LEVEMIR INNOLET
Clinical safety rating: caution
Comprehensive 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. |
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 |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for LEVEMIR INNOLET (LEVEMIR INNOLET).
| Breastfeeding | Insulin detemir is excreted in human milk in low amounts, unlikely to affect the infant. M/P ratio not reported. It is a peptide that is degraded in infant GI tract. Use during breastfeeding is considered compatible with caution to monitor infant blood glucose if maternal dose is high. |
| 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. |
■ FDA Black Box Warning
None
| Serious Effects |
["Hypoglycemia episodes","Hypersensitivity to insulin detemir or excipients","Not recommended for diabetic ketoacidosis (use short-acting insulin)"]
| 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)"] |
Loading safety data…
| 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. |
| 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. |