LEVEMIR PENFILL
Clinical safety rating: caution
Comprehensive 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. |
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 | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for LEVEMIR PENFILL (LEVEMIR PENFILL).
| Breastfeeding | Insulin detemir is a large protein molecule and is not expected to transfer into breast milk in clinically relevant amounts. M/P ratio not established; endogenous insulin is present in breast milk. Considered compatible with breastfeeding; monitor infant for hypoglycemia if large doses are used. |
| 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. |
■ 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 excipients","During episodes of hypoglycemia"]
| 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"] |
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| 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. |