Levemir insulin detemir 100 [iU]/mL Injection, Solution
🆔 Identity & classification
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🏷️ RxNorm drug class
This medicine belongs to the Insulin Analog class.
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🏭 Manufacturer & labeler
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🩺 Clinical
- Levemir is a long-acting 'basal' insulin — it works slowly and steadily in the background for up to 24 hours to keep your blood sugar from running too high between meals and overni...
- What exactly is Levemir, and why did my doctor prescribe it instead of a regular insulin?
- You inject Levemir just under the skin (subcutaneously) in your thigh, upper arm, or abdomen — not into a vein and not through an insulin pump. The most important habit is to rotat...
- Low blood sugar (hypoglycemia) is the most common and important risk with any insulin, including Levemir. Early signs include shakiness, sweating, rapid heartbeat, dizziness, and c...
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🧪 Inactive Ingredients / Excipients
Inactive ingredients, also called excipients, are components of the drug product other than the active ingredient. They may include fillers, dyes, coatings, preservatives, flavors, or other formulation ingredients.
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💲 Pricing
A drug doesn't have one price. Each row is a different public payment system, and none is what you'd pay at the counter — that depends on your insurance. The ⓘ on each row explains what it measures.
| Price system | Per mL | Per package |
|---|---|---|
| Retail pharmacies payNADAC · weekly | $10.361 | $103.61 / 10 ml |
| Medicaid paysCMS SDUD · 12 mo | $10.97 | $109.70 / 10 ml |
| Medicare drug plans payPart D · quarterly | No Part D plan price is available for this NDC in our data. | |
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🔁 Therapeutic equivalents
| Product | Labeler | Pack | NADAC/unit | TE | Status | Price vs. this |
|---|---|---|---|---|---|---|
| Levemir 100 [iU]/mL 00169-6432-10 | Novo | 5 syringes | $10.356 | — | Discontinued | +0% |
| Levemir 100 [iU]/mLthis 00169-3687-12 | Novo | 1 vial | $10.361 | — | Discontinued | — |
| Levemir 100 [iU]/mL 50090-1276-00 | A-S | 1 vial | — | — | FDA listed | — |
| Levemir 100 [iU]/mL 50090-6391-00 | A-S | 5 syringes | — | — | Discontinued | — |
| Levemir 100 [iU]/mL 50090-6414-00 | A-S | 5 syringes | — | — | Discontinued | — |
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⏳ Availability & biosimilar status
Biologics have no small-molecule generics; biosimilar competition is tracked in the FDA Purple Book.
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🗺️ Medicaid utilization & spend
📊 Medicare Part D spend CMS · PART D · 2026 (Q1)
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📦 Packaging — all sizes for this product
| Package NDC | Description | Marketing start | Status |
|---|---|---|---|
| 00169-3687-12 You're viewing this | 1 VIAL, GLASS in 1 CARTON (0169-3687-12) / 10 mL in 1 VIAL, GLASS | 2006-03-27 | Discontinued by firm |
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| NDC identity (package / product / labeler codes) | ✓ Available |
| Labeler | ✓ Available |
| Product & package description | ✓ Available |
| Marketing category & status | ✓ Available |
| Active ingredient / dosage form / route | ✓ Available |
| FDA label (SPL via DailyMed) | ✓ Available |
| Package photos | — Not published for this NDC No photo available yet for this listing. |
| Inactive ingredients (structured) | — Not published for this NDC The labeler did not submit a structured excipient list, or no SPL is available. |
| NADAC pharmacy acquisition price (CMS) | ✓ Available |
| Orange Book / therapeutic-equivalence data | — Not published for this NDC Applies only to products approved under an NDA/ANDA; many listings are out of scope. |
| HCPCS J-code billing crosswalk | — Not published for this NDC Most self-administered / retail products have no J-code — that is normal. |
| Medicaid utilization (CMS SDUD) | ✓ Available |
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📄 Full prescribing information FDA SPL
🎯 Indications and Usage ▾
1 INDICATIONS AND USAGE LEVEMIR is indicated to improve glycemic control in adult and pediatric patients with diabetes mellitus. Limitations of Use LEVEMIR is not recommended for the treatment of diabetic ketoacidosis. LEVEMIR is a long-acting human insulin analog indicated to improve glycemic control in adult and pediatric patients with diabetes mellitus ( 1 ). Limitations of Use: Not recommended for the treatment of diabetic ketoacidosis.
⏱️ Dosage and Administration ▾
2 DOSAGE AND ADMINISTRATION • See Full Prescribing Information for important administration instructions ( 2.1 ). • Inject subcutaneously into the thigh, upper arm, or abdomen ( 2.1 ). • Rotate injection sites to reduce risk of lipodystrophy and localized cutaneous amyloidosis ( 2.1 ). • Individualize and titrate the dose of LEVEMIR based on the patient’s metabolic needs, blood glucose monitoring results, and glycemic control goal ( 2.2 ). • Administer subcutaneously once daily or in divided doses twice daily ( 2.2 ). • See Full Prescribing Information for recommended starting dose in insulin naïve patients and patients already on insulin therapy ( 2.3 , 2.4 ).
2.1Important Administration Instructions • Always check insulin labels before administration [see Warnings and Precautions ( 5.4 )]. • Visually inspect for particulate matter and discoloration. Only use LEVEMIR if the solution appears clear and colorless. • Inject LEVEMIR subcutaneously into the thigh, upper arm, or abdomen. • 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 ( 5.2 ), Adverse Reactions ( 6 )] . • During changes to a patient’s insulin regimen, increase the frequency of blood glucose monitoring [see Warnings and Precautions ( 5.2 )]. • Do not dilute or mix LEVEMIR with any other insulin or solution. • Do not administer LEVEMIR intravenously or in an insulin infusion pump. • LEVEMIR FlexPen dials in 1-unit increments. • Use the LEVEMIR FlexPen with caution in patients with visual impairment who may rely on audible clicks to dial their dose.
2.2General Dosing Instructions • LEVEMIR can be administered by subcutaneous injection once or twice daily. Administer once daily doses with the evening meal or at bedtime. For twice daily dosing, administer the evening dose with the evening meal, at bedtime, or 12 hours after the morning dose. • Individualize and titrate the dose of LEVEMIR based on the patient’s metabolic needs, blood glucose monitoring results, and glycemic control goal. • Dose 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 to minimize the risk of hypoglycemia or hyperglycemia [see Warnings and Precautions ( 5.3 )]. • In patients with type 1 diabetes, LEVEMIR must be used in a regimen with rapid-acting or short-acting insulin.
2.3Starting Dose in Insulin Naïve Patients Recommended Starting Dosage in Patients with Type 1 Diabetes The recommended starting dose of LEVEMIR in patients with type 1 diabetes mellitus is approximately one-third to one-half of the total daily insulin dose. The remainder of the total daily insulin dose should be administered as short-acting pre-meal insulin. As a general rule, 0.2 to 0.4 units of insulin per kilogram of body weight can be used to calculate the initial total daily insulin dose in insulin naïve patients with type 1 diabetes.
Recommended Starting Dosage in Patients with Type 2 Diabetes The recommended starting dose of LEVEMIR in patients with type 2 diabetes mellitus inadequately controlled on oral antidiabetic medications or a GLP-1 receptor agonist is 10 units (or 0.1 units/kg to 0.2 units/kg) given once daily in the evening or divided into a twice daily regimen.
2.4Switching to LEVEMIR from Other Insulin Therapies Dosage adjustments are recommended to lower the risk of hypoglycemia when switching patients to LEVEMIR from another insulin therapy [see Warnings and Precautions ( 5.3 )]. • 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 mellitus may require more LEVEMIR than NPH insu…
💊 Dosage Forms and Strengths ▾
3 DOSAGE FORMS AND STRENGTHS Injection: 100 units/mL (U-100), is a clear, colorless, solution available as: • 3 mL single-patient-use FlexPen prefilled pen • 10 mL multiple-dose vial Injection: 100 units/mL (U-100) of insulin detemir available as: • 3 mL single-patient-use FlexPen ® prefilled pen ( 3 ) • 10 mL multiple-dose vial ( 3 )
⛔ Contraindications ▾
4 CONTRAINDICATIONS LEVEMIR is contraindicated: • During episodes of hypoglycemia [see Warnings and Precautions (5.3)] • In patients with hypersensitivity to insulin detemir or any of the excipients in LEVEMIR. Reactions have included anaphylaxis [ see Warnings and Precautions (5.5) and Adverse Reactions (6.1) ] . • During episodes of hypoglycemia ( 4 ) • Hypersensitivity to insulin detemir or any of the excipients in LEVEMIR ( 4 )
⚠️ Warnings and Cautions ▾
5 WARNINGS AND PRECAUTIONS • Never Share a LEVEMIR FlexPen, insulin syringe, or needle between patients, even if the needle is changed ( 5.1 ). • Hyperglycemia or hypoglycemia with changes in insulin regimen: Make changes to a patient’s insulin regimen (e.g., insulin strength, manufacturer, type, injection site or method of administration) under close medical supervision with increased frequency of blood glucose monitoring ( 5.2 ). • Hypoglycemia: May be life-threatening. Increase frequency of glucose monitoring with changes to: insulin dosage, concomitant drugs, meal pattern, physical activity; and in patients with renal impairment or hepatic impairment or hypoglycemia unawareness ( 5.3 ). • Hypoglycemia due to medication errors: Accidental mix-ups between insulin products can occur.
Instruct patients to check insulin labels before injection ( 5.4 ). • Hypersensitivity reactions: Severe, life-threatening, generalized allergy, including anaphylaxis, can occur. Discontinue LEVEMIR, monitor and treat if indicated ( 5.5 ). • Hypokalemia: May be life-threatening. Monitor potassium levels in patients at risk for hypokalemia and treat if indicated ( 5.6 ). • Fluid retention and heart failure with concomitant use of thiazolidinediones (TZDs): Observe for signs and symptoms of heart failure; consider dosage reduction or discontinuation if heart failure occurs ( 5.7 ).
5.1Never Share a LEVEMIR FlexPen, Needle, or Insulin Syringe between Patients LEVEMIR FlexPen prefilled pens must never be shared between patients, even if the needle is changed. Patients using LEVEMIR vials should never share needles or syringes with another person. Sharing poses a risk for transmission of blood-borne pathogens.
5.2Hyperglycemia 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 ( 5.4 )] 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 )].
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 antidiabetic products may be needed [see Dosage and Administration ( 2.4 )].
5.3Hypoglycemia Hypoglycemia is the most common adverse reaction of insulin, including LEVEMIR [see Adverse Reactions ( 6.1 )]. Severe hypoglycemia can cause seizures, may be life-threatening or cause death. Hypoglycemia can impair concentration ability and reaction time; this may place the patient and others at risk in situations where these abilities are important (e.g., driving or operating other machinery).
LEVEMIR, or any insulin, should not be used during episodes of hypoglycemia [see Contraindications ( 4 )]. Hypoglycemia can happen suddenly and symptoms may differ in each patient and change over time in the same patient. Symptomatic awareness of hypoglycemia may be less pronounced in patients with longstanding diabetes, in patients with diabetic neuropathy, using drugs that block the sympathetic nervous system (e.g., beta-blockers) [see Drug Interactions ( 7 )], or who experience recurrent hypoglycemia.
Risk Factors for Hypoglycemia The risk of hypoglycemia generally increases with intensity of glycemic control. The risk of hypoglycemia after an injection is related to the duration of action of the insulin [see Clinical Pharmacology ( 12.2 )] and, in general, is highest when the glucose lowering effec…
🤒 Adverse Reactions ▾
6 ADVERSE REACTIONS The following adverse reactions are discussed elsewhere: • Hypoglycemia [see Warnings and Precautions ( 5.3 )] • Hypoglycemia Due to Medication errors [see Warnings and Precautions ( 5.4 )] • Hypersensitivity Reactions [see Warnings and Precautions ( 5.5 )] • Hypokalemia [see Warnings and Precautions ( 5.6 )] Adverse reactions associated with LEVEMIR include hypoglycemia, allergic reactions, injection site reactions, lipodystrophy, rash and pruritus ( 6 ). To report SUSPECTED ADVERSE REACTIONS, contact Novo Nordisk Inc. at 1-800-727-6500 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch
6.1Clinical Trial Experience 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.
In two pooled trials, adults with type 1 diabetes were exposed to individualized doses of LEVEMIR (n=767) or NPH (n=388). The mean duration of exposure to LEVEMIR was 153 days, and the total exposure to LEVEMIR was 321 patient-years. The most common adverse reactions are summarized in Table 1.
Table 1: Adverse Reactions Occurring in ≥ 5% of LEVEMIR-Treated Adult Patients with Type 1 Diabetes Mellitus in Two Trials of 16 Weeks and 24 Weeks Duration LEVEMIR, % (n = 767) Upper respiratory tract infection
26.1 Headache
22.6 Pharyngitis
9.5 Influenza-like illness
7.8 Abdominal Pain
6.0Adults with type 1 diabetes were exposed to LEVEMIR (n=161) or insulin glargine (n=159). The mean duration of exposure to LEVEMIR was 176 days, and the total exposure to LEVEMIR was 78 patient-years. The most common adverse reactions are summarized in Table 2. Table 2: Adverse Reactions Occurring in ≥ 5% of LEVEMIR-Treated Adult Patients with Type 1 Diabetes Mellitus in a 26-week Trial LEVEMIR, % (n = 161) Upper respiratory tract infection
26.7 Headache
14.3 Back pain
8.1 Influenza-like illness
6.2 Gastroenteritis
5.6 Bronchitis
5.0In two pooled trials, adults with type 2 diabetes were exposed to LEVEMIR (n=432) or NPH (n=437). The mean duration of exposure to LEVEMIR was 157 days, and the total exposure to LEVEMIR was 186 patient-years. The most common adverse reactions were comparable to that observed in adult patients with type 1 diabetes mellitus; see Table 1.
Pediatric patients with type 1 diabetes were exposed to individualized doses of LEVEMIR (n=232) or NPH (n=115). The mean duration of exposure to LEVEMIR was 180 days, and the total exposure to LEVEMIR was 114 patient-years. The most common adverse reactions are summarized in Table 3.
Table 3: Adverse Reactions Occurring in ≥ 5% of LEVEMIR-Treated Pediatric Patients with Type 1 Diabetes Mellitus in a 26-week Trial LEVEMIR, % (n = 232) Upper respiratory tract infection
35.8 Headache
31.0 Pharyngitis
17.2 Gastroenteritis
16.8 Influenza-like illness
13.8 Abdominal pain
13.4 Pyrexia
10.3 Cough
8.2 Viral infection
7.3 Nausea
6.5 Rhinitis
6.5 Vomiting
6.5Hypoglycemia Hypoglycemia was the most commonly observed adverse reaction in patients treated with LEVEMIR. The rates of reported hypoglycemia depend on the definition of hypoglycemia used, diabetes type, insulin dose, intensity of glucose control, background therapies, and other intrinsic and extrinsic patient factors. For these reasons, comparing rates of hypoglycemia in clinical trials for LEVEMIR with the incidence of hypoglycemia for other products may be misleading and also, may not be representative of hypoglycemia rates that will occur in clinical practice.
Table 4 (type 1 diabetes) and Table 5 (type 2 diabetes) summarize the incidence of severe and non-severe hypoglycemia in the LEVEMIR…
🔄 Drug Interactions ▾
7 DRUG INTERACTIONS Table 6 includes clinically significant drug interactions with LEVEMIR. Table 6: Clinically Significant Drug Interactions with LEVEMIR Drugs That May Increase the Risk of Hypoglycemia Drugs: Antidiabetic agents, ACE inhibitors, angiotensin II receptor blocking agents, disopyramide, fibrates, fluoxetine, monoamine oxidase inhibitors, pentoxifylline, pramlintide, salicylates, somatostatin analogs (e.g., octreotide), and sulfonamide antibiotics, GLP-1 receptor agonists, DPP-4 inhibitors, SGLT-2 inhibitors.
Intervention: Dosage reductions and increased frequency of glucose monitoring may be required when LEVEMIR is co-administered with these drugs. Drugs That May Decrease the Blood Glucose Lowering Effect of LEVEMIR Drugs: Atypical antipsychotics (e.g., olanzapine and clozapine), corticosteroids, danazol, diuretics, estrogens, glucagon, isoniazid, niacin, oral contraceptives, phenothiazines, progestogens (e.g., in oral contraceptives), protease inhibitors, somatropin, sympathomimetic agents (e.g., albuterol, epinephrine, terbutaline), and thyroid hormones.
Intervention: Dosage increases and increased frequency of glucose monitoring may be required when LEVEMIR is co-administered with these drugs. Drugs That May Increase or Decrease the Blood Glucose Lowering Effect of LEVEMIR Drugs: Alcohol, beta-blockers, clonidine, and lithium salts. Pentamidine may cause hypoglycemia, which may sometimes be followed by hyperglycemia.
Intervention: Dosage adjustment and increased frequency of glucose monitoring may be required when LEVEMIR is co-administered with these drugs. Drugs That May Blunt Signs and Symptoms of Hypoglycemia Drugs: Beta-blockers, clonidine, guanethidine, and reserpine Intervention: Increased frequency of glucose monitoring may be required when LEVEMIR is co-administered with these drugs. • Drugs that Affect Glucose Metabolism: Adjustment of insulin dosage may be needed. ( 7 ) • Antiadrenergic Drugs (e.g., beta-blockers, clonidine, guanethidine, and reserpine): Signs and symptoms of hypoglycemia may be reduced or absent.
( 5.3 , 7 )
👥 Use in Specific Populations ▾
8 USE IN SPECIFIC POPULATIONS
8.1Pregnancy Risk Summary Available data from published studies and postmarketing case reports with LEVEMIR use in pregnant women have not identified a drug-associated risk of major birth defects, miscarriage, or adverse maternal or fetal outcomes. In a randomized, parallel-group, open-label clinical trial that included 152 pregnant women with type 1 diabetes who were administered LEVEMIR once or twice daily, beginning in gestational weeks 8 to 12 or prior to conception, no clear evidence of maternal or fetal risk associated with LEVEMIR was observed (see Data).
There are risks to the mother and fetus associated with poorly controlled diabetes in pregnancy (see Clinical Considerations). Animal reproduction studies were conducted in non-diabetic pregnant rats and rabbits with insulin detemir administration at 3 and 135 times the human dose of 0.5 units/kg/day, respectively, throughout pregnancy. Overall, the effects of insulin detemir did not generally differ from those observed with 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 peri-conceptional HbA 1c >7 and has been reported to be as high as 20 to 25% in women with a peri-conceptional HbA 1c >10. The estimated background risk of miscarriage for the indicated population is unknown.
Clinical Considerations Disease-Associated Maternal and/or Embryo/Fetal Risk Hypoglycemia and hyperglycemia occur more frequently during pregnancy in patients with pre-gestational diabetes. 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 In an open-label clinical trial, pregnant females with type 1 diabetes (n=310) were treated with LEVEMIR (once or twice daily) or NPH insulin (once, twice, or thrice daily); both groups also received preprandial insulin aspart. Approximately half of the study participants in each arm were randomized as pregnant and were exposed to NPH or to other insulins prior to conception and in the first 8 weeks of gestation. The rates of preeclampsia observed in the study were within expected rates for pregnancy complicated by diabetes.
No differences in pregnancy outcomes or the health of the fetus and newborn were seen between the two groups. In this study, the proportion of subjects with severe hypoglycemia and non-severe hypoglycemia was similar between the two treatment arms; for the definitions of severe hypoglycemia and non-severe hypoglycemia [see Adverse Reactions ( 6.1 )]. In about a quarter of infants, LEVEMIR was detected in the infant cord blood at levels above the lower level of quantification (<25 pmol/L).
Animal Data 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 and 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 embryo-fetal development studies that included concurrent human insulin control groups indicated that insulin detemir and human insulin had similar effects regarding e…
🤰 Pregnancy ▾
8.1Pregnancy Risk Summary Available data from published studies and postmarketing case reports with LEVEMIR use in pregnant women have not identified a drug-associated risk of major birth defects, miscarriage, or adverse maternal or fetal outcomes. In a randomized, parallel-group, open-label clinical trial that included 152 pregnant women with type 1 diabetes who were administered LEVEMIR once or twice daily, beginning in gestational weeks 8 to 12 or prior to conception, no clear evidence of maternal or fetal risk associated with LEVEMIR was observed (see Data).
There are risks to the mother and fetus associated with poorly controlled diabetes in pregnancy (see Clinical Considerations). Animal reproduction studies were conducted in non-diabetic pregnant rats and rabbits with insulin detemir administration at 3 and 135 times the human dose of 0.5 units/kg/day, respectively, throughout pregnancy. Overall, the effects of insulin detemir did not generally differ from those observed with 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 peri-conceptional HbA 1c >7 and has been reported to be as high as 20 to 25% in women with a peri-conceptional HbA 1c >10. The estimated background risk of miscarriage for the indicated population is unknown.
Clinical Considerations Disease-Associated Maternal and/or Embryo/Fetal Risk Hypoglycemia and hyperglycemia occur more frequently during pregnancy in patients with pre-gestational diabetes. 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 In an open-label clinical trial, pregnant females with type 1 diabetes (n=310) were treated with LEVEMIR (once or twice daily) or NPH insulin (once, twice, or thrice daily); both groups also received preprandial insulin aspart. Approximately half of the study participants in each arm were randomized as pregnant and were exposed to NPH or to other insulins prior to conception and in the first 8 weeks of gestation. The rates of preeclampsia observed in the study were within expected rates for pregnancy complicated by diabetes.
No differences in pregnancy outcomes or the health of the fetus and newborn were seen between the two groups. In this study, the proportion of subjects with severe hypoglycemia and non-severe hypoglycemia was similar between the two treatment arms; for the definitions of severe hypoglycemia and non-severe hypoglycemia [see Adverse Reactions ( 6.1 )]. In about a quarter of infants, LEVEMIR was detected in the infant cord blood at levels above the lower level of quantification (<25 pmol/L).
Animal Data 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 and 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 embryo-fetal development studies that included concurrent human insulin control groups indicated that insulin detemir and human insulin had similar effects regarding embryotoxicity and teratogenici…
🧒 Pediatric Use ▾
8.4Pediatric Use The safety and effectiveness of LEVEMIR to improve glycemic control in pediatric patients with diabetes mellitus have been established. The use of LEVEMIR for this indication is supported by evidence from adequate and well-controlled trials (Studies D and I) in 694 pediatric patients aged 2 to 17 years with type 1 diabetes mellitus [see Clinical Studies ( 14.2 )] and from other studies in pediatric patients and adults with diabetes mellitus [see Clinical Pharmacology ( 12.3 ), Clinical Studies ( 14.3 )].
🧓 Geriatric Use ▾
8.5Geriatric Use In clinical trials of LEVEMIR, 64 of 1624 patients (4%) in the type 1 diabetes trials and 309 of 1082 patients (29%) in the type 2 diabetes trials were 65 years or older. A total of 52 (7 type 1 and 45 type 2) patients (2%) were 75 years or older. No overall differences in safety or effectiveness were observed between these patients and younger patients, but small sample sizes limits conclusions.
Greater sensitivity of some older individuals cannot be ruled out. In geriatric patients, the initial dosing, dosage increments, and maintenance dosage should be conservative to avoid hypoglycemia. Hypoglycemia may be difficult to recognize in the geriatric patients.
🆘 Overdosage ▾
10 OVERDOSAGE An excess of insulin relative to food intake, energy expenditure, or both may lead to severe and sometimes prolonged and life-threatening hypoglycemia and hypokalemia [see Warnings and Precautions ( 5.3 , 5.6 )] . Mild episodes of hypoglycemia usually can be treated with oral glucose. Lowering the insulin dosage, and adjustments in meal patterns, or exercise may be needed.
More severe episodes with coma, seizure, or neurologic impairment may be treated with a glucagon product for emergency use or concentrated intravenous glucose. After apparent clinical recovery from hypoglycemia, continued observation and additional carbohydrate intake may be necessary to avoid recurrence of hypoglycemia. Hypokalemia must be corrected appropriately.
🧬 Clinical Pharmacology ▾
12 CLINICAL PHARMACOLOGY
12.1Mechanism of Action The primary activity of insulin, including LEVEMIR, is regulation of glucose metabolism. Insulins and its analogs lower blood glucose by stimulating peripheral glucose uptake, especially by skeletal muscle and fat, and by inhibiting hepatic glucose production. Insulin also inhibits lipolysis and proteolysis, and enhances protein synthesis.
12.2Pharmacodynamics 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. 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: Glucose Lowering Effect 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: Glucose Lowering Effect in Patients with Type 2 Diabetes in a 16-hour Glucose Clamp Study Figure 2: Graph of glucose lowering effect in patients with type 1 diabetes Figure 3: graph of glucose lowering effect in patients with type 2 diabetes
12.3Pharmacokinetics Absorption 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 AUC 0-5h was 30-40% lower and AUC 0-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 Insulin detemir has an apparent volume of distribution of approximately
0.1L/kg. 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.
Elimination 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 Pediatric Patients The pharmacokinetic properties of LEVEMIR were studied in pediatric patients 6-12 years, 13-17 years, and adults with type 1 diabetes. In pediatric patients 6-12 years, the insulin detemir plasma area under the curve (AUC) and C max were increased by 10% and 24%, respectively, as compared to adults.
There was no difference in pharmacokinetics between pediatric patients 13-17 years and adults. Geriatrics In a clinical trial studying 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 [see Use in Specific Populations (8.5)] . Gender No clinically relevant differences in pharmacokinetic parameters of LEVEMIR are observed between males and females.
Race In two clinical pharmacology s…
🧬 Mechanism of Action ▾
12.1Mechanism of Action The primary activity of insulin, including LEVEMIR, is regulation of glucose metabolism. Insulins and its analogs lower blood glucose by stimulating peripheral glucose uptake, especially by skeletal muscle and fat, and by inhibiting hepatic glucose production. Insulin also inhibits lipolysis and proteolysis, and enhances protein synthesis.
📦 How Supplied / Storage and Handling ▾
16 HOW SUPPLIED/STORAGE AND HANDLING
16.1How Supplied LEVEMIR (insulin detemir) injection 100 units/mL (U-100) is a clear and colorless solution available in the following presentations: Presentation NDC 3 mL Single-patient-use FlexPen pen 0169-6432-10 10 mL Multiple-dose vial 0169-3687-12 Additional Information about LEVEMIR FlexPen: • The pen dials in 1-unit increments. • Use NovoFine ® or NovoFine Plus ® disposable needles. • Each pen for use by a single patient. LEVEMIR FlexPen must never be shared between patients, even if the needle is changed.
16.2Storage Dispense in the original sealed carton with the enclosed Instructions for Use. Store unused (unopened) LEVEMIR in the refrigerator between 36° to 46°F (2° and 8°C). 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. Keep unused LEVEMIR in the carton so that it stays clean and protected from light.
Remove the needle from the LEVEMIR FlexPen pen after each injection and store without a needle attached. Use a new needle for each injection. The storage conditions for vials and LEVEMIR FlexPen prefilled pens are summarized in Table 11: Table 11: Storage Conditions for LEVEMIR FlexPen and Vial LEVEMIR Presentation Not in-use (unopened) In-use (opened) Refrigerated (36°F to 46°F [2°C and 8°C]) Room Temperature (up to 86°F [30°C]) Refrigerated (36°F to 46°F [2°C and 8°C]) Room Temperature (up to 86°F [30°C]) 3 mL single-patient-use LEVEMIR FlexPen Until expiration date 42 days Do not refrigerate 42 days 10 mL multiple-dose vial Until expiration date 42 days 42 days 42 days
📋 Description ▾
11 DESCRIPTION Insulin detemir is a long-acting recombinant human insulin analog 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 C 267 H 402 O 76 N 64 S 6 and a molecular weight of 5.917 kDa.
It has the following structure: Figure 1: Structural Formula of Insulin Detemir LEVEMIR (insulin detemir) injection is a clear, colorless, aqueous, neutral sterile solution for subcutaneous use. Each milliliter of LEVEMIR contains 100 units insulin detemir, dibasic sodium phosphate (0.71 mg), glycerin (16 mg), metacresol (2.06 mg), phenol (1.8 mg), sodium chloride (1.17 mg), zinc (65.4 mcg), and Water for Injection, USP. Hydrochloric acid and/or sodium hydroxide may be added to adjust pH.
LEVEMIR has a pH of approximately 7.4. Levemir Chemical Structure.jpg
💬 Information for Patients ▾
17 PATIENT COUNSELING INFORMATION See FDA-Approved Patient Labeling (Patient Information and Instructions for Use). There are separate Instructions for Use for the Vials and LEVEMIR FlexPen Prefilled Pen. Never Share a LEVEMIR FlexPen or Insulin Syringe Between Patients Advise patients that they must never share a LEVEMIR FlexPen with another person, even if the needle is changed.
Advise patients using LEVEMIR vials not to share needles or insulin syringes with another person. Sharing poses a risk for transmission of blood-borne pathogens [see Warnings and Precautions ( 5.1 )]. Hyperglycemia or Hypoglycemia Inform patients that hypoglycemia is the most common adverse reaction with insulin.
Inform patients of the symptoms of hypoglycemia (e.g., impaired ability to concentrate and react). This may present a risk in situations where these abilities are especially important, such as driving or operating other machinery. Advise patients who have frequent hypoglycemia or reduced or absent warning signs of hypoglycemia to use caution when driving or operating machinery [see Warnings and Precautions ( 5.3 )] .
Advise patients that changes in insulin regimen can predispose to hyperglycemia or hypoglycemia and that changes in insulin regimen should be made under close medical supervision [see Warnings and Precautions ( 5.2 )] . Hypersensitivity Reactions Advise patients that hypersensitivity reactions have occurred with LEVEMIR. Inform patients on the symptoms of hypersensitivity reactions [see Warnings and Precautions ( 5.5 )].
Hypoglycemia Due to Medication Errors Instruct patients to always check the insulin label before each injection to avoid mix-ups between insulin products [see Warnings and Precautions (5.4)] . Novo Nordisk ® , Levemir ® , NovoLog ® , FlexPen ® , and NovoFine ® are registered trademarks of Novo Nordisk A/S. Patent Information: https://www.novonordisk-us.com/products/product-patents.html © 2005-2022 Novo Nordisk Manufactured by: Novo Nordisk Inc.
800 Scudders Mill Road Plainsboro, NJ 08536 U.S. License Number 1261 For information about LEVEMIR contact: Novo Nordisk Inc. 800 Scudders Mill Road Plainsboro, New Jersey 08536 1-800-727-6500 www.novonordisk-us.com