Rx Drugs Info

novolog mix 70/30 (insulin aspartinjection, suspension 
[Novo Nordisk Inc.]

DESCRIPTION

NovoLog® Mix 70/30 (70% insulin aspart protamine suspension and 30% insulin aspart injection, [rDNA origin]) is a human insulin analog suspension containing 70% insulin aspart protamine crystals and 30% soluble insulin aspart. NovoLog® Mix 70/30 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 production organism. Insulin aspart (NovoLog®) has the empirical formula C256H381N65O79S6 and a molecular weight of 5825.8 Da.

Structural formula:

Image from Drug Label Content

Figure 1. Structural formula of insulin aspart

NovoLog® Mix 70/30 is a uniform, white, sterile suspension that contains insulin aspart (B28 asp regular human insulin analog) 100 Units/mL.

Inactive ingredients for the 10 mL vial are mannitol 36.4 mg/mL, phenol 1.50 mg/mL, metacresol 1.72 mg/mL, zinc 19.6 μg/mL, disodium hydrogen phosphate dihydrate 1.25 mg/mL, sodium chloride 0.58 mg/mL, and protamine sulfate 0.32 mg/mL. Inactive ingredients for the NovoLog® Mix 70/30 FlexPen® prefilled syringe are glycerol 16.0 mg/mL, phenol 1.50 mg/mL, metacresol 1.72 mg/mL, zinc 19.6 μg/mL, disodium hydrogen phosphate dihydrate 1.25 mg/mL, sodium chloride 0.877 mg/mL, and protamine sulfate 0.32 mg/mL.

NovoLog® Mix 70/30 has a pH of 7.20 - 7.44. Hydrochloric acid or sodium hydroxide may be added to adjust pH.

CLINICAL PHARMACOLOGY

Mechanism of action

The primary activity of NovoLog® Mix 70/30 is the regulation of glucose metabolism. Insulins, including NovoLog® Mix 70/30, 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, simultaneously inhibiting the output of glucose from the liver.

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. However, the effect of NovoLog® Mix 70/30 is more rapid in onset compared to Novolin® (human insulin) 70/30 due to its faster absorption after subcutaneous injection.

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 tendency to form hexamers as observed with regular human insulin. The rapid absorption characteristics of NovoLog® are maintained by NovoLog® Mix 70/30. The insulin aspart in the soluble component of NovoLog® Mix 70/30 is absorbed more rapidly from the subcutaneous layer than regular human insulin. The remaining 70% is in crystalline form as insulin aspart protamine which has a prolonged absorption profile after subcutaneous injection.

The relative bioavailability of NovoLog® Mix 70/30 compared to NovoLog® and Novolin® 70/30 indicates that they are absorbed to similar degrees. In euglycemic clamp studies in healthy volunteers (n=23) after dosing with 0.2 U/kg of NovoLog® Mix 70/30, a mean maximum serum concentration (Cmax) of 23.4 ± 5.3 mU/L was reached after 60 minutes. The mean half-life (t1/2) of NovoLog® Mix 70/30 was about 8 to 9 hours. Serum insulin levels returned to baseline 15 to 18 hours after a subcutaneous dose. Similar data were seen in a separate euglycemic clamp study in healthy volunteers (n=24) after dosing with 0.3 U/kg of NovoLog® Mix 70/30. A Cmax of 61.3 ± 20.1 mU/L was reached after 85 minutes. Serum insulin levels returned to baseline 12 hours after a subcutaneous dose.

The Cmax and the area under the insulin concentration-time curve (AUC) after administration of NovoLog® Mix 70/30 differed by approximately 20% from those after administration of NovoLog® Mix 50/50 (investigational drug, not marketed) and Novolin® 70/30 (see Fig. 2 and 3 for pharmacokinetic profiles).

Image from Drug Label Content

Figure 2. Pharmacokinetic Profiles of NovoLog® Mix 70/30 and Novolin® 70/30

Image from Drug Label Content

Figure 3. Pharmacokinetic profiles for NovoLog® Mix 70/30 and other proportional mixes (* investigational drugs, not marketed).

Pharmacokinetic measurements were generated in clamp studies employing insulin doses of 0.3 U/kg. Insulin kinetics exhibit significant inter- and intra-patient variability. The rate of insulin absorption and consequently the onset of activity is known to be affected by the site of injection, exercise, and other variables (see PRECAUTIONS, General). Differences in pharmacokinetics between NovoLog® Mix 70/30 and products to which it has been compared are not associated with differences in overall glycemic control.

Distribution and Elimination- NovoLog® has a low binding to plasma proteins, 0 to 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

The two euglycemic clamp studies described above assessed glucose utilization after dosing of healthy volunteers. NovoLog® Mix 70/30 has a more rapid onset of action than regular human insulin in studies of normal volunteers and patients with diabetes. The peak pharmacodynamic effect of NovoLog® Mix 70/30 occurs between 1 and 4 hours after injection. The duration of action may be as long as 24 hours (see Figures 4 and 5).

Image from Drug Label Content

Figure 4. Pharmacodynamic Activity Profile of NovoLog® Mix 70/30 and Novolin® 70/30 in healthy subjects.

Image from Drug Label Content

Figure 5. Pharmacodynamic Activity Profiles for NovoLog® Mix 70/30 and other proportional mixes (* investigational drugs, not marketed)

Pharmacodynamic measurements were generated in clamp studies employing insulin doses of 0.3 U/kg. Insulin pharmacodynamics exhibit significant inter- and intra-patient variability. The rate of insulin absorption and consequently the onset of activity is known to be affected by the site of injection, exercise, and other variables (see PRECAUTIONS, General). Differences in pharmacodynamics between NovoLog® Mix 70/30 and products to which it has been compared are not associated with differences in overall glycemic control. 

Special populations

Children and adolescents-The pharmacokinetic and pharmacodynamic properties of NovoLog® Mix 70/30 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 70/30 has not been studied.

Gender- The effect of gender on the pharmacokinetics and pharmacodynamics of NovoLog® Mix 70/30 has not been studied.

Obesity-The effect of obesity and/or subcutaneous fat thickness on the pharmacokinetics and pharmacodynamics of NovoLog® Mix 70/30 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 70/30 has not been studied.

Renal impairment-The effect of renal function on the pharmacokinetics and pharmacodynamics of NovoLog® Mix 70/30 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 70/30, may be necessary in patients with renal dysfunction (see PRECAUTIONS, Renal Impairment).

Hepatic impairment- The effect of hepatic impairment on the pharmacokinetics and pharmacodynamics of NovoLog® Mix 70/30 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 70/30, may be necessary in patients with hepatic dysfunction (see PRECAUTIONS, Hepatic Impairment).

Pregnancy-The effect of pregnancy on the pharmacokinetics and pharmacodynamics of NovoLog® Mix 70/30 has not been studied (see PRECAUTIONS, Pregnancy).

Smoking-The effect of smoking on the pharmacokinetics and pharmacodynamics of NovoLog® Mix 70/30 has not been studied.

Clinical Studies

In a three-month, open-label trial, patients with Type 1 (n=146) or Type 2 (n=178) diabetes were treated BID (before breakfast and before supper) with NovoLog® Mix 70/30 or Novolin® 70/30. The small changes in HbA1c were comparable across the treatment groups (see Table 1).

Table 1: Glycemic Parameters at the End of Treatment [Mean (SD)]
NovoLog® Mix 70/30 Novolin® 70/30
Type 1, N=92
Fasting Blood Glucose (mg/dL) 173 (62) 141 (59)
1.5 Hour Post Breakfast 185 (80) 198 (80)
1.5 Hour Post Dinner 158 (77) 169 (66)
HbA1c (%) 8.4 (1.1) 8.3 (1.0)
Type 2, N=169
Fasting Blood Glucose (mg/dL) 151 (39) 151 (68)
1.5 Hour Post Breakfast 180 (64) 198 (80)
1.5 Hour Post Dinner 166 (50) 189 (50)
HbA1c (%) 7.9 (1.0) 8.1 (1.1)

The significance, with respect to the long-term clinical sequelae of diabetes, of the differences in postprandial hyperglycemia between treatment groups has not been established.

Specific anti-insulin antibodies as well as cross-reacting anti-insulin antibodies were monitored in the 3-month, open-label comparator trial as well as in a long-term extension trial (see PRECAUTIONS, Allergy).

In a 28-week, open-label trial, insulin-naïve patients with type 2 diabetes with fasting plasma glucose above 140 mg/dL currently treated with metformin ± thiazolidinedione therapy were randomized to receive either NovoLog® Mix 70/30 twice daily [before breakfast and before supper] or basal (long acting) insulin analog once daily1 (see Table 2). NovoLog® Mix 70/30 was started at an average dose of 5-6 IU (0.07 ± 0.03 IU/kg) twice daily (before breakfast and before supper), and bedtime basal (long acting) insulin analog was started at 10-12 IU (0.13 ± 0.03 IU/kg). Insulin doses were titrated weekly by decrements or increments of -2 to +6 units per injection to a pre-meal glucose goal of 80-110 mg/dL. The metformin dose was adjusted to 2550 mg/day. Approximately one-third of the patients in each group were also treated with pioglitazone (30 mg/day). Insulin secretagogues were discontinued in order to reduce the risk of hypoglycemia. Most patients were Caucasian (53%), and the mean initial weight was 90 kg.

Table 2: Combination Therapy with Oral Agents and Insulin In Patients with Type 2 Diabetes Mellitus [Mean (SD)]
Treatment duration 28-weeks NovoLog® Mix 70/30 Basal (Long Acting) Insulin Analog
Number of patients 117 116
HbA1c
Baseline mean (%) 9.7 (1.5) 9.8 (1.4)
End-of-study mean (± SD) 6.9 (1.2) 7.4 (1.2)
Mean change from baseline -2.8 -2.4
Percentage of subjects reaching HbA1c <7.0% 66% 40%
Total Daily Insulin Dose at end of study (U) 79 (40) 51 (27)
Number of patients with severe hypoglycemia 0 0
Minor hypoglycemic event/month/patient 0.28 0.06
Weight gain at end of study 5.4 (4.8) 3.5 (4.5)

INDICATIONS AND USAGE

NovoLog® Mix 70/30 is indicated for the treatment of patients with diabetes mellitus for the control of hyperglycemia.

CONTRAINDICATIONS

NovoLog® Mix 70/30 is contraindicated during episodes of hypoglycemia and in patients hypersensitive to NovoLog® Mix 70/30 or one of its excipients.

WARNINGS

Because NovoLog® Mix 70/30 has peak pharmacodynamic activity one hour after injection, it should be administered with meals.

NovoLog® Mix 70/30 should not be administered intravenously.

NovoLog® Mix 70/30 is not to be used in insulin infusion pumps.

NovoLog® Mix 70/30 should not be mixed with any other insulin product.

Hypoglycemia is the most common adverse effect of insulin therapy, including NovoLog® Mix 70/30. 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), species (animal, human), or method of manufacture (rDNA versus animal-source insulin) may result in the need for a change in dosage.

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 70/30 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).

Fixed ratio insulins are typically dosed on a twice daily basis, i.e., before breakfast and supper, with each dose intended to cover two meals or a meal and snack (see DOSAGE AND ADMINISTRATION). The dose of insulin required to provide adequate glycemic control for one of the meals may result in hyper- or hypoglycemia for the other meal. The pharmacodynamic profile may also be inadequate for patients (e.g. pregnant women) who require more frequent meals.

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.

Lipodystrophy 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 70/30. 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 70/30 in diabetic patients with various degrees of renal impairment have not been conducted. As with other insulins, the requirements for NovoLog® Mix 70/30 may be reduced in patients with renal impairment.

Hepatic Impairment

Clinical or pharmacology studies with NovoLog® Mix 70/30 in diabetic patients with various degrees of hepatic impairment have not been conducted. As with other insulins, the requirements for NovoLog® Mix 70/30 may be reduced in patients with hepatic impairment.

Allergy

Local Reactions- Erythema, swelling, and pruritus at the injection site have been observed with NovoLog® Mix 70/30 as with other 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

Specific anti-insulin antibodies as well as cross-reacting anti-insulin antibodies were monitored in the 3-month, open-label comparator trial as well as in a long-term extension trial. Changes in cross-reactive antibodies were more common after NovoLog® Mix 70/30 than with Novolin® 70/30 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

Patients should be informed about potential risks and advantages of NovoLog® Mix 70/30 therapy including the possible side effects. 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 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 70/30 during pregnancy or lactation (see PRECAUTIONS, Pregnancy).

Laboratory tests

The therapeutic response to NovoLog® Mix 70/30 should be assessed by measurement of serum or blood glucose and glycosylated hemoglobin.

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, 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).

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.

In addition, under the influence of sympatholytic medical products such as beta-blockers, clonidine, guanethidine, and reserpine, the signs of hypoglycemia may be reduced or absent (see CLINICAL PHARMACOLOGY).

Mixing of insulins

NovoLog® Mix 70/30 should not be mixed with any other insulin product.

Carcinogenesis, mutagenesis, impairment of fertility

Standard 2-year carcinogenicity studies in animals have not been performed to evaluate the carcinogenic potential of NovoLog® Mix 70/30. In 52-week studies, Sprague-Dawley rats were dosed subcutaneously with NovoLog®, the rapid-acting component of NovoLog® Mix 70/30, 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

Animal reproduction studies have not been conducted with NovoLog® Mix 70/30. However, reproductive toxicology and teratology studies have been performed with NovoLog® (the rapid-acting component of NovoLog® Mix 70/30) 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.

It is not known whether NovoLog® Mix 70/30 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 70/30 in pregnant women. NovoLog® Mix 70/30 should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

Nursing mothers

It is unknown whether NovoLog® Mix 70/30 is excreted in human milk as is human insulin. There are no adequate and well-controlled studies of the use of NovoLog® Mix 70/30 or NovoLog® in lactating women. 

Pediatric use

Safety and effectiveness of NovoLog® Mix 70/30 in children have not been established.

Geriatric use

Clinical studies of NovoLog® Mix 70/30 did not include sufficient numbers of patients aged 65 and over to determine whether they respond differently than younger patients. In general, dose selection for an elderly patient should be cautious, usually starting at the low end of the dosing range reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy in this population.

ADVERSE REACTIONS

Clinical trials comparing NovoLog® Mix 70/30 with Novolin® 70/30 did not demonstrate a difference in frequency of adverse events between the two treatments.

Adverse events commonly associated with human insulin therapy include the following:

Body as whole: Allergic reactions (see PRECAUTIONS, Allergy).

Skin and Appendages: Local injection site reactions or rash or pruritus, as with other insulin therapies, occurred in 7% of all patients on NovoLog® Mix 70/30 and 5% on Novolin® 70/30. Rash led to withdrawal of therapy in <1% of patients on either drug (see PRECAUTIONS, Allergy).

Hypoglycemia: see WARNINGS and PRECAUTIONS.

Other: Small elevations in alkaline phosphatase were observed in patients treated in NovoLog® controlled clinical trials. There have been no clinical consequences of these laboratory findings.

OVERDOSAGE

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 glucagon or concentrated intravenous glucose. Sustained carbohydrate intake and observation may be necessary because hypoglycemia may recur after apparent clinical recovery.

DOSAGE AND ADMINISTRATION

General

Fixed ratio insulins are typically dosed on a twice daily basis, i.e. before breakfast and supper, with each dose intended to cover two meals or a meal and snack. NovoLog® Mix 70/30 is intended only for subcutaneous injection (into the abdominal wall, thigh, or upper arm). NovoLog® Mix 70/30 should not be administered intravenously. The absorption rate of NovoLog® Mix 70/30 from the subcutaneous tissue allows dosing within 15 minutes of meal initiation.

Dose regimens of NovoLog® Mix 70/30 will vary among patients and should be determined by the health care professional familiar with the patient’s metabolic needs, eating habits, and other 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.

Table 3. Summary of pharmacodynamic properties of insulin products (pooled cross-study comparison) and recommended interval between dosing and meal initiation
*
Applicable only to Novolin® R and NovoLog® alone or as components of insulin mixes.
Insulin Products

Dose (U/kg)

Used in Study
Recommended interval between dosing and meal initiation (minutes)*

Time of Peak Activity (hours after dosing)

(mean± SD)
Percent of Total Activity Occurring in the First 4 hours (mean, range)
NovoLog® 0.3 10-20 2.2 ± 0.98 65% ± 11%
Novolin R® 0.2 30 3.3 60% ± 16%
Novolin 50/50® 0.5 30 4.0 ± 0.6 54% ± 12%
NovoLog Mix 70/30® 0.3 10-20 2.4 ± 0.80 45% ± 22%
Novolin 70/30® 0.3 30 4.2 ± 0.39 25% ± 5%
Novolin N® 0.3 n/a 8.0 ± 5.3 21% ±11%

Administration using NovoLog Mix 70/30 FlexPen® Prefilled Syringes or vials:

Disposable NovoLog® Mix 70/30 FlexPen® Prefilled Syringes:

 NovoLog® Mix 70/30 suspension should be visually inspected and resuspended immediately before use. The resuspended NovoLog® Mix 70/30 must appear uniformly white and cloudy. Before use, roll the disposable NovoLog® Mix 70/30 FlexPen® prefilled syringe between your palms 10 times. This procedure should be carried out with the FlexPen® cartridge in a horizontal position. Thereafter, turn the disposable NovoLog® Mix 70/30 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 70/30 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. After use, needles on the disposable NovoLog® Mix 70/30 FlexPen® prefilled syringes should not be recapped. Used syringes, 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.

Vial: NovoLog® Mix 70/30 vial must be resuspended immediately before use. Roll the vial gently 10 times in your hand to mix it. This procedure should be carried out with the vial in a horizontal position. The rolling procedure must be repeated until the suspension appears uniformly white and cloudy. Inject immediately.

HOW SUPPLIED

NovoLog® Mix 70/30 is available in the following package sizes: each presentation contains 100 Units of insulin aspart per mL (U-100).

10 mL vials NDC 0169-3685-12
3 mL NovoLog® Mix 70/30 FlexPen® prefilled syringe NDC 0169-3696-19

RECOMMENDED STORAGE

NovoLog® Mix 70/30 should be stored between 2°C and 8°C (36°F to 46°F). Do not freeze. Do not use NovoLog® Mix 70/30 if it has been frozen.

Vials:

The vials should be stored in a refrigerator, not in a freezer. If refrigeration is not possible, the bottle in use can be kept unrefrigerated at room temperature below 30°C (86°F) for up to 28 days, as long as it is kept as cool as possible and away from direct heat and light.

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.

NovoLog Mix 70/30 FlexPen® Prefilled Syringes:

Once a NovoLog® Mix 70/30 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). NovoLog® Mix 70/30 FlexPen® prefilled syringes in use must NOT be stored in the refrigerator. Keep all disposable NovoLog® Mix 70/30 FlexPen® prefilled syringes away from direct heat and sunlight. Unpunctured NovoLog® Mix 70/30 FlexPen® prefilled syringes can be used until the expiration date printed on the label if they are stored in a refrigerator. Keep unused NovoLog® Mix 70/30 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°C - 8°C [36°F- 46°F])

In-use (opened)

Room Temperature

(below 30°C[86°F])
10 mL vial 28 days Until expiration date 28 days (refrigerated/room temperature)
3ml FlexPen® 14 days Until expiration date 14 days (Do not refrigerate)

REFERENCES

1. Raskin R, Allen E, Hollander P, et al. Initiating insulin therapy in type 2 diabetes: a comparison of biphasic and basal insulin analogs. Diabetes Care. 2005; 28:260-265.

Date of issue: October 2007

Version: 7

Novo Nordisk®, NovoLog®, FlexPen®, Novolin® and NovoFine® are trademarks owned by Novo Nordisk® A/S.

© 2002-2007 Novo Nordisk A/S

NovoLog® Mix 70/30 is covered by US Patent Nos. 5,547,930, 5,618,913, 5,834,422, 5,840,680, 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

2880 Bagsvaerd, Denmark

Manufactured for:

Novo Nordisk Inc.

Princeton, NJ 08540

www.novonordisk-us.com

PATIENT INFORMATION

Patient Information for 10 mL vials (100 Units/mL, U-100)

NovoLog® Mix 70/30

70% insulin aspart protamine suspension and

30% insulin aspart injection, (rDNA origin)

What is the most important information I should know about NovoLog® Mix 70/30?

WARNINGS

THIS NOVO NORDISK® HUMAN INSULIN ANALOG MIXTURE IS DIFFERENT FROM OTHER INSULIN MIXTURES BECAUSE IT HAS A RAPID ONSET OF ACTION. THE RAPID ONSET OF ACTION MEANS THAT YOU SHOULD TAKE YOUR DOSE OF NOVOLOG® MIX 70/30 (70% INSULIN ASPART PROTAMINE SUSPENSION AND 30% INSULIN ASPART INJECTION, [rDNA ORIGIN]) WITHIN 15 MINUTES OF A MEAL.

ANY CHANGE OF INSULIN SHOULD BE MADE CAUTIOUSLY AND ONLY UNDER MEDICAL SUPERVISION. CHANGES IN STRENGTH, MANUFACTURER, TYPE (E.G., REGULAR, NPH, ANALOG), SPECIES (BEEF, PORK, BEEF-PORK, HUMAN), OR METHOD OF MANUFACTURE (rDNA VERSUS ANIMAL-SOURCE INSULIN) MAY RESULT IN THE NEED FOR A CHANGE IN THE TIMING OR DOSAGE OF NOVOLOG® MIX 70/30.

PATIENTS TAKING NOVOLOG® MIX 70/30 MAY REQUIRE A CHANGE IN DOSAGE FROM THAT USED WITH OTHER INSULINS. IF AN ADJUSTMENT IS NEEDED, IT MAY OCCUR WITH THE FIRST DOSE OR DURING THE FIRST SEVERAL WEEKS OR MONTHS.

What is NovoLog® Mix 70/30?

NovoLog® Mix 70/30 (NO-voe-log-MIX-SEV-en-tee-THIR-tee) is a mixed insulin analog similar to human insulin mixes used to treat diabetes. The active ingredient in NovoLog® Mix 70/30 is insulin aspart, which is made through biotechnology. Another ingredient, protamine, is used to slow the absorption of the insulin analog by your body.

NovoLog® Mix 70/30 comes in:

 

Who should NOT take NovoLog® Mix 70/30?

Do NOT take NovoLog® Mix 70/30 if:

Tell your doctor if:

 

How should I take NovoLog® Mix 70/30?

See the end of this patient information for instructions about preparing and giving the injection.

What should I do during illness?

Even if you have a short term (acute) illness, especially with vomiting or fever, continue taking your insulin. If possible, stay on your regular diet. If you have trouble eating, drink fruit juices, regular soft drinks, or clear soups. If you can, eat small amounts of bland foods. Test your urine for glucose and ketones and, if possible, test your blood glucose. Note the results and contact your health care provider for possible insulin dose adjustment. If you have severe and continued vomiting, get emergency medical care.

What should I avoid while taking NovoLog® Mix 70/30?

Alcohol, including beer and wine, may increase and lengthen the risk of hypoglycemia (too low blood sugar) when you take NovoLog® Mix 70/30.

Be careful when you drive a car or operate machinery. Your ability to concentrate or react may be reduced if you have hypoglycemia.

Ask your doctor if you should drive if you have:

What are the possible side effects of NovoLog® Mix 70/30?

Common side effects include blood sugar that is too low (hypoglycemia).

Hypoglycemia (too little glucose in the blood) is one of the most frequent problems experienced by insulin users. It can be brought about by:

  1. Missing or delaying meals
  2. Taking too much insulin
  3. Exercising or working more than usual
  4. An infection or illness (especially with diarrhea or vomiting)
  5. A change in the body’s need for insulin
  6. Diseases of the adrenal, pituitary, or thyroid gland, or kidney or liver disease that is getting worse
  7. Interactions with other drugs that lower blood glucose, such as oral (taken by mouth) antidiabetic medicines, salicylates (for example, aspirin), sulfa antibiotics, and certain antidepressants
  8. Drinking of alcohol

What are symptoms of mild to moderate hypoglycemia?

What are symptoms of severe hypoglycemia?

If you develop serious hypoglycemic reactions, get medical help right away.

Without recognition of early warning symptoms, you may not be able to take steps to avoid more serious hypoglycemia. Be alert for all of the various types of symptoms that may indicate hypoglycemia. Patients who experience hypoglycemia without early warning symptoms should monitor their blood glucose frequently, especially prior to activities such as driving. If the blood glucose is below your normal fasting glucose, you should consider eating or drinking sugar-containing foods to treat your hypoglycemia. Mild to moderate hypoglycemia may be treated by eating foods or drinks that contain sugar. Patients should always carry a quick source of sugar, such as candy mints or glucose tablets. More severe hypoglycemia may require the assistance of another person. Patients who are unable to take sugar orally or who are unconscious require an injection of glucagon or should be treated with intravenous administration of glucose at a medical facility. You should learn to recognize your own symptoms of hypoglycemia. If you are uncertain about these symptoms, you should monitor your blood glucose frequently to help you learn to recognize the symptoms that you experience with hypoglycemia.

If you have frequent episodes of hypoglycemia or experience difficulty in recognizing the symptoms, you should consult your doctor to discuss possible changes in therapy, meal plans, and/or exercise programs to help you avoid hypoglycemia.

Common side effects include blood sugar that is too high (hyperglycemia) and diabetic ketoacidosis.

Hyperglycemia (too much glucose in the blood) may develop if your body has too little insulin. Hyperglycemia can be brought about by any of the following:

  1. Not taking your insulin or taking less than the doctor has prescribed
  2. Eating much more than your meal plan suggests
  3. Developing a fever, infection, or being under stress

In patients with type 1 or insulin-dependent diabetes, long-lasting hyperglycemia can cause diabetic ketoacidosis (DKA). The first symptoms of DKA usually come on slowly, over a period of hours or days, and include feeling drowsy, flushed face, thirst, loss of appetite, and fruity odor on the breath. With DKA, urine tests show large amounts of glucose and ketones. Heavy breathing and a rapid pulse are more severe symptoms. If uncorrected, long-lasting hyperglycemia or DKA can lead to nausea, vomiting, stomach pains, dehydration, loss of consciousness, or even death. Therefore, it is important that you obtain medical help right away.

Other possible side effects include the following:

Get medical help right away if you develop a rash over your whole body, have trouble breathing, a fast heartbeat, or sweating. These are signs of a dangerous allergic reaction (systemic allergic reaction). These reactions are not common.

There are other possible side effects from NovoLog® Mix 70/30. Ask your doctor or pharmacist for further information. Tell your doctor or pharmacist if you have any other unwanted effects that you believe are caused by this insulin.

How should I store NovoLog®Mix 70/30?

Store insulin in a refrigerator (2°C to 8°C [36°F to 46°F]), but not in a freezer. Do not use NovoLog® Mix 70/30 if it has been frozen. Keep unused vials in the carton so they will stay clean and protected from light.

The vials should be stored in a refrigerator, not in a freezer. If refrigeration is not possible, the bottle that you are currently using can be kept unrefrigerated at room temperature (below 30ºC [86ºF]) up to 28 days, as long as it is kept as cool as possible. Keep all vials away from direct heat and sunlight.

General information about NovoLog Mix 70/30

Use NovoLog® Mix 70/30 only to treat your diabetes. Do not share it with anyone else. Ask your doctor or pharmacist about any concerns you have. They can answer your questions and give you written information about NovoLog® Mix 70/30 written for health care professionals.

How should I prepare and deliver the injection using the 10 ml vial?

  1. At your first use, remove the tamper-resistant cap of the vial. If the cap has already been removed, do not use this vial and return it to your pharmacy.
  2. Wipe the rubber stopper with an alcohol swab.
  3. Roll the vial gently 10 times in your hands to mix it. This procedure should be carried out with the vial in a horizontal position. Do not shake it vigorously. Vigorous shaking right before the dose is drawn into the syringe may cause bubbles or froth, which could cause dosage errors. The insulin should be used only if it uniformly appears white and cloudy.
  4. Pull back the plunger until the black tip reaches the marking for the number of units you will inject.
  5. Push the needle through the rubber stopper into the vial.
  6. Push the plunger all the way in. This inserts air into the vial.
  7. Turn the vial and syringe upside down together and slowly pull the plunger back to a few units beyond the correct dose.
  8. If there are air bubbles in the syringe, tap the syringe gently with your finger to raise the air bubbles to the needle. Then slowly push the plunger to the correct unit marking.
  9. Lift the vial off the syringe.
  10. Inject right away. If there is a delay after you rolled the vial, you will have to roll it again to remix the insulin. (See injection instructions “How should I inject NovoLog® Mix 70/30 with a syringe)
  11. After the injection, remove the needle without recapping and dispose of it in a puncture-resistant container. Used syringes, 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 should I inject NovoLog® Mix 70/30 insulin with a syringe?

  1. Pinch your skin between two fingers, push the needle into the skinfold, and push the plunger to inject the insulin under your skin. The needle should be perpendicular to the skin. This means the needle will be straight in.
  2. Keep the needle under your skin for at least 6 seconds to make sure you have injected all the insulin.
  3. If blood appears after you pull the needle from your skin, press the injection site lightly with a finger. Do not rub the area.

Helpful information for people with diabetes is published by the American Diabetes Association, 1660 Duke Street, Alexandria, VA 22314.

Date of Issue: October 2007

Version: 5

Novo Nordisk®, NovoLog®, FlexPen® and NovoFine® are trademarks owned by Novo Nordisk A/S.

© 2002–2007 Novo Nordisk A/S

NovoLog® Mix 70/30 is covered by US Patent Nos. 5,547,930, 5,618,913, 5,834,422, 5,840,680, 5,866,538 and other patents pending.

For information about NovoLog® Mix 70/30 contact:

Novo Nordisk Inc.

100 College Road West

Princeton, New Jersey 08540

1-800-727-6500

www.novonordisk-us.com

Manufactured by

Novo Nordisk A/S

DK-2880 Bagsvaerd, Denmark

PATIENT INFORMATION

Patient Information for NovoLog® Mix 70/30 FlexPen® Prefilled Syringe (100 Units/mL, U-100)

NovoLog® Mix 70/30 FlexPen®

70% insulin aspart protamine suspension and

30% insulin aspart injection, (rDNA origin)

What is the most important information I should know about NovoLog® Mix 70/30?

WARNINGS

THIS NOVO NORDISK® HUMAN INSULIN ANALOG MIXTURE IS DIFFERENT FROM OTHER INSULIN MIXTURES BECAUSE IT HAS A RAPID ONSET OF ACTION. THE RAPID ONSET OF ACTION MEANS THAT YOU SHOULD TAKE YOUR DOSE OF NOVOLOG® MIX 70/30 (70% INSULIN ASPART PROTAMINE SUSPENSION AND 30% INSULIN ASPART INJECTION, [rDNA ORIGIN]) WITHIN 15 MINUTES OF A MEAL.

ANY CHANGE OF INSULIN SHOULD BE MADE CAUTIOUSLY AND ONLY UNDER MEDICAL SUPERVISION. CHANGES IN STRENGTH, MANUFACTURER, TYPE (E.G., REGULAR, NPH, ANALOG), SPECIES (BEEF, PORK, BEEF-PORK, HUMAN), OR METHOD OF MANUFACTURE (rDNA VERSUS ANIMAL-SOURCE INSULIN) MAY RESULT IN THE NEED FOR A CHANGE IN THE TIMING OR DOSAGE OF NOVOLOG® MIX 70/30.

PATIENTS TAKING NOVOLOG® MIX 70/30 MAY REQUIRE A CHANGE IN DOSAGE FROM THAT USED WITH OTHER INSULINS. IF AN ADJUSTMENT IS NEEDED, IT MAY OCCUR WITH THE FIRST DOSE OR DURING THE FIRST SEVERAL WEEKS OR MONTHS.

What is NovoLog® Mix 70/30?

NovoLog® Mix 70/30 (NO-voe-log-MIX-SEV-en-tee-THIR-tee) is a mixed insulin analog similar to human insulin mixes used to treat diabetes. The active ingredient in NovoLog® Mix 70/30 is insulin aspart, which is made through biotechnology. Another ingredient, protamine, is used to slow the absorption of the insulin analog by your body.

NovoLog®. Mix 70/30 comes in:

  

Who should NOT take NovoLog®  Mix 70/30?

Do NOT take NovoLog® Mix 70/30 if:

 

Tell your doctor if:

 

How should I take NovoLog® Mix 70/30?

See the end of this patient information for instructions about preparing and giving the injection.

What should I do during illness?

Even if you have a short-term (acute) illness, especially with vomiting or fever, continue taking your insulin. If possible, stay on your regular diet. If you have trouble eating, drink fruit juices, regular soft drinks, or clear soups. If you can, eat small amounts of bland foods. Test your urine for glucose and ketones and, if possible, test your blood glucose. Note the results and contact your health care provider for possible insulin dose adjustment. If you have severe and continued vomiting, get emergency medical care.

What should I avoid while taking NovoLog® Mix 70/30?

Alcohol, including beer and wine, may increase and lengthen the risk of hypoglycemia (too low blood sugar) when you take NovoLog® Mix 70/30.

Be careful when you drive a car or operate machinery. Your ability to concentrate or react may be reduced if you have hypoglycemia. Ask your doctor if you should drive if you have:

What are the possible side effects of NovoLog® Mix 70/30?

Common side effects include blood sugar that is too low (hypoglycemia).

Hypoglycemia (too little glucose in the blood) is one of the most frequent problems experienced by insulin users. It can be brought about by:

  1. Missing or delaying meals
  2. Taking too much insulin
  3. Exercising or working more than usual
  4. An infection or illness (especially with diarrhea or vomiting)
  5. A change in the body’s need for insulin
  6. Diseases of the adrenal, pituitary, or thyroid gland, or kidney or liver disease that is getting worse
  7. Interactions with other drugs that lower blood glucose, such as oral (taken by mouth) antidiabetic medicines, salicylates (for example, aspirin), sulfa antibiotics, and certain antidepressants
  8. Drinking of alcohol

What are symptoms of mild to moderate hypoglycemia:

What are symptoms of severe hypoglycemia:

If you develop serious hypoglycemic reactions, get medical help right away.

Without recognition of early warning symptoms, you may not be able to take steps to avoid more serious hypoglycemia. Be alert for all of the various types of symptoms that may indicate hypoglycemia. Patients who experience hypoglycemia without early warning symptoms should monitor their blood glucose frequently, especially prior to activities such as driving. If the blood glucose is below your normal fasting glucose, you should consider eating or drinking sugar-containing foods to treat your hypoglycemia. Mild to moderate hypoglycemia may be treated by eating foods or drinks that contain sugar. Patients should always carry a quick source of sugar, such as candy mints or glucose tablets. More severe hypoglycemia may require the assistance of another person. Patients who are unable to take sugar orally or who are unconscious require an injection of glucagon or should be treated with intravenous administration of glucose at a medical facility. You should learn to recognize your own symptoms of hypoglycemia. If you are uncertain about these symptoms, you should monitor your blood glucose frequently to help you learn to recognize the symptoms that you experience with hypoglycemia.

If you have frequent episodes of hypoglycemia or experience difficulty in recognizing the symptoms, you should consult your doctor to discuss possible changes in therapy, meal plans, and/or exercise programs to help you avoid hypoglycemia.

Common side effects include blood sugar that is too high (hyperglycemia) and diabetic ketoacidosis.

Hyperglycemia (too much glucose in the blood) may develop if your body has too little insulin. Hyperglycemia can be brought about by any of the following:

  1. Not taking your insulin or taking less than the doctor has prescribed
  2. Eating much more than your meal plan suggests
  3. Developing a fever, infection, or being under stress

In patients with type 1 or insulin-dependent diabetes, long-lasting hyperglycemia can cause diabetic ketoacidosis (DKA). The first symptoms of DKA usually come on slowly, over a period of hours or days, and include feeling drowsy, flushed face, thirst, loss of appetite, and fruity odor on the breath. With DKA, urine tests show large amounts of glucose and ketones. Heavy breathing and a rapid pulse are more severe symptoms. If uncorrected, long-lasting hyperglycemia or DKA can lead to nausea, vomiting, stomach pains, dehydration, loss of consciousness, or even death. Therefore, it is important that you obtain medical help right away.

Other possible side effects include the following:

There are other possible side effects from NovoLog® Mix 70/30. Ask your doctor or pharmacist for further information. Tell your doctor or pharmacist if you have any other unwanted effects that you believe are caused by this insulin.

How should I store NovoLog® Mix 70/30?

Store insulin in a refrigerator (2°C to 8°C [36°F to 46°F]), but not in a freezer. Do not use NovoLog® Mix 70/30 if it has been frozen. Keep unused disposable NovoLog® Mix 70/30 FlexPen® prefilled syringes in the carton so they will stay clean and protected from light.

Do not refrigerate disposable NovoLog® Mix 70/30 FlexPen® prefilled syringe in use (the rubber stopper has been punctured). However, keep them as cool as possible (below 30ºC [86ºF]). Keep all disposable NovoLog® Mix 70/30 FlexPen® prefilled syringes away from direct heat and sunlight.

General information about NovoLog® Mix 70/30

Use NovoLog® Mix 70/30 only to treat your diabetes. Do not share it with anyone else. Ask your doctor or pharmacist about any concerns you have. They can answer your questions and give you written information about NovoLog® Mix 70/30 written for health care professionals.

Call 1-800-727-6500 for additional information.

Helpful information for people with diabetes is published by the American Diabetes Association, 1660 Duke Street, Alexandria, VA 22314.

Date of Issue: October 2007

Version: 5

Novo Nordisk®, NovoLog®, FlexPen®, Novolin® and NovoFine® are trademarks owned by Novo Nordisk A/S.

© 2002–2007 Novo Nordisk A/S

NovoLog® Mix 70/30 is covered by US Patent Nos. 5,547,930, 5,618,913, 5,834,422, 5,840,680, 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® Mix 70/30 contact:

Novo Nordisk Inc.

100 College Road West

Princeton, New Jersey 08540

www.novonordisk-us.com

NovoLog® Mix 70/30 FlexPen®

Using the disposable 3mL NovoLog® Mix 70/30 3mL FlexPen® Prefilled Syringe

NovoLog® Mix 70/30 FlexPen® prefilled syringe is a disposable dial-a-dose insulin delivery system able to deliver 1 to a maximum of 60 units. The dose can be adjusted in increments of 1 unit. NovoLog® Mix 70/30 FlexPen® prefilled syringe is designed for use with NovoFine® single use needles. NovoLog® Mix 70/30 FlexPen® prefilled syringe is not recommended for the blind or severely visually impaired without the assistance of a sighted individual trained in the proper use of the product.

Please read these instructions completely before using this device.

Image from Drug Label Content

NovoFine® needle

Image from Drug Label Content

1. PREPARING THE FLEXPEN® PREFILLED SYRINGE:

a. Pull off the device cap.

b. Wipe the rubber stopper with an alcohol swab.

Image from Drug Label Content

c. Before using the disposable NovoLog® Mix 70/30 FlexPen® prefilled syringe for the first time, roll the disposable NovoLog® Mix 70/30 FlexPen® prefilled syringe between your palms 10 times. This procedure should be carried out with the FlexPen® cartridge in a horizontal position (see diagram A). Thereafter, turn the pen up and down between position 1 and 2 so that the glass ball moves from one end of the insulin reservoir to the other (see diagram A). Do this at least 10 times. This procedure must be repeated until the insulin appears uniformly white and cloudy. Mixing is easier when the insulin has reached room temperature.

To ensure even mixing of the remaining insulin, there must be at least 12 units of insulin left in the reservoir. If there are less than 12 units left, do not use the disposable NovoLog® Mix 70/30 FlexPen® prefilled syringe.

The numbers on the insulin reservoir can be used to estimate the amount of insulin left in the syringe. Do not use these numbers to measure the insulin dose. You cannot set a dose greater than the number of units remaining in the reservoir.

d. Place the needle onto the disposable prefilled syringe immediately before use. Remove the protective tab from the disposable needle and screw the needle tightly onto the disposable NovoLog® Mix 70/30 FlexPen® prefilled syringe (see diagram B)

e. Pull off the outer and inner needle caps (see diagram C). Do not discard the outer needle cap. Never place a disposable needle on your NovoLog® Mix 70/30 FlexPen® prefilled syringe until you are ready to give an injection. Remove the needle immediately after use. If the needle is not removed, some liquid may be expelled from the NovoLog® Mix 70/30 FlexPen® prefilled syringe causing a change in insulin concentration (strength).

If there is a delay between mixing of the insulin and the injection, the insulin will need to be mixed again. The NovoLog® Mix 70/30 FlexPen® prefilled syringe should be turned upside down between positions 1 and 2 (see diagram A), so that the glass ball moves from one end of the insulin reservoir to the other. Do this until the insulin appears uniformly white and cloudy.

Image from Drug Label Content

f. Giving the airshot before each injection:

Small amounts of air may collect in the needle and insulin reservoir during normal use. To avoid injecting air and to ensure proper dosing, hold the syringe with the needle pointing up and tap the syringe gently with your finger so any air bubbles collect in the top of the reservoir. Remove both the plastic outer cap and the needle cap.

g. Dial 2 units (see diagram D).

h. Holding the syringe with the needle pointing up, tap the reservoir gently with your finger a few times (see diagram E). Still with the needle pointing up, press the push button as far as it will go and see if a drop of insulin appears at the needle tip. If not, repeat the procedure until insulin appears. Before the first use of each disposable NovoLog® Mix 70/30 FlexPen® prefilled syringe, you may need to perform up to 6 airshots to get a droplet of insulin at the needle tip. If you need to make more than 6 airshots, do not use the syringe, and contact Novo Nordisk at 1-800-727-6500. A small air bubble may remain but it will not be injected because the operating mechanism prevents the reservoir from being completely emptied.

2. SETTING THE DOSE

Check that the dose selector is set at 0 (see diagram F). Dial the number of units you need to inject. The dose can be corrected either up or down by turning the dose selector in either direction. When dialing back, be careful not to push the push button as insulin will come out. You cannot set a dose larger than the number of units left in the reservoir.

3. GIVING THE INJECTION

Use the injection technique recommended by your doctor or health care professionals.

Image from Drug Label Content

a. Pinch the skin between two fingers; push the needle into the skinfold (see diagram G).

b. Deliver the dose by pressing the push button all the way in (see diagram H). Be careful only to push the push button when injecting.

c. After the injection, the needle should remain under the skin for at least 6 seconds. Keep the push button fully depressed until the needle is withdrawn from the skin. This will ensure that the full dose has been delivered. If blood appears after you pull the needle from your skin, press the injection site lightly with a finger. Do not rub the area.

d. After the injection, remove the needle without recapping and dispose of it in a puncture-resistant container. Used syringes, 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.

It is important that you use a new needle for each injection. Health care professionals, relatives, and other caregivers, should follow general precautionary measures for removal and disposal of needles to eliminate the risk of unintended needle stick.

 

4. LATER (SUBSEQUENT) INJECTIONS

It is important that you use a new needle for each injection. Follow the directions in steps 1 – 3.

Before each injection: turn the disposable NovoLog® Mix 70/30 FlexPen® prefilled syringe up and down between position 1 and 2 (diagram A) so that the glass ball moves from one end of the insulin reservoir to the other. Do this at least 10 times. This procedure must be repeated until the insulin appears uniformly white and cloudy. Inject immediately. If there is a delay between mixing of the insulin and the injection, the insulin will need to be mixed again as described above.

To ensure even mixing of the remaining insulin, there must be at least 12 units of insulin left in the reservoir. If there are less than 12 units left, do not use the disposable NovoLog® Mix 70/30 FlexPen® prefilled syringe.

The numbers on the insulin reservoir can be used to estimate the amount of insulin left in the syringe. Do not use these numbers to measure the insulin dose.

You cannot set a dose greater than the number of units remaining in the reservoir.

5. FUNCTION CHECK

Image from Drug Label Content

If your disposable NovoLog® Mix 70/30 FlexPen® prefilled syringe is not working properly, follow this procedure:

The insulin should fill the lower part of the cap (as shown in diagram I). If the disposable NovoLog® Mix 70/30 FlexPen® prefilled syringe has released too much, or too little insulin, repeat the test. If it happens again, do not use your disposable NovoLog® Mix 70/30 FlexPen® prefilled syringe and contact Novo Nordisk at 1-800-727-6500.

Dispose of the used NovoLog® Mix 70/30 FlexPen® prefilled syringe carefully without the needle attached.

6. IMPORTANT NOTES


NovoLog Mix 70/30 (insulin aspart)
PRODUCT INFO
Product Code 0169-3685 Dosage Form INJECTION, SUSPENSION
Route Of Administration SUBCUTANEOUS DEA Schedule
INGREDIENTS
Name (Active Moiety) Type Strength
INSULIN ASPART (insulin aspart) Active 100 UNITS  In 1 MILLILITER
disodium hydrogen phosphate dihydrate Inactive 1.25 MILLIGRAM  In 1 MILLILITER
hydrochloric acid Inactive  
MANNITOL Inactive 36.4 MILLIGRAM  In 1 MILLILITER
metacresol Inactive 1.72 MILLIGRAM  In 1 MILLILITER
phenol Inactive 1.50 MILLIGRAM  In 1 MILLILITER
protamine sulfate Inactive 0.32 MILLIGRAM  In 1 MILLILITER
SODIUM CHLORIDE Inactive 0.58 MILLIGRAM  In 1 MILLILITER
sodium hydroxide Inactive  
zinc Inactive 19.6 MICROGRAM  In 1 MILLILITER
IMPRINT INFORMATION
Characteristic Appearance Characteristic Appearance
Color Score
Shape Symbol
Imprint Code Coating
Size
PACKAGING
# NDC Package Description Multilevel Packaging
1 0169-3685-12 1 VIAL In 1 CARTON contains a VIAL, GLASS
1 10 MILLILITER In 1 VIAL, GLASS This package is contained within the CARTON (0169-3685-12)

NovoLog Mix 70/30 (insulin aspart)
PRODUCT INFO
Product Code 0169-3696 Dosage Form INJECTION, SUSPENSION
Route Of Administration SUBCUTANEOUS DEA Schedule
INGREDIENTS
Name (Active Moiety) Type Strength
INSULIN ASPART (insulin aspart) Active 100 UNITS  In 1 MILLILITER
disodium hydrogen phosphate dihydrate Inactive 1.25 MILLIGRAM  In 1 MILLILITER
glycerol Inactive 16.0 MILLIGRAM  In 1 MILLILITER
hydrochloric acid Inactive  
metacresol Inactive 1.72 MILLIGRAM  In 1 MILLILITER
phenol Inactive 1.50 MILLIGRAM  In 1 MILLILITER
protamine sulfate Inactive 0.32 MILLIGRAM  In 1 MILLILITER
SODIUM CHLORIDE Inactive 0.877 MILLIGRAM  In 1 MILLILITER
sodium hydroxide Inactive  
zinc Inactive 19.6 MICROGRAM  In 1 MILLILITER
IMPRINT INFORMATION
Characteristic Appearance Characteristic Appearance
Color Score
Shape Symbol
Imprint Code Coating
Size
PACKAGING
# NDC Package Description Multilevel Packaging
1 0169-3696-19 5 SYRINGE In 1 CARTON contains a SYRINGE, PLASTIC
1 3 MILLILITER In 1 SYRINGE, PLASTIC This package is contained within the CARTON (0169-3696-19)

Revised: 10/2007Novo Nordisk Inc.

Data are from FDA and U.S. National Library of Medicine.