idarucizumab (Rx)

1-10%

Hypokalemia (7%)

Delirium (7%)

Constipation (7%)

Pyrexia (6%)

Pneumonia (6%)

Headache (5%)

Frequency Not Defined

Thromboembolic events

Hypersensitivity

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

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.

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)

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; solution in vials may be stored at room temperature (25°C [77°F]), but must be used within 6 hr (also see storage)

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