insulin glulisine (Rx)

Frequency Not Defined

Hypoglycemia

Insulin resistance

Lipodystrophy

Lipohypertrophy

Local allergic rxn

Hypokalemia

Contraindications

During episodes of hypoglycemia

Documented hypersensitivity

Cautions

Adjust dosage and monitoring when medically warranted

Decreased insulin requirements: Diarrhea, N/V, malabsorption, hypothyroidism, renal impairment, hepatic impairment

Increased insulin requirements: fever, hyperthyroidism, trauma, infection, surgery

Hypoglycemia is the most common adverse reaction

May cause a shift in potassium from extracellular to intracellular space, possibly leading to hypokalemia; caution when coadministered with potassium-lowing drugs or conditions that may decrease potassium

Frequent glucose monitoring and insulin dose reduction may be required with renal or hepatic impairment

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 and treat accordingly and consider discontinuing thiazolidinediones

Never share a pen between patients even if the needle is changed

Patients using vials must never share needles or syringes with another person

Accidental mix-ups between insulin products reported; to avoid medication errors between APIDRA and other insulins, instruct patients to always check insulin label before each injection

If hypersensitivity reactions occur, discontinue therapy; treat per standard of care and monitor until symptoms and signs resolve; drug is contraindicated in patients who have had a hypersensitivity reaction to it or any of its excipients

Do not mix SC injection with insulin preparations other than NPH insulin

Hyperglycemia or hypoglycemia with changes in insulin regimen

• 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

SC insulin infusion

• Do not dilute or mix with any other insulin
• Insulin in the reservoir must be changed at least every 48 hr
• Do not expose to temperatures >98.6 F (37 C)
• Malfunction of the insulin pump or infusion set, or handling errors or insulin degradation can rapidly lead to hyperglycemia, ketosis and diabetic ketoacidosis; prompt identification and correction of cause of hyperglycemia or ketosis necessary; patients using continuous subcutaneous insulin infusion pump therapy must be trained to administer insulin by injection and have alternate insulin therapy available in case of pump failure

Pregnancy

Available pharmacovigilance data have not established an association with insulin glulisine 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

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

Animal data

• Animal reproduction studies have been conducted with insulin glulisine in rats and rabbits using regular human insulin as a comparator; insulin glulisine was given to female rats throughout pregnancy at subcutaneous doses up to 10 units/kg/day (2 times the average human dose, based on body surface area comparison) and to rabbits during organogenesis at subcutaneous doses up to 1.5 units/kg/day (0.5 times the average human dose, based on body surface area comparison); effects did not differ from those observed with subcutaneous regular human insulin

Lactation

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

Protein hormone

Insulins lower blood glucose by stimulating peripheral glucose uptake by skeletal muscle and fat, and by inhibiting hepatic glucose production

Absorption

Bioavailability: 70% following SC

Onset: 20 min (SC abdominal or deltoid injection); 30 min (SC femoral injection)

Peak Plasma Time: 1 hr

Peak Plasma Concentration: 83 microUnits/mL

Duration of action: 5 hr

Distribution

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

Vd: 13 L

Metabolism

Liver >50%; kidney 30%; adipose tissue/muscle 20%

Elimination

Half-Life: 13 minutes (IV); 42 min (SC)