Medically reviewed on March 25, 2018
(IN soo lin LYE sproe)
- Humalog Junior KwikPen
- Lispro Insulin
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Admelog: 100 units/mL (10 mL) [contains metacresol]
HumaLOG: 100 units/mL (3 mL, 10 mL) [contains metacresol, phenol]
Solution Pen-injector, Subcutaneous:
Admelog SoloStar: 100 units/mL (3 mL) [contains metacresol]
HumaLOG Junior KwikPen: 100 units/mL (3 mL) [contains metacresol, phenol]
HumaLOG KwikPen: 100 units/mL (3 mL); 200 units/mL (3 mL) [contains metacresol, phenol]
Brand Names: U.S.
- Admelog SoloStar
- HumaLOG Junior KwikPen
- HumaLOG KwikPen
- Insulin, Rapid-Acting
Insulin acts via specific membrane-bound receptors on target tissues to regulate metabolism of carbohydrate, protein, and fats. Target organs for insulin include the liver, skeletal muscle, and adipose tissue.
Within the liver, insulin stimulates hepatic glycogen synthesis. Insulin promotes hepatic synthesis of fatty acids, which are released into the circulation as lipoproteins. Skeletal muscle effects of insulin include increased protein synthesis and increased glycogen synthesis. Within adipose tissue, insulin stimulates the processing of circulating lipoproteins to provide free fatty acids, facilitating triglyceride synthesis and storage by adipocytes; also directly inhibits the hydrolysis of triglycerides. In addition, insulin stimulates the cellular uptake of amino acids and increases cellular permeability to several ions, including potassium, magnesium, and phosphate. By activating sodium-potassium ATPases, insulin promotes the intracellular movement of potassium.
Normally secreted by the pancreas, insulin products are manufactured for pharmacologic use through recombinant DNA technology using either E. coli or Saccharomyces cerevisiae. Insulin lispro differs from human insulin by containing a lysine and proline at positions B28 and B29, respectively, in comparison to the proline and lysine found at B28 and B29 in human insulin. Insulins are categorized based on the onset, peak, and duration of effect (eg, rapid-, short-, intermediate-, and long-acting insulin). Insulin lispro is a rapid-acting insulin analog.
Vd: IV: 0.72-1.55 L/kg (inversely related to dose)
Onset of Action
SubQ: 0.25-0.5 hours; Peak effect: SubQ: 0.5-2.5 hours
Time to Peak
Plasma: SubQ: 0.5-1.5 hours
Duration of Action
SubQ: ≤5 hours
Special Populations: Renal Function Impairment
Insulin clearance may be reduced in patients with impaired renal function.
Use: Labeled Indications
Diabetes mellitus, types 1 and 2: Treatment of type 1 diabetes mellitus and type 2 diabetes mellitus to improve glycemic control
Off Label Uses
Diabetic ketoacidosis (mild-to-moderate)
Data from a prospective, randomized open trial in a limited number of patients with uncomplicated diabetic ketoacidosis comparing the use of subcutaneous insulin lispro to a standard low-dose IV infusion protocol of regular insulin supports the use of insulin lispro in the treatment of mild-to-moderate diabetic ketoacidosis [Umpierrez 2004]. Additional trials may be necessary to further define the role of insulin lispro in the management of this condition.
Based on a consensus statement from the American Diabetic Association for the treatment of patients with hyperglycemic crises in adult patients with diabetes, the use of rapid-acting insulin analogues (eg, insulin lispro) is an effective alternative to intravenous regular insulin in the management of mild to moderate diabetic ketoacidosis.
Gestational diabetes mellitus
Data from a randomized, active-controlled, open-label trial, comparing the metabolic and immunologic effects of insulin lispro and regular human insulin in gestational diabetic women demonstrated similar anti-insulin antibody levels, mean fasting and postprandial glucose concentrations, and HbA1c between groups; however, the insulin lispro group had lower areas under the curve for glucose, insulin, C-peptide, and fewer hypoglycemic episodes than the group treated with regular human insulin [Jovanovic 1999].
Based on the American College of Obstetricians and Gynecologists (ACOG) Practice Bulletin for the management of gestational diabetes mellitus and the American Diabetes Association Standards of Medical Care in Diabetes, insulin may be used to treat GDM when nutrition and exercise therapy are not effective. The Endocrine Society Clinical Practice Guideline on Diabetes and Pregnancy as well as ACOG recommend the use of rapid-acting insulin analogs lispro and aspart in preference to regular insulin in pregnant patients with diabetes [ACOG 190 2018], [Blumer 2018]
Additional Off-Label Uses
Mild-to-moderate hyperosmolar hyperglycemic state (HHS)
Hypersensitivity to insulin lispro or any component of the formulation; during episodes of hypoglycemia
Note: Insulin lispro is a rapid-acting insulin analog which is normally administered SubQ as a premeal component of the insulin regimen or as a continuous SubQ infusion and should be used with intermediate- or long-acting insulin. When compared to insulin regular, insulin lispro has a more rapid onset and shorter duration of activity. In carefully controlled clinical settings with close medical supervision and monitoring of blood glucose and potassium, insulin lispro U 100 (100 units/mL) may also be administered IV in some situations; insulin lispro U 200 (200 units/mL) may not be administered IV. Insulin requirements vary dramatically between patients and dictate frequent monitoring and close medical supervision. When switching between insulin lispro products (eg, Humalog, Admelog), continue with the same insulin dose.
Diabetes mellitus, type 1: SubQ:
General insulin dosing (off-label):
Type 1: Note: Multiple daily doses or continuous subcutaneous infusions guided by blood glucose monitoring are the standard of diabetes care. Combinations of insulin formulations are commonly used. The daily doses presented below are expressed as the total units/kg/day of all insulin formulations combined.
Initial total insulin dose: 0.2 to 0.6 units/kg/day in divided doses. Conservative initial doses of 0.2 to 0.4 units/kg/day are often recommended to avoid the potential for hypoglycemia.
Usual maintenance range: 0.5 to 1 units/kg/day in divided doses. An estimate of anticipated needs may be based on body weight and/or activity factors as follows:
Nonobese: 0.4 to 0.6 units/kg/day
Obese: 0.8 to 1.2 units/kg/day
Division of daily insulin requirement (“conventional therapy”): Generally, 50% to 75% of the total daily dose (TDD) is given as an intermediate- or long-acting form of insulin (in 1 to 2 daily injections). The remaining portion of the TDD is then divided and administered before or at mealtimes (depending on the formulation) as a rapid-acting (eg, lispro, aspart, glulisine) or short-acting (regular) form of insulin. Some patients may benefit from the use of CSII which delivers rapid-acting insulin as a continuous infusion throughout the day and as boluses at mealtimes via an external pump device.
Division of daily insulin requirement (“intensive therapy”): Basal insulin delivery with 1 or 2 doses of intermediate- or long-acting insulin formulations superimposed with doses of short-acting (regular) or rapid-acting insulin (eg, lispro, aspart, glulisine) formulations 3 or more times daily.
Dosage adjustment: Dosage must be titrated to achieve glucose control and avoid hypoglycemia. Since combinations of agents are frequently used, dosage adjustment must address the individual component of the insulin regimen which most directly influences the blood glucose value in question, based on the known onset and duration of the insulin component. Treatment and monitoring regimens must be individualized. Also see Additional Information or Pharmacotherapy Pearls.
Continuous SubQ insulin infusion (insulin pump): A combination of a "basal" continuous insulin infusion rate with preprogrammed, premeal bolus doses which are patient controlled. When converting from multiple daily SubQ doses of maintenance insulin, it is advisable to reduce the basal rate to less than the equivalent of the total daily units of the longer acting insulin (eg, NPH); divide the total number of units by 24 to get the basal rate in units/hour. Do not include the total units of regular insulin or other rapid-acting insulin formulations in this calculation. The same prandial insulin dosage may be used empirically.
Diabetes mellitus, type 2: SubQ:
Initial: 4 units or 0.1 unit/kg or 10% of the basal insulin dose; insulin lispro (ie, a rapid acting insulin) is administered before the largest meal of the day and is usually given in addition to a regimen that includes basal insulin (ie, a long-acting insulin such as glargine, degludec, or detemir) and metformin +/- other noninsulin agents. If HbA1c is still not controlled despite titrations to reach glycemic targets, one option is to advance to ‘basal-bolus’ (ie, insulin lispro administered before ≥2 meals per day) in addition to basal insulin and usually given in addition to metformin +/- other noninsulin agent (ADA 2017f).
To reach self-monitoring glucose target: Adjust dose by 10% to 15% or 1 to 2 units; may adjust at weekly or twice weekly intervals (ADA 2017f)
For hypoglycemia: If no clear reason for hypoglycemia, decrease dose by 2 to 4 units or by 10% to 20% (ADA 2017f)
Surgical patients: On the morning of surgery or procedure, give 60% to 80% of the usual dose of long-acting analogs (eg, detemir, glargine, or degludec) or pump “basal” insulin (rapid-or short-acting insulins) (ADA 2017d)
General considerations for insulin use in type 2 diabetes:
Timing of initiation: Dual therapy (metformin + a second antihyperglycemic agent) and then triple therapy (metformin + two antihyperglycemic agents) is recommended in patients who fail to achieve glycemic goals after ~3 months with lifestyle intervention and metformin monotherapy or dual therapy, respectively (unless contraindications to metformin exist). Preference is not given for which agent(s) should be added to metformin (drug choice should be individualized based on patient characteristics). If HbA1c target not achieved after ~3 months of triple therapy, consider initiating basal insulin (usually with metformin +/- other noninsulin agent) or if patient already receiving an optimally titrated basal insulin (ie, a long-acting insulin such as glargine, degludec, or detemir) as part of their regimen, consider combination injectable therapy (ADA 2017f).
Combination injectable therapy: If HbA1c target has not been met with basal insulin (ie, long-acting insulin such as glargine, degludec or detemir) (usually combined with metformin +/- other noninsulin agent), despite titrating basal insulin to provide acceptable fasting blood glucose concentrations, combination injectable therapy should be considered. Options include: adding a rapid-acting insulin (eg, lispro, aspart, glulisine) prior to largest meal or adding a GLP-1 receptor agonist or changing from basal insulin to a twice daily premixed insulin. If HbA1c still not adequately controlled, consider advancing from one rapid-acting insulin prior to largest meal to ‘basal-bolus’ regimen (ie, rapid-acting insulin administered before ≥2 meals) or consider advancing from a twice daily premixed insulin to a three times daily premixed insulin (ADA 2017f).
Patients with elevated HbA1C at therapy initiation: If HbA1c is ≥9% at initiation of therapy, dual therapy (metformin + a second antihyperglycemic agent) should be considered. If HbA1c ≥10%, blood glucose is ≥300 mg/dL or if patient is symptomatic (eg, polyuria, polydipsia), insulin therapy (with or without additional agents) should be considered (ADA 2017f).
Diabetic ketoacidosis, mild-to-moderate (off-label use): SubQ: Initial: 0.3 units/kg, followed by 0.1 units/kg every hour until blood glucose <250 mg/dL, then decrease to 0.05 units/kg/hour until resolution of ketoacidosis (Umpierrez 2004). Also, refer to institution-specific protocols where appropriate.
Refer to adult dosing.
Note: Insulin lispro is a rapid-acting insulin analog that is normally administered SubQ as a premeal component of the insulin regimen or as a continuous SubQ infusion and should be used with intermediate- or long-acting insulin. When compared to insulin regular, insulin lispro has a more rapid onset and shorter duration of activity. In carefully controlled clinical settings with close medical supervision and monitoring of blood glucose and potassium, insulin lispro may also be administered IV in some situations; insulin requirements vary dramatically between patients and dictate frequent monitoring and close medical supervision. See Insulin Regular for additional information. When switching between insulin lispro products (eg, Humalog, Admelog), continue with the same insulin dose.
General insulin dosing (off-label):
Diabetes mellitus, type 1: Children and Adolescents: Note: Multiple daily doses or continuous subcutaneous infusions guided by blood glucose monitoring are the standard of diabetes care. Combinations of insulin formulations are commonly used. The daily doses presented below are expressed as the total units/kg/day of all insulin formulations combined.
Initial dose: SubQ: 0.2 to 0.6 units/kg/day in divided doses. Conservative initial doses of 0.2 to 0.4 units/kg/day are often recommended to avoid the potential for hypoglycemia.
Usual maintenance range: SubQ: 0.5 to 1 unit/kg/day in divided doses. An estimate of anticipated needs may be based on body weight and/or activity factors as follows:
Nonobese: 0.4 to 0.6 units/kg/day
Obese: 0.8 to 1.2 units/kg/day
Pubescent Children and Adolescents: During puberty, requirements may substantially increase to >1 unit/kg/day and in some cases up to 2 units/kg/day (IDF/ISPAD 2011)
Dosage adjustment: Dosage must be titrated to achieve glucose control and avoid hypoglycemia. Since combinations of agents are frequently used, dosage adjustment must address the individual component of the insulin regimen that most directly influences the blood glucose value in question, based on the known onset and duration of the insulin component.
Continuous SubQ insulin infusion (insulin pump): A combination of a "basal" continuous insulin infusion rate with preprogrammed, premeal bolus doses which are patient controlled. When converting from multiple daily SubQ doses of maintenance insulin, it is advisable to reduce the basal rate to less than the equivalent of the total daily units of longer-acting insulin (eg, NPH); divide the total number of units by 24 to get the basal rate in units/hour. Do not include the total units of regular insulin or other rapid-acting insulin formulations in this calculation. The same prandial insulin dosage may be used empirically.
Dosing: Renal Impairment
Adults: There are no specific dosage adjustments provided in the manufacturer's labeling; however, dosage adjustment may be needed as insulin requirements may be reduced due to changes in insulin clearance or metabolism.
Dosing: Hepatic Impairment
There are no specific dosage adjustments provided in the manufacturer's labeling; however, dosage adjustment may be needed as insulin requirements may be reduced due to changes in insulin clearance or metabolism; monitor blood glucose closely.
Refer to indication-specific dosing for obesity-related information (may not be available for all indications).
For SubQ administration: Do not dilute insulin contained in a cartridge, prefilled pen, or external insulin pump.
Humalog vials: May be diluted with Sterile Diluent for Humalog to a concentration of 10 units/mL (U-10) or 50 units/mL (U-50).
Admelog vials: May be diluted with sterile normal saline in equal parts to yield a concentration of 50 units/mL (U-50).
For IV infusion: Insulin lispro U 100 may be diluted in NS to concentrations of 0.1 to 1 units/mL. Humalog U 200 may not be administered intravenously.
Use only if solution is clear and colorless; do not use if solution is viscous, cloudy, colored, or if it has lumps or particles in it.
SubQ administration: Insulin lispro should be administered within 15 minutes before or immediately after a meal. Cold injections should be avoided. SubQ administration is usually made into the thighs, arms, buttocks, or abdomen; rotate injection sites within the same region to avoid lipodystrophy.
Humalog: Do not dilute or mix other insulins with insulin lispro contained in a cartridge or prefilled pen. Do not mix insulin lispro U 200 with any other insulin. May mix insulin lispro U 100 (eg, 100 units/mL) from a vial only with insulin NPH (do not mix with other types of insulin); insulin lispro should be drawn into syringe first; perform injection immediately. Kwikpens are designed to dial doses in 1-unit increments (U-100 or U-200 pens) or in 0.5-unit increments (Junior KwikPen). Do not perform dose conversion when using Humalog KwikPen devices; the dose window shows the number of units to be delivered and no conversion is needed. Do not transfer insulin lispro U 200 KwikPen to a syringe for administration.
Admelog: Do not mix with any other insulin.
CSII administration: Only administer insulin lispro U 100 (eg, 100 units/mL) via CSII; do not administer insulin lispro U 200 (eg, 200 units/mL) in a CSII pump. Patients should be trained in the proper use of their external insulin pump and in intensive insulin therapy. Infusion sets and infusion set insertion sites should be changed every 3 days; rotate infusion sites. Insulin in reservoir should be changed at least every 7 days. Do not dilute or mix other insulins with insulin lispro U 100 (eg, 100 units/mL) contained in an external insulin pump.
IV administration: May be administered IV with close monitoring of blood glucose and serum potassium; appropriate medical supervision is required. Do not administer insulin lispro U 200 (200 units/mL) IV. Do not administer insulin mixtures IV.
IV infusions: To minimize adsorption to IV tubing: At low concentrations and flow rates, insulin lispro has been shown to adsorb to PVC IV bags and tubing (Ling 1999). Therefore, flush the IV tubing with a priming infusion of 20 mL from the insulin infusion, whenever a new IV tubing set is added to the insulin infusion container (SCCM [Jacobi 2012; Thompson 2012]).
Note: Also refer to institution-specific protocols where appropriate.
Because of insulin adsorption to IV tubing or infusion bags, the actual amount of insulin being administered via IV infusion could be substantially less than the apparent amount. Therefore, adjustment of the IV infusion rate should be based on effect and not solely on the apparent insulin dose. The apparent dose may be used as a starting point for determining the subsequent SubQ dosing regimen (Moghissi 2009); however, the transition to SubQ administration requires continuous medical supervision, frequent monitoring of blood glucose, and careful adjustment of therapy. Transition to a protocol-driven basal/bolus insulin regimen should begin prior to stopping the IV infusion in order to avoid significant loss of glucose control (Jacobi 2012; Moghissi 2009).
Individualized medical nutrition therapy (MNT) based on ADA recommendations is an integral part of therapy.
Unopened vials, cartridges, and prefilled pens may be stored under refrigeration between 2°C and 8°C (36°F to 46°F) until the expiration date or at room temperature <30°C (<86°F) for 28 days; do not freeze; keep away from heat and light. Once punctured (in use), vials may be stored under refrigeration or at room temperature <30°C (<86°F); use within 28 days. Cartridges and prefilled pens that have been punctured (in use) should be stored at room temperatures <30°C (<86°F) and used within 28 days; do not freeze or refrigerate. When used for CSII, insulin lispro contained within an external insulin pump reservoir should be changed every 7 days and insulin lispro contained within a 3 mL cartridge should be discarded after 7 days; discard if exposed to temperatures >37°C (>98.6°F).
Diluted solution for SubQ administration:
Humalog: After dilution may store at 30°C (86°F) for 14 days or at 5°C (41°F) for 28 days.
Admelog: After dilution may store at 2°C to 8°C (36°F to 46°F) for up to 24 hours or at 30°C (86°F) for up to 4 hours.
Diluted solution for IV infusion:
Humalog: Stable in NS for 48 hours when stored under refrigeration between 2°C and 8°C (36°F to 46°F); may then be used at room temperature for an additional 48 hours.
Admelog: Stable in NS for 24 hours when stored at 2°C to 8°C (36°F to 46°F) or for up to 4 hours room temperature.
Alpha-Lipoic Acid: May enhance the hypoglycemic effect of Antidiabetic Agents. Monitor therapy
Androgens: May enhance the hypoglycemic effect of Blood Glucose Lowering Agents. Exceptions: Danazol. Monitor therapy
Antidiabetic Agents: May enhance the hypoglycemic effect of Hypoglycemia-Associated Agents. Monitor therapy
Beta-Blockers: May enhance the hypoglycemic effect of Insulins. Exceptions: Levobunolol; Metipranolol. Monitor therapy
Dipeptidyl Peptidase-IV Inhibitors: May enhance the hypoglycemic effect of Insulins. Management: Consider a decrease in insulin dose when initiating therapy with a dipeptidyl peptidase-IV inhibitor and monitor patients for hypoglycemia. Consider therapy modification
Edetate CALCIUM Disodium: May enhance the hypoglycemic effect of Insulins. Monitor therapy
Edetate Disodium: May enhance the hypoglycemic effect of Insulins. Monitor therapy
Glucagon-Like Peptide-1 Agonists: May enhance the hypoglycemic effect of Insulins. Management: Consider insulin dose reductions when used in combination with glucagon-like peptide-1 agonists. Avoid the use of lixisenatide in patients receiving both basal insulin and a sulfonylurea. Exceptions: Liraglutide. Consider therapy modification
Guanethidine: May enhance the hypoglycemic effect of Antidiabetic Agents. Monitor therapy
Herbs (Hypoglycemic Properties): May enhance the hypoglycemic effect of Hypoglycemia-Associated Agents. Monitor therapy
Hyperglycemia-Associated Agents: May diminish the therapeutic effect of Antidiabetic Agents. Monitor therapy
Hypoglycemia-Associated Agents: May enhance the hypoglycemic effect of other Hypoglycemia-Associated Agents. Monitor therapy
Hypoglycemia-Associated Agents: Antidiabetic Agents may enhance the hypoglycemic effect of Hypoglycemia-Associated Agents. Monitor therapy
Liraglutide: May enhance the hypoglycemic effect of Insulins. Management: If liraglutide is used for the treatment of diabetes (Victoza), consider insulin dose reductions. The combination of liraglutide and insulin should be avoided if liraglutide is used exclusively for weight loss (Saxenda). Consider therapy modification
Macimorelin: Insulins may diminish the diagnostic effect of Macimorelin. Avoid combination
Metreleptin: May enhance the hypoglycemic effect of Insulins. Management: Insulin dosage adjustments (including potentially large decreases) may be required to minimize the risk for hypoglycemia with concurrent use of metreleptin. Monitor closely. Consider therapy modification
Monoamine Oxidase Inhibitors: May enhance the hypoglycemic effect of Blood Glucose Lowering Agents. Monitor therapy
Pegvisomant: May enhance the hypoglycemic effect of Blood Glucose Lowering Agents. Monitor therapy
Pioglitazone: May enhance the adverse/toxic effect of Insulins. Specifically, the risk for hypoglycemia, fluid retention, and heart failure may be increased with this combination. Management: If insulin is combined with pioglitazone, dose reductions should be considered to reduce the risk of hypoglycemia. Monitor patients for fluid retention and signs/symptoms of heart failure. Consider therapy modification
Pramlintide: May enhance the hypoglycemic effect of Insulins. Management: Upon initiation of pramlintide, decrease mealtime insulin dose by 50% to reduce the risk of hypoglycemia. Monitor blood glucose frequently and individualize further insulin dose adjustments based on glycemic control. Consider therapy modification
Prothionamide: May enhance the hypoglycemic effect of Blood Glucose Lowering Agents. Monitor therapy
Quinolones: May enhance the hypoglycemic effect of Blood Glucose Lowering Agents. Quinolones may diminish the therapeutic effect of Blood Glucose Lowering Agents. Specifically, if an agent is being used to treat diabetes, loss of blood sugar control may occur with quinolone use. Monitor therapy
Ritodrine: May diminish the therapeutic effect of Antidiabetic Agents. Monitor therapy
Rosiglitazone: Insulins may enhance the adverse/toxic effect of Rosiglitazone. Specifically, the risk of fluid retention, heart failure, and hypoglycemia may be increased with this combination. Avoid combination
Salicylates: May enhance the hypoglycemic effect of Blood Glucose Lowering Agents. Monitor therapy
Selective Serotonin Reuptake Inhibitors: May enhance the hypoglycemic effect of Blood Glucose Lowering Agents. Monitor therapy
Sodium-Glucose Cotransporter 2 (SLGT2) Inhibitors: May enhance the hypoglycemic effect of Insulins. Management: Consider a decrease in insulin dose when initiating therapy with a sodium-glucose cotransporter 2 inhibitor and monitor patients for hypoglycemia. Consider therapy modification
Thiazide and Thiazide-Like Diuretics: May diminish the therapeutic effect of Antidiabetic Agents. Monitor therapy
Endocrine & metabolic: Severe hypoglycemia (2% to 14%)
Immunologic: Antibody development (type 2 diabetics; 19%; type 1 diabetics: 23%)
Local: Infusion site reaction (type 1 diabetes: 21% to 24%; includes erythema and occlusion)
1% to 10%: Neuromuscular & skeletal: Myalgia (7%; most likely secondary to excipient metacresol)
Frequency not defined:
Cardiovascular: Peripheral edema
Endocrine & metabolic: Hypoglycemia, hypokalemia, weight gain
Hypersensitivity: Hypersensitivity reaction
Local: Hypertrophy at injection site, injection site reaction (including local reactions secondary to excipient metacresol), lipoatrophy at injection site
Concerns related to adverse effects:
• Glycemic control: The most common adverse effect of insulin is hypoglycemia. The timing of hypoglycemia differs among various insulin formulations. Hypoglycemia may result from changes in meal pattern (eg, macronutrient content or timing of meals), changes in the level of physical activity, increased work or exercise without eating or changes to coadministered medications. Hyperglycemia is also a concern; may occur with CSII pump or infusion set malfunctions or insulin degradation; hyper- or hypoglycemia may result from changes in insulin strength, manufacturer, type or administration method. Use of long-acting insulin preparations (eg, insulin detemir, insulin glargine) may delay recovery from hypoglycemia. Patients with renal or hepatic impairment may be at a higher risk. Symptoms differ in patients and may change over time in the same patient; awareness may be less pronounced in those with long standing diabetes, diabetic nerve disease, patients taking beta-blockers or in those who experience recurrent hypoglycemia. Profound and prolonged episodes of hypoglycemia may result in convulsions, unconsciousness, temporary or permanent brain damage, or even death. Insulin requirements may be altered during illness, emotional disturbances, or other stressors. Instruct patients to use caution with ethanol; may increase risk of hypoglycemia.
• Hypersensitivity: Hypersensitivity reactions (serious, life-threatening and anaphylaxis) have occurred. If hypersensitivity reactions occur, discontinue administration and initiate supportive care measures.
• Hypokalemia: Insulin (especially IV insulin) causes a shift of potassium from the extracellular space to the intracellular space, possibly producing hypokalemia. If left untreated, hypokalemia may result in respiratory paralysis, ventricular arrhythmia and even death. Use with caution in patients at risk for hypokalemia (eg, loop diuretic use). Monitor serum potassium frequently with IV insulin use and supplement potassium when necessary.
• Hepatic impairment: Use with caution in patients with hepatic impairment. Dosage requirements may be reduced and patients may require more frequent dose adjustment and glucose monitoring.
• Renal impairment: Use with caution in patients with renal impairment. Dosage requirements may be reduced and patients may require more frequent dose adjustment and glucose monitoring.
Concurrent drug therapy issues:
• Drug-drug interactions: Potentially significant interactions may exist, requiring dose or frequency adjustment, additional monitoring, and/or selection of alternative therapy. Consult drug interactions database for more detailed information.
• Hospitalized patients with diabetes: Exclusive use of a sliding scale insulin regimen (insulin regular) in the inpatient hospital setting is strongly discouraged. In the critical care setting, continuous IV insulin infusion (insulin regular) has been shown to best achieve glycemic targets. In noncritically ill patients with either poor oral intake or taking nothing by mouth, basal insulin or basal plus bolus is preferred. In noncritically ill patients with adequate nutritional intake, a combination of basal insulin, nutritional, and correction components is preferred. An effective insulin regimen will achieve the goal glucose range without the risk of severe hypoglycemia). A blood glucose value <70 mg/dL should prompt a treatment regimen review and change, if necessary, to prevent further hypoglycemia (ADA 2017d).
Dosage form specific issues:
• Humalog KwikPen devices: Do not perform dose conversion when using KwikPen; the dose window shows the number of units to be delivered and no conversion is needed.
• Humalog U 200 (200 units/mL) KwikPen: Do not transfer product from the KwikPen to a syringe for administration. Do not mix with other insulins, administer in a CSII pump, or administer IV.
• Multiple-dose injection pens: According to the CDC, pen-shaped injection devices should never be used for more than one person (even when the needle is changed) because of the risk of infection. The injection device should be clearly labeled with individual patient information to ensure that the correct pen is used (CDC 2012).
• Appropriate use: Diabetes mellitus: The general objective of exogenous insulin therapy is to approximate the physiologic pattern of insulin secretion which is characterized by two distinct phases. Phase 1 insulin secretion suppresses hepatic glucose production and phase 2 insulin secretion occurs in response to carbohydrate ingestion; therefore, exogenous insulin therapy may consist of basal insulin (eg, intermediate- or long-acting insulin via continuous subcutaneous insulin infusion [CSII]) and/or preprandial insulin (eg, short- or rapid-acting insulin [eg, insulin lispro]) (see Related Information: Insulin Products). Patients with type 1 diabetes do not produce endogenous insulin; therefore, these patients require both basal and preprandial insulin administration. Patients with type 2 diabetes retain some beta-cell function in the early stages of their disease; however, as the disease progresses, phase 1 insulin secretion may become completely impaired and phase 2 insulin secretion becomes delayed and/or inadequate in response to meals. Therefore, patients with type 2 diabetes may be treated with oral antidiabetic agents, basal insulin, and/or preprandial insulin depending on the stage of disease and current glycemic control. Since treatment regimens often consist of multiple agents, dosage adjustments must address the specific phase of insulin release that is primarily contributing to the patient's impaired glycemic control. Treatment and monitoring regimens must be individualized.
Due to the short duration of action of insulin lispro, a longer acting insulin or CSII via an external insulin pump is needed to maintain adequate glucose control in patients with type 1 diabetes mellitus. In both type 1 and type 2 diabetes, preprandial administration of insulin lispro should be immediately followed by a meal within 15 minutes.
• CSII administration: Insulin lispro U-100 (eg, 100 units/mL) may be administered via CSII; do not dilute or mix with other insulins. Rule out external pump failure if unexplained hyperglycemia or ketosis occurs; temporary SubQ insulin administration may be required until the problem is identified and corrected.
• IV administration: Insulin lispro U 100 (eg, 100 units/mL) may be administered IV in selected clinical situations to control hyperglycemia; close monitoring of blood glucose and serum potassium as well as medical supervision is required.
• Patient education: Diabetes self-management education (DSME) is essential to maximize the effectiveness of therapy.
Diabetes mellitus: Plasma glucose, electrolytes, HbA1c (at least twice yearly in patients who have stable glycemic control and are meeting treatment goals; quarterly in patients not meeting treatment goals or with therapy change [ADA 2017a]); renal function, hepatic function, weight
IV administration: Close monitoring of blood glucose and serum potassium
Pregnancy Risk Factor
Insulin lispro has not been shown to cross the placenta at standard clinical doses (Boskovic 2003; Holcberg 2004; Jovanovic 1999).
In women with diabetes, maternal hyperglycemia can be associated with congenital malformations as well as adverse effects in the fetus, neonate, and the mother (ACOG 2005; ADA 2018c; Metzger 2007). To prevent adverse outcomes, prior to conception and throughout pregnancy maternal blood glucose and HbA1c should be kept as close to target goals as possible but without causing significant hypoglycemia (ADA 2018c; Blumer 2013; Lambert 2013).
Insulin requirements tend to fall during the first trimester of pregnancy and increase in the later trimesters, peaking at 28 to 32 weeks' gestation. Following delivery, insulin requirements decrease rapidly (ACOG 2005).
Insulin therapy is the preferred treatment of type 1 and type 2 diabetes in pregnant women, as well as GDM when pharmacologic therapy is needed (ACOG 190 2018; ADA 2018c). Insulin lispro may be used to treat diabetes in pregnant women (ACOG 190 2018; Blumer 2013; Lambert 2013).
• Discuss specific use of drug and side effects with patient as it relates to treatment. (HCAHPS: During this hospital stay, were you given any medicine that you had not taken before? Before giving you any new medicine, how often did hospital staff tell you what the medicine was for? How often did hospital staff describe possible side effects in a way you could understand?)
• Have patient report immediately to prescriber signs of low blood sugar (dizziness, headache, fatigue, feeling weak, shaking, a fast heartbeat, confusion, hunger, or sweating), signs of low potassium (muscle pain or weakness, muscle cramps, or an abnormal heartbeat), severe injection site irritation, vision changes, chills, severe dizziness, passing out, mood changes, seizures, slurred speech, difficulty breathing, shortness of breath, excessive weight gain, swelling of arms or legs, or change in skin to thick or thin at injection site (HCAHPS).
• Educate patient about signs of a significant reaction (eg, wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat). Note: This is not a comprehensive list of all side effects. Patient should consult prescriber for additional questions.
Intended Use and Disclaimer: Should not be printed and given to patients. This information is intended to serve as a concise initial reference for healthcare professionals to use when discussing medications with a patient. You must ultimately rely on your own discretion, experience and judgment in diagnosing, treating and advising patients.
Always consult your healthcare provider to ensure the information displayed on this page applies to your personal circumstances.
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