Praxbind 50 mL Solution for infusion

PRAXBIND is a specific reversal agent for dabigatran and is indicated in patients treated with PRADAXA (dabigatran etexilate) when rapid reversal of the anticoagulant effects of dabigatran is required:

• For emergency surgery/urgent procedures
• In life-threatening or uncontrolled bleeding

Posology
The recommended dose of PRAXBIND is 5 g (2 vials of 2,5 g/50 mL). In a limited number of patients, recurrence of plasma concentrations of unbound dabigatran and concomitant prolongation of clotting tests have occurred up to 24 hours after administration of PRAXBIND (see section 5.1). Administration of a second 5 g dose of PRAXBIND may be considered in the following situations:

• recurrence of clinically relevant bleeding together with prolonged clotting times, or
• patients require a second emergency surgery/urgent procedure and have prolonged clotting times.

Relevant coagulation parameters are activated Partial Thromboplastin Time (aPTT), diluted Thrombin Time (dTT) or Ecarin Clotting Time (ECT) (see section 5.1).
Restarting antithrombotic therapy
PRADAXA (dabigatran etexilate) treatment can be re-initiated 24 hours after administration of PRAXBIND, if the patient is clinically stable and adequate haemostasis has been achieved. After administration of PRAXBIND, other antithrombotic therapy (e.g. low-molecular weight heparin) can be started at any time, if the patient is clinically stable and adequate haemostasis has been achieved. Absence of antithrombotic therapy exposes patients to the thrombotic risk of their underlying disease or condition.
Renal impairment
No dose adjustment is required in renally impaired patients. Renal impairment did not impact the reversal effect of idarucizumab (as in PRAXBIND) (see section 5.2).
Hepatic impairment
An impact of hepatic impairment, assessed by hepatic injury as determined by elevated liver function tests, on the pharmacokinetics of idarucizumab has not been observed. No dose adjustment is required in patients with hepatic injury.
Geriatric patients/Sex/Race
Based on population pharmacokinetic analyses, sex, age and race do not have a clinically meaningful effect on the pharmacokinetics of idarucizumab (as in PRAXBIND).
Paediatric patients
The safety and efficacy of PRAXBIND in the paediatric population has not been established.
Method of administration
PRAXBIND (2 vials of 2,5 g/50 mL) is administered intravenously, as two consecutive infusions over 5 to 10 minutes each or as a bolus injection. For additional instructions for use and handling see section 6.6.

None.

Idarucizumab (as in PRAXBIND) binds specifically to dabigatran and reverses its anticoagulant effect. It will not reverse the effects of other anticoagulants (see section 5.1).
PRAXBIND treatment can be used in conjunction with standard supportive measures, which should be considered as medically appropriate.
Traceability
In order to improve traceability of biological medicinal products, the trade name and the batch number of the administered product should be clearly recorded in the patient file.
Hypersensitivity
The risk of using PRAXBIND in patients with known hypersensitivity (e.g. anaphylactoid reaction) to idarucizumab or to any of the excipients needs to be weighed cautiously against the potential benefit of such an emergency treatment. If an anaphylactic reaction or other serious allergic reaction occurs, administration of PRAXBIND should be discontinued immediately and appropriate therapy initiated.
Hereditary fructose intolerance
The recommended dose of PRAXBIND contains 4 g sorbitol as an excipient. In patients with hereditary fructose intolerance, parenteral administration of sorbitol has been associated with reports of hypoglycaemia, hypophosphatemia, metabolic acidosis, increase in uric acid, acute liver failure with breakdown of excretory and synthetic function and death. Therefore, in patients with hereditary fructose intolerance the risk of treatment with PRAXBIND must be weighed against the potential benefit of such an emergency treatment.
Sodium content
This medicinal product contains 2,2 mmol (or 50 mg) sodium per dose. To be taken into consideration by patients on a controlled sodium diet.
Thromboembolic Events
Patients being treated with dabigatran have underlying disease states that predispose them to thromboembolic events. Reversing dabigatran 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 section 4.2).
Urinary protein testing
Praxbind causes transient proteinuria as a physiologic reaction to renal protein overflow after bolus/short term application of 5 g idarucizumab intravenously. The transient proteinuria is not indicative of renal damage, which should be taken into account for urine testing.

No formal interaction studies with PRAXBIND and other medicinal products have been performed. Based on the pharmacokinetic properties and the high specificity in binding to dabigatran, clinically relevant interactions with other medicinal products are considered unlikely. Preclinical investigations have shown no interactions with volume expanders, coagulation factor concentrates and anticoagulants other than dabigatran (see section 5.1).

The safety of PRAXBIND in pregnancy and lactation has not been established.

Not relevant.

In a phase III trial the safety of PRAXBIND has been evaluated in 503 patients, who had uncontrolled bleeding or required emergency surgery or procedures and were under treatment with PRADAXA, as well as in 224 volunteers in phase I trials. No adverse reactions have been identified.
Reporting of suspected adverse reactions
Reporting suspected adverse reactions after authorisation of the medicine is important. It allows continued monitoring of the benefit/risk balance of the medicine. Healthcare professionals are asked to report any suspected adverse reactions to SAHPRA via the Med Safety App (Medsafety X SAHPRA) and eReporting platform (who-umc.org) found on the SAHPRA website. Suspected adverse reactions can also be reported directly to the holder of the certificate of registration using the email address [email protected].

Symptoms
There is no clinical experience with overdoses of PRAXBIND. The highest dose of PRAXBIND studied in healthy subjects was 8 g. No safety signals have been identified in this group.
Treatment
If symptoms of overdosage should occur, treatment is symptomatic and supportive.