NDC 0002-8233 Insulin Lispro Protamine And Insulin Lispro Injectable Suspension Mix75/25 Kwikpen

Insulin Lispro

NDC Product Code 0002-8233

NDC CODE: 0002-8233

Proprietary Name: Insulin Lispro Protamine And Insulin Lispro Injectable Suspension Mix75/25 Kwikpen What is the Proprietary Name?
The proprietary name also known as the trade name is the name of the product chosen by the medication labeler for marketing purposes.

Non-Proprietary Name: Insulin Lispro What is the Non-Proprietary Name?
The non-proprietary name is sometimes called the generic name. The generic name usually includes the active ingredient(s) of the product.

Drug Use Information

Drug Use Information
The drug use information is a summary and does NOT have all possible information about this product. This information does not assure that this product is safe, effective, or appropriate. This information is not individual medical advice and does not substitute for the advice of a health care professional. Always ask a health care professional for complete information about this product and your specific health needs.

  • Insulin lispro is used with a proper diet and exercise program to control high blood sugar in people with diabetes. 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. Insulin lispro is a man-made product that is similar to human insulin. It replaces the insulin that your body would normally make. Insulin lispro starts working faster and lasts for a shorter time than regular insulin. It works by helping blood sugar (glucose) get into cells so your body can use it for energy. This medication is usually used with a medium- or long-acting insulin product. Insulin lispro may also be used with other oral diabetes medications (such as sulfonylureas like glyburide or glipizide).

NDC Code Structure

  • 0002 - Eli Lilly And Company
    • 0002-8233 - Insulin Lispro Protamine And Insulin Lispro Injectable Suspension

NDC 0002-8233-05

Package Description: 5 SYRINGE in 1 CARTON > 3 mL in 1 SYRINGE (0002-8233-01)

NDC Product Information

Insulin Lispro Protamine And Insulin Lispro Injectable Suspension Mix75/25 Kwikpen with NDC 0002-8233 is a a human prescription drug product labeled by Eli Lilly And Company. The generic name of Insulin Lispro Protamine And Insulin Lispro Injectable Suspension Mix75/25 Kwikpen is insulin lispro. The product's dosage form is injection, suspension and is administered via subcutaneous form.

Labeler Name: Eli Lilly And Company

Dosage Form: Injection, Suspension - A liquid preparation, suitable for injection, which consists of solid particles dispersed throughout a liquid phase in which the particles are not soluble. It can also consist of an oil phase dispersed throughout an aqueous phase, or vice-versa.

Product Type: Human Prescription Drug What kind of product is this?
Indicates the type of product, such as Human Prescription Drug or Human Over the Counter Drug. This data element matches the “Document Type” field of the Structured Product Listing.

Insulin Lispro Protamine And Insulin Lispro Injectable Suspension Mix75/25 Kwikpen Active Ingredient(s)

What is the Active Ingredient(s) List?
This is the active ingredient list. Each ingredient name is the preferred term of the UNII code submitted.

  • INSULIN LISPRO 100 [iU]/mL

Inactive Ingredient(s)

About the Inactive Ingredient(s)
The inactive ingredients are all the component of a medicinal product OTHER than the active ingredient(s). The acronym "UNII" stands for “Unique Ingredient Identifier” and is used to identify each inactive ingredient present in a product.

  • PROTAMINE SULFATE (UNII: 0DE9724IHC)
  • GLYCERIN (UNII: PDC6A3C0OX)
  • SODIUM PHOSPHATE, DIBASIC (UNII: GR686LBA74)
  • METACRESOL (UNII: GGO4Y809LO)
  • ZINC (UNII: J41CSQ7QDS)
  • PHENOL (UNII: 339NCG44TV)
  • WATER (UNII: 059QF0KO0R)
  • HYDROCHLORIC ACID (UNII: QTT17582CB)
  • SODIUM HYDROXIDE (UNII: 55X04QC32I)

Administration Route(s)

What are the Administration Route(s)?
The translation of the route code submitted by the firm, indicating route of administration.

  • Subcutaneous - Administration beneath the skin; hypodermic. Synonymous with the term SUBDERMAL.
  • Subcutaneous - Administration beneath the skin; hypodermic. Synonymous with the term SUBDERMAL.

Pharmacological Class(es)

What is a Pharmacological Class?
These are the reported pharmacological class categories corresponding to the SubstanceNames listed above.

  • Insulin - [Chemical/Ingredient]
  • Insulin Analog - [EPC] (Established Pharmacologic Class)

Product Labeler Information

What is the Labeler Name?
Name of Company corresponding to the labeler code segment of the Product NDC.

Labeler Name: Eli Lilly And Company
Labeler Code: 0002
FDA Application Number: BLA021017 What is the FDA Application Number?
This corresponds to the NDA, ANDA, or BLA number reported by the labeler for products which have the corresponding Marketing Category designated. If the designated Marketing Category is OTC Monograph Final or OTC Monograph Not Final, then the Application number will be the CFR citation corresponding to the appropriate Monograph (e.g. “part 341”). For unapproved drugs, this field will be null.

Marketing Category: BLA - A product marketed under an approved Biologic License Application. What is the Marketing Category?
Product types are broken down into several potential Marketing Categories, such as NDA/ANDA/BLA, OTC Monograph, or Unapproved Drug. One and only one Marketing Category may be chosen for a product, not all marketing categories are available to all product types. Currently, only final marketed product categories are included. The complete list of codes and translations can be found at www.fda.gov/edrls under Structured Product Labeling Resources.

Start Marketing Date: 02-12-2020 What is the Start Marketing Date?
This is the date that the labeler indicates was the start of its marketing of the drug product.

Listing Expiration Date: 12-31-2021 What is the Listing Expiration Date?
This is the date when the listing record will expire if not updated or certified by the product labeler.

Exclude Flag: N What is the NDC Exclude Flag?
This field indicates whether the product has been removed/excluded from the NDC Directory for failure to respond to FDA’s requests for correction to deficient or non-compliant submissions. Values = ‘Y’ or ‘N’.

* Please review the disclaimer below.

Insulin Lispro Protamine And Insulin Lispro Injectable Suspension Mix75/25 Kwikpen Product Labeling Information

The product labeling information includes all published material associated to a drug. Product labeling documents include information like generic names, active ingredients, ingredient strength dosage, routes of administration, appearance, usage, warnings, inactive ingredients, etc.

Product Labeling Index

1 Indications And Usage

Insulin Lispro Protamine and Insulin Lispro Injectable Suspension Mix75/25 is indicated to improve glycemic control in patients with diabetes mellitus.

Other

Limitations of Use:The proportions of rapid-acting and intermediate-acting insulins in Insulin Lispro Protamine and Insulin Lispro Injectable Suspension Mix75/25 are fixed and do not allow for basal versus prandial dose adjustments.

Risk Factors for HypoglycemiaThe risk of hypoglycemia after an injection is related to the duration of action of the insulin and in general, is highest when the glucose lowering effect of the insulin is maximal. As with all insulin preparations, the glucose lowering effect time course of Insulin Lispro Protamine and Insulin Lispro Injectable Suspension Mix75/25 may vary in different individuals or at different times in the same individual and depends on many conditions, including the area of injection as well as the injection site blood supply and temperature [see Clinical Pharmacology (12.2)]. Other factors which may increase the risk of hypoglycemia include changes in meal pattern (e.g., macronutrient content or timing of meals), changes in level of physical activity, or changes to co-administered medication [see Drug Interactions (7)]. Patients with renal or hepatic impairment may be at higher risk of hypoglycemia [see Use in Specific Populations (8.6, 8.7)].

Risk Mitigation Strategies for HypoglycemiaPatients and caregivers must be educated to recognize and manage hypoglycemia. Self-monitoring of blood glucose plays an essential role in the prevention and management of hypoglycemia. In patients at higher risk for hypoglycemia and patients who have reduced symptomatic awareness of hypoglycemia, increased frequency of blood glucose monitoring is recommended.

Adverse Reactions from Clinical Studies or Postmarketing ReportsThe following adverse reactions have been identified during post-marketing use of Insulin Lispro Protamine and Insulin Lispro Injectable Suspension Mix75/25. Because some of these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.

Adverse reactions associated with insulin initiation and glucose control intensificationIntensification or rapid improvement in glucose control has been associated with a transitory, reversible ophthalmologic refraction disorder, worsening of diabetic retinopathy, and acute painful peripheral neuropathy. Over the long-term, improved glycemic control decreases the risk of diabetic retinopathy and neuropathy.

Hypersensitivity reactionsSevere, life-threatening, generalized allergy, including anaphylaxis.

HypoglycemiaHypoglycemia is the most commonly observed adverse reaction in Insulin Lispro Protamine and Insulin Lispro Injectable Suspension Mix75/25.

HypokalemiaInsulin Lispro Protamine and Insulin Lispro Injectable Suspension Mix75/25 can cause a shift in potassium from the extracellular to intracellular space, possibly leading to hypokalemia.

Injection site reactionsInsulin Lispro Protamine and Insulin Lispro Injectable Suspension Mix75/25 can cause local injection site reactions including redness, swelling, or itching at the site of injection. These reactions usually resolve in a few days to a few weeks, but in some occasions, may require discontinuation. Localized reactions and generalized myalgias have been reported with the use of meta-cresol, which is an excipient in Insulin Lispro Protamine and Insulin Lispro Injectable Suspension Mix75/25.

LipodystrophyAdministration of insulin subcutaneously, including Insulin Lispro Protamine and Insulin Lispro Injectable Suspension Mix75/25, has resulted in lipoatrophy (depression in the skin) or lipohypertrophy (enlargement or thickening of tissue) [see Dosage and Administration (2.1)] in some patients.

Localized cutaneous amyloidosisLocalized cutaneous amyloidosis at the injection site has occurred. Hyperglycemia has been reported with repeated insulin injections into areas of localized cutaneous amyloidosis; hypoglycemia has been reported with a sudden change to an unaffected injection site.

Medication ErrorsMedication errors in which other insulins have been accidentally substituted for Insulin Lispro Protamine and Insulin Lispro Injectable Suspension Mix75/25 have been identified during postapproval use.

Peripheral EdemaInsulin, including Insulin Lispro Protamine and Insulin Lispro Injectable Suspension Mix75/25, may cause sodium retention and edema, particularly if previously poor metabolic control is improved by intensified insulin therapy.

Weight gainWeight gain can occur with insulin therapy, including Insulin Lispro Protamine and Insulin Lispro Injectable Suspension Mix75/25, and has been attributed to the anabolic effects of insulin and the decrease in glycosuria.

ImmunogenicityAs with all therapeutic peptides, insulin administration may cause anti-insulin antibodies to form. The incidence of antibody formation with Insulin Lispro Protamine and Insulin Lispro Injectable Suspension Mix75/25 is unknown.

Risk SummaryThe limited available data with Insulin Lispro Protamine and Insulin Lispro Injectable Suspension Mix75/25 in pregnant women are insufficient to inform a drug-associated risk of adverse developmental outcomes. Published studies with insulin lispro used during pregnancy have not reported an association between insulin lispro and the induction of major birth defects, miscarriage, or adverse maternal or fetal outcomes (see Data). There are risks to the mother and fetus associated with poorly controlled diabetes in pregnancy (see Clinical Considerations).Pregnant rats and rabbits were exposed to insulin lispro in animal reproduction studies during organogenesis. No adverse effects on embryo/fetal viability or morphology were observed in offspring of rats exposed to insulin lispro at a dose approximately 3 times the human subcutaneous dose of 1 unit insulin lispro/kg/day. No adverse effects on embryo/fetal development were observed in offspring of rabbits exposed to insulin lispro at doses up to approximately 0.2 times the human subcutaneous dose of 1 unit/kg/day (see Data).
The estimated background risk of major birth defects is 6-10% in women with pre-gestational diabetes with a HbA1c >7 and has been reported to be as high as 20-25% in women with a HbA1c >10. The estimated background risk of miscarriage for the indicated population is unknown. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2-4% and 15-20%, respectively.

Clinical Considerations

Disease-associated maternal and/or embryo/fetal riskPoorly controlled diabetes in pregnancy increases the maternal risk for diabetic ketoacidosis, pre-eclampsia, spontaneous abortions, preterm delivery, and delivery complications. Poorly controlled diabetes increases the fetal risk for major birth defects, still birth, and macrosomia related morbidity.

Data

Human DataPublished data from retrospective studies and meta-analyses do not report an association with insulin lispro and major birth defects, miscarriage, or adverse maternal or fetal outcomes when insulin lispro is used during pregnancy. However, these studies cannot definitely establish or exclude the absence of any risk because of methodological limitations including small sample size, selection bias, confounding by unmeasured factors, and some lacking comparator groups.

Animal DataAnimal reproduction studies have not been performed with Insulin Lispro Protamine and Insulin Lispro Injectable Suspension Mix75/25. However, subcutaneous reproduction and teratology studies have been conducted with insulin lispro (a component of Insulin Lispro Protamine and Insulin Lispro Injectable Suspension Mix75/25). In a combined fertility and embryo-fetal development study, female rats were given subcutaneous insulin lispro injections of 1, 5, and 20 units/kg/day (0.2, 0.8, and 3 times the human subcutaneous dose of 1 unit insulin lispro/kg/day, based on units/body surface area, respectively) from 2 weeks prior to cohabitation through Gestation Day 19. There were no adverse effects on female fertility, implantation, or fetal viability and morphology. However, fetal growth retardation was produced at the 20 units/kg/day-dose as indicated by decreased fetal weight and an increased incidence of fetal runts/litter.
In an embryo-fetal development study in pregnant rabbits, insulin lispro doses of 0.1, 0.25, and 0.75 unit/kg/day (0.03, 0.08, and 0.2 times the human subcutaneous dose of 1 unit insulin lispro/kg/day, based on units/body surface area, respectively) were injected subcutaneously on Gestation days 7 through 19. There were no adverse effects on fetal viability, weight, and morphology at any dose.

Risk SummaryThere are no data on the presence of Insulin Lispro Protamine and Insulin Lispro Injectable Suspension Mix75/25 in human milk, the effects on the breastfed infant, or the effect on milk production. One small published study reported that exogenous insulin was present in human milk. However, there is insufficient information to determine the effects of Insulin Lispro Protamine and Insulin Lispro Injectable Suspension Mix75/25 on the breastfed infant and no available information on the effects of Insulin Lispro Protamine and Insulin Lispro Injectable Suspension Mix75/25 on milk production. The developmental and health benefits of breastfeeding should be considered along with the mother's clinical need for insulin, any potential adverse effects on the breastfed child from Insulin Lispro Protamine and Insulin Lispro Injectable Suspension Mix75/25 or from the underlying maternal condition.

Absorption — Insulin Lispro Protamine and Insulin Lispro Injectable Suspension Mix75/25 has two phases of absorption. The early phase represents insulin lispro and its distinct characteristics of rapid onset. The late phase represents the prolonged absorption of insulin lispro protamine suspension.
In 31 healthy subjects given subcutaneous doses (0.3 unit/kg) of Insulin Lispro Protamine and Insulin Lispro Injectable Suspension Mix75/25, the median peak serum concentration was 60 minutes (range: 30 minutes to 4 hours) after dosing. Identical results were found in patients with type 1 diabetes. The rapid absorption characteristics of HUMALOG are maintained with Insulin Lispro Protamine and Insulin Lispro Injectable Suspension Mix75/25. Insulin Lispro Protamine and Insulin Lispro Injectable Suspension Mix75/25 has a more rapid absorption than HUMULIN 70/30, which has been confirmed in patients with type 1 diabetes.

Metabolism — Human metabolism studies of Insulin Lispro Protamine and Insulin Lispro Injectable Suspension Mix75/25 have not been conducted. However, studies in animals indicate that the metabolism of HUMALOG, the rapid-acting component of Insulin Lispro Protamine and Insulin Lispro Injectable Suspension Mix75/25, is identical to that of regular human insulin.

Elimination — Because of the absorption-rate limited kinetics of insulin mixtures, a true half-life cannot be accurately estimated from the terminal slope of the concentration versus time curve.

Specific PopulationsThe effects of age, race, obesity, pregnancy, smoking, or renal or hepatic impairment on the pharmacokinetics of Insulin Lispro Protamine and Insulin Lispro Injectable Suspension Mix75/25 have not been studied.

Gender — Pharmacokinetic and pharmacodynamic comparisons between men and women administered Insulin Lispro Protamine and Insulin Lispro Injectable Suspension Mix75/25 showed no gender differences.

Never Share an Insulin Lispro Protamine and Insulin Lispro Injectable Suspension Mix75/25 KwikPen Between PatientsAdvise patients using Insulin Lispro Protamine and Insulin Lispro Injectable Suspension Mix75/25 KwikPens not to share needles or KwikPens with another person. Sharing poses a risk for transmission of blood-borne pathogens [see Warnings and Precautions (5.1)].

Hyperglycemia or HypoglycemiaInform patients that hypoglycemia is the most common adverse reaction with insulin. Instruct patients on self-management procedures including glucose monitoring, proper injection technique, and management of hypoglycemia and hyperglycemia, especially at initiation of Insulin Lispro Protamine and Insulin Lispro Injectable Suspension Mix75/25 therapy. Instruct patients on handling of special situations such as intercurrent conditions (illness, stress, or emotional disturbances), an inadequate or skipped insulin dose, inadvertent administration of an increased insulin dose, inadequate food intake, and skipped meals. Instruct patients on the management of hypoglycemia [see Warnings and Precautions (5.3)].Inform patients that their ability to concentrate and react may be impaired as a result of hypoglycemia. Advise patients who have frequent hypoglycemia or reduced or absent warning signs of hypoglycemia to use caution when driving or operating machinery.
Advise patients that changes in insulin regimen can predispose to hyperglycemia or hypoglycemia and that changes in insulin regimen should be made under close medical supervision [see Warnings and Precautions (5.2)].

Hypoglycemia due to Medication ErrorsInstruct patients to always check the insulin label before each injection to avoid mix-ups between insulin products [see Warnings and Precautions (5.4)].

Hypersensitivity ReactionsAdvise patients that hypersensitivity reactions have occurred with Insulin Lispro Protamine and Insulin Lispro Injectable Suspension Mix75/25. Inform patients on the symptoms of hypersensitivity reactions and to seek medical attention if they occur [see Warnings and Precautions (5.5)].
Manufactured by Eli Lilly and CompanyIndianapolis, IN 46285, USACopyright © 1999, 2020, Eli Lilly and Company. All rights reserved.
ILPILIS7525-0001-USPI-20200110

2.1 Important Administration Instructions

  • Always check insulin labels before administration [see Warnings and Precautions (5.4)].
  • Insulin Lispro Protamine and Insulin Lispro Injectable Suspension Mix75/25 is a suspension that must be resuspended immediately before use. Resuspension is easier when the insulin has reached room temperature.
  • To resuspend KwikPen, gently roll the KwikPen at least 10 times and then carefully invert the Kwikpen at least 10 times until the suspension appears uniformly white and cloudy. Inject immediately.
  • Inspect Insulin Lispro Protamine and Insulin Lispro Injectable Suspension Mix75/25 visually before use. Do not use if discoloration or particulate matter is seen.
  • Administer Insulin Lispro Protamine and Insulin Lispro Injectable Suspension Mix75/25 by subcutaneous injection into the abdominal wall, thigh, upper arm, or buttocks.
  • Rotate the injection site within the same region from one injection to the next to reduce the risk of lipodystrophy and localized cutaneous amyloidosis. Do not inject into areas of lipodystrophy or localized cutaneous amyloidosis [see Warnings and Precautions (5.2) and Adverse Reactions (6)].
  • During changes to a patient's insulin regimen, increase the frequency of blood glucose monitoring [see Warnings and Precautions (5.2)].
  • The Insulin Lispro Protamine and Insulin Lispro Injectable Suspension Mix75/25 KwikPen dials in 1 unit increments.
  • Use Insulin Lispro Protamine and Insulin Lispro Injectable Suspension Mix75/25 KwikPen with caution in patients with visual impairment that may rely on audible clicks to dial their dose.
  • Do not administer Insulin Lispro Protamine and Insulin Lispro Injectable Suspension Mix75/25 intravenously, intramuscularly or by a continuous subcutaneous insulin infusion pump.
  • Do not mix Insulin Lispro Protamine and Insulin Lispro Injectable Suspension Mix75/25 with any other insulins or diluents.

2.2 Dosage Information

  • Individualize and adjust the dosage of Insulin Lispro Protamine and Insulin Lispro Injectable Suspension Mix75/25 based on the individual's metabolic needs, blood glucose monitoring results and glycemic control goal.
  • Inject Insulin Lispro Protamine and Insulin Lispro Injectable Suspension Mix75/25 subcutaneously within 15 minutes before a meal.
  • Insulin Lispro Protamine and Insulin Lispro Injectable Suspension Mix75/25 is typically dosed twice-daily (with each dose intended to cover 2 meals or a meal and a snack)
  • Dosage adjustments may be needed with changes in physical activity, changes in meal patterns (i.e., macronutrient content or timing of food intake), changes in renal or hepatic function or during acute illness [see Warnings and Precautions (5.2, 5.3) and Use in Specific Populations (8.6, 8.7)].
  • Dosage adjustment may be needed when switching from another insulin to Insulin Lispro Protamine and Insulin Lispro Injectable Suspension Mix75/25.

2.3 Dosage Adjustment Due To Drug Interactions

  • Dosage adjustment may be needed when Insulin Lispro Protamine and Insulin Lispro Injectable Suspension Mix75/25 is coadministered with certain drugs [see Drug Interactions (7)].

3 Dosage Forms And Strengths

  • Insulin Lispro Protamine and Insulin Lispro Injectable Suspension Mix75/25 100 units per mL (U-100) is 75% insulin lispro protamine and 25% insulin lispro, a white and cloudy suspension available as:
  • 3 mL single-patient-use KwikPen (prefilled)

4 Contraindications

  • Insulin Lispro Protamine and Insulin Lispro Injectable Suspension Mix75/25 is contraindicated:
  • During episodes of hypoglycemia [see Warnings and Precautions (5.3)]in patients who have had hypersensitivity reactions to Insulin Lispro Protamine and Insulin Lispro Injectable Suspension Mix75/25 or to any of its excipients. [see Warnings and Precautions (5.5)]

5.1 Never Share An Insulin Lispro Protamine And Insulin Lispro Injectable Suspension Mix75/25 Kwikpen Between Patients

Insulin Lispro Protamine and Insulin Lispro Injectable Suspension Mix75/25 KwikPens must never be shared between patients, even if the needle is changed. Sharing poses a risk for transmission of blood-borne pathogens.

5.2 Hyperglycemia Or Hypoglycemia With Changes In Insulin Regimen

Changes in an insulin regimen (e.g., insulin strength, manufacturer, type, injection site or method of administration) may affect glycemic control and predispose to hypoglycemia [see Warnings and Precautions (5.3)] or hyperglycemia. Repeated insulin injections into areas of lipodystrophy or localized cutaneous amyloidosis have been reported to result in hyperglycemia; and a sudden change in the injection site (to an unaffected area) has been reported to result in hypoglycemia [see Adverse Reactions (6)].
Make any changes to a patient's insulin regimen under close medical supervision with increased frequency of blood glucose monitoring. Advise patients who have repeatedly injected into areas of lipodystrophy or localized cutaneous amyloidosis to change the injection site to unaffected areas and closely monitor for hypoglycemia. For patients with type 2 diabetes, dosage adjustments of concomitant anti-diabetic products may be needed.

5.3 Hypoglycemia

Hypoglycemia is the most common adverse reaction associated with all insulin therapies, including Insulin Lispro Protamine and Insulin Lispro Injectable Suspension Mix75/25. Severe hypoglycemia can cause seizures, may lead to unconsciousness, may be life-threatening, or cause death. Hypoglycemia can impair concentration ability and reaction time; this may place an individual and others at risk in situations where these abilities are important (e.g., driving or operating other machinery).
Hypoglycemia can happen suddenly and symptoms may differ in each individual and change over time in the same individual. Symptomatic awareness of hypoglycemia may be less pronounced in patients with longstanding diabetes, in patients with diabetic nerve disease, in patients using medications that block the sympathetic nervous system (e.g., beta-blockers) [see Drug Interactions (7)], or in patients who experience recurrent hypoglycemia.

5.4 Hypoglycemia Due To Medication Errors

Accidental mix-ups between Insulin Lispro Protamine and Insulin Lispro Injectable Suspension Mix75/25 and other insulin products have been reported. To avoid medication errors between Insulin Lispro Protamine and Insulin Lispro Injectable Suspension Mix75/25 and other insulins, instruct patients to always check the insulin label before each injection.

5.5 Hypersensitivity Reactions

Severe, life-threatening, generalized allergy, including anaphylaxis, can occur with insulin products, including Insulin Lispro Protamine and Insulin Lispro Injectable Suspension Mix75/25. If hypersensitivity reactions occur, discontinue Insulin Lispro Protamine and Insulin Lispro Injectable Suspension Mix75/25; treat per standard of care and monitor until symptoms and signs resolve. Insulin Lispro Protamine and Insulin Lispro Injectable Suspension Mix75/25 is contraindicated in patients who have had hypersensitivity reactions to Insulin Lispro Protamine and Insulin Lispro Injectable Suspension Mix75/25 or any of its excipients [see Contraindications (4)].

5.6 Hypokalemia

All insulin products, including Insulin Lispro Protamine and Insulin Lispro Injectable Suspension Mix75/25, cause a shift in potassium from the extracellular to intracellular space, possibly leading to hypokalemia. Untreated hypokalemia may cause respiratory paralysis, ventricular arrhythmia, and death. Monitor potassium levels in patients at risk for hypokalemia if indicated (e.g., patients using potassium-lowering medications, patients taking medications sensitive to serum potassium concentrations).

5.7 Fluid Retention And Heart Failure With Concomitant Use Of Ppar-Gamma Agonists

Thiazolidinediones (TZDs), which are peroxisome proliferator-activated receptor (PPAR)-gamma agonists, can cause dose-related fluid retention, particularly when used in combination with insulin. Fluid retention may lead to or exacerbate heart failure. Patients treated with insulin, including Insulin Lispro Protamine and Insulin Lispro Injectable Suspension Mix75/25, and a PPAR-gamma agonist should be observed for signs and symptoms of heart failure. If heart failure develops, it should be managed according to current standards of care, and discontinuation or dose reduction of the PPAR-gamma agonist must be considered.

6 Adverse Reactions

  • The following adverse reactions are discussed elsewhere in the labeling:
  • Hypoglycemia [see Warnings and Precautions (5.3)]
  • Medication Errors [see Warnings and Precautions (5.4)]Hypersensitivity Reactions [see Warnings and Precautions (5.5)]Hypokalemia [see Warnings and Precautions (5.6)]

7 Drug Interactions

Table 1: Clinically Significant Drug Interactions with Insulin Lispro Protamine and Insulin Lispro Injectable Suspension Mix75/25
Drugs that May Increase the Risk of HypoglycemiaDrugs:Antidiabetic agents, ACE inhibitors, angiotensin II receptor blocking agents, disopyramide, fibrates, fluoxetine, monoamine oxidase inhibitors, pentoxifylline, pramlintide, salicylates, somatostatin analog (e.g., octreotide), and sulfonamide antibiotics.
Intervention:Dose adjustment and increased frequency of glucose monitoring may be required when Insulin Lispro Protamine and Insulin Lispro Injectable Suspension Mix75/25 is co-administered with these drugs.
Drugs that May Decrease the Blood Glucose Lowering Effect of Insulin Lispro Protamine and Insulin Lispro Injectable Suspension Mix75/25Drugs:Atypical antipsychotics (e.g., olanzapine and clozapine), corticosteroids, danazol, diuretics, estrogens, glucagon, isoniazid, niacin, oral contraceptives, phenothiazines, progestogens (e.g., in oral contraceptives), protease inhibitors, somatropin, sympathomimetic agents (e.g., albuterol, epinephrine, terbutaline), and thyroid hormones.
Intervention:Dose adjustment and increased frequency of glucose monitoring may be required when Insulin Lispro Protamine and Insulin Lispro Injectable Suspension Mix75/25 is co-administered with these drugs.
Drugs that May Increase or Decrease the Blood Glucose Lowering Effect of Insulin Lispro Protamine and Insulin Lispro Injectable Suspension Mix75/25Drugs:Alcohol, beta-blockers, clonidine, and lithium salts. Pentamidine may cause hypoglycemia, which may sometimes be followed by hyperglycemia.
Intervention:Dose adjustment and increased frequency of glucose monitoring may be required when Insulin Lispro Protamine and Insulin Lispro Injectable Suspension Mix75/25 is co-administered with these drugs.
Drugs that May Blunt Signs and Symptoms of HypoglycemiaDrugs:Beta-blockers, clonidine, guanethidine, and reserpine.
Intervention:Increased frequency of glucose monitoring may be required when Insulin Lispro Protamine and Insulin Lispro Injectable Suspension Mix75/25 is co-administered with these drugs.

8.4 Pediatric Use

Safety and effectiveness of Insulin Lispro Protamine and Insulin Lispro Injectable Suspension Mix75/25 in patients less than 18 years of age has not been established.

8.5 Geriatric Use

Clinical studies of Insulin Lispro Protamine and Insulin Lispro Injectable Suspension Mix75/25 did not include sufficient numbers of patients aged 65 and over to determine whether they respond differently than younger patients. In elderly patients with diabetes, the initial dosing, dose increments, and maintenance dosage should be conservative to reduce the risk of hypoglycemia [see Warnings and Precautions (5.3)].

8.6 Renal Impairment

The effect of renal impairment on the pharmacokinetics of Insulin Lispro Protamine and Insulin Lispro Injectable Suspension Mix75/25 has not been studied. Patients with renal impairment may be at increased risk of hypoglycemia and may require more frequent Insulin Lispro Protamine and Insulin Lispro Injectable Suspension Mix75/25 dose adjustment and more frequent glucose monitoring [see Warnings and Precautions (5.3)].

8.7 Hepatic Impairment

The effect of hepatic impairment on the pharmacokinetics of Insulin Lispro Protamine and Insulin Lispro Injectable Suspension Mix75/25 has not been studied. Patients with hepatic impairment may be at increased risk of hypoglycemia and may require more frequent Insulin Lispro Protamine and Insulin Lispro Injectable Suspension Mix75/25 dose adjustment and more frequent glucose monitoring [see Warnings and Precautions (5.3)].

10 Overdosage

Excess insulin administration may cause hypoglycemia and hypokalemia. Mild episodes of hypoglycemia usually can be treated with oral glucose. Adjustments in drug dosage, meal patterns, or exercise may be needed. More severe episodes with coma, seizure, or neurologic impairment may be treated with intramuscular or subcutaneous glucagon or concentrated intravenous glucose. Sustained carbohydrate intake and observation may be necessary because hypoglycemia may recur after apparent clinical recovery. Hypokalemia must be corrected appropriately [see Warnings and Precautions (5.3, 5.6)].

11 Description

Insulin Lispro Protamine and Insulin Lispro Injectable Suspension Mix75/25 is a mixture of 75% insulin lispro protamine, an intermediate-acting human insulin analog, and 25% insulin lispro, a rapid-acting human insulin analog. Insulin lispro is produced by recombinant DNA technology utilizing a non-pathogenic laboratory strain of Escherichia coli. Insulin lispro differs from human insulin in that the amino acid proline at position B28 is replaced by lysine and the lysine in position B29 is replaced by proline. Chemically, it is Lys(B28), Pro(B29) human insulin analog and has the empirical formula C257H383N65O77S6 and a molecular weight of 5808, both identical to that of human insulin. Insulin lispro protamine suspension is a suspension of crystals produced from combining insulin lispro and protamine sulfate under appropriate conditions for crystal formation.
Insulin lispro has the following primary structure:
Insulin Lispro Protamine and Insulin Lispro Injectable Suspension Mix75/25 KwikPens contain a white and cloudy, sterile suspension of insulin lispro protamine suspension mixed with soluble insulin lispro for use as an injection.
Each milliliter of Insulin Lispro Protamine and Insulin Lispro Injectable Suspension Mix75/25 injection contains insulin lispro 100 units, 0.28 mg protamine sulfate, 16 mg glycerin, 3.78 mg dibasic sodium phosphate, 1.76 mg Metacresol, zinc oxide content adjusted to provide 0.025 mg zinc ion, 0.715 mg phenol, and Water for Injection. The pH is 7.0 to 7.8. Sodium hydroxide and/or hydrochloric acid may be added during manufacture to adjust the pH.

12.1 Mechanism Of Action

The primary activity of insulin, including Insulin Lispro Protamine and Insulin Lispro Injectable Suspension Mix75/25, is the regulation of glucose metabolism. Insulins lower blood glucose by stimulating peripheral glucose uptake by skeletal muscle and fat, and by inhibiting hepatic glucose production. Insulins inhibit lipolysis and proteolysis, and enhance protein synthesis.

12.2 Pharmacodynamics

In a glucose clamp study performed in 30 healthy subjects, the onset of action and glucose-lowering activity of HUMALOG, HUMALOG® Mix50/50™, Insulin Lispro Protamine and Insulin Lispro Injectable Suspension Mix75/25, and insulin lispro protamine suspension (ILPS) were compared (see
Figure 1). Graphs of mean glucose infusion rate versus time showed a distinct insulin activity profile for each formulation. The rapid onset of glucose-lowering activity characteristic of HUMALOG was maintained in Insulin Lispro Protamine and Insulin Lispro Injectable Suspension Mix75/25. The median maximum pharmacologic effect of Insulin Lispro Protamine and Insulin Lispro Injectable Suspension Mix75/25 after administration of a 0.3 unit/kg dose to healthy subjects occurred at approximately 2 hours (range: 1-6 hours); glucose lowering activity was detectable for a median of 22 hours (range: 13 to 22 hours), which was the end of the clamp.
In separate glucose clamp studies performed in healthy subjects, pharmacodynamics of Insulin Lispro Protamine and Insulin Lispro Injectable Suspension Mix75/25 and HUMULIN® 70/30 were assessed and are presented in Figure 2. Insulin Lispro Protamine and Insulin Lispro Injectable Suspension Mix75/25 has a duration of activity similar to that of HUMULIN 70/30.
Figures 1 and 2 should be considered only as representative examples since the time course of action of insulin and insulin analogs, may vary in different individuals or within the same individual.Figure 1: Mean Insulin Activity Versus Time Profiles After Injection of 0.3 units/kg of HUMALOG, HUMALOG Mix50/50, Insulin Lispro Protamine and Insulin Lispro Injectable Suspension Mix75/25, or Insulin Lispro Protamine Suspension (ILPS) in 30 Healthy Subjects.Figure 2: Mean Insulin Activity Versus Time Profiles After Injection of 0.3 units/kg of Insulin Lispro Protamine and Insulin Lispro Injectable Suspension Mix75/25 or HUMULIN 70/30 in Healthy Subjects.

13.1 Carcinogenesis, Mutagenesis, Impairment Of Fertility

Standard 2-year carcinogenicity studies in animals have not been performed with Insulin Lispro Protamine and Insulin Lispro Injectable Suspension Mix75/25. In Fischer 344 rats, a 12-month repeat-dose toxicity study was conducted with insulin lispro (a component of Insulin Lispro Protamine and Insulin Lispro Injectable Suspension Mix75/25) at subcutaneous doses of 20 and 200 units/kg/day (approximately 3 and 32 times the human subcutaneous dose of 1 unit insulin lispro/kg/day, based on units/body surface area). Insulin lispro did not produce important target organ toxicity including mammary tumors at any dose.
Insulin lispro was not mutagenic in the following genetic toxicity assays: bacterial mutation, unscheduled DNA synthesis, mouse lymphoma, chromosomal aberration and micronucleus assays.
Male fertility was not compromised when male rats given subcutaneous insulin lispro injections of 5 and 20 units/kg/day (0.8 and 3 times the human subcutaneous dose of 1 unit insulin lispro/kg/day, based on units/body surface area) for 6 months were mated with untreated female rats. In a combined fertility, perinatal, and postnatal study in male and female rats given 1, 5, and 20 units/kg/day subcutaneously (0.2, 0.8, and 3 times the human subcutaneous dose of 1 unit insulin lispro/kg/day, based on units/body surface area), mating and fertility were not adversely affected in either gender at any dose.

16.1 How Supplied

Insulin Lispro Protamine and Insulin Lispro Injectable Suspension Mix75/25 100 units per mL (U-100) is 75% insulin lispro protamine and 25% insulin lispro, a white and cloudy suspension available as:
3 mL single-patient-use KwikPen (prefilled)
NDC 0002-8233-05
Insulin Lispro Protamine and Insulin Lispro Injectable Suspension Mix75/25 KwikPens must never be shared between patients, even if the needle is changed. Always use a new needle for each injection to prevent contamination.
The Insulin Lispro Protamine and Insulin Lispro Injectable Suspension Mix75/25 KwikPen dials in 1 unit increments.

16.2 Storage And Handling

Dispense in the original sealed carton with the enclosed Instructions for Use.
Do not use after the expiration date. Protect from direct heat and light. Do not freeze. See storage table below:
Not In-Use (Unopened)Refrigerated(36° to 46°F [2° to 8°C])Not In Use (unopened) Room Temperature (Below 86°F [30°C])In-Use (Opened)Room Temperature, (Below 86°F [30°C])3 mL single-patient-use KwikPen
Until expiration date
10 days
10 days, room temperature.Do not refrigerate.

17 Patient Counseling Information

Advise the patient to read the FDA-approved patient labeling (Patient Information and Instructions for Use).

Spl Patient Package Insert

  • This Patient Information has been approved by the U.S. Food and Drug Administration.
  • Issued: February 2020
  • Patient InformationInsulin Lispro Protamine and Insulin Lispro Injectable Suspension Mix75/25™for subcutaneous useDo not share your Insulin Lispro Protamine and Insulin Lispro Injectable Suspension Mix75/25 KwikPen with other people, even if the needle has been changed. You may give other people a serious infection or get a serious infection from them.What is Insulin Lispro Protamine and Insulin Lispro Injectable Suspension Mix75/25?Insulin Lispro Protamine and Insulin Lispro Injectable Suspension Mix75/25 is a man-made insulin that is used to control high blood sugar in people with diabetes mellitus.
  • It is not known if Insulin Lispro Protamine and Insulin Lispro Injectable Suspension Mix75/25 is safe and effective in children under 18 years of age.
  • Who should not take Insulin Lispro Protamine and Insulin Lispro Injectable Suspension Mix75/25?Do not take Insulin Lispro Protamine and Insulin Lispro Injectable Suspension Mix75/25 if you:are having an episode of low blood sugar (hypoglycemia).
  • Have an allergy to Insulin Lispro Protamine and Insulin Lispro Injectable Suspension Mix75/25 or any of the ingredients in Insulin Lispro Protamine and Insulin Lispro Injectable Suspension Mix75/25. See the end of this Patient Information leaflet for a complete list of ingredients in Insulin Lispro Protamine and Insulin Lispro Injectable Suspension Mix75/25.
  • What should I tell my healthcare provider before taking Insulin Lispro Protamine and Insulin Lispro Injectable Suspension Mix75/25?Before taking Insulin Lispro Protamine and Insulin Lispro Injectable Suspension Mix75/25, tell your healthcare provider about all of your medical conditions, including if you:have liver or kidney problems.
  • Take any other medicines, especially ones called TZDs (thiazolidinediones).
  • Have heart failure or other heart problems. If you have heart failure, it may get worse while you take TZDs with Insulin Lispro Protamine and Insulin Lispro Injectable Suspension Mix75/25.
  • Are pregnant or plan to become pregnant. Talk with your healthcare provider about the best way to control your blood sugar if you plan to become pregnant or while you are pregnant.
  • Are breastfeeding or plan to breastfeed. Talk with your healthcare provider about the best way to feed your baby while taking Insulin Lispro Protamine and Insulin Lispro Injectable Suspension Mix75/25.Tell your healthcare provider about all the medicines you take, including prescription and over-the-counter medicines, vitamins, and herbal supplements.Before you start taking Insulin Lispro Protamine and Insulin Lispro Injectable Suspension Mix75/25, talk to your healthcare provider about low blood sugar and how to manage it.How should I take Insulin Lispro Protamine and Insulin Lispro Injectable Suspension Mix75/25?Read the Instructions for Use that comes with your Insulin Lispro Protamine and Insulin Lispro Injectable Suspension Mix75/25.
  • Take Insulin Lispro Protamine and Insulin Lispro Injectable Suspension Mix75/25 exactly as your healthcare provider tells you to. Your healthcare provider should tell you how much Insulin Lispro Protamine and Insulin Lispro Injectable Suspension Mix75/25 to take and when to take it.
  • Insulin Lispro Protamine and Insulin Lispro Injectable Suspension Mix75/25 starts acting fast. Inject Insulin Lispro Protamine and Insulin Lispro Injectable Suspension Mix75/25 within 15 minutes before you eat a meal.Know the type, strength, and amount of insulin you take. Do not change the type or amount of insulin you take unless your healthcare provider tells you to. The amount of insulin and the best time for you to take your insulin may need to change if you take different types of insulin.
  • Check your insulin label each time you give your injection to make sure you are taking the correct insulin.
  • Inject Insulin Lispro Protamine and Insulin Lispro Injectable Suspension Mix75/25 under the skin (subcutaneously) of your stomach area (abdomen), buttocks, upper legs or upper arms. Do not inject Insulin Lispro Protamine and Insulin Lispro Injectable Suspension Mix75/25 into your vein (intravenously) or muscle (intramuscularly) or use in an insulin infusion pump.
  • Change (rotate) your injection sites within the area you choose with each dose to reduce your risk of getting lipodystrophy (pits in skin or thickened skin) and localized cutaneous amyloidosis (skin with lumps) at the injection sites.Do not use the exact same spot for each injection.
  • Do not inject where the skin has pits, is thickened, or has lumps.
  • Do not inject where the skin is tender, bruised, scaly or hard, or into scars or damaged skin.
  • Do not mix Insulin Lispro Protamine and Insulin Lispro Injectable Suspension Mix75/25 with other insulins or liquids.
  • Check your blood sugar levels. Ask your healthcare provider what your blood sugars should be and when you should check your blood sugar levels.Keep Insulin Lispro Protamine and Insulin Lispro Injectable Suspension Mix75/25 and all medicines out of the reach of children.Your dose of Insulin Lispro Protamine and Insulin Lispro Injectable Suspension Mix75/25 may need to change because of a:change in physical activity or exercise, weight gain or loss, increased stress, illness, change in diet, or because of other medicines you take.
  • What should I avoid while taking Insulin Lispro Protamine and Insulin Lispro Injectable Suspension Mix75/25?While taking Insulin Lispro Protamine and Insulin Lispro Injectable Suspension Mix75/25 do not:drive or operate heavy machinery until you know how Insulin Lispro Protamine and Insulin Lispro Injectable Suspension Mix75/25 affects you.
  • Drink alcohol or take prescription or over-the-counter medicines that contain alcohol.
  • What are the possible side effects of Insulin Lispro Protamine and Insulin Lispro Injectable Suspension Mix75/25?Insulin Lispro Protamine and Insulin Lispro Injectable Suspension Mix75/25 may cause serious side effects that can lead to death, including:low blood sugar (hypoglycemia). Signs and symptoms of low blood sugar may include:dizziness or light-headedness
  • Sweating
  • Confusion
  • Headache
  • Blurred vision
  • Slurred speech
  • Shakiness
  • Fast heartbeat
  • Anxiety, irritability or mood changes
  • Hunger
  • Your healthcare provider may prescribe a glucagon emergency kit so that someone else can give you glucagon if your blood sugar becomes too low (severe hypoglycemia) and you are unable to take sugar by mouth.severe allergic reaction (whole body reaction). Get medical help right away, if you have any of these signs or symptoms of a severe allergic reaction:a rash over your whole body
  • Trouble breathing
  • A fast heartbeat
  • Sweating
  • Low potassium in your blood (hypokalemia).heart failure. Taking certain diabetes pills called thiazolidinediones or “TZDs” with Insulin Lispro Protamine and Insulin Lispro Injectable Suspension Mix75/25 may cause heart failure in some people. This can happen even if you have never had heart failure or heart problems before. If you already have heart failure it may get worse while you take TZDs with Insulin Lispro Protamine and Insulin Lispro Injectable Suspension Mix75/25. Your healthcare provider should monitor you closely while you are taking TZDs with Insulin Lispro Protamine and Insulin Lispro Injectable Suspension Mix75/25. Tell your healthcare provider if you have any new or worse symptoms of heart failure including:shortness of breath
  • Swelling of your ankles or feet
  • Sudden weight gain
  • Treatment with TZDs and Insulin Lispro Protamine and Insulin Lispro Injectable Suspension Mix75/25 may need to be adjusted or stopped by your healthcare provider if you have new or worse heart failure.Get emergency medical help if you have:trouble breathing
  • Shortness of breath
  • Fast heartbeat
  • Swelling of your face, tongue, or throat
  • Sweating
  • Extreme drowsiness
  • Dizziness
  • Confusion
  • The most common side effects of Insulin Lispro Protamine and Insulin Lispro Injectable Suspension Mix75/25 include:low blood sugar (hypoglycemia)
  • Reactions at your injection site
  • Skin thickening or pits at the injection site (lipodystrophy)
  • Weight gain
  • Swelling in your hands or feet
  • Itching
  • Rash
  • These are not all the possible side effects of Insulin Lispro Protamine and Insulin Lispro Injectable Suspension Mix75/25. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.
  • General information about the safe and effective use of Insulin Lispro Protamine and Insulin Lispro Injectable Suspension Mix75/25.Medicines are sometimes prescribed for purposes other than those listed in a Patient Information leaflet. Do not take Insulin Lispro Protamine and Insulin Lispro Injectable Suspension Mix75/25 for a condition for which it was not prescribed. Do not give Insulin Lispro Protamine and Insulin Lispro Injectable Suspension Mix75/25 to other people, even if they have the same symptoms that you have. It may harm them.This Patient Information leaflet summarizes the most important information about Insulin Lispro Protamine and Insulin Lispro Injectable Suspension Mix75/25. If you would like more information, talk with your healthcare provider. You can ask your pharmacist or healthcare provider for information about Insulin Lispro Protamine and Insulin Lispro Injectable Suspension Mix75/25 that is written for health professionals.
  • What are the ingredients in Insulin Lispro Protamine and Insulin Lispro Injectable Suspension Mix75/25?Active ingredients: insulin lisproInactive ingredients: protamine sulfate, glycerin, dibasic sodium phosphate, metacresol, zinc oxide (zinc ion), phenol and water for injection.Mix75/25™ and KwikPen® are trademarks of Eli Lilly and Company.Manufactured by Eli Lilly and Company, Indianapolis, IN 46285, USACopyright © 1999, 2020, Eli Lilly and Company. All rights reserved.For more information, call 1-800-545-5979.
  • ILPILIS7525-0001-PPI-20200207

Instructions For Use

  • Instructions for UseInsulin Lispro Protamine and Insulin Lispro Injectable Suspension Mix75/25™ KwikPen®for subcutaneous use3 mL single-patient-use pen (100 units/mL)Read this Instructions for Use before you start taking Insulin Lispro Protamine and Insulin Lispro Injectable Suspension Mix75/25 and each time you get another KwikPen. There may be new information. This information does not take the place of talking to your healthcare provider about your medical condition or your treatment.
  • Do not share your Insulin Lispro Protamine and Insulin Lispro Injectable Suspension Mix75/25 KwikPen with other people, even if the needle has been changed. You may give other people a serious infection or get a serious infection from them.Insulin Lispro Protamine and Insulin Lispro Injectable Suspension Mix75/25 KwikPen (“Pen”) is a disposable single-patient-use prefilled pen containing 300 units of Insulin Lispro Protamine and Insulin Lispro Injectable Suspension Mix75/25.
  • • You can give yourself more than 1 dose from the Pen.
  • • By turning the Dose Knob, you can dial doses from 1 to 60 units in 1 unit increments.
  • • If your dose is more than 60 units, you will need to give yourself more than 1 injection. • The Plunger only moves a little with each injection, and you may not notice that it moves. The Plunger will only reach the end of the cartridge when you have used all 300 units in the Pen.
  • People who are blind or have vision problems should not use this Pen without help from a person trained to use the Pen.How to recognize your Insulin Lispro Protamine and Insulin Lispro Injectable Suspension Mix75/25 KwikPenPen color: Dark blue
  • Dose Knob: Dark blue
  • Labels: White label with yellow stripe
  • Supplies you will need to give your injectionInsulin Lispro Protamine and Insulin Lispro Injectable Suspension Mix75/25 KwikPen
  • KwikPen compatible Needle (Becton, Dickinson and Company Pen Needles recommended)
  • Alcohol swab
  • Gauze
  • Preparing your PenWash your hands with soap and water.
  • Check your Pen to make sure you are taking the right type of insulin. This is especially important if you use more than 1 type of insulin.
  • Always use a new needle for each injection to help prevent infections and blocked needles. Do not reuse or share your needles with other people. You may give other people a serious infection or get a serious infection from them.Step 1:Pull the Pen Cap straight off.-
  • Do not remove the Pen Label.
  • Wipe the Rubber Seal with an alcohol swab.-
  • Do not attach the Needle before mixing.
  • Step 2:Gently roll the Pen between your hands at least 10 times.
  • Step 3:Move the Pen up and down (invert) at least 10 times.Mixing by rolling and inverting the Pen is important to make sure you get the right dose. After mixing Insulin Lispro Protamine and Insulin Lispro Injectable Suspension Mix75/25, inject your dose right away. If you wait to inject your dose, the insulin will need to be mixed again.Step 4:Check the liquid in the Pen. Insulin Lispro Protamine and Insulin Lispro Injectable Suspension Mix75/25 should look white and cloudy after mixing. Do not use if it looks clear or has any lumps or particles in it.
  • Step 5:Select a new Needle.Pull off the Paper Tab from the Outer Needle Shield.
  • Step 6:Push the capped Needle straight onto the Pen and twist the Needle on until it is tight.
  • Step 7:Pull off the Outer Needle Shield. Do not throw it away.
  • Pull off the Inner Needle Shield and throw it away.
  • Priming your PenPrime your Pen before each injection.Priming your Pen means removing the air from the Needle and Cartridge that may collect during normal use and ensures that the Pen is working correctly.
  • If you do not prime before each injection, you may get too much or too little insulin.
  • Step 8:To prime your Pen, turn the Dose Knob to select 2 units.
  • Step 9:Hold your Pen with the Needle pointing up. Tap the Cartridge Holder gently to collect air bubbles at the top.
  • Step 10:Continue holding your Pen with Needle pointing up. Push the Dose Knob in until it stops, and “0” is seen in the Dose Window. Hold the Dose Knob in and count to 5 slowly.
  • You should see insulin at the tip of the Needle.-
  • If you do not see insulin, repeat priming steps 8 to 10, no more than 4 times.
  • -
  • If you still do not see insulin, change the Needle and repeat priming steps 8 to 10.
  • Small air bubbles are normal and will not affect your dose.
  • Selecting your doseYou can give from 1 to 60 units in a single injection.
  • If your dose is more than 60 units, you will need to give more than one injection.-
  • If you need help with dividing up your dose the right way, ask your healthcare provider.
  • -
  • Use a new Needle for each injection and repeat the priming steps.
  • Step 11:Turn the Dose Knob to select the number of units you need to inject. The Dose Indicator should line up with your dose.-
  • The Pen dials 1 unit at a time.
  • -
  • The Dose Knob clicks as you turn it.
  • -
  • Do not dial your dose by counting the clicks. You may dial the wrong dose. This may lead to you getting too much insulin or not enough insulin.
  • -
  • The dose can be corrected by turning the Dose Knob in either direction until the correct dose lines up with the Dose Indicator.
  • -
  • The even numbers (for example, 12) are printed on the dial.
  • -
  • The odd numbers, (for example, 25) after the number 1, are shown as full lines.
  • Always check the number in the Dose Window to make sure you have dialed the correct dose.(Example: 12 units shown in the Dose Window)(Example: 25 units shown in the Dose Window)
  • The Pen will not let you dial more than the number of units left in the Pen.
  • If you need to inject more than the number of units left in the Pen, you may either:-
  • Inject the amount left in your Pen and then use a new Pen to give the rest of your dose, or-
  • Get a new Pen and inject the full dose.
  • It is normal to see a small amount of insulin left in the Pen that you can not inject.
  • Giving your injectionInject your insulin as your healthcare provider has shown you.
  • Change (rotate) your injection sites within the area you choose for each dose to reduce your risk of getting lipodystrophy (pits in skin or thickened skin) and localized cutaneous amyloidosis (skin with lumps) at the injection sites.
  • Do not inject where the skin has pits, is thickened, or has lumps.
  • Do not inject where the skin is tender, bruised, scaly or hard, or into scars or damaged skin.
  • Do not try to change your dose while injecting.
  • Step 12:Choose your injection site.Insulin Lispro Protamine and Insulin Lispro Injectable Suspension Mix75/25 is injected under the skin (subcutaneously) of your stomach area, buttocks, upper legs or upper arms.
  • Wipe your skin with an alcohol swab, and let your skin dry before you inject your dose.
  • Step 13:Insert the Needle into your skin.
  • Push the Dose Knob all the way in.
  • Continue to hold the Dose Knob in and slowly count to 5 before removing the Needle.Do not try to inject your insulin by turning the Dose Knob. You will not receive your insulin by turning the Dose Knob.Step 14:Pull the Needle out of your skin.A drop of insulin at the Needle tip is normal. It will not affect your dose.
  • Check the number in the Dose Window.-
  • If you see “0” in the Dose Window, you have received the full amount you dialed.
  • -
  • If you do not see “0” in the Dose Window, do not redial. Insert the Needle into your skin and finish your injection.
  • -
  • If you still do not think you received the full amount you dialed for your injection, do not start over or repeat the injection. Monitor your blood glucose as instructed by your healthcare provider.
  • -
  • If you normally need to give 2 injections for your full dose, be sure to give your second injection.
  • The Plunger only moves a little with each injection, and you may not notice that it moves.If you see blood after you take the Needle out of your skin, press the injection site lightly with a piece of gauze or an alcohol swab. Do not rub the area.After your injectionStep 15:Carefully replace the Outer Needle Shield.
  • Step 16:Unscrew the capped Needle and throw it away (see Disposing of Pens and Needles section).
  • Do not store the Pen with the Needle attached to prevent leaking, blocking the Needle, and air from entering the Pen.
  • Step 17:Replace the Pen Cap by lining up the Cap Clip with the Dose Indicator and pushing straight on.
  • Disposing of Pens and NeedlesPut your used needles in a FDA-cleared sharps disposal container right away after use. Do not throw away (dispose of) loose needles in your household trash.
  • If you do not have a FDA-cleared sharps disposal container, you may use a household container that is:-
  • Made of a heavy-duty plastic,
  • -
  • Can be closed with a tight-fitting, puncture-resistant lid, without sharps being able to come out,
  • -
  • Upright and stable during use,
  • -
  • Leak-resistant, and
  • -
  • Properly labeled to warn of hazardous waste inside the container.
  • When your sharps disposal container is almost full, you will need to follow your community guidelines for the right way to dispose of your sharps disposal container. There may be state or local laws about how you should throw away used needles and syringes. For more information about safe sharps disposal, and for specific information about sharps disposal in the state that you live in, go to the FDA's website at: http://www.fda.gov/safesharpsdisposal
  • Do not dispose of your used sharps disposal container in your household trash unless your community guidelines permit this. Do not recycle your used sharps disposal container.
  • The used Pen may be discarded in your household trash after you have removed the needle.
  • Storing your PenUnused PensStore unused Pens in the refrigerator at 36°F to 46°F (2°C to 8°C).
  • Do not freeze your insulin. Do not use if Insulin Lispro Protamine and Insulin Lispro Injectable Suspension Mix75/25 has been frozen.
  • Unused Pens may be used until the expiration date printed on the Label, if the Pen has been kept in the refrigerator.
  • Unused Pens stored at room temperature, below 86°F (30°C), should be thrown away after 10 days.
  • In-use PenStore the Pen you are currently using at room temperature [up to 86°F (30°C)]. Keep away from heat and light.
  • Throw away the Insulin Lispro Protamine and Insulin Lispro Injectable Suspension Mix75/25 Pen you are using after 10 days, even if it still has insulin left in it.
  • General information about the safe and effective use of your PenKeep your Pen and needles out of the reach of children.Do not use your Pen if any part looks broken or damaged.
  • Always carry an extra Pen in case yours is lost or damaged.
  • TroubleshootingIf you can not remove the Pen Cap, gently twist the cap back and forth, and then pull the cap straight off.
  • If the Dose Knob is hard to push:-
  • Pushing the Dose Knob more slowly will make it easier to inject.
  • -
  • Your Needle may be blocked. Put on a new Needle and prime the Pen.
  • -
  • You may have dust, food, or liquid inside the Pen. Throw the Pen away and get a new Pen.
  • If you have any questions or problems with your Insulin Lispro Protamine and Insulin Lispro Injectable Suspension Mix75/25 KwikPen, contact Lilly at 1-800-LillyRx (1-800-545-5979) or call your healthcare provider for help.
  • This Instructions for Use has been approved by the U.S. Food and Drug Administration.
  • Mix75/25™ and KwikPen® are trademarks of Eli Lilly and Company.
  • Issued: February 2020
  • Manufactured by Eli Lilly and CompanyIndianapolis, IN 46285, USACopyright © 2007, 2020, Eli Lilly and Company. All rights reserved.
  • Insulin Lispro Protamine and Insulin Lispro Injectable Suspension Mix75/25 KwikPen meets the current dose accuracy and functional requirements of ISO 11608-1.
  • ILPILIS7525KP-0001-IFU-20200207

* Please review the disclaimer below.