REBINYN ®
Coagulation Factor IX ( Recombinant ), GlycoPEGylated
Rx Only
BRIEF SUMMARY : Please consult package insert for full prescribing information
INDICATIONS AND USAGE : REBINYN ® , Coagulation Factor IX ( Recombinant ), GlycoPEGylated , is a recombinant DNA-derived coagulation Factor IX concentrate indicated for use in adults and children with hemophilia B for : On-demand treatment and control of bleeding episodes ; Perioperative management of bleeding . Limitations of Use : REBINYN ® is not indicated for routine prophylaxis in the treatment of patients with hemophilia B . REBINYN ® is not indicated for immune tolerance induction in patients with hemophilia B .
CONTRAINDICATIONS : REBINYN ® is contraindicated in patients who have known hypersensitivity to REBINYN ® or its components ( including hamster proteins )
WARNINGS AND PRECAUTIONS : Hypersensitivity Reactions : Allergic-type hypersensitivity reactions , including anaphylaxis , are possible with REBINYN ® . The product may contain traces of hamster proteins which in some patients may cause allergic reactions . Early signs of allergic reactions , which can progress to anaphylaxis , may include angioedema , chest tightness , difficulty breathing , wheezing , urticaria , and itching . Observe patients for signs and symptoms of acute hypersensitivity reactions , particularly during the early phases of exposure to the product . Discontinue use of REBINYN ® if allergic- or anaphylactic- type reactions occur , and initiate appropriate treatment . Inhibitors : The formation of inhibitors ( neutralizing antibodies ) to Factor IX may occur during Factor replacement therapy in the treatment of hemophilia B . Monitor all patients using clinical observations and laboratory tests for the development of inhibitors . An association between the development of Factor IX inhibitors and allergic reactions has been reported . Evaluate patients experiencing allergic reactions for the presence of an inhibitor . Patients with Factor IX inhibitors may be at an increased risk of severe allergic reactions with subsequent exposure to Factor IX . Thrombotic Events : The use of Factor IX-containing products has been associated with thrombotic complications . Due to the potential risk of thrombotic complications , monitor patients for early signs of thrombotic and consumptive coagulopathy when administering this product to patients with liver disease , post-operatively , to newborn infants , or to patients at risk of thrombosis or disseminated intravascular coagulation ( DIC ). In each of these situations , the benefit of treatment with REBINYN ® should be weighed against the risk of these complications . Nephrotic Syndrome : Nephrotic syndrome has been reported following immune tolerance induction therapy with Factor IX products in hemophilia B patients with Factor IX inhibitors , often with a history of allergic reactions to Factor IX . The safety and efficacy of using REBINYN ® for immune tolerance induction have not been established . Monitoring Laboratory Tests : If monitoring of Factor IX activity is performed , use a chromogenic assay or selected one-stage clotting assay validated for use with REBINYN ® . The one-stage clotting assay results can be significantly affected by the type of activated partial thromboplastin time ( aPTT ) reagent used , which can result in over- or under-estimation of Factor IX activity . Avoid the use of silicabased reagents , as some may overestimate the activity of REBINYN ® . If a validated one-stage clotting or chromogenic assay is not available locally , then use of a reference laboratory is recommended . If bleeding is not controlled with the recommended dose of REBINYN ® , or if the expected Factor IX activity levels in plasma are not attained , then perform a Bethesda assay to determine if Factor IX inhibitors are present .
ADVERSE REACTIONS : Common adverse reactions ( incidence ≥ 1 %) reported in clinical trials for REBINYN ® were itching and injection site reactions . 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 program , 115 previously treated male patients received at least one dose of REBINYN ® . A previously treated patient was defined as a subject with a history of at least 150 exposure days to other Factor IX products ( adolescent / adult subjects ) or 50 exposure days to other Factor IX products ( pediatric subjects ), and no history of inhibitors . There were a total of 8801 exposure days , equivalent to 170 patient-years . A total of 40 patients ( 35 %) were treated for more than 2 years . Adverse reactions are shown in Table 3 .
Table 3 : Summary of Adverse Reactions in Previously Treated Patients System Organ Class Adverse Reaction Number of subjects (%) General disorders and
Injection site reactions 4 ( 4 ) administration site conditions Immune system disorders Hypersensitivity 1 ( 1 ) Skin and subcutaneous tissue
Itching 3 ( 3 ) disorders
Immunogenicity : Subjects were monitored for inhibitory antibodies to factor IX prior to dosing , on a monthly basis for the first three months , every two months up to one year , every three months for an additional year , and then every 6 months until end of trial . No inhibitors were reported in the clinical trials in previously treated patients . In an ongoing trial in previously untreated patients , anaphylaxis has occurred with development of a factor IX inhibitor following treatment with REBINYN ® . Inhibitor development and anaphylactic reactions are more likely to occur during the early phases of factor IX replacement therapy . 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 . Neurologic Considerations : Animals administered repeat doses of REBINYN ® showed accumulation of PEG in the choroid plexus . The potential clinical implications of these animal findings are unknown . The physician should consider whether the patient may be vulnerable , such as infants and children who have developing brains and patients who are cognitively impaired . Physician ’ s discretion is advised with regard to neurocognitive assessments , taking into consideration factors such as duration of use , cumulative dose , age of the patient and related comorbidities that are likely to increase the risks to patients . Adverse neurologic reactions should be reported .
USE IN SPECIFIC POPULATIONS : Pregnancy : Risk Summary : There are no data with REBINYN ® use in pregnant women to determine whether there is a drug-associated risk . Animal reproduction studies have not been conducted with REBINYN ® . It is unknown whether REBINYN ® can cause fetal harm when administered to a pregnant woman or can affect fertility . REBINYN ® should be given to a pregnant woman only if clearly needed . 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 . Lactation : Risk Summary : There is no information regarding the presence of REBINYN ® 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 REBINYN ® and any potential adverse effects on the breastfed infant from REBINYN ® or from the underlying maternal condition . Pediatric Use : Safety and efficacy of REBINYN ® were evaluated in 43 previously treated pediatric patients . Twelve of these subjects ( 28 %) were 1 to 6 years of age ; 13 subjects ( 30 %) were 7 to 12 years of age ; and 18 subjects ( 42 %) were 13 to 17 years of age . Pharmacokinetic parameters were evaluated for 28 of these subjects who were treated with REBINYN ® 40 IU / kg . No difference in the safety profile of REBINYN ® was observed between previously treated pediatric subjects and adult subjects . Body weight-adjusted clearance was higher for pediatric subjects than for adult subjects . Fixed doses were studied in the clinical trials and no dose adjustment was required for pediatric subjects . Twenty-eight of the fortythree previously treated pediatric subjects ( 1 to 17 years old ) were treated with REBINYN ® for 137 bleeding episodes . Results are provided in Table 4 .
Table 4 : Efficacy in treatment of bleeding episodes in pediatric subjects by age
≤ 6 years 7-12 years 13-17 years New bleeding episodes n = 11 n = 31 n = 95 * Efficacy assessment ** Excellent or good 10 ( 91 %) 29 ( 94 %) 91 ( 97 %) Moderate or poor 1 ( 9 %) 2 ( 6 %) 3 ( 3 %)
Number of injections to treat a bleeding episode
1 injection 9 ( 82 %) 27 ( 87 %) 78 ( 82 %) 2 injections 1 ( 9 %) 4 ( 13 %) 12 ( 13 %) > 2 injections 1 ( 9 %) – 5 ( 5 %)
* Efficacy assessment was missing for one bleeding episode . ** Efficacy assessment [ Response ] was assessed according to a four-point scale using : Excellent : Abrupt pain relief and / or clear improvement in objective signs of bleeding within 8 hours after a single injection ; Good : Noticeable pain relief and / or improvement in signs of bleeding within 8 hours after a single injection ; Moderate : Probable or slight beneficial effect within the first 8 hours after the first injection but requiring more than one injection within 8 hours ; Poor : No improvement , or worsening of symptoms within 8 hours after the second of two injections .
Animals administered repeat doses of REBINYN ® showed accumulation of PEG in the choroid plexus . The potential clinical implications of these animal findings are unknown . No adverse neurologic effects of PEG have been reported in infants , children , and adolescents exposed to REBINYN ® during clinical trials . The potential consequences of long term exposure have not been fully evaluated . Geriatric Use : Clinical studies of REBINYN ® did not include sufficient numbers of subjects age 65 and over to determine whether or not they respond differently than younger subjects . Animals administered repeat doses of REBINYN ® showed accumulation of PEG in the choroid plexus . The potential clinical implications of these animal findings are unknown . No adverse neurologic effects of PEG have been reported in adults exposed to REBINYN ® during clinical trials , however use in older adults with baseline cognitive dysfunction has not been fully evaluated .
More detailed information is available upon request . Version : 1 REBINYN ® and MixPro ® are trademarks of Novo Nordisk A / S .
For Patent Information , refer to : http :// novonordisk-us . com / patients / products / product-patents . html
For information contact : Novo Nordisk Inc ., 800 Scudders Mill Road , Plainsboro , NJ 08536 , USA 1-844-REB-INYN
Manufactured by : Novo Nordisk A / S , Novo Allé , DK-2880 Bagsværd , Denmark
© 2017 Novo Nordisk USA17BIO02000 7 / 2017