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Insulin Lispro


General


Pronunciation

(IN soo lin LYE sproe)


Brand Names: U.S.

  • HumaLOG
  • HumaLOG KwikPen

Indications


Use: Labeled Indications

Diabetes mellitus: Treatment of type 1 diabetes mellitus (insulin dependent, IDDM) and type 2 diabetes mellitus (noninsulin dependent, NIDDM) to improve glycemic control

According to the manufacturer 's labeling, only the U 100 (eg, 100 units/mL) strength is approved for use in children ≥3 years by continuous subcutaneous insulin infusion (CSII) pumps.


Contraindications


Hypersensitivity to insulin lispro or any component of the formulation; during episodes of hypoglycemia


Dosing and Administration


Dosing: Adult

Diabetes mellitus: 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. Insulin requirements vary dramatically between patients and dictate frequent monitoring and close medical supervision.

Diabetes mellitus, type 1: SubQ:

General insulin dosing:

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. A rapid-acting insulin may be the only insulin formulation used initially.

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

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).

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, insulin aspart) or short-acting form of insulin. Some patients may benefit from the use of CSII which delivers rapid-acting insulin (insulin aspart) 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- or rapid-acting insulin (eg, insulin aspart) formulations 3 or more times daily.

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. 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 premeal regular insulin dosage may be used.

Diabetes mellitus, type 2: SubQ:

General considerations for insulin use in type 2 diabetes:

Timing of initiation: The goal of therapy is to achieve an HbA1c <7%. According to a position statement by the ADA and European Association for the Study of Diabetes (EASD), dual therapy (metformin + a second antihyperglycemic agent) is recommended in patients with type 2 diabetes who fail to achieve glycemic goals after ~3 months with lifestyle interventions and metformin monotherapy (unless contraindications to metformin exist). Preference is not given for adding insulin or a noninsulin agent as the second antihyperglycemic agent (drug choice should be individualized based on patient characteristics). However, insulin should be considered as part of a combination regimen when hyperglycemia is severe, particularly if patient is symptomatic or has catabolic features (eg, weight loss, ketosis). If insulin is selected, the addition of basal insulin (ie, a long-acting insulin such as glargine or detemir [not insulin lispro]) is recommended. If HbA1c target not achieved after ~3 months of dual therapy, may proceed to triple therapy (Inzucchi, 2015).

Intensification of therapy: If HbA1c target has not been met, despite titrating basal insulin (ie, long-acting insulin) to provide acceptable fasting blood glucose concentrations, intensification of therapy should be considered to cover postprandial glucose excursions. Options include adding a GLP-1 receptor agonist (eg, exenatide, liraglutide) or adding a mealtime insulin (1 injection of a rapid-acting insulin analog [lispro, aspart, glulisine]) initiated at a dose of 4 units or 0.1 units/kg or 10% basal dose before largest meal; may progress to "basal-bolus " � dosing of 3 injections of a rapid-acting insulin analog [lispro, aspart, glulisine] per meal or dose by adding up the total current insulin dose, and provide one-half of this amount as basal and one-half as mealtime insulin (split evenly between 3 meals). Alternatively, although less studied, may transition from basal insulin (ie, long-acting insulin) to a twice daily premixed (or biphasic) insulin analog (70/30 aspart mix, 75/25 or 50/50 lispro mix) (Inzucchi, 2015).


Dosing: Geriatric

Refer to adult dosing.


Dosing: Pediatric

Diabetes mellitus, type 1: Children ≥3 years and Adolescents: Refer to adult dosing.

Diabetic ketoacidosis (DKA), mild-to-moderate (off-label use): Children and Adolescents: Treatment should continue until reversal of acid-base derangement/ketonemia. Serum glucose is not a direct indicator of these abnormalities, and may decrease more rapidly than correction of the metabolic abnormalities. Also refer to institution-specific protocols where appropriate.

SubQ (Note: Use of IV regular insulin is preferred; only use the SubQ route if IV infusion access is unavailable): 0.3 units/kg followed in 1 hour by 0.1 units/kg given every hour or 0.15-0.2 units/kg every 2 hours; continue until acidosis clears, then decrease to 0.05 units/kg given every hour until maintenance SubQ replacement dosing can be initiated (Kitabchi, 2004; Wolfsdorf, 2007).


Dosing: Renal Impairment

Adults: Insulin requirements are reduced due to changes in insulin clearance or metabolism. There are no dosage adjustments provided in the manufacturer 's labeling; however, the following adjustments have been recommended (Aronoff, 2007):

CrCl >50 mL/minute: No adjustment necessary

CrCl 10-50 mL/minute: Administer at 75% of recommended dose

CrCl <10 mL/minute: Administer at 50% of recommended dose and monitor glucose closely

Hemodialysis: Because of a large molecular weight (6000 daltons), insulin is not significantly removed by either peritoneal or hemodialysis; supplemental dose is not necessary

Peritoneal dialysis: Supplemental dose is not necessary

Continuous renal replacement therapy: Administer at 75% of recommended dose


Dosing: Hepatic Impairment

There are no dosage adjustments provided in the manufacturer 's labeling; dosage requirements may be reduced and patients may require more frequent dose adjustment and glucose monitoring.


Reconstitution

For SubQ administration: Humalog vials: May be diluted with the universal diluent, Sterile Diluent for Humalog U 100, Humulin N, Humulin R, Humulin 70/30, and Humulin R U-500, to a concentration of 10 units/mL (U-10) or 50 units/mL (U-50). Do not dilute insulin contained in a cartridge, prefilled pen, or external insulin pump.

For IV infusion: Humalog U 100 may be diluted in NS to concentrations of 0.1 to 1 units/mL.


Administration

SubQ administration: Do not use if solution is viscous or cloudy; use only if clear and colorless. 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. Do not mix insulin lispro U 200 with any other insulin. May mix insulin lispro U 100 (eg, 100 units/mL) only with insulin NPH; insulin lispro should be drawn into syringe first; perform injection immediately. Do not dilute or mix other insulins with insulin lispro contained in a cartridge or prefilled pen. 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.

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. Do not use if solution is viscous or cloudy; use only if clear and colorless. 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 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: Do not use if solution is viscous or cloudy; use only if clear and colorless. 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 solution bag: Note: Refer to institution-specific protocols where appropriate.

If new tubing is not needed: Wait a minimum of 30 minutes between the preparation of the solution and the initiation of the infusion. Wait a minimum of 30 minutes between the preparation of the solution and the initiation of the infusion.

If new tubing is needed: After receiving the insulin drip solution, the administration set should be attached to the IV container and the entire line should be flushed with a priming infusion of 20 to 50 mL of the insulin solution (Goldberg, 2006; Hirsch, 2006). Wait 30 minutes, and then flush the line again with the insulin solution prior to initiating the infusion.

Because of adsorption, 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. In addition, SubQ insulin should be given 1 to 4 hours prior to the discontinuation of IV insulin to prevent hyperglycemia (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 sunlight. 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 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).

For SubQ administration: Humalog vials: According to the manufacturer, diluted insulin lispro should be stored at 30 � �C (86 � �F) and used within 14 days or 5 � �C (41 � �F) and used within 28 days.

For IV infusion: 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.


Dosage Forms/Strengths


Dosage Forms

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Solution, Subcutaneous:

HumaLOG: 100 units/mL (3 mL, 10 mL) [contains metacresol, phenol]

Solution Pen-injector, Subcutaneous:

HumaLOG KwikPen: 100 units/mL (3 mL); 200 units/mL (3 mL) [contains metacresol, phenol]


Compatibility

Stable in D5W, D10W and NS. Note: A universal sterile diluent, Sterile Diluent for Humalog U 100, Humulin N, Humulin R, Humulin 70/30, and Humulin R U-500, is available from the manufacturer for SubQ administration.

Compatibility in syringe: Incompatible with insulin aspart, insulin detemir, insulin glargine, insulin glulisine, insulin lispro, insulin regular.


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 Insulin. Exceptions: Levobunolol; Metipranolol. Monitor therapy

DPP-IV Inhibitors: May enhance the hypoglycemic effect of Insulin. 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 Insulin. Monitor therapy

Edetate Disodium: May enhance the hypoglycemic effect of Insulin. Monitor therapy

GLP-1 Agonists: May enhance the hypoglycemic effect of Insulin. 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

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 Insulin. 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

MAO Inhibitors: May enhance the hypoglycemic effect of Blood Glucose Lowering Agents. Monitor therapy

Metreleptin: May enhance the hypoglycemic effect of Insulin. 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

Pegvisomant: May enhance the hypoglycemic effect of Blood Glucose Lowering Agents. Monitor therapy

Pioglitazone: May enhance the adverse/toxic effect of Insulin. 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 Insulin. 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

Quinolone Antibiotics: May enhance the hypoglycemic effect of Blood Glucose Lowering Agents. Quinolone Antibiotics 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

Rosiglitazone: Insulin 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

SGLT2 Inhibitors: May enhance the hypoglycemic effect of Insulin. 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


Monitoring Parameters

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 2016a])

IV administration: Close monitoring of blood glucose and serum potassium


Adverse Reactions


Frequency not always defined.

Cardiovascular: Peripheral edema

Central nervous system: Headache (type 1 diabetes: 30%; type 2 diabetes: 12%), pain (11% to 20%)

Endocrine & metabolic: Hypoglycemia, hypokalemia, weight gain

Gastrointestinal: Diarrhea (type 1 diabetes: 9%), nausea (type 1 diabetes: 6%)

Genitourinary: Urinary tract infection (type 1 diabetes: 6%)

Hypersensitivity: Hypersensitivity reaction

Immunologic: Antibody development

Infection: Infection (10% to 14%)

Local: Hypertrophy at injection site, injection site reaction, lipoatrophy at injection site

Neuromuscular & skeletal: Myalgia (type 1 diabetes: 7%; most likely secondary to excipient metacresol)

Respiratory: Flu-like symptoms (type 1 diabetes: 35%; type 2 diabetes: 6%), pharyngitis (type 1 diabetes: 33%; type 2 diabetes: 7%), rhinitis (type 1 diabetes: 25%; type 2 diabetes: 8%)


Warnings/Precautions


Special Populations: Renal Function Impairment

Insulin clearance may be reduced in patients with impaired renal function.


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:

- 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.

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 Centers for Disease Control and Prevention (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:

- 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: 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. Only insulin lispro U 100 (eg, 100 units/mL) is approved for use in children ≥3 years by CSII pump.

- 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.


Pregnancy Risk Factor

B


Pregnancy Considerations

Adverse events have not been observed in animal reproduction studies. 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 2016d; Kitzmiller 2008; 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 (ACOG 2013; ADA 2016d; Blumer 2013; Kitzmiller 2008; Lambert 2013). Prior to pregnancy, effective contraception should be used until glycemic control is achieved (ADA 2016d; Kitzmiller 2008)

Insulin requirements tend to fall during the first trimester of pregnancy and increase in the later trimesters, peaking at 28 to 32 weeks of gestation. Following delivery, insulin requirements decrease rapidly (ACOG 2005). Insulin lispro may be used to treat diabetes in pregnant women (ACOG 2013; Blumer 2013; Kitzmiller 2008; Lambert 2013)


Actions


Pharmacology

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.


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


Patient and Family Education


Patient Education

- 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.

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