HUMULIN N
Clinical safety rating: caution
Comprehensive clinical and safety monograph for HUMULIN N (HUMULIN N).
Insulin isophane (NPH) is an intermediate-acting insulin that lowers blood glucose by promoting peripheral glucose uptake, especially in muscle and adipose tissue, and inhibiting hepatic glucose production. It binds to the insulin receptor, activating tyrosine kinase activity and downstream signaling pathways.
| Metabolism | Insulin is metabolized primarily by insulin-degrading enzyme (IDE) and possibly protein disulfide isomerase; degradation occurs in liver, kidney, and muscle. |
| Excretion | Renal: 60-80% as intact insulin; hepatic and renal clearance; negligible biliary/fecal elimination. |
| Half-life | Terminal half-life: 1.5-2.5 hours (subcutaneous); longer in renal impairment. |
| Protein binding | ~5% bound to serum proteins (primarily albumin); low binding reduces buffer effect. |
| Volume of Distribution | 0.05-0.1 L/kg (approx 50-70% of total body water); reflects distribution into extracellular fluid. |
| Bioavailability | Subcutaneous: 50-80% (inverse of insulin-degrading enzyme activity). |
| Onset of Action | Subcutaneous: 2-4 hours. Intravenous: 30-60 minutes (NPH not for IV use). |
| Duration of Action | Subcutaneous: 10-20 hours (peak 4-12 hours). Duration varies with dose, injection site, and individual response. |
0.5-1 unit/kg/day subcutaneously, divided into 2 doses (morning and evening).
| Dosage form | INJECTABLE |
| Renal impairment | No specific dose adjustment for renal impairment is recommended, but patients with renal impairment may require lower doses due to decreased insulin clearance. |
| Liver impairment | Dose adjustment may be necessary; start with lower doses and titrate carefully based on glucose monitoring. |
| Pediatric use | Weight-based: 0.5-1 unit/kg/day subcutaneously divided into 2 doses; for prepubertal children, use lower end of range; for pubertal adolescents, may need higher doses (up to 1.2 units/kg/day). |
| Geriatric use | Lower initial doses recommended (e.g., 0.5 units/kg/day) due to increased risk of hypoglycemia; titrate slowly based on glucose response. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for HUMULIN N (HUMULIN N).
| Breastfeeding | Insulin is a large protein molecule and minimal transfer into breast milk occurs; it is not orally bioavailable to the infant. Humulin N is considered compatible with breastfeeding. M/P ratio not established. |
| Teratogenic Risk | Insulin does not cross the placenta in significant amounts. Humulin N (NPH insulin) is not associated with increased risk of congenital malformations. Poor glycemic control increases risks for spontaneous abortion, stillbirth, and congenital anomalies. Second and third trimester hyperglycemia is associated with macrosomia, neonatal hypoglycemia, and preeclampsia. |
■ FDA Black Box Warning
None.
| Serious Effects |
["History of hypersensitivity to insulin isophane or any component of the formulation.","Hypoglycemic episodes."]
| Precautions | ["Hypoglycemia: Most common adverse effect; monitor blood glucose closely.","Hyperglycemia or ketoacidosis may result from missed doses or illness.","Dosage adjustment required in renal or hepatic impairment.","Allergic reactions: local or systemic; anaphylaxis rare.","Hypokalemia: if not adequately treated; monitor potassium.","Changes in insulin regimen may affect glycemic control; adjust doses carefully.","Do not mix with other insulins without specific instruction."] |
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| Fetal Monitoring | Monitor blood glucose levels frequently (preprandial and postprandial). HbA1c every 1-3 months. Fetal surveillance: ultrasound for anatomy and growth, nonstress tests, biophysical profiles, and kick counts as clinically indicated. Assess for gestational hypertension and preeclampsia. |
| Fertility Effects | Good glycemic control is essential for fertility and reducing risks of early pregnancy loss. Insulin does not impair fertility. Uncontrolled diabetes may cause ovulatory dysfunction. |