ESPEROCT by is a Other medication manufactured, distributed, or labeled by Novo Nordisk, Vetter Pharma Fertigung GmbH & Co. KG. Drug facts, warnings, and ingredients follow.
ESPEROCT [antihemophilic factor (recombinant), glycopegylated-exei] is a coagulation Factor VIII concentrate indicated for use in adults and children with hemophilia A for:
ESPEROCT is not indicated for the treatment of von Willebrand disease. (1)
For intravenous infusion after reconstitution only
ESPEROCT is available as a lyophilized powder in single-dose vials of dosage strengths at 500, 1000, 1500, 2000 and 3000 IU per vial. (3)
Do not use in patients who have known hypersensitivity to ESPEROCT or its components, including hamster proteins. (4)
The most frequently reported adverse reactions (≥ 1%) were rash, redness, itching and injection site reactions. (6)
To report SUSPECTED ADVERSE REACTIONS, contact Novo Nordisk Inc. at 1-800-727-6500 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.
Pediatric Use: Higher clearance (based on kg body weight), a shorter half-life and lower incremental recovery are seen in children. Higher and more frequent dosing may be needed. (8.4)
See 17 for PATIENT COUNSELING INFORMATION and FDA-approved patient labeling.
Revised: 10/2019
ESPEROCT [antihemophilic factor (recombinant), glycopegylated-exei] is a recombinant DNA-derived coagulation Factor VIII concentrate indicated for use in adults and children with hemophilia A for:
Limitation of Use:
ESPEROCT is not indicated for the treatment of von Willebrand disease. (1)
For intravenous infusion after reconstitution only.
On–demand Treatment and Control of Bleeding Episodes
Table 1 can be used to guide dosing of ESPEROCT for treatment of bleeding episodes.
Type of bleeding | Adolescents/Adults
≥12 years Dose (IU/kg) | Children
<12 years Dose (IU/kg) | Additional doses |
---|---|---|---|
Minor Early hemarthrosis, mild muscle bleeding, or oral bleeding |
40 |
65 |
One dose should be sufficient |
Moderate More extensive hemarthrosis, muscle bleeding, or hematoma |
40 |
65 |
An additional dose may be administered after 24 hours |
Major Life- or limb-threatening hemorrhages, gastro- intestinal bleeding, intracranial, intra-abdominal or intrathoracic bleeding, fractures |
50 |
65 |
Additional dose(s) may be administered approximately every 24 hours |
Perioperative Management
The dose level and dosing intervals for surgery depend on the procedure and local practice. A guide for dosing with ESPEROCT during surgery (perioperative management) is provided in Table 2 below.
Type of surgery |
Adolescents/Adults ≥12 years Pre-operative Dose (IU/kg) |
Children <12 years Pre-operative Dose (IU/kg) |
Additional Doses |
Minor Including tooth extraction |
50 |
65 |
Additional dose(s) can be administered after 24 hours if necessary |
Major Intracranial, intra-abdominal, intrathoracic, or joint replacement surgery |
50 |
65 |
Additional doses can be administered approximately every 24 hours for the first week and then approximately every 48 hours until wound healing has occurred |
Routine Prophylaxis
Adults and adolescents (≥ 12 years): The recommended starting dose is 50 IU of ESPEROCT per kg body weight every 4 days. This regimen may be individually adjusted to less or more frequent dosing based on bleeding episodes.
Children (< 12 years): A dose of 65 IU of ESPEROCT per kg body weight twice weekly. This regimen may be individually adjusted to less or more frequent dosing based on bleeding episodes.
Overview of ESPEROCT Package
Reconstitution
For intravenous infusion only.
Caution: The pre-filled diluent syringe is made of glass with an internal tip diameter of 0.037 inches and is compatible with a standard Luer-lock connector.
Some needleless connectors for intravenous catheters are incompatible with the glass diluent syringes (for example, certain connectors with an internal spike, such as Clave®/MicroClave®, InVision-Plus®, InVision-Plus CS®, Invision-Plus Junior®, Bionector®), and their use can damage the connector and affect administration. To administer ESPEROCT through incompatible needleless connectors, withdraw the reconstituted product into a standard 10 mL sterile Luer-lock plastic syringe.
ESPEROCT is available as a sterile white to off-white lyophilized powder supplied in single-dose vials containing nominally 500, 1000, 1500, 2000 or 3000 IU. The actual FVIII activity is printed on each ESPEROCT vial and carton.
After reconstitution with 4 mL of saline diluent, the reconstituted solution contains approximately 125, 250, 375, 500 or 750 IU per mL of ESPEROCT, respectively.
Allergic-type hypersensitivity reactions, including anaphylaxis, are possible with ESPEROCT. The product contains traces of hamster proteins, which in some patients may cause allergic reactions [see Description (11)]. Early signs of allergic reactions, which can progress to anaphylaxis, may include angioedema, chest tightness, difficulty breathing, wheezing, rash, hives, 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 ESPEROCT if allergic- or anaphylactic-type reactions occur, and initiate appropriate treatment.
The formation of neutralizing antibodies (inhibitors) to Factor VIII has occurred following administration of ESPEROCT. Monitor patients for the development of Factor VIII inhibitors by appropriate clinical observations and laboratory tests. If expected Factor VIII activity plasma levels are not attained, or if bleeding is not controlled after ESPEROCT administration, suspect the presence of an inhibitor (neutralizing antibody) [see Warnings and Precautions (5.3)].
If monitoring of Factor VIII is performed, use a chromogenic or one-stage clotting assay appropriate for use with ESPEROCT [see Dosage and Administration (2)].
Factor VIII activity levels can be affected by the type of activated partial thromboplastin time (aPTT) reagent used in the assay. Some silica-based aPTT reagents can underestimate the activity of ESPEROCT by up to 60%; other reagents may overestimate the activity by 20%. If an appropriate one-stage clotting or chromogenic assay is not available locally, then use a reference laboratory.
If bleeding is not controlled with the recommended dose of ESPEROCT or if the expected Factor VIII activity levels in plasma are not attained, then perform a Bethesda assay to determine if Factor VIII inhibitors are present.
The most frequently reported adverse reactions (incidence ≥1%) in clinical trials were rash, redness, itching (pruritus), and injection site reactions.
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.
The safety of ESPEROCT has been evaluated in 270 subjects (202 adolescents/adults and 68 children) in five prospective, multi-center clinical studies in previously treated patients (PTPs) with severe hemophilia A (<1% endogenous Factor VIII activity) and no history of inhibitors. All subjects received at least one dose of ESPEROCT. A previously treated patient was defined as a subject with a history of at least 150 exposure days to other Factor VIII products (adolescent/adult subjects) or 50 exposure days to other Factor VIII products (pediatric subjects). Total exposure to ESPEROCT was 80,425 exposure days corresponding to 889 patient years of treatment.
During the clinical trials in PTPs, adverse reactions occurred at a rate of 0.10 events per patient year of exposure. The most frequently reported adverse reactions were rash (5.2%), injection site reaction (2.6%), redness (1.9%), and itching (pruritus) (1.5%).
Subjects were monitored for neutralizing and non-neutralizing antibodies to Factor VIII, polyethylene glycol (PEG), and CHO host cell protein. One previously treated subject developed confirmed neutralizing antibodies to Factor VIII (13.5 Bethesda Units). In addition, two subjects had transient low titer FVIII antibody (<5 Bethesda Units) test results at a single occasion. Anti-PEG antibodies of no clinical consequence were detected in 45 subjects, 32 of whom had pre-existing anti-PEG antibodies. Nine subjects developed anti-CHO host cell protein antibodies of no clinical consequence.
The detection of antibodies 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.
There are no data with ESPEROCT use in pregnant women to determine whether there is a drug-associated risk. Animal reproduction studies have not been conducted with ESPEROCT. It is unknown whether ESPEROCT can cause fetal harm when administered to a pregnant woman or can affect fertility.
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.
Risk Summary
There is no information regarding the presence of ESPEROCT 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 ESPEROCT and any potential adverse effects on the breastfed infant from ESPEROCT or from the underlying maternal condition.
Safety and efficacy were evaluated in 93 previously treated pediatric patients <18 years of age, who received at least one dose of ESPEROCT; all received routine prophylaxis [see Clinical Studies (14)]. Thirty-four (34) of these subjects (36.6%) were 1 to <6 years of age; 34 subjects (36.6%) were 6 to <12 years of age; and 25 subjects (27%) were 12 to <18 years of age. Pharmacokinetic parameters were evaluated for 27 of these subjects who were treated with ESPEROCT [see Clinical Pharmacology (12.3)].
No difference in the safety profile of ESPEROCT was observed between previously treated pediatric subjects and adult subjects. Pharmacokinetic studies in children <12 years of age demonstrated higher clearance, a shorter half-life, and lower incremental recovery of Factor VIII compared to adults, but the pharmacokinetic parameters are comparable between young children (1–<6 years) and older children (6–<12 years). Because clearance (per kg body weight) is higher in children (<12 years), a higher dose and more frequent dosing may be needed in this population [seeClinical Pharmacology (12.3)].
Clinical studies of ESPEROCT did not include sufficient numbers of subjects age 65 years and over to determine whether or not they respond differently than younger subjects. Other reported clinical experience has not identified differences in responses between the elderly and younger patients. In general, dose selection for an elderly patient should be cautious, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease and other drug therapy.
ESPEROCT is a sterile, preservative-free, non-pyrogenic lyophilized powder for intravenous injection after reconstitution with the provided saline diluent. The active ingredient in ESPEROCT is a recombinant analogue of human coagulation Factor VIII (FVIII) conjugated with a 40-kDa polyethylene glycol (PEG) molecule. ESPEROCT is formulated with the following excipients: sodium chloride, L-histidine, sucrose, polysorbate 80, L-methionine, and calcium chloride.
FVIII activity in ESPEROCT is determined using the chromogenic assay described in the European Pharmacopoeia. The activity assignment employs a FVIII reference material that is traceable to the current World Health Organization (WHO) international standard for FVIII concentrate, and evaluated by appropriate methodologies to ensure the accuracy of the results. ESPEROCT is available in single-dose vials that contain nominally 500, 1000, 1500, 2000, or 3000 IU of FVIII. Each vial of ESPEROCT is labeled with the actual FVIII activity. After reconstitution with the supplied diluent (0.9% saline), each mL of the solution contains approximately 125, 250, 375, 500, or 750 IU of FVIII, respectively.
The FVIII protein in ESPEROCT is produced in Chinese Hamster Ovary (CHO) cells using recombinant DNA technology, and contains a truncated B domain, which is O-glycosylated. The polypeptide part of the molecule has a molecular mass of 166 kDa (calculated excluding post-translational modifications) and represents a heterodimer of a heavy chain and a light chain, which are held together by non-covalent interactions. The recombinant FVIII protein is purified using a series of chromatographic steps, one of which is affinity chromatography, with the use of a monoclonal antibody to selectively isolate the rFVIII from the cell culture medium. The 40-kDa PEG molecule is conjugated to the O-glycan moiety of the B domain using an enzymatic reaction to produce a glycopegylated FVIII (FVIII-PEG). The purification process includes two viral clearance steps, namely detergent (Triton X-100) treatment for inactivation of enveloped viruses, and 20-nm filtration for removal of enveloped and non-enveloped viruses. No additives of human or animal origin are used during the manufacturing process and formulation of ESPEROCT.
In the blood circulation, when FVIII-PEG is activated by thrombin, the B-domain portion with the attached PEG moiety is cleaved off, and the resulting activated FVIII (FVIIIa) is similar in structure and function to native FVIIIa.
ESPEROCT, a glycopegylated form of recombinant anti-hemophilic factor, temporarily replaces the missing coagulation Factor VIII needed for effective hemostasis in congenital hemophilia A patients. The Factor VIII in ESPEROCT is conjugated to a 40-kDa polyethylene glycol molecule which increases the half-life and decreases the clearance compared to the non-pegylated molecule.
The administration of ESPEROCT increases plasma levels of Factor VIII and can temporarily correct the coagulation defect in hemophilia A patients, as reflected by a decrease in activated partial thromboplastin time (aPTT).
All pharmacokinetic studies with ESPEROCT were conducted in previously treated subjects with severe hemophilia A (Factor VIII<1%). In total, 129 single-dose pharmacokinetic profiles of ESPEROCT were evaluated in 86 subjects (including 24 pediatric subjects, 1–<12 years).
Table 3 shows data for subjects who each received a single dose of 50 IU/kg. The plasma samples were analyzed using the one-stage clotting assay. There was a trend of increasing incremental recovery and AUC, and decreasing clearance, with age.
Table 3: Single-dose PK parameters of ESPEROCT 50 IU/kg, by age, using one-stage clotting assay (geometric mean (CV%))
PK Parameter
No. of subjects | 1 to <6 years
N=12 | 6 to <12 years
N=10 | 12 to <18 years
N=3 | >18 years
N=42 |
---|---|---|---|---|
No. of profiles |
12 |
10 |
5 |
78 |
IR (IU/dL) per IU/kg)a |
1.82 (32) |
1.67 (22) |
2.45 (16) |
2.53 (24) |
FVIII recovery (IU/dL)a |
103.2 (27) |
98.7 (18) |
117.7 (14) |
130.4 (26) |
t1/2 (hours) |
14.7 (27) |
13.8 (32) |
17.4 (39) |
21.7 (33) |
AUCinf (IU*hour/dL) |
2305 (42) |
2197 (38) |
3063 (40) |
4110 (38) |
CL (mL/hour/kg) |
2.4 (42) |
2.7 (42) |
1.6 (39) |
1.2 (34) |
Vss (mL/kg) |
44.2 (25) |
47.3 (28) |
36.4 (12) |
37.3 (26) |
MRT (hours) |
18.1 (27) |
17.8 (35) |
23.4 (43) |
27.4 (28)b |
PK parameters are presented in geometric mean.
Abbreviations: IR = Incremental recovery; t1/2 = terminal half-life; AUC = area under the FVIII activity time profile; CL = clearance; Vss = volume of distribution at steady-state; MRT = mean residence time; CV% = coefficient of variation
a IR and FVIII recovery were assessed 30 minutes post-dosing 50 IU/kg for patients ≥12 years and 60 minutes post-dosing 50 IU/kg (first sample) for children <12 years.
b Calculation based on 64 profiles.
In the single-dose PK assessment in adult subjects, whose body mass index (BMI) ranged from 17-35 kg/m2, differences were noted for individuals who were overweight (BMI 25 - <30 kg/m2) and obese (BMI 30 - <35 kg/m2). Incremental recovery was increased by approximately 17% and 41%, AUC was increased by approximately 10% and 27%, and clearance was decreased by approximately 8% and 23% respectively, all in comparison to those subjects with BMI <25 kg/m2. There is insufficient data to recommend specific dose adjustments for overweight and obese patients. The dose may be adjusted as necessary per prescriber’s discretion.
Observed pre-dose (trough) and post-dose (peak) plasma Factor VIII activity levels at steady-state during prophylactic treatment with ESPEROCT are presented in Table 4 by dose regimen and age range.
Table 4: Steady-state trough and peak plasma FVIII activity by age and dose regimen, chromogenic assay (geometric mean [95% CI])
Dose Regimen | 60 IU/kg twice weekly**
(50–75 IU/kg) | 50 IU/kg Q4D* | 75 IU/kg Q7D* | |||
---|---|---|---|---|---|---|
Age range No. patients |
<6 years N=31 |
6–<12 years N=34 |
12–<18 years N=23 |
≥18 years N=143 |
12–<18 years N=6 |
≥18 years N=29 |
Trough, IU/dL |
1.2 (0.8; 1.6) |
2.0 (1.5; 2.7) |
2.7 (1.8; 4.0) |
3.0 (2.6; 3.5) |
0.6 (0.2; 1.6) |
1.3 (0.9; 2.0) |
Peak, IU/dL |
125.0 (118.7; 131.6) |
143.3 (136.8; 150.2) |
125.1 (116.0; 135.0) |
137.9 (133.9; 142.2) |
198.0 (166.8; 235.2) |
197.9 (184.9; 212.7) |
*Data included in analysis: adolescents/adults Main Phase until Visit 8 (end of the Main Phase) 50 IU/kg Q4D, and extension 1 for 75 IU/kg Q7D. Only measurements collected at steady-state for the given prophylaxis treatment are included in the analyses.
**Data included in analysis: pediatric Main Phase 60 IU/kg (50–75 IU/kg) twice weekly. Only measurements collected at steady-state for the given prophylaxis treatment are included in the analyses.
Time of Factor VIII Activity Above 5%
Steady-state Factor VIII activity profiles were estimated using a one-compartment model with first-order elimination with PK parameters of clearance (CL) and volume of distribution (Table 5). Pharmacokinetic predictions showed that in all age groups, patients dosed twice weekly (dosing interval alternating between 3 and 4 days) or Q4D will be above 5% Factor VIII activity (i.e., in the range of mild hemophilia) for the majority of time (72–95% of time). Patients dosed with 50 IU/kg every 4 days will be above 1% Factor VIII activity 100% of the dosing interval. Patients dosed with 75 IU/kg every 7 days are predicted to be above 5% for 57% of time and above 1% for 83% of time.
Table 5: Estimation of steady-state peak and trough FVIII activity and time to 5% FVIII activity for ESPEROCT
Dose regimen
Age range | 60 IU/kg (50–75 IU/kg) twice weekly <12 years | 50 IU/kg twice weekly ≥12 years | 50 IU/kg Q4D ≥12 years | 75 IU/kg Q7D ≥12 years |
---|---|---|---|---|
Peak FVIII activity (%) |
110/112* |
133/138* |
132 |
194 |
Trough FVIII activity (%) |
2.8/0.8* |
8.6/3.6* |
3.5 |
0.3 |
Time to 5% FVIII activity (days) |
2.5/2.5* |
3.6/3.6* |
3.6 |
4.0 |
% of time in dosing interval above 5% FVIII activity |
72 |
95 |
90 |
57 |
*Twice weekly values are shown as 3 day/4 day. Only 50 IU/kg data are used for the analysis.
Carcinogenesis, mutagenesis, and impairment of fertility studies in animals have not been performed.
No adverse effects were observed in immune-deficient rats intravenously injected with ESPEROCT (50-1200 IU/kg/ injection), once every 4th day for 52 weeks. No evidence of polyethylene glycol accumulation was detected by immunohistochemical staining of brain tissue, including the choroid plexus.
The safety and efficacy of ESPEROCT have been evaluated in five multinational, open-label trials in male subjects with severe hemophilia A (<1% endogenous Factor VIII activity). One trial was subsequently partially randomized to evaluate two different prophylaxis regimens. All subjects were previously treated, which was defined as having received other Factor VIII products for ≥150 exposure days for adolescents and adults, and ≥50 exposure days for pediatric subjects. The key exclusion criteria across trials included known or suspected hypersensitivity to trial or related products and known history of Factor VIII inhibitors or current inhibitor ≥0.6 Bethesda units (BU).
The efficacy evaluation included 254 subjects, who received at least one dose of ESPEROCT, in the following trials:
On-demand Treatment and Control of Bleeding Episodes
There were 1506 bleeds reported in 171 of 254 subjects across the completed clinical trials, and the most common bleed types were joint (65.2%), muscle (14.5%), and subcutaneous (8.9%). Table 6 summarizes the efficacy in control of bleeding episodes by age.
Doses used for treatment of bleeding episodes depended on age, treatment regimen and the severity of the bleed.
Of the 1407 mild and moderate bleeding episodes in all subjects in the adolescent/adult study, the median dose used was 42 IU/kg. For subjects who were on the on-demand arm the median initial dose was 28 IU/kg and 88.4% of the bleeds were treated successfully with a single dose. In subjects receiving routine prophylaxis, the median initial dose was 52 IU/kg, and 76.4% of the bleeds were successfully treated with a single dose. Of the 15 severe bleeds, 12 (80%) required more than one dose with a total median dose of 111 IU/kg.
In the pediatric study, 70 mild/moderate bleeds in children < 12 years old receiving routine prophylaxis were treated with a median initial dose of 64 IU/kg per injection, with 63% treated with a single injection. When needed, additional median doses of 62 IU/kg were used at approximately 24 hour intervals. The median total dose was 70 IU/kg per bleed.
Table 6: Summary of efficacy in control of bleeding episodes by age
Age range
# of subjects | <6 years
N=34 | 6 - <12 years
N=34 | 12 - <18years
N=25 | ≥ 18 years
N=161 | Total
N= 254 |
|
---|---|---|---|---|---|---|
# of bleeds |
30 |
40 |
112 |
1324 |
1506 |
|
# of injections |
1–2 |
76.7% |
82.5% |
88.4% |
95.5% |
94.3% |
> 2 |
23.3% |
17.5% |
11.6% |
4.5% |
5.7% |
|
Response to first treatment |
Excellent/ |
80.0% |
77.5% |
75.0% |
88.7% |
87.3% |
Moderate |
13.3% |
17.5% |
17.9% |
10.3% |
11.1 % |
Definition of Hemostatic Response:
Excellent: Abrupt pain relief and/or unequivocal improvement in objective signs of bleeding within approximately 8 hours after a single injection.
Good: Definite pain relief and/or improvement in signs of bleeding within approximately 8 hours after one injection, but possibly requiring more than one injection for complete resolution.
Moderate: Probable or slight beneficial effect within approximately 8 hours after the first injection; usually requiring more than one injection.
Perioperative Management
The efficacy analysis of ESPEROCT in perioperative management included 45 major surgical procedures performed in 33 adolescent and adult subjects. The procedures included 15 joint replacements, 9 arthroscopic orthopedic interventions, 17 other orthopedic interventions, and 4 non-orthopedic surgeries.
The clinical evaluation of hemostatic response during major surgery was assessed using a 4-point scale of excellent, good, moderate, or none. The hemostatic effect of ESPEROCT was rated as “excellent” or “good” in 43 of 45 surgeries (95.6%), while the effect was rated as “moderate” in 2 surgeries (4.4%). No surgery had an outcome rated as “none” or “missing.”
The median pre-operative dose for adults and adolescents undergoing major surgeries was 52 IU/kg, and the median total dose was 702 IU/kg. During post-operative days 1-6, the median dose was 32 IU/kg at approximately 24 hour intervals. During post-operative days 7-14, the median dose was 36 IU/kg at approximately 28 hour intervals. The number of doses and duration of treatment varied by procedure.
Routine Prophylaxis in Adolescents/Adults
The efficacy of ESPEROCT in routine prophylaxis with Q4D dosing was demonstrated for the adult/adolescent population (see Table 7). In the extension part of the study, treatment success of the Q7D arm was not established. During the Main Phase of the adolescent/adult trial, 186 subjects had a total of 159 exposure years. The median annualized bleeding rate (ABR) for treated bleeds in adults and adolescents treated every 4 days was 1.2 (IQR: 0.0:4.3), and mean ABR was 3.0 (SD: 4.7). When including all bleeds (treated and non-treated), the median ABR was 1.2 (IQR: 0.0; 4.7) and the mean ABR was 3.3 (SD: 4.9).
Table 7: Efficacy in adolescent/adult prophylaxis, median and mean ABRs by age, treatment regimen, and bleed type
Prophylaxis | On-demand | |||
---|---|---|---|---|
Age Range | 12–17 years | 18–70 years | 12–70 years | 18–70 years |
# of subjects | 25 | 150 | 175 | 12 |
Mean treatment duration (years) |
0.85 |
0.81 |
0.82 |
1.33 |
Treated bleeds # of subjects with bleeds (%) # of subjects without bleeds (%) # of bleeds Median ABR (IQR) Mean ABR (SD) |
19 (76) 6 (24) 67 2.2 (0.9;4.7) 3.5 (3.9) |
86 (57) 64 (43) 369 1.2 (0.0;3.7) 2.9 (4.8) |
105 (60) 70 (40) 436 1.2 (0.0;4.3) 3.0 (4.7) |
12 (100) 0 532 30.9 (18.6;38.5) 31.9 (19.1) |
All bleeds (treated and untreated) # of subjects with bleeds (%) # of subjects without bleeds (%) # of bleeds* Median ABR (IQR) Mean ABR (SD) |
19 (76) 6 (24) 72 2.2 (0.9;6.0) 3.7 (4.1) |
88 (59) 62 (41) 386 1.2 (0.0;4.3) 3.2 (5.1) |
107 (61) 68 (39) 458 1.2 (0.0;4.7) 3.3 (4.9) |
12 (100) 0 536 31.3 (18.6;38.9) 32.2 (19.1) |
Treated spontaneous bleeds # of subjects with bleeds (%) # of subjects without bleeds (%) Median AsBR (IQR) Mean AsBR (SD) |
11 (44) 14 (56) 30 0.0 (0.0;1.5) 1.4 (2.4) |
65 (43) 85 (57) 221 0.0 (0.0;1.9) 1.8 (3.7) |
76 (43) 99 (57) 0.0 (0.0;1.8) 1.7 (3.5) |
12 (100) 0 415 19.4 (12.1;31.0) 24.5 (17.3) |
Treated traumatic bleeds
# of subjects without bleeds (%) # of bleeds Mean AtBR (SD) |
16 (64) 9 (36) 37 1.3 (0.0;2.6) 2.1 (2.9) |
57 (38) 93 (62) 146 0.0 (0.0;1.4) 1.1 (2.2) |
73 (42) 102 (58) 183 1.2 (2.3) |
10 (83) 2 (17) 110 6.1 (6.2) |
Treated joint bleeds
# of subjects without bleeds (%) # of bleeds Mean AjBR (SD) |
16 (64) 9 (36) 37 1.2 (0.0;2.8) 1.8 (2.2) |
74 (49) 76 (51) 288 0.0 (0.0;2.8) 2.3 (4.3) |
90 (51) 85 (49) 325 0.9 (0.0;2.8) 2.2 (4.1) |
12 (100) 0 309 19.7 (15.1) |
ABR = annualized bleed rate; IQR = interquartile range, 25th percentile to 75th percentile; SD = standard deviation; AsBR = annualized spontaneous bleed rate; AtBR = annualized traumatic bleed rate; AjBR = annualized joint bleed rate.
*Reflects all bleeds reported by patients including those where no ESPEROCT was administered
Routine Prophylaxis in Children <12 Years of Age
Overall, 68 children below 12 years received prophylactic treatment with ESPEROCT at an average dose of approximately 65 IU/kg twice weekly. The prophylactic effect of ESPEROCT was demonstrated with a median ABR rate of 2.0 (IQR: 0.0; 2.8) and 2.0 (IQR: 0.0; 4.2) for treated bleeds and all bleeds respectively (see Table 8). The mean ABR (SD) for treated bleeds and all bleeds were 3.1 (7.1) and 4.4 (8.7), respectively. Of the 68 children, 22 (32%) did not experience any bleeding episodes and 29 (43%) did not experience any bleeding episodes that required treatment during the Main Phase of the trial. Of the 13 subjects with 17 documented target joints at baseline, 10 subjects (77%) and 14 target joints (82%) did not have any bleeds during the Main Phase of the trial.
Table 8: Efficacy in pediatric prophylaxis, median and mean ABR by age and bleed type
Prophylaxis Regimen | |||
---|---|---|---|
Age range | < 6 years** | 6 to < 12 years | 0 to < 12 years |
# of subjects | N=34 | N=34 | N=68 |
Mean treatment duration (years) |
0.46 |
0.51 |
0.48 |
Treated bleeds # of subjects with bleeds (%) # of subjects without bleeds (%) # of bleeds Median ABR (IQR) Mean ABR (SD) |
19 (56) 15 (44) 30 1.9 (0.0;2.1) 3.9 (9.7) |
20 (59) 14 (41) 40 2.0 (0.0;3.9) 2.3 (2.9) |
39 (57) 29 (43) 70 2.0 (0.0;2.8) 3.1 (7.1) |
All Bleeds (treated and untreated) # of subjects with bleeds (%) # of subjects without bleeds (%) # of bleeds* Median ABR (IQR) Mean ABR (SD) |
20 (59) 14 (41) 41 2.0 (0.0;4.0) 5.0 (11.9) |
26 (77) 8 (24) 65 2.0 (1.9;6.0) 3.8 (3.6) |
46 (68) 22 (32) 106 2.0 (0.0;4.2) 4.4 (8.7) |
Treated spontaneous bleeds # of subjects with bleeds (%) # of subjects without bleeds (%) # of bleeds Median AsBR (IQR) Mean AsBR (SD) |
6 (18) 28 (82) 9 0.0 (0.0;0.0) 2.1 (7.3) |
7 (21) 27 (79) 10 0.0 (0.0; 0.0) 0.6 (1.5) |
13 (19) 55 (81) 19 0.0 (0.0; 0.0) 1.3 (5.3) |
Treated traumatic bleeds # of subjects with bleeds (%) # of subjects without bleeds (%) # of bleeds Median AtBR (IQR) Mean AtBR (SD) |
15 (44) 19 (56) 20 0.0 (0.0; 2.0) 1.7 (4.0) |
17 (50) 17 (50) 30 0.9 (0.0;2.0) 1.7 (2.5) |
32 (47) 36 (53) 50 0.0 (0.0;2.0) 1.7 (3.3) |
Treated joint bleeds # of subjects with bleeds (%) # of subjects without bleeds (%) # of bleeds Median AjBR (IQR) Mean AjBR (SD) |
7 (21) 27 (79) 10 0.0 (0.0;0.0) 1.5 (6.3) |
12 (35) 22 (65) 24 0.0 (0.0;2.0) 1.4 (2.4) |
19 (28) 49 (72) 34 0.0 (0.0;2.0) 1.5 (4.7) |
ABR = annualized bleed rate; IQR = interquartile range, 25th percentile to 75th percentile; SD = standard deviation; AsBR = annualized spontaneous bleed rate; AtBR = annualized traumatic bleed rate; AjBR = annualized joint bleed rate
*Reflects all bleeds reported by patients including those where no ESPEROCT was administered
**Elevated mean ABRs are due to subjects who withdrew from the study, whose bleeding rates were extrapolated to one year
How Supplied
Table 9: ESPEROCT Presentations
Nominal Dosage Strength | Cap Color
Indicator | Carton NDC Number | Components |
---|---|---|---|
500 IU |
Red |
NDC 0169 8500 01 |
|
1000 IU |
Green |
NDC 0169 8100 01 |
|
1500 IU |
Gray |
NDC 0169 8150 01 |
|
2000 IU |
Yellow |
NDC 0169 8200 01 |
|
3000 IU |
Black |
NDC 0169 8300 01 |
|
IU = International Units
Storage and Handling
Advise patients:
Version: 2
License Number: 1261
ESPEROCT® and MixPro® are registered trademarks of Novo Nordisk Health Care AG.
Patent Information: http://novonordisk-us.com/patients/products/product-patents.html
Clave® and MicroClave® are registered trademarks of ICU Medical Inc.
InVision-Plus®, InVision-Plus CS®, Invision-Plus® Junior® are registered trademarks of RyMed Technologies, Inc. Bionector® is a registered trademark of Vygon.
© 2019 Novo Nordisk
For information contact:
Novo Nordisk Inc.
800 Scudders Mill Road
Plainsboro, NJ 08536, USA
1-800-727-6500
Manufactured by:
Novo Nordisk A/S
Novo Allé, DK-2880 Bagsvaerd
Patient Information
ESPEROCT®
[antihemophilic factor (recombinant), glycopegylated-exei]
Read the Patient Information and the Instructions For Use that come with ESPEROCT before you start taking this medicine and each time you get a refill. There may be new information.
This Patient Information does not take the place of talking with your healthcare provider about your medical condition or treatment. If you have questions about ESPEROCT after reading this information, ask your healthcare provider.
What is the most important information I need to know about ESPEROCT?
Do not attempt to do an infusion yourself unless you have been taught how by your healthcare provider or hemophilia treatment center.
You must carefully follow your healthcare provider's instructions regarding the dose and schedule for infusing ESPEROCT so that your treatment will work best for you.
What is ESPEROCT?
ESPEROCT is an injectable medicine used to replace clotting Factor VIII that is missing in patients with hemophilia A. Hemophilia A is an inherited bleeding disorder in all age groups that prevents blood from clotting normally.
ESPEROCT is used to treat and prevent or reduce the number of bleeding episodes in people with hemophilia A.
Your healthcare provider may give you ESPEROCT when you have surgery.
Who should not use ESPEROCT?
You should not use ESPEROCT if you
If you are not sure, talk to your healthcare provider before using this medicine.
Tell your healthcare provider if you are pregnant or nursing because ESPEROCT might not be right for you.
What should I tell my healthcare provider before I use ESPEROCT?
You should tell your healthcare provider if you:
How should I use ESPEROCT?
Treatment with ESPEROCT should be started by a healthcare provider who is experienced in the care of patients with hemophilia A.
ESPEROCT is given as an infusion into the vein.
You may infuse ESPEROCT at a hemophilia treatment center, at your healthcare provider's office or in your home. You should be trained on how to do infusions by your hemophilia treatment center or healthcare provider. Many people with hemophilia A learn to infuse the medicine by themselves or with the help of a family member.
Your healthcare provider will tell you how much ESPEROCT to use based on your weight, the severity of your hemophilia A, and where you are bleeding. Your dose will be calculated in international units, IU.
Call your healthcare provider right away if your bleeding does not stop after taking ESPEROCT.
If your bleeding is not adequately controlled, it could be due to the development of Factor VIII inhibitors. This should be checked by your healthcare provider. You might need a higher dose of ESPEROCT or even a different product to control bleeding. Do not increase the total dose of ESPEROCT to control your bleeding without consulting your healthcare provider.
Use in children
ESPEROCT can be used in children. Your healthcare provider will decide the dose of ESPEROCT you will receive.
If you forget to use ESPEROCT
If you forget a dose, infuse the missed dose when you discover the mistake. Do not infuse a double dose to make up for a forgotten dose. Proceed with the next infusions as scheduled and continue as advised by your healthcare provider.
If you stop using ESPEROCT
Do not stop using ESPEROCT without consulting your healthcare provider.
If you have any further questions on the use of this product, ask your healthcare provider.
What if I take too much ESPEROCT?
Always take ESPEROCT exactly as your healthcare provider has told you. You should check with your healthcare provider if you are not sure. If you infuse more ESPEROCT than recommended, tell your healthcare provider as soon as possible.
What are the possible side effects of ESPEROCT?
Common Side Effects Include:
Other Possible Side Effects:
You could have an allergic reaction to coagulation Factor VIII products. Call your healthcare provider right away or get emergency treatment right away if you get any signs of an allergic reaction,such as: hives, chest tightness, wheezing, dizziness, difficulty breathing, and/or swelling of the face.
Your body can also make antibodies called “inhibitors” against ESPEROCT, which may stop ESPEROCT from working properly. Your healthcare provider may need to test your blood for inhibitors from time to time.
These are not all of the possible side effects from ESPEROCT. Ask your healthcare provider for more information. You are encouraged to report side effects to FDA at 1-800-FDA-1088.
Tell your healthcare provider about any side effect that bothers you or that does not go away.
What are the ESPEROCT dosage strengths?
ESPEROCT comes in five different dosage strengths. The actual number of international units (IU) of Factor VIII in the vial will be imprinted on the label and on the box. The five different strengths are as follows:
Cap Color Indicator |
Nominal Strength |
Red |
500 IU per vial |
Green |
1000 IU per vial |
Gray |
1500 IU per vial |
Yellow |
2000 IU per vial |
Black |
3000 IU per vial |
Always check the actual dosage strength printed on the label to make sure you are using the strength prescribed by your healthcare provider.
How should I store ESPEROCT?
Prior to Reconstitution (mixing the dry powder in the vial with the diluent):
Protect from light. Do not freeze ESPEROCT.
ESPEROCT can be stored in refrigeration at 36°F to 46°F (2°C to 8°C) for up to 30 months until the expiration date stated on the label. During the 30 month shelf life, ESPEROCT may be kept at room temperature (not to exceed 86°F/30°C) for up to 12 months, or up to 104°F (40°C) for no longer than 3 months.
If you choose to store ESPEROCT at room temperature:
Do not use this medicine after the expiration date which is on the outer carton and the vial. The expiration date refers to the last day of that month.
After Reconstitution:
The reconstituted (the final product once the powder is mixed with the diluent) ESPEROCT should appear clear and colorless without visible particles.
The reconstituted ESPEROCT should be used immediately.
If you cannot use the reconstituted ESPEROCT immediately, it must be used within 4 hours when stored at or below 86ºF (30°C) or within 24 hours when stored in a refrigerator at 36°F to 46°F (2°C to 8°C). Store the reconstituted product in the vial.
Keep this medicine out of the sight and out of reach of children.
What else should I know about ESPEROCT and hemophilia A?
Medicines are sometimes prescribed for purposes other than those listed here. Do not use ESPEROCT for a condition for which it is not prescribed. Do not share ESPEROCT with other people, even if they have the same symptoms that you have.
For more information about ESPEROCT, please call Novo Nordisk at 1-800-727-6500.
Revised: 10/2019
ESPEROCT® is a trademark of Novo Nordisk Health Care AG.
For Patent Information, refer to: http://novonordisk-us.com/patients/products/product-patents.html
© 2019 Novo Nordisk
Manufactured by:
Novo Nordisk A/S
Novo Allé
DK-2880 Bagsværd, Denmark
For information about ESPEROCT contact:
Novo Nordisk Inc.
800 Scudders Mill Road
Plainsboro, NJ 08536, USA
Instructions for Use
Instructions on how to use ESPEROCT® [antihemophilic factor (recombinant), glycopegylated-exei] MixPro®
READ THESE INSTRUCTIONS CAREFULLY BEFORE USING ESPEROCT.
ESPEROCT is supplied as a powder. Before infusion (administration) it must be mixed (reconstituted) with the liquid diluent supplied in the syringe. The liquid diluent is a sodium chloride solution. The mixed ESPEROCT must be infused into your vein (intravenous infusion). The equipment in this package is designed to mix and infuse ESPEROCT.
You will also need an infusion set (butterfly needle with tubing), sterile alcohol swabs, gauze pads, and bandages.
Don’t use the equipment without proper training from your doctor or nurse.
Always wash your hands and ensure that the area around you is clean.
When you prepare and infuse medication directly into the veins, it is important to use a clean and germ free (aseptic) technique. Improper technique can introduce germs that can infect the blood.
Don’t open the equipment until you are ready to use it.
Don’t use the equipment if it has been dropped, or if it is damaged. Use a new package instead.
Don’t use the equipment if it is expired. Use a new package instead.The expiration date is printed on the outer carton and on the vial, the vial adapter and the pre-filled syringe.
Don’t use the equipment if you suspect it is contaminated. Use a new package instead.
Don’t dispose of any of the items until after you have infused the mixed solution.
The equipment is for single use only.
Single-dose container. Discard unused portion.
Content
The package contains:
Vial with ESPEROCT powder
Vial adapter
Pre-filled syringe with diluent
Plunger rod (placed under the syringe)
1. Prepare the vial and the syringe
2. Attach the vial adapter
3. Attach the plunger rod and the syringe
4. Mix the powder with the diluent
ESPEROCT is recommended to be used immediately after it is mixed.
If you cannot use the mixed ESPEROCT solution immediately, it must be used within 4 hours when stored at ≤86°F (30°C) or within 24 hours when stored in a refrigerator at 36°F to 46°F (2°C to 8°C). Store the reconstituted product in the vial.
Do not freeze mixed ESPEROCT solution or store it in syringes.
Keep reconstituted ESPEROCT solution out of direct light.
If your dose requires more than one vial, repeat step A to J with additional vials, vial adapters and pre-filled syringes until you have reached your required dose.
Don’t touch the syringe tip. If you touch the syringe tip germs from your fingers can be transferred.
Caution: The pre-filled diluent syringe is made of glass with an internal tip diameter of 0.037 inches, and is compatible with a standard Luer-lock connector.
Some needleless connectors for intravenous catheters are incompatible with the glass diluent syringes (for example, certain connectors with an internal spike, such as Clave® /MicroClave®, InVision-Plus®, InVision-Plus CS®, Invision-Plus® Junior®, Bionector®).
To administer ESPEROCT through incompatible needleless connectors, withdraw reconstituted product into a standard 10 mL sterile Luer-lock plastic syringe.
If you have encountered any problems with attaching the pre-filled sodium chloride syringe to any Luer‐lock compatible device, please contact Novo Nordisk at (800) 727-6500.
5. Infuse the mixed solution
ESPEROCT is now ready to infuse into your vein.
Infusing the solution via a central venous access device (CVAD) such as a central venous catheter or subcutaneous port:
The peel-off label found on the ESPEROCT vial can be used to record the lot number.
Disposal
Don’t throw it out with the ordinary household trash.
Don’t disassemble the vial and vial adapter before disposal.
Don’t reuse the equipment.
Important information
Contact your healthcare provider or local hemophilia treatment center if you experience any problems.
For full Prescribing Information please read the other insert included in this package.
ESPEROCT® and MixPro® are trademarks of Novo Nordisk Health Care AG.
For Patent Information, refer to: http://novonordisk-us.com/patients/products/product-patents.html
© 2019 Novo Nordisk
Manufactured by:
Novo Nordisk A/S
DK-2880 Bagsvaerd, Denmark
For information about ESPEROCT contact:
Novo Nordisk Inc.
800 Scudders Mill Road
Plainsboro, NJ 08536, USA
License No: 1261
Revised: 10/2019
500 IU Carton
NDC 0169 8500 01 List: 850001
[antihemophilic factor (recombinant), glycopegylated-exei]
500 IU
Intravenous use, after reconstitution.
Single-dose. Discard unused portion
Contains no preservatives.
Rx Only
Includes MixPro®
a vial adapter and pre-filled diluent syringe
ESPEROCT
antihemophilic factor (recombinant), glycopegylated-exei kit |
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antihemophilic factor (recombinant), glycopegylated-exei kit |
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antihemophilic factor (recombinant), glycopegylated-exei kit |
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antihemophilic factor (recombinant), glycopegylated-exei kit |
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antihemophilic factor (recombinant), glycopegylated-exei kit |
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Labeler - Novo Nordisk (622920320) |
Establishment | |||
Name | Address | ID/FEI | Business Operations |
---|---|---|---|
Novo Nordisk A/S | 306711800 | MANUFACTURE(0169-8500, 0169-8100, 0169-8150, 0169-8200, 0169-8300) |
Establishment | |||
Name | Address | ID/FEI | Business Operations |
---|---|---|---|
Novo Nordisk US Bio Production Inc. | 079783898 | API MANUFACTURE(0169-8500, 0169-8100, 0169-8150, 0169-8200, 0169-8300) |
Mark Image Registration | Serial | Company Trademark Application Date |
---|---|
ESPEROCT 79152765 4697829 Live/Registered |
Novo Nordisk Health Care AG 2014-07-24 |