ONDEXXYA 200 MG POWDER FOR SOLUTION FOR INFUSION - patient leaflet, side effects, dosage

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Ondexxya ® 200 mg powder for solution for infusion andexanet alfa

Package Leaflet: Information for the patient and user

Ondexxya ® 200 mg powder for solution for infusion andexanet alfa

This medicine is subject to additional monitoring. This will allow quick identification of new safety information. You can help by reporting any side effects you may get. See the end of section 4 for how to report side effects.

Read all of this leaflet carefully, because it contains important information for you. Please note this medicine is mainly used in emergency situations, and the doctor will have decided that you needed it.

• Keep this leaflet. You may need to read it again.
• If you have any further questions, ask your doctor or nurse.
• If you get any side effects, talk to your doctor or nurse. This includes any possible side effects not listed in this leaflet. See section 4.

What is in this leaflet

1. What Ondexxya is and what it is used for 2. What you need to know before you receive Ondexxya

• 3. How Ondexxya is used

• 4. Possible side effects

• 5. How Ondexxya is stored

• 6. Contents of the pack and other information

Tell your doctor if you are taking, have recently i taken, or might take, any other medicines. j This medicine has been designed to reverse i the effects of factor Xa inhibitor medicines only. It is unlikely that Ondexxya will influence * the effect of other medicines or that other j medicines will influence Ondexxya. j

Ondexxya is not recommended during j pregnancy or if you have the potential to become i pregnant and are not using birth control. j Do not breast-feed your child while you j are taking this medicine. It is unknown if i andexanet alfa is excreted in human milk. j

This medicine is for hospital use only. X Your doctor or nurse will give you this i medicine by injection or infusion into a vein. i Your doctor or nurse will work out the j dose of this medicine that you need. This i is based on the specific anticoagulant i medicine you take as well as on the dose j and the time since your last dose of j

Like all medicines, this medicine can cause side i effects, although not everybody gets them.

The most common side effects associated i with Ondexxya in clinical trials of healthy j people were infusion-related reactions with j usually mild symptoms such as flushing i or feeling hot (very common side effects j which may affect more than 1 in 10 people). i Headache, cough, or shortness of breath i (common side effects which may affect up j to 1 in 10 people) happened within a few j minutes to a few hours of the infusion. In j clinical trials of patients with life-threatening i bleeding, fever and stroke may affect up j to 1 in 10 people; transient ischaemic i

The following information is intended for healthcare professionals only.

Andexanet has not been shown to be effective for, and is not indicated for, the treatment of bleeding related to any FXa) inhibitor other than rivaroxaban or apixaban. Also, it will not reverse the effects of non-FXa inhibitors.

Dosage and administration

Andexanet alfa is administered as an intravenous (IV) bolus at a target rate of approximately 30 mg/min over 15 (low dose) or 30 minutes (high dose), immediately 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).

Table 1: Dosing regimens

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

Dosage recommendations have been defined from the effects of andexanet alfa in healthy volunteers administered a direct FXa inhibitor and from the ability to reverse the levels of anti-FXa activity. The posology was confirmed in a study in patients with acute major bleeding.

Reversal of apixaban

The recommended dose regimen of andexanet alfa 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).

Table 2: Summary of dosing for reversal of apixaban

FXa inhibitor	FXa inhibitor last dose	Timing of FXa inhibitor last dose before andexanet alfa initiation
		< 8 hours or unknown	> 8 hours
Apixaban	< 5 mg	Low dose	Low dose
	> 5 mg/ Unknown	High dose

Reversal of rivaroxaban

The recommended dose regimen of andexanet alfa 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).

Table 3: Summary of dosing for reversal of rivaroxaban

FXa inhibitor	FXa inhibitor last dose	Timing of FXa inhibitor last dose before andexanet alfa initiation
		< 8 hours or unknown	> 8 hours
Rivaroxaban	< 10 mg	Low dose	Low dose
	> 10 mg/ Unknown	High dose

Patients being treated with FXa inhibitor therapy 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.

Handling instructions

Andexanet alfa is to be reconstituted and the 10 mg/mL solution then transferred without further dilution to sterile large volume syringes in case a syringe pump is used for administration or to suitable empty IV bags comprised of polyolefin (PO) or polyvinyl chloride (PVC) material. 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.

For reconstituted solutions, chemical and physical in-use stability have been demonstrated for at least eight hours at 25°C. From a microbiological point of view, once opened, the product should be used immediately. If not used immediately, in-use storage times and conditions prior to use are the responsibility of the user.

Reconstitution

Before starting reconstitution, you will need the following:

• Calculated number of vials as given in table 1.
• Same number of 20 mL (or larger) solvent syringes equipped with a 20 gauge (or larger) needle.
• Alcohol swabs.
• Large (50 mL or larger) sterile syringe. If administration is done with a syringe pump, multiple syringes should be used to contain the final volume of reconstituted product.
• Intravenous bags of polyolefin (PO) or polyvinyl chloride (PVC) material (150 mL or larger) to contain the final volume of reconstituted product (if administration is done with IV bags).
• Water for injection
• 0.2 or 0.22 micron in-line polyethersulfone (PES) or equivalent low protein-binding filter

Andexanet alfa does not need to be brought to room temperature before reconstitution or administration to the patient. Use aseptic technique during the reconstitution procedure.

Reconstitute each vial according to the following instructions:

• 1. Remove the flip-top from each vial.

• 2. Wipe the rubber stopper of each vial with an alcohol swab.

• 3. Using a 20 mL (or larger) syringe and a 20 gauge (or larger) needle, withdraw 20 mL of water for injection.

• 4. Insert the syringe needle through the centre of the rubber stopper.

• 5. Push the plunger down to slowly inject the 20 mL of water for injections into the vial, directing the stream toward the inside wall of the vial to minimise foaming.

• 6. Gently swirl each vial until all of the powder is completely dissolved. DO NOT SHAKE the vials, as this can lead to foaming. The dissolution time for each vial is approximately three to five minutes.

• 7. The reconstituted solution should be inspected for particulate matter and/or discolouration prior to administration. Do not use if opaque particles or discolouration are present.

• 8. For the most efficient reconstitution of the needed dose, and to minimise errors, inject each vial needed with 20 mL of water for injections before proceeding to the next step.

• 9. Use andexanet alfa within eight hours after reconstitution when stored at room temperature.

Administration using a syringe pump

• 1. Once all required vials are reconstituted, withdraw the reconstituted solution from each vial, using the large volume (50 mL or larger) syringe equipped with a 20 gauge (or larger) needle.

• 2. Prepare the bolus and infusion in separate large volume syringes.

	Common (may affect up to 1 in 10 people)	Manufacturer
	hives	Alexion Pharma International Operations
	dizziness	Unlimited Company
	rapid or irregular heartbeat	Alexion Dublin Manufacturing Facility
	stomach pain or discomfort	College Business and Technology Park
	dry mouth	Blanchardstown Rd North
	disturbance of taste	Dublin D15 R925
A	nausea (feeling sick) chest discomfort	Ireland
	feeling cold	This leaflet was last revised in July 2021.
	excessive sweating	This medicine has been given ‘conditional approval. This means that there is more
	itching	evidence to come about this medicine.
	back pain	The Medicines and Healthcare products
	muscle spasms	Regulatory Agency (MHRA) will review new information on this medicine at least every
	Reporting of side effects	year and this leaflet will be updated as
	If you get any side effects, talk to your doctor or nurse. This includes any possible side effects not listed in this leaflet. You	necessary.
	can also report side effects directly via the national reporting system below: Yellow Card Scheme
	Website: or search for MHRA Yellow Card in the Google Play or Apple App Store. Adverse events should also be
	reported to Alexion Pharma UK Ltd on , Freephone (UK): 0800321 3902 By reporting side effects, you can help provide more information on the safety of this medicine.
	5. How Ondexxya is stored This medicine will be stored in the hospital, and these instructions are intended for hospital staff only.
	Keep this medicine out of the sight and reach of children.
	Do not use this medicine after the expiry date which is stated on the vial and the carton after EXP. The expiry date refers to the last day of that month.
	Store in a refrigerator (2°C to 8°C). Do not freeze.
	Once reconstituted, Ondexxya is for immediate use.