Rx Product News: Profile: A Closer Look at New FDA Actions: NovoSeven RT

Mr. Eckel is professor and director ofthe Office of Practice Developmentand Education at the School ofPharmacy, University of North Carolinaat Chapel Hill.

Novo Nordisk's NovoSeven RT

The FDA has approved Novo Nordisk'sNovoSeven RT (Coagulation FactorVIIa [Recombinant] Room TemperatureStable). NovoSeven RT is approved forthe treatment of bleeding episodes andthe prevention of bleeding during surgeryor invasive procedures in patientswith hemophilia A or B with inhibitorsto factor VIII or factor IX and in patientswith acquired hemophilia or congenitalfactor VII deficiency.¹

Hemophilia can be categorized into2 classes: patients with hemophilia A(classic hemophilia) who lack factor VIII;patients with hemophilia B (Christmasdisease) who lack factor IX. Severecases may result in spontaneous internalbleeding or bleeding after an injuryor surgery, often requiring managementby replacing the missing factor via anintravenous (IV) infusion. In some cases,patients receiving IV factor preparationsmay develop inhibitors, which are antibodiesthat form in response to thesupplemental factor products and neutralizeclotting factors, thus resulting incontinued bleeding. Cases of strong orhigh-responding inhibitors may requirebypassing agents, such as recombinantfactor VIIa or activated prothrombincomplex concentrates.²

NovoSeven RT is a new formulation ofNovo Nordisk's NovoSeven (CoagulationFactor VIIa [Recombinant]) and no longerrequires refrigeration during storage.Unopened vials of NovoSeven RT canbe stored for up to 2 years, or untilthe manufacturer's expiration date, ata temperature between 36?F and 77?F(2?C-25?C).^2,3 The original formulation ofNovoSeven required storage between36?F and 46?F (2?C-8?C).^3,4

Mechanism of Action

NovoSeven RT complexes with tissuefactor to activate coagulation factor X tofactor Xa and factor IX to factor IXa. Afteractivation, factor Xa complexes withother factors to convert prothrombin tothrombin, which then prompts fibrinogento convert to fibrin, and thus leadsto local hemostasis.¹

Dosage

For the treatment of bleeding episodesin patients with hemophilia A or Bwith inhibitors, the recommended doseof NovoSeven RT is 90 ?g/kg via IV bolusinfusion every 2 hours until either hemostasisoccurs or treatment has beendetermined as inadequate. The durationof dosing after hemostasis is achievedhas not been studied; however, treatmentof a severe bleed is recommendedto continue at 3- to 6-hour intervals afterhemostasis is established.

When used for surgical interventionsin patients with hemophilia A or B withinhibitors, the recommended initial doseof NovoSeven RT is 90 ?g/kg immediatelybefore the procedure and at 2-hourintervals throughout the surgery. Afterminor surgery, dosing should continueat 2-hour intervals for 48 hours, then at2- to 6-hour intervals until the patienthas healed. After major surgery, dosingshould continue at 2-hour intervals for5 days, then at 4-hour intervals until thepatient has healed.

For the treatment of bleeding episodesor surgical interventions in patients withcongenital factor VII deficiency, the recommendeddose of NovoSeven RT is15 to 30 ?g/kg every 4 to 6 hours untilhemostasis occurs. For the treatmentof patients with acquired hemophilia,the recommended dose is 70 to 90?g/kg every 2 to 3 hours until hemostasisoccurs.

NovoSeven RT should be administeredwithin 3 hours of reconstitution.NovoSeven RT should never be frozen ormixed with other infusion solutions.¹

Contraindications, Warnings, and Precautions

No documented contraindications totreatment exist with NovoSeven RT. Onestudy demonstrated an increased riskof arterial thromboembolic events inelderly patients; however, the indicationsfor which NovoSeven RT was usedin these cases were outside its licensedindications. NovoSeven RT should beused cautiously in patients with a knownhypersensitivity to any of its components.Patients with factor VII deficiency shouldhave their prothrombin time and factorVII coagulant activity monitored beforeand after treatment with NovoSevenRT. NovoSeven RT should not be usedconcomitantly with any other forms ofNovoSeven.

NovoSeven RT is a Pregnancy CategoryC drug. It is unknown if NovoSeven RT isexcreted into human milk; however,many drugs are excreted into breastmilk and given the potential for adverseharm in nursing infants—either nursingor the drug should be discontinued asbased on the importance of treatmentto the mother.

The most common adverse reactionsto NovoSeven RT include fever, bleeding,reactions at the injection site, arthralgia,headache, hypertension, hypotension,nausea, vomiting, pain, edema, andrash.¹

References

• NovoSevenRT [package insert]. Princeton, NJ: Novo Nordisk Inc; 2008. www.novosevenrt.com/pdfs/PI_novosevenrt.pdf. Accessed June 2008.
• FDA approves Novo Nordisk's NovoSeven RT (Coagulation Factor VIIa [Recombinant] Room Temperature Stable) for Hemophilia Patients with Inhibitors [press release]. Princeton, NJ: Novo Nordisk Inc; May 13, 2008. press.novonordisk-us.com/novopress.Actions.ShowPressReleaseAction.do?rid=422&type=pdf. Accessed June 2008.
• News Briefs. Am J Health Syst Pharm. 2008;65(12):1114.
• FDA approves new formulation of Coagulation Therapy: NovoSeven RT Can Be Stored at Room Temperature. FDA Web site. www.fda.gov/bbs/topics/NEWS/2008/NEW01833.html. Accessed June 2008.