Dosing and uses of Praxbind (idarucizumab)
Adult dosage forms and strengths
intravenous solution
- 2.5g/50mL vial
Dabigatran Reversal
Humanized monoclonal antibody fragment (Fab) indicated in patients treated with dabigatran (Pradaxa) when reversal of the anticoagulant effects are needed for emergency surgery or urgent procedures, or in the event of life-threatening or uncontrolled bleeding
5 g IV, provided as 2 separate vials each containing 2.5 g/50 mL (see Administration)
Limited data support administration of an additional 5 g
Dosage modifications
Renal impairment: Renal impairment did not impact the reversal effect of idarucizumab; no dosage adjustment required
Hepatic impairment: Not studied
Dosing Considerations
This indication is approved under accelerated approval based on a reduction in unbound dabigatran and normalization of coagulation parameters in healthy volunteers; continued approval for this indication may be contingent upon the results of an ongoing cohort case series study
Pediatric dosage forms and strengths
Safety and efficacy not established
Praxbind (idarucizumab) adverse (side) effects
1-10%
Hypokalemia (7%)
Delirium (7%)
Constipation (7%)
Pyrexia (6%)
Pneumonia (6%)
Headache (5%)
Frequency not defined
Thromboembolic events
Hypersensitivity
Warnings
Contraindications
None
Cautions
Patients 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, resume anticoagulant therapy as soon as medically appropriate
There is insufficient clinical experience to evaluate risk of hypersensitivity to idarucizumab; discontinue if a serious hypersensitivity reaction occurs
Caution with hereditary fructose intolerance; the recommended dose of idarucizumab contains 4 g sorbitol as an excipient; when prescribing to patients with hereditary fructose intolerance, consider the combined daily metabolic load of sorbitol/fructose from all sources; administration of sorbitol in these patients is known to cause serious adverse reactions, including fatal reactions including hypoglycemia, hypophosphatemia, metabolic acidosis, increase in uric acid, and acute liver failure with breakdown of excretory and synthetic function
Re-elevation of coagulation parameters
- In a limited number of patients in the clinical program, between 12-24 hr after administrating idarucizumab 5 g, elevated coagulation parameters (eg, aPTT, ECT) have been observed
- If reappearance of clinically relevant bleeding together with elevated coagulation parameters is observed after administering idarucizumab 5 g, administration of an additional 5 g dose may be considered
- Similarly, patients who require a second emergency surgery/urgent procedure and have elevated coagulation parameters may receive an additional 5-g dose
- The safety and effectiveness of repeat treatment with idarucizumab have not been established
Pregnancy
Pregnancy
There are no adequate and well-controlled studies of idarucizumab in pregnant women to inform on associated risks
Animal reproductive and development studies have not been conducted; it is also not known whether idarucizumab can cause fetal harm when administered to a pregnant woman or can affect reproduction capacity
Has not been studied for use during labor and delivery
Lactation
Unknown if distributed in human breast milk
Consider the developmental and health benefits of breastfeeding along with the mother’s clinical need for the drug, and any potential adverse effects on the breastfed infant from the drug or from the underlying maternal condition
Pregnancy categories
A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.
B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.
C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.
D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.
X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.
NA: Information not available.
Pharmacology of Praxbind (idarucizumab)
Mechanism of action
Specific reversal agent for dabigatran
It is a humanized monoclonal antibody fragment (Fab) that binds to dabigatran and its acylglucuronide metabolites with higher affinity than the binding affinity of dabigatran to thrombin, and thereby neutralizes dabigatran and its metabolites anticoagulant effect
Distribution
Vd: 8.9 L
Metabolism
Several pathways have been described that may contribute to the metabolism of antibodies
All of these pathways involve biodegradation of the antibody to smaller molecules (ie, small peptides or amino acids), which are then reabsorbed and incorporated in the general protein synthesis
Elimination
Half-life: 47 minutes (initial); 10.3 hr (terminal)
Total clearance: 47 mL/min
Excretion: 32.1% urine (within 6 hr after administration); <1% urine (6-24 hr after administration)
Administration
IV Preparation
Ensure aseptic handling when preparing
Inspect visually for particulates and discoloration before infusion
Once solution has been removed from the vial, administration should begin promptly or within 1 hr (preservative-free solution)
Do not mix with other medications
IV Administration
Infuse 5-g dose IV as 2 consecutive 2.5-g infusions or give as a bolus injections by injecting both 2.5-g vials consecutively one after another via syringe
A preexisting IV line may be used for administration; flush with sterile 0.9% NaCl solution prior to infusion
No other infusion should be administered in parallel via the same IV access
Can be used in conjunction with standard supportive measures, which should be considered as medically appropriate
Restarting antithrombotic therapy
- Patients being treated with dabigatran therapy 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
- Idarucizumab is a specific reversal agent for dabigatran, with no impact on the effect of other anticoagulant or antithrombotic therapies
- Dabigatran treatment can be initiated 24 hr after administration of idarucizumab
Storage
Store refrigerated at 2-8ºC (36-46ºF)
Do not freeze
Do not shake
Prior to use, the unopened vial may be kept at room temperature (25°C [77°F]) for up to 48 hr if stored in the original package in order to protect from light or up to 6 hr when exposed to light
