New Release: Alpha testing version has been released.

insulin lispro

A10A - Insulins and analogues ATC A10AB04 Protein approved 1996 Parenteral

JFDA label: HUMALOG Vial

Mechanism of Action

Agonist of Insulin receptor — Insulin receptor agonist

TargetActionGene / class
Insulin receptor efficacy AGONIST INSR

Indications

Approved

  • Diabetes mellitus, types 1 and 2

Off-label

  • Diabetic ketoacidosis (mild-to-moderate)
  • Gestational diabetes mellitus
  • Mild-to-moderate hyperosmolar hyperglycemic state (HHS)

Contraindications

Source: Lexicomp

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

Adverse Reactions

Very Common >10%Common 1–10%Uncommon 0.1–1% Rare 0.01–0.1%Very Rare <0.01%Not Known

Cardiac disorders (1)

Not Known Peripheral edema

Immune system disorders (2)

Very Common Antibody development

Not Known Hypersensitivity reaction

Metabolism and nutrition disorders (4)

Very Common Severe hypoglycemia

Not Known Hypoglycemia · hypokalemia · weight gain

General disorders and administration site conditions (4)

Very Common Infusion site reaction

Not Known Hypertrophy at injection site · injection site reaction (including local reactions secondary to excipient metacresol) · lipoatrophy at injection site

Other (1)

Common Neuromuscular & skeletal: Myalgia

Dosing

Source: Lexicomp

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. Conti
(For additional information see "Insulin lispro: Pediatric drug information") 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.
Refer to adult dosing.
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.
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.

Warnings & Precautions

Source: Lexicomp

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. 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 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). 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

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.

Pregnancy & Lactation

Pregnancy

FDA category B

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 2017c; 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 2017c; Blumer 2013; Kitzmiller 2008; 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

Lactation

Both exogenous and endogenous insulin are present in breast milk (study not conducted with this preparation) (Whitmore 2012). Breastfeeding is encouraged for all women, including those with type 1, type 2, or GDM (ACOG 2005; ADA 2017c; Blumer 2013; Metzger 2007). A small snack (such as milk) before breastfeeding may help decrease the risk of hypoglycemia in women with pregestational diabetes (ACOG 2005; Reader 2004). All types of insulin may be used while breastfeeding (Metzger 2007). The manufa

Monitoring

Clinical pearlDiabetes 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

Chemistry & Properties

2D structure
CAS133107-64-9
PubChem CID16132438
SMILESCCC(C)C(C(=O)NC(C(C)C)C(=O)NC(CCC(=O)O)C(=O)NC(CCC(=O)N)C(=O)NC(CS)C(=O)NC(CS)C(=O)NC(C(C)O)C(=O)NC(CO)C(=O)NC(C(C)CC)C(=O)NC(CS)C(=O)NC(CO)C(=O)NC(CC(C)C)C(=O)NC(CC1=CC=C(C=C1)O)C(=O)NC(CCC(=O)N)C(=O)NC(CC(C)C)C(=O)NC(CCC(=O)O)C(=O)NC(CC(=O)N)C(=O)NC(CC2=CC=C(C=C2)O)C(=O)NC(CS)C(=O)NC(CC(=O)N)C(=O)O)NC(=O)CN.CC(C)CC(C(=O)NC(CC1=CC=C(C=C1)O)C(=O)NC(CC(C)C)C(=O)NC(C(C)C)C(=O)NC(CS)C(=O)NCC(=O)NC(CCC(=O)O)C(=O)NC(CCCNC(=N)N)C(=O)NCC(=O)NC(CC2=CC=CC=C2)C(=O)NC(CC3=CC=CC=C3)C(=O)NC(CC4=CC=C(C=C4)O)C(=O)NC(C(C)O)C(=O)NC(CCCCN)C(=O)N5CCCC5C(=O)NC(C(C)O)C(=O)O)NC(=O)C(C)NC(=O)C(CCC(=O)O)NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC6=CN=CN6)NC(=O)C(CO)NC(=O)CNC(=O)C(CS)NC(=O)C(CC(C)C)NC(=O)C(CC7=CN=CN7)NC(=O)C(CCC(=O)N)NC(=O)C(CC(=O)N)NC(=O)C(C(C)C)NC(=O)C(CC8=CC=CC=C8)N

Biology & Pharmacokinetics

Pharmacokinetics predicted

Bioavailability70.0%
Half-life3.553 h
Volume of distribution0.232 L/kg
Protein binding17.7%
BBB penetrantNo

Transporters

BCRP (Inhibitor)BSEP (Inhibitor)MRP1 (Inhibitor)OATP1B1 (Inhibitor)OATP1B3 (Inhibitor)P-gp (Inhibitor)P-gp (Substrate)

Drug–drug interactions (100+, DDInter)

Interacting drugSeverityManagement
Cinoxacin major
Ciprofloxacin major
Delafloxacin major
Enoxacin major
Gatifloxacin major
Gemifloxacin major
Grepafloxacin major
Levofloxacin major
Lomefloxacin major
Moxifloxacin major
Nalidixic acid major
Norfloxacin major
Ofloxacin major
Sparfloxacin major
Trovafloxacin major
Acebutolol moderate
Acetazolamide moderate
Acetohexamide moderate
Acetylsalicylic acid moderate
Albiglutide moderate
Alimemazine moderate
Aloe Vera Leaf moderate
Alogliptin moderate
Alpelisib moderate
Amprenavir moderate
Aripiprazole moderate
Asenapine moderate
Asparaginase Erwinia chrysanthemi moderate
Asparaginase Escherichia coli moderate
Atazanavir moderate
Atenolol moderate
Azilsartan medoxomil moderate
Benazepril moderate
Bendroflumethiazide moderate
Benzphetamine moderate
Benzthiazide moderate
Betamethasone moderate
Betaxolol moderate
Betaxolol (ophthalmic) moderate
Bexarotene moderate

Showing 40 of 100+.

Registered Products (4)

BrandForm / strengthPackAgentCitizen (JOD)
HUMALOG Vial Vial 100 IU/ml 10 ml THE ARAB DRUG STORE P.S.C 21.720
Humalog Cartridge 100iu/ml Cartridge 100 IU/ml 3 ml THE ARAB DRUG STORE P.S.C 27.410
Humalog Mix 25/ 100IU/ml Solution 25 %, 75 % 3 ml THE ARAB DRUG STORE P.S.C 27.410
Humalog Mix 50 Injection 100 IU/ml 3 ml THE ARAB DRUG STORE P.S.C 27.410