Humalog: Uses, Side Effects & Dosage | Healio

For education only

This guide cannot diagnose a condition or recommend a personal treatment plan. Discuss medical questions with a qualified professional.

Topics

Humalog

Brand Names

Humalog Mix

Generic Name

insulin lispro

Phonetic Name

(IN-sue-lin LISS-pro PRO-tah-meen(NPL)/IN-sue-lin LISS-pro)

Clinical Uses

Insulin lispro protamine/insulin lispro is used along with a proper diet and exercise program to control high blood sugar in people with diabetes. This product is a combination of two man-made insulins: intermediate-acting insulin lispro protamine and rapid-acting insulin lispro. This combination starts working faster and lasts for a longer time than regular insulin. Insulin is a natural substance that allows the body to properly use sugar from the diet. It replaces the insulin that your body no longer produces, thereby lowering your blood sugar. Controlling high blood sugar helps prevent kidney damage, blindness, nerve problems, loss of limbs, and sexual function problems. Proper control of diabetes may also lessen your risk of a heart attack or stroke.

Dosage and Administration

Administration Notes

Read the Patient Information Leaflet and Instructions for Use if available from your pharmacist before you start using this medication and each time you get a refill. Ask your health care professional how to prepare and use this medication. If you have any questions, ask your doctor or pharmacist. Inject this medication under the skin as directed by your doctor, usually twice daily (15 minutes or less before the morning and evening meal). Because this product contains a short-acting insulin, not eating right after a dose of this insulin may lead to low blood sugar (hypoglycemia). The injection is given in the stomach area, the thigh, or the back of the upper arm. Do not inject into a vein or muscle because very low blood sugar may occur. The dosage is based on your medical condition and response to treatment. Measure each dose very carefully because even small changes in the amount of insulin may have a large effect on your blood sugar. Before using, gently roll and turn the product between your palms at least 10 times. Then, turn it upside down and right side up 10 times to mix the medication. Do not shake the container. Check this product for particles or discoloration. If either is present, do not use the insulin. This product should look evenly cloudy/milky after mixing. Do not use if you see clumps of white material, a "frosty" appearance, or particles stuck to the sides of the product. Before injecting each dose, clean the skin you are going to inject into (the injection site) with rubbing alcohol. Change the injection site each time to lessen injury under the skin (for example, pits/lumps or thickened skin). Do not inject into skin that is red, swollen, itchy, or damaged. To lessen bruising, do not rub the injection site after a shot. Do not inject cold insulin because this can be painful. The insulin container you are currently using can be kept at room temperature. Learn how to store and discard medical supplies safely. Do not mix this product with other insulins or use it in an insulin pump. Do not change brands or types of insulin without directions on how to do so from your doctor. Do not share your pen device with another person, even if the needle is changed. You may give other people a serious infection, or get a serious infection from them. Use this medication regularly to get the most benefit from it. To help you remember, use it at the same times each day. Tell your doctor if your condition does not get better or if it gets worse (your blood sugar is too high or too low).

Missed Dose Instructions

It is very important to follow your insulin regimen exactly. Ask your doctor ahead of time what you should do if you miss a dose of insulin.

Label Warnings

Refrigerate unopened product. May store at room temperature after opening for use. Bottles in use or stored at room temperature should be discarded after 28 days. If you drink alcohol, discuss the safe use of alcohol while using this medication with your healthcare professional. Roll gently in your hands to mix well before each injection. Injection of cold insulin can be uncomfortable. The insulin container you are currently using may be kept at room temperature. DO NOT dilute or mix this insulin with any other insulin or solution. It is very important that you take or use this exactly as directed. Do not skip doses or discontinue unless directed by your doctor.

Indications

diabetes mellitus

type 1 diabetes mellitus
type 2 diabetes mellitus

gestational diabetes mellitus

Contraindications

hypoglycemic disorder

disease of liver
hypokalemia
kidney disease with reduction in glomerular filtration rate (GFR)

Common Adverse Effects

Cough
Edema
Flu-like symptoms
Headache disorder
Injection site sequelae
Lipodystrophy
Pain
Pharyngitis
Pruritus of skin
Rhinitis
Skin rash
Weight gain

Fever
Nausea
Peripheral edema

Serious Adverse Effects

Hypoglycemic disorder

Infection

Anaphylaxis
Dyspnea
Hypersensitivity drug reaction
Hypokalemia
Localized cutaneous amyloidosis
Wheezing

Elderly Precautions

Pregnancy Precautions

Lactation Precautions

SeverityNarrativeNo Known RiskDATA SUGGEST EXCRETION INTO BREASTMILK; NO ADV EFFECTS IN INFANTS REPORTED

Pediatric Precautions

SeverityNarrativeManagement or Monitoring PrecautionNot studied in pediatrics age < 1 year.

Drug Interactions

Drug interactions may change how your medications work or increase your risk for serious side effects. This document does not contain all possible drug interactions. Keep a list of all the products you use (including prescription/nonprescription drugs and herbal products) and share it with your doctor and pharmacist. Do not start, stop, or change the dosage of any medicines without your doctor's approval. Beta-blocker medications (such as metoprolol, propranolol, glaucoma eye drops such as timolol) may prevent the fast/pounding heartbeat you would usually feel when your blood sugar falls too low (hypoglycemia). Other symptoms of low blood sugar such as dizziness, hunger, or sweating are unaffected by these drugs. Many drugs can affect your blood sugar, making it harder to control. Before you start, stop, or change any medication, talk with your doctor or pharmacist about how the medication may affect your blood sugar. Check your blood sugar regularly as directed and share the results with your doctor. Tell your doctor right away if you have symptoms of high or low blood sugar. (See also Side Effects section.) Your doctor may need to adjust your diabetes medication, exercise program, or diet.

Drug Interactions Table

Toxicology

No evidence of mutagenicity or chromosomal damage with insulin lispro was observed in vivo in a micronucleus test or chromosome aberration test or in in vitro test systems, including microbial (bacterial mutation tests) and mammalian (mouse lymphoma) assays. There was no increase in DNA repair when insulin lispro was tested in an unscheduled DNA synthesis test. . In addition, no evidence of carcinogenicity was observed in a study in rats receiving up to 200 units/kg daily of insulin lispro subcutaneously for 12 months.

Chemical Properties

Insulin lispro is a biosynthetic human insulin analog that is structurally identical to insulin human except for reversal of the sequence of lysine and proline on the B chain of the molecule; in insulin lispro, lysine and proline occur at positions 28 and 29, respectively, of the B chain. The inversion of lysine and proline in the amino acid sequence eliminates hydrophobic interactions and weakens some of the hydrogen bonds that contribute to the stability of dimer subunits composing the hexameric form of insulin lispro. Endogenous insulin is stored in the pancreas as a stable, zinc-containing hexamer; stabilization of insulin lispro in the commercial formulation is accomplished by addition of zinc and m-cresol. The hexamers formed with zinc and insulin lispro are weak compared with those of human insulin and dissociate rapidly into monomers of the insulin analog that are absorbed through vascular endothelial cells. Consequently, insulin lispro has a more rapid onset of action than insulin human when given subcutaneously while retaining the conformation of critical sites necessary for binding to and activating the insulin receptor. Biosynthetic insulin lispro (Humalog(R)) is prepared using recombinant DNA technology and special laboratory strains of nonpathogenic E. coli. The E. coli bacteria have been genetically modified by the addition of plasmids that incorporate genes for the lispro form of human proinsulin. Commercially available biosynthetic insulin lispro injection consists of zinc insulin lispro crystals that are prepared by precipitating insulin lispro in the presence of zinc oxide and dissolving the crystals in water for injection, resulting in a clear aqueous solution. Each mL contains 100 USP units of biosynthetic insulin lispro solution and 19.7 mcg of zinc. Each mL of insulin lispro also contains dibasic sodium phosphate 1.88 mg, glycerin 16 mg, m-cresol 3.15 mg, and trace amounts of phenol. Sodium hydroxide and/or hydrochloric acid may be added during manufacture of biosynthetic insulin lispro zinc injection to adjust pH to 7-7.8. Insulin lispro also is commercially available in fixed combination with insulin lispro protamine (neutral protamine lispro (NPL)), an intermediate-acting insulin. Insulin lispro protamine is prepared by crystallizing insulin lispro with protamine sulfate to produce a suspension with similar pharmacokinetics as isophane (NPH) insulin human. Each mL of the fixed combination of insulin lispro and insulin lispro protamine suspension (Humalog(R) Mix75/25(R)) contains 100 USP units of insulin lispro, 25 mcg of zinc (as zinc oxide), and 0.28 mg of protamine sulfate. Each mL of Humalog(R) Mix75/25(R) also contains dibasic sodium phosphate 3.78 mg, glycerin 16 mg, cresol 1.76 mg, and phenol 0.715 mg. Sodium hydroxide and/or hydrochloric acid may be added during manufacture of Humalog(R) Mix75/25(R) or Humalog(R) Mix50/50(R) injection to adjust pH to 7-7.8. Each mL of Humalog(R) Mix50/50(R) contains 100 units of insulin lispro, 0.03 mg of zinc ion (as zinc oxide), and 0.19 mg of protamine sulfate. Each mL of Humalog(R) Mix50/50(R) also contains dibasic sodium phosphate 3.78 mg, glycerin 16 mg, m-cresol 2.2 mg, and phenol 0.89 mg.

Pharmacokinetics

Absorption: Insulin lispro is more rapidly absorbed than soluble preparations of insulin human or insulins of animal origin following subcutaneous administration because of its ability to dissociate faster from the insulin hexamer in solution. Absorption of other insulins (e.g., insulin human) from subcutaneous sites is delayed by the time required for dissociation of insulin hexamers into dimers and monomers that can diffuse into the systemic circulation. Therefore, insulin lispro has a faster onset and shorter duration of action than other insulins and, when administered subcutaneously 15 minutes before a meal, more closely mimics the endogenous postprandial insulin response. After subcutaneous administration of 0.1-0.4 units/kg of insulin lispro or insulin human in healthy individuals or patients with type 1 diabetes mellitus, peak plasma insulin concentrations are higher and occur earlier with insulin lispro (at 30-90 minutes) than with insulin human (at 50-120 minutes). Addition of zinc to the commercially available formulation of insulin lispro reduces peak serum concentrations somewhat compared with an insulin lispro formulation without zinc (not commercially available in the US) but does not appreciably alter the time to peak concentration. Unlike with insulin human, the time to peak serum concentration following subcutaneous administration of insulin lispro does not increase with increasing doses. Serum concentrations of insulin lispro also exhibit less intraindividual and interindividual variability than those of insulin human, possibly because of differences in the intrinsic properties of these insulins. The fixed combination of insulin lispro and insulin lispro protamine (Humalog(R) Mix75/25(R), Humalog(R) Mix50/50(R)) exhibits 2 phases of absorption. The early phase represents insulin lispro and its rapid onset of action; the late phase represents the prolonged action of insulin lispro protamine suspension. In a limited number of nondiabetic individuals, peak serum insulin concentrations were observed 30-240 minutes (median: 60 minutes) following subcutaneous administration of the fixed combination (0.3 units/kg) of insulin lispro and insulin lispro protamine (Humalog(R) Mix75/25(R)); results were identical in diabetic patients. In patients with type 1 diabetes mellitus, peak serum (immunoreactive) insulin concentrations were observed at 45-120 minutes (median: 60 minutes) following administration of the Humalog(R) Mix50/50(R) fixed combination. The fixed combinations of insulin lispro and insulin lispro protamine (Humalog(R) Mix75/25(R), Humalog(R) Mix50/50(R)) are absorbed more rapidly than the fixed combination of insulin human (regular) and isophane insulin human (Humulin(R) 70/30(R), Humulin(R) 50/50), including in patients with type 1 diabetes mellitus. The duration of action of Humalog(R) Mix75/25(R) and Humalog(R) Mix50/50(R) also is similar to that of Humulin(R) 70/30(R) and Humulin(R) 50/50(R). The pharmacokinetics and pharmacodynamics of insulin human and insulin lispro are similar following IV administration in healthy individuals; however, the safety and efficacy of IV insulin lispro have not been evaluated in clinical trials in patients with diabetes mellitus. Following single IV doses of 0.1-0.2 units/kg, the absolute bioavailabilities of insulin lispro and insulin human were similar, ranging from 55-77%. The onset of glycemic response following subcutaneous injection of insulin lispro in healthy individuals or in patients with type 1 or 2 diabetes mellitus generally ranges from 0.25-0.5 hours versus 0.5-1 hours for insulin human; peak glycemic response for insulin lispro or insulin human occurs at 0.5-2.5 or 1-5 hours, respectively. Following subcutaneous administration in these individuals or patients, the duration of hypoglycemic action of insulin lispro is 3-6.5 hours compared with 6-10 hours for insulin human. Many factors can affect the onset, degree, and duration of insulin activity, including injection technique, presence of insulin antibodies, site of injection, tissue blood supply, temperature, excipients in insulin formulations, and interindividual and intraindividual differences in response. After subcutaneous administration, onset of action of insulin lispro from abdominal, deltoid, and thigh sites is similar, and variations in absorption related to site of administration are smaller than those observed with regular insulin. However, the effects of age, obesity, gender, and type of diabetes mellitus on glycemic response do not appear to differ in patients receiving insulin lispro versus insulin human. Distribution: The volume of distribution of insulin lispro reportedly is identical to that of insulin human and ranges from 0.26-0.36 L/kg. Distribution of insulin lispro when given in the fixed-combination formulation containing protamine sulfate (Humalog(R) Mix75/25(R)) has not been determined. It is not known whether insulin lispro is distributed into human milk; however, other insulins (e.g., insulin human) are distributed into milk. In a study in a limited number of pregnant women with gestational diabetes, the drug did not appear to cross the placenta. Elimination: In healthy adults, the half-life of subcutaneously administered insulin lispro or insulin human is 1 or 1.5 hours, respectively, while systemic clearance of insulin lispro and insulin human is similar. Following IV administration, insulin lispro and insulin human reportedly exhibit identical dose-dependent elimination, with half-lives of 26 or 52 minutes at doses of 0.1 or 0.2 units/kg, respectively. The metabolic fate of insulin lispro alone or in fixed combination with insulin lispro protamine has not been determined in humans; however, in animals, metabolism of insulin lispro is identical to that of insulin human. Some studies with insulin human have shown increased circulating insulin concentrations in patients with renal or hepatic failure; information on the use of insulin lispro in such patients is limited. In a study in a limited number of patients with type 2 diabetes mellitus and various degrees of renal function, sensitivity to insulin lispro increased as renal function declined. (See Cautions: Precautions and Contraindications and see Dosage and Administration: Dosage in Renal and Hepatic Impairment.)

Pharmacology

Studies in animals, healthy adults, and patients with type 1 (insulin-dependent) diabetes mellitus indicate that insulin lispro has pharmacologic effects comparable to those of insulin human. The fixed combination of insulin lispro and insulin lispro protamine (Humalog(R) Mix75/25(R)) has glucose-lowering effects similar to those of the fixed combination of insulin human (regular) and isophane insulin human (Humulin(R) 70/30) on a unit-for-unit basis. The potency of insulin lispro, with respect to its efficacy for replacement therapy in patients with type 1 diabetes mellitus, is similar to that of insulin human. Short-term, in vitro receptor-binding studies demonstrate that insulin lispro and insulin human have similar affinity for insulin receptor binding sites. However, the number and affinity of insulin receptors on circulating monocytes in a limited number of patients with type 1 diabetes mellitus increased to levels similar to those in healthy individuals following 3 months of therapy with insulin lispro, while patients receiving insulin human (regular) had a decrease in insulin receptor affinity and binding capacity. It has been suggested that the improvement in insulin receptor status during prolonged therapy with insulin lispro may be related to its more physiologic pharmacokinetic profile relative to that of regular insulin. Insulin lispro and insulin human have similar short-term hypoglycemic effects when given IV. In patients with type 1 diabetes mellitus in whom hypoglycemia was induced experimentally, the counterregulatory hormone response to hypoglycemia was similar with insulin lispro and insulin human; similar counterregulatory hormone responses to ingestion of a meal have been reported in other studies. Limited data suggest that insulin lispro suppresses hepatic glucose production and promotes peripheral glucose utilization to a greater extent than does insulin human when the drugs are given subcutaneously. In patients with type 1 diabetes mellitus who received insulin lispro or insulin human (regular) by continuous subcutaneous infusion for 3 months, glycosylated hemoglobin (hemoglobin A1c (HbA1c)) values and postprandial blood glucose concentrations were lower with insulin lispro therapy; however, timing of insulin human administration was not optimized since both insulin human and insulin lispro were administered within 5 minutes before meals. (See Insulin Regimens, under Dosage and Administration: Dosage in the Insulins General Statement 68:20.08.) The incidence of hypoglycemic episodes was lower than baseline levels and similar for both drugs. For further information on the pharmacology of insulin, see the Insulins General Statement 68:20.08.

Stability Information

Insulin lispro injection should be dispensed in the original, unopened, multiple-dose vial, disposable injection pen, or injection cartridge supplied by the manufacturer. When stored as directed, the vials and cartridges have an expiration date of not later than 2 years after the date of manufacture. Unopened vials or disposable injection pens of insulin lispro alone or in fixed combination with insulin lispro protamine or cartridges of the drug that have not been placed in a delivery device should be stored at 2-8degreesC and should not be subjected to freezing; the drug vial or cartridge should be discarded if it is frozen. Vials or cartridges of insulin lispro that cannot be refrigerated or vials and disposable injection pens that are in use may be stored at room temperature not exceeding 30degreesC for up to 28 days; exposure to extremes in temperature or direct sunlight should be avoided. Disposable injection pens of insulin lispro in fixed combination with insulin lispro protamine (Humalog(R) Mix75/25(R) Pen, Humalog(R) Mix50/50(R) Pen) that are in use may be stored at room temperature (below 30degreesC) for up to 10 days; exposure to extremely hot temperatures or direct light should be avoided. The manufacturer states that, once assembled by placement in the injectable pen (Owen Mumford Autopen(R)), insulin lispro cartridges and the injection device should be stored at room temperature and should not be refrigerated nor exposed to extremely hot temperatures or direct sunlight. Any unused insulin lispro in unrefrigerated vials, disposable injection pens, or cartridges should be discarded after 28 days. With the fixed combination of insulin lispro and insulin lispro protamine in disposable injection pens (Humalog(R) Mix75/25(R) Pen, Humalog(R) Mix50/50(R) Pen) or in vials, any unused portion should be discarded after 10 or 28 days, respectively. When insulin lispro is diluted with the sterile diluent supplied by the manufacturer for improved accuracy in preparing pediatric dosages (see Dosage and Administration: Administration), the diluted solution should be discarded after 28 days when stored at 5degreesC or after 14 days when stored at 30degreesC. Insulin lispro injection should be inspected visually prior to administration whenever the solution and the container permit. If the solution exhibits discoloration, turbidity, or unusual viscosity, the vial or cartridge should be discarded, since these changes indicate deterioration or contamination. Insulin lispro in fixed combination with insulin lispro protamine should be not be used if resuspension cannot be achieved (suspension should appear uniformly cloudy). (See Dosage and Administration: Administration.)Patients observing unexplained increases in blood glucose concentrations during insulin therapy should be particularly vigilant for any indications of loss of insulin potency and should contact a clinician if insulin requirements change markedly. The compatibility of insulin lispro injection with other drugs depends on several factors (e.g., pH of the injection, concentration of the drugs, specific diluents used, temperature, resulting pH); specialized references should be consulted for specific compatibility information. For convenience, insulin lispro has been administered with a longer-acting insulin (e.g., isophane (NPH) insulin human) in the same syringe. Mixing of insulin lispro with other insulins may be associated with physicochemical changes that could alter the physiologic response to the insulins. When insulin lispro (Humalog(R)) was mixed with isophane (NPH) insulin human (Humulin N(R)), binding of insulin lispro with stabilizers/excipients (e.g., zinc, protamine) in the NPH insulin decreased the absorption rate and the peak concentration, but not the total bioavailability, of insulin lispro. (See Dosage and Administration: Administration.) Mixtures of insulin lispro and a longer-acting insulin (e.g., NPH insulin human should be given within 5 minutes after mixing; insulin mixtures should not be given IV. The manufacturer states that the effect of mixing Humalog(R) with insulins of animal origin (no longer commercially available in the US) or human insulins produced by other manufacturers has not been studied. Whenever insulin lispro is mixed with a longer-acting insulin preparation, insulin lispro should be drawn into the syringe first in order to prevent precipitation or turbidity of the insulin lispro solution by the longer-acting insulin. When insulin lispro is administered via an external subcutaneous controlled-infusion device (pump), the drug should not be diluted or mixed with any other insulin. Insulin lispro in the external infusion device should not be exposed to temperatures exceeding 37degreesC during administration. Infusions sets (reservoir syringe, tubing, and catheter), the Disetronic(R) D-TRON(R) or Disetronic(R) D-TRON(R)plus cartridge adapter, and insulin lispro in the pump reservoir should be replaced and a new infusion site selected at least every 48 hours. The 3-mL cartridges used in the Disetronic(R) D-TRON(R) or Disetronic(R) D-TRON(R)plus insulin pumps should be discarded after 7 days, even if some drug remains in the reservoir. Simulated administration of insulin lispro by continuous subcutaneous infusion in several external infusion pump systems (i.e., Disetronic H-Tron, MiniMed Model 504 pumps) revealed no changes in the potency, purity, or physical stability of insulin lispro when stored within each of these devices for 48 hours. However, precipitation of insulin lispro on infusion catheters (i.e., Silhouette, Soft-Set catheters) has been noted in several patients who were receiving insulin lispro via one of several external pump systems (i.e., Disetronic H-Tron V-100, MiniMed 507C pumps).

Storage Requirements

Store all unopened insulin containers in the refrigerator. Do not freeze, and do not use insulin that has been frozen. If you are using the vials, store open vials in the refrigerator or at room temperature away from direct heat and light. Store in the carton to protect from light. Do not refrigerate cartridges or pens that are currently in use. Discard cartridges and vials in use after 28 days, and pens in use after 10 days, even if there is insulin left. Do not store in the bathroom. Keep all medications away from children and pets. Do not flush medications down the toilet or pour them into a drain unless instructed to do so. Properly discard this product when it is expired or no longer needed. Consult your pharmacist or local waste disposal company.

Ask a clinical question and tap into Healio AI's knowledge base.

PubMed, enrolling/recruiting trials, guidelines
Clinical Guidance, Healio CME, FDA news
Healio's exclusive daily news coverage of clinical data

Selected from data included with permission and copyrighted by FDB, Inc. This copyrighted material has been downloaded from a licensed data provider and is not for distribution in professional health care settings.

CONDITIONS OF USE: The information in this database is intended to supplement, not substitute for, the expertise and judgment of your healthcare professional. The information is not intended to cover all possible uses, directions, precautions, drug interactions or adverse effects, nor should it be construed to indicate that use of a particular drug is safe, appropriate or effective for you. You should consult your healthcare professional before taking any drug, changing your diet or commencing or discontinuing any course of treatment. See our full terms of use.

This information is generalized and not intended as specific medical advice. Consult your healthcare professional before taking any drug or commencing or discontinuing any course of treatment.