insulin lispro (Rx)

>10%

Admelog

• Severe hypoglycemia, after 52 weeks (13.5%)
• Nasopharyngitis, in combination with insulin glargine (13.1%)

Humalog (Type 1 Diabetes)

• Flu syndrome (34.6%)
• Pharyngitis (33.3%)
• Rhinitis (29.6%)
• Headache (24.7%)
• Pain (19.8%)
• Increased cough (17.3%)
• Infection (13.6%)

Humalog (Type 2 Diabetes)

• Headache (11.6%)
• Pain (10.8%)
• Infection (10.1%)

Admelog

• Upper respiratory tract infection, in combination with insulin glargine (6%)
• Severe hypoglycemia, after 26 weeks (2.4%)

Humalog, continuous SC insulin infusion

• Infusion site reactions (2.6%)

Humalog (Type 1 Diabetes)

• Accidental injury (8.6%)
• Diarrhea (8.6%)
• Myalgia (7.4%)
• Abdominal pain (7.4%)
• Asthenia (7.4%)
• Bronchitis (7.4%)
• Urinary tract infection (6.2%)
• Dysmenorrhea (6.2%)
• Surgical procedure (6.2%)
• Fever (6.2%)
• Nausea (6.2%)

Humalog (Type 2 Diabetes)

• Rhinitis (8.1%)
• Surgical procedure (7.4%)
• Pharyngitis (6.6%)

Frequency Not Defined

Hypoglycemia

Pallor

Palpitation

Redness

Hunger

Nausea

Tachycardia

Lipodystrophy

Lipohypertrophy

Local allergic reaction

Hypokalemia

Postmarketing Reports

Medication errors

Localized cutaneous amyloidosis

Contraindications

During episodes of hypoglycemia

Hypersensitivity to drug or excipients

Cautions

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

Changes in insulin strength, manufacturer, type, or method of administration may affect glycemic control and predispose to hypoglycemia or hyperglycemia; adjust dosage cautiously and closely monitor blood glucose

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

Do not transfer Humalog U-200 from the KwikPen to a syringe for administration; the markings on the insulin syringe will not measure the dose correctly and can result in overdosage and severe hypoglycemia

Insulin pump or insulin infusion set malfunction or insulin degradation can rapidly lead to hyperglycemia and ketoacidosis; promptly identify and correct the cause of hyperglycemia or ketosis is necessary; interim insulin lispro injections may be required; patients using continuous SC insulin infusion pump therapy must be trained to administer insulin by injection and have alternate insulin therapy available in case of pump failure

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

Severe, life-threatening, generalized allergy including anaphylaxis may occur; if hypersensitivity reactions occur, discontinue treatment; treat accordingly and monitor until resolution of signs and symptoms

Hyperglycemia or hypoglycemia with changes in insulin regimen

• Hypoglycemia is the most common adverse reaction; severe hypoglycemia can cause seizures, may be life-threatening, or cause death
• Decreased insulin requirements may require dose adjustment (eg, diarrhea, nausea, vomiting, malabsorption, hypothyroidism, renal impairment, hepatic impairment)
• Increased insulin requirements may require dose adjustment (eg, fever, hyperthyroidism, trauma, infection, surgery)
• Self-monitoring of blood glucose is essential in preventing and managing of hypoglycemia; closely monitor high-risk patients and patients who have reduced symptomatic awareness of hypoglycemia
• Risk of hypoglycemia after an injection correlates to the insulin’s duration of action and highest when the glucose lowering effect of the insulin is maximal; glucose lowering effect time course of insulin lispro may vary in different individuals or at different times in the same individual and depends on many conditions, (eg, area of injection, injection site blood supply, temperature
• Other factors which may increase the risk of hypoglycemia include changes in meal pattern (eg, macronutrient content or timing of meals), changes in level of physical activity, or changes to concomitant medications
• Patients with renal or hepatic impairment may be at higher risk of hypoglycemia
• 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

Drug interactions overview

• Coadministration with antidiabetic agents, salicylates, sulfonamide antibiotics, monoamine oxidase inhibitors, fluoxetine, pramlintide, disopyramide, fibrates, propoxyphene, pentoxifylline, ACE inhibitors, angiotensin II receptor blocking agents, and somatostatin analogs (eg, octreotide) may increase the risk of hypoglycemia (see Dosage Modifications)
• Coadministered with corticosteroids, isoniazid, niacin, estrogens, oral contraceptives, phenothiazines, danazol, diuretics, sympathomimetic agents (eg, epinephrine, albuterol, terbutaline), somatropin, atypical antipsychotics, glucagon, protease inhibitors, and thyroid hormones may decrease glucose lowering effects of insulin lispro (see Dosage Modifications)
• Glucose lowering effect of insulin lispro may be increased or decreased with coadministered with beta blockers, clonidine, lithium salts, and alcohol; pentamidine may cause hypoglycemia, which may sometimes be followed by hyperglycemia
• Signs and symptoms of hypoglycemia may be blunted when beta blockers, clonidine, guanethidine, and reserpine are coadministered with insulin lispro

Pregnancy

Published studies with insulin lispro used during pregnancy have not reported an association between insulin lispro and induction of major birth defects, miscarriage, or adverse maternal or fetal outcomes; there are risks to mother and fetus associated with poorly controlled diabetes in pregnancy

Diabetes or gestational diabetes patients’ insulin requirements may decrease during the first trimester, generally increase during the second and third trimesters, and rapidly decline after delivery

Female patients should be advised to tell their physicians if they intend to become, or if they become pregnant while taking insulin lispro

Published studies with human insulins suggest optimizing overall glycemic control (eg, postprandial control, before conception, during pregnancy) improves fetal outcome

Limited available data with Admelog in pregnant women are insufficient to inform a drug-associated risk of adverse developmental outcomes

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

Animal data

• In a combined fertility and embryo-fetal development study, female rats were given SC insulin lispro injections of 5 and 20 units/kg/day (0.8 and 3 times the human SC dose of 1 unit/kg/day, based on units/body surface area, respectively) from 2 weeks prior to cohabitation through gestation day 19; fetal growth retardation was produced at the 20 units/kg/day-dose as indicated by decreased fetal weight and an increased incidence of fetal runts/litter

Lactation

There are no data on presence of drug in human milk, effects on breastfed infant, or on milk production; one small published study reported that exogenous insulin was present in human milk; however, there is insufficient information to determine effects of drug on breastfed infant and no available information on effects on milk production; developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for insulin, any potential adverse effects on breastfed child 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

Protein hormone; stimulates glucose uptake by peripheral cells

Regulates glucose metabolism; insulins lower blood glucose by stimulating peripheral glucose uptake by skeletal muscle and fat and by inhibiting hepatic glucose production. Insulins inhibit lipolysis and proteolysis and enhance protein synthesis; targets include skeletal muscle, liver, and adipose tissue

Absorption

Humalog

• Average time required to attain near normoglycemia for IV administration was 129 minutes
• Mean area under the glucose infusion rate curves: 125 g (Humalog U-200) and 126 g (Humalog U-100)
• Bioavailability: 55-77% following SC; well absorbed
• Onset: 0.5-5 hr (initial); 0.5-2.5 hr Duration of action: ≤5 hr
• Peak plasma time, 0.1 to 0.4 unit/kg dose: 0.5-1.5 hr
• Mean observed area under the serum insulin concentration-time curve from time zero to infinity was 2360 pmol·hr/L (Humalog U-200) and 2390 pmol·hr/L (Humalog U-200)

Admelog

• Mean area under the glucose infusion rate curves, SC use: 1953.5 mg/kg
• Mean maximum glucose infusion rate, SC use: 9.97 mg/min/kg
• Mean observed area under the serum insulin concentration-time curve from time zero to infinity was 12800 pg⋅hr/mL
• Peak insulin lispro concentration: 5070 pg/mL
• Median peak plasma time: 0.83 hr

Distribution

Vd: 1.55 L/kg (0.1 unit/kg-dose); 0.72 L/kg (0.2 unit/kg-dose)

Metabolism

Human metabolism studies have not been conducted Animal studies indicate that the metabolism of insulin lispro is identical to regular human insulin

Elimination

Half-life, SC use: 1 hr

Mean clearance, IV use: 21.0 mL/min/kg (0.1 unit/kg dose); 9.6 mL/min/kg (0.2 unit/kg dose)

Mean half-life: 0.85 hr (0.1 unit/kg); 0.92 hr (0.2 unit/kg)

IV Preparation

Dilute insulin lispro to concentrations from 0.1 unit/mL to 1 unit/mL using 0.9% NaCl

SC Preparation

Admelog

• Dilute with sterile 0.9% NaCl
• Diluting 1 part Admelog to 1 part 0.9% NaCl will yield a concentration one-half of Admelog (equivalent to U-50)

Humalog U-100

• Dilute with sterile diluent for Humalog
• Diluting 1 part Humalog to 9 parts diluent will yield a concentration one-tenth of Humalog (equivalent to U-10)
• Diluting 1 part Humalog to 1 part diluent will yield a concentration one-half of Humalog (equivalent to U-50)

Continuous SC Infusion (Insulin Pump) Preparation

Do not dilute or mix insulin lispro when administering by continuous subcutaneous infusion

Change insulin lispro in the pump reservoir

Change infusion sets and the infusion set insertion site

Do not expose insulin lispro in pump reservoir to temperatures >98.6°F (37°C)

Use insulin lispro in accordance with the insulin infusion pump systems instructions for use

See insulin infusion pump system labeling to determine if insulin lispro can be used with the pump system

SC Administration

SC use only

Administer dose within 15 minutes before a meal or immediately after a meal

Should generally be used in regimens with intermediate or long-acting insulin Administer by SC injection in the abdominal wall, thigh, upper arm, or buttocks

Rotate injection site within the same region (abdomen, thigh, upper arm, or buttocks) from one injection to the next to reduce the risk of lipodystrophy

Continuous subcutaneous infusion (insulin pump)

• Administer by continuous subcutaneous infusion into SC tissue of the abdominal wall
• Rotate infusion sites within the same region to reduce the risk of lipodystrophy

IV Administration

Administer insulin IV only under medical supervision with close monitoring of blood glucose and potassium levels to avoid hypoglycemia and hypokalemia

Storage

Admelog

• Unopened 10 mL vials and 3 mL SoloStar pen

  • Refrigerate at 36-46°F [2-8°C] until expiration date OR Store at room temperature, <86°F [30°C] for up to 28 days

• Opened 10 mL vials

  • Store at room temperature, <86°F [30°C] OR refrigerate at 36-46°F [2-8°C] for up to 28 days

• Opened 3 mL SoloStar pen

  • Store at room temperature, <86°F [30°C] for up to 28 days
  • Do not refrigerate

• Diluted Admelog for SC injection and infusion bags

  • Refrigerate at 36-46°F [2-8°C] for up to 24 hr OR
  • Store at room temperature, <86°F [30°C] for up to 4 hr

Humalog

• Unopened Humalog U-100 10 mL vials, 3 mL cartridge, KwikPen (prefilled), Junior KwikPen (prefilled)

  • Refrigerate at 36-46°F [2-8°C] until expiration date OR
  • Store at room temperature, <86°F [30°C] for up to 28 days

• Unopened 3 mL Humalog U-200 KwikPen (prefilled)

  • Refrigerate at 36-46°F [2-8°C] until expiration date OR
  • Store at room temperature, <86°F [30°C] for up to 28 days

• Opened 10 mL Humalog U-100 vials

  • Store at room temperature, <86°F [30°C] OR refrigerate at 36-46°F [2-8°C] for up to 28 days

• Opened Humalog U-100 3 mL cartridge, KwikPen (prefilled), Junior KwikPen (prefilled)

  • Store at room temperature, <86°F [30°C] for up to 28 days
  • Do not refrigerate

• Opened 3 mL Humalog U-200 KwikPen (prefilled)

  • Store at room temperature, <86°F [30°C] for up to 28 days
  • Do not refrigerate

• Diluted Humalog U-100 for SC Injection

  • Stored at 41°F (5°C) use for 28 days OR store at 86°F (30°C) for up to 14 days
  • Do not dilute Humalog contained in a cartridge or used in an external insulin pump

• Diluted infusion bags

  • Refrigerate at 36-46°F (2-8°C) for 48 hr and then may be used at room temperature, <86°F [30°C] for up to an additional 48 hr