Andexanet alfa parenteral
- Drugs List
- Therapeutic Indications
- Dosage
- Administration
- Contraindications
- Precautions and Warnings
- Pregnancy and Lactation
- Side Effects
- Monograph
Presentation
Parenteral formulations of andexanet alfa.
These products have been produced by recombinant technology using Chinese Hamster Ovary (CHO) cell lines.
Drugs List
Therapeutic Indications
Uses
Rapid reversal of direct factor Xa inhibitor anticoagulant effect
For patients treated with a direct factor Xa (FXa) inhibitor (apixaban or rivaroxaban) when reversal of anticoagulation is needed due to life-threatening or uncontrolled bleeding.
Dosage
If available in the given time frame, baseline anti-factor FXa should be measured to support the clinical decision to initiate treatment.
Adults
Treatment of andexanet alfa is dependant on the previous dose of direct factor Xa inhibitor and the time since the last dose.
Low Dose
Initial Intravenous Bolus: 400mg at a rate of 30mg per minute
Continuous Intravenous Infusion: 4mg per minute for 120 minutes (480mg)
High Dose
Initial Intravenous Bolus: 800mg at a rate of 30mg per minute
Continuous Intravenous Infusion: 8mg per minute for 120 minutes (960mg)
Reversal of Apixaban
Last dose of apixaban less than or equal to 5mg:Low dose treatment (irrespective of time since last dose)
Last dose of apixaban greater than 5mg, or dose unknown
Unknown time since last dose of apixaban: High dose treatment (see above)
Under 8 hours from the time of last dose: High dose treatment (see above)
8 hours or more since the time of last dose of apixaban: Low dose treatment (see above)
Reversal of Rivaroxaban
Last dose of rivaroxaban less than or equal to 10mg: Low dose treatment (irrespective of time since last dose)
Last dose of rivaroxaban greater than 10mg, or dose unknown
Unknown time of last dose of rivaroxaban: High dose treatment (see above)
Under 8 hours from the time of last dose of rivaroxaban: High dose treatment (see above)
8 hours or more since the time of last dose of rivaroxaban: Low dose treatment (see above)
Administration
For intravenous administration.
Contraindications
Children under 18 years
Breastfeeding
Pregnancy
Precautions and Warnings
Not suitable for pre-treatment of urgent surgery
Provide supportive therapy in conjunction with treatment
Do not mix with other drugs or substances
Suspend treatment or reduce rate until infusion reactions resolve
Monitor for signs and symptoms of thrombosis
May affect results of some laboratory tests
Resume anticoagulant therapy as soon as medically appropriate
Hospital use only
Female: Ensure adequate contraception during treatment
Andexanet alfa will not reverse the effects of non-FXa inhibitors.
Treatment monitoring should be based mainly on clinical parameters indicative of appropriate response, lack of efficiency and adverse events. Monitoring should not be based on the anti-FXa activity as commercial assays are unsuitable and may result in falsely elevated anti-FXa activity levels with underestimation of the reversal activity following administration of andexanet alfa.
The safety of andexanet alfa has not been evaluated in patients who receive prothrombin complex concentrates, recombinant factor VIIa, or whole blood within seven days prior to the bleeding event, as they were excluded from the clinical trials. Pro-coagulant factor treatments (e.g., 3- or 4-factor prothrombin complex concentrate (PCC/activated PCC, recombinant factor VIIa, fresh frozen plasma) and whole blood should be avoided unless absolutely required.
Avoid use of andexanet alfa prior to heparinisation.
Pregnancy and Lactation
Pregnancy
Andexanet alfa is contraindicated during pregnancy.
The manufacturer does not recommend using andexanet alfa during pregnancy. At the time of writing there is limited published information regarding the use of andexanet alfa during pregnancy. Potential risks are unknown.
Lactation
Andexanet alfa is contraindicated during breastfeeding.
Use of andexanet alfa when breastfeeding is contraindicated by the manufacturer. The presence of andexanet alfa in human breast milk is unknown but due to its large molecular weight, transfer is not expected. Effects on exposed infants are unknown.
Side Effects
Abdominal discomfort
Abdominal pain
Back pain
Cardiac arrest
Cerebral infarct
Cerebrovascular accident
Chest discomfort
Cough
Deep vein thrombosis (DVT)
Dry mouth
Dysgeusia
Dyspnoea
Feeling hot
Flushing
General pruritus
Headache
Hyperhidrosis
Iliac artery occlusion
Infusion related reaction
Ischaemic stroke
Muscle spasm
Myocardial infarction
Nausea
Palpitations
Peripheral coldness
Postural dizziness
Pruritus
Pulmonary embolism
Pyrexia
Transient elevations of D-dimer and F1+2 fragments
Transient ischaemic attack
Urticaria
Effects on Laboratory Tests
Dose-dependant increases in coagulation markers F1+2, TAT, and D-dimer after administration of andexanet alfa were observed, but no thromboembolic events were reported.
Overdosage
It is strongly recommended that the UK National Poisons Information Service be consulted on cases of suspected or actual overdose where there is doubt over the degree of risk or about appropriate management.
The following number will direct the caller to the relevant local centre (0844) 892 0111
Information may be obtained if you have access to ToxBase the primary clinical toxicology database of the National Poisons Information Service. This is available via password on the internet ( www.toxbase.org ) or if this is unavailable at the backup site ( www.toxbasebackup.org ).
Further Information
Last Full Review Date: March 2021
Reference Sources
Summary of Product Characteristics: Ondexxya 200mg powder for solution for infusion. Portola Pharma UK Ltd. Revised November 2022.
MHRA Drug Safety Update June 2020
Available at: https://www.mhra.gov.uk
Last accessed: 16 March 2021
MHRA Drug Safety Update November 2020
Available at: https://www.mhra.gov.uk
Last accessed: 16 March 2021
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