insulin lispro
JFDA label: HUMALOG Vial
Mechanism of Action
Agonist of Insulin receptor — Insulin receptor agonist
| Target | Action | Gene / 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
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
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
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 pearl | 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 |
|---|
Chemistry & Properties
| CAS | 133107-64-9 |
|---|---|
| PubChem CID | 16132438 |
SMILES
CCC(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)NBiology & Pharmacokinetics
Pharmacokinetics predicted
| Bioavailability | 70.0% |
|---|---|
| Half-life | 3.553 h |
| Volume of distribution | 0.232 L/kg |
| Protein binding | 17.7% |
| BBB penetrant | No |
Transporters
BCRP (Inhibitor)BSEP (Inhibitor)MRP1 (Inhibitor)OATP1B1 (Inhibitor)OATP1B3 (Inhibitor)P-gp (Inhibitor)P-gp (Substrate)
Drug–drug interactions (100+, DDInter)
| Interacting drug | Severity | Management |
|---|---|---|
| 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)
| Brand | Form / strength | Pack | Agent | Citizen (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 |