Document Details

Generated Narrative: Bundle TEST PURPOSES ONLY - ondexxya

Document Subject

Generated Narrative: MedicinalProductDefinition mp44ebb648c2633169fc2072c9adc62d64

identifier: http://ema.europa.eu/identifier/EU/1/18/1345/001 4 vials

type: Medicinal Product

domain: Human use

status: active

legalStatusOfSupply: Medicinal product subject to medical prescription

name

productName: Ondexxya 200 mg powder for solution for infusion

type: Full name

part

part: nan

type: Invented name part

part

part: nan

type: Scientific name part

part

part: nan

type: Strength part

part

part: nan

type: Pharmaceutical dose form part

Usages

-	Country	Jurisdiction	Language
*	EU	EU	en

Document Content

Generated Narrative: Composition composition-en-44ebb648c2633169fc2072c9adc62d64

identifier: http://ema.europa.eu/identifier/EU/1/18/1345/001 4 vials

status: Final

type: Package Leaflet

category: Raw

date: 2022-02-16 13:28:17+0000

author: Organization ACME industry

title: TEST PURPOSES ONLY - ondexxya

Attesters

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

Ondexxya contains the active ingredient andexanet alfa. It reverses the effects of certain anticoagulants called factor Xa inhibitors (apixaban or rivaroxaban). Factor Xa inhibitors are given to prevent clots in your blood vessels. Your doctor may decide to give you Ondexxya to rapidly reverse the effects of the anticoagulant in case of a life-threatening or uncontrolled bleeding situation.

if you are allergic to andexanet alfa or any of the other ingredients of this medicine (listed in section 6).

if you are allergic to hamster proteins

if you are receiving heparin Warnings and precautions Reversing the effect of a factor Xa inhibitor with Ondexxya may increase the risk of blood clots. After treatment with Ondexxya, your doctor will decide when to restart anticoagulant therapy. An independent pro-coagulant effect of andexanet alfa may pose an additional risk of developing thrombosis. If you suffer side effects when you are being given Ondexxya by infusion (drip), your doctor may decide to slow down or pause your treatment. Your doctor may give you an antihistamine medicine to help with any side effects (see section 4). If a surgery is planned for you which requires anticoagulation with heparin, Ondexxya should be avoided. Children and adolescents There is no information on the use of Ondexxya in children and adolescents. Other medicines and Ondexxya Tell your doctor if you are taking, have recently taken, or might take, any other medicines. This medicine has been designed to reverse the effects of factor Xa inhibitor medicines only. It is unlikely that Ondexxya will influence the effect of other medicines or that other medicines will influence Ondexxya. Ondexxya-treatment should be avoided if anticoagulation with heparin might become necessary. Ondexxya causes unresponsiveness to heparin. Pregnancy and breast-feeding Tell your doctor if you are pregnant or breast-feeding, think you may be pregnant, or are planning to have a baby. Ondexxya is not recommended during pregnancy or if you have the potential to become pregnant and are not using birth control. Do not breast-feed your child while you are taking this medicine. It is unknown if andexanet alfa is excreted in human milk. Driving and using machines This medicine is unlikely to affect your ability to drive and use machines.

This medicine is for hospital use only. Your doctor or nurse will give you this medicine by injection or infusion into a vein. Your doctor or nurse will work out the dose of this medicine that you need. This is based on the specific anticoagulant medicine you take as well as on the dose and the time since your last dose of anticoagulant medicine. After you have received Ondexxya, your doctor will decide when to restart your anticoagulant treatment. Detailed instructions for your doctor or nurse on how to give Ondexxya are given at the end of this package leaflet (see Handling instructions ). If you have any further questions on the use of this medicine, ask your doctor.

Like all medicines, this medicine can cause side effects, although not everybody gets them. List of side effects seen in bleeding people Common (may affect up to 1 in 10 people)

Stroke

Heart-attack

Blood clot in the leg, arm, lung or brain

Fever Uncommon (may affect up to 1 in 100 people)

Mini stroke

Cardiac arrest

Signs/symptoms of infusion related reactions such as chills, high blood pressure, shortness of breath, confusion or agitation. Reporting of side effects If you get any side effects, talk to your doctor or nurse. This includes any possible side effects not listed in this leaflet. You can also report side effects directly via the national reporting system listed in Appendix V. By reporting side effects, you can help provide more information on the safety of this medicine.

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.

What Ondexxya contains

The active substance is andexanet alfa.

The other ingredients are Tris base, Tris hydrochloride, L-arginine hydrochloride, sucrose, mannitol, and polysorbate 80. What Ondexxya looks like and contents of the pack Ondexxya is supplied in glass vials as a white to off-white powder for solution for infusion, which is reconstituted (dissolved) before use. The reconstituted solution is a clear, colourless, or slightly yellow solution. Each pack contains four or five vials. Not all pack sizes may be marketed. Marketing Authorisation Holder AstraZeneca AB SE-151 85 S dert lje Sweden Manufacturer Alexion Pharma International Operations Limited Alexion Dublin Manufacturing Facility College Business and Technology Park Blanchardstown Rd North Dublin D15 RIreland For any information about this medicine, please contact the local representative of the Marketing Authorisation Holder: Belgi /Belgique/Belgien AstraZeneca S.A./N.V. Tel: +32 2 370 48 Lietuva UAB AstraZeneca Lietuva Tel: +370 5 2660

.: +359 24455Luxembourg/Luxemburg AstraZeneca S.A./N.V. T l/Tel: +32 2 370 48 esk republika AstraZeneca Czech Republic s.r.o. Tel: +420 222 807 Magyarorsz g AstraZeneca Kft. Tel.: +36 1 883 6Danmark AstraZeneca A/S Tlf: +45 43 66 64 Malta Associated Drug Co. Ltd Tel: +356 2277 8Deutschland AstraZeneca GmbH Tel: +49 40 809034Nederland AstraZeneca BV Tel: +31 85 808 9Eesti AstraZeneca Tel: +372 6549 Norge AstraZeneca AS Tlf: +47 21 00 64
AstraZeneca A.E. : +30 210 6871 sterreich AstraZeneca sterreich GmbH Tel: +43 1 711 31 0 Espa a AstraZeneca Farmac utica Spain, S.A. Tel: +34 91 301 91 Polska AstraZeneca Pharma Poland Sp. z o.o. Tel.: +48 22 245 73 France AstraZeneca T l: +33 1 41 29 40 Portugal AstraZeneca Produtos Farmac uticos, Lda. Tel: +351 21 434 61 Hrvatska AstraZeneca d.o.o. Tel: +385 1 4628 Rom nia AstraZeneca Pharma SRL Tel: +40 21 317 60 Ireland AstraZeneca Pharmaceuticals (Ireland) DAC Tel: +353 1609 7Slovenija AstraZeneca UK Limited Tel: +386 1 51 35 sland Vistor hf. S mi: +354 535 7Slovensk republika AstraZeneca AB, o.z. Tel: +421 2 5737 7Italia AstraZeneca S.p.A. Tel: +39 02 00704Suomi/Finland AstraZeneca Oy Puh/Tel: +358 10 23

Sverige AstraZeneca AB : +357 22490Tel: +46 8 553 26 Latvija SIA AstraZeneca Latvija Tel: +371 67377United Kingdom (Northern Ireland) AstraZeneca UK Ltd Tel: +44 1582 836 This leaflet was last revised in . This medicine has been given conditional approval . This means that there is more evidence to come about this medicine. The European Medicines Agency will review new information on this medicine at least every year and this leaflet will be updated as necessary. Other sources of information Detailed information on this medicine is available on the European Medicines Agency web site: http://www.ema.europa.eu

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 dosage was used 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). If the strength of the last dose of anticoagulant or the interval between the last dosage and the bleeding episode are unknown, no dose recommendation is available. 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 FXa inhibitor FXa inhibitor last dose Timing of FXa inhibitor last dose before andexanet alfa initiation < 8 hours 8 hours Apixaban 5 mg Low dose Low dose

5 mg 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). If the strength of the last dose of anticoagulant or the interval between the last dosage and the bleeding episode are unknown, no dose recommendation is available. 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 FXa inhibitor FXa inhibitor last dose Timing of FXa inhibitor last dose before andexanet alfa initiation < 8 hours 8 hours Rivaroxaban 10 mg Low dose Low dose 10 mg 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
10. 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.
11. Prepare the bolus and infusion in separate large volume syringes.
12. Due to the additional volume, the high dose bolus and infusion will need to be further separated into additional syringes (two syringes apiece for bolus and infusion).
13. To prevent the inadvertent transfer of air, be careful to hold the syringe needle up, and do not set the syringe down between multiple withdrawals from vials.
14. Attach ancillary equipment (i.e., extension tubing, 0.2 or 0.22 micron in-line polyethersulfone (PES) or equivalent low protein-binding filter, syringe pump) in preparation for administration.
15. Administer the reconstituted solution at the appropriate rate.
16. Discard all used syringes, needles, and vials, including any unused portion of reconstituted solution. Administration using intravenous bags
17. 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.
18. Transfer the reconstituted solution from the syringe into appropriate IV bags.
19. Repeat steps 1 and 2 as necessary to transfer the complete volume of the bolus and the infusion into PO or PVC IV bags.
20. It is recommended that the bolus and infusion be split into two separate bags to ensure the correct administration rate. Although it is also permissible to use one PO or PVC IV bag for the bolus and infusion, the correct infusion rate must be ensured when switching from the bolus to the infusion.
21. Attach ancillary equipment (i.e., extension tubing, 0.2 or 0.22 micron in-line polyethersulfone (PES) or equivalent low protein-binding filter, IV pump) in preparation for administration.
22. Administer the reconstituted solution at the appropriate rate. Disposal All used syringes, needles, and vials, including any unused portion of reconstituted solution, should be disposed of in accordance with local requirements.