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Idarucizumab

Medically reviewed by Drugs.com. Last updated on July 18, 2020.

Pronunciation

(eye da roo SIZ uh mab)

Index Terms

  • aDabi-Fab

Dosage Forms

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Solution, Intravenous [preservative free]:

Praxbind: 2.5 g/50 mL (50 mL)

Brand Names: U.S.

  • Praxbind

Pharmacologic Category

  • Antidote
  • Monoclonal Antibody

Pharmacology

Idarucizumab, a specific reversal agent for dabigatran, is a humanized monoclonal antibody fragment (Fab) that binds specifically to dabigatran and its acylglucuronide metabolites with an affinity for dabigatran that is ~350 times greater than that of thrombin, and neutralizes the anticoagulant effect within minutes (Das 2015; Schiele 2013).

Distribution

Vdss: 8.9 L

Metabolism

Biodegradation of small peptides and amino acids

Excretion

Urine (~32% within the first 6 hours and <1% in the following 18 hours)

Onset of Action

Uncontrolled bleeding: Effects observed within minutes and hemostasis is restored at a median of 11.4 hours (Pollack 2015)

Duration of Action

Usually at least 24 hours

Half-Life Elimination

47 minutes (initial); 10.3 hours (terminal)

Special Populations: Renal Function Impairment

Total clearance was reduced and mean exposure (AUC) was increased in varying degrees of renal impairment. However, renal impairment did not impact the reversal effect of idarucizumab.

Use: Labeled Indications

Reversal of dabigatran: Reversal of the anticoagulant effects of dabigatran for emergency surgery/urgent procedures or in life-threatening or uncontrolled bleeding.

Contraindications

There are no contraindications listed in the manufacturer's labeling.

Canadian labeling: Additional contraindications (not in US labeling): Hypersensitivity to idarucizumab or any component of the formulation.

Dosing: Adult

Reversal of dabigatran:

Note: Generally used for life-threatening bleeding, bleeding into a critical organ, or prior to an emergency procedure if maximal supportive measures (eg, activated charcoal [if ingestion is within ~2 to 4 hours], antifibrinolytic agent, hemodialysis) are not adequately effective (ACC [Tomaselli 2020]; Baugh 2019; Cuker 2019).

IV: 5 g (administered as 2 separate 2.5 g doses no more than 15 minutes apart). Note: Repeat dosing is not usually required. However, another dose may be considered (despite limited data) if bleeding continues and there is laboratory evidence of persistent dabigatran effect or before an emergent invasive procedure if there is concern for a persistent anticoagulant effect (ACC [Tomaselli 2020).

Dosing: Geriatric

Refer to adult dosing.

Administration

IV: For IV use only. Do not shake. Prior to administration, flush preexisting IV line with sodium chloride 0.9%. Administer dose undiluted as an IV bolus either via syringe or as an infusion by hanging the vials. Do not mix with other drugs or administer any other infusion in the same IV line. Administer promptly once solution has been removed from vial. Infusion of each vial should take no longer than 5 to 10 minutes with the second vial of 2.5 g administered no later than 15 minutes after the end of the first 2.5 g vial (Pollack 2015 [protocol]).

Storage

Store intact vials at 2ºC to 8ºC (36ºF to 46ºF) in original packaging (to protect from light). Do not freeze. May store intact vials in the original packaging (to protect from light) at room temperature, 25°C (77°F), for up to 48 hours or up to 6 hours if exposed to light.

Drug Interactions

There are no known significant interactions.

Adverse Reactions

The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified.

1% to 10%:

Central nervous system: Headache (5%)

Gastrointestinal: Constipation (7%), nausea (5%)

Frequency not defined:

Hypersensitivity: Hypersensitivity reaction (including bronchospasm, fever, hyperventilation, pruritus, skin rash)

<1%, postmarketing, and/or case reports (Pollack 2015): Acute ischemic stroke, circulatory shock, deep vein thrombosis, intracardiac thrombus (left atrium), multiorgan failure, myocardial infarction (NSTEMI), pulmonary edema, pulmonary embolism, right heart failure, thromboembolic complications (Pollack 2017)

Warnings/Precautions

Concerns related to adverse effects:

• Hypersensitivity reactions: Although there is insufficient clinical experience with idarucizumab to fully evaluate the risk of hypersensitivity reactions, some reported adverse events possibly indicative of hypersensitivity reactions could not exclude a potential relationship. The risk of using idarucizumab in patients with known hypersensitivity (eg, anaphylactoid reaction) to idarucizumab or any of the components of the formulation should be evaluated cautiously against the potential benefit of emergency dabigatran reversal. Discontinue use if serious allergic reaction occurs (eg, anaphylaxis) and institute appropriate management.

• Thromboembolic risk: Since patients being treated with dabigatran, have underlying disease states predisposing them to thromboembolic events and reversing the effects of dabigatran will expose the patient to an elevated thrombotic risk; resume anticoagulant therapy as soon as it is appropriate. Dabigatran can be re-initiated 24 hours after idarucizumab administration if appropriate. In the phase 3 clinical trial, not all thromboembolic events that occurred reflected the underlying disease state being treated with dabigatran; adverse thromboembolic events included DVT, PE, atrial thrombus, NSTEMI, and ischemic stroke (Giannandrea 2018; Pollack 2015).

Disease-related concerns:

• Hereditary fructose intolerance: Formulation contains 4 grams of sorbitol as an excipient. Since IV administration of sorbitol in patients with hereditary fructose intolerance has been reported to result in serious reactions (eg, acute hepatic failure, hypoglycemia, hypophosphatemia, metabolic acidosis, uric acid elevations) including fatalities, consider the combined daily metabolic load of sorbitol/fructose from all sources including idarucizumab and other drugs containing sorbitol; minimum amount of sorbitol known to cause serious adverse reactions is unknown.

Other warnings/precautions:

• Coagulation parameter re-elevation: Although the duration of effect typically lasts at least 24 hours, in the phase 3 clinical trial, coagulation parameters (eg, aPTT, TT, ecarin clotting time [not routinely available]) re-elevated in a limited number of patients between 12 and 24 hours after administration; some patients experienced re-elevation as early as 1 to 4 hours after administration which may have been due to high initial baseline dabigatran concentrations. If clinically relevant bleeding in conjunction with elevated coagulation parameters reoccurs following an idarucizumab 5 g dose, administration of a second dose should be considered (Pollack 2015; Pollack 2017).

• Incomplete reversal: Potential for incomplete reversal of dabigatran exists with idarucizumab. Case reports have described patients with very high initial serum dabigatran concentrations who experienced unsuccessful reversal of the anticoagulant effects of dabigatran after idarucizumab and required repeat doses; early detection of excessive dabigatran concentrations measured using the chromogenic ecarin clotting time assay or reflected as elevated coagulation parameters (ie, INR or thrombin time) is essential (Steele 2017).

Monitoring Parameters

Monitor for re-elevation of coagulation parameters (eg, aPTT); signs/symptoms of clinically relevant bleeding and thromboembolic events.

In patients overdosed with dabigatran, consider the following monitoring schedule (Alikhan 2014): Baseline aPTT (at presentation), repeat at 2 hours postexposure (if exposure time is known) or post-presentation (if exposure time is unknown) and every 12 hours thereafter until aPTT returns to normal.

Pregnancy Considerations

Animal reproduction studies have not been conducted.

Patient Education

What is this drug used for?

• It is used to undo the effects of a certain blood thinner.

All drugs may cause side effects. However, many people have no side effects or only have minor side effects. Call your doctor or get medical help if any of these side effects or any other side effects bother you or do not go away:

• Headache

• Nausea

• Constipation

WARNING/CAUTION: Even though it may be rare, some people may have very bad and sometimes deadly side effects when taking a drug. Tell your doctor or get medical help right away if you have any of the following signs or symptoms that may be related to a very bad side effect:

• Blood clots like numbness or weakness on one side of the body; pain, redness, tenderness, warmth, or swelling in the arms or legs; change in color of an arm or leg; chest pain; shortness of breath; fast heartbeat; or coughing up blood.

• Bleeding

• Shortness of breath

• Fast breathing

• Signs of an allergic reaction, like rash; hives; itching; red, swollen, blistered, or peeling skin with or without fever; wheezing; tightness in the chest or throat; trouble breathing, swallowing, or talking; unusual hoarseness; or swelling of the mouth, face, lips, tongue, or throat.

Note: This is not a comprehensive list of all side effects. Talk to your doctor if you have questions.

Consumer Information Use and Disclaimer: This information should not be used to decide whether or not to take this medicine or any other medicine. Only the healthcare provider has the knowledge and training to decide which medicines are right for a specific patient. This information does not endorse any medicine as safe, effective, or approved for treating any patient or health condition. This is only a limited summary of general information about the medicine’s uses from the patient education leaflet and is not intended to be comprehensive. This limited summary does NOT include all information available about the possible uses, directions, warnings, precautions, interactions, adverse effects, or risks that may apply to this medicine. This information is not intended to provide medical advice, diagnosis or treatment and does not replace information you receive from the healthcare provider. For a more detailed summary of information about the risks and benefits of using this medicine, please speak with your healthcare provider and review the entire patient education leaflet.

Further information

Always consult your healthcare provider to ensure the information displayed on this page applies to your personal circumstances.