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NovoLog® Mix 50/50 (50% insulin aspart protamine suspension and 50% insulin aspart injection) (50% insulin aspart protamine suspension and 50% insulin
aspart injection, [rDNA origin]) is an insulin analog suspension containing
50% insulin aspart protamine crystals and 50% soluble insulin aspart. NovoLog®
Mix 50/50 is a blood glucose-lowering agent with a rapid onset and an
intermediate duration of action. Insulin aspart 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) as the on organism.
Insulin aspart (NovoLog® ) has the empirical formula C256H381N65O79S6
and a molecular weight of 5825.8 Da.
Structural formula:
NovoLog® Mix 50/50 (50% insulin aspart protamine suspension and 50% insulin aspart injection) is a uniform, white, sterile suspension that contains
insulin aspart (B28 asp regular human insulin analog) 100 Units/ml, 16
mg glycerol, 1.50 mg phenol, 1.72 mg metacreÂsol, 19.6 μg zinc, 1.25 mg disodium
hydrogen phosphate dihydrate, 1.17 mg sodium chloride, and 0.23 mg protamine
sulfate. NovoLog® Mix 50/50 (50% insulin aspart protamine suspension and 50% insulin aspart injection) has a pH of 7.10 - 7.44. Hydrochloric acid or
sodium hydroxide may be added to adjust pH.
Indications & Dosage
INDICATIONS
NovoLog® Mix 50/50 (50% insulin aspart protamine suspension and 50% insulin aspart injection) is indicated as an adjunct to diet and exercise to improve
glycemic control in patients with diabetes mellitus.
DOSAGE AND ADMINISTRATION
The written prescription for NovoLog® Mix 50/50 (50% insulin aspart protamine suspension and 50% insulin aspart injection) should include the full
name, to avoid confusion with NovoLog® (insulin aspart) and NovoLog®
Mix 70/30 (70% insulin aspart protamine suspension and 30% insulin aspart injection,
(rDNA origin).
NovoLog® Mix 50/50 (50% insulin aspart protamine suspension and 50% insulin aspart injection) should be administered within 15 minutes of meal initiation
up to three times daily. It is intended only for subcutaneous injection into
the abdominal wall, thigh, or upper arm. NovoLog® Mix 50/50 (50% insulin aspart protamine suspension and 50% insulin aspart injection) should not be
administered intravenously.
No clinical studies have been conducted comparing NovoLog® Mix 50/50 (50% insulin aspart protamine suspension and 50% insulin aspart injection) to
proportionate doses of insulin aspart (NovoLog®) and an intermediate-acting
insulin that are mixed by the patient prior to injection. Initiating or switching
to a regimen that contains a NovoLog® Mix formulation, as with any change
in an insulin regimen, will require careful blood glucose monitoring to ensure
adequacy of glycemic control and to avoid hypoglycemia.
Dose regimens of NovoLog® Mix 50/50 (50% insulin aspart protamine suspension and 50% insulin aspart injection) will vary among patients and should
be determined by the health care professional familiar with the patient's lifestyle
variables. As with all insulins, the duration of action may vary according to
the dose, injection site, blood flow, temperature, and level of physical activity
and conditioning.
Administration using PenFill® Cartridges for 3 mL PenFill® cartridge
compatible delivery devices and NovoLog® Mix 50/50 (50% insulin aspart protamine suspension and 50% insulin aspart injection) FlexPen ® Prefilled
syringes
PenFill®Cartridges for 3 mL PenFill® cartridge compatible delivery
devices*
NovoLog® Mix 50/50 (50% insulin aspart protamine suspension and 50% insulin aspart injection) PenFill® suspension should be visually inspected
and resuspended immediately before use. The resuspended NovoLog® Mix 50/50 (50% insulin aspart protamine suspension and 50% insulin aspart injection)
must appear uniformly white and cloudy. Before inserting the cartridge into
the insulin delivery system, roll the cartridge between your palms 10 times.
The cartridge should be kept horizontal while rolling. Thereafter, turn the
cartridge upside down so that the glass ball moves from one end of the cartridge
to the other. Do this at least 10 times. The rolling and turning procedure must
be repeated until the suspension appears uniformly white and cloudy. Mixing
is easier when the insulin has reached room temperature. Inject immediately.
Before each subsequent injection, turn the 3 mL PenFill® cartridge compatible
delivery devices* upside down so that the glass ball moves from one end of the
cartridge to the other. Repeat this at least 10 times until the suspension appears
uniformly white and cloudy. Inject immediately.
Always remove the needle after each injection and store the 3 mL PenFill®
cartridge compatible delivery device without a needle attached. This prevents
contamination and/or infection, entry of air into the insulin reservoir, or
leakage of insulin and will ensure accurate dosing. Always use a new needle
for each injection to prevent contamination. Used needles or lancets should
be placed in sharps containers (such as red biohazard containers), hard plastic
containers (such as detergent bottles), or metal containers (such as an empty
coffee can). Such containers should be sealed and disposed of properly.
*NovoLog® Mix 50/50 (50% insulin aspart protamine suspension and 50% insulin aspart injection) 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®, and NovoFine®
disposable needles.
NovoLog® Mix 50/50 (50% insulin aspart protamine suspension and 50% insulin aspart injection) suspension should be visually inspected and resuspended
immediately before use. The resuspended NovoLog® Mix 50/50 (50% insulin aspart protamine suspension and 50% insulin aspart injection) must appear uniformly
white and cloudy. Before use, roll the disposable NovoLog® Mix 50/50 (50% insulin aspart protamine suspension and 50% insulin aspart injection) FlexPen®
Prefilled syringe between your palms 10 times. This procedure should be carried
out with the NovoLog® Mix 50/50 (50% insulin aspart protamine suspension and 50% insulin aspart injection) FlexPen® Prefilled syringe in a horizontal
position. Thereafter, turn the disposable NovoLog® Mix 50/50 (50% insulin aspart protamine suspension and 50% insulin aspart injection) FlexPen®
Prefilled syringe upside down so that the glass ball moves from one end of the
reservoir to the other. Do this at least 10 times. The rolling and turning procedure
must be repeated until the suspension appears uniformly white and cloudy. Mixing
is easier when the insulin has reached room temperature. Inject immediately.
Before each subsequent injection, turn the disposable NovoLog® Mix 50/50 (50% insulin aspart protamine suspension and 50% insulin aspart injection)
FlexPen® Prefilled syringe upside down so that the glass ball moves from
one end of the reservoir to the other at least 10 times and until the suspension
appears uniformly white and cloudy. Inject immediately.
Always remove the needle after each injection and store the NovoLog®Mix
50/50 FlexPen® Prefilled Syringe without a needle attached. This prevents
contamination and/or infection, entry of air into the insulin reservoir, or
leakage of insulin and will ensure accurate dosing. Always use a new needle
for each injection to prevent contamination. Used needles, or lancets should
be placed in sharps containers (such as red biohazard containers), hard plastic
containers (such as detergent bottles), or metal containers (such as an empty
coffee can). Such containers should be sealed and disposed of properly.
HOW SUPPLIED
NovoLog® Mix 50/50 (50% insulin aspart protamine suspension and 50% insulin aspart injection) is available in the following package sizes: each presentation
containing 100 Units of insulin aspart per mL (U-100).
3 mL PenFill® cartridges* NDC xxxx-xxxx-xx
3 mL NovoLog® Mix 50/50 (50% insulin aspart protamine suspension and 50% insulin aspart injection) FlexPen® Prefilled Syringe
NDC xxxx-xxxx-xx
* NovoLog® Mix 50/50 (50% insulin aspart protamine suspension and 50% insulin aspart injection) 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®, and NovoFine®
disposable needles.
Recommended Storage
Unused NovoLog® Mix 50/50 (50% insulin aspart protamine suspension and 50% insulin aspart injection) should be stored in a refrigerator between 2o
and 8oC (36o to 46oF). Do not store in the freezer or directly adjacent to the
refrigerator cooling element. Do not freeze or use NovoLog®Mix 50/50
if it has been frozen.
PenFill® cartridges or NovoLog®Mix 50/50 FlexPen®Prefilled
syringes:
Once a cartridge or a NovoLog® Mix 50/50 (50% insulin aspart protamine suspension and 50% insulin aspart injection) FlexPen® Prefilled syringe
is punctured, it may be used for up to 14 days if it is kept at room temperature
below 30°C (86°F). Cartridges or NovoLog® Mix 50/50 (50% insulin aspart protamine suspension and 50% insulin aspart injection) FlexPen®
Prefilled syringes in use should not be stored in the refrigerator. Keep all
PenFill® cartridges and NovoLog® Mix 50/50 (50% insulin aspart protamine suspension and 50% insulin aspart injection) FlexPen® Prefilled syringes
away from direct heat and light.
Unpunctured PenFill® cartridges and NovoLog® Mix 50/50 (50% insulin aspart protamine suspension and 50% insulin aspart injection) FlexPen®
Prefilled syringes can be used until the expiration date printed on the label
if they are stored in a refrigerator. After removing NovoLog® Mix 50/50 (50% insulin aspart protamine suspension and 50% insulin aspart injection)
PenFill® cartridges or NovoLog® Mix 50/50 (50% insulin aspart protamine suspension and 50% insulin aspart injection) FlexPen® Prefilled syringes
from the refrigerator it is recommended to let the PenFill® cartridges or
NovoLog® Mix 50/50 (50% insulin aspart protamine suspension and 50% insulin aspart injection) FlexPen® Prefilled syringe reach room temperature
before resuspending the insulin as recommended for first time use. Keep unused
PenFill® cartridges and NovoLog® Mix 50/50 (50% insulin aspart protamine suspension and 50% insulin aspart injection) FlexPen® Prefilled syringes
in the carton so they will stay clean and protected from light.
These storage conditions are summarized in the following table:
Not in-use (unopened)
Room Temperature
(below 30°C [86°F])
Not in-use (unopened)
Refrigerated
(2°-8°C [36° to 46°F])
In-use (opened)
Room Temperature
(at or below 30°C [86°F])
3 mL PenFill® cartridges
14 days
Until expiration date
14 days (Do not refrigerate)
3 mL NovoLog® Mix 50/50 FlexPen®
14 days
Until expiration date
14 days (Do not refrigerate)
Manufactured by: Novo Nordisk A/S, 2880 Bagsvaerd, Denmark.
Manufactured for: Novo Nordisk Inc., Princeton, NJ 08540, www.novonordisk-us.com.
FDA rev date: 8/26/2008
QUESTION
Diabetes is defined best as...See Answer
Side Effects
SIDE EFFECTS
During clinical trials the overall adverse event profile of NovoLog® Mix
50/50 was comparable to Novolin® 70/30.
Adverse events commonly associated with human insulin therapy include the following:
Body as whole: allergic reactions (see PRECAUTIONS,
Allergy).
Skin and Appendages: Injection site reaction, lipodystrophy, pruritus,
rash (see PRECAUTIONS, Allergy).
Hypoglycemia: see WARNINGS and PRECAUTIONS.
Drug Interactions
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, salbutaÂmol, terbutaline), isoniazid, phenothiazine derivatives,
somatropin, thyroid hormones, estrogens, progestogens (e.g., in oral contraceptives).
Beta-blockers, clonidine, lithium salts, and alcohol may either potentiate
or weaken the bloodÂglucose-lowering effect of insulin.
Pentamidine may cause hypoglycemia, which may sometimes be followed by hyperglycemia.
In addition, under the influence of sympatholytic medical products such as
beta-blockers, cloÂnidine, guanethidine, and reserpine, the signs of hypoglycemia
may be reduced or absent (see CLINICAL PHARMACOLOGY).
Mixing of insulins
NovoLog® Mix 50/50 (50% insulin aspart protamine suspension and 50% insulin aspart injection) should not be mixed with any other insulin product.
Warnings
WARNINGS
Because NovoLog® Mix 50/50 (50% insulin aspart protamine suspension and 50% insulin aspart injection) has peak pharmacodynamic activity between 1
and 4 hours after injection, it should be administered with meals.
NovoLog® Mix 50/50 (50% insulin aspart protamine suspension and 50% insulin aspart injection) should not be administered intravenously. NovoLog®
Mix 50/50 is not to be used in insulin infusion pumps.NovoLog® Mix 50/50 (50% insulin aspart protamine suspension and 50% insulin aspart injection)
should not be mixed with any other insulin product.
Hypoglycemia is the most common adverse effect of insulin therapy, including
NovoLog® Mix 50/50 (50% insulin aspart protamine suspension and 50% insulin aspart injection) . As with all insulins, the timing of hypoglycemia may
differ among various insulin formulations.
Glucose monitoring is recommended for all patients with diabetes.
Any change of insulin dose should be made cautiously and only under medical
supervision. Changes in insulin strength, manufacturer, type (e.g., regular,
NPH, analog, premixed), species (animal, human), or method of manufacture (rDNA
versus animal-source insulin) may result in the need for a change in dosage.
Precautions
PRECAUTIONS
General
Hypoglycemia and hypokalemia are among the potential clinical adverse effects
associated with the use of all insulins. Because of differences in the action
of NovoLog® Mix 50/50 (50% insulin aspart protamine suspension and 50% insulin aspart injection) and other insulins, care should be taken in patients
in whom such potential side effects might be clinically relevant (e.g. patients
who are fasting, have autonomic neuropathy, or are using potassium-lowering
drugs or patients taking drugs sensitive to serum potassium level). Because
there is diurnal variation in insulin resistance and endogenous insulin secretion,
variability in the time and content of meals, and variability in the time and
extent of exercise, fixed ratio insulin mixtures may not provide optimal glycemic
control for all patients. Adjustments in insulin dose or insulin type may be
needed during illness, emotional stress, and other physiologic stress in addition
to changes in meals and exercise.
The pharmacokinetic and pharmacodynamic profiles of all insulins may be altered
by the site used for injection and the degree of vascularization of the site.
Smoking, temperature, and exercise contribute to variations in blood flow and
insulin absorption. These and other factors contribute to inter- and intra-patient
variability.
Insulin may cause sodium retention and edema (swelling of hands and feet),
particularly if previously poor metabolic control is improved by intensified
insulin therapy. Lipodystrophy at the injection site and hypersensitivity are
among other potential clinical adverse effects associated with the use of all
insulins.
Hypoglycemia - As with all insulin preparations, hypoglycemic reactions
may be associated with the administration of NovoLog® Mix 50/50 (50% insulin aspart protamine suspension and 50% insulin aspart injection) . Rapid changes
in serum glucose concentrations 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 long duration
of diabetes, diabetic nerve disease, use of medications such as beta-blockers,
or intensified diabetes control.
Renal Impairment - Clinical or pharmacology studies with NovoLog®
Mix 50/50 in patients with diabetes with various degrees of renal impairment
have not been conducted. As with other insulins, the requirements for NovoLog®
Mix 50/50 may be reduced in patients with renal impairment.
Hepatic Impairment - Clinical or pharmacology studies with NovoLog®
Mix 50/50 in patients with diabetes with various degrees of hepatic impairment
have not been conducted. As with other insulins, the requirements for NovoLog®
Mix 50/50 may be reduced in patients with hepatic impairment.
Allergy- Local reactions: Erythema, swelling, and pruritus at the injection
site have been observed with insulin therapy. Reactions may be related to the
insulin molecule, other components in the insulin preparation including protamine
and cresol, components in skin cleansing agents, or injection techniques.
Systemic reactions: Less common, but potentially more serious, is generalized
allergy to insulin, which may cause rash (including pruritus) over the whole
body, shortness of breath, wheezing, reduction in blood pressure, rapid pulse,
or sweating. Severe cases of generalized allergy, including anaphylactic reaction,
may be life threatening. Localized reactions and generalized myalgias have been
reported with the use of cresol as an injectable excipient.
Antibody production - Antibodies have not been extensively investigated
during the clinical development of NovoLog® Mix 50/50 (50% insulin aspart protamine suspension and 50% insulin aspart injection) . Antibodies specific
to NovoLog® and cross-reactive with both NovoLog® and human insulin
have been evaluated previously in connection with the clinical development of
NovoLog®. In addition, specific anti-insulin antibodies as well as crossreacting
anti-insulin antibodies were monitored in the 3-month, open-label comparator
trial between NovoLog® Mix 70/30 and human pre-mixed insulin and NovoLog®
as well as in a long-term extension trial. Changes in cross-reactive antibodies
were more common after NovoLog® Mix 70/30 than with human pre-mixed insulin
but these changes did not correlate with change in HbA1c or increase
in insulin dose. The clinical significance of these antibodies has not been
established. Antibodies did not increase further after long-term exposure (>6
months) to NovoLog® Mix 70/30.
Information for patients - Maintenance of normal or near-normal glucose
control is a treatment goal in diabetes mellitus and has been associated with
a reduction in diabetes complications. Patients should consult with their healthcare
provider before using NovoLog® Mix 50/50 (50% insulin aspart protamine suspension and 50% insulin aspart injection) as a mealtime insulin; the decision
should be based on the patient's insulin needs for that particular meal. Patients
should be informed that alcohol, including beer and wine, may affect their blood
sugar when taking NovoLog® Mix 50/50 (50% insulin aspart protamine suspension and 50% insulin aspart injection) . Patients should be informed about
potential risks and advantages of NovoLog® Mix 50/50 (50% insulin aspart protamine suspension and 50% insulin aspart injection) therapy including the
possible side effects. Patients should be informed that hypoglycemia may impair
the ability to concentrate and react, which may present a risk in situations
where these abilities are especially important, such as driving or operating
other machinery.
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 dosage,
instruction for use of injection devices and proper storage of insulin.
Female patients should be advised to discuss with their physician if they intend
to, or if they become, pregnant because information is not available on the
use of NovoLog® Mix 50/50 (50% insulin aspart protamine suspension and 50% insulin aspart injection) during pregnancy or lactation (see PRECAUTIONS,
Pregnancy).
Laboratory Tests - The therapeutic response to NovoLog® Mix
50/50 should be assessed by measurement of serum or blood glucose and glycosylated
hemoglobin.
Carcinogenicity, Mutagenicity, Impairment of Fertility
Standard 2-year carcinogenicity studies in animals have not been performed
to evaluate the carcinogenic potential of NovoLog® Mix 50/50 (50% insulin aspart protamine suspension and 50% insulin aspart injection) . In 52-week
studies, Sprague-Dawley rats were dosed subcutaneously with NovoLog®, the
rapid-acting component of NovoLog® Mix 50/50 (50% insulin aspart protamine suspension and 50% insulin aspart injection) , 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, NovoLog® at subcutaneous doses up to 200
U/kg/day (approximately 32 times the human subcutaneous dose, based on U/body
surface area) had no direct adverse effects on male and female fertility, or
on general reproductive performance of animals.
Pregnancy: Teratogenic Effects: Pregnancy Category C
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.
Insulin mixtures, including NovoLog Mix 50/50 (50% insulin aspart protamine suspension and 50% insulin aspart injection) , may be limited in their ability
to provide near-normal glycemic control, as recommended during pregnancy. Careful
monitoring of glucose control is essential in patients with diabetes during
pregnancy.
It is not known whether NovoLog® Mix 50/50 (50% insulin aspart protamine suspension and 50% insulin aspart injection) can cause fetal harm when administered
to a pregnant woman or can affect reproductive capacity. There are no adequate
and well-controlled studies of the use of NovoLog® Mix 50/50 (50% insulin aspart protamine suspension and 50% insulin aspart injection) in pregnant
women.
Animal reproduction studies have not been conducted with NovoLog® Mix 50/50 (50% insulin aspart protamine suspension and 50% insulin aspart injection) .
However, reproductive toxicology and teratology studies have been performed
with NovoLog® (the rapid-acting component of NovoLog® Mix 50/50 (50% insulin aspart protamine suspension and 50% insulin aspart injection) ) 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 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.
Nursing mothers - It is unknown whether NovoLog® Mix 50/50 (50% insulin aspart protamine suspension and 50% insulin aspart injection)
is excreted in human milk as is human insulin. There are no adequate and well-controlled
studies of the use of NovoLog® Mix 50/50 (50% insulin aspart protamine suspension and 50% insulin aspart injection) or NovoLog® in lactating women.
Pediatric Use - Safety and effectiveness of NovoLog® Mix
50/50 in children have not been established.
Geriatric Use - Safety and effectiveness of NovoLog® Mix
50/50 in geriatric population have not been studied. In general, dose selection
for an elderly patient should be cautious, usually starting at the low end of
the dosing range reflecting the greater frequency of decreased hepatic, renal,
or cardiac function, and of concomitant disease or other drug therapy in this
population.
Overdosage & Contraindications
OVERDOSE
Hypoglycemia may occur as a result of an excess of insulin relative to food
intake, energy expenditure, or both. 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 glucaÂgon or concentrated
intravenous glucose. Sustained carbohydrate intake and observation may be necessary
because hypoglycemia may recur after apparent clinical recovery.
CONTRAINDICATIONS
NovoLog® Mix 50/50 (50% insulin aspart protamine suspension and 50% insulin aspart injection) is contraindicated during episodes of hypoglycemia and
in patients hypersensitive to NovoLog® Mix 50/50 (50% insulin aspart protamine suspension and 50% insulin aspart injection) or any of the excipients.
Clinical Pharmacology
CLINICAL PHARMACOLOGY
Mechanism of action
The primary activity of NovoLog® Mix 50/50 (50% insulin aspart protamine suspension and 50% insulin aspart injection) is the regulation of glucose metabolism. Insulin products including the insulin in NovoLog® Mix 50/50 (50% insulin aspart protamine suspension and 50% insulin aspart injection) ,
exert their specific action through binding to insulin receptors.
Insulin binding activates mechanisms to lower blood glucose by facilitating
cellular uptake of glucose into skeletal muscle and fat while simultaneously
inhibiting the output of glucose from the liver.
In standard biological assays in mice and rabbits, one unit of NovoLog®
(insulin aspart) has the same glucose-lowering effect as one unit of regular
human insulin.
Pharmacokinetics
Bioavailability and Absorption
The single substitution of the amino acid proline with aspartic acid at position
B28 in insulin aspart (NovoLog®) reduces the molecule's rm hexamers as observed
with regular human insulin. This results in more rapid absorption from the subcutaneous
spaces than seen with regular human insulin. The rapid absorption characteristics
of NovoLog® are maintained by NovoLog® Mix 50/50 (50% insulin aspart protamine suspension and 50% insulin aspart injection) , containing 50% insulin
aspart in soluble form. The remaining 50% is in crystalline form as insulin
aspart protamine which has a prolonged absorption profile after subcutaneous
injection.
In an euglycemic clamp study in patients with type 1 diabetes (n=32) after
dosing with 0.4 U/kg of NovoLog® Mix 70/30, 50/50, and NovoLog® on three
different study days, a Cmax of 98 mU/L was reached after approximately 80 minutes
for NovoLog® Mix 50/50 (50% insulin aspart protamine suspension and 50% insulin aspart injection) (See Table 1). There was diminishing distinction
in pharmacokinetics between the two NovoLog Mix formulations at later time points
(See Figure 2).
Table 1: Pharmacokinetic Parameters comparing NovoLog®
Mix 50/50 to NovoLog® Mix 70/30 and NovoLog® in patients with Type 1
diabetes mellitus
NovoLog® Mix 50/50 versus NovoLog®
Mix 70/30
NovoLog® versus
NovoLog® Mix 50/50
Cmax
1.49 [1.34; 1.65]
2.04 [1.84; 2.26]
AUC0-2h
1.48 [1.35; 1.64]
2.01 [1.82; 2.22]
Values are expressed as mean ratios [95% confidence intervals]
Figure 2. Pharmacokinetic profiles of NovoLog® Mix 50/50 (50% insulin aspart protamine suspension and 50% insulin aspart injection) ,
70/30, and NovoLog® in Patients with Type 1 diabetes mellitus
The bioavailability of insulin aspart is decreased with increasing protamine
sulfate concentration in any NovoLog® Mix formulation. Consequently, exposure
of a subcutaneous dose of NovoLog® Mix 50/50 (50% insulin aspart protamine suspension and 50% insulin aspart injection) may be reduced in comparison
to the comparable dose of insulin aspart (NovoLog® ) and an intermediate
insulin that are mixed by the patient prior to injection. No clinical studies
have been conducted comparing NovoLog® Mix 50/50 (50% insulin aspart protamine suspension and 50% insulin aspart injection) to proportionate doses
of insulin aspart (NovoLog® ) and an intermediate-acting insulin that are
mixed by the patient prior to injection. Switching to a regimen that contains
a NovoLog® Mix formulation will require careful blood glucose monitoring
to ensure adequacy of glycemic control and to avoid hypoglycemia.
The rate of insulin absorption and consequently the onset of activity are known
to be affected by the site of injection, exercise, and other variables (see
PRECAUTIONS, General). The influence
of different injection sites on the absorption of NovoLog® Mix 50/50 (50% insulin aspart protamine suspension and 50% insulin aspart injection) has
not been investigated.
Distribution and Elimination
NovoLog® Mix 50/50 (50% insulin aspart protamine suspension and 50% insulin aspart injection) is a biphasic insulin which contains 50% soluble insulin
aspart. NovoLog® has a low binding to plasma proteins, 0 - 9%, similar to
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.
Pharmacodynamics
In an euglycemic clamp study in subjects with type 1 diabetes, a maximum glucose
infusion rate (GIRmax) of 6.0 ± 1.7 ter approximately 2.5 hours for NovoLog®
Mixmg/kg/min was 50/50 (See Table 2). There was diminishing distinction in pharmacodynamics
between the two NovoLog Mix formulations at later time points (See Figure 3).
Table 2: Pharmacodynamic Parameters comparing NovoLog®
Mix 50/50 to NovoLog® Mix 70/30 and NovoLog®in patients with Type 1
diabetes mellitus
NovoLog® Mix 50/50 versus
NovoLog® Mix 70/30
NovoLog® versus
NovoLog® Mix 50/50
GIRmax
1.29 [1.17; 1.43]
1.49 [1.35; 1.65]
AUCGIR,0-2h
1.52 [1.31; 1.78]
1.44 [1.23; 1.67]
Values are expressed as mean ratios [95% confidence intervals]
Figure 3. Pharmacodynamic profiles of NovoLog® Mix 50/50 (50% insulin aspart protamine suspension and 50% insulin aspart injection) ,
70/30, and NovoLog® in patients with Type 1 diabetes mellitus
Special populations
Children and adolescents - The pharmacokinetic and pharmacodynamic
properties of NovoLog® Mix 50/50 (50% insulin aspart protamine suspension and 50% insulin aspart injection) have not been assessed in children and
adolescents less than 18 years of age.
Geriatrics - The effect of age on the pharmacokinetics and pharmacodynamics
of NovoLog® Mix 50/50 (50% insulin aspart protamine suspension and 50% insulin aspart injection) has not been studied.
Gender - The effect of gender on the pharmacokinetics and pharmacodynamics
of NovoLog® Mix 50/50 (50% insulin aspart protamine suspension and 50% insulin aspart injection) has not been studied.
Obesity - The effect of obesity and/or subcutaneous fat thickness
on the pharmacokinetics and pharmacodynamics of NovoLog® Mix 50/50 (50% insulin aspart protamine suspension and 50% insulin aspart injection) has not
been studied but data on the rapid-acting component (NovoLog®) show no significant
effect.
Ethnic origin - The effect of ethnic origin on the pharmacokinetics
and pharmacodynamics of NovoLog® Mix 50/50 (50% insulin aspart protamine suspension and 50% insulin aspart injection) has not been studied
Renal impairment - The effect of renal function on the pharmacokinetics
and pharmacodynamics of NovoLog® Mix 50/50 (50% insulin aspart protamine suspension and 50% insulin aspart injection) has not been studied but data
on the rapid-acting component (NovoLog®) show no significant effect. Some
studies with human insulin have shown increased circulating levels of insulin
in patients with renal failure. Careful glucose monitoring and dose adjustments
of insulin, including NovoLog® Mix 50/50 may be necessary in patients with
renal dysfunction (see PRECAUTIONS, Renal
Impairment).
Hepatic impairment - The effect of hepatic impairment on the
pharmacokinetics and pharmacoÂdynamics of NovoLog® Mix 50/50 (50% insulin aspart protamine suspension and 50% insulin aspart injection) has not been
studied but data on the rapid-acting component(NovoLog®) show no significant
effect. Some studies with human insulin have shown increased circulating levels
of insulin in patients with liver failure. Careful glucose monitoring and dose
adjustments of insulin, including NovoLog® Mix 50/50, may be necessary in
patients with heÂpatic dysfunction (see PRECAUTIONS,
Hepatic Impairment).
Pregnancy - The effect of pregnancy on the pharmacokinetics and
pharmacodynamics of NovoLog® Mix 50/50 has not been studied (see PRECAUTIONS,
Pregnancy).
Smoking- The effect of smoking on the pharmacokinetics and pharmacodynamics
of NovoLog® Mix 50/50 has not been studied.
Know your insulin. Do not change the type of insulin you take unless
told to do so by your healthcare provider. The amount of insulin you take as
well as the best time for you to take your insulin may need to change if you
take a different type of insulin.
Make sure you have the type and strength of insulin prescribed for you.
Read this Patient Information that comes with NovoLog® Mix 50/50 (50% insulin aspart protamine suspension and 50% insulin aspart injection) before
you start taking it and each time you get a refill. There may be new information
since your last refill. This leaflet does not take the place of talking with
your healthcare provider about your diabetes or your treatment. Make sure that
you know how to manage your diabetes. Ask your healthcare provider if you have
any questions about managing your diabetes.
What is NovoLog® Mix 50/50 (50% insulin aspart protamine suspension and 50% insulin aspart injection) ?
NovoLog® Mix 50/50 (50% insulin aspart protamine suspension and 50% insulin aspart injection) is both a rapid-acting and long-acting man-made insulin.
NovoLog® Mix 50/50 (50% insulin aspart protamine suspension and 50% insulin aspart injection) comes in:
3 mL PenFill® cartridges.
3 mL NovoLog® Mix 50/50 (50% insulin aspart protamine suspension and 50% insulin aspart injection) FlexPen®Prefilled syringe.
Only use NovoLog® Mix 50/50 (50% insulin aspart protamine suspension and 50% insulin aspart injection) if all of the medicine looks white and cloudy
after you mix it (resuspension) (see “Patient Instructions for Use”).
If your NovoLog® Mix 50/50 (50% insulin aspart protamine suspension and 50% insulin aspart injection) looks clear, do not use it and call Novo Nordisk
at 1-800-727-6500.
Who should not take NovoLog® Mix 50/50 (50% insulin aspart protamine suspension and 50% insulin aspart injection) ?
Do not use NovoLog® Mix 50/50 (50% insulin aspart protamine suspension and 50% insulin aspart injection) if:
Your blood sugar is too low (hypoglycemia). After treating your low blood
sugar, follow your healthcare provider's instructions on the use of NovoLog®
Mix 50/50.
You are allergic to anything in NovoLog® Mix 50/50 (50% insulin aspart protamine suspension and 50% insulin aspart injection) . See the end of this
leaflet for a complete list of ingredients in NovoLog® Mix 50/50 (50% insulin aspart protamine suspension and 50% insulin aspart injection) . Check
with your healthcare provider if you are not sure.
Tell your healthcare provider:
about all of your medical conditions. Medical conditions can affect
your insulin needs and your dose of NovoLog® Mix 50/50 (50% insulin aspart protamine suspension and 50% insulin aspart injection) .
if you are pregnant or breast feeding. You and your healthcare provider
should talk about the best way to manage your diabetes while you are pregnant
or breastfeeding. NovoLog® Mix 50/50 (50% insulin aspart protamine suspension and 50% insulin aspart injection) has not been studied in pregnant
or nursing women.
about all of the medicines you take, including prescription and nonprescription
medicines, vitamins and herbal supplements. Many medicines can affect your
blood sugar levels and your insulin needs. Your NovoLog® Mix 50/50 (50% insulin aspart protamine suspension and 50% insulin aspart injection) dose
may need to change if you take other medicines.
Know the medicines you take. Keep a list of your medicines with you to show
all your healthcare providers.
How should I take NovoLog® Mix 50/50 (50% insulin aspart protamine suspension and 50% insulin aspart injection) ?
Read the instructions for use that come with your NovoLog® Mix 50/50 (50% insulin aspart protamine suspension and 50% insulin aspart injection)
product. Talk to your healthcare provider if you have any questions. Your
healthcare provider should show you how to inject NovoLog® Mix 50/50 (50% insulin aspart protamine suspension and 50% insulin aspart injection) before
you start taking it.
Take NovoLog® Mix 50/50 (50% insulin aspart protamine suspension and 50% insulin aspart injection) exactly as prescribed. NovoLog® Mix
50/50 is injected right before a meal, up to three (3) times each day.
NovoLog® Mix 50/50 (50% insulin aspart protamine suspension and 50% insulin aspart injection) starts acting fast, so inject it up to 15 minutes
before you eat a meal. Do not inject NovoLog® Mix 50/50 (50% insulin aspart protamine suspension and 50% insulin aspart injection) if you are
not planning to eat within 15 minutes.
Inject NovoLog® Mix 50/50 (50% insulin aspart protamine suspension and 50% insulin aspart injection) under the skin of your stomach area, upper
arms, or upper legs. NovoLog® Mix 50/50 (50% insulin aspart protamine suspension and 50% insulin aspart injection) may affect your blood sugar
levels sooner if you inject it into the skin of your stomach area.
Change (rotate) sites with each dose. Although you can inject insulin
in the same area, do not inject into the exact same spot for each injection.
Check your blood sugar levels. Ask your healthcare provider how often
you should check your blood sugar levels for hypoglycemia (too low blood sugar)
and hyperglycemia (too high blood sugar).
If you take too much NovoLog® Mix 50/50 (50% insulin aspart protamine suspension and 50% insulin aspart injection) , your blood sugar
may fall low (hypoglycemia). You can treat mild low blood sugar (hypoglycemia)
by drinking or eating something sugary right away (fruit juice, sugar candies,
or glucose tablets). It is important to treat low blood sugar (hypoglycemia)
right away because it could get worse and you could pass out (become unconscious).
If you pass out you will need help from another person or emergency medical
services right away, and will need treatment with a glucagon injection or
treatment at a hospital. See “What are the most common side effects
of NovoLog® Mix 50/50 (50% insulin aspart protamine suspension and 50% insulin aspart injection) ?” for more information on low blood sugar
(hypoglycemia).
If you forget to take your dose of NovoLog® Mix 50/50 (50% insulin aspart protamine suspension and 50% insulin aspart injection) , your blood
sugar may go too high (hyperglycemia). High blood sugar (hyperglycemia)
if not treated can lead to loss of consciousness (passing out), coma or even
death. Symptoms of high blood sugar may include:
increased thirst
frequent urination
drowsiness
loss of appetite
fruity odor on the breath
high amounts of sugar and ketones in your urine
nausea, vomiting (throwing up), or abdominal pain
a hard time breathing
Follow your healthcare provider's ons for treating high blood sugar, and talk
to your healthcare provider if high blood sugar is a problem for you.
Your insulin dosage may need to change because of:
illness
stress change
other medicines
change in food intake
in physical activity or
you take exercise
surgery
Follow your healthcare provider's instructions to make changes in your insulin
dose.
Never mix NovoLog® Mix 50/50 (50% insulin aspart protamine suspension and 50% insulin aspart injection) with other insulin products.
Never use NovoLog® Mix 50/50 (50% insulin aspart protamine suspension and 50% insulin aspart injection) in an insulin pump.
Never inject NovoLog® Mix 50/50 (50% insulin aspart protamine suspension and 50% insulin aspart injection) into a vein.
See the end of this patient information for instructions about preparing and
giving the injection.
What are the most common side effects of NovoLog® Mix 50/50 (50% insulin aspart protamine suspension and 50% insulin aspart injection) ?
Low blood sugar (hypoglycemia). Symptoms of low blood sugar may include:
sweating
dizziness or lightheadedness
shakiness
fast heart beat
tingling of lips or tongue
trouble concentrating or confusion
blurred vision
slurred speech
anxiety, irritability or mood changes
hunger headache
Alcohol, including beer and wine, may affect your blood sugar when you take
NovoLog®Mix 50/50.
Your ability to concentrate or react may be reduced if you have hypoglycemia.
Be careful when you drive a car or operate machinery. Ask your healthcare provider
if you should drive if you have:
frequent hypoglycemia
reduced or absent warning signs of hypoglycemia
Severe low blood sugar can cause unconsciousness (passing out), seizures, and
death. Know your symptoms of low blood sugar. Follow your healthcare provider's
instructions for treating low blood sugar. Talk to your healthcare provider
if low blood sugar is a problem for you.
Call your doctor for medical advice about side effects. You may report side
effects to FDA at 1-800-FDA-1088.
Other possible side effects include:
Serious allergic reaction (whole body allergic reaction). Get medical
help right away if you develop a rash over your whole body, have trouble breathing,
a fast heartbeat, or sweating.
Reactions at the injection site (local allergic reaction). You may
get redness, swelling and itching at the injection site. If you keep having
skin reactions or they are serious, you may need to stop taking NovoLog®
Mix 50/50 and take a different insulin. Do not inject insulin into a skin
area that is red, swollen, or itchy.
Skin thickens or pits at the injection site (lipodystrophy). Change
(rotate) where you inject your insulin to help prevent these skin changes
from happening. Do not inject insulin into this type of skin.
Swelling of your hands and feet.
Low potassium in your blood (hypokalemia).
These are not all of the possible side effects from NovoLog® Mix 50/50 (50% insulin aspart protamine suspension and 50% insulin aspart injection) .
Ask your healthcare provider or pharmacist for more information.
How should I store NovoLog® Mix 50/50 (50% insulin aspart protamine suspension and 50% insulin aspart injection) ?
Keep all unopened NovoLog® Mix 50/50 (50% insulin aspart protamine suspension and 50% insulin aspart injection) in the refrigerator between 36°
to 46° F (2° to 8° C). Do not store in the freezer or next to
the refrigerator cooling element. Do not freeze.
Keep unopened NovoLog® Mix 50/50 (50% insulin aspart protamine suspension and 50% insulin aspart injection) in the carton to protect from light.
After the package has been opened:
Do not put NovoLog® Mix 50/50 (50% insulin aspart protamine suspension and 50% insulin aspart injection) that you are using in the refrigerator.
Keep at room temperature at or below 86°F (30°C) for up to 14 days.
Keep NovoLog® Mix 50/50 (50% insulin aspart protamine suspension and 50% insulin aspart injection) away from direct heat or light.
Throw away used NovoLog® Mix 50/50 (50% insulin aspart protamine suspension and 50% insulin aspart injection) after 14 days of use, even if there
is insulin left in the cartridge or syringe.
General information about NovoLog® Mix 50/50 (50% insulin aspart protamine suspension and 50% insulin aspart injection)
Medicines are sometimes prescribed for conditions that are not mentioned in
the patient leaflet. Do not use NovoLog® Mix 50/50 (50% insulin aspart protamine suspension and 50% insulin aspart injection) for a condition for which
it was not prescribed. Do not give NovoLog Mix 50/50 (50% insulin aspart protamine suspension and 50% insulin aspart injection) to other people, even if
they have the same symptoms you have. It may harm them.
This leaflet summarizes the most important information about NovoLog® Mix
50/50. If you would like more information about NovoLog® Mix 50/50 (50% insulin aspart protamine suspension and 50% insulin aspart injection) or diabetes,
talk with your healthcare provider. You can ask your healthcare provider or
pharmacist for information about NovoLog® Mix 50/50 (50% insulin aspart protamine suspension and 50% insulin aspart injection) which is written for
healthcare professionals. For more information, call 1-800-727-6500 or visit
www.novonordisk-us.com.
Helpful information for people with diabetes is published by the American Diabetes
Association, 1660 Duke Street, Alexandria, VA 22314 and on www.diabetes.org.
What are the ingredients in NovoLog® Mix 50/50 (50% insulin aspart protamine suspension and 50% insulin aspart injection) ?
insulin aspart
glycerol
phenol
metacresol
protamine sulfate
zinc
disodium hydrogen phosphate dihydrate
sodium chloride
hydrochloric acid and/or sodium
hydroxide may be added
Patient Instructions for Use
NovoLog®Mix 50/50 FlexPen®Prefilled syringe
How to use the NovoLog®Mix 50/50 FlexPen®Prefilled syringe
NovoLog® Mix 50/50 (50% insulin aspart protamine suspension and 50% insulin aspart injection) FlexPen® Prefilled syringe is a disposable insulin
delivery system. NovoLog® Mix 50/50 (50% insulin aspart protamine suspension and 50% insulin aspart injection) FlexPen® Prefilled syringe is to
be used with NovoFine® single use needles. People who are blind or have
severe vision problems should only use the NovoLog® Mix 50/50 (50% insulin aspart protamine suspension and 50% insulin aspart injection) FlexPen®
Prefilled syringe with the help of a sighted person who is trained to use the
NovoLog® Mix 50/50 (50% insulin aspart protamine suspension and 50% insulin aspart injection) FlexPen® Prefilled syringe the right way.
Please read these instructions completely before using this device.
Figure 1: Diagram of a NovoLog® Mix 50/50 (50% insulin aspart protamine suspension and 50% insulin aspart injection) FlexPen®
Prefilled syringe
Figure 2: Diagram of a NovoFine® needle
1. PREPARING THE NOVOLOG® MIX 50/50 (50% insulin aspart protamine suspension and 50% insulin aspart injection) FLEXPEN® PREFILLED SYRINGE
Before you start to prepare your injection, check the label to make sure
that you are taking the right type of insulin. NovoLog® Mix 50/50 (50% insulin aspart protamine suspension and 50% insulin aspart injection) should
look white and cloudy (after being mixed). This is especially important if you
use 2 types of insulin.
Pull off the pen cap.
Wipe the rubber stopper with an alcohol swab.
Before using a new NovoLog® Mix 50/50 (50% insulin aspart protamine suspension and 50% insulin aspart injection) FlexPen® Prefilled syringe
for the first time, do the following to mix (resuspend) the insulin:
Hold the NovoLog® Mix 50/50 (50% insulin aspart protamine suspension and 50% insulin aspart injection) FlexPen® Prefilled syringe in a
horizontal (flat) position between your palms (see diagram A above). Roll
the NovoLog® Mix 50/50 (50% insulin aspart protamine suspension and 50% insulin aspart injection) FlexPen® Prefilled syringe between your
palms 10 times.
Then, turn the NovoLog® Mix 50/50 (50% insulin aspart protamine suspension and 50% insulin aspart injection) FlexPen® Prefilled syringe
up and down. Move the NovoLog® Mix 50/50 (50% insulin aspart protamine suspension and 50% insulin aspart injection) FlexPen® Prefilled syringe
between position 1 and 2 so that the glass ball moves from
one end of the insulin cartridge to the other (see diagram B above). Do
this at least 10 times. Repeat the rolling and turning steps until all
of the insulin looks white and cloudy. Mixing (resuspension) is easier
when the insulin is at room temperature.
After mixing, continue to do the following steps right away. If there
is a delay, the insulin will need to be mixed again.
Remove the protective tab from the disposable needle and screw the needle
tightly onto the NovoLog® Mix 50/50 (50% insulin aspart protamine suspension and 50% insulin aspart injection) FlexPen® Prefilled syringe (see
diagram C above). Do not place a disposable needle on your NovoLog® Mix
50/50 FlexPen® Prefilled syringe until you are ready to take your injection.
Pull off the outer and inner needle caps (see diagram D above). Do not throw
away the big outer needle cap.
Giving the airshot before each injection:
Small amounts of air may collect in the needle and insulin cartridge during
normal use. To avoid injecting air and to make sure you take the right
dose of insulin, do the following:
Dial 2 units by turning the dose selector so that the arrow lines
up with the “2” in the dosage indicator window (see diagram
E below).
Hold the NovoLog® Mix 50/50 (50% insulin aspart protamine suspension and 50% insulin aspart injection) FlexPen® Prefilled syringe with
the needle pointing up. Tap the insulin cartridge gently with your finger
a few times (see diagram F below). A small air bubble may remain but
it will not be injected. The NovoLog® Mix 50/50 (50% insulin aspart protamine suspension and 50% insulin aspart injection) FlexPen® Prefilled
syringe prevents the insulin cartridge from being completely emptied.
Keep the needle pointing up and press the push button (on the end of the
NovoLog® Mix 50/50 (50% insulin aspart protamine suspension and 50% insulin aspart injection) FlexPen® Prefilled syringe) all the way in (see
diagram G below). You should see a drop of insulin at the needle tip. If you
don't see a drop of insulin, repeat the procedure (dial 2 units, tap the insulin
cartridge and press the push button) until insulin appears. You may need to
do this up to 6 times. If you don't see a drop of insulin after 6 times, do
not use the NovoLog® Mix 50/50 (50% insulin aspart protamine suspension and 50% insulin aspart injection) FlexPen® Prefilled syringe and contact
Novo Nordisk at 1-800-727-6500.
2. SETTING THE DOSE
Check and make sure that the dose selector is set at zero (0) (see diagram
H above).
Dial the number of units you need to inject by turning the dose selector
so the arrow lines up with your dose.
The dose can be corrected by turning the dose selector in either direction.
When dialing back, be careful not to press the push button. Pressing the button
will cause the insulin to come out. You cannot set 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.
3. GIVING THE INJECTION
Do the injection exactly as shown to you by your healthcare provider.
Wipe the injection site with an alcohol swab and let the area dry.
Pinch a fold of skin between 2 fingers, then push the needle into the pinched
up skin (see diagram I above).
Give the dose by pressing the push button all the way in (see diagram J
below). Be careful to only press the push button when injecting.
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.
This will make sure that the full dose has been given. 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
Remove the needle from the NovoLog® Mix 50/50 (50% insulin aspart protamine suspension and 50% insulin aspart injection) FlexPen® Prefilled
syringe after each injection. This helps to prevent contamination, infection,
and leakage of insulin, and will help to make sure you inject the right dose
of insulin. Put the needle in a sharps container, or some type of hard plastic
or metal container that can be sealed such as a detergent bottle or coffee
can. These containers should be sealed and thrown away safely. Ask your healthcare
provider how to throw away a used sharps container. There may be local or
state laws about how to throw away used needles and syringe.
Put the pen cap back on the NovoLog® Mix 50/50 (50% insulin aspart protamine suspension and 50% insulin aspart injection) FlexPen® Prefilled
syringe.
Healthcare providers, relatives, and other caregivers should follow general
precautions for removing and disposing of needles to lessen the possible chance
of needle stick injury.
4. FUTURE INJECTIONS
It is important that you use a new needle for each injection. Follow
the directions in steps 1, 2, and 3 above.
Before you inject, there must be at least 12 units of insulin left in the cartridge
to make sure the remaining insulin is evenly mixed. If there are less than 12
units left, use a new NovoLog® Mix 50/50 (50% insulin aspart protamine suspension and 50% insulin aspart injection) FlexPen® Prefilled syringe.
The numbers on the insulin cartridge can be used to estimate the amount of
insulin left in the NovoLog® Mix 50/50 (50% insulin aspart protamine suspension and 50% insulin aspart injection) FlexPen® Prefilled syringe. Do
not use these numbers to measure the insulin dose. You cannot set a dose more
than the number of units remaining in the cartridge.
Mix (resuspend) the insulin before each injection:
Turn the NovoLog® Mix 50/50 (50% insulin aspart protamine suspension and 50% insulin aspart injection) FlexPen® Prefilled syringe up and down
between position 1 and 2 so that the glass ball moves from one
end of the insulin cartridge to the other (see diagram B above). Do this at
least 10 times. Repeat the procedure until all of the insulin looks white
and cloudy.
Continue to follow the directions as described in steps 1, 2, and 3 above.
If there is a delay in any step, the insulin will need to be mixed (resuspended)
again.
5. FUNCTION CHECK
If your NovoLog® Mix 50/50 (50% insulin aspart protamine suspension and 50% insulin aspart injection) FlexPen® Prefilled syringe is not working
the right way, follow this procedure:
Screw on a new NovoFine® needle.
Do an airshot as described in step 1.
Put the big outer needle cap onto the needle. Do not put on the inner needle
cap.
Turn the dose selector so that the arrow lines up with the 20 units in the
dose indicator window.
Hold the NovoLog® Mix 50/50 (50% insulin aspart protamine suspension and 50% insulin aspart injection) FlexPen® Prefilled syringe 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
K above). If the NovoLog® Mix 50/50 (50% insulin aspart protamine suspension and 50% insulin aspart injection) FlexPen® Prefilled syringe has released
too much or too little insulin, do the function check again. If it happens again,
do not use your NovoLog® Mix 50/50 (50% insulin aspart protamine suspension and 50% insulin aspart injection) FlexPen® Prefilled syringe and contact
Novo Nordisk at 1-800-727-6500.
6.IMPORTANT NOTES
If you need to do more than 6 airshots before the first use of each NovoLog®
Mix 50/50 FlexPen® Prefilled syringe to get a drop of insulin at the needle
tip, do not use the NovoLog® Mix 50/50 (50% insulin aspart protamine suspension and 50% insulin aspart injection) FlexPen® Prefilled syringe.
Contact Novo Nordisk at 1-800-727-6500.
Remember to perform an airshot before each injection. See diagrams E and
F.
Do not drop the NovoLog® Mix 50/50 (50% insulin aspart protamine suspension and 50% insulin aspart injection) FlexPen® Prefilled syringe.
Keep the NovoLog® Mix 50/50 (50% insulin aspart protamine suspension and 50% insulin aspart injection) FlexPen® Prefilled syringe with you.
Do not leave it in a car or other place where it can get too hot or too cold.
NovoLog® Mix 50/50 (50% insulin aspart protamine suspension and 50% insulin aspart injection) FlexPen® Prefilled syringe should be used with
NovoFine® disposable needles.
Do not put a disposable needle on the NovoLog® Mix 50/50 (50% insulin aspart protamine suspension and 50% insulin aspart injection) FlexPen®
Prefilled syringe until you are ready to use it. Remove the needle right after
use. Do not recap the needle.
Throw away used needles safely, so other people will not be harmed.
Talk to your healthcare provider about how to safely throw away your used
needles.
Throw away the used NovoLog® Mix 50/50 (50% insulin aspart protamine suspension and 50% insulin aspart injection) FlexPen® Prefilled syringe
without the needle attached.
Always carry an extra NovoLog® Mix 50/50 (50% insulin aspart protamine suspension and 50% insulin aspart injection) FlexPen® Prefilled syringe
with you in case the NovoLog® Mix 50/50 (50% insulin aspart protamine suspension and 50% insulin aspart injection) FlexPen® Prefilled syringe
is damaged or lost.
Keep your NovoLog® Mix 50/50 (50% insulin aspart protamine suspension and 50% insulin aspart injection) FlexPen® Prefilled syringe out of the
reach of children. Use NovoLog® Mix 50/50 (50% insulin aspart protamine suspension and 50% insulin aspart injection) FlexPen® Prefilled syringe
as directed to treat your diabetes. Do not share it with anyone else even
if he or she also has diabetes.
Patient Instructions for Use
NovoLog® Mix 50/50 (50% insulin aspart protamine suspension and 50% insulin aspart injection) cartridge
Before using the NovoLog® Mix 50/50 (50% insulin aspart protamine suspension and 50% insulin aspart injection) cartridge
Talk with your healthcare provider to find out where to inject NovoLog®
Mix 50/50 (injection sites) and how to give an injection with your insulin
delivery device.
Read the instruction manual that comes with your insulin delivery device
for complete instructions on how to use the PenFill® cartridge with the
device.
How to use the NovoLog® Mix 50/50 (50% insulin aspart protamine suspension and 50% insulin aspart injection) cartridge
1. Check your insulin. Just before using your NovoLog® Mix 50/50 (50% insulin aspart protamine suspension and 50% insulin aspart injection)
cartridge, check to make sure that you have the right type of insulin. This
is especially important if you use different types of insulin.
2. Carefully look at the cartridge and the insulin inside it. The insulin
should be white and cloudy (after being mixed). The tamper-resistant foil should
be in place before the first use. If the foil has been broken or removed before
your first use of the cartridge, or if the insulin is clear, do not use it.
Call Novo Nordisk at 1-800-727-6500.
3. Gather your supplies for injecting NovoLog® Mix 50/50 (50% insulin aspart protamine suspension and 50% insulin aspart injection) . You will
need your NovoLog® Mix 50/50 (50% insulin aspart protamine suspension and 50% insulin aspart injection) PenFill® cartridge, your insulin delivery
device, NovoFine® single use needles and an alcohol swab. Be sure to use
an insulin delivery device that is made to work with NovoLog® Mix 50/50 (50% insulin aspart protamine suspension and 50% insulin aspart injection)
PenFill® cartridges. These insulin delivery devices can be used with a NovoPen®
3 PenMate® if you would like to hide the needle from view during injection.
4. Wash your hands well with soap and water.
5. Clean your injection site with an alcohol swab and let the injection
site dry before you inject.
6.Before inserting a 3 mL cartridge into your insulin delivery device for the
first time, roll the cartridge between your palms 10 times. These steps should
be done with the 3 mL PenFill® cartridge in a horizontal(flat) position
(see Diagram 1 below). Then turn the PenFill® cartridge up and down between
positions a and b (see Diagram 2 below) so the glass ball moves
from one end of the cartridge to the other. Do this at least 10 times. Repeat
the rolling and turning steps until the insulin looks white and cloudy. Mixing
is easier when the insulin is at room temperature.
7. Insert the PenFill® cartridge into the insulin delivery device. Wipe
the front rubber stopper of the 3 mL PenFill® cartridge with an alcohol
swab, then screw on a new needle (see Diagram 3 below).
For NovoFine® needles, remove the big outer needle cap and the inner needle
cap (see Diagram 4 above). Always use a new needle for each injection to prevent
infection.
Giving the airshot before each injection:
To prevent the injection of air and make sure insulin is delivered; you must
do an air shot before each injection. Hold the device with the needle pointing
up and gently tap the PenFill® cartridge holder with your finger a few times
to raise any air bubbles to the top of the cartridge (see Diagram 5 below).
Do the airshot as described in the device instruction manual.
Giving the injection
8. Dial the number of units you need to inject on the device (see Diagram 6
below). Inject right away as you were shown by your healthcare provider. If
there is a delay between mixing of the insulin and the injection, the insulin
will need to be mixed again.
9. Pinch a fold of skin between 2 fingers, then push the needle into the pinched
up skin (see Diagram 7 below). Inject the dose by pressing the push button all
the way in. 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. This will make sure that the full dose has been given. 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
10. Remove the needle from the insulin delivery device after each injection.
Keep the 3 mL PenFill® cartridge in the insulin delivery device. The needle
should not be attached to the insulin delivery device during storage. This will
prevent infection or leakage of insulin, and will help ensure that you receive
the right dose of NovoLog® Mix 50/50 (50% insulin aspart protamine suspension and 50% insulin aspart injection) .
11. Put the used needle in a sharps container, or some type of hard plastic
or metal container that can be sealed, such as a detergent bottle or coffee
can. Ask your healthcare provider how to seal and throw away these containers
safely. There may be local or state laws about how to throw away used needles
and syringes.
12. Put the pen cap back on the insulin delivery device.
After the first use of the 3 mL PenFill® cartridge
If the 3 mL PenFill® cartridge is already in the insulin delivery device,
turn it upside down between positions a and b (see Diagram 2
above), so that the glass ball moves from one end of the 3 mL PenFill®
cartridge to the other. Do this until all of the insulin looks white and cloudy.
Before you inject, there must be at least 12 units of insulin left in the
cartridge to make sure the remaining insulin is evenly mixed. If there are
less than 12 units left, use a new 3 mL PenFill® cartridge.
An airshot should be done before each injection. Do the airshot as described
in the device instruction manual.
Do not remove the 3 mL cartridge from the insulin delivery device.
Put the pen cap back on the insulin delivery device.
IMPORTANT NOTES
Do not use if you need to do more than 6 airshots before the first use of
each NovoLog® Mix 50/50 (50% insulin aspart protamine suspension and 50% insulin aspart injection) cartridge to get a drop of insulin at the needle
tip. Contact Novo Nordisk at 1-800-727-6500.
Remember to do an airshot before each injection. See the device instruction
manual.
Do not drop the NovoLog® Mix 50/50 (50% insulin aspart protamine suspension and 50% insulin aspart injection) cartridge and insulin delivery device.
Keep the NovoLog® Mix 50/50 (50% insulin aspart protamine suspension and 50% insulin aspart injection) cartridge and insulin delivery device with
you. Do not leave it in a car or other places where it can get too hot or
too cold.
NovoLog® Mix 50/50 (50% insulin aspart protamine suspension and 50% insulin aspart injection) cartridges are designed for use with NovoFine®
disposable needles.
Do not put a disposable needle on the NovoLog® Mix 50/50 (50% insulin aspart protamine suspension and 50% insulin aspart injection) cartridge and
insulin delivery device until you are ready to use it. Remove the needle right
after use. Do not recap the needle.
Throw away used needles safely, so other people will not be harmed. Talk
to your healthcare provider about how to safely throw away your used needles.
Throw away the used NovoLog® Mix 50/50 (50% insulin aspart protamine suspension and 50% insulin aspart injection) cartridges without the needle
attached.
Always carry an extra NovoLog® Mix 50/50 (50% insulin aspart protamine suspension and 50% insulin aspart injection) cartridge with you in case
the NovoLog® Mix 50/50 (50% insulin aspart protamine suspension and 50% insulin aspart injection) cartridge is damaged or lost. Always keep the NovoLog®
Mix 50/50 cartridge in the outer carton when you are not using it in order
to protect it from light.
Keep your NovoLog® Mix 50/50 (50% insulin aspart protamine suspension and 50% insulin aspart injection) cartridge out of the reach of children.
Use NovoLog® Mix 50/50 (50% insulin aspart protamine suspension and 50% insulin aspart injection) cartridges as directed to treat your diabetes.
Do not share it with anyone else even if he or she also has diabetes.