Novolog

Important Preparation and Administration Instructions 

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Always check insulin labels before administration [see Warnings and Precautions ].

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Inspect NOVOLOG visually before use. It should appear clear and colorless. Do not use NOVOLOG if particulate matter or coloration is seen.

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In patients with visual impairment, use:

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NOVOLOG FlexPen and NOVOLOG FlexTouch with caution in those who may rely on audible clicks to dial their dose.

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PenFill cartridges with caution.

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Do not mix NOVOLOG with other insulins when administering using a continuous subcutaneous infusion pump.

Preparation and Administration Instructions for the Approved Routes of Administration

Subcutaneous Injection

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Inject NOVOLOG subcutaneously within 5-10 minutes before a meal into the abdominal area, thigh, buttocks or upper arm.

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Rotate injection sites within the same region from one injection to the next to reduce the risk of lipodystrophy and localized cutaneous amyloidosis. Do not inject into areas of lipodystrophy or localized cutaneous amyloidosis [see Warnings and Precautions and Adverse Reactions ].

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Dial the NOVOLOG FlexPen and FlexTouch in 1-unit increments.

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Generally use NOVOLOG (administered by subcutaneous injection) in regimens with an intermediate- or long-acting insulin.

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May dilute NOVOLOG with Insulin Diluting Medium for NOVOLOG for subcutaneous injection. Diluting one part NOVOLOG to:

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Nine parts diluent will yield a concentration one-tenth that of NOVOLOG (equivalent to U-10).

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One part diluent will yield a concentration one-half that of NOVOLOG (equivalent to U-50).

Continuous Subcutaneous Infusion (Insulin Pump)

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Can use this NOVOLOG product with the continuous subcutaneous insulin infusion pumps labeled for use with NOVOLOG (insulin aspart). Refer to the insulin pump user manual to see if NOVOLOG can be used. Use NOVOLOG in accordance with the insulin pump system’s instructions for use.

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Train patients using continuous subcutaneous insulin infusion pump therapy to administer insulin by injection and have alternate insulin therapy available in case of pump failure.

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Administer NOVOLOG by continuous subcutaneous infusion in a region recommended in the instructions from the pump manufacturer. Rotate infusion sites within the same region to reduce the risk of lipodystrophy or localized cutaneous amyloidosis [see Warnings and Precautions and Adverse Reactions ].

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Instruct patients to follow healthcare provider recommendations when setting basal and meal time infusion rate.

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Change the NOVOLOG in the reservoir at least every 7 days or according to the pump user manual, whichever is shorter. Follow the NOVOLOG-specific information for in-use time because NOVOLOG-specific information may differ from general pump manual instructions.

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Change the infusion set and the infusion set insertion site according to the manufacturer’s user manual.

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Do not dilute or mix NOVOLOG when administering by continuous subcutaneous infusion.

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Do not expose NOVOLOG in the pump reservoir to temperatures greater than 98.6°F (37°C).

Intravenous Administration

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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 Injection, USP.

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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 and How Supplied/Storage and Handling ].

Dosage Recommendations

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Individualize the dosage of NOVOLOG based on the route of administration, the patient’s metabolic needs, blood glucose monitoring results and glycemic control goal.

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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 and Use in Specific Populations ].

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When switching from another insulin to NOVOLOG, a different dosage of NOVOLOG may be needed [see Warnings and Precautions ].

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During changes to a patient’s insulin regimen, increase the frequency of blood glucose monitoring [see Warnings and Precautions ].

Dosage Modifications for Drug Interactions

Dosage modification may be needed when NOVOLOG is used concomitantly with certain drugs [see Drug Interactions ].

Instructions for Mixing NOVOLOG with Other Insulins

The table below includes instructions regarding mixing NOVOLOG with other insulins.

Pregnancy

Risk Summary

Available information from published randomized controlled trials with insulin aspart use during the second trimester of pregnancy have not reported an association with insulin aspart and major birth defects or adverse maternal or fetal outcomes [see Data]. There are risks to the mother and fetus associated with poorly controlled diabetes in pregnancy [see Clinical Considerations].

In animal reproduction studies, administration of subcutaneous insulin aspart to pregnant rats and rabbits during the period of organogenesis did not cause adverse developmental effects at exposures 8-times and equal to the human subcutaneous dose of 1 unit/kg/day, respectively. Pre- and post-implantation losses and visceral/skeletal abnormalities were seen at higher exposures, which are considered secondary to maternal hypoglycemia. These effects were similar to those observed in rats administered regular human insulin [see Data].

In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2 to 4% and 15 to 20%, respectively. The estimated background risk of major birth defects is 6 to 10% in women with pre-gestational diabetes with a periconceptional HbA1c >7% and has been reported to be as high as 20 to 25% in women with a periconceptional HbA1c >10%. The estimated background risk of miscarriage for the indicated population is unknown.

Clinical Considerations

Disease-Associated Maternal and/or Embryo-Fetal Risk

Poorly controlled diabetes in pregnancy increases the maternal risk for diabetic ketoacidosis, preeclampsia, spontaneous abortions, preterm delivery, and delivery complications. Poorly controlled diabetes increases the fetal risk for major birth defects, stillbirth, and macrosomia related morbidity.

Data

Human Data

Published data from 5 randomized controlled trials of 441 pregnant women with diabetes mellitus treated with insulin aspart during the late 2nd trimester of pregnancy did not identify an association of insulin aspart with major birth defects or adverse maternal or fetal outcomes. However, these studies cannot definitely establish the absence of any risk because of methodological limitations, including a variable duration of treatment and small size of the majority of the trials.

Animal Data

Fertility, embryo-fetal and pre- and postnatal development studies have been performed with insulin aspart and regular human insulin in rats and rabbits. In a combined fertility and embryo-fetal development study in rats, insulin aspart was administered before mating, during mating, and throughout pregnancy. Further, in a pre- and postnatal development study insulin aspart was given throughout pregnancy and during lactation to rats. In an embryo-fetal development study insulin aspart was given to female rabbits during organogenesis. The effects of insulin aspart did not differ from those observed with subcutaneous regular human insulin. Insulin aspart, like human insulin, 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 unit/kg/day, based on human exposure equivalents) and in rabbits at a dose of 10 units/kg/day (approximately three times the human subcutaneous dose of 1 unit/kg/day, based on human exposure equivalents). 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 unit/kg/day for rats and equal to the human subcutaneous dose of 1 unit/kg/day for rabbits, based on human exposure equivalents. The effects are considered secondary to maternal hypoglycemia.

Lactation

Risk Summary

There are no data on the presence of NOVOLOG in human milk, the effects on the breastfed infant, or the effect on milk production. One small published study reported that exogenous insulin, including insulin aspart, was present in human milk. However, there is insufficient information to determine the effects of insulin aspart on the breastfed infant. The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for NOVOLOG, and any potential adverse effects on the breastfed infant from NOVOLOG, or from the underlying maternal condition.

Pediatric Use

The safety and effectiveness of NOVOLOG to improve glycemic control have been established in pediatric patients with diabetes mellitus. Use of NOVOLOG for this indication is supported by evidence from an adequate and well-controlled study in 283 pediatric patients with type 1 diabetes mellitus aged 6 to 18 years and from studies in adults with diabetes mellitus [see Adverse Reactions , Clinical Pharmacology , and Clinical Studies ].

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 and Clinical Pharmacology ].

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 and Clinical Pharmacology ].

Never Share a NOVOLOG FlexPen, NOVOLOG FlexTouch, PenFill Cartridge, or PenFill Cartridge Device between Patients

NOVOLOG FlexPen, NOVOLOG FlexTouch, PenFill cartridge, and PenFill cartridge devices should never be shared between patients, even if the needle is changed. Patients using NOVOLOG vials must never share needles or syringes with another person. Sharing poses a risk for transmission of blood-borne pathogens.

Hyperglycemia or Hypoglycemia with Changes in Insulin Regimen

Changes in an insulin regimen (e.g., insulin strength, manufacturer, type, injection site or method of administration) may affect glycemic control and predispose to hypoglycemia [see Warnings and Precautions ] or hyperglycemia. Repeated insulin injections into areas of lipodystrophy or localized cutaneous amyloidosis have been reported to result in hyperglycemia; and a sudden change in the injection site (to an unaffected area) has been reported to result in hypoglycemia [see Adverse Reactions ( 6.1, 6.3)].

Make any changes to a patient’s insulin regimen under close medical supervision with increased frequency of blood glucose monitoring. Advise patients who have repeatedly injected into areas of lipodystrophy or localized cutaneous amyloidosis to change the injection site to unaffected areas and closely monitor for hypoglycemia. For patients with type 2 diabetes, dosage adjustments of concomitant anti-diabetic products may be needed.

Hypoglycemia

Hypoglycemia is the most common adverse reaction of all insulins, including NOVOLOG. Severe hypoglycemia can cause seizures, may lead to unconsciousness, may be life threatening or cause death. Hypoglycemia can impair concentration ability and reaction time; this may place an individual and others at risk in situations where these abilities are important (e.g., driving or operating other machinery).

Hypoglycemia can happen suddenly and symptoms may differ in each individual and change over time in the same individual. Symptomatic awareness of hypoglycemia may be less pronounced in patients with longstanding diabetes in patients with diabetic nerve disease, in patients using medications that block the sympathetic nervous system (e.g., beta-blockers) [see Drug Interactions (7)], or in patients who experience recurrent hypoglycemia.

Risk Factors for Hypoglycemia

The risk of hypoglycemia after an injection is related to the duration of action of the insulin and, in general, is highest when the glucose lowering effect of the insulin is maximal. As with all insulins, the glucose lowering effect time course of NOVOLOG may vary in different individuals or at different times in the same individual and depends on many conditions, including the area of injection as well as the injection site blood supply and temperature [see Clinical Pharmacology ]. Other factors which may increase the risk of hypoglycemia include changes in meal pattern (e.g., macronutrient content or timing of meals), changes in level of physical activity, or changes to concomitantly administered medication [see Drug Interactions (7)]. Patients with renal or hepatic impairment may be at higher risk of hypoglycemia [see Use in Specific Populations ].

Risk Mitigation Strategies for Hypoglycemia

Patients and caregivers must be educated to recognize and manage hypoglycemia. Self-monitoring of blood glucose plays an essential role in the prevention and management of hypoglycemia; increased frequency of blood glucose monitoring is recommended. In patients at higher risk for hypoglycemia and patients who have reduced symptomatic awareness of hypoglycemia; increased frequency of blood glucose monitoring is recommended.

Hypoglycemia Due to Medication Errors

Accidental mix-ups between insulin products have been reported. To avoid medication errors between NOVOLOG and other insulins, instruct patients to always check the insulin label before each injection.

Hypersensitivity Reactions

Severe, life-threatening, generalized allergy, including anaphylaxis, can occur with insulins, including NOVOLOG. If hypersensitivity reactions occur, discontinue NOVOLOG; treat per standard of care and monitor until symptoms and signs resolve [see Adverse Reactions (6)]. NOVOLOG is contraindicated in patients who have had hypersensitivity reactions to insulin aspart or one of the excipients [see Contraindications (4)].

Hypokalemia

All insulins, including NOVOLOG, can cause a shift in potassium from the extracellular to intracellular space, possibly leading to hypokalemia. Untreated hypokalemia may cause respiratory paralysis, ventricular arrhythmia, and death. Monitor potassium levels in patients at risk for hypokalemia if indicated (e.g., patients using potassium-lowering medications, patients taking medications sensitive to serum potassium concentration).

Fluid Retention and Heart Failure with Concomitant Use of PPAR-gamma Agonists

Thiazolidinediones (TZDs), which are peroxisome proliferator-activated receptor (PPAR)-gamma agonists, can cause dose-related fluid retention, particularly when used in combination with insulin. Fluid retention may lead to or exacerbate heart failure. Patients treated with insulin, including NOVOLOG, and a PPAR-gamma agonist should be observed for signs and symptoms of heart failure. If heart failure develops, it should be managed according to current standards of care, and discontinuation or dose reduction of the PPAR-gamma agonist must be considered.

Hyperglycemia and Ketoacidosis Due to Insulin Pump Device Malfunction

Malfunction of the insulin pump or insulin infusion set or insulin degradation can rapidly lead to hyperglycemia and ketoacidosis. Prompt identification and correction of the cause of hyperglycemia or ketosis is necessary. Interim subcutaneous injections with NOVOLOG may be required. Patients using continuous subcutaneous insulin infusion pump therapy must be trained to administer insulin by injection and have alternate insulin therapy available in case of pump failure [see How Supplied/Storage and Handling and Patient Counseling Information ].