Praxbind (idarucizumab)

Praxbind (idarucizumab) is an antibody used to reverse the effect of Pradaxa (dabigatran) for emergency surgery/urgent procedures or if life-threatening or uncontrolled bleeding occurs while taking dabigatran.

Dabigatran is an anticoagulant (blood thinner) used to prevent blood clots in people with non-valvular atrial fibrillation and for treating deep venous thrombosis (DVT) and pulmonary embolism (PE).

Common side effects of Praxbind include

• headache,
• low blood potassium,
• delirium,
• constipation,
• fever,
• pneumonia,
• allergic reactions,
• increased levels of laboratory markers for blood clotting, and
• idarucizumab antibodies.

Serious side effects of Praxbind include removal of the protective effect of dabigatran in people who are at risk for blood clots, and risk for adverse reactions in patients with hereditary fructose intolerance because idarucizumab contains sorbitol. 

There are no known drug interactions for Praxbind.

There are no adequate or well-controlled trials of Praxbind use in pregnant women. Praxbind should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

It is unknown if Praxbind is excreted into human milk. Consult your doctor before breastfeeding. 

Common side effects of idarucizumab include:

• Headache
• Low blood potassium
• Delirium
• Constipation
• Fever
• Pneumonia

Other reported side effects include:

• Allergic reactions
• Increased levels of laboratory markers for blood clotting
• Idarucizumab antibodies

Possible serious side effects of idarucimab include:

• Reversing the effect of dabigatran removes the protective effect of dabigatran in people who are at risk for blood clots. Therefore, anticoagulation should be started as soon as possible after treatment with idarucizumab.
• If patients continue to bleed or require a second emergency surgery/urgent procedure, an additional 5 g dose of idarucizumab may be considered.
• Idarucizumab contains sorbitol. Patients with hereditary fructose intolerance may be at risk for adverse reactions. 

The following serious adverse reactions are described in more detail elsewhere in the labeling:

• Thromboembolic Risk
• Hypersensitivity Reactions
• Risks of Serious Adverse Reactions in Patients with Hereditary Fructose Intolerance due to Sorbitol Excipient

Clinical Trials Experience

• Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in clinical practice.
• In three healthy volunteer clinical trials, 224 subjects were treated with idarucizumab. In these trials during the treatment period the overall frequency of adverse events was similar between idarucizumab-treated subjects (55/224, 25%) and placebo-treated subjects (26/105, 25%).
• Among those subjects treated with idarucizumab, adverse reactions reported in ≥5% of subjects was headache (12/224, 5%).
• In the RE-VERSE AD (RE-VERSal Effects of idarucizumab on Active Dabigatran) trial, a total of 503 dabigatran-treated patients were administered idarucizumab either because they required an emergency surgery or urgent procedure, or because they presented with life-threatening or uncontrolled bleeding.
• The adverse reactions reported in ≥5% of patients were constipation (33/503, 7%) and nausea (23/503, 5%).
• Of the 503 dabigatran-treated patients in the entire study period, 101 patients died, 19 within the first day after idarucizumab dosing; each of these deaths could be attributed either as a complication of the index event or associated with co-morbidities.

Thromboembolic Events

• In the RE-VERSE AD trial, 33 of 503 patients reported thrombotic events, 11 patients within 5 days after treatment with idarucizumab and 22 patients 6 days or more after treatment with idarucizumab.
• Most of these patients were not on antithrombotic therapy at the time of the event, and in each of these cases, the thrombotic event could be attributed to the underlying medical condition of the patient.

Hypersensitivity

• Pyrexia, bronchospasm, hyperventilation, rash, and pruritus have been reported in clinical trials with idarucizumab.

Immunogenicity

• As with all proteins there is a potential for immunogenicity with idarucizumab. Detection of antibody formation is highly dependent on the sensitivity and specificity of the assay.
• Additionally, the observed incidence of antibody (including neutralizing antibody) positivity in an assay may be influenced by several factors including assay methodology, sample handling, timing of sample collection, concomitant medications and underlying disease.
• For these reasons, comparison of the incidence of antibodies to idarucizumab in the studies described below with the incidence of antibodies in other studies or to other products may be misleading.
• Using an electro-chemiluminescence (ECL) based assay, plasma samples from 283 subjects (224 treated with idarucizumab) in phase I trials and 501 patients were tested for antibodies cross-reacting with idarucizumab. Pre-existing antibodies with cross-reactivity to idarucizumab were detected in approximately 12% (33/283) of the subjects and 4% (19/501) of patients.
• The majority of pre-existing antibodies were shown to have low titers. No impact on the pharmacokinetics or the reversal effect of idarucizumab or hypersensitivity reactions were observed.
• Treatment-emergent possibly persisting anti-idarucizumab antibodies with low titers were observed in 4% (10/224) of the subjects and 2% (8/501) of patients treated with idarucizumab. Nine patients were re-dosed with idarucizumab.
• All nine patients were re-dosed within 6 days after the first idarucizumab dose. None of these patients re-dosed with idarucizumab tested positive for anti-idarucizumab antibodies.
• The epitope specificity of antibodies to idarucizumab was characterized using probe molecules.
• For pre-existing antibodies in patients, 95% (18/19) had specificity for the C-terminus, a region of idarucizumab to which dabigatran does not bind.
• For treatment emergent antibodies in patients, 67% (6/9) had specificity for the C-terminus, 22% (2/9) had specificity for the variable region, and 11% (1/9) had mixed specificity.

No Information provided