Indications and UsageNovoSeven® RT (Coagulation Factor VIIa [Recombinant]) is a coagulation factor indicated for:

• Treatment of bleeding episodes and peri-operative management in adults and children with hemophilia A or B with inhibitors, congenital Factor VII (FVII) de� ciency, and Glanzmann’s thrombasthenia with refractoriness to platelet transfusions, with or without antibodies to platelets

• Treatment of bleeding episodes and peri-operative management in adults with acquired hemophilia

Important Safety Information

WARNING: THROMBOSIS

• Serious arterial and venous thrombotic events following administration of NovoSeven® RT have been reported.

• Discuss the risks and explain the signs and symptoms of thrombotic and thromboembolic events to patients who will receive NovoSeven® RT.

• Monitor patients for signs or symptoms of activation of the coagulation system and for thrombosis.

Please see additional Important Safety Information throughout.Please see accompanying Prescribing Information.

A delay could put your patients at riskPrompt diagnosis of acquired hemophilia may impact lives

Stop the bleed with the only bypassing agent FDA approved for acquired hemophilia7

Important Safety Information (cont’d)

Adverse Reactions

• The most common and serious adverse reactions in clinical trials are thrombotic events. Thrombotic adverse reactions following the administration of NovoSeven® RT in clinical trials occurred in 4% of patients with acquired hemophilia and 0.2% of bleeding episodes in patients with congenital hemophilia.

Please see additional Important Safety Information, including Boxed Warning, throughout.Please see accompanying Prescribing Information.

References: 1. Huth-Kühne A, Baudo F, Collins P, et al. International recommendations on the diagnosis and treatment of patients with acquired hemophilia A. Haematologica. 2009;94(4):566-575. 2. Collins PW, Hirsch S, Baglin TP, et al; for UK Haemophilia Centre Doctors’ Organisation. Acquired hemophilia A in the United Kingdom: a 2-year national surveillance study by the United Kingdom Haemophilia Centre Doctors’ Organisation. Blood. 2007;109(5):1870-1877. 3. Bitting RL, Bent S, Li Y, Kohlwes J. The prognosis and treatment of acquired hemophilia: a systematic review and meta-analysis. Blood Coagul Fibrinolysis. 2009;20(7):517-523. 4. Knoebl P, Marco P, Baudo F, et al; EACH2 Registry Contributors. Demographic and clinical data in acquired hemophilia A: results from the European Acquired Haemophilia Registry (EACH2). J Thromb Haemost. 2012;10(4):622-631. 5. Collins PW, Percy CL. Advances in the understanding of acquired haemophilia A: implications for clinical practice. Br J Haematol. 2010;148(2):183-194. 6. Konkle BA. Clinical approach to the bleeding patient. In: Colman RW, Marder VJ, Clowes AW, George JN, Goldhaber SZ, eds. Hemostasis and Thrombosis: Basic Principles and Clinical Practice. 5th ed. Philadelphia, PA: Lippincott Williams & Wilkins; 2006:1147-1158. 7. NovoSeven® RT [package insert]. Plainsboro, NJ: Novo Nordisk Inc.; 2015. 8. Sumner MJ, Geldziler BD, Pedersen M, Seremetis S. Treatment of acquired haemophilia with recombinant activated FVII: a critical appraisal. Haemophilia. 2007;13(5):451-461. 9. Centers for Disease Control and Prevention. International Classi� cation of Diseases, Ninth Revision, Clinical Modi� cation (ICD-9-CM). ftp://ftp.cdc.gov/pub/Health_Statistics/NCHS/Publications/ICD9-CM/2011/. Updated September 8, 2011. Accessed February 28, 2017. 10. Centers for Disease Control and Prevention. International Classi� cation of Diseases, Tenth Revision, Clinical Modi� cation (ICD-10-CM). http://www.cdc.gov/nchs/data/icd/icd10cm/2016/ICD10CM_FY2016_Full_PDF.ZIP. Updated May 29, 2015. Accessed February 28, 2017.

Novo Nordisk Inc., 800 Scudders Mill Road, Plainsboro, New Jersey 08536 U.S.A.

NovoSeven® is a registered trademark of Novo Nordisk Health Care AG.Novo Nordisk is a registered trademark of Novo Nordisk A/S.© 2017 Novo Nordisk Printed in the U.S.A. USA16HDM04351 April 2017

Spot it. Stop it.Spot it. Stop it.Acquired hemophilia.

A rare, spontaneous, and potentially deadly condition1

• Only 1 to 1.5 per million people are affected yearly2

• Characterized by an inhibitory autoantibody to FVIII that appears spontaneously1

Associated with severe and life-threatening bleeding1

• Up to 21% mortality rate3

Often involving a delayed diagnosis

• 35% of patients go undiagnosed for more than 7 days4

Who “acquires” acquired hemophilia? • Underlying conditions include autoimmune disorders, malignancies,

dermatologic disorders, and pregnancy; however, in approximately 50% to 60% of patients, the cause is unknown4

Signs include:

• Isolated prolonged aPTT5

• Purpura and soft-tissue hemorrhage5

• Gastrointestinal, urological, retroperitoneal, or postpartum bleeding1,2

• Prolonged bleeding following surgery5

We recommend that the diagnosis of [acquired hemophilia] be considered whenever an acute or recent onset of bleeding is accompanied by an unexplained prolonged aPTT.1

— Huth-Kühne et al,Haematologica, 2009

aPTT=activated partial thromboplastin time.

Indications and Usage

NovoSeven® RT (Coagulation Factor VIIa [Recombinant]) is a coagulation factor indicated for:

• Treatment of bleeding episodes and peri-operative management in adults and children with hemophilia A or B with inhibitors, congenital Factor VII (FVII) de� ciency, and Glanzmann’s thrombasthenia with refractoriness to platelet transfusions, with or without antibodies to platelets

• Treatment of bleeding episodes and peri-operative management in adults with acquired hemophilia

Important Safety Information

WARNING: THROMBOSIS

• Serious arterial and venous thrombotic events following administration of NovoSeven® RT have been reported.

• Discuss the risks and explain the signs and symptoms of thrombotic and thromboembolic events to patients who will receive NovoSeven® RT.

• Monitor patients for signs or symptoms of activation of the coagulation system and for thrombosis.

Warnings and Precautions

• Serious arterial and venous thrombotic events have been reported in clinical trials and postmarketing surveillance.

• Exercise caution when administering NovoSeven® RT to patients with an increased risk of thromboembolic complications, such as those with disseminated intravascular coagulation (DIC), advanced atherosclerotic disease, crush injury, septicemia, uncontrolled post-partum hemorrhage, history of coronary heart disease, liver disease, post-operative immobilization, in elderly patients, in neonates, or in patients receiving concomitant treatment with aPCCs/PCCs (activated or nonactivated prothrombin complex concentrates).

• Hypersensitivity reactions, including anaphylaxis, have been reported with NovoSeven® RT. Administer only if clearly needed in patients with known hypersensitivity to NovoSeven® RT, any of its components, or mouse, hamster, or bovine proteins. Should symptoms occur, discontinue NovoSeven® RT and administer appropriate treatment.

• Factor VII de� cient patients should be monitored for prothrombin time (PT) and factor VII coagulant activity (FVII:C). If FVII:C fails to reach the expected level, or PT is not corrected, or bleeding is not controlled after treatment with the recommended doses, antibody formation may be suspected and analysis for antibodies should be performed.

• Laboratory coagulation parameters (PT/INR, aPTT, FVII:C) have shown no direct correlation to achieving hemostasis.

Adverse Reactions

• The most common and serious adverse reactions in clinical trials are thrombotic events. Thrombotic adverse reactions following the administration of NovoSeven® RT in clinical trials occurred in 4% of patients with acquired hemophilia and 0.2% of bleeding episodes in patients with congenital hemophilia.

Drug Interactions

• Thrombosis may occur if NovoSeven® RT is administered concomitantly with Coagulation Factor XIII.

Please see accompanying Prescribing Information.

Model is used for illustrative purposes only.

Model is used for illustrative purposes only.

The only bypassing agent FDA approved for acquired hemophilia7

An international consensus recommends the use of NovoSeven® RT as � rst-line treatment1

Using NovoSeven® RT � rst-line improved ef� cacy8,a,b

Thrombotic adverse events within clinical data7

• 4% in patients with acquired hemophilia

The patient

A 60-year-old man with GI bleeding

Initial presentation

• Patient presented to the emergency department with GI bleeding and ecchymoses

• Patient had no underlying risk factors for acquired hemophilia and no bleeding history

Initial evaluation

• Local hematologist/oncologist was consulted by the emergency department physician

• aPTT was found to be prolonged at 90 seconds. With an immediate 1:1 mixing study, the aPTT was decreased to 60 seconds

• A 1:1 aPTT mixing study after 2 hours of incubation at 37°C was not performed

The delay

• Mixing study results were misinterpreted as “correcting,” and acquired hemophilia was inappropriately ruled out

• Treatment with FVIII was started for a presumed factor de� ciency. The prolonged aPTT did not correct with FVIII, and the patient did not stop bleeding

• Patient received more than 100,000 units of FVIII over 10 days, before the treating hematologist/oncologist called the nearby HTC

The diagnosis

• Patient was transferred to a hospital af� liated with the HTC

• Repeat coagulation studies showed:

- Baseline

aPTT was 85 seconds

- 1:1 aPTT mixing study

aPTT was 53 seconds after an immediate mix with normal plasma

aPTT was 88 seconds after 2 hours’ incubation at 37°C

• Inhibitor titer was 55 BUs; FVIII levels were <1%

• Patient was diagnosed with acquired hemophilia

Management

• Patient began treatment with NovoSeven® RT (Coagulation Factor VIIa [Recombinant]) 90 mcg/kg every 2 hours until hemostasis was achieved

• Immunosuppression was initiated

• Patient was followed for 6 to 12 months and was found to be in remission

Key takeaways

For nonspecialist HCPs

• Acute bleeding in combination with an isolated prolongation of the aPTT should prompt an early consult with a hematologist1

• 1:1 aPTT mixing studies and their appropriate interpretation are critical to the proper diagnosis of acquired hemophilia1,6

• Failure to properly diagnose acquired hemophilia in this case led to prolonged hospitalization and unsuccessful treatment with large doses of FVIII

For hematology/oncology specialists

• A 1:1 aPTT mixing study performed only immediately at the time of mixing is not suf� cient to diagnose acquired hemophilia1,6

• As the laboratory reports the mixing study results in seconds, not as “corrected” or “not corrected,” physicians must appropriately evaluate the study results themselves1,6

• Earlier consult with a hematologist/oncologist or benign hematologist with experience in bleeding disorders may support earlier diagnosis

• Failure to properly diagnose acquired hemophilia in this case led to prolonged hospitalization and unsuccessful treatment with large doses of FVIII

For pharmacists

• Use of 100,000 units of FVIII over 10 days could have served as a red � ag to consider the diagnosis of acquired hemophilia

• Communication between the pharmacist and health care team could support earlier diagnosis of acquired hemophilia

• Failure to properly diagnose acquired hemophilia in this case led to prolonged hospitalization and unsuccessful treatment with large doses of FVIII

• NovoSeven® RT (Coagulation Factor VIIa [Recombinant]) is an FDA-approved therapy with established reimbursement codes7

An acquired hemophilia case in which delayed diagnosis put a patient at risk

a Ef� cacy of NovoSeven® RT used � rst-line versus salvage therapy.

b Data were extracted from a review of experiences with rFVIIa for the treatment of acquired hemophilia in compassionate-use programs, the Hemophilia & Thrombosis Research Society (HTRS) registry, and independent published reports. Ef� cacy was de� ned as “effective” and “partially effective” treatment outcomes. “Ineffective” treatment was determined by the inability to stop the bleeding episode or by the physician describing treatment as not effective.8

cThe minimum effective dose has not been determined.

C A S E S T U D Y

BU=Bethesda unit; GI=gastrointestinal; HCP=health care professional; HTC=hemophilia treatment center.

Spot it. Stop it.

Important Safety Information (cont’d)

Warnings and Precautions

• Serious arterial and venous thrombotic events have been reported in clinical trials and postmarketing surveillance.

Please see additional Important Safety Information, including Boxed Warning, throughout.Please see accompanying Prescribing Information.

Model is used for illustrative purposes only.

Treatment of acute bleeding episodes

Perioperative management (major or minor surgery)

70 mcg/kg to 90 mcg/kg every 2 to 3 hours until hemostasis is achieved

70 mcg/kg to 90 mcg/kg immediately before surgery and repeat every 2 to 3 hours for the duration of the surgery and until hemostasis is achieved

Recommended dosing of NovoSeven® RTfor acquired hemophilia7,c

Reimbursement

• The ICD-9-CM code for acquired hemophilia is 286.529

• The ICD-10-CM code for acquired hemophilia is D68.31110

• The appropriate code must be included on all claim forms for patients with acquired hemophilia treated with NovoSeven® RT

Individual results may vary.

95%effective

First-line treatment

80%effective

Salvage therapy