LEVEMIR PENFILL
Clinical safety rating
cautionComprehensive clinical and safety monograph for LEVEMIR PENFILL (LEVEMIR PENFILL).
Insulin detemir is a long-acting insulin analog that binds to insulin receptors, activating downstream signaling pathways to promote glucose uptake in peripheral tissues (muscle, adipose) and inhibit hepatic glucose production. The addition of a fatty acid chain (myristic acid) to the lysine at position B29 allows reversible binding to albumin, prolonging its duration of action.
| Metabolism | Degraded by general protein catabolism. No specific CYP450 metabolism; cleared via receptor-mediated endocytosis and subsequent intracellular degradation into inactive metabolites. |
| Excretion | Renal: negligible; metabolized by proteolytic degradation, primarily in the liver and kidneys; <1% excreted unchanged in urine. Fecal: minor. |
| Half-life | Terminal half-life: approximately 13-14 hours (range 12-18 hours) after subcutaneous administration in patients with type 1 diabetes, reflecting prolonged absorption from the injection site. The long half-life supports once-daily dosing. |
| Protein binding | >98% bound to albumin; binding is reversible and concentration-dependent. |
| Volume of Distribution | Approximately 0.1 L/kg (range 0.05-0.2 L/kg), indicating distribution primarily into extracellular fluid; Vd is relatively small due to albumin binding. |
| Bioavailability | Subcutaneous: approximately 60-80% after injection; bioavailability is nearly complete compared to other insulin analogs, but may be slightly lower due to local degradation. |
| Onset of Action | Subcutaneous: approximately 3-4 hours; peak effect at 8-10 hours; gradual onset due to formation of soluble dihexamers at injection site. |
| Duration of Action | Subcutaneous: up to 24 hours (range 16-24 hours) with once-daily dosing; duration is dose-dependent and may vary with injection site, patient, and dose; provides a flat, steady basal insulin effect. |
| Molecular Weight | 5916.9 |
Subcutaneous injection, starting dose 0.2–0.3 units/kg once daily, titrated to target glucose. Type 1 diabetes: typically 0.3–0.5 units/kg/day. Type 2 diabetes: 10 units once daily, adjusted based on blood glucose.
| Dosage form | INJECTABLE |
| Renal impairment | GFR <30 mL/min: reduce dose by 25–50% due to reduced insulin clearance; monitor glucose closely. GFR 30-60 mL/min: no formal adjustment but cautious titration. Not studied in dialysis. |
| Liver impairment | Child-Pugh Class B or C: reduce dose by 25–50% due to decreased gluconeogenesis; monitor for hypoglycemia. No specific data for Class A. |
| Pediatric use | Weight-based: 0.2–0.5 units/kg/day subcutaneously, typically once daily. Titrate by 2–4 units based on fasting glucose. Not approved for children <6 years. |
| Geriatric use | Initiate at lower doses (e.g., 5–10 units once daily) due to renal impairment, polypharmacy, and increased hypoglycemia risk. Titrate slowly, monitor glucose frequently. |
| 1st trimester | Insulin detemir does not cross the placenta in significant amounts. However, human data on use in the first trimester are limited. Tight glucose control is recommended; benefits of use generally outweigh risks. |
| 2nd trimester | Insulin detemir has minimal placental transfer. Second trimester use is considered acceptable when insulin therapy is indicated, with careful glucose monitoring. |
| 3rd trimester | Insulin detemir does not cross the placenta to a significant degree. Third trimester use is acceptable, but insulin requirements often increase due to insulin resistance; dose adjustments may be necessary. |
Clinical note
Comprehensive clinical and safety monograph for LEVEMIR PENFILL (LEVEMIR PENFILL).
| Placental transfer | Insulin detemir has minimal placental transfer due to its high molecular weight and albumin binding. Studies show fetal concentrations are much lower than maternal concentrations. |
| Breastfeeding | Insulin detemir is a large protein molecule that is unlikely to pass into breast milk in significant amounts. Even if ingested, it would be broken down in the infant's gastrointestinal tract. No adverse effects on the nursing infant have been reported. However, caution is advised and glucose monitoring of the infant may be considered. |
| Lactation Rating | L2 |
| Teratogenic Risk | Insulin detemir (Levemir Penfill) does not cross the placenta in significant amounts. No increased risk of major congenital anomalies has been observed in humans. Poorly controlled diabetes increases risk for fetal malformations and neonatal complications. Strict glycemic control is recommended before conception and throughout pregnancy. |
| Fetal Monitoring | Monitor blood glucose levels frequently (pre-meal and postprandial). HbA1c every 1-2 months. Fetal ultrasound for growth and anatomy. Non-stress testing and biophysical profile in third trimester. Monitor for maternal hypoglycemia and diabetic ketoacidosis. |
| Fertility Effects | No direct adverse effects on fertility. Optimal glycemic control improves fertility outcomes in diabetic women. Insulin detemir does not impair reproductive function in animal studies. |
■ FDA Black Box Warning
Not indicated for treatment of diabetic ketoacidosis; do not use during episodes of hypoglycemia. Accidental mix-ups with other insulins (e.g., insulin degludec, insulin glargine) have caused severe hypoglycemia.
| Serious Effects |
Hypersensitivity to insulin detemir or any excipientsHypoglycemia
| Precautions | Hypoglycemia (most common adverse reaction; may be severe and life-threatening), Do not dilute or mix with other insulins in the same syringe, Thiazolidinediones (TZDs) coadministration may increase risk of fluid retention and heart failure, Renal or hepatic impairment may increase hypoglycemic risk; dose adjustment may be needed, Not recommended for insulin pump use |
| Food/Dietary | No specific food interactions. However, timing of meals should be consistent with insulin action. Carbohydrate intake must be balanced with insulin dose to prevent hyperglycemia or hypoglycemia. Alcohol may potentiate hypoglycemic effect; limit intake and monitor glucose. |
| Clinical Pearls | Insulin detemir (LEVEMIR PENFILL) is a long-acting basal insulin analogue with a duration of action up to 24 hours, but may require twice-daily dosing in some patients. It has a unique mechanism of albumin binding, resulting in less variable absorption and a flatter pharmacokinetic profile compared to NPH insulin. Do not mix with other insulins in the same syringe. Onset is gradual (3-4 hours), peakless, and duration dose-dependent. Use cautiously in renal or hepatic impairment; dose adjustments may be needed. |
| Patient Advice | Inject subcutaneously once or twice daily at the same time each day. · Rotate injection sites (abdomen, thigh, upper arm) to prevent lipodystrophy. · Do not mix with other insulins in the same syringe. · Monitor blood glucose regularly, especially when starting, changing dose, or during illness. · Store unopened pens in refrigerator (2-8°C); opened pens can be kept at room temperature (below 30°C) for up to 28 days. · Avoid alcohol consumption which can increase risk of hypoglycemia. · Recognize symptoms of hypoglycemia (sweating, dizziness, confusion) and hyperglycemia (thirst, frequent urination, blurred vision). · Do not share pens with others, even if needle changed. |
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