Novoeight ®
Antihemophilic Factor ( Recombinant )
Rx Only
BRIEF SUMMARY : Please consult package insert for full prescribing information
INDICATIONS AND USAGE : Novoeight ® , Antihemophilic Factor ( Recombinant ), is indicated for use in adults and children with hemophilia A ( congenital factor VIII deficiency or classic hemophilia ) for : Control and prevention of bleeding episodes ; Perioperative management ; Routine prophylaxis to prevent or reduce the frequency of bleeding episodes . Novoeight ® is not indicated for the treatment of von Willebrand disease .
CONTRAINDICATIONS : Novoeight ® is contraindicated in patients who have had life-threatening hypersensitivity reactions , including anaphylaxis , to Novoeight ® or its components ( including traces of hamster proteins ).
WARNINGS AND PRECAUTIONS : Hypersensitivity Reactions : Hypersensitivity reactions , including anaphylaxis , are possible with Novoeight ® . Novoeight ® contains trace amounts of hamster proteins . Patients treated with this product may develop hypersensitivity to these non-human mammalian proteins . Early signs of hypersensitivity reactions that can progress to anaphylaxis include angioedema , chest tightness , dyspnea , wheezing , urticaria , and pruritus . Immediately discontinue administration and initiate appropriate treatment if allergicor anaphylactic-type reactions occur . Neutralizing Antibodies : Formation of neutralizing antibodies ( inhibitors ) to factor VIII can occur following administration of Novoeight ® . Monitor all patients for the development of inhibitors by appropriate clinical observation and laboratory testing . If the expected plasma levels of factor VIII activity are not attained , or if bleeding is not controlled with an appropriate dose , perform testing for factor VIII inhibitors . Monitoring Laboratory Tests : Monitor plasma factor VIII activity levels by the one-stage clotting assay or the chromogenic substrate assay to confirm that adequate factor VIII levels have been achieved and maintained , when clinically indicated . Perform assay to determine if factor VIII inhibitor is present if expected plasma factor VIII activity levels are not attained , or if bleeding is not controlled with the expected dose of Novoeight ® . Determine inhibitor levels in Bethesda Units .
ADVERSE REACTIONS : The most frequently reported adverse reactions ( ≥ 0.5 %) were injection site reactions , increased hepatic enzymes , and pyrexia . 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 clinical trials of another drug and may not reflect the rates observed in clinical practice . During the clinical development of Novoeight ® , 214 male previously treated patients ( PTPs ; exposed to a factor VIII-containing product for ≥150 days ) with severe hemophilia A ( factor VIII level ≤1 %) received at least one dose of Novoeight ® as part of either routine prophylaxis , on-demand treatment of bleeding episodes , perioperative management of major and minor surgical , dental , or other invasive procedures , or pharmacokinetic evaluation of Novoeight ® . Thirty-one subjects ( 14 %) were < 6 years of age , 32 ( 15 %) were 6 to < 12 years of age , 16 ( 7 %) were adolescents ( 12 to < 16 years of age ), and 135 ( 63 %) were adults ( 16 years of age and older ). The subjects received a total of 33,272 injections with a median of 127 injections of Novoeight ® ( range 1-442 ) per subject , and had a total of 32,929 exposure days during prevention and treatment of bleeds . The most frequently reported adverse reactions in previously treated patients was injection site reactions ( 2.3 %), increased hepatic enzymes ( 1.4 %), and pyrexia ( 0.9 %). Immunogenicity : Subjects were monitored for neutralizing antibodies to factor VIII and binding antibodies to CHO and murine protein . No subjects developed confirmed neutralizing antibodies to factor VIII . One twenty-two month old child had a positive neutralizing antibody to factor VIII of 1.3 [ BU ] in the Bethesda assay after 15 exposure days that was not confirmed when checked after 20 exposure days . In vivo recovery was normal for this child and no clinical adverse findings were observed . No patients developed de novo anti-murine antibodies . Nineteen subjects were positive for anti-Chinese hamster ovary ( CHO ) cell protein antibodies . Two of these subjects changed from anti-CHO negative to anti-CHO positive and 6 subjects changed from anti-CHO positive to anti-CHO negative . The remaining 11 subjects were either positive throughout the trials ( n = 6 ), negative at baseline and end-of trial but with transient positive samples ( n = 2 ), or positive at baseline and end-of trial but with negative samples in between ( n = 3 ). No clinical adverse findings were observed in any of these subjects . The 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 .
USE IN SPECIFIC POPULATIONS : Pregnancy : Risk Summary : As hemophilia mainly affects males , there are no adequate and wellcontrolled studies using Novoeight ® in pregnant women to determine whether there is a drug-associated risk . Animal reproduction studies have not been conducted with Novoeight ® . In the U . S . general population , the estimated background risk of major birth defect and miscarriage in clinically recognized pregnancies is 2-4 % and 15-20 %, respectively . There is no reliable data on the incidences specific to the hemophilia A population . Lactation : Risk Summary : There is no information regarding the presence of Novoeight ® in human milk , the effect on the breastfed infant , and the effects on milk production . The developmental and health benefits of breastfeeding should be considered along with the mother ’ s clinical need for Novoeight ® and any potential adverse effects on the breastfed infant from Novoeight ® or from the underlying maternal condition . Pediatric Use : Children have shorter half-life and lower recovery of factor VIII than adults . Because clearance ( based on per kg body weight ) has been demonstrated to be higher in the pediatric population , higher or more frequent dosing based on body weight may be needed . Safety and efficacy studies have been performed in 79 previously treated pediatric patients < 16 years of age . Thirty-one of these subjects ( 39 %) were < 6 years of age , 32 ( 41 %) were 6 to < 12 years of age , and 16 ( 20 %) were adolescents ( 12 to < 16 years of age ). All subjects received preventive treatment every other day or three times weekly . A total of 244 bleeds in 54 subjects were treated with Novoeight ® . The majority of the bleeds ( 91 %) were of mild / moderate severity , 41 % of the bleeds were spontaneous and 58 % of the bleeds were localized in joints . Of these 244 bleeds , 210 ( 86 %) were rated excellent or good in their response to treatment with Novoeight ® and 3 ( 1.2 %) were rated as having no response . A total of 222 ( 91 %) of the bleeds were resolved with one or two injections of Novoeight ® . Routine prophylactic treatment has been shown to reduce joint bleeding . Geriatric Use : Clinical studies of Novoeight ® did not include sufficient numbers of patients aged 65 and over to determine whether they respond differently from younger patients .
More detailed information is available upon request .
Version : 5
For information contact : Novo Nordisk Inc . 800 Scudders Mill Road Plainsboro , NJ 08536 , USA 1-844-30-EIGHT
Manufactured by : Novo Nordisk A / S Novo Allé , DK-2880 Bagsvaerd
Novoeight ® is a registered trademark of Novo Nordisk Health Care AG .
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© 2016 Novo Nordisk USA16HDM05035 12 / 2016