Desmopressin (DDAVP) versus Novo-7

I keep on hearing a lot about Novo-7 and how it works with bleeding problems, but some doctors would like to use Desmopressin (DDAVP) instead of Novo-7. I was wondering why.

There can be a number of reasons. In some instances it is because of the lack of familiaraity with Novo VII. Just recently I had spoken with two Internal med doctors who did not know what Novo VII was. In my limited experience I have found that Desmopressin cannot compete with the immediate clotting abilities of Novo VII. The half life of Novo VII is quite short but it serves its purpose creating a plug that Desmopressin cannot do. Some doctors like to use what they are familiar with. (may be other reasons) Also Novo VII does not affect the kidney.

One reason why many prefer to use Desmopressin is that it's very much cheaper than NovoSeven. The bottom line is always the one with the dollar sign. Many opt for the cheaper --though less effective -- modality.

NovoSeven® RT

Rapid, effective, safe treatment for:

Congenital hemophilia with inhibitors Acquired hemophilia Congenital Factor VII deficiency Bleeding during and after surgery in the above conditions

NovoSeven® RT is bioequivalent to NovoSeven®—the same rapid efficacy, the same safety, now with added convenience.

Resolving Bleedso NovoSeven® RT effectively resolves 91% of joint bleeds and 86% of muscle bleeds in as

few as 5 hours.61

Learn More Simplified Dose Calculation

o New vial sizes make dose calculations simpler. Low-volume infusion means 2- to 5-minute administration.Learn More

Added Convenienceo With room temperature stability and needle-free reconstitution*, NovoSeven® RT is

easier to use.Learn More

NovoSeven® RT is approved for:

The treatment of bleeding episodes in hemophilia A or B patients with inhibitors to Factor VIII or Factor IX and in patients with acquired hemophilia

Prevention of bleeding in surgical interventions or invasive procedures in hemophilia A or B patients with inhibitors to Factor VIII or Factor IX and in patients with acquired hemophilia

Treatment of bleeding episodes in patients with congenital FVII deficiency Prevention of bleeding in surgical interventions or invasive procedures in patients with

congenital FVII deficiency

* With infusion kit.

PROMOTION

NovoSeven® RT

A new Room Temperature Formulation that's Ready to Travel

NovoSeven® RT is as effective and safe as NovoSeven®, but now your treatment can be stored at Room Temperature.

NovoSeven® RT acts fast to stop bleeds.

Stops most bleeds in 5 hours Works at the site of the injury Only minutes to reconstitute Short infusion time

SpeedNovoSeven ® RT Reconstitution Video Watch how the room-temperature stable forumlation is reconstituted.

Early treatment of a bleed is important. The faster a treatment can be administered and help to form stable clots, the better it is at stopping bleeds.

Works at the site of injury

NovoSeven® RT works at the spot where your injury or bleed takes place. So in addition to working quickly, NovoSeven® RT carries a much lower risk of a blood vessel's being blocked anywhere else in your body (thrombosis).

Stops bleeds quickly

The sooner a bleed can be stopped, the better. In people with inhibitors, NovoSeven® RT stops most bleeds in an average of 5 hours.

Fast to prepare

Compared with other bypassing agents, NovoSeven® RT is faster to prepare and faster to administer. Because NovoSeven® RT dissolves rapidly, it takes only minutes to reconstitute.

Fast to infuse

With NovoSeven® RT, the amount of factor needed to infuse is very small. This small infusion amount means a shorter time to infuse.

NovoSeven® RT has many safety advantages

Recombinant technology No risk of increased titers* Low rate of side effects Needle-free reconstitution

* In hemophilia A and B.

SafetyTreating bleeds safely is important. NovoSeven® RT is a recombinant product, unlike any other bypassing agent.

Safety Advantages in How NovoSeven® RT Is Made

NovoSeven® RT is a recombinant product, which means that it is made without any human blood or plasma. You can feel safe knowing that NovoSeven® RT can effectively stop bleeds. Learn more about recombinant and viral safety.

Safety Advantages in How NovoSeven® RT Works

With NovoSeven® RT, you can feel safe because of the low level of side effects. Plus, you won't have to worry about raising your titer*. And you can have peace of mind knowing that NovoSeven® RT works only at the site of injury, clotting blood only where it should. Learn more about the reasons NovoSeven ® RT is well tolerated by most patients.

Simplicity

Treatment has been improved withNovoSeven® RT

Room-temperature storage Simplified dose calculation Short infusion time Ready to Travel case

SimplicityEase of use helps make treatment fast. And for stopping bleeds, speed is important.

Use

Easy Reconstitution

With the NovoSeven® RT infusion kit, you have what you need to get your dose ready quickly and safely. Reconstitution takes only a few minutes.

Fast Infusion

Infusing NovoSeven® RT takes only 2-5 minutes.

Small Infusion Amount

With NovoSeven® RT the amount of factor needed to infuse is very small. Infusion volume is 40% less than original NovoSeven® and 94% less compared with aPCC.

Storage

Room Temperature Storage

NovoSeven® RT can be stored at room temperature (36° to 77° F) for up to 2 years. Please be sure not to use NovoSeven® RT after the expiration date.

Ready to Travel Case

A portable, reusable travel case makes storing supplies easy, at home or away.

About NovoSeven® RTNovoSeven® RT is the only recombinant Factor VIIa available. It provides rapid, effective, and safe treatment for:

Congenital hemophilia A or B with inhibitors Acquired hemophilia Congenital Factor VII deficiency Bleeding during and after surgery in the above conditions

NovoSeven® (Coagulation Factor VIIa [Recombinant]) is now NovoSeven® RT

Provides rapid efficacy61 o Resolves most joint bleeds in as few as 5 hourso 91% effective at resolving joint bleeds

Provides same safety profile o Low risk of thrombosis85

o Only recombinant bypassing agent Allows for faster initiation and administration of treatment85

o Room temperature formulation—can be stored outside of the refrigeratoro 40% less infusion volume85,79

How NovoSeven® RT Works

NovoSeven® RT targets the site of injury by binding to activated platelets and tissue factor.

NovoSeven® RT enters the bloodstream and targets the site of injury. It can support thrombin generation for FVIII or FIX deficiency64

NovoSeven® RT binds directly to activated platelets, activating Factor X to produce Factor Xa85,64

Factor Xa leads to the conversion of prothrombin to thrombin85

The burst of thrombin may cause the formation of fibrin, which is the foundation of a stable clot85

NovoSeven® RT resolves the bleed by allowing the formation of a stable hemostatic plug85

History of NovoSeven® RT1985NovoSeven project at Novo Nordisk

1988First patient with an inhibitor was successfully treated with rFVIIa

1988Compassionate Use Program began

1989Clinical Development Program—Phase I/IIDose-escalation studies evaluating efficacy, safety, and PK in bleeding and nonbleeding patients with and without inhibitors. Additional randomized, double-blind study and home treatment study

1996EU approval

1999US approval (hemophilia A or B with inhibitors)

2005US approval (surgery in people with hemophilia A or B with inhibitors and bleeding episodes/surgery in congenital Factor VII deficiency)

2006Dedication of Novo Nordisk Research USThe first research center in the US dedicated to investigating therapies to prevent or stop critical bleeding

2006US approval (bleeding episodes/surgery in people with acquired hemophilia)

History of NovoSeven® RT2008NovoSeven® RT introduced

In the 1980s, a team of Novo Nordisk scientists led by Dr. Ulla Hedner developed a genetically engineered form of Factor VII protein, recombinant Factor VIIa (rFVIIa). This particular protein was created to treat hemophilia patients who had developed inhibitors that prevented traditional treatments with FVIII and FIX from working. When NovoSeven® was launched in Europe in 1996, it signified a major advancement in the treatment of this small group of hemophilia patients for whom there were limited options. NovoSeven® was approved for use in the US in 1999.

Indications

NovoSeven® RT is approved for use in:

Patients with hemophilia A or B with inhibitors to Factor VIII or Factor IX

Treatment of bleeding episodes Prevention of bleeding in surgical interventions or invasive procedures

Patients with congenital Factor VII deficiency

Treatment of bleeding episodes Prevention of bleeding in surgical interventions or invasive procedures

Patients with acquired hemophilia

Treatment of bleeding episodes Prevention of bleeding in surgical interventions or invasive procedures

Surgery in patients with:

Hemophilia A or B with inhibitors to Factor VIII or Factor IX Congenital Factor VII deficiency Acquired hemophilia

Efficacy

NovoSeven® RT Provides Rapid Efficacy

For Hemophilia A or B with Inhibitors

Recombinant Factor VIIa resolves the majority of joint bleeds in as few as 5 hours.61*

Recombinant Factor VIIa resolves joint bleeds quickly

Median time to resolve joint bleed61

Recombinant Factor VIIa resolves bleeds effectively

Effectively resolves joint bleeds61

Effectively resolves muscle bleeds61

Adapted from Lusher et al.61

Data from a randomized, double-blind, parallel-group, multicenter study of patients with hemophilia A or B with and without an inhibitor. Patients were given recombinant Factor VIIa at

dosing intervals of 2 to 3 hours. Percentages reflect the number of patients reporting excellent, effective or partially effective results. Response was rated as “excellent” if patient demonstrated definitive relief of pain/tenderness and/or if there was a measurable decrease in the size of the bleed (or arrest of bleeding) in 8 hours or less. An “effective” response was measured by any of these 3 events occurring from 8 to 14 hours; a “partially effective” response ether occurred after 14 hours or indicated detectable relief of pain/tenderness or decrease in bleeding.61

*Median of 2.0 infusions to resolve a joint bleed; infusions given at intervals of 2.5 hours.

For Surgery in Hemophilia A or B with Inhibitors

Recombinant Factor VIIa is 96% effective at controlling bleeding during surgery.68

Recombinant Factor VIIa is effective in both major and minor surgery.68

Efficacy for 5 days after surgeryc

Adapted from Shapiro et al.68

Data from a prospective, randomized, double-blind trial of 2 doses (35mcg/kg or 90 mcg/kg) of recombinant Factor VIIa in patients with hemophilia A or B with inhibitors (N=24) undergoing

minor or major surgery. Efficacy defined as follows: intraoperative bleeding: as expected or less than expected; 0-48 hours after wound closure: bleeding stopped or reduced; days 3-5: adequate control of bleeding.

c Charts show data for recommended dose in the Prescribing Information for NovoSeven® RT (90 mcg/kg). See Dosing for more detailed dosing information.

For Congenital Factor VII Deficiency

Recombinant Factor VIIa is 93% effective in stopping nonsurgical and surgical bleeds in people with congenital Factor VII deficiency.85

Efficacy in people with congenital Factor VII deficiency

In nonsurgical bleeding episodes:

Efficacy appeared to be independent of the location of bleeding60

Recombinant Factor VIIa proved effective across a range of serious bleeds60

For Surgery in FVII Deficiency

Treatment with rFVIIa was rated as effective in 37 of 43 (86%) of non-surgical bleeding episodes and in all surgical procedures for which data were collected (25/26, 96%).60

For Acquired Hemophilia

NovoSeven® RT is effective for acquired hemophilia

Efficacy with Recombinant Factor VIIa treatment90

Adapted from Sumner et al.90

Data were extracted from a review of experiences with recombinant Factor VIIa for the treatment of acquired hemophilia from the recombinant Factor VIIa compassionate use programs, the HTRS registry, and independent published reports. Efficacy was defined by the mean time to treatment from bleeding onset to first recombinant Factor VIIa dose as determined in non-surgical bleeding episodes and is shown in the chart above for “effective” and “partially effective” treatment outcomes. “Ineffective” treatment was determined by inability to stop the bleeding episode or by the physician describing treatment as not effective.50 

Safety

The Safety of NovoSeven® RT is Proven

Only recombinant bypassing agentFree of human serum and free of human proteins, so there is no risk of human viral transmission.

No potential for anamnestic reaction in patients with hemophilia A or B with inhibitorsTreatment with recombinant Factor VIIa does not increase inhibitor titers.73

Targets the site of injuryNovoSeven® RT binds directly to activated platelets.64,65

Low risk of thrombotic events85

Recombinant Factor VIIa has a low incidence of adverse events.

No reported drug interactionsThere have been no reported drug interactions with nonhemostatic agents, including analgesics, antibiotics, and sedatives.66

Needle-free reconstitution*Needle-less vial adapters protect patients from needle-stick accidents during reconstitution.

* With infusion kit.

Convenience

Convenience Features of NovoSeven® RT

NovoSeven® RT and NovoSeven® are bioequivalent. NovoSeven® RT has these added convenience features.

Room–Temperature Stable FormulationNovoSeven® RT can be safely kept at room temperature or refrigerated (36ºF–77ºF, 2ºC–25ºC).

Rapid Reconstitution NovoSeven® RT dissolves rapidly and takes only minutes to prepare.

Fast Infusion TimeInfusing NovoSeven® RT takes only 2 to 5 minutes.

Administration time (minutes)

NovoSeven® RT2-5

aPCC86,*

42

*aPCC= activated prothrombin complex concentrate

Low-Volume InfusionNovoSeven® RT has 40% less infusion volume compared to NovoSeven®.

o 94% less infusion volume compared to aPCC

Low-volume infusion with NovoSeven® RT79,85,86

NovoSeven® RT85

7.2 ccNovoSeven®79

12 cc aPCC86

120 cc

Simplified Dose Calculation

NovoSeven® RT now is in 1.0 mg, 2.0 mg, and 5.0 mg vial sizes. Color-coded vials match corresponding diluent vials for simplified reconstitution.

Dosing & Administration

Dosing Guidelines

NovoSeven® RT should be given as early as possible after the start of a bleeding episode. Be sure to follow recommended dosing to ensure optimal efficacy.

Treatment of Bleeding Episodes—Recommended dosing of NovoSeven® RTHemophilia A or B with inhibitors90 mcg/kg every 2 hours until bleeding resolves

Congenital Factor VII deficiency 15 to 30 mcg/kg every 4 to 6 hours until bleeding resolves

Acquired Hemophilia 70 to 90 mcg/kg every 2 to 3 hours until bleeding resolves

Surgery—Recommended dosing of NovoSeven® RTHemophilia A or B with inhibitors

Preoperative and intraoperative90 mcg/kg immediately prior to surgery. Repeat 90 mcg/kg dose every 2 hours during surgery

Hemophilia A or B with inhibitors

Postoperative—Major Surgery90 mcg/kg every 2 hours for 5 days. After 5 days, 90 mcg/kg every 4 hours until healing has occurred.

Hemophilia A or B with inhibitors

Postoperative—Minor Surgery90 mcg/kg every 2 hours for the first 48 hours. After 48 hours, 90 mcg/kg every 2 to 6 hours until healing has occurred.

Congenital Factor VII deficiency

Intraoperative and postoperative dosage—Major and minor surgery

15 to 30 mcg/kg every 4 to 6 hours until bleeding resolves

NovoSeven® RT Dosing Calculator

Select an Indication

Hemophilia A or Bwith inhibitors

Congenital FVIIdeficiency

Acquiredhemophilia

Administration

NovoSeven® RT is intended for intravenous bolus administration only.

ReconstitutionNovoSeven® RT is reconstituted with the included diluent (a solution containing a histidine buffer). NovoSeven® RT dissolves rapidly and can be used up to 3 hours after reconstitution.

InfusionNovoSeven® RT is administered as a slow bolus injection over 2 to 5 minutes, depending on the dose administered.

Transition to NovoSeven® RT

Facts on NovoSeven® RT Formulation

NovoSeven® RT and NovoSeven® (Coagulation Factor VIIa [Recombinant]) are bioequivalent—the same rapid and safe bleed resolution, now with added convenience.

Features of NovoSeven® RT:

NovoSeven® RT is room temperature stable (36ºF-77ºF) Shelf life is up to 2 years An increase in factor concentration means infusion volumes are lower Vial sizes are now 1.0 mg, 2.0 mg, and 5.0 mg Vials are color-coded to match vials of diluent Diluent consists of sterile water with 10 mmol of histidine (buffer) and is prepackaged with

NovoSeven® RT Needle-free* vial adapter helps prevent needle-stick injuries

Product comparison:NovoSeven® and NovoSeven® RT 85,79

Storage

Room-temperature stable formulation 36ºF-77ºFMethionine (antioxidant), sucrose (stabilizer) added

Travel case Holds up to 5 sets of vials and 1 infusion kit

Shelf life 3 years 2 years

Dosing and Administration

Low-volume infusion40% less infusion volume1 mg = 1 mL reconstituted product

Simplified dosing 1.0 mg, 2.0 mg, 5.0 mgvial sizes

Color-coded vial sizes

Needle-free* reconstitution

Product comparison:NovoSeven® and NovoSeven® RT 85,79

Diluent Sterile water Sterile water with 10mmol of histidine (buffer)

Efficacy61

Resolves joint bleeds quickly

Resolves joint and muscle bleeds effectively

Safety

Low risk of thrombosis

Only recombinant bypassing agent

* With infusion kit.

Access to NovoSeven® RT Order by Phone

Call 1-877-NOVO-777, Select Option 2 For product orders, operators are available 24 hours a day, 7 days a week. Call 1-877-NOVO-777 and select option 2.

Contact a Distributor

To make stocking NovoSeven® RT easier, the following is a list of vendors who distribute NovoSeven® RT. Simply contact the vendor directly to place your order.

ACCREDO HEALTH GROUP, INC.*Contact: Rodger Bryant or Rex Sullivan 201 Great Circle Road Nashville, TN 37228 1-866-721-6118 hemophiliahealth.comHHSCommercialAccounts@hemophiliahealth.com

ASD Healthcare*4006 Beltline Road, Suite 200Addison, TX 75001asdhealthcare.comCustomer Service:1-800-746-6273 (PHON-ASD)

Cubixx—ASD’s RFID Dispensing Cabinet*1-877-428-24991-877-4CUBIXXconsignment@asdhealthcare.com

BioCARE/UBS*Contact: Sid Lewis 4405 E Cotton Center Blvd Suite 100 Phoenix, AZ 85040 1-800-304-3064 (phone) 1-602-850-6203 (fax) biocare-us.org

Blood Diagnostics Inc.*Contact: Jennifer Jacobson 110 Centrum Drive Irmo, SC 29063 1-800-948-9834 ivig.comjjacobson@ivig.com

Cardinal Health 108, Inc-SPD*Contact: Dominic Crocco305 Tech Park Drive, Suite 113LaVergne, TN 370861-888-413-4040 or 1-615-287-5341cardinal.comDominic.Crocco@Cardinal.Com

Caremark*Contact: Debby Lynn1127 Bryn Mawr AveRedlands, CA 92374-4558 1-909-799-4187caremark.comDebby.Lynn@caremark.com

FFF EnterprisesContact: Chris Ground Sr. Vice President National Accounts41093 Country Center DriveTemecula, California 925911-951-296-2500 x1139 (phone)fffenterprises.com

National Hospital Specialties*Contact: Elana Ducran 65 Commerce Way Hackensack, NJ 07601 1-800-344-6087 (phone) 1-201-488-1174 (fax) nhsusa.com info@nhsusa.com

Novis Pharmaceuticals, LLC.*Contact: Scott Wise 5000 SW 75th Ave #121 Miami, FL 33156 1-786-437-0700 (phone)

1-786-437-0686 (fax) novispharma.com Scott@novispharma.com

PHS Corporation*Contact: Bryan Sanders 9417 Brodie Lane Austin, TX 78748 1-877-693-4376 (phone) 1-512-693-4067 (fax) phscorporation.com

* Vendor offers consignment programs

Calculate How Much NovoSeven® RT to Order

NovoSeven® RT should be given as early as possible after the start of a bleeding episode.

The recommended initial dose for patients with hemophilia A or B with inhibitors, administered by intravenous bolus injection, is 90 mcg/kg body weight.

The recommended dose range in congenitally FVII-deficient patients is 15-30 mcg/kg body weight.

Recommended dosing for acquired hemophilia is 70-90 mcg/kg every 2-3 hours until hemostasis is achieved.

Following the initial dose of NovoSeven® RT, further injections may be repeated. The duration of treatment and the interval between injections will vary with the severity of the bleed.