LEVEMIR
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insulin detemir injection, solution
Novo Nordisk
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LEVEMIR is indicated to improve glycemic control in adults and children with diabetes mellitus.
Important Limitations of Use:
LEVEMIR is a recombinant human insulin analog for once- or twice-daily subcutaneous administration.
Patients treated with LEVEMIR once-daily should administer the dose with the evening meal or at bedtime.
Patients who require twice-daily dosing can administer the evening dose with the evening meal, at bedtime, or 12 hours after the morning dose.
The dose of LEVEMIR must be individualized based on clinical response. Blood glucose monitoring is essential in all patients receiving insulin therapy.
Patients adjusting the amount or timing of dosing with LEVEMIR should only do so under medical supervision with appropriate glucose monitoring [see Warnings and Precautions (5.1)].
In patients with type 1 diabetes, LEVEMIR must be used in a regimen with rapid-acting or short-acting insulin.
As with all insulins, injection sites should be rotated within the same region (abdomen, thigh, or deltoid) from one injection to the next to reduce the risk of lipodystrophy [see Adverse Reactions (6.1)].
LEVEMIR can be injected subcutaneously in the thigh, abdominal wall, or upper arm. As with all insulins, the rate of absorption, and consequently the onset and duration of action, may be affected by exercise and other variables, such as stress, intercurrent illness, or changes in co-administered medications or meal patterns.
The recommended starting dose of LEVEMIR in patients with type 1 diabetes should be approximately one-third of the total daily insulin requirements. Rapid-acting or short-acting, pre-meal insulin should be used to satisfy the remainder of the daily insulin requirements.
The recommended starting dose of LEVEMIR in patients with type 2 diabetes who are not currently treated with insulin is 10 Units (or 0.1-0.2 Units/kg) given once daily in the evening or divided into a twice daily regimen.
LEVEMIR doses should subsequently be adjusted based on blood glucose measurements. The dosages of LEVEMIR should be individualized under the supervision of a healthcare provider.
If converting from insulin glargine to LEVEMIR, the change can be done on a unit-to-unit basis.
If converting from NPH insulin, the change can be done on a unit-to-unit basis. However, some patients with type 2 diabetes may require more LEVEMIR than NPH insulin, as observed in one trial [see Clinical Studies (14)].
As with all insulins, close glucose monitoring is recommended during the transition and in the initial weeks thereafter. Doses and timing of concurrent rapid-acting or short-acting insulins or other concomitant antidiabetic treatment may need to be adjusted.
LEVEMIR solution for injection 100 Unit per mL is available as:
LEVEMIR is contraindicated in patients with hypersensitivity to LEVEMIR or any of its excipients. Reactions have included anaphylaxis [see Warnings and Precautions (5.4) and Adverse Reactions (6.1)]
Glucose monitoring is essential for all patients receiving insulin therapy. Changes to an insulin regimen should be made cautiously and only under medical supervision.
Changes in insulin strength, manufacturer, type, or method of administration may result in the need for a change in the insulin dose or an adjustment of concomitant anti-diabetic treatment.
As with all insulin preparations, the time course of action for LEVEMIR may vary in different individuals or at different times in the same individual and is dependent on many conditions, including the local blood supply, local temperature, and physical activity.
LEVEMIR should only be administered subcutaneously.
Do not administer LEVEMIR intravenously or intramuscularly. The intended duration of activity of LEVEMIR is dependent on injection into subcutaneous tissue. Intravenous or intramuscular administration of the usual subcutaneous dose could result in severe hypoglycemia [see Warnings and Precautions (5.3)].
Do not use LEVEMIR in insulin infusion pumps.
Do not dilute or mix LEVEMIR with any other insulin or solution. If LEVEMIR is diluted or mixed, the pharmacokinetic or pharmacodynamic profile (e.g., onset of action, time to peak effect) of LEVEMIR and the mixed insulin may be altered in an unpredictable manner.
Hypoglycemia is the most common adverse reaction of insulin therapy, including LEVEMIR. The risk of hypoglycemia increases with intensive glycemic control. Patients must be educated to recognize and manage hypoglycemia. Severe hypoglycemia can lead to unconsciousness or convulsions and may result in temporary or permanent impairment of brain function or death. Severe hypoglycemia requiring the assistance of another person or parenteral glucose infusion, or glucagon administration has been observed in clinical trials with insulin, including trials with LEVEMIR.
The timing of hypoglycemia usually reflects the time-action profile of the administered insulin formulations. Other factors such as changes in food intake (e.g., amount of food or timing of meals), exercise, and concomitant medications may also alter the risk of hypoglycemia [see Drug Interactions (7)].
The prolonged effect of subcutaneous LEVEMIR may delay recovery from hypoglycemia.
As with all insulins, use caution in patients with hypoglycemia unawareness and in patients who may be predisposed to hypoglycemia (e.g., the pediatric population and patients who fast or have erratic food intake). The patient's ability to concentrate and react may be impaired as a result of hypoglycemia. This may present a risk in situations where these abilities are especially important, such as driving or operating other machinery.
Early warning symptoms of hypoglycemia may be different or less pronounced under certain conditions, such as longstanding diabetes, diabetic neuropathy, use of medications such as beta-blockers, or intensified glycemic control [see Drug Interactions (7)]. These situations may result in severe hypoglycemia (and, possibly, loss of consciousness) prior to the patient’s awareness of hypoglycemia.
Severe, life-threatening, generalized allergy, including anaphylaxis, can occur with insulin products, including LEVEMIR.
No difference was observed in the pharmacokinetics of insulin detemir between non-diabetic individuals with renal impairment and healthy volunteers. However, some studies with human insulin have shown increased circulating insulin concentrations in patients with renal impairment. Careful glucose monitoring and dose adjustments of insulin, including LEVEMIR, may be necessary in patients with renal impairment [see Clinical Pharmacology (12.3)].
Non-diabetic individuals with severe hepatic impairment had lower systemic exposures to insulin detemir compared to healthy volunteers. However, some studies with human insulin have shown increased circulating insulin concentrations in patients with liver impairment. Careful glucose monitoring and dose adjustments of insulin, including LEVEMIR, may be necessary in patients with hepatic impairment [see Clinical Pharmacology (12.3)].
Some medications may alter insulin requirements and subsequently increase the risk for hypoglycemia or hyperglycemia [see Drug Interactions (7)].
The following adverse reactions are discussed elsewhere:
Because clinical trials are conducted under widely varying designs, the adverse reaction rates reported in one clinical trial may not be easily compared to those rates reported in another clinical trial, and may not reflect the rates actually observed in clinical practice.
The frequencies of adverse reactions (excluding hypoglycemia) reported during LEVEMIR clinical trials in patients with type 1 diabetes mellitus and type 2 diabetes mellitus are listed in Tables 1-4 below. See Tables 5 and 6 for the hypoglycemia findings.
LEVEMIR, % (n = 767) |
NPH, % (n = 388) |
|
Upper respiratory tract infection | 26.1 | 21.4 |
Headache | 22.6 | 22.7 |
Pharyngitis | 9.5 | 8.0 |
Influenza-like illness | 7.8 | 7.0 |
Abdominal Pain | 6.0 | 2.6 |
LEVEMIR, % (n = 161) |
Glargine, % (n = 159) |
|
Upper respiratory tract infection | 26.7 | 32.1 |
Headache | 14.3 | 19.5 |
Back pain | 8.1 | 6.3 |
Influenza-like illness | 6.2 | 8.2 |
Gastroenteritis | 5.6 | 4.4 |
Bronchitis | 5.0 | 1.9 |
LEVEMIR, % (n = 432) |
NPH, % (n = 437) |
|
Upper respiratory tract infection | 12.5 | 11.2 |
Headache | 6.5 | 5.3 |
LEVEMIR, % (n = 232) |
NPH, % (n = 115) |
|
Upper respiratory tract infection | 35.8 | 42.6 |
Headache | 31.0 | 32.2 |
Pharyngitis | 17.2 | 20.9 |
Gastroenteritis | 16.8 | 11.3 |
Influenza-like illness | 13.8 | 20.9 |
Abdominal pain | 13.4 | 13.0 |
Pyrexia | 10.3 | 6.1 |
Cough | 8.2 | 4.3 |
Viral infection | 7.3 | 7.8 |
Nausea | 6.5 | 7.0 |
Rhinitis | 6.5 | 3.5 |
Vomiting | 6.5 | 10.4 |
Hypoglycemia is the most commonly observed adverse reaction in patients using insulin, including LEVEMIR [see Warnings and Precautions (5.3)].
Tables 5 and 6 summarize the incidence of severe and non-severe hypoglycemia in the LEVEMIR clinical trials. Severe hypoglycemia was defined as an event with symptoms consistent with hypoglycemia requiring assistance of another person and associated with either a blood glucose below 50 mg/dL or prompt recovery after oral carbohydrate, intravenous glucose or glucagon administration. Non-severe hypoglycemia was defined as an asymptomatic or symptomatic plasma glucose < 56 mg/dL (<50 mg/dL in Study A and C) that was self-treated by the patient.
The rates of hypoglycemia in the LEVEMIR clinical trials (see Section 14 for a description of the study designs) were comparable between LEVEMIR-treated patients and non-LEVEMIR-treated patients (see Tables 5 and 6).
Study A Type 1 Diabetes Adults 16 weeks In combination with insulin aspart |
Study B Type 1 Diabetes Adults 26 weeks In combination with insulin aspart |
Study C Type 1 Diabetes Adults 24 weeks In combination with regular insulin |
Study D Type 1 Diabetes Pediatrics 26 weeks In combination with insulin aspart |
||||||
Twice-Daily LEVEMIR |
Twice-Daily NPH |
Twice-Daily LEVEMIR | Once-Daily Glargine | Once-Daily LEVEMIR | Once-Daily NPH | Once- or Twice Daily LEVEMIR | Once- or Twice Daily NPH | ||
Severe hypoglycemia |
Percent of patients with at least 1 event (n/total N) |
8.7 (24/276) |
10.6 (14/132) |
5.0 (8/161) |
10.1 (16/159) |
7.5 (37/491) |
10.2 (26/256) |
15.9 (37/232) |
20.0 (23/115) |
Event/patient/ year | 0.52 | 0.43 | 0.13 | 0.31 | 0.35 | 0.32 | 0.91 | 0.99 | |
Non-severe hypoglycemia | Percent of patients (n/total N) |
88.0 (243/276) |
89.4 (118/132) |
82.0 (132/161) |
77.4 (123/159) |
88.4 (434/491) |
87.9 (225/256) |
93.1 (216/232) |
95.7 (110/115) |
Event/patient/ year | 26.4 | 37.5 | 20.2 | 21.8 | 31.1 | 33.4 | 31.6 | 37.0 |
Study E Type 2 Diabetes Adults 24 weeks In combination with oral agents |
Study F Type 2 Diabetes Adults 22 weeks In combination with insulin aspart |
||||
Twice-Daily LEVEMIR | Twice-Daily NPH | Once- or Twice Daily LEVEMIR | Once- or Twice Daily NPH | ||
Severe hypoglycemia | Percent of patients with at least 1 event (n/total N) |
0.4 (1/237) |
2.5 (6/238) |
1.5 (3/195) |
4.0 (8/199) |
Event/patient/year | 0.01 | 0.08 | 0.04 | 0.13 | |
Non-severe hypoglycemia | Percent of patients (n/total N) |
40.5 (96/237) |
64.3 (153/238) |
32.3 (63/195) |
32.2 (64/199) |
Event/patient/year | 3.5 | 6.9 | 1.6 | 2.0 |
Intensification or rapid improvement in glucose control has been associated with a transitory, reversible ophthalmologic refraction disorder, worsening of diabetic retinopathy, and acute painful peripheral neuropathy. However, long-term glycemic control decreases the risk of diabetic retinopathy and neuropathy.
Long-term use of insulin, including LEVEMIR, can cause lipodystrophy at the site of repeated insulin injections. Lipodystrophy includes lipohypertrophy (thickening of adipose tissue) and lipoatrophy (thinning of adipose tissue), and may affect insulin adsorption. Rotate insulin injection sites within the same region to reduce the risk of lipodystrophy [see Dosage and Administration (2.1)].
Weight gain can occur with insulin therapy, including LEVEMIR, and has been attributed to the anabolic effects of insulin and the decrease in glucosuria.
Insulin, including LEVEMIR, may cause sodium retention and edema, particularly if previously poor metabolic control is improved by intensified insulin therapy.
Local Allergy
As with any insulin therapy, patients taking LEVEMIR may experience injection site reactions, including localized erythema, pain, pruritis, urticaria, edema, and inflammation. In clinical studies in adults, three patients treated with LEVEMIR reported injection site pain (0.25%) compared to one patient treated with NPH insulin (0.12%). The reports of pain at the injection site did not result in discontinuation of therapy.
Rotation of the injection site within a given area from one injection to the next may help to reduce or prevent these reactions. 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. Most minor reactions to insulin usually resolve in a few days to a few weeks.
Systemic Allergy
Severe, life-threatening, generalized allergy, including anaphylaxis, generalized skin reactions, angioedema, bronchospasm, hypotension, and shock may occur with any insulin, including LEVEMIR, and may be life-threatening [see Warnings and Precautions (5.4)].
All insulin products can elicit the formation of insulin antibodies. These insulin antibodies may increase or decrease the efficacy of insulin and may require adjustment of the insulin dose. In phase 3 clinical trials of LEVEMIR, antibody development has been observed with no apparent impact on glycemic control.
The following adverse reactions have been identified during post approval use of LEVEMIR. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.
Medication errors have been reported during post-approval use of LEVEMIR in which other insulins, particularly rapid-acting or short-acting insulins, have been accidentally administered instead of LEVEMIR [see Patient Counseling Information (17)]. To avoid medication errors between LEVEMIR and other insulins, patients should be instructed always to verify the insulin label before each injection.
A number of medications affect glucose metabolism and may require insulin dose adjustment and particularly close monitoring.
The following are examples of medications that may increase the blood-glucose-lowering effect of insulins including LEVEMIR and, therefore, increase the susceptibility to hypoglycemia: oral antidiabetic medications, pramlintide acetate, angiotensin converting enzyme (ACE) inhibitors, disopyramide, fibrates, fluoxetine, monoamine oxidase (MAO) inhibitors, propoxyphene, pentoxifylline, salicylates, somatostatin analogs, and sulfonamide antibiotics.
The following are examples of medications that may reduce the blood-glucose-lowering effect of insulins including LEVEMIR: corticosteroids, niacin, danazol, diuretics, sympathomimetic agents (e.g., epinephrine, albuterol, terbutaline), glucagon, isoniazid, phenothiazine derivatives, somatropin, thyroid hormones, estrogens, progestogens (e.g., in oral contraceptives), protease inhibitors and atypical antipsychotic medications (e.g. olanzapine and clozapine).
Beta-blockers, clonidine, lithium salts, and alcohol may either increase or decrease the blood-glucose-lowering effect of insulin. Pentamidine may cause hypoglycemia, which may sometimes be followed by hyperglycemia.
The signs of hypoglycemia may be reduced or absent in patients taking anti-adrenergic drugs such as beta-blockers, clonidine, guanethidine, and reserpine.
Pregnancy Category C: In a fertility and embryonic development study, insulin detemir was administered to female rats before mating, during mating, and throughout pregnancy at doses up to 300 nmol/kg/day (3 times a human dose of 0.5 Units/kg/day, based on plasma area under the curve (AUC) ratio). Doses of 150 and 300 nmol/kg/day produced numbers of litters with visceral anomalies. Doses up to 900 nmol/kg/day (approximately 135 times a human dose of 0.5 Units/kg/day based on AUC ratio) were given to rabbits during organogenesis. Drug-dose related increases in the incidence of fetuses with gallbladder abnormalities such as small, bilobed, bifurcated, and missing gallbladders were observed at a dose of 900 nmol/kg/day. The rat and rabbit embryofetal development studies that included concurrent human insulin control groups indicated that insulin detemir and human insulin had similar effects regarding embryotoxicity and teratogenicity.
There are no well-controlled clinical studies of the use of LEVEMIR in pregnant women. Patients should be advised to discuss with their healthcare provider if they intend to, or if they become, pregnant. Because animal reproduction studies are not always predictive of human response, LEVEMIR should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. It is essential for patients with diabetes or a 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.
It is unknown whether LEVEMIR is excreted in human milk. Because many drugs, including human insulin, are excreted in human milk, use caution when administering LEVEMIR to a nursing woman. Use of LEVEMIR is compatible with breastfeeding, but women with diabetes who are lactating may require adjustments of their insulin doses.
The pharmacokinetics, safety and effectiveness of subcutaneous injections of LEVEMIR have been established in pediatric patients (age 6 to 17 years) with type 1 diabetes [see Clinical Pharmacology (12.3) and Clinical Studies (14)]. LEVEMIR has not been studied in pediatric patients younger than 6 years of age with type 1 diabetes. LEVEMIR has not been studied in pediatric patients with type 2 diabetes.
The dose recommendation when converting to LEVEMIR is the same as that described for adults [see Dosage and Administration (2) and Clinical Studies (14)]. As in adults, the dosage of LEVEMIR must be individualized in pediatric patients based on metabolic needs and frequent monitoring of blood glucose.
In controlled clinical trials comparing LEVEMIR to NPH insulin or insulin glargine, 64 of 1624 patients (3.9%) in the type 1 diabetes trials and 309 of 1082 patients (28.6%) in the type 2 diabetes trials were ≥65 years of age. A total of 52 (7 type 1 and 45 type 2) patients (1.9%) were ≥75 years of age. No overall differences in safety or effectiveness were observed between these patients and younger patients, but small sample sizes, particularly for patients ≥65 years of age in the type 1 diabetes trials and for patients ≥75 years of age in all trials limits conclusions. Greater sensitivity of some older individuals cannot be ruled out. In elderly patients with diabetes, the initial dosing, dose increments, and maintenance dosage should be conservative to avoid hypoglycemia. Hypoglycemia may be difficult to recognize in the elderly.
An excess of insulin relative to food intake, energy expenditure, or both may lead to severe and sometimes prolonged and life-threatening hypoglycemia. 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. After apparent clinical recovery from hypoglycemia, continued observation and additional carbohydrate intake may be necessary to avoid recurrence of hypoglycemia [see Warnings and Precautions (5.3)].
LEVEMIR (insulin detemir [rDNA origin] injection) is a sterile solution of insulin detemir for use as a subcutaneous injection. Insulin detemir is a long-acting (up to 24-hour duration of action) recombinant human insulin analog. LEVEMIR is produced by a process that includes expression of recombinant DNA in Saccharomyces cerevisiae followed by chemical modification.
Insulin detemir differs from human insulin in that the amino acid threonine in position B30 has been omitted, and a C14 fatty acid chain has been attached to the amino acid B29. Insulin detemir has a molecular formula of C267H402O76N64S6 and a molecular weight of 5916.9. It has the following structure:
Figure 1: Structural Formula of insulin detemir
LEVEMIR is a clear, colorless, aqueous, neutral sterile solution. Each milliliter of LEVEMIR contains 100 units (14.2 mg/mL) insulin detemir, 65.4 mcg zinc, 2.06 mg m-cresol, 16.0 mg glycerol, 1.80 mg phenol, 0.89 mg disodium phosphate dihydrate, 1.17 mg sodium chloride, and water for injection. Hydrochloric acid and/or sodium hydroxide may be added to adjust pH. LEVEMIR has a pH of approximately 7.4.
The primary activity of insulin detemir is the regulation of glucose metabolism. Insulins, including insulin detemir, exert their specific action through binding to insulin receptors. Receptor-bound insulin lowers blood glucose by facilitating cellular uptake of glucose into skeletal muscle and adipose tissue and by inhibiting the output of glucose from the liver. Insulin inhibits lipolysis in the adipocyte, inhibits proteolysis, and enhances protein synthesis.
Insulin detemir is a soluble, long-acting basal human insulin analog with up to a 24-hour duration of action. The pharmacodynamic profile of LEVEMIR is relatively constant with no pronounced peak.
The duration of action of LEVEMIR is mediated by slowed systemic absorption of insulin detemir molecules from the injection site due to self-association of the drug molecules. In addition, the distribution of insulin detemir to peripheral target tissues is slowed because of binding to albumin.
Figure 2 shows results from a study in patients with type 1 diabetes conducted for a maximum of 24 hours after the subcutaneous injection of LEVEMIR or NPH insulin. The mean time between injection and the end of pharmacological effect for insulin detemir ranged from 7.6 hours to > 24 hours (24 hours was the end of the observation period).
Figure 2: Activity Profiles in Patients with Type 1 Diabetes in a 24-hour Glucose Clamp Study
For doses in the interval of 0.2 to 0.4 Units/kg, insulin detemir exerts more than 50% of its maximum effect from 3 to 4 hours up to approximately 14 hours after dose administration.
Figure 3 shows glucose infusion rate results from a 16-hour glucose clamp study in patients with type 2 diabetes. The clamp study was terminated at 16 hours according to protocol.
Figure 3: Activity Profiles in Patients with Type 2 Diabetes in a 16-hour Glucose Clamp Study
Absorption and Bioavailability
After subcutaneous injection of LEVEMIR in healthy subjects and in patients with diabetes, insulin detemir serum concentrations had a relatively constant concentration/time profile over 24 hours with the maximum serum concentration (Cmax) reached between 6-8 hours post-dose. Insulin detemir was more slowly absorbed after subcutaneous administration to the thigh where AUC0-5h was 30-40% lower and AUC0-inf was 10% lower than the corresponding AUCs with subcutaneous injections to the deltoid and abdominal regions.
The absolute bioavailability of insulin detemir is approximately 60%.
Distribution and Elimination
More than 98% of insulin detemir in the bloodstream is bound to albumin. The results of in vitro and in vivo protein binding studies demonstrate that there is no clinically relevant interaction between insulin detemir and fatty acids or other protein-bound drugs.
Insulin detemir has an apparent volume of distribution of approximately 0.1 L/kg. After subcutaneous administration in patients with type 1 diabetes, insulin detemir has a terminal half-life of 5 to 7 hours depending on dose.
Specific Populations
Children and Adolescents- The pharmacokinetic properties of LEVEMIR were investigated in children (6-12 years), adolescents (13-17 years), and adults with type 1 diabetes. In children, the insulin detemir plasma area under the curve (AUC) and Cmax were increased by 10% and 24%, respectively, as compared to adults. There was no difference in pharmacokinetics between adolescents and adults.
Geriatrics- In a clinical trial investigating differences in pharmacokinetics of a single subcutaneous dose of LEVEMIR in young (20 to 35 years) versus elderly (≥68 years) healthy subjects, the insulin detemir AUC was up to 35% higher among the elderly subjects due to reduced clearance. As with other insulin preparations, LEVEMIR should always be titrated according to individual requirements.
Gender- No clinically relevant differences in pharmacokinetic parameters of LEVEMIR are observed between males and females.
Race- In two clinical pharmacology studies conducted in healthy Japanese and Caucasian subjects, there were no clinically relevant differences seen in pharmacokinetic parameters. The pharmacokinetics and pharmacodynamics of LEVEMIR were investigated in a clamp study comparing patients with type 2 diabetes of Caucasian, African-American, and Latino origin. Dose-response relationships for LEVEMIR were comparable in these three populations.
Renal impairment- A single subcutaneous dose of 0.2 Units/kg (1.2 nmol/kg) of LEVEMIR was administered to healthy subjects and those with varying degrees of renal impairment (mild, moderate, severe, and hemodialysis-dependent). In this study, there were no differences in the pharmacokinetics of LEVEMIR between healthy subjects and those with renal impairment. However, some studies with human insulin have shown increased circulating levels of insulin in patients with renal impairment. Careful glucose monitoring and dose adjustments of insulin, including LEVEMIR, may be necessary in patients with renal impairment [see Warnings and Precautions (5.5)].
Hepatic impairment- A single subcutaneous dose of 0.2 Units/kg (1.2 nmol/kg) of LEVEMIR was administered to healthy subjects and those with varying degrees of hepatic impairment (mild, moderate and severe). LEVEMIR exposure as estimated by AUC decreased with increasing degrees of hepatic impairment with a corresponding increase in apparent clearance. However, some studies with human insulin have shown increased circulating levels of insulin in patients with liver impairment. Careful glucose monitoring and dose adjustments of insulin, including LEVEMIR, may be necessary in patients with hepatic impairment [see Warnings and Precautions (5.6)].
Pregnancy- The effect of pregnancy on the pharmacokinetics and pharmacodynamics of LEVEMIR has not been studied [see Use in Specific Populations (8.1)].
Smoking- The effect of smoking on the pharmacokinetics and pharmacodynamics of LEVEMIR has not been studied.
Standard 2-year carcinogenicity studies in animals have not been performed. Insulin detemir tested negative for genotoxic potential in the in vitro reverse mutation study in bacteria, human peripheral blood lymphocyte chromosome aberration test, and the in vivo mouse micronucleus test.
In a fertility and embryonic development study, insulin detemir was administered to female rats before mating, during mating, and throughout pregnancy at doses up to 300 nmol/kg/day (3 times a human dose of 0.5 Units/kg/day, based on plasma AUC ratio). There were no effects on fertility in the rat.
The efficacy and safety of LEVEMIR given once-daily at bedtime or twice-daily (before breakfast and at bedtime, before breakfast and with the evening meal, or at 12-hour intervals) was compared to that of once-daily or twice-daily NPH insulin in open-label, randomized, parallel studies of 1155 adults with type 1 diabetes mellitus, 347 pediatric patients with type 1 diabetes mellitus, and 869 adults with type 2 diabetes mellitus. The efficacy and safety of LEVEMIR given twice-daily was compared to once-daily insulin glargine in an open-label, randomized, parallel study of 320 patients with type 1 diabetes. The evening LEVEMIR dose was titrated in all trials according to pre-defined targets for fasting blood glucose. The pre-dinner blood glucose was used to titrate the morning LEVEMIR dose in those trials that also administered LEVEMIR in the morning. In general, the reduction in glycosylated hemoglobin (HbA1c) with LEVEMIR was similar to that with NPH insulin or insulin glargine.
Type 1 Diabetes – Adult
In a 16-week open-label clinical study (Study A, n=409), adults with type 1 diabetes were randomized to treatment with either LEVEMIR at 12-hour intervals, LEVEMIR administered in the morning and bedtime or NPH insulin administered in the morning and bedtime. Insulin aspart was also administered before each meal. At 16 weeks of treatment, the combined LEVEMIR-treated patients had similar HbA1c and fasting plasma glucose (FPG) reductions compared to the NPH-treated patients (Table 7). Differences in timing of LEVEMIR administration had no effect on HbA1c, fasting plasma glucose (FPG), or body weight.
In a 26-week, open-label clinical study (Study B, n=320), adults with type 1 diabetes were randomized to twice-daily LEVEMIR (administered in the morning and bedtime) or once-daily insulin glargine (administered at bedtime). Insulin aspart was administered before each meal. LEVEMIR-treated patients had a decrease in HbA1c similar to that of insulin glargine-treated patients.
In a 24-week, non-blinded clinical study (Study C, n=749), adults with type 1 diabetes were randomized to once-daily LEVEMIR or once-daily NPH insulin, both administered at bedtime and in combination with regular human insulin before each meal. LEVEMIR and NPH insulin had a similar effect on HbA1c.
Study A | Study B | Study C | ||||
Treatment duration | 16 weeks | 26 weeks | 24 weeks | |||
Treatment in combination with |
NovoLog® (insulin aspart) |
NovoLog® (insulin aspart) |
Human Soluble Insulin (regular insulin) |
|||
Twice-daily LEVEMIR |
Twice-daily NPH | Twice-daily LEVEMIR | Once-daily insulin glargine | Once-daily LEVEMIR | Once-daily NPH | |
Number of patients treated | 276 | 133 | 161 | 159 | 492 | 257 |
HbA1c (%) | ||||||
Baseline HbA1c | 8.6 | 8.5 | 8.9 | 8.8 | 8.4 | 8.3 |
Adj. mean change from baseline | -0.8 | -0.7 | -0.6 | -0.5 | -0.1 | 0.0 |
LEVEMIR – NPH 95% CI for Treatment difference |
-0.2 (-0.3, -0.0) |
-0.0 (-0.2, 0.2) |
-0.1 (-0.3, 0.0) |
|||
Basal insulin dose (units/day) | ||||||
Baseline mean | 21 | 24 | 27 | 23 | 12 | 24 |
Mean change from baseline | 16 | 10 | 10 | 4 | 9 | 2 |
Total insulin dose (units/day) | ||||||
Baseline mean | 48 | 54 | 56 | 51 | 46 | 57 |
Mean change from baseline | 17 | 10 | 9 | 6 | 11 | 3 |
Fasting blood glucose (mg/dL) | ||||||
Baseline mean | 209 | 220 | 153 | 150 | 213 | 206 |
Adj. mean change from baseline | -44 | -9 | -38 | -41 | -30 | -9 |
Body weight (kg) | ||||||
Baseline mean | 74.6 | 75.5 | 77.5 | 75.1 | 76.5 | 76.9 |
Mean change from baseline | 0.2 | 0.8 | 0.5 | 1.0 | -0.3 | 0.3 |
Baseline values were included as covariates in an ANCOVA analysis.
Type 1 Diabetes – Pediatric
In an open-label clinical study (Study D, n=347), pediatric patients (age range 6 to 17) with type 1 diabetes were randomized to 26 weeks of treatment with LEVEMIR or NPH insulin both of which were administered either once- or twice-daily (bedtime or morning and bedtime), at a dosing frequency consistent with the number of daily basal insulin injections a patient was taking prior to trial entry. Insulin aspart was administered before each meal. LEVEMIR-treated patients had a decrease in HbA1c similar to that of NPH insulin (Table 8).
Study D | ||
Treatment duration | 26 weeks | |
Treatment in combination with |
NovoLog® (insulin aspart) |
|
Once- or Twice Daily LEVEMIR |
Once- or Twice Daily NPH |
|
Number of subjects treated | 232 | 115 |
HbA1c (%) | ||
Baseline HbA1c | 8.8 | 8.8 |
Adj. mean change from baseline | -0.7 | -0.8 |
LEVEMIR – NPH 95% CI for Treatment difference |
0.1 (-0.1, 0.3) |
|
Basal insulin dose (units/day) | ||
Baseline mean | 24 | 26 |
Mean change from baseline | 8 | 6 |
Total insulin dose (units/day) | ||
Baseline mean | 48 | 50 |
Mean change from baseline | 9 | 7 |
Fasting blood glucose (mg/dL) | ||
Baseline mean | 181 | 181 |
Adj. mean change from baseline | -39 | -21 |
Body weight (kg) | ||
Baseline mean | 46.3 | 46.2 |
Mean change from baseline | 1.6 | 2.7 |
Type 2 Diabetes – Adult
In a 24-week, open-label, randomized, clinical study (Study E, n=476), LEVEMIR administered twice-daily (before breakfast and evening) was compared to NPH insulin administered twice-daily (before breakfast and evening) as part of a regimen of stable combination therapy with one or two of the following oral antidiabetic medications: metformin, an insulin secretagogue, or an alpha–glucosidase inhibitor. All patients were insulin-naïve at the time of randomization. LEVEMIR and NPH insulin similarly lowered HbA1c from baseline (Table 9).
In a 22-week, open-label, randomized, clinical study (Study F, n=395) in adults with type 2 diabetes, LEVEMIR and NPH insulin were given once- or twice-daily as part of a basal-bolus regimen with insulin aspart. As measured by HbA1c or FPG, LEVEMIR had efficacy similar to that of NPH insulin.
Study E | Study F | |||
Treatment duration | 24 weeks | 22 weeks | ||
Treatment in combination with | oral agents | insulin aspart | ||
Twice-daily LEVEMIR |
Twice-daily NPH | Once- or Twice Daily LEVEMIR |
Once- or Twice Daily NPH |
|
Number of subjects treated | 237 | 239 | 195 | 200 |
HbA1c (%) | ||||
Baseline HbA1c | 8.6 | 8.5 | 8.2 | 8.1 |
Adj. mean change from baseline | -2.0 | -2.1 | -0.6 | -0.6 |
LEVEMIR – NPH 95% CI for Treatment difference |
0.1 (-0.0, 0.3) |
-0.1 (-0.2, 0.1) |
||
Basal insulin dose (units/day) | ||||
Baseline mean | 18 | 17 | 22 | 22 |
Mean change from baseline | 48 | 28 | 26 | 15 |
Total insulin dose* (units/day) | ||||
Baseline mean | - | - | 22 | 22 |
Mean change from baseline | - | - | 57 | 42 |
Fasting blood glucose† (mg/dL) | ||||
Baseline mean | 179 | 173 | - | - |
Adj. mean change from baseline | -69 | -74 | - | - |
Body weight (kg) | ||||
Baseline mean | 82.7 | 82.5 | 82.0 | 79.6 |
Mean change from baseline | 1.2 | 2.7 | 0.5 | 1.2 |
LEVEMIR is available in the following package sizes: each presentation containing 100 Units of insulin detemir per mL (U-100).
3 mL LEVEMIR FlexPen® NDC 0169-6439-10
10 mL vial NDC 0169-3687-12
FlexPen is for use with NovoFine® disposable needles. Each FlexPen is for use by a single patient. LEVEMIR FlexPen should never be shared between patients, even if the needle is changed.
Unused (unopened) LEVEMIR should be stored in the refrigerator between 2° and 8°C (36° to 46°F). Do not store in the freezer or directly adjacent to the refrigerator cooling element. Do not freeze. Do not use LEVEMIR if it has been frozen.
Unused (unopened) LEVEMIR can be kept until the expiration date printed on the label if it is stored in a refrigerator. Keep unused LEVEMIR in the carton so that it stays clean and protected from light.
If refrigeration is not possible, unused (unopened) LEVEMIR can be kept unrefrigerated at room temperature, below 30°C (86°F) as long as it is kept as cool as possible and away from direct heat and light. Unrefrigerated LEVEMIR should be discarded 42 days after it is first kept out of the refrigerator, even if the FlexPen or vial still contains insulin.
Vials:
After initial use, vials should be stored in a refrigerator, never in a freezer. If refrigeration is not possible, the in-use vial can be kept unrefrigerated at room temperature, below 30°C (86°F) as long as it is kept as cool as possible and away from direct heat and light. Refrigerated LEVEMIR vials should be discarded 42 days after initial use. Unrefrigerated LEVEMIR vials should be discarded 42 days after they are first kept out of the refrigerator.
LEVEMIR FlexPen:
After initial use, the LEVEMIR FlexPen must NOT be stored in a refrigerator and must NOT be stored with the needle in place. Keep the opened (in use) LEVEMIR FlexPen away from direct heat and light at room temperature, below 30°C (86°F). Unrefrigerated LEVEMIR FlexPens should be discarded 42 days after they are first kept out of the refrigerator.
The storage conditions are summarized in Table 10:
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Not in-use (unopened) Refrigerated | Not in-use (unopened) Room Temperature (below 30°C) | In-use (opened) |
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3 mL LEVEMIR FlexPen | Until expiration date | 42 days* |
42 days* Room Temperature |
10 mL vial | Until expiration date | 42 days* |
42 days * Refrigerated or Room Temperature (below 30°C) |
Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit. LEVEMIR should be inspected visually prior to administration and should only be used if the solution appears clear and colorless.
Mixing and diluting: LEVEMIR must NOT be mixed or diluted with any other insulin or solution [See Warnings and Precautions (5.2)].
See FDA-Approved Patient Labeling (Patient Information and Instructions for Use)
Patients should be informed that changes to insulin regimens must be made cautiously and only under medical supervision. Patients should be informed about the potential side effects of insulin
therapy, including hypoglycemia, weight gain, lipodystrophy (and the need to rotate injection sites within the same body region), and allergic reactions. Patients should be informed that the ability to concentrate and react may be impaired as a result of hypoglycemia. This may present a risk in situations where these abilities are especially important, such as driving or operating other machinery. Patients who have frequent hypoglycemia or reduced or absent warning signs of hypoglycemia should be advised to use caution when driving or operating machinery.
Accidental mix-ups between LEVEMIR and other insulins, particularly short-acting insulins, have been reported. To avoid medication errors between LEVEMIR and other insulins, patients should be instructed to always check the insulin label before each injection.
LEVEMIR must only be used if the solution is clear and colorless with no particles visible. Patients must be advised that LEVEMIR must NOT be diluted or mixed with any other insulin or solution.
Patients should be instructed on self-management procedures including glucose monitoring, proper injection technique, and management of hypoglycemia and hyperglycemia. Patients should be instructed on handling of special situations such as intercurrent conditions (illness, stress, or emotional disturbances), an inadequate or skipped insulin dose, inadvertent administration of an increased insulin dose, inadequate food intake, and skipped meals.
Patients with diabetes should be advised to inform their healthcare professional if they are pregnant or are contemplating pregnancy. Refer patients to the LEVEMIR "Patient Information" for additional information.
Counsel patients that they should never share a LEVEMIR FlexPen with another person, even if the needle is changed. Sharing of the FlexPen between patients may pose a risk of transmission of infection.
Novo Nordisk®, Levemir®, NovoLog®, FlexPen®, and NovoFine® are registered trademarks of Novo Nordisk A/S.
LEVEMIR is covered by US Patent Nos. 5,750,497, 5,866,538, 6,011,007, 6,869,930 and other patents pending.
FlexPen is covered by US Patent Nos. 6,582,404, 6,004,297, 6,235,400 and other patents pending.
© 2005-2012 Novo Nordisk
Manufactured by:
Novo Nordisk A/S
DK-2880 Bagsvaerd, Denmark
For information about LEVEMIR contact:
Novo Nordisk Inc.
100 College Road West
Princeton, NJ 08540
1-800-727-6500
www.novonordisk-us.com
LEVEMIR® (LEV–uh-mere)
(insulin detemir [rDNA origin] injection)
solution for subcutaneous injection
Read the Patient Information that comes with LEVEMIR® before you start taking it and each time you get a refill. There may be new information. This leaflet does not take the place of talking with your healthcare provider about your diabetes or your treatment. Make sure that you know how to manage your diabetes. Ask your healthcare provider, if you have any questions about managing your diabetes.
What is LEVEMIR?
LEVEMIR is a man-made long-acting insulin, that is used to control high blood sugar in adults and children with diabetes mellitus.
It is not recommended to use LEVEMIR to treat diabetic ketoacidosis.
Who should not use LEVEMIR?
Do not take LEVEMIR if:
What should I tell my healthcare provider before taking LEVEMIR?
Before you take LEVEMIR, tell your healthcare provider if you:
Tell your healthcare provider about all the medicines you take, including prescription and non-prescription medicines, vitamins and herbal supplements. LEVEMIR may affect the way other medicines work, and other medicines may affect how LEVEMIR works.
Know the medicines you take. Keep a list of your medicines with you to show your healthcare provider and pharmacist when you get a new medicine.
How should I take LEVEMIR?
Know your insulin. Make sure you know:
LEVEMIR comes in:
Ask your healthcare provider how you should use LEVEMIR.
If you pass out you will need help from another person or emergency medical services right away. See “What are the possible side effects of LEVEMIR?” for more information on low blood sugar (hypoglycemia).
Follow your healthcare provider’s instructions for treating high blood sugar.
Know your symptoms of high blood sugar, which may include:
Your insulin dosage may need to change because of:
What should I avoid while taking LEVEMIR?
What are the possible side effects of LEVEMIR?
LEVEMIR can cause serious side effects, including:
Very low blood sugar (hypoglycemia) can cause loss of consciousness (passing out), seizures, and death. Talk to your healthcare provider about how to tell if you have low blood sugar and what to do if this happens while taking LEVEMIR. Know your symptoms of low blood sugar. Follow your healthcare provider’s instructions for treating low blood sugar.
Talk to your healthcare provider if low blood sugar is a problem for you. Your dose of LEVEMIR may need to be changed.
Common side effects of LEVEMIR include:
Tell your healthcare provider if you have any side effect that bothers you or does not go away.
These are not all of the possible side effects from LEVEMIR. Ask your healthcare provider or pharmacist for more information.
Call your doctor for medical advice about side effects.
You may report side effects to FDA at 1-800-FDA-1088.
How should I store LEVEMIR?
Unopened LEVEMIR:
LEVEMIR in use:
Keep LEVEMIR and all medicines out of the reach of children.
General information about LEVEMIR
Medicines are sometimes prescribed for conditions that are not mentioned in the patient leaflet. Do not use LEVEMIR for a condition for which it was not prescribed. Do not give LEVEMIR to other people, even if they have the same symptoms you have. It may harm them.
This leaflet summarizes the most important information about LEVEMIR. If you would like more information about LEVEMIR or diabetes, talk with your healthcare provider. You can ask your healthcare provider for information about LEVEMIR that is written for healthcare professionals.
For more information about LEVEMIR, call 1-800-727-6500 or go to www.novonordisk-us.com.
What are the ingredients in LEVEMIR?
Active Ingredient: Insulin detemir
Inactive Ingredients: zinc, m-cresol, glycerol, phenol, disodium phosphate dehydrate, sodium chloride and water for injection. Hydrochloric acid or sodium hydroxide may be added.
This Patient Information has been approved by the U.S. Food and Drug Administration.
Revised: January 2012
Novo Nordisk®, LEVEMIR®, and FlexPen® are registered trademarks of Novo Nordisk A/S.
LEVEMIR® is covered by US Patent Nos. 5,750,497, 5,866,538, 6,011,007, 6,869,930 and other patents pending.
FlexPen® is covered by US Patent Nos. 6,582,404, 6,004,297, 6,235,004 and other patents pending.
© 2005-2012 Novo Nordisk
Manufactured by:
Novo Nordisk A/S
DK-2880 Bagsvaerd, Denmark
For information about LEVEMIR® contact:
Novo Nordisk Inc.
100 College Road West
Princeton, New Jersey 08540
www.novonordisk-us.com
1-800-727-6500
Patient Instructions For Use
LEVEMIR® 10 mL vial
Please read the following Instructions for use carefully before using your LEVEMIR® 10 mL vial and each time you get a refill. You should read the instructions in this manual even if you have used an insulin 10 mL vial before.
How should I use the LEVEMIR 10 mL vial?
Using the 10 mL vial:
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Before each use, wipe the rubber stopper with an alcohol wipe. |
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How should I inject LEVEMIR with a syringe?
If you clean your injection site with an alcohol swab, let the injection site dry before you inject. Talk with your healthcare provider about how to rotate injection sites and how to give an injection.
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3. If blood appears after you pull the needle from your skin, press the injection site lightly with an alcohol swab. Do not rub the area. | |
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Revised: January 2012
Novo Nordisk® and LEVEMIR® are registered trademarks of Novo Nordisk A/S.
LEVEMIR® is covered by US Patent Nos. 5,750,497, 5,866,538, 6,011,007, 6,869,930, and other patents pending.
© 2005-2012 Novo Nordisk
Manufactured by:
Novo Nordisk A/S
DK-2880 Bagsvaerd, Denmark
For information about LEVEMIR® contact:
Novo Nordisk Inc.
100 College Road West,
Princeton, New Jersey 08540
Instructions For Use
LEVEMIR® FlexPen®
Please carefully read the following Instructions for use before using your LEVEMIR® FlexPen® and each time you get a refill. You should read the instructions in this manual even if you have used a LEVEMIR FlexPen before.
LEVEMIR FlexPen is a disposable dial-a-dose insulin pen. You can select doses from 1 to 60 units in increments of 1 unit. LEVEMIR FlexPen is designed to be used with NovoFine® needles.
Getting ready
Make sure you have the following items:
PREPARING YOUR LEVEMIR FLEXPEN
Wash your hands with soap and water. Before you start to prepare your injection, check the label to make sure that you are taking the right type of insulin. This is especially important if you take more than 1 type of insulin. LEVEMIR should look clear and colorless.
A. Pull off the pen cap (see diagram A). Wipe the rubber stopper with an alcohol swab. | |
B.Attaching the needle Remove the protective tab from a new disposable needle. |
Attach the needle tightly onto your FlexPen. It is important that the needle is put on straight (see diagram B). Never place a disposable needle on your LEVEMIR FlexPen until you are ready to give your injection. |
C. Pull off the big outer needle cap (see diagram C). | |
D. Pull off the inner needle cap and throw it away (see diagram D). |
Giving the airshot before each injection
Before each injection, small amounts of air may collect in the cartridge during normal use. To avoid injecting air and to ensure you take the right dose of insulin:
E. Turn the dose selector to select 2 units (see diagram E). | |
F. Hold your LEVEMIR FlexPen with the needle pointing up. Tap the cartridge gently with your finger a few times to make any air bubbles collect at the top of the cartridge (see diagram F). | |
G. While you keep the needle pointing upwards, press the push-button all the way in (see diagram G). The dose selector returns to 0. A drop of insulin should appear at the needle tip. If not, change the needle and repeat the procedure no more than 6 times. If you do not see a drop of insulin after 6 times, do not use the LEVEMIR FlexPen and contact Novo Nordisk at 1-800-727-6500. A small air bubble may remain at the needle tip, but it will not be injected. |
SELECTING YOUR DOSE
Check and make sure that the dose selector is set at 0.
H. Turn the dose selector to the number of units you need to inject. The pointer should line up with your dose. The dose can be corrected either up or down by turning the dose selector in either direction until the correct dose lines up with the pointer (see diagram H). When turning the dose selector, be careful not to press the push-button as insulin will come out. You cannot select a dose larger than the number of units left in the cartridge. You will hear a click for every single unit dialed. Do not set the dose by counting the number of clicks you hear. Δ Do not use the cartridge scale printed on the cartridge to measure your dose of insulin. |
GIVING THE INJECTION
Do the injection exactly as shown to you by your healthcare provider. Your healthcare provider should tell you if you need to pinch the skin before injecting. Wipe the skin with an alcohol swab and let the area dry.
I. Insert the needle into your skin. Inject the dose by pressing the push-button all the way in until the 0 lines up with the pointer (see diagram I). Be careful only to push the button after the needle is in the skin. Turning the dose selector will not inject insulin. |
J. Keep the needle in the skin for at least 6 seconds, and keep the push-button pressed all the way in until the needle has been pulled out from the skin (see diagram J). This will make sure that the full dose has been given. You may see a drop of LEVEMIR at the needle tip. This is normal and has no effect on the dose you just received. If blood appears after you take the needle out of your skin, press the injection site lightly with an alcohol swab. Do not rub the area. |
After the injection
Carefully remove the needle from the pen after each injection. This helps to prevent infection and leakage of insulin. You can carefully recap the needle with the bigger outer cap to help make it easier to remove the needle.
K. Put the pen cap on the LEVEMIR FlexPen and store the LEVEMIR FlexPen without the needle attached (see diagram K). The LEVEMIR FlexPen prevents the cartridge from being completely emptied. It can deliver 300 units then you should throw it away in a sharps container or some type of hard plastic or metal container with a screw top, such as a detergent bottle or empty coffee can. |
FUNCTION CHECK
L. If your LEVEMIR FlexPen is not working the right way, follow the steps below:
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The insulin should fill the lower part of the big outer needle cap to the marker (see diagram L). If LEVEMIR FlexPen has released too much or too little insulin, do the function check again. If the same problem happens again, do not use your LEVEMIR FlexPen and contact Novo Nordisk at 1-800-727-6500.
Maintenance
Your FlexPen is designed to work accurately and safely. It must be handled with care. If you drop your FlexPen it could get damaged. If you are concerned that your FlexPen is damaged, use a new one. You can clean the outside of your FlexPen by wiping it with a damp cloth. Do not soak or wash your FlexPen. Soaking or washing the FlexPen could damage it. Do not refill your FlexPen.
Revised: January 2012
Novo Nordisk® , LEVEMIR® , FlexPen® , NovoPen® , and NovoFine® are registered trademarks of Novo Nordisk A/S.
LEVEMIR® is covered by US Patent Nos. 5,750,497, 5,866,538, 6,011,007, 6,869,930, and other patents pending.
FlexPen® is covered by US Patent Nos. 6,582,404, 6,004,297, 6,235,004, and other patents pending.
© 2005-2012 Novo Nordisk
Manufactured by:
Novo Nordisk A/S
DK-2880 Bagsvaerd, Denmark
For information about LEVEMIR® contact:
Novo Nordisk Inc.
100 College Road West,
Princeton, New Jersey 08540
Levemir®
Insulin detemir (rDNA origin) injection
NDC 0169-3687-12
List 368712
100 units/mL (U-100)
10 mL
For subcutaneous use only
Rx Only
novo nordisk®
NDC 0169-3439-10
List 643910
Levemir® FlexPen®
Insulin detemir (rDNA origin) injection
100 units/mL (U-100)
5x3 mL Prefilled Pens
For subcutaneous use only
Rx Only
Single Patient use only
For use with NovoFine® disposable needles.
Keep in a cold place.
Store at 2° - 8°C (36° - 46°F).
Avoid freezing.
Protect from light.
novo nordisk®
LEVEMIR
insulin detemir injection, solution |
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Marketing Information | |||
Marketing Category | Application Number or Monograph Citation | Marketing Start Date | Marketing End Date |
NDA | NDA021536 | 03/27/2006 |
LEVEMIR
insulin detemir injection, solution |
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Marketing Information | |||
Marketing Category | Application Number or Monograph Citation | Marketing Start Date | Marketing End Date |
NDA | NDA021536 | 03/27/2006 |
Labeler - Novo Nordisk (622920320) |
Establishment | |||
Name | Address | ID/FEI | Operations |
Novo Nordisk A/S | 312296002 | MANUFACTURE, MANUFACTURE |
Revised: 01/2012 Novo Nordisk