in an acceptable timely frame).

Table 3: Summary of dosing for reversal of rivaroxaban

Timing of last dose before
Ondexxya initiation
FXa inhibitor          Last dose
< 8 hours or unknown                      ≥ 8 hours
≤ 10 mg                     Low dose

Rivaroxaban           > 10 mg/                     High dose                         Low dose Unknown


Restarting antithrombotic therapy
Following administration of Ondexxya and cessation of a major bleed, re-anticoagulation should be considered to prevent thrombotic events due to the patient’s underlying medical condition.

Antithrombotic therapy can be re-initiated as soon as medically indicated following treatment if the patient is clinically stable and adequate haemostasis has been achieved.
Medical judgement should balance the benefits of anticoagulation with the risks of re- bleeding (see section 4.4).

Special populations
Elderly patients (aged 65 years and over): No dose adjustment is required in elderly patients (see section 5.2).

Renal impairment: The effect of renal impairment on andexanet alfa exposure levels has not been evaluated. Based on the existing data on clearance, no dose adjustment is recommended.

Hepatic impairment: Based on the existing data on clearance of andexanet alfa, no dose adjustment is recommended. The safety and efficacy have not been studied in patients with hepatic impairment (see section 5.2).

Paediatric population: The safety and efficacy of andexanet alfa in children and adolescents have not been established. No data are available.

Method of administration
Intravenous use
After an appropriate number of vials of Ondexxya has been reconstituted, the reconstituted solution (10 mg/mL) without further dilution is transferred to sterile large volume syringes in case a syringe pump is used for administration or to suitable empty intravenous bags comprised of polyolefin (PO) or polyvinyl chloride (PVC) material (see section 6.6). Prior to administration by IV infusion a 0.2 or 0.22 micron in-line polyethersulfone (PES) or equivalent low protein- binding filter should be used.

Ondexxya is administered as an IV bolus at a target rate of approximately 30 mg/min over 15 minutes (low dose) or 30 minutes (high dose), followed by administration of a continuous infusion of 4 mg (low dose) or 8 mg (high dose) per minute for 120 minutes (see table 1).

For instructions on reconstitution of the medicinal product before administration, see section 6.6.