Novo Nordisk NovoLog User manual

1
——— WARNINGS AND PRECAUTIONS ———
•
Hypoglycemia is the most common adverse effect of insulin
therapy. Glucose monitoring is recommended for all patients with
diabetes. Any change of insulin dose should be made cautiously
and only under medical supervision (5.1, 5.2).
•
Insulin, particularly when given intravenously or in settings of
poor glycemic control, can cause hypokalemia. Use caution in
patients predisposed to hypokalemia (5.3).
•
Like all insulins, NovoLog®requirements may be reduced in
patients with renal impairment or hepatic impairment (5.4, 5.5).
•
Severe, life-threatening, generalized allergy, including
anaphylaxis, may occur with insulin products, including
NovoLog®(5.6).
•
Fluid retention and heart failure can occur with concomitant use
of thiazolidinediones (TZDs), which are PPAR-gamma agonists,
and insulin, including NovoLog®(5.10).
——— ADVERSE REACTIONS ———
Adverse reactions observed with NovoLog®include hypoglycemia,
allergic reactions, local injection site reactions, lipodystrophy, rash
and pruritus (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.
——— DRUG INTERACTIONS ———
•
The following may increase the blood-glucose-lowering effect
and susceptibility to hypoglycemia: oral antidiabetic products,
pramlintide, ACE inhibitors, disopyramide, fibrates, fluoxetine,
monoamine oxidase inhibitors, propoxyphene, salicylates,
somatostatin analogs, sulfonamide antibiotics (7).
•
The following may reduce the blood-glucose-lowering effect:
corticosteroids, niacin, danazol, diuretics, sympathomimetic
agents (e.g., epinephrine, salbutamol, terbutaline), isoniazid,
phenothiazine derivatives, somatropin, thyroid hormones,
estrogens, progestogens (e.g., in oral contraceptives), atypical
antipsychotics (7).
•
Beta-blockers, clonidine, lithium salts, and alcohol may either
potentiate or weaken the blood-glucose-lowering effect of insulin
(7).
•
Pentamidine may cause hypoglycemia, which may sometimes be
followed by hyperglycemia (7).
•
The signs of hypoglycemia may be reduced or absent in patients
taking sympatholytic products such as beta-blockers, clonidine,
guanethidine, and reserpine (7).
——— USE IN SPECIFIC POPULATIONS ———
•
Pediatric: Has not been studied in children with type 2 diabetes.
Has not been studied in children with type 1 diabetes <2 years of
age (8.4).
See 17 for PATIENT COUNSELING INFORMATION and
FDA approved patient labeling.
Revised: 4/2014
FULL PRESCRIBING INFORMATION: CONTENTS*
1 INDICATIONS AND USAGE
1.1 Treatment of Diabetes Mellitus
2 DOSAGE AND ADMINISTRATION
2.1 Dosing
2.2 Subcutaneous Injection
2.3 Continuous Subcutaneous Insulin Infusion (CSII) by External
Pump
2.4 Intravenous Use
3DOSAGE FORMS AND STRENGTHS
4CONTRAINDICATIONS
5 WARNINGS AND PRECAUTIONS
5.1 Administration
5.2 Hypoglycemia
5.3 Hypokalemia
5.4 Renal Impairment
5.5 Hepatic Impairment
5.6 Hypersensitivity and Allergic Reactions
5.7 Antibody Production
5.8 Mixing of Insulins
5.9 Continuous Subcutaneous Insulin Infusion by External Pump
5.10 Fluid retention and heart failure with concomitant use of
PPAR-gamma agonists
6 ADVERSE REACTIONS
7DRUG INTERACTIONS
8USE IN SPECIFIC POPULATIONS
8.1 Pregnancy
8.3 Nursing Mothers
8.4 Pediatric Use
8.5 Geriatric Use
10 OVERDOSAGE
11 DESCRIPTION
12 CLINICAL PHARMACOLOGY
12.1 Mechanism of Action
12.2 Pharmacodynamics
12.3 Pharmacokinetics
13 NONCLINICAL TOXICOLOGY
13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility
13.2 Animal Toxicology and/or Pharmacology
14 CLINICAL STUDIES
14.1 Subcutaneous Daily Injections
14.2 Continuous Subcutaneous Insulin Infusion (CSII) by External
Pump
14.3 Intravenous Administration of NovoLog®
16 HOW SUPPLIED/STORAGE AND HANDLING
16.1 How Supplied
16.2 Recommended Storage
17 PATIENT COUNSELING INFORMATION
17.1 Physician Instructions
17.2 Patients Using Pumps
17.3 FDA Approved Patient Labeling
* Sections or subsections omitted from the full prescribing information are
not listed.
HIGHLIGHTS OF PRESCRIBING INFORMATION
These highlights do not include all the information
needed to use NovoLog®safely and effectively. See full
prescribing information for NovoLog®.
NovoLog®(insulin aspart [rDNA origin] injection)
solution for subcutaneous use
Initial U.S. Approval: 2000
——— INDICATIONS AND USAGE ———
•NovoLog®is an insulin analog indicated to improve glycemic
control in adults and children with diabetes mellitus (1.1).
——— DOSAGE AND ADMINISTRATION ———
•The dosage of NovoLog®must be individualized.
•
Subcutaneous injection: NovoLog®should generally be given
immediately (within 5-10 minutes) prior to the start of a meal
(2.2).
•
Use in pumps: Change the NovoLog®in the reservoir at least
every 6 days, change the infusion set, and the infusion set
insertion site at least every 3 days. NovoLog®should not be
mixed with other insulins or with a diluent when it is used in
the pump (2.3).
•
Intravenous use: NovoLog®should be used at concentrations
from 0.05 U/mL to 1.0 U/mL insulin aspart in infusion systems
using polypropylene infusion bags. NovoLog®has been shown
to be stable in infusion fluids such as 0.9% sodium chloride
(2.4).
——— DOSAGE FORMS AND STRENGTHS ———
Each presentation contains 100 Units of insulin aspart per mL
(U-100)
•
10 mL vials (3)
•3 mL PenFill®cartridges for the 3 mL PenFill®cartridge device (3)
•3 mL NovoLog®FlexPen®(3)
•
3 mL NovoLog®FlexTouch®(3)
——— CONTRAINDICATIONS ———
•
Do not use during episodes of hypoglycemia (4).
•
Do not use in patients with hypersensitivity to NovoLog®or one
of its excipients.

2 NovoLog®(insulin aspart [rDNA origin] injection)
5.8 Mixing of Insulins
•Mixing NovoLog®with NPH human insulin immediately before injection
attenuates the peak concentration of NovoLog®, without significantly
affecting the time to peak concentration or total bioavailability of NovoLog®.
If NovoLog®is mixed with NPH human insulin, NovoLog®should be drawn
into the syringe first, and the mixture should be injected immediately after
mixing.
•The efficacy and safety of mixing NovoLog®with insulin preparations
produced by other manufacturers have not been studied.
•Insulin mixtures should not be administered intravenously.
5.9 Continuous Subcutaneous Insulin Infusion by External Pump
When used in an external subcutaneous insulin infusion pump,
NovoLog®should not be mixed with any other insulin or diluent.
When using NovoLog®in an external insulin pump, the NovoLog®-specific
information should be followed (e.g., in-use time, frequency of changing
infusion sets) because NovoLog®-specific information may differ from general
pump manual instructions.
Pump or infusion set malfunctions or insulin degradation can lead to a rapid
onset of hyperglycemia and ketosis because of the small subcutaneous depot
of insulin. This is especially pertinent for rapid-acting insulin analogs that are
more rapidly absorbed through skin and have a shorter duration of action.
Prompt identification and correction of the cause of hyperglycemia or ketosis
is necessary. Interim therapy with subcutaneous injection may be required [see
Dosage and Administration (2.3), Warnings and Precautions (5.8, 5.9), How
Supplied/Storage and Handling (16.2), and Patient Counseling Information
(17.2)].
NovoLog®should not be exposed to temperatures greater than 37°C (98.6°F).
NovoLog®that will be used in a pump should not be mixed with
other insulin or with a diluent [see Dosage and Administration (2.3),
Warnings and Precautions (5.8, 5.9), How Supplied/Storage and Handling
(16.2), and Patient Counseling Information (17.2)].
5.10 Fluid retention and heart failure with concomitant use of
PPAR-gamma agonists
Thiazolidinediones (TZDs), which are peroxisome proliferator-activated
receptor (PPAR)-gamma agonists, can cause dose-related fluid retention,
particularly when used in combination with insulin. Fluid retention may lead to
or exacerbate heart failure. Patients treated with insulin, including NovoLog®,
and a PPAR-gamma agonist should be observed for signs and symptoms
of heart failure. If heart failure develops, it should be managed according
to current standards of care, and discontinuation or dose reduction of the
PPAR-gamma agonist must be considered.
6 ADVERSE REACTIONS
Clinical Trial Experience
Because clinical trials are conducted under widely varying designs, the adverse
reaction rates reported in one clinical trial may not be easily compared to those
rates reported in another clinical trial, and may not reflect the rates actually
observed in clinical practice.
•Hypoglycemia
Hypoglycemia is the most commonly observed adverse reaction in patients
using insulin, including NovoLog®[see Warnings and Precautions (5)].
•Insulin initiation and glucose control intensification
Intensification or rapid improvement in glucose control has been
associated with a transitory, reversible ophthalmologic refraction disorder,
worsening of diabetic retinopathy, and acute painful peripheral neuropathy.
However, long-term glycemic control decreases the risk of diabetic
retinopathy and neuropathy.
•Lipodystrophy
Long-term use of insulin, including NovoLog®, can cause lipodystrophy at
the site of repeated insulin injections or infusion. Lipodystrophy includes
lipohypertrophy (thickening of adipose tissue) and lipoatrophy (thinning of
adipose tissue), and may affect insulin absorption. Rotate insulin injection
or infusion sites within the same region to reduce the risk of lipodystrophy.
•Weight gain
Weight gain can occur with some insulin therapies, including NovoLog®,
and has been attributed to the anabolic effects of insulin and the decrease
in glucosuria.
•Peripheral Edema
Insulin may cause sodium retention and edema, particularly if previously
poor metabolic control is improved by intensified insulin therapy.
•Frequencies of adverse drug reactions
The frequencies of adverse drug reactions during NovoLog®clinical trials
in patients with type 1 diabetes mellitus and type 2 diabetes mellitus are
listed in the tables below.
Table 1: Treatment-Emergent Adverse Events in Patients with Type
1 Diabetes Mellitus (Adverse events with frequency ≥5% and
occurring more frequently with NovoLog®compared to human
regular insulin are listed)
NovoLog®+ NPH
N= 596
Human Regular Insulin + NPH
N= 286
Preferred Term N(%) N(%)
Hypoglycemia* 448 75% 205 72%
Headache 70 12% 28 10%
Injury accidental 65 11% 29 10%
Nausea 43 7% 13 5%
Diarrhea 28 5% 93%
*Hypoglycemia is defined as an episode of blood glucose concentration <45 mg/dL,
with or without symptoms. See Section 14 for the incidence of serious hypoglycemia in
the individual clinical trials.
of action, a longer acting insulin should also be used in patients with type 1
diabetes and may also be needed in patients with type 2 diabetes. Glucose
monitoring is recommended for all patients with diabetes and is particularly
important for patients using external pump infusion therapy.
Any change of insulin dose should be made cautiously and only under medical
supervision. Changing from one insulin product to another or changing the
insulin strength may result in the need for a change in dosage. As with all
insulin preparations, the time course of NovoLog®action may vary in different
individuals or at different times in the same individual and is dependent on many
conditions, including the site of injection, local blood supply, temperature, and
physical activity. Patients who change their level of physical activity or meal
plan may require adjustment of insulin dosages. Insulin requirements may be
altered during illness, emotional disturbances, or other stresses.
Patients using continuous subcutaneous insulin infusion pump therapy must
be trained to administer insulin by injection and have alternate insulin therapy
available in case of pump failure.
Needles, NovoLog®FlexPen®and NovoLog®FlexTouch®must not
be shared.
5.2 Hypoglycemia
Hypoglycemia is the most common adverse effect of all insulin therapies,
including NovoLog®. Severe hypoglycemia may lead to unconsciousness and/
or convulsions and may result in temporary or permanent impairment of brain
function or death. Severe hypoglycemia requiring the assistance of another
person and/or parenteral glucose infusion or glucagon administration has
been observed in clinical trials with insulin, including trials with NovoLog®.
The timing of hypoglycemia usually reflects the time-action profile of the
administered insulin formulations [see Clinical Pharmacology (12)]. Other
factors such as changes in food intake (e.g., amount of food or timing of
meals), injection site, exercise, and concomitant medications may also alter
the risk of hypoglycemia [see Drug Interactions (7)]. As with all insulins, use
caution in patients with hypoglycemia unawareness and in patients who may
be predisposed to hypoglycemia (e.g., patients who are fasting or have erratic
food intake). The patient’s ability to concentrate and react may be impaired as
a result of hypoglycemia. This may present a risk in situations where these
abilities are especially important, such as driving or operating other machinery.
Rapid changes in serum glucose levels may induce symptoms of
hypoglycemia in persons with diabetes, regardless of the glucose value. Early
warning symptoms of hypoglycemia may be different or less pronounced under
certain conditions, such as longstanding diabetes, diabetic nerve disease, use
of medications such as beta-blockers, or intensified diabetes control [see
Drug Interactions (7)]. These situations may result in severe hypoglycemia
(and, possibly, loss of consciousness) prior to the patient’s awareness of
hypoglycemia. Intravenously administered insulin has a more rapid onset
of action than subcutaneously administered insulin, requiring more close
monitoring for hypoglycemia.
5.3 Hypokalemia
All insulin products, including NovoLog®, cause a shift in potassium from the
extracellular to intracellular space, possibly leading to hypokalemia that, if left
untreated, may cause respiratory paralysis, ventricular arrhythmia, and death.
Use caution in patients who may be at risk for hypokalemia (e.g., patients using
potassium-lowering medications, patients taking medications sensitive to serum
potassium concentrations, and patients receiving intravenously administered
insulin).
5.4 Renal Impairment
As with other insulins, the dose requirements for NovoLog®may be reduced in
patients with renal impairment [see Clinical Pharmacology (12.3)].
5.5 Hepatic Impairment
As with other insulins, the dose requirements for NovoLog®may be reduced in
patients with hepatic impairment [see Clinical Pharmacology (12.3)].
5.6 Hypersensitivity and Allergic Reactions
Local Reactions - As with other insulin therapy, patients may experience
redness, swelling, or itching at the site of NovoLog®injection. These reactions
usually resolve in a few days to a few weeks, but in some occasions, may
require discontinuation of NovoLog®. In some instances, these reactions may
be related to factors other than insulin, such as irritants in a skin cleansing
agent or poor injection technique. Localized reactions and generalized
myalgias have been reported with injected metacresol, which is an excipient
in NovoLog®.
Systemic Reactions - Severe, life-threatening, generalized allergy, including
anaphylaxis, may occur with any insulin product, including NovoLog®.
Anaphylactic reactions with NovoLog®have been reported post-approval.
Generalized allergy to insulin may also cause whole body rash (including
pruritus), dyspnea, wheezing, hypotension, tachycardia, or diaphoresis. In
controlled clinical trials, allergic reactions were reported in 3 of 735 patients
(0.4%) treated with regular human insulin and 10 of 1394 patients (0.7%)
treated with NovoLog®. In controlled and uncontrolled clinical trials, 3 of 2341
(0.1%) NovoLog®-treated patients discontinued due to allergic reactions.
5.7 Antibody Production
Increases in anti-insulin antibody titers that react with both human insulin and
insulin aspart have been observed in patients treated with NovoLog®. Increases
in anti-insulin antibodies are observed more frequently with NovoLog®than
with regular human insulin. Data from a 12-month controlled trial in patients
with type 1 diabetes suggest that the increase in these antibodies is transient,
and the differences in antibody levels between the regular human insulin and
insulin aspart treatment groups observed at 3 and 6 months were no longer
evident at 12 months. In this study these antibodies did not appear to cause
deterioration in glycemic control or necessitate increases in insulin dose.
In rare cases, the presence of such insulin antibodies may necessitate
adjustment of the insulin dose in order to correct a tendency towards
hyperglycemia or hypoglycemia.
FULL PRESCRIBING INFORMATION
1 INDICATIONS AND USAGE
1.1 Treatment of Diabetes Mellitus
NovoLog®is an insulin analog indicated to improve glycemic control in adults
and children with diabetes mellitus.
2 DOSAGE AND ADMINISTRATION
2.1 Dosing
NovoLog®is an insulin analog with an earlier onset of action than regular
human insulin. The dosage of NovoLog®must be individualized. NovoLog®
given by subcutaneous injection should generally be used in regimens with an
intermediate or long-acting insulin [see Warnings and Precautions (5), How
Supplied/Storage and Handling (16.2)]. The total daily insulin requirement
may vary and is usually between 0.5 to 1.0 units/kg/day. When used in a meal-
related subcutaneous injection treatment regimen, 50 to 70% of total insulin
requirements may be provided by NovoLog®and the remainder provided
by an intermediate-acting or long-acting insulin. Because of NovoLog®’s
comparatively rapid onset and short duration of glucose lowering activity,
some patients may require more basal insulin and more total insulin to prevent
pre-meal hyperglycemia when using NovoLog®than when using human
regular insulin.
Do not use NovoLog®that is viscous (thickened) or cloudy; use only if it is
clear and colorless. NovoLog®should not be used after the printed expiration
date.
2.2 Subcutaneous Injection
NovoLog®should be administered by subcutaneous injection in the abdominal
region, buttocks, thigh, or upper arm. Because NovoLog®has a more rapid
onset and a shorter duration of activity than human regular insulin, it should
be injected immediately (within 5-10 minutes) before a meal. Injection sites
should be rotated within the same region to reduce the risk of lipodystrophy.
As with all insulins, the duration of action of NovoLog®will vary according to
the dose, injection site, blood flow, temperature, and level of physical activity.
NovoLog®may be diluted with Insulin Diluting Medium for NovoLog®for
subcutaneous injection. Diluting one part NovoLog®to nine parts diluent will
yield a concentration one-tenth that of NovoLog®(equivalent to U-10). Diluting
one part NovoLog®to one part diluent will yield a concentration one-half that
of NovoLog®(equivalent to U-50).
2.3 Continuous Subcutaneous Insulin Infusion (CSII) by External
Pump
NovoLog®can also be infused subcutaneously by an external insulin pump
[see Warnings and Precautions (5.8, 5.9), How Supplied/Storage and Handling
(16.2)]. Diluted insulin should not be used in external insulin pumps. Because
NovoLog®has a more rapid onset and a shorter duration of activity than human
regular insulin, pre-meal boluses of NovoLog®should be infused immediately
(within 5-10 minutes) before a meal. Infusion sites should be rotated within
the same region to reduce the risk of lipodystrophy. The initial programming
of the external insulin infusion pump should be based on the total daily
insulin dose of the previous regimen. Although there is significant interpatient
variability, approximately 50% of the total dose is usually given as meal-related
boluses of NovoLog®and the remainder is given as a basal infusion. Change
the NovoLog®in the reservoir at least every 6 days, change the
infusion sets and the infusion set insertion site at least every 3
days.
The following insulin pumps†have been used in NovoLog®clinical or in vitro
studies conducted by Novo Nordisk, the manufacturer of NovoLog®:
•Medtronic Paradigm®512 and 712
•MiniMed 508
•Disetronic®D-TRON®and H-TRON®
Before using a different insulin pump with NovoLog®, read the pump label to
make sure the pump has been evaluated with NovoLog®.
2.4 Intravenous Use
NovoLog®can be administered intravenously under medical supervision for
glycemic control with close monitoring of blood glucose and potassium levels
to avoid hypoglycemia and hypokalemia [see Warnings and Precautions (5),
How Supplied/Storage and Handling (16.2)]. For intravenous use, NovoLog®
should be used at concentrations from 0.05 U/mL to 1.0 U/mL insulin aspart
in infusion systems using polypropylene infusion bags. NovoLog®has been
shown to be stable in infusion fluids such as 0.9% sodium chloride.
Inspect NovoLog®for particulate matter and discoloration prior to parenteral
administration.
3 DOSAGE FORMS AND STRENGTHS
NovoLog®is available in the following package sizes: each presentation
contains 100 units of insulin aspart per mL (U-100).
•10 mL vials
•3 mL PenFill cartridges for the 3 mL PenFill®cartridge delivery device
(with or without the addition of a NovoPen®3 PenMate®) with NovoFine®
disposable needles
•3 mL NovoLog®FlexPen®
•3 mL NovoLog®FlexTouch®
4 CONTRAINDICATIONS
NovoLog®is contraindicated
•during episodes of hypoglycemia
•in patients with hypersensitivity to NovoLog®or one of its excipients.
5 WARNINGS AND PRECAUTIONS
5.1 Administration
NovoLog®has a more rapid onset of action and a shorter duration of activity
than regular human insulin. An injection of NovoLog®should immediately be
followed by a meal within 5-10 minutes. Because of NovoLog®’s short duration

3 NovoLog®(insulin aspart [rDNA origin] injection)
A double-blind, randomized, two-way cross-over study in 16 patients with
type 1 diabetes demonstrated that intravenous infusion of NovoLog®resulted
in a blood glucose profile that was similar to that after intravenous infusion
with regular human insulin. NovoLog®or human insulin was infused until
the patient’s blood glucose decreased to 36 mg/dL, or until the patient
demonstrated signs of hypoglycemia (rise in heart rate and onset of sweating),
defined as the time of autonomic reaction (R) (see Figure 3).
180
162
144
126
108
90
72
54
36
18
0
0 10 R–20 R R+40 R+50
R+60
Time (min)
Mean Blood Glucose (mg/dL)
R–10 R+10 R+20 R+30
Note: The slashes on the mean profile indicate a jump on the time axis
Figure 3. Mean blood glucose profiles following intravenous
infusion of NovoLog®(hatched curve) and regular human insulin
(solid curve) in 16 patients with type 1 diabetes. R represents the
time of autonomic reaction.
12.3 Pharmacokinetics
The single substitution of the amino acid proline with aspartic acid at position
B28 in NovoLog®reduces the molecule’s tendency to form hexamers as
observed with regular human insulin. NovoLog®is, therefore, more rapidly
absorbed after subcutaneous injection compared to regular human insulin.
In a randomized, double-blind, crossover study 17 healthy Caucasian male
subjects between 18 and 40 years of age received an intravenous infusion of
either NovoLog®or regular human insulin at 1.5 mU/kg/min for 120 minutes.
The mean insulin clearance was similar for the two groups with mean values
of 1.2 l/h/kg for the NovoLog®group and 1.2 l/h/kg for the regular human
insulin group.
Bioavailability and Absorption - NovoLog®has a faster absorption, a faster
onset of action, and a shorter duration of action than regular human insulin
after subcutaneous injection (see Figure 2 and Figure 4). The relative
bioavailability of NovoLog®compared to regular human insulin indicates that
the two insulins are absorbed to a similar extent.
80
60
40
20
0
012345
6
Time (h)
Free serum insulin (mU/L)
Figure 4. Serial mean serum free insulin concentration collected
up to 6 hours following a single pre-meal dose of NovoLog®
(solid curve) or regular human insulin (hatched curve) injected
immediately before a meal in 22 patients with type 1 diabetes.
In studies in healthy volunteers (total n=107) and patients with type 1 diabetes
(total n=40), NovoLog®consistently reached peak serum concentrations
approximately twice as fast as regular human insulin. The median time to
maximum concentration in these trials was 40 to 50 minutes for NovoLog®
versus 80 to 120 minutes for regular human insulin. In a clinical trial in patients
with type 1 diabetes, NovoLog®and regular human insulin, both administered
subcutaneously at a dose of 0.15 U/kg body weight, reached mean
maximum concentrations of 82 and 36 mU/L, respectively. Pharmacokinetic/
pharmacodynamic characteristics of insulin aspart have not been established
in patients with type 2 diabetes.
The intra-individual variability in time to maximum serum insulin concentration
for healthy male volunteers was significantly less for NovoLog®than for
regular human insulin. The clinical significance of this observation has not
been established.
In a clinical study in healthy non-obese subjects, the pharmacokinetic
differences between NovoLog®and regular human insulin described above,
were observed independent of the site of injection (abdomen, thigh, or upper
arm).
Distribution and Elimination - NovoLog®has low binding to plasma proteins
(<10%), similar to that seen with regular human insulin. After subcutaneous
administration in normal male volunteers (n=24), NovoLog®was more rapidly
eliminated than regular human insulin with an average apparent half-life of 81
minutes compared to 141 minutes for regular human insulin.
Specific Populations
Children and Adolescents - The pharmacokinetic and pharmacodynamic
properties of NovoLog®and regular human insulin were evaluated in a
single dose study in 18 children (6-12 years, n=9) and adolescents (13-17
years [Tanner grade ≥2], n=9) with type 1 diabetes. The relative differences
in pharmacokinetics and pharmacodynamics in children and adolescents with
type 1 diabetes between NovoLog®and regular human insulin were similar to
those in healthy adult subjects and adults with type 1 diabetes.
Gender - In healthy volunteers, no difference in insulin aspart levels was
seen between men and women when body weight differences were taken into
8.3 Nursing Mothers
It is unknown whether insulin aspart is excreted in human milk. Use of
NovoLog®is compatible with breastfeeding, but women with diabetes who are
lactating may require adjustments of their insulin doses.
8.4 Pediatric Use
NovoLog®is approved for use in children for subcutaneous daily injections
and for subcutaneous continuous infusion by external insulin pump.
NovoLog®has not been studied in pediatric patients younger than 2 years of
age. NovoLog®has not been studied in pediatric patients with type 2 diabetes.
Please see Section 14 CLINICAL STUDIES for summaries of clinical studies.
8.5 Geriatric Use
Of the total number of patients (n= 1,375) treated with NovoLog®in 3 controlled
clinical studies, 2.6% (n=36) were 65 years of age or over. One-half of these
patients had type 1 diabetes (18/1285) and the other half had type 2 diabetes
(18/90). The HbA1c response to NovoLog®, as compared to human insulin, did
not differ by age, particularly in patients with type 2 diabetes. Additional studies
in larger populations of patients 65 years of age or over are needed to permit
conclusions regarding the safety of NovoLog®in elderly compared to younger
patients. Pharmacokinetic/pharmacodynamic studies to assess the effect of
age on the onset of NovoLog®action have not been performed.
10 OVERDOSAGE
Excess insulin administration may cause hypoglycemia and, particularly when
given intravenously, hypokalemia. Mild episodes of hypoglycemia usually
can be treated with oral glucose. Adjustments in drug dosage, meal patterns,
or exercise, may be needed. More severe episodes with coma, seizure, or
neurologic impairment may be treated with intramuscular/subcutaneous
glucagon or concentrated intravenous glucose. Sustained carbohydrate intake
and observation may be necessary because hypoglycemia may recur after
apparent clinical recovery. Hypokalemia must be corrected appropriately.
11 DESCRIPTION
NovoLog®(insulin aspart [rDNA origin] injection) is a rapid-acting human
insulin analog used to lower blood glucose. NovoLog®is homologous with
regular human insulin with the exception of a single substitution of the amino
acid proline by aspartic acid in position B28, and is produced by recombinant
DNA technology utilizing Saccharomyces cerevisiae (baker’s yeast). Insulin
aspart has the empirical formula C256H381N65079S6and a molecular weight
of 5825.8.
Figure 1. Structural formula of insulin aspart.
NovoLog®is a sterile, aqueous, clear, and colorless solution, that contains
insulin aspart 100 Units/mL, glycerin 16 mg/mL, phenol 1.50 mg/mL,
metacresol 1.72 mg/mL, zinc 19.6 mcg/mL, disodium hydrogen phosphate
dihydrate 1.25 mg/mL, sodium chloride 0.58 mg/mL and water for injection.
NovoLog®has a pH of 7.2-7.6. Hydrochloric acid 10% and/or sodium
hydroxide 10% may be added to adjust pH.
12 CLINICAL PHARMACOLOGY
12.1 Mechanism of Action
The primary activity of NovoLog®is the regulation of glucose metabolism.
Insulins, including NovoLog®, bind to the insulin receptors on muscle and fat
cells and lower blood glucose by facilitating the cellular uptake of glucose and
simultaneously inhibiting the output of glucose from the liver.
12.2 Pharmacodynamics
Studies in normal volunteers and patients with diabetes demonstrated that
subcutaneous administration of NovoLog®has a more rapid onset of action
than regular human insulin.
In a study in patients with type 1 diabetes (n=22), the maximum glucose-
lowering effect of NovoLog®occurred between 1 and 3 hours after
subcutaneous injection (see Figure 2). The duration of action for NovoLog®
is 3 to 5 hours. The time course of action of insulin and insulin analogs such
as NovoLog®may vary considerably in different individuals or within the same
individual. The parameters of NovoLog®activity (time of onset, peak time and
duration) as designated in Figure 2 should be considered only as general
guidelines. The rate of insulin absorption and onset of activity is affected by the
site of injection, exercise, and other variables [see Warnings and Precautions
(5.1)].
300
200
100
50
0
012345
6
Time (h)
Serum glucose (mg/dL)
250
150
Figure 2. Serial mean serum glucose collected up to 6 hours
following a single pre-meal dose of NovoLog®(solid curve) or
regular human insulin (hatched curve) injected immediately
before a meal in 22 patients with type 1 diabetes.
Table 2: Treatment-Emergent Adverse Events in Patients with
Type 2 Diabetes Mellitus (except for hypoglycemia, adverse
events with frequency ≥5% and occurring more frequently with
NovoLog®compared to human regular insulin are listed)
NovoLog®+ NPH
N= 91
Human Regular Insulin + NPH
N= 91
N(%) N(%)
Hypoglycemia* 25 27% 33 36%
Hyporeflexia 10 11% 67%
Onychomycosis 910% 55%
Sensory disturbance 89% 67%
Urinary tract infection 78% 67%
Chest pain 55% 33%
Headache 55% 33%
Skin disorder 55% 22%
Abdominal pain 55% 11%
Sinusitis 55% 11%
*Hypoglycemia is defined as an episode of blood glucose concentration <45 mg/dL,
with or without symptoms. See Section 14 for the incidence of serious hypoglycemia in
the individual clinical trials.
Postmarketing Data
The following additional adverse reactions have been identified during
postapproval use of NovoLog®. Because these adverse reactions are reported
voluntarily from a population of uncertain size, it is generally not possible to
reliably estimate their frequency. Medication errors in which other insulins
have been accidentally substituted for NovoLog®have been identified during
postapproval use [see Patient Counseling Information (17)].
7 DRUG INTERACTIONS
A number of substances affect glucose metabolism and may require insulin
dose adjustment and particularly close monitoring.
•The following are examples of substances that may increase the
blood-glucose-lowering effect and susceptibility to hypoglycemia:
oral antidiabetic products, pramlintide, ACE inhibitors, disopyramide,
fibrates, fluoxetine, monoamine oxidase (MAO) inhibitors, propoxyphene,
salicylates, somatostatin analog (e.g., octreotide), sulfonamide antibiotics.
•The following are examples of substances that may reduce the blood-
glucose-lowering effect: corticosteroids, niacin, danazol, diuretics,
sympathomimetic agents (e.g., epinephrine, salbutamol, terbutaline),
isoniazid, phenothiazine derivatives, somatropin, thyroid hormones,
estrogens, progestogens (e.g., in oral contraceptives), atypical
antipsychotics.
•Beta-blockers, clonidine, lithium salts, and alcohol may either potentiate or
weaken the blood-glucose-lowering effect of insulin.
•Pentamidine may cause hypoglycemia, which may sometimes be followed
by hyperglycemia.
•The signs of hypoglycemia may be reduced or absent in patients taking
sympatholytic products such as beta-blockers, clonidine, guanethidine,
and reserpine.
8 USE IN SPECIFIC POPULATIONS
8.1 Pregnancy
Pregnancy Category B. All pregnancies have a background risk of birth
defects, loss, or other adverse outcome regardless of drug exposure. This
background risk is increased in pregnancies complicated by hyperglycemia
and may be decreased with good metabolic control. It is essential for patients
with diabetes or history of gestational diabetes to maintain good metabolic
control before conception and throughout pregnancy. Insulin requirements
may decrease during the first trimester, generally increase during the second
and third trimesters, and rapidly decline after delivery. Careful monitoring of
glucose control is essential in these patients. Therefore, female patients should
be advised to tell their physician if they intend to become, or if they become
pregnant while taking NovoLog®.
An open-label, randomized study compared the safety and efficacy of
NovoLog®(n=157) versus regular human insulin (n=165) in 322 pregnant
women with type 1 diabetes. Two-thirds of the enrolled patients were already
pregnant when they entered the study. Because only one-third of the patients
enrolled before conception, the study was not large enough to evaluate the risk
of congenital malformations. Both groups achieved a mean HbA1c of ~ 6%
during pregnancy, and there was no significant difference in the incidence of
maternal hypoglycemia.
Subcutaneous reproduction and teratology studies have been performed
with NovoLog®and regular human insulin in rats and rabbits. In these
studies, NovoLog®was given to female rats before mating, during mating,
and throughout pregnancy, and to rabbits during organogenesis. The effects
of NovoLog®did not differ from those observed with subcutaneous regular
human insulin. NovoLog®, like human insulin, caused pre- and post-
implantation losses and visceral/skeletal abnormalities in rats at a dose of 200
U/kg/day (approximately 32 times the human subcutaneous dose of 1.0 U/
kg/day, based on U/body surface area) and in rabbits at a dose of 10 U/kg/
day (approximately three times the human subcutaneous dose of 1.0 U/kg/day,
based on U/body surface area). The effects are probably secondary to maternal
hypoglycemia at high doses. No significant effects were observed in rats at a
dose of 50 U/kg/day and in rabbits at a dose of 3 U/kg/day. These doses are
approximately 8 times the human subcutaneous dose of 1.0 U/kg/day for rats
and equal to the human subcutaneous dose of 1.0 U/kg/day for rabbits, based
on U/body surface area.

4 NovoLog®(insulin aspart [rDNA origin] injection)
account. There was no significant difference in efficacy noted (as assessed by
HbA1c) between genders in a trial in patients with type 1 diabetes.
Obesity - A single subcutaneous dose of 0.1 U/kg NovoLog®was administered
in a study of 23 patients with type 1 diabetes and a wide range of body mass
index (BMI, 22-39 kg/m2). The pharmacokinetic parameters, AUC and Cmax,
of NovoLog®were generally unaffected by BMI in the different groups – BMI
19-23 kg/m2(N=4); BMI 23-27 kg/m2(N=7); BMI 27-32 kg/m2(N=6) and BMI
>32 kg/m2(N=6). Clearance of NovoLog®was reduced by 28% in patients with
BMI >32 kg/m2compared to patients with BMI <23 kg/m2.
Renal Impairment - Some studies with human insulin have shown increased
circulating levels of insulin in patients with renal failure. A single subcutaneous
dose of 0.08 U/kg NovoLog®was administered in a study to subjects with
either normal (N=6) creatinine clearance (CLcr) (>80 ml/min) or mild (N=7;
CLcr = 50-80 ml/min), moderate (N=3; CLcr = 30-50 ml/min) or severe (but
not requiring hemodialysis) (N=2; CLcr = <30 ml/min) renal impairment. In
this small study, there was no apparent effect of creatinine clearance values
on AUC and Cmax of NovoLog®. Careful glucose monitoring and dose
adjustments of insulin, including NovoLog®, may be necessary in patients
with renal dysfunction [see Warnings and Precautions (5.4)].
Hepatic Impairment - Some studies with human insulin have shown increased
circulating levels of insulin in patients with liver failure. A single subcutaneous
dose of 0.06 U/kg NovoLog®was administered in an open-label, single-dose
study of 24 subjects (N=6/group) with different degree of hepatic impairment
(mild, moderate and severe) having Child-Pugh Scores ranging from 0
(healthy volunteers) to 12 (severe hepatic impairment). In this small study,
there was no correlation between the degree of hepatic failure and any
NovoLog®pharmacokinetic parameter. Careful glucose monitoring and dose
adjustments of insulin, including NovoLog®, may be necessary in patients with
hepatic dysfunction [see Warnings and Precautions (5.5)].
The effect of age, ethnic origin, pregnancy and smoking on the pharmacokinetics
and pharmacodynamics of NovoLog®has not been studied.
13 NONCLINICAL TOXICOLOGY
13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility
Standard 2-year carcinogenicity studies in animals have not been performed to
evaluate the carcinogenic potential of NovoLog®. In 52-week studies, Sprague-
Dawley rats were dosed subcutaneously with NovoLog®at 10, 50, and 200 U/
kg/day (approximately 2, 8, and 32 times the human subcutaneous dose of
1.0 U/kg/day, based on U/body surface area, respectively). At a dose of 200
U/kg/day, NovoLog®increased the incidence of mammary gland tumors in
females when compared to untreated controls. The incidence of mammary
tumors for NovoLog®was not significantly different than for regular human
insulin. The relevance of these findings to humans is not known. NovoLog®
was not genotoxic in the following tests: Ames test, mouse lymphoma cell
forward gene mutation test, human peripheral blood lymphocyte chromosome
aberration test, in vivo micronucleus test in mice, and in ex vivo UDS test in rat
liver hepatocytes. In fertility studies in male and female rats, at subcutaneous
doses up to 200 U/kg/day (approximately 32 times the human subcutaneous
dose, based on U/body surface area), no direct adverse effects on male and
female fertility, or general reproductive performance of animals was observed.
13.2 Animal Toxicology and/or Pharmacology
In standard biological assays in mice and rabbits, one unit of NovoLog®
has the same glucose-lowering effect as one unit of regular human insulin.
In humans, the effect of NovoLog®is more rapid in onset and of shorter
duration, compared to regular human insulin, due to its faster absorption after
subcutaneous injection (see Section 12 CLINICAL PHARMACOLOGY Figure
2 and Figure 4).
14 CLINICAL STUDIES
14.1 Subcutaneous Daily Injections
Two six-month, open-label, active-controlled studies were conducted to
compare the safety and efficacy of NovoLog®to Novolin®R in adult patients
with type 1 diabetes. Because the two study designs and results were similar,
data are shown for only one study (see Table 3). NovoLog®was administered
by subcutaneous injection immediately prior to meals and regular human
insulin was administered by subcutaneous injection 30 minutes before meals.
NPH insulin was administered as the basal insulin in either single or divided
daily doses. Changes in HbA1c and the incidence rates of severe hypoglycemia
(as determined from the number of events requiring intervention from a third
party) were comparable for the two treatment regimens in this study (Table 3)
as well as in the other clinical studies that are cited in this section. Diabetic
ketoacidosis was not reported in any of the adult studies in either treatment
group.
Table 3. Subcutaneous NovoLog®Administration in Type 1
Diabetes (24 weeks; n=882)
NovoLog®+ NPH Novolin®R + NPH
N596 286
Baseline HbA1c (%)* 7.9 ± 1.1 8.0 ± 1.2
Change from Baseline HbA1c (%) -0.1 ± 0.8 0.0 ± 0.8
Treatment Difference in HbA1c, Mean
(95% confidence interval) -0.2 (-0.3, -0.1)
Baseline insulin dose (IU/kg/24 hours)* 0.7 ± 0.2 0.7 ± 0.2
End-of-Study insulin dose (IU/kg/24 hours)* 0.7 ± 0.2 0.7 ± 0.2
Patients with severe hypoglycemia (n, %)** 104 (17%) 54 (19%)
Baseline body weight (kg)*
Weight Change from baseline (kg)*
75.3 ± 14.5
0.5 ± 3.3
75.9 ± 13.1
0.9 ± 2.9
*Values are Mean ± SD
**Severe hypoglycemia refers to hypoglycemia associated with central nervous system
symptoms and requiring the intervention of another person or hospitalization.
A 24-week, parallel-group study of children and adolescents with type 1
diabetes (n = 283) aged 6 to 18 years compared two subcutaneous multiple-
dose treatment regimens: NovoLog®(n = 187) or Novolin®R (n = 96). NPH
insulin was administered as the basal insulin. NovoLog®achieved glycemic
control comparable to Novolin®R, as measured by change in HbA1c (Table 4)
and both treatment groups had a comparable incidence of hypoglycemia.
Subcutaneous administration of NovoLog®and regular human insulin have
also been compared in children with type 1 diabetes (n=26) aged 2 to 6 years
with similar effects on HbA1c and hypoglycemia.
Table 4. Pediatric Subcutaneous Administration of NovoLog®in
Type 1 Diabetes (24 weeks; n=283)
NovoLog®+ NPH Novolin®R + NPH
N187 96
Baseline HbA1c (%)* 8.3 ± 1.2 8.3 ± 1.3
Change from Baseline HbA1c (%) 0.1 ± 1.0 0.1 ± 1.1
Treatment Difference in HbA1c, Mean
(95% confidence interval) 0.1 (-0.5, 0.1)
Baseline insulin dose (IU/kg/24 hours)* 0.4 ± 0.2 0.6 ± 0.2
End-of-Study insulin dose (IU/kg/24 hours)* 0.4 ± 0.2 0.7 ± 0.2
Patients with severe hypoglycemia (n, %)** 11 (6%) 9 (9%)
Diabetic ketoacidosis (n, %) 10 (5%) 2 (2%)
Baseline body weight (kg)*
Weight Change from baseline (kg)*
50.6 ± 19.6
2.7 ± 3.5
48.7 ± 15.8
2.4 ± 2.6
*Values are Mean ± SD
**Severe hypoglycemia refers to hypoglycemia associated with central nervous system
symptoms and requiring the intervention of another person or hospitalization.
One six-month, open-label, active-controlled study was conducted to compare
the safety and efficacy of NovoLog®to Novolin®R in patients with type 2
diabetes (Table 5). NovoLog®was administered by subcutaneous injection
immediately prior to meals and regular human insulin was administered
by subcutaneous injection 30 minutes before meals. NPH insulin was
administered as the basal insulin in either single or divided daily doses.
Changes in HbA1c and the rates of severe hypoglycemia (as determined from
the number of events requiring intervention from a third party) were comparable
for the two treatment regimens.
Table 5. Subcutaneous NovoLog®Administration in Type 2
Diabetes (6 months; n=176)
NovoLog®+ NPH Novolin®R + NPH
N90 86
Baseline HbA1c (%)* 8.1 ± 1.2 7.8 ± 1.1
Change from Baseline HbA1c (%) -0.3 ± 1.0 -0.1 ± 0.8
Treatment Difference in HbA1c, Mean
(95% confidence interval) -0.1 (-0.4, -0.1)
Baseline insulin dose (IU/kg/24 hours)* 0.6 ± 0.3 0.6 ± 0.3
End-of-Study insulin dose (IU/kg/24 hours)* 0.7 ± 0.3 0.7 ± 0.3
Patients with severe hypoglycemia (n, %)** 9 (10%) 5 (8%)
Baseline body weight (kg)*
Weight Change from baseline (kg)*
88.4 ± 13.3
1.2 ± 3.0
85.8 ± 14.8
0.4 ± 3.1
*Values are Mean ± SD
**Severe hypoglycemia refers to hypoglycemia associated with central nervous system
symptoms and requiring the intervention of another person or hospitalization.
14.2 Continuous Subcutaneous Insulin Infusion (CSII) by External
Pump
Two open-label, parallel design studies (6 weeks [n=29] and 16 weeks
[n=118]) compared NovoLog®to buffered regular human insulin (Velosulin) in
adults with type 1 diabetes receiving a subcutaneous infusion with an external
insulin pump. The two treatment regimens had comparable changes in HbA1c
and rates of severe hypoglycemia.
Table 6. Adult Insulin Pump Study in Type 1 Diabetes (16 weeks;
n=118)
NovoLog®Buffered human insulin
N59 59
Baseline HbA1c (%)* 7.3 ± 0.7 7.5 ± 0.8
Change from Baseline HbA1c (%) 0.0 ± 0.5 0.2 ± 0.6
Treatment Difference in HbA1c, Mean
(95% confidence interval) 0.3 (-0.1, 0.4)
Baseline insulin dose (IU/kg/24 hours)* 0.7 ± 0.8 0.6 ± 0.2
End-of-Study insulin dose (IU/kg/24 hours)* 0.7 ± 0.7 0.6 ± 0.2
Patients with severe hypoglycemia (n, %)** 1 (2%) 2 (3%)
Baseline body weight (kg)*
Weight Change from baseline (kg)*
77.4 ± 16.1
0.1 ± 3.5
74.8 ± 13.8
-0.0 ± 1.7
*Values are Mean ± SD
**Severe hypoglycemia refers to hypoglycemia associated with central nervous system
symptoms and requiring the intervention of another person or hospitalization.
A randomized, 16-week, open-label, parallel design study of children and
adolescents with type 1 diabetes (n=298) aged 4-18 years compared two
subcutaneous infusion regimens administered via an external insulin pump:
NovoLog®(n=198) or insulin lispro (n=100). These two treatments resulted
in comparable changes from baseline in HbA1c and comparable rates of
hypoglycemia after 16 weeks of treatment (see Table 7).
Table 7. Pediatric Insulin Pump Study in Type 1 Diabetes (16
weeks; n=298)
NovoLog®Lispro
N198 100
Baseline HbA1c (%)* 8.0 ± 0.9 8.2 ± 0.8
Change from Baseline HbA1c (%) -0.1 ± 0.8 -0.1 ± 0.7
Treatment Difference in HbA1c, Mean
(95% confidence interval) -0.1 (-0.3, 0.1)
Baseline insulin dose (IU/kg/24 hours)* 0.9 ± 0.3 0.9 ± 0.3
End-of-Study insulin dose (IU/kg/24 hours)* 0.9 ± 0.2 0.9 ± 0.2
Patients with severe hypoglycemia (n, %)** 19 (10%) 8 (8%)
Diabetic ketoacidosis (n, %) 1 (0.5%) 0 (0)
Baseline body weight (kg)*
Weight Change from baseline (kg)*
54.1 ± 19.7
1.8 ± 2.1
55.5 ± 19.0
1.6 ± 2.1
*Values are Mean ± SD
**Severe hypoglycemia refers to hypoglycemia associated with central nervous system
symptoms and requiring the intervention of another person or hospitalization.
An open-label, 16-week parallel design trial compared pre-prandial NovoLog®
injection in conjunction with NPH injections to NovoLog®administered
by continuous subcutaneous infusion in 127 adults with type 2 diabetes.
The two treatment groups had similar reductions in HbA1c and rates of
severe hypoglycemia (Table 8) [see Indications and Usage (1), Dosage and
Administration (2), Warnings and Precautions (5) and How Supplied/Storage
and Handling (16.2)].
Table 8. Pump Therapy in Type 2 Diabetes (16 weeks; n=127)
NovoLog®pump NovoLog®+ NPH
N66 61
Baseline HbA1c (%)* 8.2 ± 1.4 8.0 ± 1.1
Change from Baseline HbA1c (%) -0.6 ± 1.1 -0.5 ± 0.9
Treatment Difference in HbA1c, Mean
(95% confidence interval) 0.1 (0.4, 0.3)
Baseline insulin dose (IU/kg/24 hours)* 0.7 ± 0.3 0.8 ± 0.5
End-of-Study insulin dose (IU/kg/24 hours)* 0.9 ± 0.4 0.9 ± 0.5
Baseline body weight (kg)*
Weight Change from baseline (kg)*
96.4 ± 17.0
1.7 ± 3.7
96.9 ± 17.9
0.7 ± 4.1
*Values are Mean ± SD
14.3 Intravenous Administration of NovoLog®
See Section 12.2 CLINICAL PHARMACOLOGY/Pharmacodynamics.
16 HOW SUPPLIED/STORAGE AND HANDLING
16.1 How Supplied
NovoLog®is available in the following package sizes: each presentation
containing 100 Units of insulin aspart per mL (U-100).
10 mL vials NDC 0169-7501-11
3 mL PenFill®cartridges* NDC 0169-3303-12
3 mL NovoLog®FlexPen®NDC 0169-6339-10
3 mL NovoLog®FlexTouch®NDC 0169-6338-10
*NovoLog®PenFill®cartridges are designed for use with Novo Nordisk 3 mL
PenFill®cartridge compatible insulin delivery devices (with or without the
addition of a NovoPen®3 PenMate®) with NovoFine®disposable needles.
FlexPen®and FlexTouch®can be used with NovoFine®or NovoTwist®
disposable needles.
16.2 Recommended Storage
Unused NovoLog®should be stored in a refrigerator between 2° and 8°C
(36° to 46°F). Do not store in the freezer or directly adjacent to the refrigerator
cooling element. Do not freeze NovoLog®and do not use NovoLog®
if it has been frozen. NovoLog®should not be drawn into a syringe and
stored for later use.
Vials: After initial use a vial may be kept at temperatures below 30°C (86°F)
for up to 28 days, but should not be exposed to excessive heat or light. Opened
vials may be refrigerated.
Unpunctured vials can be used until the expiration date printed on the label if
they are stored in a refrigerator. Keep unused vials in the carton so they will stay
clean and protected from light.
PenFill cartridges or NovoLog®FlexPen®and NovoLog®
FlexTouch®:
Once a cartridge or NovoLog®FlexPen®or NovoLog®FlexTouch®is
punctured, it should be kept at temperatures below 30°C (86°F) for up to 28
days, but should not be exposed to excessive heat or sunlight. A NovoLog®
FlexPen®or NovoLog®FlexTouch®or cartridge in use must NOT be stored
in the refrigerator. Keep the NovoLog®FlexPen®or NovoLog®FlexTouch®
and all PenFill cartridges away from direct heat and sunlight. Unpunctured
NovoLog®FlexPen®or NovoLog®FlexTouch®and PenFill cartridges can
be used until the expiration date printed on the label if they are stored in a
refrigerator. Keep unused NovoLog®FlexPen®or NovoLog®FlexTouch®and
PenFill cartridges in the carton so they will stay clean and protected from light.
Always remove the needle after each injection and store the 3
mL PenFill cartridge delivery device or NovoLog®FlexPen®or
NovoLog®FlexTouch®without a needle attached. This prevents
contamination and/or infection, or leakage of insulin, and will
ensure accurate dosing. Always use a new needle for each
injection to prevent contamination.

5
NovoLog®(insulin aspart [rDNA origin] injection)
To avoid insulin degradation, infusion set occlusion, and loss
of the preservative (metacresol), insulin in the reservoir should
be replaced at least every 6 days; infusion sets and infusion set
insertion sites should be changed at least every 3 days.
Insulin exposed to temperatures higher than 37°C (98.6°F)
should be discarded. The temperature of the insulin may exceed ambient
temperature when the pump housing, cover, tubing, or sport case is exposed
to sunlight or radiant heat. Infusion sites that are erythematous, pruritic, or
thickened should be reported to medical personnel, and a new site selected
because continued infusion may increase the skin reaction and/or alter
the absorption of NovoLog®. Pump or infusion set malfunctions or insulin
degradation can lead to hyperglycemia and ketosis in a short time because
of the small subcutaneous depot of insulin. This is especially pertinent for
rapid-acting insulin analogs that are more rapidly absorbed through skin and
have shorter duration of action. These differences are particularly relevant when
patients are switched from multiple injection therapy. Prompt identification and
correction of the cause of hyperglycemia or ketosis is necessary. Problems
include pump malfunction, infusion set occlusion, leakage, disconnection
or kinking, and degraded insulin. Less commonly, hypoglycemia from pump
malfunction may occur. If these problems cannot be promptly corrected,
patients should resume therapy with subcutaneous insulin injection and
contact their physician [see Dosage and Administration (2), Warnings and
Precautions (5) and How Supplied/Storage and Handling (16.2)].
17.3 FDA Approved Patient Labeling
See separate leaflet.
Pump:
NovoLog®in the pump reservoir should be discarded after at least every 6
days of use or after exposure to temperatures that exceed 37°C (98.6°F). The
infusion set and the infusion set insertion site should be changed at least every
3 days.
Summary of Storage Conditions:
The storage conditions are summarized in the following table:
Table 9. Storage conditions for vial, PenFill cartridges, NovoLog®
FlexPen®, and NovoLog®FlexTouch®
NovoLog®
presentation
Not in-use (unopened)
Room Temperature
(below 30°C)
Not in-use
(unopened)
Refrigerated
In-use (opened)
Room Temperature
(below 30°C)
10 mL vial 28 days Until
expiration date
28 days
(refrigerated/room
temperature)
3 mL PenFill®
cartridges
28 days Until
expiration date
28 days
(Do not refrigerate)
3 mL NovoLog®
FlexPen®28 days Until expiration date
28 days
(Do not refrigerate)
3 mL NovoLog®
FlexTouch®28 days Until expiration date
28 days
(Do not refrigerate)
Storage of Diluted NovoLog®
NovoLog®diluted with Insulin Diluting Medium for NovoLog®to a
concentration equivalent to U-10 or equivalent to U-50 may remain in patient
use at temperatures below 30°C (86°F) for 28 days.
Storage of NovoLog®in Infusion Fluids
Infusion bags prepared as indicated under Dosage and Administration (2) are
stable at room temperature for 24 hours. Some insulin will be initially adsorbed
to the material of the infusion bag.
17 PATIENT COUNSELING INFORMATION
[See FDA Approved Patient Labeling (17.3)]
17.1 Physician Instructions
Maintenance of normal or near-normal glucose control is a treatment goal
in diabetes mellitus and has been associated with a reduction in diabetic
complications. Patients should be informed about potential risks and benefits
of NovoLog®therapy including the possible adverse reactions. Patients should
also be offered continued education and advice on insulin therapies, injection
technique, life-style management, regular glucose monitoring, periodic
glycosylated hemoglobin testing, recognition and management of hypo-
and hyperglycemia, adherence to meal planning, complications of insulin
therapy, timing of dose, instruction in the use of injection or subcutaneous
infusion devices, and proper storage of insulin. Patients should be informed
that frequent, patient-performed blood glucose measurements are needed to
achieve optimal glycemic control and avoid both hyper- and hypoglycemia.
Patients should receive proper training on how to use NovoLog®. Instruct
patients that when injecting NovoLog®, they must press and hold down the
dose button until the dose counter shows 0 and then keep the needle in the
skin and count slowly to 6. When the dose counter returns to 0, the prescribed
dose is not completely delivered until 6 seconds later. If the needle is removed
earlier, they may see a stream of insulin coming from the needle tip. If so, the
full dose will not be delivered (a possible under-dose may occur by as much as
20%), and they should increase the frequency of checking their blood glucose
levels and possible additional insulin administration may be necessary.
• If 0 does not appear in the dose counter after continuously pressing the
dose button, the patient may have used a blocked needle. In this case they
would not have received any insulin – even though the dose counter has
moved from the original dose that was set.
• If the patient did have a blocked needle, instruct them to change the needle
as described in Section 5 of the Instructions for Use and repeat all steps in
the IFU starting with Section 1: Prepare your pen with a new needle. Make
sure the patient selects the full dose needed.
The patient’s ability to concentrate and react may be impaired as a result of
hypoglycemia. This may present a risk in situations where these abilities are
especially important, such as driving or operating other machinery. Patients
who have frequent hypoglycemia or reduced or absent warning signs of
hypoglycemia should be advised to use caution when driving or operating
machinery.
Accidental substitutions between NovoLog®and other insulin products have
been reported. Patients should be instructed to always carefully check that they
are administering the appropriate insulin to avoid medication errors between
NovoLog®and any other insulin. The written prescription for NovoLog®
should be written clearly, to avoid confusion with other insulin
products, for example, NovoLog®Mix 70/30.
17.2 Patients Using Pumps
Patients using external pump infusion therapy should be trained in intensive
insulin therapy with multiple injections and in the function of their pump and
pump accessories.
The following insulin pumps†have been used in NovoLog®clinical or in vitro
studies conducted by Novo Nordisk, the manufacturer of NovoLog®:
•Medtronic Paradigm®512 and 712
•MiniMed 508
•Disetronic®D-TRON®and H-TRON®
Before using another insulin pump with NovoLog®, read the pump label to
make sure the pump has been evaluated with NovoLog®.
NovoLog®is recommended for use in any reservoir and infusion sets that
are compatible with insulin and the specific pump. Please see recommended
reservoir and infusion sets in the pump manual.
Rx only
Date of Issue: April 25, 2014
Version: 22
Novo Nordisk®, NovoLog®, NovoPen®3, PenFill®, Novolin®, FlexPen®,
FlexTouch®, PenMate®, NovoFine®, and NovoTwist®are registered
trademarks of Novo Nordisk A/S.
NovoLog®is covered by US Patent Nos. 5,618,913, 5,866,538, and other
patents pending.
FlexPen®is covered by US Patent Nos. RE 41,956, 6,004,297, RE 43,834,
and other patents pending.
FlexTouch®pen is covered by US Patent Nos. 7,686,786, 6,899,699, and
other patents pending.
PenFill®is covered by US Patent No. 5,693,027.
†The brands listed are the registered trademarks of their respective owners
and are not trademarks of Novo Nordisk A/S.
Manufactured by:
Novo Nordisk A/S
DK-2880 Bagsvaerd, Denmark
For information about NovoLog®contact:
Novo Nordisk Inc.
800 Scudders Mill Road
Plainsboro, New Jersey 08536
1-800-727-6500
www.novonordisk-us.com
© 2002-2014 Novo Nordisk
0714-00022409-1 7/2014

6 NovoLog®(insulin aspart [rDNA origin] injection)
Patient Information
NovoLog®(NŌ-vō-log)
(insulin aspart [rDNA origin] injection)
What is NovoLog®?
• NovoLog®is a man-made insulin that is used to control high blood sugar in adults and children with diabetes mellitus.
Who should not take NovoLog®?
Do not take NovoLog®if you:
• are having an episode of low blood sugar (hypoglycemia).
• have an allergy to NovoLog®or any of the ingredients in NovoLog®.
Before taking NovoLog®, tell your healthcare provider about all your medical conditions including, if you are:
• pregnant, planning to become pregnant, or are breastfeeding.
• taking new prescription or over-the-counter medicines, vitamins, or herbal supplements.
Before you start taking NovoLog®, talk to your healthcare provider about low blood sugar and how to manage it.
How should I take NovoLog®?
• Read the Instructions for Use that come with your NovoLog®.
• Take NovoLog®exactly as your healthcare provider tells you to.
• NovoLog®starts acting fast. You should eat a meal within 5 to 10 minutes after you take your dose of NovoLog®.
• Know the type and strength of insulin you take. Do not change the type of insulin you take unless your healthcare provider tells you to. The amount of insulin
and the best time for you to take your insulin may need to change if you take different types of insulin.
• Check your blood sugar levels. Ask your healthcare provider what your blood sugars should be and when you should check your blood sugar levels.
• Do not share your NovoLog®FlexPen®, FlexTouch®or needles with another person. You may give another person an infection or get an infection from
them.
What should I avoid while taking NovoLog®?
While taking NovoLog®do not:
• Drive or operate heavy machinery, until you know how NovoLog®affects you.
• Drink alcohol or use prescription or over-the-counter medicines that contain alcohol.
What are the possible side effects of NovoLog®?
NovoLog®may cause serious side effects that can lead to death, including:
Low blood sugar (hypoglycemia). Signs and symptoms that may indicate low blood sugar include:
• dizziness or light-headedness •blurred vision •anxiety, irritability, or mood changes
• sweating •slurred speech •hunger
• confusion •shakiness
• headache •fast heart beat
Your insulin dose may need to change because of:
• change in level of physical activity or exercise •increased stress •change in diet
•weight gain or loss •illness
Other common side effects of NovoLog®may include:
• low potassium in your blood (hypokalemia), reactions at the injection site, itching, rash, serious allergic reactions (whole body reactions), skin thickening or
pits at the injection site (lipodystrophy), weight gain, and swelling of your hands and feet.
Get emergency medical help if you have:
• trouble breathing, shortness of breath, fast heartbeat, swelling of your face, tongue, or throat, sweating, extreme drowsiness, dizziness, confusion.
These are not all the possible side effects of NovoLog®. Call your doctor for medical advice about side effects. You may report side effects to FDA at
1-800-FDA-1088.
General information about the safe and effective use of NovoLog®.
Medicines are sometimes prescribed for purposes other than those listed in a Patient Information leaflet. You can ask your pharmacist or healthcare provider
for information about NovoLog®that is written for health professionals. Do not use NovoLog®for a condition for which it was not prescribed. Do not give
NovoLog®to other people, even if they have the same symptoms that you have. It may harm them.
What are the ingredients in NovoLog®?
Active Ingredient: insulin aspart (rDNA origin)
Inactive Ingredients: glycerin, phenol, metacresol, zinc, disodium hydrogen phosphate dihydrate, sodium chloride and water for injection
Manufactured by:
Novo Nordisk A/S
DK-2880 Bagsvaerd, Denmark
For more information, go to www.novonordisk-us.com or call 1-800-727-6500.
This Patient Information has been approved by the U.S. Food and Drug Administration
Revised: 10/2013
For more information go to www.novologflextouch.com
NovoLog®is a registered trademark of Novo Nordisk A/S.
© 2002-2014 Novo Nordisk
0714-00022409-1 7/2014

7 NovoLog®(insulin aspart [rDNA origin] injection)
Instructions for Use
NovoLog®
(N Ō -v ō -log)
(insulin aspart [rDNA origin] injection)
10 mL vial (100 Units/mL, U-100)
Read this Instructions for Use before you start taking NovoLog®
and each time you get a refill. There may be new information. This
information does not take the place of talking to your healthcare
provider about your medical condition or your treatment.
Supplies you will need
to give your NovoLog®
injection:
• 10 mL NovoLog®vial
• insulin syringe and needle
•alcohol swab
Preparing your NovoLog®
dose:
• Wash your hands with soap
and water.
• Before you start to prepare
your injection, check the
NovoLog®label to make
sure that you are taking the
right type of insulin. This is
especially important if you use
more than 1 type of insulin.
• NovoLog®should look clear
and colorless. Do not use NovoLog®if it is thick, cloudy, or is
colored.
• Do not use NovoLog®past the expiration date printed on the
label.
Step 1: Pull off the tamper
resistant cap (See Figure A).
Step 2: Wipe the rubber
stopper with an alcohol swab
(See Figure B).
(Figure A Figure B)
Step 3: Hold the syringe with
the needle pointing up. Pull down
on the plunger until the black tip
reaches the line for the number
of units for your prescribed dose
(See Figure C).
(Figure C)
Step 4: Push the needle
through the rubber stopper of the
NovoLog®vial (See Figure D).
(Figure D)
Step 5: Push the plunger all
the way in. This puts air into the
NovoLog®vial (See Figure E).
(Figure E)
Step 6: Turn the NovoLog®
vial and syringe upside down
and slowly pull the plunger
down until the black tip is a
few units past the line for your
dose (See Figure F).
(Figure F)
• If there are air bubbles,
tap the syringe gently a
few times to let any air
bubbles rise to the top
(See Figure G).
(Figure G)
Step 7: Slowly push
the plunger up until the
black tip reaches the line
for your NovoLog®dose
(See Figure H).
(Figure H)
Step 8: Check the syringe to make sure you have the right dose
of NovoLog®.
Step 9: Pull the syringe out
of the vial’s rubber stopper
(See Figure I).
(Figure I)
Giving your Injection:
•Inject your NovoLog®exactly as your healthcare provider has
shown you. Your healthcare provider should tell you if you
need to pinch the skin before injecting.
• NovoLog®can be injected under the skin (subcutaneously)
of your stomach area, buttocks, upper legs or upper arms,
infused in an insulin pump, or given through a needle in your
arm (intravenously) by your healthcare provider.
• If you inject NovoLog®, change (rotate) your injection sites
within the area you choose for each dose. Do not use the
same injection site for each injection.
• If you use NovoLog®in an insulin pump, you should change
your insertion site every 3 days. The insulin in the reservoir
should be changed at least every 6 days even if you have not
used all of the insulin.
• If you use NovoLog®in an insulin pump, see your insulin
pump manual for instructions or talk to your healthcare
provider.
• NPH insulin is the only type of insulin that can be mixed
with NovoLog®. Do not mix NovoLog®with any other type
of insulin.
• NovoLog®should only be mixed with NPH insulin if
it is going to be injected right away under your skin
(subcutaneously).
• NovoLog®should be drawn up into the syringe before you
draw up your NPH insulin.
• Talk to your healthcare provider if you are not sure about the
right way to mix NovoLog®and NPH insulin.
Step 10: Choose your injection
site and wipe the skin with an
alcohol swab. Let the injection site
dry before you inject your dose
(See Figure J).
(Figure J)
Back
Front
Step 11: Insert the needle into
your skin. Push down on the
plunger to inject your dose (See
Figure K). Needle should
remain in the skin for at least
6 seconds to make sure you
have injected all the insulin.
(Figure K)
Step 12: Pull the needle out of
your skin. After that, you may see a
drop of NovoLog®at the needle tip.
This is normal and does not affect
the dose you just received (See
Figure L).
• If you see blood after you take
the needle out of your skin, press
the injection site lightly with
a piece of gauze or an alcohol
swab. Do not rub the area.
(Figure L)
After your injection:
• Do not recap the needle. Recapping the needle can lead to a needle
stick injury.
• Throw away empty insulin vials, used syringes, and needles in a
sharps container or some type of hard plastic or metal container
with a screw on cap such as a detergent bottle or empty coffee can.
Check with your healthcare provider about the right way to throw
away the container. There may be local or state laws about how to
throw away used syringes and needles. Do not throw away used
syringes and needles in household trash or recycling bins.
How should I store NovoLog®?
Do not freeze NovoLog®. Do not use NovoLog®if it has been
frozen.
• Keep NovoLog®away from heat or light.
• Store opened and unopened NovoLog®vials in the refrigerator at
36°F to 46°F (2°C to 8°C). Opened NovoLog®vials can also be
stored out of the refrigerator below 86°F (30°C).
• Unopened vials may be used until the expiration date printed on the
label, if they are kept in the refrigerator.
• Opened NovoLog®vials should be thrown away after 28 days, even
if they still have insulin left in them.
General information about the safe and effective use of
NovoLog®
• Always use a new syringe and needle for each injection.
• Do not share syringes or needles.
• Keep NovoLog®vials, syringes, and needles out of the reach of
children.
This Instructions for Use has been approved by the U.S. Food and
Drug Administration.
Tamper
resistant cap
Rubber
stopper
(Under cap)
Vial
Revised: March 2013
NovoLog®is a registered trademark of Novo Nordisk A/S.
NovoLog®is covered by US Patent Nos. 5,618,913, 5,866,538, and other
patents pending.
Manufactured by:
Novo Nordisk A/S
DK-2880 Bagsvaerd, Denmark
For information about NovoLog®contact:
Novo Nordisk Inc.
800 Scudders Mill Road
Plainsboro, New Jersey 08536
1-800-727-6500
www.novonordisk-us.com
© 2002-2014 Novo Nordisk
0714-00022409-1 7/2014

8 NovoLog®(insulin aspart [rDNA origin] injection)
I. Insert the needle into your skin.
Inject the dose by pressing the push-button all the way in until the 0
lines up with the pointer (see diagram I). Be careful only to push the
button when injecting.
Turning the dose selector will not inject insulin.
J. Keep the needle in the skin for at least 6 seconds, and keep the push-
button pressed all the way in until the needle has been pulled out from
the skin (see diagram J). This will make sure that the full dose has
been given.
You may see a drop of NovoLog®at the needle tip. This is normal and
has no effect on the dose you just received. If blood appears after you
take the needle out of your skin, press the injection site lightly with a
finger. Do not rub the area.
After the injection
Do not recap the needle. Recapping can lead to a needle stick injury. Remove the needle from the
NovoLog®FlexPen®after each injection. This helps to prevent infection, leakage of insulin, and will
help to make sure you inject the right dose of insulin.
Put the needle and any empty NovoLog®FlexPen®or any used NovoLog®FlexPen®still
containing insulin in a sharps container or some type of hard plastic or metal container with a
screw top such as a detergent bottle or empty coffee can. These containers should be sealed
and thrown away the right way. Check with your healthcare provider about the right way to throw
away used syringes and needles. There may be local or state laws about how to throw away
used needles and syringes. Do not throw away used needles and syringes in household trash or
recycling bins.
The NovoLog®FlexPen®prevents the cartridge from being completely emptied. It is designed to
deliver 300 units.
K. Put the pen cap on the NovoLog®FlexPen®and store the
NovoLog®FlexPen®without the needle attached (see diagram K).
L. Function Check
If your NovoLog®FlexPen®is not working the right way, follow the
steps below:
• Screw on a new NovoFine®needle.
• Remove the big outer needle cap and the inner needle cap.
• Do an airshot as described in “Giving the airshot before each
injection”.
• Put the big outer needle cap onto the needle. Do not put on the
inner needle cap.
• Turn the dose selector so the dose indicator window shows 20 units.
• Hold the NovoLog®FlexPen®so the needle is pointing down.
• Press the push-button all the way in.
The insulin should fill the lower part of the big outer needle cap (see diagram L). If the
NovoLog®FlexPen®has released too much or too little insulin, do the function check again.
If the same problem happens again, do not use your NovoLog®FlexPen®and contact
Novo Nordisk at 1-800-727-6500.
Maintenance
Your FlexPen®is designed to work accurately and safely. It must be handled with care. Avoid dropping
your FlexPen®as it may damage it. If you are concerned that your FlexPen®is damaged, use a new
one. You can clean the outside of your FlexPen®by wiping it with a damp cloth. Do not soak or wash
your FlexPen®as it may damage it. Do not refill your FlexPen®.
Remove the needle from the NovoLog®FlexPen®after each injection. This helps to ensure
sterility, prevent leakage of insulin, and will help to make sure you inject the right dose of insulin
for future injections.
Be careful when handling used needles to avoid needle sticks and transfer of infectious diseases.
Keep your NovoLog®FlexPen®and needles out of the reach of children.
Use NovoLog®FlexPen®as directed to treat your diabetes.
Needles and NovoLog®FlexPen®must not be shared. Always use a new needle for each injection.
Novo Nordisk is not responsible for harm due to using this insulin pen with products not
recommended by Novo Nordisk.
As a precautionary measure, always carry a spare insulin delivery device in case your NovoLog®
FlexPen®is lost or damaged.
Remember to keep the disposable NovoLog®FlexPen®with you. Do not leave it in a car or other
location where it can get too hot or too cold.
P
atient Instructions for Use
NovoLog®FlexPen®
Introduction
Please read the following instructions carefully before using your NovoLog®FlexPen®.
NovoLog®FlexPen®is a disposable dial-a-dose insulin pen. You can select doses from 1 to 60 units
in increments of 1 unit. NovoLog®FlexPen®is designed to be used with NovoFine®needles.
NovoLog®FlexPen®should not be used by people who are blind or have severe visual problems
without the help of a person who has good eyesight and who is trained to use the NovoLog®
FlexPen®the right way.
Getting ready
Make sure you have the
following items:
• NovoLog®FlexPen®
• New NovoFine®needle
• Alcohol swab
Preparing Your
NovoLog®FlexPen®
Wash your hands with soap and
water. Before you start to prepare your injection,
check the label to make sure that you are taking the right type of insulin.
This is especially important if you take more than 1 type of insulin.
NovoLog®should look clear.
A. Pull off the pen cap (see diagram A).
Wipe the rubber stopper with an alcohol swab.
B. Attaching the needle
Remove the protective tab from a disposable needle.
Screw the needle tightly onto your FlexPen®. It is important that the
needle is put on straight (see diagram B).
Never place a disposable needle on your NovoLog®FlexPen®until
you are ready to take your injection.
C. Pull off the big outer needle cap (see diagram C).
D. Pull off the inner needle cap and dispose of it (see diagram D).
Always use a new needle for each injection to help ensure sterility
and prevent blocked needles.
Be careful not to bend or damage the needle before use.
To reduce the risk of unexpected needle sticks, never put the inner
needle cap back on the needle.
Giving the airshot before each injection
Before each injection small amounts of air may collect in the cartridge
during normal use. To avoid injecting air and to ensure proper dosing:
E. Turn the dose selector to select 2 units (see diagram E).
F. Hold your NovoLog®FlexPen®with the needle pointing up.
Tap the cartridge gently with your finger a few times to make any air
bubbles collect at the top of the cartridge (see diagram F).
G. Keep the needle pointing upwards, press the push-button all the way
in (see diagram G). The dose selector returns to 0.
A drop of insulin should appear at the needle tip. If not, change the
needle and repeat the procedure no more than 6 times.
If you do not see a drop of insulin after 6 times, do not use the
NovoLog®FlexPen®and contact Novo Nordisk at 1-800-727-6500.
A small air bubble may remain at the needle tip, but it will not be
injected.
Selecting your dose
Check and make sure that the dose selector is set at 0.
H. Turn the dose selector to the number of units you need to inject.
The pointer should line up with your dose.
The dose can be corrected either up or down by turning the dose
selector in either direction until the correct dose lines up with the
pointer (see diagram H). When turning the dose selector, be careful not
to press the push-button as insulin will come out.
You cannot select a dose larger than the number of units left in the
cartridge.
You will hear a click for every single unit dialed. Do not set the dose
by counting the number of clicks you hear.
Do not use the cartridge scale printed on the cartridge to measure
your dose of insulin.
Giving the injection
Do the injection exactly as shown to you by your healthcare provider.
Your healthcare provider should tell you if you need to pinch the skin
before injecting.
4
6
0
I
J
K
20
L
Pen cap
NovoLog®FlexPen®
Big outer
needle cap Inner needle cap Needle
Protective
tab
NovoFine®needle
Rubber
stopper Cartridge
Cartridge
scale Pointer
Dose
selector
Push-
button
A
24 units
selected
24
5 units
selected
4
6
H
B
C
D
2 units
selected
E
F
G
Novo Nordisk®, NovoLog®, FlexPen®, and NovoFine®are registered trademarks of Novo Nordisk A/S.
NovoLog®is covered by US Patent Nos. 5,618,913, 5,866,538, and other patents pending. FlexPen®is covered by
US Patent Nos. 6,582,404, 6,004,297, 6,235,004, and other patents pending.
Manufactured by:
Novo Nordisk A/S
DK-2880 Bagsvaerd, Denmark
For information about NovoLog®contact:
Novo Nordisk Inc.
800 Scudders Mill Road
Plainsboro, New Jersey 08536
1-800-727-6500
www.novonordisk-us.com
© 2002-2014 Novo Nordisk
0714-00022409-1 7/2014

9 NovoLog®(insulin aspart [rDNA origin] injection)
Instructions for Use
NovoLog®(NŌ-vō-log) FlexTouch®Pen
(insulin aspart [rDNA origin] injection)
• NovoLog®FlexTouch®Pen (“Pen”) is a prefilled
disposable pen containing 300 units of U-100 NovoLog®
(insulin aspart [rDNA origin] injection) insulin. You can inject
from 1 to 80 units in a single injection.
• Do not share your NovoLog®FlexTouch®Pen with
another person. You may give an infection to them or
get an infection from them.
• This Pen is not recommended for use by the blind or
visually impaired without the assistance of a person
trained in the proper use of the product.
Supplies you will need to give your NovoLog®injection:
• NovoLog®FlexTouch®Pen
• a new NovoFine®or NovoTwist®needle
• alcohol swab
• 1 sharps container for throwing away used Pens and needles.
See “Disposing of used NovoLog®FlexTouch®Pens
and needles” at the end of these instructions.
Preparing your NovoLog®FlexTouch®Pen:
• Wash your hands with soap and water.
• Before you start to prepare your injection, check the
NovoLog®FlexTouch®Pen label to make sure you
are taking the right type of insulin. This is especially
important if you take more than 1 type of insulin.
• NovoLog®should look clear and colorless. Do not use
NovoLog®if it is thick, cloudy, or is colored.
• Do not use NovoLog®past the expiration date printed on the
label or 28 days after you start using the Pen.
• Always use a new needle for each injection to help
ensure sterility and prevent blocked needles.
N
ovoFine®
Outer
need
le cap
Inner
needle capNeedle
Paper
tab
N
ovoTwist®
Outer
need
le cap
Inner
needle capNeedle
Paper
tab
Pen cap
0
2
NovoLog®
FlexTouch®
insulin aspart (rDNA origin)
injection
250
200
150
100
50
Insulin
scale
Insulin
window
Dose
counter
Dose
selector
Dose
pointer
(Figure A) Dose
button
Step 1:
• Pull Pen cap straight off
(See Figure B).
(Figure B)
Step 2:
• Check the liquid in
the Pen (See Figure
C). NovoLog®should
look clear and colorless.
Do not use it if it looks
cloudy or colored.
(Figure C)
Step 9:
• Hold the Pen with the
needle pointing up.
Press and hold in the
dose button until the dose
counter shows “0”. The
“0” must line up with the
dose pointer.
• A drop of insulin should
be seen at the needle tip
(See Figure J).
If you do not see a
drop of insulin, repeat
steps 7 to 9, no more
than 6 times.
If you still do not
see a drop of insulin,
change the needle and
repeat steps 7 to 9.
0
2
250
200
150
100
50
(Figure J)
Selecting your dose:
Step 10:
• Turn the dose selector
to select the number
of units you need to
inject. The dose pointer
should line up with your
dose (See Figure K).
If you select the wrong
dose, you can turn the
dose selector forwards
or backwards to the
correct dose.
The even numbers
are printed on the dial.
The odd numbers are
shown as lines.
0
2
24 units
selected
22
24
26
5 units
selected
Examples
4
6
8
3
(Figure K)
• The NovoLog®
FlexTouch®Pen insulin
scale will show you how
much insulin is left in
your Pen (See Figure L).
250
200
150
100
50
Example:
Approx.
200 units
left
(Figure L)
• To see how much insulin is left in your NovoLog®
FlexTouch®Pen:
Turn the dose selector until it stops. The dose counter will
line up with the number of units of insulin that is left in
your Pen. If the dose counter shows 80, there are at least
80 units left in your Pen.
If the dose counter shows less than 80, the number
shown in the dose counter is the number of units left in
your Pen.
Step 3:
• Select a new
needle.
• Pull off the paper tab
from the outer needle
cap (See Figure D).
NovoFine®NovoTwist®
(Figure D)
Step 4:
• Push the capped
needle straight onto
the Pen and twist the
needle on until it is
tight (See Figure E).
NovoFine®NovoTwist®
(Figure E)
Step 5:
• Pull off the outer
needle cap. Do not
throw it away
(See Figure F).
NovoFine®NovoTwist®
(Figure F)
Step 6:
• Pull off the inner
needle cap and
throw it away
(See Figure G).
NovoFine®NovoTwist®
(Figure G)
Priming your NovoLog®FlexTouch®Pen:
Step 7:
• Turn the dose selector
to select 2 units
(See Figure H).
0
2
2 units
selected
0
2
4
(Figure H)
Step 8:
• Hold the Pen with the
needle pointing up. Tap
the top of the Pen gently
a few times to let any air
bubbles rise to the top
(See Figure I).
250
200
150
100
50
(Figure I)

10
NovoLog®(insulin aspart [rDNA origin] injection)
Step 15:
• Carefully remove
the needle from the
Pen and throw it
away (See Figure R).
Do not recap the
needle. Recapping
the needle can
lead to needle stick
injury.
• If you do not have
a sharps container,
carefully slip the
needle into the outer
needle cap (See Figure
S). Safely remove the
needle and throw it
away as soon as you
can.
Do not store
the Pen with the
needle attached.
Storing without the
needle attached
helps prevent
leaking, blocking
of the needle, and
air from entering
the Pen.
NovoFine®
150
100
50
NovoTwist®
150
100
50
(Figure R)
50
(Figure S)
Step 16:
• Replace the Pen cap by
pushing it straight on
(See Figure T).
(Figure T)
After your injection:
• Put your used NovoLog®FlexTouch®Pen and needles in a
FDA-cleared sharps disposal container right away after use. Do
not throw away (dispose of) loose needles and Pens in your
household trash.
• If you do not have a FDA-cleared sharps disposal container, you
may use a household container that is:
made of a heavy-duty plastic
can be closed with a tight-fitting, puncture-resistant lid,
without sharps being able to come out
upright and stable during use
leak-resistant
properly labeled to warn of hazardous waste inside the
container
• When your sharps disposal container is almost full, you will
need to follow your community guidelines for the right way to
dispose of your sharps disposal container. There may be state or
local laws about how you should throw away used needles and
syringes. For more information about the safe sharps disposal,
and for specific information about sharps disposal in the state
that you live in, go to the FDA’s website at: http://www.fda.gov/
safesharpsdisposal.
• Do not dispose of your used sharps disposal container in your
household trash unless your community guidelines permit this.
Do not recycle your used sharps disposal container.
How should I store my NovoLog®FlexTouch®Pen?
• Store unused NovoLog®FlexTouch®Pens in the refrigerator at
36°F to 46°F (2°C to 8°C).
• Store the Pen you are currently using out of the refrigerator
below 86°F.
• Do not freeze NovoLog®. Do not use NovoLog®if it has been
frozen.
• Keep NovoLog®away from heat or light.
• Unused Pens may be used until the expiration date printed on
the label, if kept in the refrigerator.
• The NovoLog®FlexTouch®Pen you are using should be thrown
away after 28 days, even if it still has insulin left in it.
General Information about the safe and effective use of
NovoLog®.
• Keep NovoLog®FlexTouch®Pens and needles out of
the reach of children.
• Always use a new needle for each injection.
• Do not share Pens or needles.
Giving your injection:
• Inject your NovoLog®exactly as your healthcare provider has
shown you. Your healthcare provider should tell you if you need
to pinch the skin before injecting.
• NovoLog®can be injected under the skin (subcutaneously) of
your stomach area (abdomen), buttocks, upper legs (thighs) or
upper arms.
• Change (rotate) your injection sites within the area you choose
for each dose. Do not use the same injection site for each
injection.
Step 11:
• Choose your injection site
and wipe the skin with
an alcohol swab. Let the
injection site dry before
you inject your dose
(See Figure M).
(Figure M)
Step 12:
• Insert the needle into
your skin (See Figure N).
Make sure you
can see the dose
counter. Do not
cover it with your
fingers, this can stop
your injection.
6
8
4
250
200
150
100
50
(Figure N)
Step 13:
• Press and hold down
the dose button until
the dose counter shows
“0” (See Figure O).
The “0” must line up
with the dose pointer.
You may then hear or
feel a click.
• Keep the needle in
your skin after the dose
counter has returned to “0”
and slowly count to 6
(See Figure P).
When the dose
counter returns to
“0”, you will not
get your full dose
until 6 seconds
later.
If the needle is
removed before you
count to 6, you may
see a stream of
insulin coming from
the needle tip.
If you see a stream
of insulin coming
from the needle
tip you will not get
your full dose. If
this happens you
should check your
blood sugar levels
more often because
you may need more
insulin.
0
2
250
200
150
100
50
0
2
(Figure O)
0
2
250
200
150
100
50
Count slowly:
1-2-3-4-5-6
(Figure P)
Step 14:
• Pull the needle out of
your skin (See Figure Q).
If you see blood after
you take the needle
out of your skin, press
the injection site
lightly with a piece of
gauze or an alcohol
swab. Do not rub the
area.
250
200
150
100
50
(Figure Q)
This Instructions for Use has been approved by the U.S. Food and
Drug Administration.
Manufactured By:
Novo Nordisk A/S
DK-2880 Bagsvaerd, Denmark
Revised: 10/2013
© 2005-2014 Novo Nordisk
0714-00022409-1 7/2014