1 Dosing Considerations For intravenous (IV) use only. Patients being treated with FXa inhibitors have underlying disease states that predispose them to thromboembolic events. Reversing FXa inhibitor therapy exposes patients to the thrombotic risk of their underlying disease.
To reduce this risk, resumption of anticoagulant therapy should be considered as soon as medically appropriate (see 7 WARNINGS AND PRECAUTIONS, Hematologic). 2 Recommended Dose and Dosage Adjustment • Select the appropriate dosing regimen following the guidance in Table 1.
• Administer ONDEXXYA as an IV bolus followed by administration of a continuous infusion as per Table 2. The recommended dosing of ONDEXXYA is based on the specific FXa inhibitor, dose of FXa inhibitor, and time since the patient’s last dose of FXa inhibitor (see Table 1).
Table 1 - ONDEXXYA Dose Based on Rivaroxaban or Apixaban Dose and Timing of Last Dose of FXa Inhibitor before ONDEXXYA Initiation FXa Inhibitor FXa Inhibitor Last Dose < 8 Hours or Unknown ≥ 8 Hours Rivaroxaban ≤ 10 mg Low Dose Low Dose > 10 mg or Unknown High Dose Apixaban ≤ 5 mg Low Dose > 5 mg or Unknown High Dose The low- and high-dose regimens are described in Table 2.
Table 2 - ONDEXXYA dosing regimens Dose* Initial IV Bolus Follow-On IV Infusion** Total number of 200 mg vials Low Dose 400 mg at a target rate of 30 mg/min 4 mg/min for 120 minutes (480 mg) 5 (2 vials bolus + 3 vials infusion) High Dose 800 mg at a target rate of 30 mg/min 8 mg/min for 120 minutes (960 mg) 9 (4 vials bolus + 5 vials infusion) * The safety and efficacy of more than one dose have not been evaluated.
** Because the recommended infusion doses are lower than the andexanet alfa content of the vials, there will be a small amount of solution remaining in the bag after completion of the infusion. IV=intravenous infusion ONDEXXYA® (andexanet alfa) Page 6 of 32 Special Populations Pediatrics (< 18 years of age): Health Canada has not authorized an indication for pediatric use.
Geriatrics (≥ 65 years of age):
No dose adjustment is recommended for elderly patients (≥ 65 years of age) (see 7 WARNINGS AND PRECAUTIONS and 10 CLINICAL PHARMACOLOGY).
Renal Impairment:
The effect of renal impairment on ONDEXXYA exposure levels has not been evaluated. Because andexanet alfa is a protein and is given as a one-time treatment, no dose adjustment is recommended.
Hepatic Impairment:
The safety and efficacy of ONDEXXYA have not been studied in patients with hepatic impairment. Biliary and/or feces elimination of protein therapeutics is not a known route of protein elimination. Because andexanet alfa is a protein and is given as a one-time treatment, no dose adjustment is recommended.
3 Reconstitution ONDEXXYA does not need to be brought to room temperature before reconstitution or administration to the patient. Aseptic technique during the reconstitution procedure should be used. Two IV infusion bags will be prepared to deliver the selected ONDEXXYA regimen.
One bag containing the bolus dose and one bag containing the follow-on IV infusion. The reconstituted solution contains andexanet alfa at a concentration of 10 mg/mL. Chemical and physical in-use stability has been demonstrated over a 24-hour period.
The reconstituted solution in the primary packaging vials can be stored for 16 hours at 2°C to 8°C. If necessary, the reconstituted solution can be stored at room temperature for an additional eight hours after being transferred to the IV bag.
To minimize the risk of microbial growth, once reconstituted, it is recommended that the product be used immediately. ONDEXXYA® (andexanet alfa) Page 7 of 32 IV Bolus Preparation Determine total number of vials required (see Table 2).
200 mg vials: Reconstitute the 200 mg vial of ONDEXXYA with 20 mL of Sterile Water for Injection (SWFI). Use a 20-mL (or larger) syringe and 20-gauge (or higher) needle. Slowly inject the SWFI, directing the solution onto the inside wall of the vial to minimize foaming.
To reduce the total reconstitution time needed during preparation, reconstitute all required vials in succession. To ensure dissolution of the cake or powder, gently swirl each vial until complete dissolution of powder occurs (A). Do not shake (B); shaking could lead to foaming.
Typical dissolution time for each vial is approximately three to five minutes. If dissolution is incomplete, discard the vial, and do not use the product. Upon reconstitution, the parenteral drug product should be inspected visually for particulate matter and discoloration prior to administration.
(A) (B) Use 60-mL (or larger) syringe with a 20-gauge (or higher) needle to withdraw the reconstituted ONDEXXYA solution from each of the vials until the required dosing volume is achieved. Note the total volume withdrawn into the syringe.
Transfer the ONDEXXYA solution from the syringe into an empty polyolefin or polyvinyl chloride IV bag with a volume of 250 mL or less. ONDEXXYA® (andexanet alfa) Page 8 of 32 Discard the syringe, needle and vials (including any unused product) in accordance with local requirements.
Continuous IV Infusion Preparation Follow the same procedure outlined above for IV bolus preparation. Reconstitute the total number of vials needed based on the dose requirements (see Table 2). More than one 40 to 60 mL syringe, or an equivalent 100-mL syringe, may be used for transfer of reconstituted solution to the IV bag.
Discard the syringe, needle and vials (including any unused product) in accordance with local requirements. 4 Administration Upon reconstitution, the parenteral drug product should be inspected visually for particulate matter and discoloration prior to administration.
22 micron in-line polyethersulfone or equivalent low protein-binding filter. Start the bolus at a target rate of approximately 30 mg/min. Within two minutes following the bolus dose, administer the continuous IV infusion for up to 120 minutes.
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