Insulin Lispro Protamine and Insulin Lispro Mix75/25 is indicated to improve glycemic control in adults with diabetes mellitus. Limitations of Use: The proportions of rapid-acting and intermediate-acting insulins in Insulin Lispro Protamine and Insulin Lispro Mix75/25 are fixed and do not allow for basal versus prandial dose adjustments.
Preparation Instructions Always check insulin labels before administration. This product is HUMALOG Mix75/25 [see Warnings and Precautions ( 5.4 )] . Insulin Lispro Protamine and Insulin Lispro 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 carefu...
Insulin Lispro Protamine and Insulin Lispro, injectable suspension, is a white and cloudy suspension of 100 units/mL (U-100) of 75% insulin lispro protamine and 25% insulin lispro available as: 3 mL single-patient-use KwikPen prefilled pen NDC 0002-8233-05 Insulin Lispro Protamine and Insulin Lispro Mix75/25 KwikPens must never be shared between patients, even if the needle is changed. Always use a new needle for ...
www.fda.gov/medwatchwww.fda.gov/safesharpsdisposalInsulin Lispro Protamine and Insulin Lispro Mix75/25 is indicated to improve glycemic control in adults with diabetes mellitus.
Limitations of Use:
The proportions of rapid-acting and intermediate-acting insulins in Insulin Lispro Protamine and Insulin Lispro Mix75/25 are fixed and do not allow for basal versus prandial dose adjustments.
Preparation Instructions
Administration Instructions
Dosage modification may be needed when Insulin Lispro Protamine and Insulin Lispro Mix75/25 is used concomitantly with certain drugs [see Drug Interactions (7)].
Injectable Suspension: 100 units/mL (U-100) of Insulin Lispro Protamine and Insulin Lispro, 75% insulin lispro protamine and 25% insulin lispro is a white and cloudy suspension available as:
Insulin Lispro Protamine and Insulin Lispro Mix75/25 is contraindicated:
Insulin Lispro Protamine and Insulin Lispro 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.
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.
Hypoglycemia is the most common adverse reaction associated with all insulins, including Insulin Lispro Protamine and Insulin Lispro 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.
Risk Factors for Hypoglycemia
The 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 insulins, the glucose lowering effect time course of Insulin Lispro Protamine and Insulin Lispro 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 Hypoglycemia
Patients 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.
Accidental mix-ups between insulin products have been reported. To avoid medication errors between Insulin Lispro Protamine and Insulin Lispro Mix75/25 and other insulins, instruct patients to always check the insulin label before each injection.
Severe, life-threatening, generalized allergy, including anaphylaxis, can occur with insulins, including Insulin Lispro Protamine and Insulin Lispro Mix75/25. If hypersensitivity reactions occur, discontinue Insulin Lispro Protamine and Insulin Lispro Mix75/25; treat per standard of care and monitor until symptoms and signs resolve. Insulin Lispro Protamine and Insulin Lispro Mix75/25 is contraindicated in patients who have had hypersensitivity reactions to Insulin Lispro Protamine and Insulin Lispro Mix75/25 or any of its excipients [see Contraindications (4)].
All insulins, including Insulin Lispro Protamine and Insulin Lispro 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).
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 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.
The following adverse reactions are discussed elsewhere in the labeling:
Adverse Reactions from Clinical Studies or Postmarketing Reports
The following adverse reactions have been identified during post-marketing use of Insulin Lispro Protamine and Insulin Lispro 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 intensification
Intensification 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 reactions
Severe, life-threatening, generalized allergy, including anaphylaxis.
Hypoglycemia
Hypoglycemia is the most commonly observed adverse reaction in Insulin Lispro Protamine and Insulin Lispro Mix75/25.
Hypokalemia
Insulin Lispro Protamine and Insulin Lispro Mix75/25 can cause a shift in potassium from the extracellular to intracellular space, possibly leading to hypokalemia.
Injection site reactions
Insulin Lispro Protamine and Insulin Lispro 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 Mix75/25.
Lipodystrophy
Administration of insulin subcutaneously, including Insulin Lispro Protamine and Insulin Lispro 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 amyloidosis
Localized 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 Errors
Medication errors in which other insulins have been accidentally substituted for Insulin Lispro Protamine and Insulin Lispro Mix75/25 have been identified during postapproval use.
Peripheral Edema
Insulins, including Insulin Lispro Protamine and Insulin Lispro Mix75/25, may cause sodium retention and edema, particularly if previously poor metabolic control is improved by intensified insulin therapy.
Weight gain
Weight gain can occur with insulins, including Insulin Lispro Protamine and Insulin Lispro Mix75/25, and has been attributed to the anabolic effects of insulin and the decrease in glycosuria.
Immunogenicity
As with all therapeutic proteins, insulin administration may cause anti-insulin antibodies to form. The incidence of antibody formation with Insulin Lispro Protamine and Insulin Lispro Mix75/25 is unknown.
Table 1 below presents clinically significant drug interactions with Insulin Lispro Protamine and Insulin Lispro Mix75/25.
| Drugs that May Increase the Risk of Hypoglycemia | |
| Drugs: | 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 Mix75/25 is co-administered with these drugs. |
| Drugs that May Decrease the Blood Glucose Lowering Effect of Insulin Lispro Protamine and Insulin Lispro Mix75/25 | |
| Drugs: | 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 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 Mix75/25 | |
| Drugs: | 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 Mix75/25 is co-administered with these drugs. |
| Drugs that May Blunt Signs and Symptoms of Hypoglycemia | |
| Drugs: | Beta-blockers, clonidine, guanethidine, and reserpine. |
| Intervention: | Increased frequency of glucose monitoring may be required when Insulin Lispro Protamine and Insulin Lispro Mix75/25 is co-administered with these drugs. |
Risk Summary
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 risk
Poorly 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 Data
Published 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 Data
Animal reproduction studies have not been performed with Insulin Lispro Protamine and Insulin Lispro Mix75/25. However, subcutaneous reproduction and teratology studies have been conducted with insulin lispro (a component of Insulin Lispro Protamine and Insulin Lispro 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 Summary
Available data from published literature suggests that exogenous human insulin products, including Insulin Lispro Protamine and Insulin Lispro Mix75/25, are transferred into human milk. There are no adverse reactions reported in breastfed infants in the literature. There are no data on the effects of exogenous human insulin products, including Insulin Lispro Protamine and Insulin Lispro 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 Mix75/25 or from the underlying maternal condition.
Safety and effectiveness of Insulin Lispro Protamine and Insulin Lispro Mix75/25 in pediatric patients have not been established.
Clinical studies of Insulin Lispro Protamine and Insulin Lispro Mix75/25 did not include sufficient numbers of patients aged 65 and over to determine whether they respond differently than younger patients. In patients aged 65 and over 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)].
The effect of renal impairment on the pharmacokinetics of Insulin Lispro Protamine and Insulin Lispro 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 Mix75/25 dose adjustment and more frequent glucose monitoring [see Warnings and Precautions (5.3)].
The effect of hepatic impairment on the pharmacokinetics of Insulin Lispro Protamine and Insulin Lispro 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 Mix75/25 dose adjustment and more frequent glucose monitoring [see Warnings and Precautions (5.3)].
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 a glucagon product for emergency use 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)].
Insulin lispro is a rapid-acting insulin analog 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 5.808 kDa, both identical to that of human insulin.
Insulin Lispro Protamine and Insulin Lispro 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 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 Mix75/25 injectable suspension is a white and cloudy, sterile suspension for subcutaneous use.
Each mL of Insulin Lispro Protamine and Insulin Lispro Mix75/25 contains 100 units of insulin lispro; dibasic sodium phosphate (2.0 mg), glycerin (16 mg), metacresol (1.76 mg), phenol (0.715 mg), protamine sulfate (0.28 mg), zinc oxide content adjusted to provide zinc ion (0.025 mg), and Water for Injection, USP. The pH is 7.0 to 7.8. Sodium hydroxide and/or hydrochloric acid is added during manufacture to adjust the pH.
The primary activity of insulin, including Insulin Lispro Protamine and Insulin Lispro 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.
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 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 Mix75/25. The median maximum pharmacologic effect of Insulin Lispro Protamine and Insulin Lispro 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 Mix75/25 and HUMULIN® 70/30 were assessed and are presented in Figure 2. Insulin Lispro Protamine and Insulin Lispro 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 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 Mix75/25 or HUMULIN 70/30 in Healthy Subjects.
Absorption — Insulin Lispro Protamine and Insulin Lispro 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 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 Mix75/25. Insulin Lispro Protamine and Insulin Lispro 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 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 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 Populations
The effects of age, race, obesity, pregnancy, smoking, or renal or hepatic impairment on the pharmacokinetics of Insulin Lispro Protamine and Insulin Lispro Mix75/25 have not been studied.
Gender — Pharmacokinetic and pharmacodynamic comparisons between men and women administered Insulin Lispro Protamine and Insulin Lispro Mix75/25 showed no gender differences.
Standard 2-year carcinogenicity studies in animals have not been performed with Insulin Lispro Protamine and Insulin Lispro 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 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.
Insulin Lispro Protamine and Insulin Lispro, injectable suspension, is a white and cloudy suspension of 100 units/mL (U-100) of 75% insulin lispro protamine and 25% insulin lispro available as:
| 3 mL single-patient-use KwikPen prefilled pen | NDC 0002-8233-05 |
Insulin Lispro Protamine and Insulin Lispro 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 Mix75/25 KwikPen dials in 1 unit increments.
Dispense in the original sealed carton with the enclosed Instructions for Use.
Protect from direct heat and light. Do not freeze and do not use if it has been frozen. See storage table below:
| Not In-Use (Unopened) Refrigerated (36° to 46°F [2° to 8°C]) | Not In Use (Unopened) Room Temperature (up to 86°F [30°C]) | In-Use (Opened) (see temperature below) | |
| 3 mL single-patient-use KwikPen | Until expiration date | 10 days | 10 days Room temperature only (Do not refrigerate) |
Advise the patient to read the FDA-approved patient labeling (Patient Information and Instructions for Use).
Never Share an Insulin Lispro Protamine and Insulin Lispro Mix75/25 KwikPen Between Patients
Advise patients using Insulin Lispro Protamine and Insulin Lispro 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 Hypoglycemia
Inform 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 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 Errors
Instruct patients to always check the insulin label before each injection to avoid mix-ups between insulin products [see Warnings and Precautions (5.4)].
Hypersensitivity Reactions
Advise patients that hypersensitivity reactions have occurred with Insulin Lispro Protamine and Insulin Lispro 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 Company
Indianapolis, IN 46285, USA
US License Number 1891
Humalog® Mix75/25™ and KwikPen® are trademarks of Eli Lilly and Company.
Copyright © 1999, 2023, Eli Lilly and Company. All rights reserved.
ILPILIS7525-0002-USPI-20230721
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| PATIENT INFORMATION Insulin Lispro Protamine and Insulin Lispro [IHN-soo-lihn LIYS-proh] injectable suspension, for subcutaneous use This product is HUMALOG® Mix75/25™ (insulin lispro protamine and insulin lispro). | ||
| Do not share your Insulin Lispro Protamine and Insulin Lispro 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 Mix75/25?
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| Who should not take Insulin Lispro Protamine and Insulin Lispro Mix75/25? Do not take Insulin Lispro Protamine and Insulin Lispro Mix75/25 if you:
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| What should I tell my healthcare provider before taking Insulin Lispro Protamine and Insulin Lispro Mix75/25? Before taking Insulin Lispro Protamine and Insulin Lispro Mix75/25, tell your healthcare provider about all of your medical conditions, including if you:
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| 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 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 Mix75/25?
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| Keep Insulin Lispro Protamine and Insulin Lispro Mix75/25 and all medicines out of the reach of children. | ||
| Your dose of Insulin Lispro Protamine and Insulin Lispro 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 Mix75/25? While taking Insulin Lispro Protamine and Insulin Lispro Mix75/25 do not:
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| What are the possible side effects of Insulin Lispro Protamine and Insulin Lispro Mix75/25? Insulin Lispro Protamine and Insulin Lispro Mix75/25 may cause serious side effects that can lead to death, including:
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Your healthcare provider may prescribe a glucagon product for emergency use 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.
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| Treatment with TZDs and Insulin Lispro Protamine and Insulin Lispro 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: | ||
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| The most common side effects of Insulin Lispro Protamine and Insulin Lispro Mix75/25 include: | ||
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| These are not all the possible side effects of Insulin Lispro Protamine and Insulin Lispro 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 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 Mix75/25 for a condition for which it was not prescribed. Do not give Insulin Lispro Protamine and Insulin Lispro 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 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 Mix75/25 that is written for health professionals. | ||
| What are the ingredients in Insulin Lispro Protamine and Insulin Lispro Mix75/25? Active ingredients: insulin lispro Inactive ingredients: dibasic sodium phosphate, glycerin, hydrochloric acid, metacresol, phenol, protamine sulfate, sodium hydroxide, zinc oxide (zinc ion), and Water for Injection, USP. Humalog® Mix75/25™ and KwikPen® are trademarks of Eli Lilly and Company. Manufactured by: Eli Lilly and Company, Indianapolis, IN 46285, USA, US License Number 1891 Copyright © 1999, 2023, Eli Lilly and Company. All rights reserved. For more information, call 1-800-545-5979. | ||
ILPILIS7525-0002-PPI-20230721
INSTRUCTIONS FOR USE
Insulin Lispro Protamine and Insulin Lispro [IHN-soo-lihn LIYS-proh] Mix75/25™ KwikPen®
injectable suspension, for subcutaneous use
3 mL single-patient-use pen (100 units per mL)
This product is HUMALOG® Mix75/25™ (insulin lispro protamine and insulin lispro).
Read this Instructions for Use before you start taking Insulin Lispro Protamine and Insulin Lispro 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 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 Mix75/25 KwikPen (“Pen”) is a disposable single-patient-use prefilled pen containing 300 units of Insulin Lispro Protamine and Insulin Lispro Mix75/25.
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 Mix75/25 KwikPen
Supplies you will need to give your injection
Preparing your Pen
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Priming your Pen
Prime your Pen before each injection.
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Selecting your dose
Step 11:
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Giving your injection
Step 12:
|  |
Step 13:
|  |
Step 14:
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 injection
Step 15:
|  |
Step 16:
|  |
Step 17:
|  |
Disposing of Pens and Needles
www.fda.gov/safesharpsdisposal
Storing your Pen
Unused Pens
In-use Pen
General information about the safe and effective use of your Pen
Troubleshooting
If you have any questions or problems with your Insulin Lispro Protamine and Insulin Lispro Mix75/25 KwikPen, contact Lilly at 1-800-LillyRx (1-800-545-5979) or call your healthcare provider for help.
Manufactured by:
Eli Lilly and Company
Indianapolis, IN 46285, USA
US License Number 1891
This Instructions for Use has been approved by the U.S. Food and Drug Administration.
Revised: 07/2023
Humalog® Mix75/25™ and KwikPen® are trademarks of Eli Lilly and Company.
Copyright © 2007, 2023, Eli Lilly and Company. All rights reserved.
| Insulin Lispro Protamine and Insulin Lispro Mix75/25 KwikPen meets the current dose accuracy and functional requirements of ISO 11608-1. |
ILPILIS7525KP-0003-IFU-20230721
PACKAGE CARTON – Insulin Lispro Protamine and Insulin Lispro Injectable Suspension KwikPen Mix75/25™ 5ct
NDC 0002-8233-05
Insulin Lispro Protamine and Insulin Lispro KwikPen Mix75/25™ Injectable Suspension
For Single Patient Use Only
Dispense in this sealed carton.
Needles not included
100 units per mL (U-100)
This device is recommended for use with Becton, Dickinson and Company's insulin pen needles
For subcutaneous use only.
prefilled insulin delivery device
Rx only
This product is Humalog Mix75/25.
5 x 3 mL Prefilled Pens
Read Insulin Delivery Device Instructions for Use
| RxCUI | RxNorm string | TTY | SPL version |
|---|---|---|---|
| 847252 | insulin lispro protamine / insulin lispro 75/25 in 3 ML Pen Injector | PSN | 11 |
| 847252 | 3 ML insulin lispro 25 UNT/ML / insulin lispro protamine, human 75 UNT/ML Pen Injector | SCD | 11 |
| 847252 | insulin lispro protamine 75 UNT/ML / insulin lispro 25 UNT/ML per 3 ML Pen Injector | SY | 11 |
| Class | Version | Type | Effective |
|---|---|---|---|
| INSULIN LISPRO Pharmacologic Class Indexing | 2 | Indexing - Pharmacologic Class | 20110223 |
| Product concept | Relation | Version | Effective |
|---|---|---|---|
| a42609d2-d76b-4c21-bc65-ace5fa0da69d | Product name | 1 | 20210105 |
| 0c5ba5d1-c81f-5bcc-49a8-b8e264edfb14 | Product name | 3 | 20200325 |
| 4477e8cc-8057-4880-8829-dfea528a2efa | Product name | 2 | 20200325 |
| Package NDC | Product | Description | Form | Quantity | Strength | SPL version |
|---|---|---|---|---|---|---|
| 0002-8233-01 | Insulin Lispro Protamine and Insulin Lispro Injectable Suspension Mix75/25 KwikPen | 3 mL in 1 SYRINGE | INJECTION, SUSPENSION | 3 | 11 | |
| 0002-8233-05 | Insulin Lispro Protamine and Insulin Lispro Injectable Suspension Mix75/25 KwikPen | 5 in 1 CARTON | INJECTION, SUSPENSION | 5 | 11 |
| NDC | Dashboard title | SPL version | Validation | Dashboard ZIP |
|---|---|---|---|---|
| 0002-8233 | INSULIN LISPRO PROTAMINE AND INSULIN LISPRO INJECTABLE SUSPENSION MIX75/25 KWIKPEN (INSULIN LISPRO) INJECTION, SUSPENSION [ELI LILLY AND COMPANY] | 11 | Current NDC, Legacy NDC, 2 package rows | 20240809_e49f701d-c19f-4cb2-b63f-01a917b33abc.zip |
| Package NDC | Billing unit | Product NDC | DailyMed indexing SPL | SPL version | Effective |
|---|---|---|---|---|---|
| 0002-8233-01 | ML - Milliliter | 0002-8233 | 4a2fed7b-72a3-4e42-8e76-f48c3c1a3e7b | 1 | 2020-04-20 |
| 0002-8233-05 | ML - Milliliter | 0002-8233 | d0f86a34-6362-454b-9fdf-b12594c4825c | 1 | 2020-04-20 |
Every source-derived product name is available through these pages.
| Product NDC | Package NDC |
|---|---|
| 0002-8233 | 0002-8233-01, 0002-8233-05 |
| BLA | Proprietary name | Proper name | License type | Status | Latest source |
|---|---|---|---|---|---|
| 021017 | Humalog Mix 75/25 | insulin lispro protamine and insulin lispro | 351(a) | Rx | 2026-09-01 |
Every source-derived ingredient row is available through these pages.
| Name | UNII | Kind |
|---|---|---|
| Insulin lispro | GFX7QIS1II | ACTIB |
| Protamine sulfate | 0DE9724IHC | IACT |
| Glycerin | PDC6A3C0OX | IACT |
| Sodium Phosphate, Dibasic, Unspecified Form | GR686LBA74 | IACT |
| Metacresol | GGO4Y809LO | IACT |
| Zinc oxide | SOI2LOH54Z | IACT |
| Phenol | 339NCG44TV | IACT |
| Water | 059QF0KO0R | IACT |
| Hydrochloric acid | QTT17582CB | IACT |
| Sodium hydroxide | 55X04QC32I | IACT |
OpenFDA label data provides additional search and identifier links. DailyMed’s Structured Product Label is the canonical label on FDA.report. Matching records are deduplicated before they are shown below.
| Brand | Generic | Manufacturer | SPL set ID | Effective date | Available safety fields | Join |
|---|---|---|---|---|---|---|
| Insulin Lispro Protamine and Insulin Lispro Injectable Suspension Mix75/25 KwikPen | INSULIN LISPRO | Eli Lilly and Company | e49f701d-c19f-4cb2-b63f-01a917b33abc | 2024-08-06 | Warnings, Adverse reactions | 0002-8233-01 0002-8233-05 0002-8233 00002823301 00002823305 03dce3f6-da85-4635-9c62-478226005b60 e49f701d-c19f-4cb2-b63f-01a917b33abc |
Adverse event summaries are temporarily unavailable. Other product information remains available.
