Praxbind Special Precautions

Idarucizumab binds specifically to dabigatran and reverses its anticoagulant effect. It will not reverse the effects of other anticoagulants (see Pharmacology: Pharmacodynamics under Actions).
Idarucizumab (Praxbind) treatment can be used in conjunction with standard supportive measures, which should be considered as medically appropriate.
Hypersensitivity: The risk of using Idarucizumab (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 Idarucizumab (Praxbind) should be discontinued immediately and appropriate therapy initiated.
Hereditary fructose intolerance: The recommended dose of Idarucizumab (Praxbind) contains 4 g 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 (Praxbind) must be weighed against the potential benefit of such an emergency treatment.
If Idarucizumab (Praxbind) is administered in these patients, intensified medical care during Idarucizumab (Praxbind) exposure and within 24 hours of exposure is required.
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 Dosage & Administration).
Urinary protein testing: Idarucizumab (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.
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.
Renal impairment: No dose adjustment is required in renally impaired patients. Renal impairment did not impact the reversal effect of idarucizumab.
In Phase I studies Idarucizumab (Praxbind) has been investigated in subjects with a creatinine clearance ranging from 44 to 213 mL/min. Subjects with a creatinine clearance below 44 mL/min have not been studied in Phase I.
Depending on the degree of renal impairment the total clearance was reduced compared to healthy subjects, leading to an increased exposure of idarucizumab.
Based on pharmacokinetic data from 347 patients with different degrees of renal function (median creatinine clearance 21 - 99 mL/min) it is estimated that mean idarucizumab exposure (AUC_0-24h) increases by 38% in patients with mild (CrCl 50-< 80 mL/min), by 90% in moderate (30 <50 mL/min) and by 146% in severe (0-<30 mL/min) renal impairment. Since dabigatran is also excreted primarily via the kidneys, increases in the exposure to dabigatran are also seen with worsening renal function.
Based on these data and the extent of reversal of the anticoagulant effect of dabigatran in patients, renal impairment does not impact the reversal effect of idarucizumab.
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.
Idarucizumab has been studied in 58 patients with varying degrees of hepatic impairment. Compared to 272 patients without hepatic impairment, the median AUC of idarucizumab was changed by -6%, 37% and 10% in patients with AST/ALT elevations of 1 to <2x ULN (N=34), 2 to <3x ULN (N=3) and >3x ULN (N=21), respectively. Based on pharmacokinetic data from 12 patients with liver disease, the AUC of idarucizumab was increased by 10% as compared to patients without liver disease.
Use in Children: The safety and efficacy of Idarucizumab (Praxbind) in the paediatric population has not been established.
Use in Elderly/Sex/Race: Based on population pharmacokinetic analyses, sex, age, and race do not have a clinically meaningful effect on the pharmacokinetics of idarucizumab.