HIGHLIGHTS OF PRESCRIBING INFORMATION ——— CONTRAINDICATIONS ———

These highlights do not include all the information Do not use in patients who have had life-threatening hypersen-
needed to use NOVOEIGHT® safely and effectively. sitivity reactions, including anaphylaxis, to Novoeight® or its
See full prescribing information for NOVOEIGHT®. components, including hamster proteins. (4)
NOVOEIGHT® (antihemophilic factor, recombinant) ——— WARNINGS AND PRECAUTIONS ———
lyophilized powder for solution, for intravenous use • Anaphylaxis and severe hypersensitivity reactions are possible.
Initial U.S. Approval: 2013 Patients may develop hypersensitivity to hamster proteins, which
are present in trace amounts in the product. Should symptoms
——— RECENT MAJOR CHANGES ——— occur, discontinue Novoeight® and administer appropriate
Indications and Usage (1) 11/2018 treatment. (5.1)
Dosage and Administration (2) 11/2018 • Development of activity-neutralizing antibodies (inhibitors)
Warnings and Precautions (5.2) 11/2018 may occur. If expected plasma factor VIII activity levels are not
attained, or if bleeding is not controlled with an appropriate
——— INDICATIONS AND USAGE ——— dose, perform an assay that measures factor VIII inhibitor
Novoeight® is an Antihemophilic Factor (Recombinant) indicated concentration. (5.2, 5.3)
for use in adults and children with hemophilia A for:
——— ADVERSE REACTIONS ———
• On-demand treatment and control of bleeding episodes
The most frequently reported adverse reactions (≥ 1%) were
• Perioperative management inhibitors in Previously Untreated Patients (PUPs), injection site
• Routine prophylaxis to reduce the frequency of bleeding reactions, and pyrexia. (6)
episodes.
To report SUSPECTED ADVERSE REACTIONS,
Novoeight® is not indicated for the treatment of von Willebrand contact Novo Nordisk Inc. at 1-844-303-4448 or FDA at
disease. (1) 1-800-FDA-1088 or www.fda.gov/medwatch.
——— DOSAGE AND ADMINISTRATION ——— ——— USE IN SPECIFIC POPULATIONS ———
For intravenous injection after reconstitution only (2) • Pediatric Use: Clearance (based on per kg body weight) is
• Each vial of Novoeight® contains the labeled amount of higher in children. Higher or more frequent dosing may be
recombinant Factor VIII in international units (IU). (2) needed. (8.4)
• The required dosage is determined using the following formula: • Obesity: The area under the curve (AUC) is higher and clearance
Dosage Required (IU) = Body Weight (kg) × Desired Factor VIII lower in adult patients with body mass index (BMI) ≥ 30 kg/m2
Increase (IU/dL or % normal) × 0.5 (IU/kg per IU/dL) than in patients with BMI < 30kg/m2. Adjust dose as necessary.
• Frequency of Novoeight® administration is determined by the (8.6, 12.3)
type of bleeding episode and the recommendation of the treating See 17 for PATIENT COUNSELING INFORMATION and
physician. (2.1) FDA-approved patient labeling.
——— DOSAGE FORMS AND STRENGTHS ——— 11/2018
Novoeight® is available as a lyophilized powder in single-use vials
of 250, 500, 1000, 1500, 2000 and 3000 international units. (3)

FULL PRESCRIBING INFORMATION: CONTENTS* 8.5 Geriatric Use

1 INDICATIONS AND USAGE 8.6 Obesity
2 DOSAGE AND ADMINISTRATION 11 DESCRIPTION
2.1 Dose 12 CLINICAL PHARMACOLOGY
2.2 Preparation and Reconstitution 12.1 Mechanism of Action
2.3 Administration 12.2 Pharmacodynamics
3 DOSAGE FORMS AND STRENGTHS 12.3 Pharmacokinetics
4 CONTRAINDICATIONS 13 NONCLINICAL TOXICOLOGY
5 WARNINGS AND PRECAUTIONS 13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility
5.1 Hypersensitivity Reactions 14 CLINICAL STUDIES
5.2 Neutralizing Antibodies 16 HOW SUPPLIED/STORAGE AND HANDLING
5.3 Monitoring Laboratory Tests 17 PATIENT COUNSELING INFORMATION
6 ADVERSE REACTIONS *Sections or subsections omitted from the full prescribing
6.1 Clinical Trials Experience information are not listed.
6.2 Postmarketing Experience
8 USE IN SPECIFIC POPULATIONS
8.1 Pregnancy
8.2 Lactation
8.4 Pediatric Use

1
 Novoeight®, Antihemophilic Factor (Recombinant) 2

FULL PRESCRIBING INFORMATION Routine Prophylaxis 7. Grasp the plunger rod as shown F
A guide for dosing Novoeight® for routine prophylaxis is included in the diagram. Attach the plunger
1 INDICATIONS AND USAGE rod to the syringe by holding the
below in Table 3.
N ovoeight , Antihemophilic Factor (Recombinant), is a human
®
plunger rod by the wide top end.
antihemophilic factor (human blood coagulation factor VIII (FVIII)) Table 3: Dosing for Routine Prophylaxis Turn the plunger rod clockwise
indicated for use in adults and children with hemophilia A for: Factor VIII Dose into the rubber plunger inside
• On-demand treatment and control of bleeding episodes Patient Population Required (IU/kg) Frequency of Doses the pre-filled diluent syringe until
• Perioperative management Adults and adolescents 20-50 3 times weekly resistance is felt.
• Routine prophylaxis to reduce the frequency of bleeding episodes (≥ 12 years) 20-40 Every other day 8. Break off the syringe cap from G
Novoeight® is not indicated for the treatment of von Willebrand the pre-filled diluent syringe by
disease. 25-60 3 times weekly snapping the perforation of the cap.
Children (<12 years)
25-50 Every other day
2 DOSAGE AND ADMINISTRATION
For intravenous injection after reconstitution only. 2.2 Preparation and Reconstitution
2.1 Dose • Always wash hands and ensure that the area is clean before
• Dosage and duration of treatment depend on the severity of the performing the procedures.
factor VIII deficiency, on the location and extent of bleeding, and • Use aseptic technique during the reconstitution procedures. 9. Connect the pre-filled diluent
the patient’s clinical condition. Careful monitoring of replacement • If the dose requires more than one vial of Novoeight® per H
syringe to the vial adapter by turning
therapy is necessary in cases of major surgery or life-threatening injection, reconstitute each vial according to the following
bleeding episodes. it clockwise until it is secured.
instructions:
• Each vial of Novoeight® contains the labeled amount of Overview of Novoeight® Package
recombinant factor VIII in international units (IU). One IU of Vial with NovoEight® powder Vial adapter
factor VIII activity corresponds to the quantity of factor VIII in one
milliliter of normal human plasma. The calculation of the required Plastic cap Rubber stopper Protective cap
dosage of factor VIII is based on the empirical finding that one (under plastic cap) 10. Push the plunger rod to slowly inject I
IU of factor VIII per kg body weight raises the plasma factor VIII all the diluent into the vial.
activity by two IU/dL. This relationship causes a factor of 0.5 to
be present in the dose calculation formula shown below.
Spike (under Protective
• The required dosage can be determined using the following protective paper) paper
formula: Pre-filled syringe with diluent Plunger rod
Dosage (IU) = Body Weight (kg) × Desired Factor VIII Syringe tip Rubber plunger Thread Wide
Increase (IU/dL or % normal) × 0.5 (under syringe top
cap) Scale end
The final dose calculated is expressed as IU 11. Without removing the syringe, J
• Base the dose and frequency of Novoeight® on the individual gently swirl the Novoeight®
clinical response. Patients may vary in their pharmacokinetic and vial until all of the powder is
clinical responses [See Clinical Pharmacology (12.3)]. dissolved.
On-demand Treatment and Control of Bleeding Episodes Syringe cap

A guide for dosing Novoeight® for on-demand treatment and Reconstitution

control of bleeding episodes is provided in Table 1. Dose to
1. Bring the Novoeight® vial and the
maintain a plasma factor VIII activity level at or above the plasma A
pre-filled diluent syringe to room
levels (in % of normal or in IU/dL) outlined in Table 1.
temperature.
Table 1: Dosing for On-demand Treatment and Control of
Bleeding Episodes
Factor VIII Level Frequency Duration of
Type of Required (IU/dL of Doses Therapy
Bleeding Episodes or % of normal) (hours) (days) 12. Use the Novoeight® solution immediately. If not, store the
solution in the vial with the vial adapter and the syringe attached.
Minor At least 1 day until Use Novoeight® within 4 hours after reconstitution when stored
Early hemarthrosis, minor 20-40 12-24 bleeding resolution is 2. Remove the plastic cap from the B
muscle or oral bleeding achieved Novoeight® vial. at <86°F (30°C) or within 2 hours when stored between 86°F
(30°C) to 104°F (40°C).
Moderate Until pain and acute
Muscle bleeding, bleeding 2.3 Administration
12-24 disability are resolved
30-60
into the oral cavity or mild (approximately 3-4 For intravenous injection only.
head trauma days) • Inspect the reconstituted Novoeight® solution visually for
Major particulate matter and discoloration prior to administration,
Life or limb threatening Until resolution of whenever solution and container permit. Do not use if particulate
hemorrhage, Gastrointestinal 60-100 8-24 bleed (approximately 3. Wipe the rubber stopper on the vial matter or discoloration is observed.
bleeding, intracranial, intra- C
7-10 days) with a sterile alcohol swab and allow • Do not administer Novoeight® in the same tubing or container
abdominal or intrathoracic
bleeding, fractures it to dry prior to use. with other medicinal products.
4. Remove the protective paper from 1. Invert the Novoeight® vial and K
Perioperative Management the vial adapter. Do not remove slowly draw the solution into the
A guide for dosing Novoeight® during surgery (perioperative the vial adapter from the syringe.
management) is provided in Table 2. Consider maintaining a protective cap.
plasma factor VIII activity level at or above the plasma levels
(in % of normal or in IU/dL) outlined in Table 2.
5. Place the vial on a flat and solid D
Table 2: Dosing for Perioperative Management surface. While holding the protective
Factor VIII Level Frequency Duration of cap, place the vial adapter over the
Type of Required (IU/dL of Doses Therapy Novoeight® vial and press down
Surgery or % of normal) (hours) (days) firmly on the protective cap until
Minor At least 1 day until the vial adapter spike penetrates the
30–60 24 rubber stopper.
Including tooth extraction healing is achieved 2. Detach the syringe from the vial adapter by turning the
Major Until adequate wound syringe counterclockwise.
Intracranial, intra- 80-100 healing, then continue 6. Carefully remove the protective cap 3. Attach the syringe to the luer end of an infusion needle set.
abdominal, intrathoracic, therapy for at least E
(pre-and 8-24 from the vial adapter. 4. Inject the reconstituted Novoeight® intravenously slowly over
or joint replacement post-operative) 7 days to maintain a
surgery factor VIII activity of 2 to 5 minutes.
30% to 60% (IU/dL) 5. After injection, safely dispose of the syringe with the infusion
set, the vial with the vial adapter, any unused Novoeight® and
other waste materials. Accidental needle stick with a needle
contaminated with blood can transmit infectious viruses
including HIV (AIDS) and hepatitis. Obtain immediate
medical attention if injury occurs. Place needles in a sharps
container after single-use.
 Novoeight®, Antihemophilic Factor (Recombinant) 3

Caution: Table 4: Summary of Adverse Reactions (ARs) with a 8.5 Geriatric Use
The pre-filled diluent syringe is made of glass with an internal Frequency ≥ 1% in 301 Subjects Clinical studies of Novoeight® did not include sufficient numbers
tip diameter of 0.037 inches, and is compatible with a standard MedDRA System Organ class Adverse Reactions Frequency N (%) of patients aged 65 and over to determine whether they respond
Luer-lock connector. differently from younger patients.
General disorders and administration Pyrexia 3 (1.0%)
Some needleless connectors for intravenous catheters are site conditions Injection site reaction 3 (1.0%) 8.6 Obesity
incompatible with the glass diluent syringes (for example, certain In the extension trial, in six adult patients with body mass index
connectors with an internal spike, such as Clave® /MicroClave®, Immunogenicity (BMI) ≥ 30 kg/m2, the AUC was higher and clearance lower than
InVision-Plus®, InVision-Plus CS®, Invision-Plus Junior®, Subjects were monitored for neutralizing antibodies to factor VIII and in patients with BMI < 30 kg/m2. There is insufficient data to
Bionector®), and their use can damage the connector and affect binding antibodies to CHO and murine protein. No PTPs developed recommend specific dose adjustments for patients with BMI ≥ 30
administration. To administer Novoeight® through incompatible confirmed neutralizing antibodies to factor VIII. One twenty-two month kg/m2. Adjust dose as necessary and per prescriber’s discretion for
needleless connectors, withdraw the reconstituted product into a old previously treated child had a positive neutralizing antibody to patients with BMI ≥ 30 kg/m2. [See Clinical Pharmacology (12.3)].
standard 10 mL sterile Luer-lock plastic syringe. factor VIII of 1.3 [BU] in the Bethesda assay after 15 exposure days
11 DESCRIPTION
that was not confirmed when checked after 20 exposure days. In vivo
3 DOSAGE FORMS AND STRENGTHS recovery was normal for this child and no clinical adverse findings Novoeight® is formulated as a sterile, non-pyrogenic, lyophilized
were observed. In the completed main phase of the clinical trial in powder for intravenous injection after reconstitution with the diluent
Novoeight® is available as a white lyophilized powder in single-use
PUPs, 24 of 56 (42.9%) patients developed inhibitors with a mean (0.9% sodium chloride). Novoeight® is available in single-dose
vials containing 250, 500, 1000, 1500, 2000 and 3000 international vials that contain nominally 250, 500, 1000, 1500, 2000 or 3000
units per vial. of 14.1 exposure days at the time of the first positive inhibitor test;
international units (IU) per vial. When reconstituted with the
After reconstitution with 4 mL of 0.9% sodium chloride solution, 15 (26.8%) PUPs developed high titer (≥ 5 BU) inhibitors. High risk
appropriate volume of diluent, the product contains the following
genetic mutations were identified in 91.7% of the overall inhibitors
each mL of reconstituted solution contains approximately 62.5, 125, components per mL: 18 mg sodium chloride, 1.5 mg L-histidine,
and 93.3% of the high titer inhibitors.
250, 375, 500 or 750 international units of Novoeight®, respectively. 3 mg sucrose, 0.1 mg polysorbate 80, 0.055 mg L-methionine
No patients developed de novo anti-murine antibodies. Nineteen and 0.25 mg calcium chloride dihydrate. The product contains no
4 CONTRAINDICATIONS subjects were positive for anti-Chinese hamster ovary (CHO) cell preservative. Each vial of Novoeight® is labeled with the actual
Novoeight® is contraindicated in patients who have had protein antibodies. Two of these subjects changed from anti-CHO rFVIII activity expressed in IU determined by the one-stage clotting
life-threatening hypersensitivity reactions, including anaphylaxis, to negative to anti-CHO positive and 6 subjects changed from anti-CHO assay, using a reference material calibrated against a World Health
Novoeight® or its components (including traces of hamster proteins). positive to anti-CHO negative. The remaining 11 subjects were either Organization (WHO) International Standard for FVIII Concentrates.
positive throughout the trials (n=6), negative at baseline and end-of One IU, as defined by the WHO standard for human FVIII, is
5 WARNINGS AND PRECAUTIONS trial but with transient positive samples (n=2), or positive at baseline approximately equal to the level of FVIII activity in 1 mL of fresh
and end-of trial but with negative samples in between (n=3). No pooled human plasma. The specific activity of Novoeight® is
5.1 Hypersensitivity Reactions
clinical adverse findings were observed in any of these subjects. approximately 8340 IU per milligram of protein.
Hypersensitivity reactions, including anaphylaxis, are possible
The detection of antibody formation is highly dependent on the The active ingredient in Novoeight® is a recombinant (r) analogue
with Novoeight®. Novoeight® contains trace amounts of hamster sensitivity and specificity of the assay. Additionally, the observed of human coagulation factor VIII (FVIII) with a molecular mass of
proteins. Patients treated with this product may develop hypersen- incidence of antibody (including neutralizing antibody) positivity 166 kDa, calculated excluding post-translational modifications.
sitivity to these non-human mammalian proteins. Early signs of in an assay may be influenced by several factors, including assay The rFVIII molecule in Novoeight® is a glycoprotein containing a
hypersensitivity reactions that can progress to anaphylaxis include methodology, sample handling, timing of sample collection, heavy chain and a light chain, with 21 of the 908 amino acids of the
angioedema, chest tightness, dyspnea, wheezing, urticaria, and concomitant medications, and underlying disease. For these B-domain of endogenous FVIII connected to the C-terminus of the
pruritus. Immediately discontinue administration and initiate reasons, it may be misleading to compare the incidence of antibodies heavy chain. Once activated, the resulting rFVIIIa has a comparable
appropriate treatment if allergic- or anaphylactic-type reactions to Novoeight® with the incidence of antibodies to other products. structure to the endogenous FVIIIa.
occur. Novoeight® is synthesized by a genetically engineered Chinese
6.2 Postmarketing Experience
5.2 Neutralizing Antibodies hamster ovary (CHO) cell line which secretes rFVIII into the cell
Adverse reactions reported during post marketing period were culture medium. The rFVIII protein is purified using a series of
Formation of neutralizing antibodies (inhibitors) to factor VIII can similar in nature to those observed during clinical trials. chromatography steps, one of which is the use of an immunoaffinity
occur following administration of Novoeight®. Previously untreated column in which a monoclonal antibody, produced in CHO cells and
8 USE IN SPECIFIC POPULATIONS
patients (PUPs) are at greatest risk for inhibitor development with directed against FVIII, is employed to selectively isolate the rFVIII
all factor VIII products. Inhibitors have been reported following 8.1 Pregnancy from the medium. The production process includes two dedicated
administration of Novoeight® in PUPs [see Adverse Reactions Risk Summary viral clearance steps – a detergent treatment step for inactivation
(6.1)]. Monitor all patients for the development of inhibitors by As hemophilia mainly affects males, there are no adequate and and a 20-nm filtration step for removal of viruses. No additives of
appropriate clinical observation and laboratory testing. If the well-controlled studies using Novoeight® in pregnant women human or animal origin are used in the cell culture, purification and
expected plasma levels of factor VIII activity are not attained, or if to determine whether there is a drug-associated risk. Animal formulation of Novoeight®.
bleeding is not controlled with an appropriate dose, perform testing reproduction studies have not been conducted with Novoeight®. 12 CLINICAL PHARMACOLOGY
for factor VIII inhibitors. In the U.S. general population, the estimated background risk 12.1 Mechanism of Action
5.3 Monitoring Laboratory Tests of major birth defect and miscarriage in clinically recognized
pregnancies is 2-4% and 15-20%, respectively. There is no reliable Novoeight® temporarily replaces the missing clotting factor VIII that
• Monitor plasma factor VIII activity levels by the one-stage is needed for effective hemostasis.
data on the incidences specific to the hemophilia A population.
clotting assay or the chromogenic substrate assay to confirm that
8.2 Lactation 12.2 Pharmacodynamics
adequate factor VIII levels have been achieved and maintained,
when clinically indicated. [See Dosage and Administration (2.1)] The activated partial thromboplastin time (aPTT) is prolonged in
Risk Summary
patients with hemophilia A. Determination of aPTT is a conventional
• Perform assay to determine if factor VIII inhibitor is present if There is no information regarding the presence of Novoeight® in in vitro assay for the biological activity of FVIII. Treatment with
expected plasma factor VIII activity levels are not attained, or if human milk, the effect on the breastfed infant, and the effects on milk Novoeight® normalizes the aPTT over the effective dosing period.
bleeding is not controlled with the expected dose of Novoeight®. production. The developmental and health benefits of breastfeeding
Determine inhibitor levels in Bethesda Units. should be considered along with the mother’s clinical need for 12.3 Pharmacokinetics
Novoeight® and any potential adverse effects on the breastfed infant All pharmacokinetic studies with Novoeight® were conducted in
6 ADVERSE REACTIONS from Novoeight® or from the underlying maternal condition. previously treated patients with severe hemophilia A (factor VIII ≤
The most frequently reported adverse reactions observed in clinical 8.4 Pediatric Use 1%). Analysis of plasma samples was conducted using both the
trials (≥ 1%) were injection site reactions, and pyrexia. one-stage clotting assay and the chromogenic assay.
Children have shorter half–life and lower recovery of factor VIII than In a multi-center, multi-national, open-label, single dose pharma-
6.1 Clinical Trials Experience adults. Because clearance (based on per kg body weight) has been cokinetic study, 23 patients with severe hemophilia A received 50
Because clinical trials are conducted under widely varying demonstrated to be higher in the pediatric population, higher or more international units/kg of Novoeight® intravenously. Two patients
conditions, adverse reaction rates observed in the clinical trials of a frequent dosing based on body weight may be needed. [See Clinical were below the age of 18 years (13 and 17 years). The pharma-
drug cannot be directly compared to rates in clinical trials of another Pharmacology (12.3)] cokinetic parameters for 20 patients who completed the study are
drug and may not reflect the rates observed in clinical practice. Safety and efficacy studies have been performed in 146 pediatric summarized in Table 5.
During the clinical development of Novoeight®, 301 male patients patients <18 years of age. Ninety (including all 59 PUPs) of these
(242 previously treated patients (PTPs); exposed to a factor subjects (62%) were <6 years of age, 32 (22%) were 6 to <12 years
of age, and 24 (16%) were adolescents (12 to <18 years of age).
VIII-containing product for ≥150 days and 59 Previously Untreated
Subjects during routine prophylaxis and treatment of bleeds received
Patients (PUPs)) with severe hemophilia A (factor VIII level Novoeight® at the dose levels described in Tables 1 and 3. A total
≤1%) received at least one dose of Novoeight® as part of either of 1290 bleeds in 127 subjects were treated with Novoeight®. The
routine prophylaxis, on-demand treatment of bleeding episodes, majority of the bleeds 1162 (90%) were of mild/moderate severity. Of
perioperative management of major and minor surgical, dental, these 1290 bleeds, 1140 (88%) were rated excellent or good in their
or other invasive procedures, Immune Tolerance Induction (ITI) or response to treatment with Novoeight® and in 17 (1%) the response
pharmacokinetic evaluation of Novoeight® with more than 140,000 to treatment was unknown. A total of 1100 (85%) of the bleeds
exposure days (corresponding to over 900 patient years). During were resolved with one or two injections of Novoeight®. Routine
prophylaxis treatment subjects received a median of 468 injections prophylactic treatment has been shown to reduce joint bleeding.
of Novoeight® (range 1-1317). [See Clinical Studies (14)]
 Novoeight®, Antihemophilic Factor (Recombinant) 4

Table 5: Pharmacokinetics of Novoeight® in 20 adult and routine prophylaxis and perioperative management in patients with Table 9: Annualized Bleeding Rate (ABRa) for previously
adolescent patients with hemophilia Aa hemophilia A. Three of these trials were performed in PTPs (two treated patients from the extension trial
Clotting Assay Chromogenic Assay trials and one extension trial) and the fourth in PUPs. The analysis Small Older Adolescents
Parameters included 297 exposed subjects: 175 previously treated adolescents children children 12 – <18 Adults
Mean (SD) Mean (SD) or adult subjects from the age of 12 years (≥150 exposure days), 0 – <6 years 6 – <12 years years ≥18 years Total
Incremental Recovery 63 previously treated pediatric subjects below the age of 12 years
0.020 (0.002) 0.028 (0.006) (≥50 exposure days) and 59 PUPs below 6 years of age. Immuno- Nb 27 28 23 128 206
(IU/mL)/(IU/kg)
AUC (IU*h/mL) 14.2 (3.8) 18.7 (5.1) competent patients with severe hemophilia A (factor VIII activity Median (IQR) 1.08 (2.83) 1.57 (3.82) 1.57 (2.34) 1.38 (2.96) 1.39 (2.94)
≤1%) and no history of FVIII inhibitors were eligible for the trials. Mean 1.87 2.90 1.93 2.61 2.45
CL (mL/h/kg) 3.74 (0.95) 2.87 (0.80) Subjects during routine prophylaxis and treatment of bleeds (95%CI) (1.14; 3.09) (2.01; 4.17) (1.33; 2.82) (2.08; 3.28) (2.07; 2.90)
t½ (h) 10.8 (4.9) 12.0 ( 9.3) received Novoeight® at the dose levels described in Tables 1 and
3. Breakthrough bleeds were treated at the investigator’s discretion a: The ABRs were estimated using a Poisson model allowing for overdispersion.
Vss (mL/kg) 53.4 (10.9) 44.3 (28.2)
aiming for a FVIII activity level above 0.5 IU/mL. Treatment during b: Patients dosed every other day or three times weekly
Cmax (IU/mL) 1.07 (0.16) 1.54 (0.29) surgery was at the investigator’s discretion aiming for a FVIII trough Abbreviations: N: number of patients; IQR: interquartile range defined as the difference
MRT (h) 15.4 (6.4) 16.4 (10.1) activity level above 0.5 IU/mL. between the 75th percentile and the 25th percentile; CI: confidence interval.
aDose: 50 IU/kg turoctocog alfa (single i.v. dose) On-demand Treatment and Control of Bleeding Episodes In the trial with previously untreated patients, 56 subjects below
A total of 3153 bleeds in 260 subjects were treated with Novoeight®. 6 years of age received Novoeight® for routine prophylaxis. The
In a single dose PK assessment in adult patients with BMI ≥ 30 kg/ median annualized bleeding rate in the previously untreated patients
m2 in the extension trial [See Clinical Studies (14)], the AUC was The majority of the bleeds (90%) were of mild/moderate severity,
54% of the bleeds were spontaneous and 67% of the bleeds were was 2.9 (IQR 5.4) and the mean (95%CI) was 4.4 (3.3; 5.8).
59% higher and clearance was 33% lower in 6 subjects with BMI ≥
30 kg/m2 compared to subjects with normal BMI, see Table 6. localized in joints. Perioperative Management
An overall assessment of efficacy was performed by the subject A total of 30 surgeries were performed in 25 previously treated
Table 6: Pharmacokinetics of Novoeight® in 6 adult subjects between 8 and 58 years of age, of which 26 were major
(for home treatment) or study site investigator (for treatment
patients with BMI ≥ 30 kg/m2a surgeries (20 orthopaedic, 5 non-orthopaedic and a circumcision),
under medical supervision) using a four-point scale of excellent,
Clotting Assay Chromogenic Assay good, moderate, or none. If the hemostatic response was rated as and 4 were minor (2 dental, 1 circumcision and 1 insertion of
Parameters “excellent” or “good”, the treatment of the bleed was considered a port-a-cath).
Mean (SD) Mean (SD)
success. If the hemostatic response was rated as “moderate or none” The investigator’s ratings of intra- and post-operative quality of
33.35 (2.367) the treatment was considered a failure. Of these 3,153 bleeds, 2,809
BMI (kg/m )
2
hemostasis for these subjects were “excellent” or “good” for all
Range 30.5 – 37.2 (89%) were rated excellent or good in their response to treatment cases.
Incremental Recovery (IU/mL)/(IU/kg) 0.024 (0.01) 0.035 (0.01) with Novoeight®, 274 (9%) were rated as moderate, 25 (0.8%)
AUC (IU*h/mL) 22.64 (5.74) 31.02 (9.78) were rated as having no response and for 45 (1%) the response to 16 HOW SUPPLIED/STORAGE AND HANDLING
treatment was unknown. A total of 2,794 (89%) of the bleeds were How Supplied
CL (mL/h/kg) 2.49 (0.77) 1.94 (0.95) resolved with one or two injections of Novoeight®. • Novoeight® is supplied in packages comprised of a single-use
t½ (h) 12.80 (2.99) 12.40 (3.16) Of the 238 PTPs, 206 patients experienced 2,793 bleeds of which vial containing nominally 250, 500, 1000, 1500, 2000, or 3000
Vss (mL/kg) 39.67 (10.03) 29.79 (7.87) 2,492 (89%) were rated excellent or good in their response to international units (IU) of FVIII potency, a MixPro® pre-filled
Cmax (IU/mL) 1.49 (0.36) 2.03 (0.51) treatment with Novoeight®, 244 (9%) were moderate, 23 (0.8%) diluent syringe containing 0.9% sodium chloride solution, and
were rated as having no response, and for 34 (1%) the response to sterile vial adapter with 25 micrometer filter, which serves as a
MRT (h) 16.84 (4.78) 16.58 (4.26) treatment was unknown. Of the 2,793 reported bleeds observed in needleless reconstitution device.
aDose: 50 IU/kg turoctocog alfa (single i.v. dose) 206 of the patients, 2,504 (90%) of the bleeds were resolved with • The actual amount of FVIII potency in IU is stated on each carton
In a separate pharmacokinetic study, 28 pediatric patients with severe 1–2 injections of Novoeight®. The majority of the bleeds were of and vial.
hemophilia A (14 patients were below 6 years of age and 14 patients mild/moderate severity.
Of the 59 PUPs, 54 patients experienced 360 bleeds of which 317 Presentation
were between 6 to <12 years of age) received a single dose of 50 (Nominal Product Carton
international units/kg Novoeight®. The pharmacokinetic parameters (88%) were rated excellent or good in their response to treatment
with Novoeight®, 30 (8%) were moderate, 2 (0.6%) were rated as Strength) NDC Number Components
of Novoeight® are summarized in Table 7 for both age groups.
having no response, and for 11 (3%) the response to treatment • Novoeight® in single-use vial
Table 7: Pharmacokinetics of Novoeight® in 28 pediatric was unknown. Of the 360 reported bleeds observed in 54 of the [NDC 0169-7829-11]
patients with hemophilia A patients, 290 (81%) of the bleeds were resolved with 1–2 injections 250 International Units NDC 0169 7825 01 • P re-filled sodium chloride diluent in
Clotting Assay Chromogenic Assay of Novoeight®. The majority of the bleeds were of mild/moderate syringe, 4 mL [NDC 0169-7008-98]
Parameters severity and the most frequent bleeds were subcutaneous.
0 to <6 years 6 to <12 years 0 to <6 years 6 to <12 years • V ial adapter
Mean (SD) Mean (SD) Routine Prophylaxis
• Novoeight® in single-use vial
In the two trials, one trial including 150 adult/adolescent subjects (6 [NDC 0169-7851-11]
Incremental Recovery
0.018 (0.007) 0.020 (0.004) 0.022 (0.006) 0.025 (0.006) months duration) and the other trial including 63 pediatric subjects
(IU/mL)/(IU/kg) 500 International Units NDC 0169 7850 01 • P re-filled sodium chloride diluent in
(4 months duration) received Novoeight® for routine prophylaxis
AUC (IU*h/mL) 9.9 (4.1) 11.1 (3.7) 12.2 (4.4) 14.4 (3.5) (Table 8). These previously treated patients received prophylaxis syringe, 4 mL [NDC 0169-7008-98]
CL (mL/h/kg) 6.26 (3.73) 5.02 (1.67) 4.60 (1.75) 3.70 (1.00) treatment every other day or three times weekly at the dose levels • V ial adapter
described in Table 3.
t½ (h) 7.7 (1.8) 8.0 (1.9) 10.0 (1.7) 9.4 (1.5) • Novoeight® in single-use vial
Vss (mL/kg) 57.3 (26.8) 46.8 (10.6) 55.8 (23.7) 41.2 (6.0) Table 8: Annualized Bleeding Rate (ABRa) for previously [NDC 0169-7811-11]
treated patients from the two trials 1000 International Units NDC 0169 7810 01 • P re-filled sodium chloride diluent in
Cmax (IU/mL) 1.00 (0.58) 1.07 (0.35) 1.12 (0.31) 1.25 (0.27)
Small Older Adolescents syringe, 4 mL [NDC 0169-7008-98]
MRT (h) 9.7 (2.5) 9.9 (2.6) 12.1 (1.9) 11.6 (2.3) children children 12 – <18 Adults • V ial adapter
The pharmacokinetic parameters were comparable between younger 0 – <6 years 6 – <12 years years ≥18 years Total
• Novoeight® in single-use vial
(0 to < 6 years) and older (6 to < 12 years) children. The mean Nb 31 32 24 126 213 [NDC 0169-7855-11]
clearance of Novoeight® in younger and older children was 67% and Median (IQR) 2.97 (6.30) 3.65 (8.93) 3.98 (6.21) 3.70 (9.02) 3.67 (8.70)
1500 International Units NDC 0169 7815 01 • Pre-filled sodium chloride diluent in
34% higher (based on per kg body weight) than in adults (3.74 mL/h/
syringe, 4 mL [NDC 0169-7008-98]
kg) when using the clotting assay, and 60% and 29% higher than Mean 4.77 5.93 5.48 6.69 6.24
in adults (2.87 mL/h/kg) when using the chromogenic assay. The (95%CI) (3.07; 7.41) (3.81; 9.22) (3.29; 9.14) (5.36; 8.36) (5.25; 7.41) • Vial adapter
mean half-life of Novoeight® in younger and older children was 29% a: The ABRs were estimated using a Poisson model allowing for overdispersion. • Novoeight® in single-use vial
and 26% shorter than in adults (10.8 hours) when using the clotting b: Patients dosed every other day or three times weekly [NDC 0169-7821-11]
assay, and 16% and 21% shorter than in adults (12 hours) when Abbreviations: N: number of patients; IQR: interquartile range defined as the difference
2000 International Units NDC 0169 7820 01 • Pre-filled sodium chloride diluent in
using the chromogenic assay. between the 75th percentile and the 25th percentile; CI: confidence interval.
syringe, 4 mL [NDC 0169-7008-98]
13 NONCLINICAL TOXICOLOGY One hundred and eighty-eight (188) subjects from the two trials
• Vial adapter
above continued into the extension trial (up to 6 years duration)
13.1 Carcinogenesis, Mutagenesis, Impairment of (Table 9). Additionally, 18 subjects (7 subjects from an on-demand • Novoeight® in single-use vial
Fertility sub-trial and 11 subjects from a pharmacokinetic trial) were included [NDC 0169-7831-11]
Long-term studies in animals to evaluate the carcinogenic potential in the extension trial. These previously treated patients received 3000 International Units NDC 0169 7830 01 • Pre-filled sodium chloride diluent in
of Novoeight®, or studies to determine the effects of Novoeight® on prophylaxis treatment every other day or three times weekly at the syringe, 4 mL [NDC 0169-7008-98]
genotoxicity or fertility have not been performed. An assessment of dose levels described in Table 3.
• Vial adapter
the carcinogenic potential of Novoeight was completed, and no
®

carcinogenic risk from product use has been identified. • The Novoeight® vials are made of glass, closed with a
14 CLINICAL STUDIES chlorobutyl rubber stopper not made with natural rubber latex,
and sealed with an aluminum cap.
Four multi-center, open-label, non-controlled trials have been
conducted to evaluate the safety and efficacy of Novoeight® in
the on-demand treatment and control of breakthrough bleeds,
 Novoeight®, Antihemophilic Factor (Recombinant) 5

• The pre-filled diluent syringes are made of glass, with a

siliconised bromobutyl rubber plunger not made with natural
rubber latex.
• The closed vials and pre-filled diluent syringes are equipped with
a tamper-evident snap-off cap which is made of polypropylene.
Storage and Handling
• Store Novoeight® in the original package in order to protect from
light.
• Store Novoeight® under refrigeration at a temperature of 36°F
to 46°F (2°C to 8°C) for up to 30 months from the date of
manufacture until the expiration date stated on the carton.
During the 30-month shelf life, Novoeight® may be kept at room
temperature:
• up to 86°F (≤30°C) for no longer than 12 months
or
• up to 104°F(≤40°C) for no longer than 3 months
• Clearly record the date when the product was removed from the
refrigerator in the space provided on the outer carton. Do not
return the product to the refrigerator. Do not freeze Novoeight®.
• Use Novoeight® within 4 hours after reconstitution when stored
at <86°F (30°C) or within 2 hours when stored between 86°F
(30°C) to 104°F (40°C). Store the reconstituted product in the
vial.
• Discard any unused reconstituted product.
17 PATIENT COUNSELING INFORMATION
• Advise patients to read the FDA-approved patient labeling
(Patient Information and Instructions for Use).
• Allergic-type hypersensitivity reactions or anaphylaxis are
possible with use of Novoeight®. Inform patients of the early
signs of hypersensitivity reactions including rash, hives, itching,
facial swelling, tightness of the chest and wheezing. Advise
patients to discontinue use of Novoeight® immediately and
contact their physician, and go to the emergency department if
these symptoms occur.
• Advise patients to contact their physician or treatment facility for
further treatment and/or assessment if they experience a lack of
a clinical response to factor VIII replacement therapy, as this may
be a manifestation of an inhibitor.
• Advise patients to consult with their healthcare provider prior to
traveling. While traveling, patients should be advised to bring an
adequate supply of Novoeight® based on their current treatment
regimen.

Version: 7
License Number: 1261
Novoeight® 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.
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
© 2018 Novo Nordisk
US18NEGT00163 12/2018
 Novoeight®, Antihemophilic Factor (Recombinant) 6

Patient Product Information Development of factor VIII inhibitors Novoeight ® vials can be stored in the refrigerator (36°F to 46°F
Novoeight ® (NŌ-vō-eyt) Your body can also make antibodies called “inhibitors” against [2°C to 8°C]) for up to 30 months or up to the expiration date.
Antihemophilic Factor (Recombinant) Novoeight ®, which may stop Novoeight ® from working properly. During the 30 month shelf life, the product may be kept at room
temperature up to 86°F (30°C) for no longer than 12 months, or
If your bleeding is not adequately controlled, it could be due to up to 104°F (40°C) for no longer than 3 months.
Read the Patient Product Information and the the development of factor VIII inhibitors. This should be checked
Instructions For Use that come with Novoeight ® before by your healthcare provider. You might need a higher dose of If you choose to store Novoeight ® at room temperature:
you start taking this medicine and each time you get a Novoeight ® or even a different product to control bleeding. • Note the date that the product is removed from refrigeration
refill. There may be new information. Do not increase the total dose of Novoeight ® to control your on the box.
This Patient Product Information does not take the place of bleeding without consulting your healthcare provider. • Do not return the product to the refrigerator.
talking with your healthcare provider about your medical Use in children • Do not use after 12 months if stored up to 86°F (30°C) or
condition or treatment. If you have questions about Novoeight ® after 3 months if stored up to 104°F (40°C) or the expiration
Novoeight ® can be used in children. Your healthcare provider date listed on the vial, whichever is earlier.
after reading this information, ask your healthcare provider. will decide the dose of Novoeight ® you will receive.
Do not use this medicine after the expiration date which is on the
What is the most important information I need to If you forget to use Novoeight ® outer carton and the vial. The expiration date refers to the last day
know about Novoeight ®? Do not inject a double dose to make up for a forgotten dose. of that month.
Do not attempt to do an infusion yourself unless you Proceed with the next injections as scheduled and continue as After Reconstitution (mixing the dry powder in the vial with
have been taught how by your healthcare provider or advised by your healthcare provider. the diluent):
hemophilia center. If you stop using Novoeight ® The reconstituted Novoeight ® should appear clear to slightly
You must carefully follow your healthcare provider’s instructions If you stop using Novoeight ® you are not protected against unclear without particles.
regarding the dose and schedule for infusing Novoeight ® so that bleeding. Do not stop using Novoeight ® without consulting your The reconstituted Novoeight ® should be used immediately.
your treatment will work best for you. healthcare provider.
If you cannot use the Novoeight ® immediately after it is mixed,
What is Novoeight ®? If you have any further questions on the use of this product, ask it must be used within 4 hours when stored at ≤ 86ºF (30°C)
your healthcare provider. or within 2 hours when stored between 86°F (30°C) to 104°F
Novoeight ® is an injectable medicine used to replace clotting
factor VIII that is missing in patients with hemophilia A. What if I take too much Novoeight ®? (40°C). Store the reconstituted product in the vial.
Hemophilia A is an inherited bleeding disorder that prevents Always take Novoeight ® exactly as your healthcare provider has Keep this medicine out of the sight and out of reach of children.
blood from clotting normally. told you. You should check with your healthcare provider if you What else should I know about Novoeight ® and
Novoeight ® is used to control and prevent bleeding in people are not sure. If you inject more Novoeight ® than recommended, hemophilia A?
with hemophilia A. tell your healthcare provider as soon as possible.
Medicines are sometimes prescribed for purposes other than
Your healthcare provider may give you Novoeight ® when you What are the possible side effects of Novoeight ®? those listed here. Do not use Novoeight ® for a condition for
have surgery. which it is not prescribed. Do not share Novoeight ® with other
Common Side Effects Include:
Novoeight ® is not used to treat von Willebrand Disease. people, even if they have the same symptoms that you have.
• Inhibitors in patients who were not previously treated with
Who should not use Novoeight ®? Factor VIII products
You should not use Novoeight ® if you • Swelling or itching at the location of injection
• Fever
• are allergic to factor VIII or any of the other ingredients of
Novoeight Other Possible Side Effects:
• if you are allergic to hamster proteins You could have an allergic reaction to coagulation factor VIII
Tell your healthcare provider if you are pregnant or nursing products. Call your healthcare provider right away and
because Novoeight ® might not be right for you. stop treatment if you get any of the following signs of
an allergic reaction:
What should I tell my healthcare provider before • rashes including hives
I use Novoeight ®? • difficulty breathing, shortness of breath or wheezing
You should tell your healthcare provider if you • tightness of the chest or throat, difficulty swallowing
• Have or have had any medical conditions. • swelling of the lips and tongue
• Take any medicines, including non-prescription medicines • light-headedness, dizziness or loss of consciousness
and dietary supplements. • pale and cold skin, fast heart beat which may be signs of low
• Are nursing. blood pressure
• Are pregnant or planning to become pregnant. • red or swollen face or hands
• Have been told that you have inhibitors to factor VIII. These are not all of the possible side effects from Novoeight ®.
Ask your healthcare provider for more information. You are
How should I use Novoeight ®? encouraged to report side effects to FDA at 1-800-FDA-1088.
Treatment with Novoeight ® should be started by a healthcare Tell your healthcare provider about any side effect that bothers
provider who is experienced in the care of patients with you or that does not go away.
hemophilia A.
Novoeight ® is given as an injection into the vein.
What are the Novoeight ® dosage strengths?
Novoeight ® comes in six different dosage strengths. The actual
You may infuse Novoeight ® at a hemophilia treatment center, at
number of international units (IU) of factor VIII in the vial will be
your healthcare provider’s office or in your home. You should
imprinted on the label and on the box. The six different strengths
be trained on how to do infusions by your hemophilia treatment For more information about Novoeight ®, please call
are as follows: Novo Nordisk at 1-844-30-EIGHT.
center or healthcare provider. Many people with hemophilia A
learn to infuse the medicine by themselves or with the help of a Dosage strength of approximately 250 IU per vial Revised: 11/2018
family member. Dosage strength of approximately 500 IU per vial Novoeight® is a registered trademark of Novo Nordisk
Your healthcare provider will tell you how much Novoeight ® to Dosage strength of approximately 1000 IU per vial Health Care AG.
use based on your weight, the severity of your hemophilia A, and Dosage strength of approximately 1500 IU per vial Patent Information: http://novonordisk-us.com/patients/
where you are bleeding. products/product-patents.html
Dosage strength of approximately 2000 IU per vial
You may need to have blood tests done after getting Novoeight ® For information about Novoeight ® contact:
to be sure that your blood level of factor VIII is high enough to Dosage strength of approximately 3000 IU per vial
Novo Nordisk Inc.
clot your blood. This is particularly important if you are having Always check the actual dosage strength printed on the label to 800 Scudders Mill Road
major surgery. make sure you are using the strength prescribed by your doctor. Plainsboro, NJ 08536, USA
Your healthcare provider will calculate your dose of Novoeight ® Manufactured by:
How should I store Novoeight ®?
(in international units, IU) depending on your condition and body Novo Nordisk A/S
weight. Prior to Reconstitution: DK-2880 Bagsvaerd, Denmark
Call your healthcare provider right away if your Store in original package in order to protect from light. Do not © 2018 Novo Nordisk
bleeding does not stop after taking Novoeight ®. freeze Novoeight ®. US18NEGT00163 12/2018
 Novoeight®, Antihemophilic Factor (Recombinant) 7

Instructions on how to use Novoeight ® MixPro®

1. Prepare the vial and the syringe A 3. A
 ttach the plunger rod F
READ THESE INSTRUCTIONS CAREFULLY BEFORE USING • Take out the number of and the syringe
NOVOEIGHT®. Novoeight ® packages you need. • Grasp the plunger rod by the
Novoeight ® is supplied as a powder. Before injection • Check the expiry date. wide top end and take it out
(administration) it must be mixed (reconstituted) with the liquid • Check the name and the color of the carton. Don’t touch
diluent supplied in the syringe. The liquid diluent is a sodium of the package, to make sure it the sides or the thread
chloride solution. The mixed Novoeight ® must be injected into contains the correct product. of the plunger rod. If you
your vein (intravenous injection). The equipment in this package • Wash your hands and dry them touch the sides or the thread
is designed to mix and inject Novoeight ®. properly using a clean towel or air germs from your fingers can
You will also need an infusion set (tubing and butterfly needle), dry. be transferred.
sterile alcohol swabs, gauze pads, and bandages. • Take the vial, the vial adapter and • Immediately connect the plunger rod to the syringe by
Don’t use the equipment without proper training the pre-filled syringe out of the turning it clockwise into the rubber plunger inside the
from your doctor or nurse. carton. Leave the plunger rod pre-filled syringe until resistance is felt.
untouched in the carton.
Always wash your hands and ensure that the area
• Bring the vial and the pre-filled • Remove the syringe cap from G
around you is clean.
syringe to room temperature. the pre-filled syringe by bending it
When you prepare and inject medication directly into the veins, You can do this by holding them in down until the perforation breaks.
it is important to use a clean and germ free (aseptic) your hands until they feel as warm as Don’t touch the syringe tip
technique. Improper technique can introduce germs that can your hands. under the syringe cap. If you
infect the blood. touch the syringe tip germs from
Don’t open the equipment until you are ready to use it. • Remove the plastic cap B your fingers can be transferred.
Don’t use the equipment if it has been dropped, or if it from the vial. If the plastic
If the syringe cap is loose
is damaged. Use a new package instead. cap is loose or missing,
or missing, don’t use the
don’t use the vial.
Don’t use the equipment if it is expired. Use a new pre-filled syringe.
• Wipe the rubber stopper
package instead. The expiration date is printed on the outer with a sterile alcohol
carton and on the vial, the vial adapter and the pre-filled syringe. • Screw the pre-filled syringe H
swab and allow it to air dry securely onto the vial adapter until
Don’t use the equipment if you suspect it is for a few seconds before use resistance is felt.
contaminated. Use a new package instead. to ensure that it is as germ
Don’t dispose of any of the items until after you have free as possible.
injected the mixed solution. • Don’t touch the rubber
stopper with your fingers
The equipment is for single use only.
as this can transfer germs.
Content 4. Mix the powder with the I
2. Attach the vial adapter C diluent
The package contains: • Remove the protective • Hold the pre-filled
• Vial with Novoeight ® powder paper from the vial adapter. syringe slightly tilted
• Vial adapter Don’t take the vial with the vial pointing
• Pre-filled syringe with diluent adapter out of the downwards.
• Plunger rod (placed under the syringe) protective cap with your • Push the plunger rod
fingers. If you touch the to inject all the diluent into
Overview spike on the vial adapter the vial.
Vial with NovoEight® powder Vial adapter germs from your fingers can
Plastic cap Protective cap be transferred.
Rubber stopper
(under plastic cap) If the protective paper • Keep the plunger rod J
is not fully sealed or if it pressed down and swirl
is broken, don’t use the the vial gently until all the
Spike (under Protective vial adapter. powder is dissolved.
protective paper) paper Don’t shake the vial as
Pre-filled syringe with diluent Plunger rod • Place the vial on a flat D this will cause foaming.
Syringe tip Rubber plunger Thread Wide and solid surface. • Check the mixed
(under syringe top
cap) Scale end • Turn over the protective solution. It must be clear to
cap, and snap the vial slightly opalescent (slightly
adapter onto the vial. unclear). If you notice
Once attached, don’t visible particles or
Syringe cap remove the vial adapter discoloration, don’t
from the vial. use it. Use a new package
instead.
• Lightly squeeze the E
protective cap with your Novoeight ® is recommended to be used immediately
thumb and index finger after it is mixed. This is because if left, the medicine may no
as shown. Remove the longer be sterile and could cause infections.
protective cap from the If you cannot use the mixed Novoeight ® solution
vial adapter. immediately, it must be used within 4 hours when stored at
Don’t lift the vial ≤ 86ºF (30°C) or within 2 hours when stored between 86°F
adapter from the (30°C) to 104°F (40°C). Store the reconstituted product in
vial when removing the the vial.
protective cap. Do not freeze mixed Novoeight ® solution or store it in
syringes.
Keep mixed Novoeight ® 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.
 Novoeight®, Antihemophilic Factor (Recombinant) 8

• Keep the plunger rod pushed K Disposal M

completely in. • After injection, safely dispose
• Turn the syringe with the vial of all unused Novoeight ® solution,
upside down. the syringe with the infusion set, the
• Stop pushing the plunger rod vial with the vial adapter, and other
and let it move back on its own waste materials in an appropriate
while the mixed solution fills the container for throwing away medical
syringe. waste.
• Pull the plunger rod slightly  Don’t throw it out with the ordinary
downwards to draw the mixed household trash.
solution into the syringe.
• In case you only need part of Don’t disassemble the vial and vial adapter before
the entire vial, use the scale disposal.
on the syringe to see how much
mixed solution you withdraw, Don’t reuse the equipment.
as instructed by your doctor or
nurse. Important information
• While holding the vial upside down, Contact your healthcare provider or local hemophilia
tap the syringe gently to let any treatment center if you experience any problems.
air bubbles rise to the top. For full Prescribing Information please read the other
• Push the plunger rod slowly until insert included in this package.
all air bubbles are gone.

• Unscrew the vial adapter with L

the vial.
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 ®).
The use of these needleless connectors can damage
the connector and affect administration.
To administer Novoeight ® 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 diluent syringe to any
Luer-lock compatible device, please contact Novo
Nordisk at (844) 303-4448.

5. Inject the mixed solution

Novoeight ® is now ready to inject into your vein.
• Do not mix Novoeight ® with any other intravenous infusions
or medications.
• Inject the mixed solution slowly over 2 to 5 minutes as
instructed by your doctor or nurse.
License No: 1261
Injecting the solution via a central venous access device (CVAD)
such as a central venous catheter or subcutaneous port: Revised: 05/2018
• Use a clean and germ free (aseptic) technique. Follow the Novoeight ® and MixPro ® are registered trademarks of
instructions for proper use for your connector and central Novo Nordisk Health Care AG.
venous access device in consultation with your doctor or Patent Information: http://novonordisk-us.com/patients/
nurse. products/product-patents.html
• Injecting into a CVAD may require using a sterile 10 mL Clave® and MicroClave® are registered trademarks of
plastic syringe for withdrawal of the mixed solution and ICU Medical Inc.
injection.
• If necessary, use 0.9% Sodium Chloride Injection, USP to InVision-Plus®, InVision-Plus CS®, Invision-Plus®Junior® are
flush the CVAD line before or after Novoeight ® injection. registered trademarks of RyMed Technologies, Inc.
The peel-off label found on the Novoeight ® vial can be used to Bionector® is a registered trademark of Vygon
record the lot number. For information about Novoeight ® contact:
Novo Nordisk Inc.
800 Scudders Mill Road
Plainsboro, NJ 08536, USA
Manufactured by:
Novo Nordisk A/S
DK-2880 Bagsvaerd, Denmark
© 2018 Novo Nordisk
US18NEGT00163 12/2018