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NovoLog ® (insulin aspart [rDNA origin] injection) is a human insulin analog that is a rapid-acting, parenteral blood glucose-lowering agent.
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) as the production organism. Insulin aspart has the empirical formula C 256 H 381 N 65 O 79 S 6 and a molecular weight of 5825.8.
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Figure 1. Structural formula of insulin aspart.
NovoLog is a sterile, aqueous, clear, and colorless solution, that contains insulin aspart (B28 asp regular human insulin analog) 100 Units/mL, glycerin 16 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, and sodium chloride 0.58 mg/mL. NovoLog has a pH of 7.2-7.6. Hydrochloric acid 10% and/or sodium hydroxide 10% may be added to adjust pH.
The primary activity of NovoLog is the regulation of glucose metabolism. Insulins, including NovoLog, bind to the insulin receptors on muscle and fat cells and lower blood glucose by facilitating the cellular uptake of glucose and simultaneously inhibiting the output of glucose from the liver.
In standard biological assays in mice and rabbits, one unit of NovoLog has the same glucose-lowering effect as one unit of regular human insulin. In humans, the effect of NovoLog is more rapid in onset and of shorter duration, compared to regular human insulin, due to its faster absorption after subcutaneous injection (see Figure 2 and Figure 3).
The single substitution of the amino acid proline with aspartic acid at position B28 in NovoLog reduces the molecule' tendency to form hexamers as observed with regular human insulin. NovoLog is therefore more rapidly absorbed after subcutaneous injection compared to regular human insulin.
Bioavailability and Absorption --NovoLog has a faster absorption, a faster onset of action, and a shorter duration of action than regular human insulin after subcutaneous injection (see Figure 2 and Figure 3). The relative bioavailability of NovoLog compared to regular human insulin indicates that the two insulins are absorbed to a similar extent.
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Figure 2. Serial mean serum free insulin concentration collected up to 6 hours following a single pre-meal dose of NovoLog (solid curve) or regular human insulin (hatched curve) injected immediately before a meal in 22 patients with Type 1 diabetes.
In studies in healthy volunteers (total n=107) and patients with Type 1 diabetes (total n=40), NovoLog consistently reached peak serum concentrations approximately twice as fast as regular human insulin. The median time to maximum concentration in these trials was 40 to 50 minutes for NovoLog versus 80 to 120 minutes for regular human insulin. In a clinical trial in patients with Type 1 diabetes, NovoLog and regular human insulin, both administered subcutaneously at a dose of 0.15 U/kg body weight, reached mean maximum concentrations of 82.1 and 35.9 mU/L, respectively. Pharmacokinetic/pharmacodynamic characteristics of insulin aspart have not been established in patients with Type 2 diabetes.
The intra-individual variability in time to maximum serum insulin concentration for healthy male volunteers was significantly less for NovoLog than for regular human insulin. The clinical significance of this observation has not been established.
In a clinical study in healthy non-obese subjects, the pharmacokinetic differences between NovoLog and regular human insulin described above, were observed independent of the injection site (abdomen, thigh, or upper arm).
Distribution and Elimination --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.
Studies in normal volunteers and patients with diabetes demonstrated that NovoLog has a more rapid onset of action than regular human insulin.
In a 6-hour study in patients with Type 1 diabetes (n=22), the maximum glucose-lowering effect of NovoLog occurred between 1 and 3 hours after subcutaneous injection (see Figure 3).
The duration of action for NovoLog is 3 to 5 hours compared to 5 to 8 hours for regular human insulin. The time course of action of insulin and insulin analogs such as NovoLog may vary considerably in different individuals or within the same individual. The parameters of NovoLog activity (time of onset, peak time and duration) as designated in Figure 3 should be considered only as general guidelines. 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 ).
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Figure 3. Serial mean serum glucose collected up to 6 hours following a single pre-meal dose of NovoLog (solid curve) or regular human insulin (hatched curve) injected immediately before a meal in 22 patients with Type 1 diabetes.
Children and Adolescents --The pharmacokinetic and pharmacodynamic properties of NovoLog and regular human insulin were evaluated in a single dose study in 18 children (6-12 years, n=9) and adolescents (13-17 years [Tanner grade >/= 2], n=9) with Type 1 diabetes. The relative differences in pharmacokinetics and pharmacodynamics in children and adolescents with Type 1 diabetes between NovoLog and regular human insulin were similar to those in healthy adult subjects and adults with Type 1 diabetes.
Geriatrics --The effect of age on the pharmacokinetics and pharmacodynamics of NovoLog has not been studied.
Gender --In healthy volunteers, no difference in insulin aspart levels was seen between men and women when body weight differences were taken into account. There was no significant difference in efficacy noted (as assessed by HbA1c) between genders in a trial in patients with Type 1 diabetes.
Obesity --The effect of obesity and/or subcutaneous fat thickness on the pharmacokinetics and glucodynamics of NovoLog has not been studied.
Ethnic Origin --The effect of ethnic origin on the pharmacokinetics of NovoLog has not been studied.
Renal Impairment --Some studies with human insulin have shown increased circulating levels of insulin in patients with renal failure. The effect of renal impairment on the pharmacokinetics of NovoLog has not been studied. Careful glucose monitoring and dose adjustments of insulin, including NovoLog, may be necessary in patients with renal dysfunction (see PRECAUTIONS , Renal Impairment ).
Hepatic Impairment --Some studies with human insulin have shown increased circulating levels of insulin in patients with liver failure. The effect of hepatic impairment on the pharmacokinetics of NovoLog has not been studied. Careful glucose monitoring and dose adjustments of insulin, including NovoLog, may be necessary in patients with hepatic dysfunction (see PRECAUTIONS , Hepatic Impairment ).
Pregnancy --The effect of pregnancy on the pharmacokinetics and glucodynamics of Novolog has not been studied (see PRECAUTIONS , Pregnancy ).
Smoking --The effect of smoking on the pharmacokinetics/pharmacodynamics of NovoLog has not been studied.
To evaluate the safety and efficacy of NovoLog in patients with Type 1 diabetes, two six-month, open-label, active-control (NovoLog vs. Novolin ® R) studies were conducted (see Table 1). NovoLog was administered by subcutaneous injection immediately prior to meals and regular human insulin was administered by subcutaneous injection 30 minutes before meals. NPH insulin was administered as the basal insulin in either single or divided daily doses. Glycemic control (as measured by HbA1c), the rates of hypoglycemia (as determined from the number of events requiring intervention from a third party), and the incidence of ketosis were clinically comparable for the two treatment regimens. The mean total daily doses of insulin were greater (1-3 U/day) in the NovoLog-treated patients compared to patients who received regular human insulin. This difference was primarily due to basal insulin requirements. To achieve the stated levels of glycemic control, some patients required more than three doses of meal-related insulin and/or more than one dose of basal insulin (see Table 1). No serum glucose measurements were obtained in these studies. To evaluate the safety and efficacy of NovoLog in patients with Type 2 diabetes, one six-month, open-label, active-control (NovoLog vs. Novolin R) study was conducted (see Table 1). NovoLog was administered by subcutaneous injection immediately prior to meals and regular human insulin was administered by subcutaneous injection 30 minutes before meals. NPH insulin was administered as the basal insulin in either single or divided daily doses. Glycemic control (as measured by HbA1c) and the rates of hypoglycemia (as determined from the number of events requiring intervention from a third party) were clinically comparable for the two treatment regimens. The mean total daily dose of insulin was greater (2 U/day) in the NovoLog-treated patients compared to patients who received regular human insulin. This difference was primarily due to basal insulin requirements. To achieve the stated levels of glycemic control, some patients required more than three doses of meal-related insulin and/or more than one dose of basal insulin (see Table 1).
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NovoLog is indicated for the treatment of adult patients with diabetes mellitus, for the control of hyperglycemia. Because NovoLog has a more rapid onset and a shorter duration of action than human regular insulin, NovoLog should normally be used in regimens together with an intermediate or long-acting insulin.
NovoLog is contraindicated during episodes of hypoglycemia and in patients hypersensitive to NovoLog or one of its excipients.
NovoLog differs from regular human insulin by its rapid onset of action and a shorter duration of action. Because of the fast onset of action, the injection of NovoLog ® should immediately be followed by a meal. Because of the short duration of action of NovoLog ® , patients with Type 1 diabetes also require a longer-acting insulin to maintain adequate glucose control.
Hypoglycemia is the most common adverse effect of insulin therapy, including NovoLog ® .
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.
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 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).
Lipodystrophy and hypersensitivity are among other potential clinical adverse effects associated with the use of all insulins.
As with all insulin preparations, the time course of NovoLog action may vary in different individuals or at different times in the same individual and is dependent on site of injection, blood supply, temperature, and physical activity. Adjustment of dosage of any insulin may be necessary if patients change their physical activity or their usual meal plan. Insulin requirements may be altered during illness, emotional disturbances, or other stresses.
Hypoglycemia --As with all insulin preparations, hypoglycemic reactions may be associated with the administration of NovoLog. Rapid changes in serum glucose levels may induce symptoms of hypoglycemia in persons with diabetes, regardless of the glucose value. Early warning symptoms of hypoglycemia may be different or less pronounced under certain conditions, such as long duration of diabetes, diabetic nerve disease, use of medications such as beta-blockers, or intensified diabetes control (see PRECAUTIONS , Drug Interactions ). Such situations may result in severe hypoglycemia (and, possibly, loss of consciousness) prior to patients' awareness of hypoglycemia.
Renal Impairment --Although there are no specific data in patients with diabetes and renal impairment treated with NovoLog, NovoLog dose requirements may be reduced in the presence of renal impairment, similar to observations with other insulins (see CLINICAL PHARMACOLOGY , Pharmacokinetics ).
Hepatic Impairment --Although there are no specific data in patients with diabetes and hepatic disease treated with NovoLog, NovoLog dose requirements may be reduced in the presence of impaired hepatic function, similar to observations found with other insulins (see CLINICAL PHARMACOLOGY , Pharmacokinetics ).
Allergy--Local Allergy --As with other insulin therapy, patients may experience redness, swelling, or itching at the site of injection. These minor reactions usually resolve in a few days to a few weeks, but in some occasions, may require discontinuation of NovoLog. In some instances, these reactions may be related to factors other than insulin, such as irritants in a skin cleansing agent or poor injection technique.
Systemic Allergy --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.
In controlled clinical trials, allergic reactions were reported in 3 of 735 patients (0.4%) who received regular human insulin and 10 of 1394 patients (0.7%) who received NovoLog. During these trials and their extensions, 2 of 2136 patients treated with NovoLog were discontinued due to allergic reactions.
Antibody Production --Insulin antibodies may develop during treatment with insulin. In large clinical trials, levels of antibodies that cross react with human insulin and insulin aspart were higher in patients treated with NovoLog compared to regular human insulin. The clinical significance of these antibodies is uncertain.
Patients should be informed about potential risks and advantages of NovoLog 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.
The need for patient-performed regular blood glucose measurements should be considered when using NovoLog in order to obtain optimal glycemic control. 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 during pregnancy or lactation (see PRECAUTIONS , Pregnancy ).
As with all insulin therapy, the therapeutic response to NovoLog should be monitored by periodic blood glucose tests. Periodic measurement of glycosylated hemoglobin is recommended for the monitoring of long-term glycemic control.
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 contaceptives). 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 medicinal products such as beta-blockers, clonidine, guanethidine, and reserpine, the signs of hypoglycemia may be reduced or absent (see CLINICAL PHARMACOLOGY ).
Mixing of Insulins --A clinical study in healthy male volunteers (n=24) demonstrated that mixing NovoLog with NPH human insulin immediately before injection produced some attenuation in the peak concentration of NovoLog, but that the time to peak and the total bioavailability of NovoLog were not significantly affected. If NovoLog is mixed with NPH human insulin, NovoLog should be drawn into the syringe first. The injection should be made immediately after mixing. Because there are no data on the compatibility of NovoLog and crystalline zinc insulin preparations, NovoLog should not be mixed with these preparations.
The effects of mixing NovoLog with insulins of animal source or insulin preparations produced by other manufacturers have not been studied (see WARNINGS ).
Mixtures should not be administered intravenously.
Standard 2-year carcinogenicity studies in animals have not been performed to evaluate the carcinogenic potential of NovoLog. In 52 week studies, Sprague-Dawley rats were dosed subcutaneously with NovoLog at 10, 50, and 200 U/kg/day (approximately 2, 8, and 32 times the human subcutaneous dose of 1.0 U/kg/day, based on U/body surface area, respectively). At a dose of 200 U/kg/day, NovoLog increased the incidence of mammary gland tumors in females when compared to untreated controls. The incidence of mammary tumors for NovoLog was not significantly different than for regular human insulin. The relevance of these findings to humans is not known. NovoLog was not genotoxic in the following tests: Ames test, mouse lymphoma cell forward gene mutation test, human peripheral blood lymphocyte chromosome aberration test, in vivo micronucleus test in mice, and in ex vivo UDS test in rat liver hepatocytes. In fertility studies in male and female rats, at subcutaneous doses up to 200 U/kg/day (approximately 32 times the human subcutaneous dose, based on U/body surface area), no direct adverse effects on male and female fertility, or general reproductive performance of animals was observed.
Subcutaneous reproduction and teratology studies have been performed with NovoLog and regular human insulin in rats and rabbits. In these studies, NovoLog was given to female rats before mating, during mating, and throughout pregnancy, and to rabbits during organogenesis. The effects of NovoLog did not differ from those observed with subcutaneous regular human insulin. NovoLog, like human insulin, caused pre- and post-implantation losses and visceral/skeletal abnormalities in rats at a dose of 200 U/kg/day (approximately 32 times the human subcutaneous dose of 1.0 U/kg/day, based on U/body surface area) and in rabbits at a dose of 10 U/kg/day (approximately three times the human subcutaneous dose of 1.0 U/kg/day, based on U/body surface area). The effects are probably secondary to maternal hypoglycemia at high doses. No significant effects were observed in rats at a dose of 50 U/kg/day and 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.
There are no well-controlled clinical studies of the use of NovoLog in pregnant women. 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 such patients. Because animal reproduction studies are not always predictive of human response, NovoLog should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.
It is unknown whether insulin aspart is excreted in human milk. Many drugs, including human insulin, are excreted in human milk. For this reason, caution should be exercised when NovoLog is administered to a nursing mother.
Safety and effectiveness of NovoLog in children have not been studied.
In the large controlled clinical trials, 36 patients </= 65 years of age were treated with NovoLog. No conclusions regarding the safety and efficacy of NovoLog in the elderly patients compared to younger adults can be reached from this limited data set.
Clinical trials comparing NovoLog with regular human insulin 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 a Whole -- Allergic reactions (see PRECAUTIONS , Allergy ).
Skin and Appendages -- Injection site reaction, lipodystrophy, pruritus, rash (see PRECAUTIONS , Allergy ).
Other -- Hypoglycemia (see WARNINGS and PRECAUTIONS ).
In controlled clinical trials, small, but persistent elevations in alkaline phosphatase result were observed in some patients treated with NovoLog. The clinical significance of this finding is unknown.
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.
NovoLog should generally be given immediately before a meal. The dosage of NovoLog should be individualized and determined, based on the physician' advice, in accordance with the needs of the patient. The total daily individual insulin requirement is usually between 0.5-1.0 U/kg/day. In a meal-related treatment regimen, 50-70% of this requirement may be provided by NovoLog and the remainder provided by an intermediate-acting or long-acting insulin. Patients may require more basal insulin in relation to bolus insulin and more total insulin when using NovoLog compared to regular human insulin to prevent pre-meal hyperglycemia. Additional basal insulin injections may be necessary.
Because of the fast onset of action of NovoLog, it should generally be given close to a meal (start of meal within 5-10 minutes after injection). The dose of NovoLog should be regularly adjusted according to blood glucose measurements. NovoLog should be administered by subcutaneous injection in the abdominal wall, the thigh, or the upper arm. Injection sites should be rotated within the same region. As with all insulins, the duration of action will vary according to the dose, injection site, blood flow, temperature, and level of physical activity.
Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit. Never use any NovoLog if it has become viscous (thickened) or cloudy; use it only if it is clear and colorless. NovoLog should not be used after its expiration date.
NovoLog is available in the following package sizes: each presentation containing 100 Units of insulin aspart per mL (U-100).
10 mL vials NDC 0169-7501-11
3 mL PenFill cartridges * NDC 0169-3303-12
NovoLog should be stored between 2° and 8°C (36° to 46°F). Do not freeze. Do not use NovoLog ® if it has been frozen. Cartridges or vials in use may be kept at ambient temperature below 30°C (86°F) for up to 28 days, but should not be exposed to excessive heat or sunlight.
Rx only
Date of Issue: March 2001
Manufactured For
Novo Nordisk
Pharmaceuticals, Inc.
Princeton, New Jersey 08540
By Novo Nordisk A/S
2880 Bagsvaerd, Denmark
Novo Nordisk
®
, NovoLog
®
, Novolin
®
,
NovoPen
®
, PenFill
®
and NovoFine
®
are trademarks owned by
Novo Nordisk A/S
Insulin aspart (recombinant DNA origin)
10 mL Vial (1000 units per vial)
100 units/mL (U-100)
What is the most important information I should know about NovoLog ® ?
For your safety, read the section "What are the possible side effects of insulins?" for symptoms of low blood sugar (hypoglycemia) and high blood sugar (hyperglycemia).
NovoLog is a human insulin analog that lowers your blood sugar faster than human regular insulin. NovoLog is a clear, colorless, sterile solution for injection under the skin (subcutaneously). The active ingredient in NovoLog is insulin aspart. Insulin aspart is identical to human insulin except for one amino acid, which has been changed in the insulin molecule. Insulin aspart is produced by recombinant DNA technology.
NovoLog also contains: glycerin, phenol, metacresol, zinc, disodium hydrogen phosphate dihydrate, and sodium chloride. Hydrochloric acid and/or sodium hydroxide may be added to adjust the pH.
The concentration of NovoLog is 100 units of insulin aspart per milliliter (U-100).
Insulin is normally produced by the pancreas, a gland that lies behind the stomach. Without insulin, glucose is trapped in the bloodstream and cannot enter the cells of the body. Glucose is a simple sugar made from the food you eat. Some people who do not make any, or enough, of their own insulin, or who cannot use the insulin they do make, must take insulin by injection to control the amount of glucose in their blood (their blood glucose levels). Treatment for diabetes may involve injections of insulin, injections of insulin combined with an oral (taken by mouth) antidiabetic medicine, or an oral antidiabetic medicine alone.
Each case of diabetes is different and requires direct and continued medical supervision. Your health care provider has told you the type, strength and amount of insulin you should use and the time(s) when you should inject it. Your health care provider has also discussed a diet and exercise schedule with you. Contact your health care provider if you have any problems or if you have questions.
There are 3 types of insulin: animal insulins, human insulins, and insulin analogs. Animal insulins may vary in animal source and how pure they are. Human insulin is identical in structure to the insulin produced by the human pancreas, and thus differs from animal insulins. Insulin analogs differ slightly from human insulin in their chemical structure and are synthetic. Insulin analogs differ in time of action from human insulin because the rate of absorption after injection under the skin (subcutaneous) is different. However, they work the same way as human insulin once they are absorbed. The animal insulins differ slightly from human insulin in their chemical structure. Your health care provider has prescribed the insulin that is right for you; be sure you have purchased the correct insulin and check it carefully before you use it.
Do not take NovoLog ® if:
Talk with your health care provider if you intend to become pregnant or nurse a baby or if you become pregnant during treatment with NovoLog. You may need to use a different medicine. The effects of NovoLog on an unborn child or on a nursing baby are not known.
Always consult your health care provider if you have any questions about your condition or the use of insulin.
Inject NovoLog immediately before a meal.
Due to this shorter duration of action, NovoLog is usually taken in combination with intermediate or longer-acting insulins. The effects of insulin may be different for different people. Even in the same person, the effects may vary from day to day. Because of this variation, the time periods listed here are general guidelines only.
See the section "How should I give a NovoLog ® injection?" at the end of this Information For The Patient for detailed instructions.
Even if you have an 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.
If you are traveling across more than two time zones, consult your health care provider about adjusting your insulin schedule.
Exercise may lower your body' need for insulin during and for some time after physical activity. Exercise may also speed up the effect of a NovoLog dose, especially if the exercise involves the area of the injection site. Discuss with your health care provider how you should adjust your treatment to account for exercise.
It is especially important to maintain good control of your diabetes during pregnancy. Pay special attention to your diet, exercise, and insulin regimens. If you are planning to have a baby, are pregnant, or are nursing a baby, consult your health care provider or diabetes educator. NovoLog has not been tested for use in pregnant women or women who are nursing.
Insulin requirements may increase or decrease when taken in combination with other medicines. Drugs such as birth control pills, niacin, corticosteroids, or thyroid replacement therapy may increase insulin requirements. Drugs such as antidiabetic medicines, salicylates (for example, aspirin), sulfa antibiotics, and certain antidepressants may decrease insulin requirements. Your health care provider is aware of other medicines that may affect your diabetes control. Always discuss any medicines you are taking with your health care provider. Beta blocking agents (used for the treatment of certain heart conditions and high blood pressure) may mask the symptoms of hypoglycemia or may increase or decrease the effects of NovoLog. ACE inhibitors (used for the treatment of certain heart conditions and high blood pressure) may increase the effects of NovoLog. Drinking alcohol may lead to hypoglycemia.
Insulin reaction (hypoglycemia) is the most common side effect of insulins. Hypoglycemia occurs when the blood glucose falls very low. The first symptoms of an insulin reaction usually begin suddenly. Hypoglycemia can be caused by:
Symptoms of mild to moderate hypoglycemia may occur suddenly and can include:
If you drink or eat something right away (a glass of milk or orange juice, or several sugar candies), you can often stop symptoms from getting worse. If symptoms continue, call your health care provider right away--hypoglycemia can lead to unconsciousness. If hypoglycemia causes loss of consciousness, you must have emergency medical care right away. If you have had repeated hypoglycemic reactions or if hypoglycemia has led to a loss of consciousness, contact your health care provider. Severe hypoglycemia can result in temporary or permanent harm to your heart function, brain function, or death.
In certain cases, the type and strength of the warning symptoms of hypoglycemia may change. This may happen especially with very tight glucose control or in patients with diabetic nerve problems (neuropathy). If you do not recognize early warning symptoms, you may not be able to take steps to avoid more serious hypoglycemia. Symptoms of severe hypoglycemia can include disorientation, unconsciousness, or seizures. Hypoglycemia can result in death. Be alert for all of the various types of symptoms that can indicate hypoglycemia. Patients who develop hypoglycemia without early warning symptoms should monitor their blood glucose frequently, especially before activities such as driving. If the blood glucose is below your normal fasting glucose, you should eat or drink sugar-containing foods to treat your hypoglycemia.
Patients should always carry a quick source of sugar, such as candy, mints, or glucose tablets. More severe hypoglycemia may require the help 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 glucose at a medical facility.
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 have trouble recognizing the symptoms, consult your health care provider to discuss possible changes in therapy, meal plan, and exercise programs to help you avoid hypoglycemia.
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:
In patients with insulin-dependent diabetes (Type 1 diabetes), continued hyperglycemia can result in diabetic acidosis. The first symptoms of diabetic acidosis usually come on slowly, over a period of hours or days. Symptoms include a drowsy feeling, flushed face, thirst, loss of appetite, and fruity odor on the breath. With acidosis, urine tests show large amounts of glucose and acetone. More severe symptoms are heavy breathing and a rapid pulse. If uncorrected, continued hyperglycemia or diabetic acidosis can lead to nausea, vomiting, dehydration, loss of consciousness, or death. Therefore, it is important that you obtain medical help right away.
Generalized Allergy: An uncommon, but potentially serious reaction to insulins, is generalized allergy, which may cause a rash over the whole body, shortness of breath, wheezing, reduced blood pressure, fast pulse, or sweating. Severe cases of generalized allergy may be life threatening. If you think you are having a generalized allergic reaction, notify a health care provider right away.
Local Allergy: Patients sometimes develop redness, swelling, and itching at the site of injection. This condition, called "local allergy", usually clears up in a few days to a few weeks. Sometimes, this condition may be related to factors other than insulin, such as irritants in skin cleansing agents or poor injection technique. If you have a local reaction, contact your health care provider.
Sometimes, getting insulin subcutaneously can result in lipoatrophy (depression in the skin) or lipohypertrophy (enlargement or thickening of tissue at the injection site). If you notice either of these conditions, consult your health care provider. A change in your injection technique may help reduce the problem.
Always consult your health care provider if you have any questions about your condition or the use of insulin.
Do not share your medicine with other persons. It may harm them. If you have any questions about diabetes or NovoLog, ask your health care provider. Your pharmacist or health care provider can give you the written information about NovoLog that is written for health care professionals.
Never share needles and syringes. Sharing may cause infections.
Doses of insulin are measured in units. NovoLog is available as a U-100 insulin. One milliliter (mL) of U-100 contains 100 units of insulin aspart (1mL=1cc). Always use a syringe marked for U-100 insulin preparations. If you do not use the proper syringe, you can get the wrong dose.
NovoLog vials (small bottles) are for use with standard insulin syringes. The use of these vials with other devices for insulin delivery or with devices that help in giving injections has not been evaluated by Novo Nordisk. Consult your health care provider and the manufacturer of these devices before use with NovoLog.
Disposable syringes and needles require no sterilization if the package is sealed. Disposable needles are for single use. Use the disposable needle once and throw it away properly, to protect others from harm.
If you do not follow the instructions and advice in this leaflet about antiseptic measures for avoiding germs, you may develop infections, most commonly, at the injection site.
Do not use NovoLog ® after the expiration date printed on the label and carton.
Use the injection technique recommended by your health care provider.
NovoLog may be mixed with NPH human insulin. Mixtures of NovoLog with other types of insulin have not been studied.
Helpful information for people with diabetes is published by American Diabetes Association, 1660 Duke Street, Alexandria, VA 22314
For information contact:
Novo Nordisk Pharmaceuticals, Inc.
100 College Road West
Princeton, New Jersey 08540
1-800-727-6500
Manufactured by
Novo Nordisk A/S
2880 Bagsvaerd, Denmark
License under U.S. Patent No. 5,618,913
and Des. 347,894
Novo Nordisk ® , NovoLog ® , Novolin ® and
Lente ® , are trademarks owned by
Novo Nordisk A/S
Date of Issue: March 2001
Printed in Denmark