Idarucizumab

Registered South African indications:

• Dabigatran etexilate reversal agent
  - For emergency surgery/urgent procedures
  - In life-threatening or uncontrolled bleeding

Cautions

• Known hypersensitivity to idarucizumab
• Hereditary fructose intolerance (see additional prescribing points)
• Patients at risk of thromboembolic events
• Sodium restricted diets  

Forms avail. in SA and covered in this monograph: inj

Reversal of dabigatran etexilate when rapid reversal of its anticoagulant effects is required
- For emergency surgery/urgent procedures
- In life-threatening or uncontrolled bleeding

• IV: 5g, as two consecutive infusions over 5-10mins OR as a bolus injection; Give a further 5g if necessary

A second 5g dose may be considered in the following situations:
- Recurrence of clinically relevant bleeding together with prolonged clotting times, or
- If potential re-bleeding would be life-threatening and prolonged clotting times are observed, or
- Patients require a second emergency surgery/urgent procedure and have prolonged clotting times

Dabigatran etexilate treatment can be re-initiated 24 hours after administration of idarucizumab if the patient is clinically stable and adequate haemostasis has been achieved

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 acheived

Absence of antithrombotic therapy exposes patients to the thrombotic risk of their underlying disease or condition. To reduce this risk, resumption of anticoagulant therapy should be considered as soon as medically appropriate

Maximum daily dose of idarucizumab has not been investigated

Not established for use in children below 18 years

Pregnancy

• Caution
• There are no data for the use of idarucizumab in pregnant women. Reproductive and developmental toxicity studies have not been performed, given the nature and the intended clinical use of the medicinal product
• Idarucizumab may be used during pregnancy if the expected clinical benefit outweighs the potential risks

Breastfeeding

• Caution
• It is unknown whether idarucizumab/metabolites are excreted in human milk

Fertility

• There are no data on the effect of idarucizumab on fertility

Renal Impairment

• No dose adjustment recommended

Hepatic Impairment

• No dose adjustment recommended

Elderly

• No dose adjustment recommended

Drugs in Sport

• Permitted - No warnings

None known

• Dabigatran (as per indication)

• Activated partial thromboplastin time
• Diluted thrombin time
• Ecarin clotting time

Additional observations

• Signs and symptoms of clinically relevant bleeding and thromboembolic events

Hereditary fructose intolerance

• The recommended dose of idarucizumab contains 4g sorbitol as an excipient
• In patients with hereditary fructose intolerance, parenteral administration of sorbitol has been associated with reports of hypoglycemia, 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 idarucizumab must be weighed against the potential benefit of such an emergency treatment
• If idarucizumab is administered in these patients, intensified medical care during idarucizumab exposure and within 24 hours of exposure is required

Urinary protein testing

• Idarucizumab 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

Traceability

• In order to improve the traceability of biological medicinal products, the name and the batch number of the administered product should be clearly recorded

Idarucizumab is a specific reversal agent for dabigatran. It is a humanised monoclonal antibody fragment (Fab) that binds to dabigatran with very high affinity, approximately 300-fold more potent than the binding affinity of dabigatran for thrombin. The idarucizumab-dabigatran complex is characterised by a rapid on-rate and extremely slow off-rate resulting in a very stable complex. Idarucizumab potently and specifically binds to dabigatran and its metabolites and neutralises their anticoagulant effect.

Injection (2.5g/50ml)

• Praxbind (Boehringer Ingelheim) originator