Precautions from the idarucizumab Product Information
There are no contraindications to idarucizumab use, although there are precautions.
When there are precautions, risk of idarucizumab use needs to be weighed against the potential benefit of emergency treatment.1
A summary of idarucizumab precautions is provided below. See the idarucizumab Product Information for complete information.1
Thromboembolic events: reversal of dabigatran exposes patients to the thrombotic risk of their underlying disease.
Hereditary fructose intolerance: the recommended dose of idarucizumab contains 4 g sorbitol as an excipient.
Urinary protein testing: idarucizumab causes transient proteinuria as a physiological reaction to renal protein overflow.
Re-elevation of coagulation parameters: in a limited number of patients, recurrence of plasma concentrations of unbound dabigatran and concomitant elevated coagulation parameters have occurred up to 24 hours after idarucizumab administration.
Sodium: idarucizumab contains 2.2 mmol (50 mg) of sodium per dose, which should be taken into consideration for patients on a controlled sodium diet.
Based on pharmacokinetic analyses in healthy volunteers, sex, age, race and body weight are not expected to have a clinically meaningful effect on the pharmacokinetics of idarucizumab.1
Idarucizumab may be used during pregnancy, if the expected clinical benefit outweighs the potential risks.1
The safety and efficacy of idarucizumab in children has not been established.1
No dose adjustment is required in patients with renal impairment, and hepatic impairment is not expected to impact the pharmacokinetics of idarucizumab.1
Safety data from RE-VERSE AD
Safety data for idarucizumab are limited, although no safety concerns have been identified to date.5,6
In RE-VERSE AD, mortality rates after 90 days of follow-up were 18.7% (n = 148) in the bleeds group and 18.5% (n = 105) in the surgery group.5,6
Causes of death are not yet summarised for the updated RE-VERSE AD study, but all reported serious adverse events were considered to be related to the index event or comorbidities.6
In a full publication of results from the first 90 participants enrolled in RE-VERSE AD there were 18 deaths, 10 due to vascular causes.8
Deaths within 96 hours of idarucizumab administration were associated with the index event (septic shock, intracranial haemorrhage, multi-organ failure, haemodynamic collapse, respiratory failure or cardiac arrest).8
Deaths at later timepoints were associated with coexisting conditions, including Parkinson’s disease (43 days) and progression of cancer (101 days).8
In total, 21 patients experienced a serious adverse event. In addition to the 18 deaths and the thrombotic events that occurred in five patients, these included gastrointestinal haemorrhage, postoperative wound infection, delirium, right ventricular failure, and pulmonary oedema.8