LEVEMIR INNOLET
Clinical safety rating
cautionComprehensive clinical and safety monograph for LEVEMIR INNOLET (LEVEMIR INNOLET).
Insulin detemir is a long-acting recombinant human insulin analog. It binds to insulin receptors, activating tyrosine kinase signaling, which promotes cellular glucose uptake, inhibits hepatic gluconeogenesis, and suppresses lipolysis and proteolysis.
| Metabolism | Insulin detemir is metabolized via non-CYP450 pathways, primarily proteolytic degradation. The main metabolite is inactive. |
| Excretion | Hepatic metabolism (deamidation at B30 and deacetylation at B29) and subsequent renal excretion; ~30% of dose excreted unchanged in urine. |
| Half-life | Terminal elimination half-life is 13–14 hours after subcutaneous administration, providing a flat, protracted pharmacokinetic profile suitable for once-daily dosing. |
| Protein binding | >98% bound to albumin; binding is reversible and saturated at therapeutic concentrations. |
| Volume of Distribution | Volume of distribution is approximately 0.26–0.38 L/kg, reflecting distribution primarily into interstitial fluid. |
| Bioavailability | Subcutaneous: approximately 60–80% absolute bioavailability; not administered by other routes. |
| Onset of Action | Subcutaneous: onset of action occurs approximately 60–120 minutes after injection. |
| Duration of Action | Duration of action is up to 24 hours (range 16–24 hours) depending on dose; time-action profile is flat and peakless, designed for basal insulin coverage. |
| Molecular Weight | 5916.9 |
0.2 units/kg subcutaneously once daily in the evening or twice daily (morning and evening) when used as basal insulin; titrate to target fasting glucose. For insulin-naive patients with type 2 diabetes, start at 10 units once daily in the evening. Dose adjustment of 1-4 units per day based on blood glucose monitoring.
| Dosage form | INJECTABLE |
| Renal impairment | For GFR <30 mL/min: consider dose reduction and more frequent monitoring due to decreased insulin clearance; start with lower doses and titrate cautiously. No specific dose adjustment guidelines for GFR 30-89 mL/min, but monitor closely. |
| Liver impairment | Child-Pugh Class A (mild): no dose adjustment required. Child-Pugh Class B (moderate): start with lower doses and titrate slowly due to impaired gluconeogenesis and reduced insulin clearance. Child-Pugh Class C (severe): use with caution; consider starting at 50% of standard dose and titrate based on response. |
| Pediatric use | For children aged 2 years and older with type 1 diabetes: start at 0.2-0.5 units/kg subcutaneously once daily in the evening. For type 2 diabetes: limited data; based on adult dosing. Adjust dose based on blood glucose targets. Do not mix with other insulins. |
| Geriatric use | In elderly patients (age ≥65 years), start at lower doses (e.g., 0.1 units/kg subcutaneously once daily) due to increased risk of hypoglycemia. Titrate slowly and monitor renal function. Avoid aggressive dose escalation. |
| 1st trimester | Insulin detemir does not cross the placenta extensively due to albumin binding; limited data suggest no increased risk of major malformations. Human insulin is preferred but detemir may be used if glycemic control is inadequate. |
| 2nd trimester | No known increased risk of fetal harm; placental transfer is minimal. Dose adjustments may be necessary due to physiologic changes in pregnancy. |
| 3rd trimester | Insulin requirements often increase; detemir is considered compatible. Monitor closely for glycemic control. |
Clinical note
Comprehensive clinical and safety monograph for LEVEMIR INNOLET (LEVEMIR INNOLET).
| Placental transfer | Minimal placental transfer due to high albumin binding and large molecular weight; less than 0.1% of maternal dose crosses placenta. |
| Breastfeeding | Insulin detemir is a large protein molecule and is not expected to pass into breast milk in clinically significant amounts. Endogenous insulin normally present in milk. Use is considered compatible with breastfeeding. |
| Lactation Rating | L1 (Safest) |
| Teratogenic Risk | Insulin detemir does not cross the placenta in significant amounts. Animal studies show no evidence of teratogenicity. In humans, no increased risk of major malformations in first trimester; risks in second and third trimesters relate to maternal hyperglycemia, not drug. Poor glycemic control increases risk of fetal anomalies, macrosomia, neonatal hypoglycemia. |
| Fetal Monitoring | Monitor maternal blood glucose levels frequently; HbA1c every 1-3 months. Fetal monitoring includes ultrasound for growth, anatomy, and amniotic fluid; nonstress test or biophysical profile in third trimester as indicated. Watch for signs of maternal hypoglycemia, especially in first trimester. |
| Fertility Effects | No direct adverse effects on fertility reported. Uncontrolled diabetes can impair fertility due to ovulatory dysfunction; improved glycemic control with insulin detemir may restore fertility. |
■ FDA Black Box Warning
None
| Serious Effects |
Hypersensitivity to insulin detemir or any excipientsDuring episodes of hypoglycemia
| Precautions | Hypoglycemia: May be life-threatening; dose adjustment needed with renal/hepatic impairment, Medication errors: Do not confuse with other insulins; not for IV or IM use, Hypokalemia: Can cause low potassium, leading to cardiac arrhythmias, Fluid retention and heart failure: When used with thiazolidinediones (TZDs) |
| Food/Dietary | No specific food interactions. Advise consistent carbohydrate intake to match insulin dose. Alcohol may increase hypoglycemia risk; avoid or limit alcohol consumption. |
| Clinical Pearls | Levemir (insulin detemir) is a long-acting basal insulin analog with a duration of action up to 24 hours. It has a lower risk of hypoglycemia compared to NPH insulin due to its flat pharmacokinetic profile. Administer once or twice daily at the same time(s) each day. Do not mix with other insulins in the same syringe. Store unopened vials/penfills in refrigerator; opened pens can be kept at room temperature (<30°C) for up to 42 days. Monitor renal and hepatic function as dose adjustments may be needed. |
| Patient Advice | Inject subcutaneously into abdomen, thigh, or upper arm; rotate injection sites to avoid lipodystrophy. · Do not mix with other insulins; use a separate injection site if combining therapies. · Check blood glucose regularly and record results; know symptoms of hypoglycemia and hyperglycemia. · Do not use if solution appears cloudy or has particles; it should be clear and colorless. · Store unopened pens in refrigerator; opened pens can be kept at room temperature for up to 42 days away from heat or light. · Missed dose: take as soon as remembered unless next dose is due within 6 hours; never double dose. |
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