Idarucizumab (Praxbind)

ED / ICU / Transport

• Life-threatening or uncontrolled bleeding on dabigatran: it reverses the anticoagulant effect (FDA-labeled)
• Emergency surgery or urgent procedure when the patient is on dabigatran (FDA-labeled)
• Dabigatran-associated intracranial hemorrhage: the AHA/ASA 2022 spontaneous ICH guideline rates idarucizumab reasonable for reversal (COR 2a, LOE B-NR)
• Dabigatran exposure with unknown timing or unknown anticoagulant: Confirm the drug first. Idarucizumab does nothing to other anticoagulants (see Interactions).

Doses vary by protocol; follow local protocols and medical direction.

Available Forms

• Single-dose vial: 2.5 g in 50 mL (50 mg/mL) idarucizumab, sterile, preservative-free; carton of two vials (NDC 0597-0197-05)
• Labeled dose: one carton (two vials, 5 g) per dose

Adult Dosing

Pediatric Dosing

Preparation & Administration

• Dilution: none. Do not mix with other medicinal products; use aseptic technique.
• Push rate: two consecutive infusions by hanging vials, or a bolus by injecting both vials one after another by syringe. The label’s healthy-volunteer study (Section 14) ran one 5 g infusion over 5 minutes. The label gives no rate for the two-infusion regimen in section 2.3.
• Flush: flush any pre-existing IV line with sterile 0.9% sodium chloride before infusion; no other infusion runs in parallel through the same access.
• Line: A pre-existing IV line may be used. The label does not specify a peripheral or central site.
• Inspection & storage: inspect for particulates and discoloration. Store at 2–8°C in the carton, protect from light, do not freeze or shake. Vials may stand at room temperature for up to 48 hours in the carton. Vials out of the carton at 25°C and exposed to light must be used within 6 hours. Once solution is withdrawn from a vial, start administration promptly (label 2.2, 16.2).
• Filter: none specified by the label.

Contraindications

• Nothing is labeled as a contraindication (label Section 4: None). Known hypersensitivity is handled as a precaution below and weighed against the emergency benefit.

Precautions

• Thromboembolic risk: reversal leaves the patient with the thrombotic risk of the underlying disease. Restart anticoagulation as soon as medically appropriate (label 2.4, 5.1). In RE-VERSE AD, 33 of 503 patients had thrombotic events.
• Re-elevated clotting tests: between 12 and 24 hours after 5 g, aPTT or ECT may climb again (label 5.2).
• Hypersensitivity (relative): clinical experience is too thin to judge the risk. Pyrexia, bronchospasm, hyperventilation, rash and pruritus were reported. If it happens, stop the infusion and treat anaphylaxis (label 5.3).
• Hereditary fructose intolerance (relative): every dose carries 4 g sorbitol. Parenteral sorbitol in this condition has been followed by serious reactions, some of them fatal (label 5.4).
• Pregnancy and lactation: there are no human data. In pregnancy, give it only if clearly needed. It is unknown whether idarucizumab enters human milk (label 8.1, 8.2).

Hold / Reassess If

• Bleeding continues with an elevated aPTT or ECT measured 12–24 hours after the dose: consider an additional 5 g dose (label 5.2) once you have confirmed the bleeding source.
• Anaphylaxis or serious hypersensitivity: stop the infusion right away and start anaphylaxis treatment per protocol (label 5.3).
• Dabigatran restart: dabigatran may restart 24 hours after the dose, if that is clinically appropriate (label 2.4). Restart anticoagulation as soon as medically appropriate.

Common

• Constipation: 7% (33 of 503) in RE-VERSE AD patients (label 6.1)
• Nausea: 5% (23 of 503) in RE-VERSE AD patients
• Headache: 5% (12 of 224) in healthy volunteers
• Pyrexia, rash, pruritus, bronchospasm, hyperventilation: reported in trials; frequency not labeled

Serious / Life-Threatening

Overdose & Toxicity Management

• No overdose data: there is no antidote for idarucizumab, and the label describes no overdose toxicity. Management is supportive. The only labeled escalation is a second 5 g dose, and its safety is not established.
• Immunogenicity: pre-existing cross-reacting antibodies turned up in about 12% of volunteers and 4% of patients. Low-titer antibodies emerged during treatment in 4% of volunteers and 2% of patients. Neither pharmacokinetics, reversal nor hypersensitivity was affected (label 6.2).
• Mortality context: in RE-VERSE AD, 101 of 503 patients died during the study. 19 died within the first day after dosing. The label attributes each death to the index event or comorbidity (label 6.1).

Clinically Significant Interactions

IV Compatibility

• Diluent: none. Do not mix with other medicinal products.
• Dedicated line: a pre-existing IV line may be used after flushing with 0.9% sodium chloride. Nothing runs in parallel through the same access.
• Y-site: the label has no Y-site compatibility data. Give it alone.
• Verify with an institutional compatibility resource.

• Pediatrics: safety and effectiveness are not established. See the Pediatric Dosing table. No pediatric dose is labeled.
• Pregnancy: there are no human data and no animal reproductive studies. Give it only if clearly needed. The background risk is 2–4% for major birth defects and 15–20% for miscarriage in clinically recognized pregnancies (label 8.1).
• Lactation: it is unknown whether idarucizumab is excreted in human milk. Weigh the mother's need for reversal against any effect on the infant (label 8.2).
• Older Adults: 90% of RE-VERSE AD patients were 65 or older, and 63% were 75 or older. No overall difference in safety or effectiveness was seen. Greater sensitivity in some older patients cannot be excluded (label 8.5).
• Renal Impairment: no dose adjustment is required (label 12.3). Exposure (AUC) rose by 38%, 90% and 146% at CrCl 50 to <80, 30 to <50 and 0 to <30 mL/min. As renal function falls, dabigatran builds up, and the need for reversal climbs with it.
• Hepatic Impairment: no specific adjustment is established. The label does not address hepatic impairment.
• Obesity / Dosing Weight: The dose is a fixed 5 g. In population pharmacokinetic analyses, body weight had no clinically important effect on exposure (label 12.3).

• Scope: usually hospital-only. Whether a field crew may give it varies by state and agency protocol.
• Storage & Stability: 2–8°C in the carton, protect from light, do not freeze. Room temperature up to 48 hours in the carton. Vials out of the carton at 25°C and exposed to light: use within 6 hours. Once solution is withdrawn from a vial, start administration promptly.
• Carried Concentration: A 5 g dose comes as two 2.5 g vials. Confirm both are present and check the expiry date on each.
• Infusions in Transport: No maintenance infusion runs. Keep the dedicated line flushed. Verify that both vials were given, and when.
• Altitude / Environment: The label does not address altitude or environment.
• Handoff Essentials: time and dose given, time of last dabigatran dose, the pre-dose and post-dose clotting test, bleeding status, and the anticoagulation restart plan.

Mechanism of Action

• Target: a humanized Fab fragment. It binds dabigatran and its acylglucuronide metabolites with higher affinity than dabigatran has for thrombin.
• Effect: unbound dabigatran drops below the lower limit of quantification right after 5 g. dTT, ECT, aPTT and ACT return to baseline (label 12.1, 12.2).
• Consequence: thrombin generation is restored. The thrombotic risk from the underlying disease returns too (label 2.4).

Pharmacokinetics

• Half-life: initial 47 minutes; terminal 10.3 hours; total clearance 47.0 mL/min (label 12.3).
• Metabolism: antibody catabolism to small peptides and amino acids; no CYP pathway.
• Active metabolites: none described.
• Elimination: 32.1% of a 5 g dose is recovered in urine over 6 hours, and less than 1% over the next 18 hours. The rest is protein catabolism, mainly in the kidney.
• Volume of distribution: steady-state Vss is 8.9 L (geometric mean) after 5 g. Distribution outside the vessels is limited.

Generic Name

Idarucizumab

Brand Names

Praxbind (US)

Pharmacologic Class

Specific dabigatran reversal agent (humanized monoclonal antibody Fab fragment)

Therapeutic Class

Anticoagulant reversal agent (antidote)

Controlled Substance

Not controlled

ISMP High-Alert

No

Look-Alike / Sound-Alike

None commonly reported