Novolog Injection

Name: Novolog Injection

Novolog Injection Dosage and Administration

Important Administration Instructions 

• Always check insulin labels before administration [see Warnings and Precautions (5.4)]. • Inspect NOVOLOG visually before use. It should appear clear and colorless. Do not use NOVOLOG if particulate matter or coloration is seen. • Do NOT mix NOVOLOG with other insulins when administering using a continuous subcutaneous infusion pump.

Route of Administration

Subcutaneous Injection

• Inject NOVOLOG subcutaneously within 5-10 minutes before a meal into the abdominal area, thigh, buttocks or upper arm. • Rotate injection sites within the same region from one injection to the next to reduce the risk of lipodystrophy [see Adverse Reactions (6.1)]. • NOVOLOG administered by subcutaneous injection should generally be used in regimens with an intermediate- or long-acting insulin. • NOVOLOG may be diluted with Insulin Diluting Medium for NOVOLOG for subcutaneous injection. Diluting one part NOVOLOG to nine parts diluent will yield a concentration one-tenth that of NOVOLOG (equivalent to U-10). Diluting one part NOVOLOG to one part diluent will yield a concentration one-half that of NOVOLOG (equivalent to U-50).

Continuous Subcutaneous Infusion (Insulin Pump)

• Train patients using continuous subcutaneous insulin fusion pump therapy to administer insulin by injection and have alternate insulin therapy available in case of pump failure. • Administer NOVOLOG by continuous subcutaneous infusion into the subcutaneous tissue of the abdominal wall. Rotate infusion sites within the same region to reduce the risk of lipodystrophy [see Adverse Reactions (6.1)]. • Follow healthcare provider recommendations when setting basal and meal time infusion rate. • Do NOT dilute or mix NOVOLOG when administering by continuous subcutaneous infusion. • Change the NOVOLOG in the reservoir at least every 6 days • Change the infusion sets and the infusion set insertion site at least every 3 days. • Do NOT expose NOVOLOG in the pump reservoir to temperatures greater than 98.6°F (37°C). • Follow the NOVOLOG-specific information (e.g., in-use time, frequency of changing infusion sets) because NOVOLOG-specific information may differ from general pump manual instructions. • The following insulin pumps† have been used in NOVOLOG clinical or in vitro studies conducted by Novo Nordisk, the manufacturer of NOVOLOG: o Medtronic Paradigm® 512 and 712 o MiniMed 508

Intravenous Administration

• Dilute NOVOLOG to concentrations from 0.05 unit/mL to 1 unit/mL insulin aspart in infusion systems using polypropylene infusion bags. NOVOLOG is stable in infusion fluids such as 0.9% sodium chloride. • Administer NOVOLOG intravenously ONLY under medical supervision with close monitoring of blood glucose and potassium levels to avoid hypoglycemia and hypokalemia [see Warnings and Precautions (5.3, 5.6) and How Supplied/Storage and Handling (16.2)].

Dosage Information

• Individualize and adjust the dosage of NOVOLOG based on route of administration, the individual's metabolic needs, blood glucose monitoring results and glycemic control goal. • Dosage adjustments may be needed with changes in physical activity, changes in meal patterns (i.e., macronutrient content or timing of food intake), changes in renal or hepatic function or during acute illness [see Warnings and Precautions (5.2, 5.3) and Use in Specific Populations (8.6, 8.7)]. • Dosage adjustment may be needed when switching from another insulin to NOVOLOG [see Warnings and Precautions (5.2)].

Dosage Adjustment Due to Drug Interactions

• Dosage adjustment may be needed when NOVOLOG is coadministered with certain drugs [see Drug Interactions (7)].

Instructions for Mixing with Other Insulins

NOVOLOG subcutaneous injection route

  NOVOLOG may be mixed with NPH insulin preparations   ONLY.

• If NOVOLOG is mixed with NPH insulin, draw NOVOLOG into the syringe first and inject immediately after mixing.

NOVOLOG continuous subcutaneous infusion route (Insulin Pump)

Do NOT mix NOVOLOG with any other insulin.

Use in specific populations

Pregnancy

Pregnancy Category B. All pregnancies have a background risk of birth defects, loss, or other adverse outcome regardless of drug exposure. This background risk is increased in pregnancies complicated by hyperglycemia and may be decreased with good metabolic control. It is essential for patients with diabetes or history of gestational diabetes to maintain good metabolic control before conception and throughout pregnancy. Insulin requirements may decrease during the first trimester, generally increase during the second and third trimesters, and rapidly decline after delivery. Careful monitoring of glucose control is essential in these patients. Therefore, female patients should be advised to tell their physician if they intend to become, or if they become pregnant while taking NOVOLOG.

An open-label, randomized study compared the safety and efficacy of NOVOLOG (n=157) versus regular human insulin (n=165) in 322 pregnant women with type 1 diabetes. Two-thirds of the enrolled patients were already pregnant when they entered the study. Because only one-third of the patients enrolled before conception, the study was not large enough to evaluate the risk of congenital malformations. Both groups achieved a mean HbA1c of ~ 6% during pregnancy, and there was no significant difference in the incidence of maternal hypoglycemia.

Subcutaneous reproduction and teratology studies have been performed with NOVOLOG and regular human insulin in rats and rabbits. In these studies, NOVOLOG was given to female rats before mating, during mating, and throughout pregnancy, and to rabbits during organogenesis. The effects of NOVOLOG did not differ from those observed with subcutaneous regular human insulin. NOVOLOG caused pre- and post-implantation losses and visceral/skeletal abnormalities in rats at a dose of 200 units/kg/day (approximately 32 times the human subcutaneous dose of 1.0 units/kg/day, based on units/body surface area) and in rabbits at a dose of 10 units/kg/day (approximately three times the human subcutaneous dose of 1.0 units/kg/day, based on units/body surface area). No significant effects were observed in rats at a dose of 50 units/kg/day and in rabbits at a dose of 3 units/kg/day. These doses are approximately 8 times the human subcutaneous dose of 1.0 units/kg/day for rats and equal to the human subcutaneous dose of 1.0 units/kg/day for rabbits, based on units/body surface area.

Nursing Mothers

Endogenous insulin is present in human milk; it is unknown whether insulin aspart is excreted in human milk. Because many drugs, including human insulin, are excreted in human milk, caution should be exercised when NOVOLOG is administered to a nursing woman. Use of NOVOLOG is compatible with breastfeeding, but women with diabetes who are lactating may require adjustments of their insulin doses.

Pediatric Use

NOVOLOG is approved for use in children for subcutaneous daily injections and for subcutaneous continuous infusion by external insulin pump [See Clinical Studies (14.1, 14.2)]. NOVOLOG has not been studied in pediatric patients younger than 2 years of age. NOVOLOG has not been studied in pediatric patients with type 2 diabetes.

Geriatric Use

Of the total number of patients (n= 1,375) treated with NOVOLOG in 3 controlled clinical studies, 2.6% (n=36) were 65 years of age or over. One-half of these patients had type 1 diabetes (18/1285) and the other half had type 2 diabetes (18/90). The HbA1c response to NOVOLOG, as compared to regular human insulin, did not differ by age.

Renal Impairment

Patients with renal impairment may be at increased risk of hypoglycemia and may require more frequent NOVOLOG dose adjustment and more frequent blood glucose monitoring [see Warnings and Precautions (5.3) and Clinical Pharmacology (12.3)].

Hepatic Impairment

Patients with hepatic impairment may be at increased risk of hypoglycemia and may require more frequent NOVOLOG dose adjustment and more frequent blood glucose monitoring [see Warnings and Precautions (5.3) and Clinical Pharmacology (12.3)].

Novolog Injection Description

NOVOLOG (insulin aspart injection) is a rapid-acting human insulin analog used to lower blood glucose. NOVOLOG is homologous with regular human insulin with the exception of a single substitution of the amino acid proline by aspartic acid in position B28, and is produced by recombinant DNA technology utilizing Saccharomyces cerevisiae (baker's yeast). Insulin aspart has the empirical formula C256H381N65079S6 and a molecular weight of 5825.8.

Figure 1. Structural formula of insulin aspart.

NOVOLOG is a sterile, aqueous, clear, and colorless solution, that contains insulin aspart 100 Units/mL, glycerin 16 mg/mL, phenol 1.50 mg/mL, metacresol 1.72 mg/mL, zinc 19.6 mcg/mL, disodium hydrogen phosphate dihydrate 1.25 mg/mL, sodium chloride 0.58 mg/mL and water for injection. NOVOLOG has a pH of 7.2-7.6. Hydrochloric acid 10% and/or sodium hydroxide 10% may be added to adjust pH.

How Supplied/Storage and Handling

How Supplied

NOVOLOG 100 units of insulin aspart per mL (U-100) is available as a clear and colorless solution for injection in:

10 mL vials

NDC 0169-7501-11

3 mL PenFill  cartridges*

NDC 0169-3303-12

3 mL NOVOLOG FlexPen

NDC 0169-6339-10

3 mL NOVOLOG FlexTouch

NDC 0169-6338-10

*NOVOLOG PenFill cartridges are designed for use with Novo Nordisk insulin delivery devices with NovoFine disposable needles. FlexPen and FlexTouch can be used with NovoFine or NovoTwist disposable needles. NOVOLOG FlexPen, NOVOLOG FlexTouch, PenFill cartridge, and PenFill cartridge insulin delivery devices manufactured by Novo Nordisk must never be shared between patients, even if the needle is changed.

Recommended Storage

Unused NOVOLOG should be stored in a refrigerator between 2° and 8°C (36° to 46°F).  Do not freeze NOVOLOG and do not use NOVOLOG if it hasbeen frozen. Do not expose NOVOLOG to excessive heat or light.

NOVOLOG should not be drawn into a syringe and stored for later use.

Always remove and discard the needle after each injection from the NOVOLOG FlexPenor NOVOLOG FlexTouchand store without a needle attached. This prevents contamination and/or infection, or leakage of insulin, and will ensure accurate dosing.

The storage conditions are summarized in the following table:

Table 9. Storage conditions for vial, PenFill cartridges, NOVOLOG FlexPen, and NOVOLOG FlexTouch

NOVOLOG

presentation

Not in-use (unopened) Room Temperature (below 30°C [86°F])

Not in-use (unopened) Refrigerated

In-use (opened) Room Temperature (below 30°C [86°F])

10 mL vial

28 days

Until expiration date

28 days (refrigerated/room temperature)

3 mL PenFill cartridges

28 days

Until expiration date

28 days

(Do not refrigerate)

3 mL NOVOLOG FlexPen

28 days

Until expiration date

28 days

(Do not refrigerate)

3 mL NOVOLOG FlexTouch

28 days

Until expiration date

28 days

(Do not refrigerate)

Storage in External Insulin Pump:

NOVOLOG in the pump reservoir should be discarded after at least every 6 days of use or after exposure to temperatures that exceed 37°C (98.6°F). The infusion set and the infusion set insertion site should be changed at least every 3 days.

Storage of Diluted NOVOLOG

NOVOLOG diluted with Insulin Diluting Medium for NOVOLOG to a concentration equivalent to U-10 or equivalent to U-50 prepared as indicated under Dosage and Administration (2.2) may remain in patient use at temperatures below 30°C (86°F) for 28 days.

Storage of NOVOLOG in Intravenous Infusion Fluids

Infusion bags prepared as indicated under Dosage and Administration (2.2) are stable at room temperature for 24 hours. Some insulin will be initially adsorbed to the material of the infusion

PRINCIPAL DISPLAY PANEL - 10 mL NovoLog Vial

NDC 0169-7501-11

List 750111

NovoLog®

Insulin aspart Injection

10 mL 100 units/mL

Rx only

U-100

PRINCIPAL DISPLAY PANEL - 3 mL NovoLog FlexPen

NDC 0169-6339-10 List 633910

NovoLog® FlexPen®

Prefilled Syringe

Insulin aspart Injection

For Single Patient Use Only

100 units/mL (U-100)

5 x 3 mL Prefilled Insulin Syringes

Rx only

For use with NovoFine®, NovoFine Plus® or
NovoTwist® disposable needles.

Keep in a cold place.

Avoid freezing.

Protect from light.

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