Dosage Forms
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Solution, Subcutaneous:
Admelog: 100 units/mL (3 mL, 10 mL) [contains metacresol]
HumaLOG: 100 units/mL (3 mL, 10 mL) [contains metacresol, phenol]
Generic: 100 units/mL (10 mL)
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]
Generic: 100 units/mL (3 mL)
Pharmacology
Mechanism of Action
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.
Pharmacokinetics/Pharmacodynamics
Distribution
Vd: IV: 0.72-1.55 L/kg (inversely related to dose)
Excretion
Urine
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
Half-Life Elimination
~1 hour
Use in Specific Populations
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
Use: Off Label
Diabetic ketoacidosis (mild-to-moderate)byes
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 mellitusbyes
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 (ACOG 190 2018; ADA 2019). 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 2013.
Contraindications
Hypersensitivity to insulin lispro or any component of the formulation; during episodes of hypoglycemia
Dosage and Administration
Dosing: Adult
Note: Insulin lispro is a rapid-acting insulin analog. 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:
Note: Insulin lispro must be used concomitantly with intermediate- or long-acting insulin (ie, multiple daily injection regimen) or in a continuous subcutaneous infusion pump. The total daily doses (TDD) presented below are expressed as the total units/kg/day of all insulin formulations combined.
General insulin dosing:
Initial TDD: ~0.4 to 0.5 units/kg/day (AACE/ACE [Handelsman] 2015]; ADA 2019); conservative initial doses of 0.2 to 0.4 units/kg/day may be considered to avoid the potential for hypoglycemia; higher initial doses may be required in patients who are obese, sedentary, or presenting with ketoacidosis (AACE/ACE [Handelsman 2015]; ADA 2019).
Usual TDD maintenance range: 0.4 to 1 units/kg/day in divided doses (ADA 2019)
Division of TDD (multiple daily injections):
Basal insulin: Generally, 40% to 50% of the TDD is given as basal insulin (intermediate- or long-acting) in 1 to 2 daily injections (AACE/ACE [Handelsman 2015]; ADA 2019).
Prandial insulin: The remaining portion (ie, 50% to 60%) of the TDD is then divided and administered before or at mealtimes (depending on the formulation) as a rapid-acting (eg, lispro, aspart, glulisine, insulin for inhalation) or short-acting (regular) insulin (AACE/ACE [Handelsman 2015]; ADA 2019).
Dosage adjustment: Dosage must be titrated to achieve glucose control and avoid hypoglycemia. Adjust dose to maintain premeal and bedtime glucose in target range. 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.
Diabetes mellitus, type 2 (AACE/ACE [Garber 2019]); ADA 2019): SubQ:
Initial: 4 to 5 units or 10% of the basal insulin dose administered before the largest meal of the day.
Note: Stepwise addition of prandial insulin starting with a single meal and progressing to 2 or more meals as needed every 3 months is associated with a lower risk of hypoglycemia and increased patient satisfaction compared with immediate introduction of a full basal-bolus regimen. Insulin lispro is usually given in addition to a regimen that includes basal insulin (ie, a long-acting insulin such as glargine, degludec, or detemir; or an intermediate-acting insulin such as NPH) and metformin +/- other noninsulin agents. Consider reducing the total daily dose by 4 units or 10% of the basal insulin dose if HbA1c is <8% when initiating prandial insulin.
Dosage adjustment:
To reach self-monitoring glucose target: Adjust dose by 10% to 15% or 1 to 2 units twice weekly.
For hypoglycemia: If no clear reason for hypoglycemia, decrease dose by 10% to 20%; for severe hypoglycemia (ie, requiring assistance from another person or blood glucose <40 mg/dL), reduce dose by 20% to 40%.
HbA1c 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 agents.
Patients with diabetes receiving enteral feedings (ADA 2019): Note: TDD of insulin is divided into a basal component (intermediate- or long-acting insulin) and nutritional and correctional components (regular insulin or rapid-acting insulins).
Nutritional/correctional component: SubQ: 1 unit of insulin lispro per 10 to 15 g of carbohydrate plus correctional insulin lispro (as needed for hyperglycemia) administered every 4 hours or prior to each bolus feeding.
Patients with diabetes undergoing surgery and using CSII pump (ADA 2019): On the morning of surgery or procedure, give 60% to 80% of the usual dose of pump "basal" insulin (rapid- or short-acting insulins) dose.
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.
Dosing: Geriatric
Refer to adult dosing.
Dosing: Pediatric
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 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.
General insulin dosing:
Type 1 diabetes mellitus: 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: 0.2-0.6 units/kg/day in divided doses. Conservative initial doses of 0.2-0.4 units/kg/day are often recommended to avoid the potential for hypoglycemia. Regular insulin may be the only insulin formulation used initially.
Usual maintenance range: SubQ: 0.5-1 unit/kg/day in divided doses. An estimate of anticipated needs may be based on body weight and/or activity factors as follows:
Nonobese: 0.4-0.6 units/kg/day
Obese: 0.8-1.2 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)
Adjustment of dose: Dosage must be titrated to achieve glucose control and avoid hypoglycemia. Adjust dose to maintain premeal and bedtime glucose in target range. 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.
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 premeal regular insulin dosage may be used.
Reconstitution
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.
Administration
Use only if solution is clear and colorless; do not use if solution contains particulate matter or is colored.
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 or localized cutaneous amyloidosis. Rotating from an injection site where lipodystrophy/cutaneous amyloidosis is present to an unaffected site may increase risk of hypoglycemia.
Admelog: Do not mix with any other insulin. For Admelog SoloStar pen, prime the needle before each injection with 2 units of insulin. Once injected, hold the SoloStar device in the skin for a count of 10 after the dose dial has returned to 0 units before removing the needle to ensure the full dose has been administered.
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. Prefilled pen devices are designed to dial doses in 1-unit increments (U-100 KwikPen, U-100 Tempo Pen, U-200 KwikPen) or in 0.5-unit increments (U-100 Junior KwikPen). Do not perform dose conversion when using Humalog prefilled pen devices; the dose window shows the number of units to be delivered and no conversion is needed. Do not transfer insulin lispro U-200 to a syringe for administration. For Humalog prefilled pen devices, prime the needle before each injection with 2 units of insulin. Once injected, hold the device in the skin for a count of 5 after the dose dial has returned to 0 units before removing the needle to ensure the full dose has been administered.
Continuous subcutaneous insulin infusion administration: Only administer insulin lispro U-100 (eg, 100 units/mL) via continuous subcutaneous insulin infusion (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 or according to CSII device user manual (whichever is shorter). Do not dilute or mix other insulins with insulin lispro U-100 that is to be used in an external insulin pump.
IV administration: Insulin lispro U-100 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).
Dietary Considerations
Individualized medical nutrition therapy (MNT) based on ADA recommendations is an integral part of therapy.
Storage
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.
Drug Interactions
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
Direct Acting Antiviral Agents (HCV): May enhance the hypoglycemic effect of Antidiabetic Agents. Monitor therapy
Edetate CALCIUM 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. 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
Maitake: May enhance the hypoglycemic effect of Blood Glucose Lowering Agents. Monitor therapy
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 (SGLT2) 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
Adverse Reactions
>10%:
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
Warnings/Precautions
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.
Disease-related concerns:
- Bariatric surgery:
– Type 2 diabetes, hypoglycemia: Closely monitor insulin dose requirement throughout active weight loss with a goal of eliminating antidiabetic therapy or transitioning to agents without hypoglycemic potential; hypoglycemia after gastric bypass, sleeve gastrectomy, and gastric band may occur (Mechanick 2013). Insulin secretion and sensitivity may be partially or completely restored after these procedures (Korner 2009; Peterli 2012). Rates and timing of type 2 diabetes improvement and resolution vary widely by patient. Insulin dose reduction of ≥75% has been suggested after gastric bypass for patients without severe β-cell failure (fasting c-peptide <0.3 nmol/L) (Cruijsen 2014). Avoid the use of bolus insulin injections or dose conservatively with close clinical monitoring in the early phases after surgery.
– Weight gain: Evaluate risk versus benefit and consider alternative therapy after gastric bypass, sleeve gastrectomy, and gastric banding; weight gain may occur (Apovian 2015).
- Cardiac disease: Concurrent use with peroxisome proliferator-activated receptor (PPAR)-gamma agonists, including thiazolidinediones (TZDs), may cause dose-related fluid retention and lead to or exacerbate heart failure, particularly when used in combination with insulin. If PPAR-gamma agonists are prescribed, monitor for signs and symptoms of heart failure. If heart failure develops, consider PPAR-gamma agonist dosage reduction or therapy discontinuation.
- 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.
Special populations:
- 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 2019).
Dosage form specific issues:
- Humalog prefilled pen devices: Do not perform dose conversion when using prefilled pen devices; the dose window shows the number of units to be delivered and no conversion is needed.
- Humalog U-200 (200 units/mL) prefilled pen: Do not transfer product from the prefilled pen 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).
Other warnings/precautions:
- 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.
Monitoring Parameters
Diabetes mellitus: Plasma glucose (typically before meals and snacks and at bedtime; occasionally additional monitoring may be required), 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 2019]); renal function, hepatic function, weight.
Gestational diabetes mellitus: Blood glucose 4 times daily (1 fasting and 3 postprandial) until well controlled, then as appropriate (ACOG 190 2018).
IV administration: Close monitoring of blood glucose and serum potassium
Pregnancy
Pregnancy Considerations
Insulin lispro has not been shown to cross the placenta at standard clinical doses (Boskovic 2003; Holcberg 2004; Jovanovic 1999).
Poorly controlled diabetes during pregnancy can be associated with an increased risk of adverse maternal and fetal outcomes, including diabetic ketoacidosis, preeclampsia, spontaneous abortion, preterm delivery, delivery complications, major birth defects, stillbirth, and macrosomia (ACOG 201 2018). 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 2020; Blumer 2013).
Due to pregnancy-induced physiologic changes, insulin requirements tend to increase as pregnancy progresses, requiring frequent monitoring and dosage adjustments. Following delivery, insulin requirements decrease rapidly (ACOG 201 2018; ADA 2020).
Insulin is the preferred treatment of type 1 and type 2 diabetes mellitus in pregnancy, as well as gestational diabetes mellitus when pharmacologic therapy is needed (ACOG 190 2018; ACOG 201 2018; ADA 2020). Insulin lispro is one of the preferred insulins for use in pregnancy (ACOG 190 2018; ACOG 201 2018; Blumer 2013).
Females with diabetes mellitus who wish to conceive should use adequate contraception until glycemic control is achieved (ADA 2020). Insulin lispro is one of the preferred insulins for use in females with diabetes mellitus planning a pregnancy (Blumer 2013).
Patient Education
What is this drug used for?
- It is used to lower blood sugar in patients with high blood sugar (diabetes).
Frequently reported side effects of this drug:
- Flu-like signs
- Nose irritation
- Throat irritation
- Headache
- Cough
- Nausea
- Abdominal pain
- Diarrhea
- Loss of strength and energy
- Injection site irritation
Other side effects of this drug: Talk with your doctor right away if you have any of these signs of:
- Low blood sugar like dizziness, headache, fatigue, feeling weak, shaking, fast heartbeat, confusion, increased hunger, or sweating.
- Low potassium like muscle pain or weakness, muscle cramps, or an abnormal heartbeat
- Infection
- Vision changes
- Chills
- Severe dizziness
- Passing out
- Mood changes
- Seizures
- Slurred speech
- Shortness of breath
- Excessive weight gain
- Swelling of arms or legs
- Injection site thick skin, pits, or lumps
- Signs of a significant reaction like 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. Talk to your doctor if you have questions.
Consumer Information Use and Disclaimer: This information should not be used to decide whether or not to take this medicine or any other medicine. Only the healthcare provider has the knowledge and training to decide which medicines are right for a specific patient. This information does not endorse any medicine as safe, effective, or approved for treating any patient or health condition. This is only a brief summary of general information about this medicine. It does NOT include all information about the possible uses, directions, warnings, precautions, interactions, adverse effects, or risks that may apply to this medicine. This information is not specific medical advice and does not replace information you receive from the healthcare provider. You must talk with the healthcare provider for complete information about the risks and benefits of using this medicine.
