insulin NPH (OTC)

Frequency Not Defined

Hypoglycemia

Lipodystrophy

Lipohypertrophy

Local allergic reaction

Hypokalemia

Muscle weakness

Paresthesia

Tremor

Edema

Pain

Itching

Nausea

Hunger

Numbness of mouth

Postmarketing Reports

Localized cutaneous amyloidosis

Contraindications

Hypoglycemia

Documented hypersensitivity reactions to product or excipients

Cautions

Never share pen between patients even if needle is changed

Intermediate-acting insulin; do not use for circumstances that require rapid-acting insulin

Caution with decreased insulin requirements: Diarrhea, nausea/vomiting, malabsorption, hypothyroidism, renal impairment, hepatic impairment

Hypokalemia may occur

Not for IV or IM administration

Use with caution in renal and hepatic impairment (dosage requirements may be reduced)

Caution with increased insulin requirements: Fever, hyperthyroidism, trauma, infection, surgery

Thiazolidinediones are peroxisome proliferator-activated receptor (PPAR)-gamma agonists and can cause dose-related fluid retention, particularly when used in combination with insulin; fluid retention may lead to or exacerbate heart failure; monitor for signs and symptoms of heart failure, treat accordingly, and consider discontinuing thiazolidinediones

When hyper-or hypoglycemia occurs, carry out changes in insulin regimen under close medical supervision; increase frequency of blood glucose monitoring

Hyperglycemia or hypoglycemia with changes in insulin regimen

• Hypoglycemia may be life-threatening; increase frequency of blood glucose monitoring with changes to: insulin dosage, co-administered glucose lowering medications, meal pattern, physical activity; in patients with renal or hepatic impairment; and in patients with hypoglycemia unawareness
• Changes in insulin, insulin strength, manufacturer, type, or method of administration may affect glycemic control and predispose to hypoglycemia or hyperglycemia
• Changes should be made cautiously and only under close medical supervision and frequency of blood glucose monitoring should be increased
• Repeated insulin injections into areas of lipodystrophy or localized cutaneous amyloidosis reported to result in hyperglycemia; a sudden change in the injection site (to unaffected area) has been reported to result in hypoglycemia
• Make any changes to a patient’s insulin regimen under close medical supervision with increased frequency of blood glucose monitoring
• Advise patients who have repeatedly injected into areas of lipodystrophy or localized cutaneous amyloidosis to change injection site to unaffected areas and closely monitor for hypoglycemia
• For patients with type 2 diabetes, dosage adjustments in concomitant oral antidiabetic treatment may be needed

Pregnancy

Available data from published studies over decades have not established association with human insulin use during pregnancy and major birth defects, miscarriage or adverse maternal or fetal Outcomes; there are risks to mother and fetus associated with poorly controlled diabetes in pregnancy; animal reproduction studies were not performed

Poorly controlled diabetes in pregnancy increases maternal risk for diabetic ketoacidosis, preeclampsia, spontaneous abortions, preterm delivery, stillbirth, and delivery complications; poorly controlled diabetes increases fetal risk for major birth defects, stillbirth, and macrosomia-related morbidity

Lactation

Available data from published literature suggests that exogenous human insulin products, are transferred into human milk; there are no adverse reactions reported in breastfed infants in the literature; there are no data on effects of exogenous human insulin products, on milk production; the developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for therapy, and any potential adverse effects on breastfed infant from drug, or from underlying maternal condition

Pregnancy Categories

A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.

B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.

C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.

D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.

X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.

NA: Information not available.

Mechanism of Action

Regulates glucose metabolism

Insulin and its analogues lower blood glucose by stimulating peripheral glucose uptake, especially by skeletal muscle and fat, and by inhibiting hepatic glucose production; insulin inhibits lipolysis and proteolysis and enhances protein synthesis; targets include skeletal muscle, liver, and adipose tissue

Insulin NPH and insulin regular is a combination insulin product with intermediate action that has more rapid onset than that of insulin NPH alone

Absorption

Bioavailability (IM, SC, IP): Well absorbed

Onset: 1-1.5 hr (a combination insulin product, insulin NPH and insulin regular, also has intermediate action, but it has a more rapid onset than does insulin NPH alone); 4-12 hr peak effect

Duration: 14-24 hr

Peak plasma time: 6-10 hr

Distribution

Protein bound: 5% (not bound to serum binding protein, but present as a monomer in plasma)

Vd: 0.15 L/kg

Elimination

Excretion: Urine