Identify appropriate patients1

3D red-blue horshoe-shaped magnet lying flat, to represent Andexxa's power to draw out FXa inhibitors

Know the facts

More than 400 patients a day are hospitalized with an apixaban- or rivaroxaban-related bleed. As prescriptions for these direct oral anticoagulants increase, the potential for serious bleeding admissions grows.2-4

Here are some facts about these patients:

  • In nonvalvular atrial fibrillation clinical trials, 45% of apixaban patients (ARISTOTLE Trial*) and 48% of rivaroxaban patients (ROCKET AF Trial) with intracranial hemorrhage died within 30 days5,6
  • In a prospective, multicenter observational study substantial hematoma expansion (defined as a volume increase of ≥33% or ≥6 mL) occurred in approximately 40% of intracerebral hemorrhage patients taking direct oral anticoagulants (DOACs)‡8
  • Gastrointestinal bleeds account for 39%-56% of all bleeding events in apixaban- and rivaroxaban-treated patients*†9,10
*ARISTOTLE study design: Based on a double-blind, double-dummy, randomized clinical trial comparing apixaban with warfarin in patients with AF (N=18,201).5
ROCKET AF study design: Based on a multinational, randomized, double-blind, double-dummy clinical trial comparing rivaroxaban with warfarin in patients with atrial fibrillation (AF) (N=14,264).6
RASUNOA study design: Based on a prospective, multicenter, observational substudy of patients with nontraumatic DOAC-related intracerebral hemorrhage (n=45).8

Meet some typical patients for ANDEXXA®

Patient stories are based on actual cases; however, images are non-patient models.

Linda | 70 | Taking rivaroxaban

Head-and-shoulders front view of older woman wearing a pastel head scarf representing a subdural hemorrhage patient

Linda slipped on her stairs at home. She didn't think she was severely injured until later that night.

  • Presented at the ER at ~5 AM, feeling dizzy and exhibiting facial bruising
  • Takes rivaroxaban (10 mg, last taken at ~9:30 PM, ~ 7.5 hours prior to ER arrival) for deep vein thrombosis (DVT) and atorvastatin for hyperlipidemia
  • Transported to the ER by a family member
  • Presented with impairment in spatial perception and stability
  • Also showed visible facial bruising and left arm and left leg weakness
  • Vitals:
    • Blood pressure: 150/90 mmHg
    • Heart rate: 90
    • Respiratory rate: 22
    • Glasgow coma scale: 12 (4/4/4)
  • Preliminary diagnosis: suspected DOAC-related hematoma
  • CT scan of head revealed, in its largest segment, a 10-mm subdural hemorrhage with 3-mm midline shift

For patients like Linda, consider ANDEXXA

Primary diagnosis:
Subdural hemorrhage

Treatment plan:

  • Get high blood pressure under control
  • Reverse rivaroxaban-related anticoagulation with a low dose of ANDEXXA1
  • Admit to intensive care unit11
  • Repeat CT scan per medical judgment12
Download Linda's Full Story

Michael | 61 | Taking apixaban

Upper torso shot of gray-bearded man lying in a hospital bed representing an intracerebral hemorrhage patient

Arriving home after dinner out with his wife, Michael suddenly had trouble forming words.

  • Presented at the ER with expressive aphasia and intense headache
  • Takes apixaban (5 mg, last taken ~8 hours prior to ER arrival) for nonvalvular atrial fibrillation and amlodipine for hypertension
  • Transported to the ER by a family member
  • Was poorly responsive upon arrival in ER
  • Intubated in ER to protect airway
  • Vitals:
    • Blood pressure: 180/80 mmHg
    • Heart rate: 110
    • Glasgow coma scale: 12 (4/3/5) upon presentation, then declined to 8 (2/1/5), leading to intubation
  • Preliminary diagnosis: suspected DOAC-related hematoma
  • CT scan of head revealed primary intraparenchymal bleed; volume of 15 cc in lobar ICH in the left temporal lobe

For patients like Michael, consider ANDEXXA

Primary diagnosis:
Intracerebral hemorrhage

Treatment plan:

  • Get high blood pressure under control
  • Reverse apixaban-related anticoagulation with a low dose of ANDEXXA1
  • Repeat CT scan of head in 6 hours7
  • Evaluate for possible secondary cause(s) of intracerebral hemorrhage
Download Michael's Full Story

References:
1. Andexxa (prescribing information). Boston, MA: Alexion Pharmaceuticals, Inc.; 2021. 2. Truven Bleeding Events Report: Commercial, Medicare & Medicaid Populations, August 16, 2016. 3. Truven Health Analytics, DOAC Market Data Report. Data month ending November 2018. 4. Truven Health Analytics, DOAC Market Data Report. Data month ending September 2019. 5. Held C, Hylek EM, Alexander JH, et al. Clinical outcomes and management associated with major bleeding in patients with atrial fibrillation treated with apixaban or warfarin: insights from the ARISTOTLE trial. Eur Heart J. 2015;36(20):1264-1272. 6. Hankey GJ, Stevens SR, Piccini JP, et al; for the ROCKET AF Steering Committee and Investigators. Intracranial hemorrhage among patients with atrial fibrillation anticoagulated with warfarin or rivaroxaban: the rivaroxaban once daily, oral, direct factor Xa inhibition compared with vitamin K antagonism for prevention of stroke and embolism trial in atrial fibrillation. Stroke. 2014;45(5):1304-1312. 7. Melmed KR, Lyden P, Gellada N, et al. Intracerebral hemorrhagic expansion occurs in patients using non-vitamin K antagonist oral anticoagulants comparable with patients using warfarin. J Stroke Cerebrovasc Dis. 2017;26(8):1874-1882. 8. Purrucker JC, Haas K, Rizos T, et al. Early clinical and radiological course, management, and outcome of intracerebral hemorrhage related to new oral anticoagulants. JAMA Neurol. 2016;73:169-177. 9. Eliquis [prescribing information]. Princeton, NJ: Bristol-Myers Squibb Company, and New York, NY: Pfizer Inc.; 2019. 10. Xarelto [prescribing information]. Titusville, NJ: Janssen Pharmaceuticals, Inc.; 2020. 11. Nates JL, Nunnally M, Kleinpell R, et al. ICU admission, discharge, and triage guidelines: a framework to enhance clinical operations, development of institutional policies, and further research. Crit Care Med. 2016;44(8):1553-1602. 12. Connolly SJ, Crowther M, Eikelboom JW, et al. Full study report of andexanet alfa for bleeding associated with factor Xa inhibitors. N Engl J Med. 2019;380:1326-1335

SELECT IMPORTANT SAFETY INFORMATION

WARNING: THROMBOEMBOLIC RISKS, ISCHEMIC RISKS, CARDIAC ARREST, AND SUDDEN DEATHS

See full prescribing information for complete boxed warning

Treatment with ANDEXXA has been associated with serious and life-threatening adverse events, including:

  • Arterial and venous thromboembolic events

  • Ischemic events, including myocardial infarction and ischemic stroke

  • Cardiac arrest

  • Sudden deaths

Monitor for thromboembolic events and initiate anticoagulation when medically appropriate. Monitor for symptoms and signs that precede cardiac arrest and provide treatment as needed.

INDICATION

ANDEXXA (coagulation factor Xa (recombinant), inactivated-zhzo) is a recombinant modified human factor Xa (FXa) protein indicated for patients treated with rivaroxaban or apixaban, when reversal of anticoagulation is needed due to life-threatening or uncontrolled bleeding.

This indication is approved under accelerated approval based on the change from baseline in anti-FXa activity in healthy volunteers. An improvement in hemostasis has not been established. Continued approval for this indication may be contingent upon the results of studies that demonstrate an improvement in hemostasis in patients.

Limitations of Use

ANDEXXA has not been shown to be effective for, and is not indicated for, the treatment of bleeding related to any FXa inhibitors other than apixaban or rivaroxaban.

Select Important Safety Information
WARNINGS AND PRECAUTIONS

Thromboembolic and Ischemic Risks

The thromboembolic and ischemic risks were assessed in 352 bleeding subjects who received ANDEXXA. Of the 63 subjects who experienced a thrombotic event, the median time to first event was 7 days, and 21 subjects experienced the event within the first three days. A total of 63 (18%) experienced 88 thromboembolic or ischemic events. Of the 352 subjects who received ANDEXXA, 223 received at least one anticoagulation dose within 30 days after treatment. Of these 223, 18 subjects (8%) had a thrombotic event and/or ischemic event after resumption.

Monitor patients treated with ANDEXXA for signs and symptoms of arterial and venous thromboembolic events, ischemic events, and cardiac arrest. To reduce thromboembolic risk, resume anticoagulant therapy as soon as medically appropriate following treatment with ANDEXXA.

The safety of ANDEXXA has not been evaluated in patients who experienced thromboembolic events or disseminated intravascular coagulation within two weeks prior to the life-threatening bleeding event requiring treatment with ANDEXXA. Safety of ANDEXXA also has not been evaluated in patients who received prothrombin complex concentrates, recombinant factor VIIa, or whole blood products within seven days prior to the bleeding event.

Re-elevation or Incomplete Reversal of Anti-FXa Activity

The time course of anti-FXa activity following ANDEXXA administration was consistent among the healthy volunteer studies and the ANNEXA-4 study in bleeding patients. Compared to baseline, there was a rapid and substantial decrease in anti-FXa activity corresponding to the ANDEXXA bolus. This decrease was sustained through the end of the ANDEXXA continuous infusion. The anti-FXa activity returned to the placebo levels approximately two hours after completion of a bolus or continuous infusion. Subsequently, the anti-FXa activity decreased at a rate similar to the clearance of the FXa inhibitors.

Seventy-one subjects were anticoagulated with apixaban and had baseline levels of anti-FXa activity > 150 ng/mL. Nineteen subjects who were anticoagulated with rivaroxaban had elevated baseline anti-FXa activity levels >300 ng/mL. Forty-eight of the 71 apixaban-treated subjects (68%) experienced a > 90% decrease from baseline anti-FXa activity after administration of ANDEXXA. Ten of the 19 rivaroxaban subjects (53%) experienced a > 90% decrease from baseline anti-FXa activity after administration of ANDEXXA.

Use of Heparin Following Administration of ANDEXXA

ANDEXXA may interfere with the anticoagulant effect of heparin. Use of ANDEXXA as an antidote for heparin has not been established. Avoid use of ANDEXXA for the reversal of direct FXa inhibitors (apixaban and rivaroxaban) prior to heparinization as ANDEXXA may cause unresponsiveness to heparin. If anticoagulation is needed, use an alternative anticoagulant to heparin.

ADVERSE REACTIONS

The most common adverse reactions (≥ 5%) in bleeding patients receiving ANDEXXA were urinary tract infections and pneumonia.

The most common adverse reactions (≥ 3%) in healthy subjects treated with ANDEXXA were infusion-related reactions.

Immunogenicity

As with all therapeutic proteins, there is the potential for immunogenicity. Using an electrochemiluminescence (ECL)-based assay, 145 ANDEXXA-treated healthy subjects were tested for antibodies to ANDEXXA as well as antibodies cross-reacting with Factor X (FX) and FXa. Low titers of anti-ANDEXXA antibodies were observed in 26/145 healthy subjects (17%); 6% (9/145) were first observed at Day 30 with 20 subjects (14%) still having titers at the last time point (Days 44 to 48). To date, the pattern of antibody response in patients in the ongoing ANNEXA-4 study has been similar to that observed in healthy volunteers. Of the 236 subjects with available samples, 6.8% (16/236) had antibodies against ANDEXXA. None of these anti-ANDEXXA antibodies were neutralizing. No neutralizing antibodies cross-reacting with FX or FXa were detected in healthy subjects (0/145) or in bleeding patients (0/209) to date.

To report SUSPECTED ADVERSE REACTIONS, call 1-844-259-6783 or contact the FDA by visiting www.fda.gov/medwatch, or calling 1-800-FDA-1088.

Please see full Prescribing Information including Boxed Warning on thromboembolic risks, ischemic risks, cardiac arrest, and sudden death.