These highlights do not include all the information needed to use INSULIN LISPRO safely and effectively. See full prescribing information for INSULIN LISPRO. INSULIN LISPRO injection, for subcutaneous or intravenous use Initial U.S. Approval: 1996

Insulin Lispro by

Drug Labeling and Warnings

Insulin Lispro by is a Prescription medication manufactured, distributed, or labeled by REMEDYREPACK INC.. Drug facts, warnings, and ingredients follow.

Drug Details [pdf]

INSULIN LISPRO- insulin lispro injection, solution 
REMEDYREPACK INC.

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FULL PRESCRIBING INFORMATION

1 INDICATIONS AND USAGE

Insulin Lispro Injection is a rapid acting human insulin analog indicated to improve glycemic control in adults and children with diabetes mellitus.

2 DOSAGE AND ADMINISTRATION

2.1 Important Administration Instructions

• Always check insulin labels before administration [see Warnings and Precautions ( 5.4)] .
• Inspect Insulin Lispro Injection visually before use. It should appear clear and colorless. Do not use Insulin Lispro Injection if particulate matter or coloration is seen.
• Use Insulin Lispro Injection prefilled pens with caution in patients with visual impairment that may rely on audible clicks to dial their dose.
• Do NOT mix Insulin Lispro Injection with other insulins when administering using a continuous subcutaneous infusion pump.
• Do NOT perform dose conversion when using any Insulin Lispro Injection prefilled pens. The dose window shows the number of insulin units to be delivered and no conversion is needed.

2.2 Route of Administration

Subcutaneous Injection

• Administer the dose of Insulin Lispro Injection within fifteen minutes before a meal or immediately after a meal by injection into the subcutaneous tissue of the abdominal wall, thigh, upper arm, or buttocks. To reduce the risk of lipodystrophy and localized cutaneous amyloidosis, rotate the injection site within the same region from one injection to the next. 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)] .
• Insulin Lispro Injection administered by subcutaneous injection should generally be used in regimens with an intermediate- or long-acting insulin.
• The Insulin Lispro Injection KwikPen dials in 1 unit increments and delivers a maximum dose of 60 units per injection.
• The Insulin Lispro Injection Junior KwikPen dials in 0.5 unit increments and delivers a maximum dose of 30 units per injection.

Continuous Subcutaneous Infusion (Insulin Pump)

• Administer Insulin Lispro Injection by continuous subcutaneous infusion in a region recommended in the instructions from the pump manufacturer. Rotate infusion sites within the same region 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)] .
• Follow healthcare professional recommendations when setting basal and meal time infusion rate.
• Do NOT dilute or mix Insulin Lispro Injection when administering by continuous subcutaneous infusion.
• Change Insulin Lispro Injection in the pump reservoir at least every 7 days.
• Change the infusion sets and the infusion set insertion site at least every 3 days.
• Do NOT expose Insulin Lispro Injection in the pump reservoir to temperatures greater than 98.6°F (37°C).
• Use Insulin Lispro Injection in pump systems suitable for insulin infusion [see Patient Counseling Information ( 17)] .

Intravenous Administration

• Dilute Insulin Lispro Injection to concentrations from 0.1 unit/mL to 1.0 unit/mL using 0.9% Sodium Chloride Injection, USP.
• Administer Insulin Lispro Injection intravenously ONLY under medical supervision with close monitoring of blood glucose and potassium levels to avoid hypoglycemia and hypokalemia [see Warnings and Precautions ( 5.3, 5.6) and How Supplied/Storage and Handling ( 16.4)] .

2.3 Dosage Information

• Individualize and adjust the dosage of Insulin Lispro Injection based on route of administration, the individual's metabolic needs, blood glucose monitoring results and glycemic control goal.
• 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)] .
• Do NOT perform dose conversion when using the Insulin Lispro Injection prefilled pens. The dose window shows the number of insulin units to be delivered and no conversion is needed.

2.4 Dosage Adjustment Due to Drug Interactions

• Dosage adjustment may be needed when Insulin Lispro Injection is coadministered with certain drugs [see Drug Interactions ( 7)] .
• Dosage adjustment may be needed when switching from another insulin to Insulin Lispro Injection [see Warnings and Precautions ( 5.2)] .
• Instructions for Mixing with Other Insulins

• Insulin Lispro Injection subcutaneous injection route:
  • Insulin Lispro Injection may be mixed with NPH insulin preparations ONLY.
  • If Insulin Lispro Injection is mixed with NPH insulin, Insulin Lispro Injection should be drawn into the syringe first. Injection should occur immediately after mixing.
• Insulin Lispro Injection continuous subcutaneous infusion route (Insulin Pump):
  • Do NOT mix Insulin Lispro Injection with any other insulin.

3 DOSAGE FORMS AND STRENGTHS

Injection: 100 units per mL (U-100) clear and colorless solution available as:

• 10 mL multiple-dose vial
• 3 mL single-patient-use Insulin Lispro Injection KwikPen
• 3 mL single-patient-use Insulin Lispro Injection Junior KwikPen

4 CONTRAINDICATIONS

Insulin Lispro Injection is contraindicated:

• during episodes of hypoglycemia
• in patients who are hypersensitive to Insulin Lispro Injection or to any of its excipients.

5 WARNINGS AND PRECAUTIONS

5.1 Never Share an Insulin Lispro Injection Prefilled Pen or Syringe Between Patients

Insulin Lispro Injection prefilled pens must never be shared between patients, even if the needle is changed. Patients using Insulin Lispro Injection vials must never share needles or syringes with another person. 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 antidiabetic products may be needed.

5.3 Hypoglycemia

Hypoglycemia is the most common adverse reaction associated with insulins, including Insulin Lispro Injection. Severe hypoglycemia can cause seizures, 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 insulin preparations, the glucose lowering effect time course of Insulin Lispro Injection 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.

5.4 Hypoglycemia Due to Medication Errors

Accidental mix-ups between basal insulin products and other insulins, particularly rapid-acting insulins, have been reported. To avoid medication errors between Insulin Lispro Injection 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 Injection. If hypersensitivity reactions occur, discontinue Insulin Lispro Injection; treat per standard of care and monitor until symptoms and signs resolve [see Adverse Reactions ( 6.1)] . Insulin Lispro Injection is contraindicated in patients who have had hypersensitivity reactions to Insulin Lispro Injection or any of its excipients [see Contraindications ( 4)] .

5.6 Hypokalemia

All insulin products, including Insulin Lispro Injection, 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 Injection, 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.

5.8 Hyperglycemia and Ketoacidosis Due to Insulin Pump Device Malfunction

Malfunction of the insulin pump or insulin infusion set or insulin degradation can rapidly lead to hyperglycemia and ketoacidosis. Prompt identification and correction of the cause of hyperglycemia or ketosis is necessary. Interim subcutaneous injections with Insulin Lispro Injection may be required. Patients using continuous subcutaneous insulin infusion pump therapy must be trained to administer insulin by injection and have alternate insulin therapy available in case of pump failure [see How Supplied/Storage and Handling ( 16.2) and Patient Counseling Information ( 17)] .

6 ADVERSE REACTIONS

The following adverse reactions are discussed elsewhere:

• Hypoglycemia [see Warnings and Precautions ( 5.3)] .
• Hypokalemia [see Warnings and Precautions ( 5.6)] .

6.1 Clinical Trial Experience

Because clinical trials are conducted under widely varying designs, the adverse reaction rates reported in one clinical trial may not be easily compared with those rates reported in another clinical trial, and may not reflect the rates actually observed in clinical practice.

The frequencies of Treatment-Emergent Adverse Events during Insulin Lispro Injection clinical trials in patients with type 1 diabetes mellitus and type 2 diabetes mellitus are listed in the tables below.

Table 1: Treatment-Emergent Adverse Events in Patients with Type 1 Diabetes Mellitus (adverse events with frequency ≥5%)

Events, n (%)	Insulin Lispro Injection; (n=81)	Regular human insulin; (n=86)
Flu syndrome	28 (34.6)	28 (32.6)
Pharyngitis	27 (33.3)	29 (33.7)
Rhinitis	20 (24.7)	25 (29.1)
Headache	24 (29.6)	19 (22.1)
Pain	16 (19.8)	14 (16.3)
Cough increased	14 (17.3)	15 (17.4)
Infection	11 (13.6)	18 (20.9)
Nausea	5 (6.2)	13 (15.1)
Accidental injury	7 (8.6)	10 (11.6)
Surgical procedure	5 (6.2)	12 (14.0)
Fever	5 (6.2)	10 (11.6)
Abdominal pain	6 (7.4)	7 (8.1)
Asthenia	6 (7.4)	7 (8.1)
Bronchitis	6 (7.4)	6 (7.0)
Diarrhea	7 (8.6)	5 (5.8)
Dysmenorrhea	5 (6.2)	6 (7.0)
Myalgia	6 (7.4)	5 (5.8)
Urinary tract infection	5 (6.2)	4 (4.7)

Table 2: Treatment-Emergent Adverse Events in Patients with Type 2 Diabetes Mellitus (adverse events with frequency ≥5%)

Events, n (%)	Insulin Lispro Injection; (n=714)	Regular human insulin; (n=709)
Headache	83 (11.6)	66 (9.3)
Pain	77 (10.8)	71 (10.0)
Infection	72 (10.1)	54 (7.6)
Pharyngitis	47 (6.6)	58 (8.2)
Rhinitis	58 (8.1)	47 (6.6)
Flu syndrome	44 (6.2)	58 (8.2)
Surgical procedure	53 (7.4)	48 (6.8)

Insulin initiation and intensification of glucose control

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. However, long-term glycemic control decreases the risk of diabetic retinopathy and neuropathy.

Lipodystrophy

Long-term use of insulin, including Insulin Lispro Injection, can cause lipodystrophy at the site of repeated insulin injections or infusion. Lipodystrophy includes lipohypertrophy (thickening of adipose tissue) and lipoatrophy (thinning of adipose tissue), and may affect insulin absorption. Rotate insulin injection or infusion sites within the same region to reduce the risk of lipodystrophy [see Dosage and Administration ( 2.2)] .

Weight gain

Weight gain can occur with insulin therapy, including Insulin Lispro Injection, and has been attributed to the anabolic effects of insulin and the decrease in glucosuria.

Peripheral Edema

Insulin, including Insulin Lispro Injection, may cause sodium retention and edema, particularly if previously poor metabolic control is improved by intensified insulin therapy.

Adverse Reactions with Continuous Subcutaneous Insulin Infusion (CSII)

In a 12-week, randomized, crossover study in adult patients with type 1 diabetes (n=39), the rates of catheter occlusions and infusion site reactions were similar for Insulin Lispro Injection and regular human insulin treated patients ( see Table 3).

Table 3: Catheter Occlusions and Infusion Site Reactions

	Insulin Lispro Injection; (n=38)	Regular human insulin; (n=39)
Catheter occlusions/month	0.09	0.10
Infusion site reactions	2.6% (1/38)	2.6% (1/39)

In a randomized, 16-week, open-label, parallel design study of children and adolescents with type 1 diabetes, adverse event reports related to infusion-site reactions were similar for Insulin Lispro Injection and insulin aspart (21% of 100 patients versus 17% of 198 patients, respectively). In both groups, the most frequently reported infusion site adverse events were infusion site erythema and infusion site reaction.

Allergic Reactions

Local Allergy — As with any insulin therapy, patients taking Insulin Lispro Injection may experience redness, swelling, or itching at the site of the injection. These minor reactions usually resolve in a few days to a few weeks, but in some occasions, may require discontinuation of Insulin Lispro Injection. In some instances, these reactions may be related to factors other than insulin, such as irritants in a skin cleansing agent or poor injection technique.

Systemic Allergy — Severe, life-threatening, generalized allergy, including anaphylaxis, may occur with any insulin, including Insulin Lispro Injection. Generalized allergy to insulin may cause whole body rash (including pruritus), dyspnea, wheezing, hypotension, tachycardia, or diaphoresis.

In controlled clinical trials, pruritus (with or without rash) was seen in 17 patients receiving regular human insulin (n=2969) and 30 patients receiving Insulin Lispro Injection (n=2944).

Localized reactions and generalized myalgias have been reported with injected metacresol, which is an excipient in Insulin Lispro Injection [see Contraindications ( 4)] .

Antibody Production

In large clinical trials with patients with type 1 (n=509) and type 2 (n=262) diabetes mellitus, anti-insulin antibody (insulin lispro-specific antibodies, insulin-specific antibodies, cross-reactive antibodies) formation was evaluated in patients receiving both regular human insulin and Insulin Lispro Injection (including patients previously treated with human insulin and naive patients). As expected, the largest increase in the antibody levels occurred in patients new to insulin therapy. The antibody levels peaked by 12 months and declined over the remaining years of the study. These antibodies do not appear to cause deterioration in glycemic control or necessitate an increase in insulin dose. There was no statistically significant relationship between the change in the total daily insulin dose and the change in percent antibody binding for any of the antibody types.

6.2 Postmarketing Experience

The following additional adverse reactions have been identified during post-approval use of Insulin Lispro Injection. Because 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.

Medication errors in which other insulins have been accidentally substituted for Insulin Lispro Injection have been identified during post-approval use [see Patient Counseling Information ( 17)] .

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.

7 DRUG INTERACTIONS

7.1 Drugs That May Increase the Risk of Hypoglycemia

The risk of hypoglycemia associated with Insulin Lispro Injection use may be increased when co-administered with antidiabetic agents, salicylates, sulfonamide antibiotics, monoamine oxidase inhibitors, fluoxetine, pramlintide, disopyramide, fibrates, pentoxifylline, ACE inhibitors, angiotensin II receptor blocking agents, and somatostatin analogs (e.g., octreotide). Dose adjustment and increased frequency of glucose monitoring may be required when Insulin Lispro Injection is co-administered with these drugs.

7.2 Drugs That May Decrease the Blood Glucose Lowering Effect of Insulin Lispro Injection

The glucose lowering effect of Insulin Lispro Injection may be decreased when co-administered with corticosteroids, isoniazid, niacin, estrogens, oral contraceptives, phenothiazines, danazol, diuretics, sympathomimetic agents (e.g., epinephrine, albuterol, terbutaline), somatropin, atypical antipsychotics, glucagon, protease inhibitors, and thyroid hormones. Dose adjustment and increased frequency of glucose monitoring may be required when Insulin Lispro Injection is co-administered with these drugs.

7.3 Drugs That May Increase or Decrease the Blood Glucose Lowering Effect of Insulin Lispro Injection

The glucose lowering effect of Insulin Lispro Injection may be increased or decreased with co-administered with beta-blockers, clonidine, lithium salts, and alcohol. Pentamidine may cause hypoglycemia, which may sometimes be followed by hyperglycemia. Dose adjustment and increased frequency of glucose monitoring may be required when Insulin Lispro Injection is co-administered with these drugs.

7.4 Drugs That May Blunt Signs and Symptoms of Hypoglycemia

The signs and symptoms of hypoglycemia [see Warnings and Precautions ( 5.3)] may be blunted when beta-blockers, clonidine, guanethidine, and reserpine are co-administered with Insulin Lispro Injection.

8 USE IN SPECIFIC POPULATIONS

8.1 Pregnancy

Risk Summary

The limited available data with Insulin Lispro Injection 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 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, stillbirth, 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

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.

8.2 Lactation

Risk Summary

There are no data on the presence of Insulin Lispro Injection 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 Injection on the breastfed infant and no available information on the effects of Insulin Lispro Injection 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 Injection or from the underlying maternal condition.

8.4 Pediatric Use

Insulin Lispro Injection is approved for use in children for subcutaneous daily injections [see Clinical Studies ( 14)]. Insulin Lispro Injection is approved for use in children by continuous subcutaneous infusion in insulin pumps. Insulin Lispro Injection has not been studied in pediatric patients younger than 3 years of age. Insulin Lispro Injection has not been studied in pediatric patients with type 2 diabetes.

As in adults, the dosage of Insulin Lispro Injection must be individualized in pediatric patients based on metabolic needs and results of frequent monitoring of blood glucose.

8.5 Geriatric Use

Of the total number of subjects (n=2834) in eight clinical studies of Insulin Lispro Injection, twelve percent (n=338) were 65 years of age or over. The majority of these had type 2 diabetes. HbA 1c values and hypoglycemia rates did not differ by age. Pharmacokinetic/pharmacodynamic studies to assess the effect of age on the onset of Insulin Lispro Injection action have not been performed.

8.6 Renal Impairment

Patients with renal impairment may be at increased risk of hypoglycemia and may require more frequent Insulin Lispro Injection dose adjustment and more frequent blood glucose monitoring [see Clinical Pharmacology ( 12.3)] .

8.7 Hepatic Impairment

Patients with hepatic impairment may be at increased risk of hypoglycemia and may require more frequent Insulin Lispro Injection dose adjustment and more frequent blood glucose monitoring [see Clinical Pharmacology ( 12.3)] .

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/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.

11 DESCRIPTION

Insulin Lispro Injection is 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 C 257H 383N 65O 77S 6 and a molecular weight of 5808, both identical to that of human insulin.

Insulin Lispro Injection has the following primary structure:

Insulin Lispro Injection is a sterile, aqueous, clear, and colorless solution for subcutaneous or intravenous use. Each milliliter of Insulin Lispro Injection contains 100 units of insulin lispro, dibasic sodium phosphate (1.88 mg), glycerin (16 mg), Metacresol (3.15 mg), zinc oxide (content adjusted to provide 0.0197 mg zinc ion), trace amounts of phenol, and Water for Injection, USP. Insulin lispro has a pH of 7.0 to 7.8.

The pH is adjusted by addition of aqueous solutions of hydrochloric acid 10% and/or sodium hydroxide 10%.

12 CLINICAL PHARMACOLOGY

12.1 Mechanism of Action

Regulation of glucose metabolism is the primary activity of insulins and insulin analogs, including insulin lispro. 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

Insulin Lispro Injection has been shown to be equipotent to human insulin on a molar basis. One unit of Insulin Lispro Injection has the same glucose-lowering effect as one unit of regular human insulin. Studies in normal volunteers and patients with diabetes demonstrated that Insulin Lispro Injection has a more rapid onset of action and a shorter duration of activity than regular human insulin when given subcutaneously.

The time course of action of insulin and insulin analogs, such as Insulin Lispro Injection, may vary considerably in different individuals or within the same individual. The parameters of Insulin Lispro Injection activity (time of onset, peak time, and duration) as designated in Figure 1 should be considered only as general guidelines. The rate of insulin absorption, and consequently the onset of activity are known to be affected by the site of injection, exercise, and other variables [see Warnings and Precautions ( 5.2)] .

a Baseline insulin concentration was maintained by infusion of 0.2 mU/min/kg human insulin.

Intravenous Administration — The glucose lowering effect of intravenously administered Insulin Lispro Injection was tested in 21 patients with type 1 diabetes. For the study, the patients' usual doses of insulin were held and blood glucose concentrations were allowed to reach a stable range of 200 to 260 mg/dL during a one to three hours run-in phase. The run-in phase was followed by a 6-hour assessment phase. During the assessment phase, patients received intravenous Insulin Lispro Injection at an initial infusion rate of 0.5 units/hour. The infusion rate of Insulin Lispro Injection could be adjusted at regular timed intervals to achieve and maintain blood glucose concentrations between 100 to 160 mg/dL.

The mean blood glucose levels during the assessment phase for patients on Insulin Lispro Injection therapy are summarized below in Table 4. All patients achieved the targeted glucose range at some point during the 6-hour assessment phase. At the endpoint, blood glucose was within the target range (100 to 160 mg/dL) for 17 of 20 patients treated with Insulin Lispro Injection. The average time (±SE) required to attain near normoglycemia was 129 ± 14 minutes for Insulin Lispro Injection.

Table 4: Mean Blood Glucose Concentrations (mg/dL) During Intravenous Infusions of Insulin Lispro Injection

a Results shown as mean ± SD
Time from Start of Infusion (minutes)	Mean Blood Glucose (mg/dL) Intravenous a
0	224 ± 16
30	205 ± 21
60	195 ± 20
120	165 ± 26
180	140 ± 26
240	123 ± 20
300	120 ± 27
360	122 ± 25

12.3 Pharmacokinetics

Absorption and Bioavailability — Studies in healthy volunteers and patients with diabetes demonstrated that Insulin Lispro Injection is absorbed more quickly than regular human insulin. In healthy volunteers given subcutaneous doses of Insulin Lispro Injection ranging from 0.1 to 0.4 unit/kg, peak serum levels were seen 30 to 90 minutes after dosing. When healthy volunteers received equivalent doses of regular human insulin, peak insulin levels occurred between 50 to 120 minutes after dosing. Similar results were seen in patients with type 1 diabetes ( see Figure 2).

a Baseline insulin concentration was maintained by infusion of 0.2 mU/min/kg human insulin.

Insulin Lispro Injection was absorbed at a consistently faster rate than regular human insulin in healthy male volunteers given 0.2 unit/kg at abdominal, deltoid, or femoral subcutaneous sites. After Insulin Lispro Injection was administered in the abdomen, serum drug levels were higher and the duration of action was slightly shorter than after deltoid or thigh administration. Bioavailability of Insulin Lispro Injection is similar to that of regular human insulin. The absolute bioavailability after subcutaneous injection ranges from 55% to 77% with doses between 0.1 to 0.2 unit/kg, inclusive.

Distribution — When administered intravenously as bolus injections of 0.1 and 0.2 U/kg dose in two separate groups of healthy subjects, the mean volume of distribution of Insulin Lispro Injection appeared to decrease with increase in dose (1.55 and 0.72 L/kg, respectively) in contrast to that of regular human insulin for which, the volume of distribution was comparable across the two dose groups (1.37 and 1.12 L/kg for 0.1 and 0.2 U/kg dose, respectively).

Metabolism — Human metabolism studies have not been conducted. However, animal studies indicate that the metabolism of Insulin Lispro Injection is identical to that of regular human insulin.

Elimination — After subcutaneous administration of Insulin Lispro Injection, the t 1/2 is shorter than that of regular human insulin (1 versus 1.5 hours, respectively). When administered intravenously, Insulin Lispro Injection and regular human insulin demonstrated similar dose-dependent clearance, with a mean clearance of 21.0 mL/min/kg and 21.4 mL/min/kg, respectively (0.1 unit/kg dose), and 9.6 mL/min/kg and 9.4 mL/min/kg, respectively (0.2 unit/kg dose). Accordingly, Insulin Lispro Injection demonstrated a mean t 1/2 of 0.85 hours (51 minutes) and 0.92 hours (55 minutes), respectively for 0.1 unit/kg and 0.2 unit/kg doses, and regular human insulin mean t 1/2 was 0.79 hours (47 minutes) and 1.28 hours (77 minutes), respectively for 0.1 unit/kg and 0.2 unit/kg doses.

Specific Populations

The effects of age, gender, race, obesity, pregnancy, or smoking on the pharmacokinetics of Insulin Lispro Injection have not been studied.

Renal Impairment — Type 2 diabetic patients with varying degree of renal impairment showed no difference in pharmacokinetics of regular insulin and Insulin Lispro Injection. However, the sensitivity of the patients to insulin did change, with an increased response to insulin as the renal function declined. Some studies with human insulin have shown increased circulating levels of insulin in patients with renal impairment. Careful glucose monitoring and dose adjustments of insulin, including Insulin Lispro Injection, may be necessary in patients with renal dysfunction.

Hepatic Impairment — Type 2 diabetic patients with impaired hepatic function showed no effect on the pharmacokinetics of Insulin Lispro Injection as compared to patients with no hepatic dysfunction. However, some studies with human insulin have shown increased circulating levels of insulin in patients with liver failure. Careful glucose monitoring and dose adjustments of insulin, including Insulin Lispro Injection, may be necessary in patients with hepatic dysfunction.

13 NONCLINICAL TOXICOLOGY

13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility

Standard 2-year carcinogenicity studies in animals have not been performed. In Fischer 344 rats, a 12-month repeat-dose toxicity study was conducted with insulin lispro at subcutaneous doses of 20 and 200 units/kg/day (approximately 3 and 32 times the human subcutaneous dose of 1 unit/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/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/kg/day, based on units/body surface area), mating and fertility were not adversely affected in either gender at any dose.

13.2 Animal Toxicology and/or Pharmacology

In standard biological assays in fasted rabbits, 0.2 unit/kg of insulin lispro injected subcutaneously had the same glucose-lowering effect and had a more rapid onset of action as 0.2 unit/kg of regular human insulin.

14 CLINICAL STUDIES

The safety and efficacy of Insulin Lispro Injection were studied in children, adolescent, and adult patients with type 1 diabetes (n=789) and adult patients with type 2 diabetes (n=722).

14.1 Type 1 Diabetes – Adults and Adolescents

A 12-month, randomized, parallel, open-label, active-controlled study was conducted in patients with type 1 diabetes to assess the safety and efficacy of Insulin Lispro Injection (n=81) compared with Humulin ® R [insulin human injection (100 units per mL)] (n=86). Insulin Lispro Injection was administered by subcutaneous injection immediately prior to meals and Humulin R was administered 30 to 45 minutes before meals. Humulin ® U [ULTRALENTE ® human insulin (rDNA origin) extended zinc suspension] was administered once or twice daily as the basal insulin. There was a 2- to 4-week run-in period with Humulin R and Humulin U before randomization. Most patients were Caucasian (97%). Forty-seven percent of the patients were male. The mean age was 31 years (range 12 to 70 years). Glycemic control, the total daily doses of Insulin Lispro Injection and Humulin R, and the incidence of severe hypoglycemia (as determined by the number of events that were not self-treated) were similar in the two treatment groups. There were no episodes of diabetic ketoacidosis in either treatment group.

Table 5: Type 1 Diabetes Mellitus – Adults and Adolescents

a Values are Mean ± SD
b Severe hypoglycemia refers to hypoglycemia for which patients were not able to self-treat.
Treatment Duration; Treatment in Combination with:	12 months; Humulin U
	Insulin Lispro Injection	Humulin R
N	81	86
Baseline HbA 1c (%) a	8.2 ± 1.4	8.3 ± 1.7
Change from baseline HbA 1c (%) a	-0.1 ± 0.9	0.1 ± 1.1
Treatment Difference in HbA 1c Mean (95% confidence interval)	0.4 (0.0, 0.8)
Baseline short-acting insulin dose (units/kg/day)	0.3 ± 0.1	0.3 ± 0.1
End-of-Study short-acting insulin dose (units/kg/day)	0.3 ± 0.1	0.3 ± 0.1
Change from baseline short-acting insulin dose (units/kg/day)	0.0 ± 0.1	0.0 ± 0.1
Baseline Body weight (kg)	72 ± 12.7	71 ± 11.3
Weight change from baseline (kg)	1.4 ± 3.6	1.0 ± 2.6
Patients with severe hypoglycemia (n, %) b	14 (17%)	18 (21%)

14.2 Type 2 Diabetes – Adults

A 6-month randomized, crossover, open-label, active-controlled study was conducted in insulin-treated patients with type 2 diabetes (n=722) to assess the safety and efficacy of Insulin Lispro Injection for 3 months followed by Humulin R for 3 months or the reverse sequence. Insulin Lispro Injection was administered by subcutaneous injection immediately before meals and Humulin R was administered 30 to 45 minutes before meals. Humulin ® N [NPH human insulin (rDNA origin) isophane suspension] or Humulin U was administered once or twice daily as the basal insulin. All patients participated in a 2- to 4-week run-in period with Humulin R and Humulin N or Humulin U. Most of the patients were Caucasian (88%), and the numbers of men and women in each group were approximately equal. The mean age was 58.6 years (range 23.8 to 85 years). The average body mass index (BMI) was 28.2 kg/m 2. During the study, the majority of patients used Humulin N (84%) compared with Humulin U (16%) as their basal insulin. The reductions from baseline in HbA 1c and the incidence of severe hypoglycemia (as determined by the number of events that were not self-treated) were similar between the two treatments from the combined groups ( see Table 6).

Table 6: Type 2 Diabetes Mellitus — Adults

a Values are Mean ± SD
b Severe hypoglycemia refers to hypoglycemia for which patients were not able to self-treat.
		End point
	Baseline	Insulin Lispro Injection; +; Basal	Humulin R; +; Basal
HbA 1c (%) a	8.9 ± 1.7	8.2 ± 1.3	8.2 ± 1.4
Change from baseline HbA 1c (%) a	—	-0.7 ± 1.4	-0.7 ± 1.3
Short-acting insulin dose (units/kg/day) a	0.3 ± 0.2	0.3 ± 0.2	0.3 ± 0.2
Change from baseline short-acting insulin dose (units/kg/day) a	—	0.0 ± 0.1	0.0 ± 0.1
Body weight (kg) a	80 ± 15	81 ± 15	81 ± 15
Weight change from baseline	—	0.8 ± 2.7	0.9 ± 2.6
Patients with severe hypoglycemia (n, %) b	—	15 (2%)	16 (2%)

14.3 Type 1 Diabetes – Pediatric and Adolescents

An 8-month, crossover study of adolescents with type 1 diabetes (n=463), aged 9 to 19 years, compared two subcutaneous multiple-dose treatment regimens: Insulin Lispro Injection or Humulin R, both administered with Humulin N (NPH human insulin) as the basal insulin. Insulin Lispro Injection achieved glycemic control comparable to Humulin R, as measured by HbA 1c ( see Table 7), and both treatment groups had a comparable incidence of hypoglycemia. In a 9-month, crossover study of prepubescent children (n=60) with type 1 diabetes, aged 3 to 11 years, Insulin Lispro Injection administered immediately before meals, Insulin Lispro Injection administered immediately after meals and Humulin R administered 30 minutes before meals resulted in similar glycemic control, as measured by HbA 1c, and incidence of hypoglycemia, regardless of treatment group.

Table 7: Pediatric Subcutaneous Administration of Insulin Lispro Injection in Type 1 Diabetes

a Values are Mean ± SD
b Severe hypoglycemia refers to hypoglycemia that required glucagon or glucose injection or resulted in coma.
		End point
	Baseline	Insulin Lispro Injection; +; NPH	Humulin R; +; NPH
HbA 1c (%) a	8.6 ± 1.5	8.7 ± 1.5	8.7 ± 1.6
Change from baseline HbA 1c (%) a	—	0.1 ± 1.1	0.1 ± 1.3
Short-acting insulin dose (units/kg/day) a	0.5 ± 0.2	0.5 ± 0.2	0.5 ± 0.2
Change from baseline short-acting insulin dose (units/kg/day) a	—	0.01 ± 0.1	-0.01 ± 0.1
Body weight (kg) a	59.1 ± 13.1	61.1 ± 12.7	61.4 ± 12.9
Weight change from baseline (kg) a	—	2.0 ± 3.1	2.3 ± 3.0
Patients with severe hypoglycemia (n, %) b	—	5 (1.1%)	5 (1.1%)
Diabetic ketoacidosis (n, %)	—	11 (2.4%)	9 (1.9%)

14.4 Type 1 Diabetes – Adults Continuous Subcutaneous Insulin Infusion

To evaluate the administration of Insulin Lispro Injection via external insulin pumps, two open-label, crossover design studies were performed in patients with type 1 diabetes. One study involved 39 patients, ages 19 to 58 years, treated for 24 weeks with Insulin Lispro Injection or regular human insulin. After 12 weeks of treatment, the mean HbA 1c values decreased from 7.8% to 7.2% in the Insulin Lispro Injection-treated patients and from 7.8% to 7.5% in the regular human insulin-treated patients. Another study involved 60 patients (mean age 39, range 15 to 58 years) treated for 24 weeks with either Insulin Lispro Injection or buffered regular human insulin. After 12 weeks of treatment, the mean HbA 1c values decreased from 7.7% to 7.4% in the Insulin Lispro Injection-treated patients and remained unchanged from 7.7% in the buffered regular human insulin-treated patients. Rates of hypoglycemia were comparable between treatment groups in both studies.

14.5 Type 1 Diabetes – Pediatric Continuous Subcutaneous Insulin Infusion

A randomized, 16-week, open-label, parallel design, study of children and adolescents with type 1 diabetes (n=298) aged 4 to 18 years compared two subcutaneous infusion regimens administered via an external insulin pump: insulin aspart (n=198) or Insulin Lispro Injection (n=100). These two treatments resulted in comparable changes from baseline in HbA 1c and comparable rates of hypoglycemia after 16 weeks of treatment ( see Table 8). Infusion site reactions were similar between groups.

Table 8: Pediatric Insulin Pump Study in Type 1 Diabetes (16 weeks; n=298)

a Values are Mean ± SD
b Severe hypoglycemia refers to hypoglycemia associated with central nervous system symptoms and requiring the intervention of another person or hospitalization.
	Insulin Lispro Injection	Aspart
N	100	198
Baseline HbA 1c (%) a	8.2 ± 0.8	8.0 ± 0.9
Change from Baseline HbA 1c (%)	-0.1 ± 0.7	-0.1 ± 0.8
Treatment Difference in HbA 1c, Mean (95% confidence interval)	0.1 (-0.3, 0.1)
Baseline insulin dose (units/kg/24 hours) a	0.9 ± 0.3	0.9 ± 0.3
End-of-Study insulin dose (units/kg/24 hours) a	0.9 ± 0.2	0.9 ± 0.2
Patients with severe hypoglycemia (n, %) b	8 (8%)	19 (10%)
Diabetic ketoacidosis (n, %)	0 (0)	1 (0.5%)
Baseline body weight (kg) a	55.5 ± 19.0	54.1 ± 19.7
Weight Change from baseline (kg) a	1.6 ± 2.1	1.8 ± 2.1

16 HOW SUPPLIED/STORAGE AND HANDLING

Insulin Lispro Injection is a clear and colorless solution available as:

NDC: 70518-2802-00

NDC: 70518-2802-01

PACKAGING: 1 in 1 CARTON

PACKAGING: 10 mL in 1 VIAL, TYPE 0

The Insulin Lispro Injection KwikPen dials in 1 unit increments. The Insulin Lispro Injection Junior KwikPen dials in 0.5 unit increments.

Each prefilled pen is for single-patient-use only. Insulin Lispro Injection prefilled pens must never be shared between patients, even if the needle is changed. Patients using Insulin Lispro Injection vials must never share needles or syringes with another person.

Dispense in the original sealed carton with the enclosed Instructions for Use.

Do not use after the expiration date.

Unopened Insulin Lispro Injection should be stored in a refrigerator (36° to 46°F [2° to 8°C]), but not in the freezer. Do not use Insulin Lispro Injection if it has been frozen. In-use Insulin Lispro Injection vials and Insulin Lispro Injection prefilled pens should be stored at room temperature, below 86°F (30°C) and must be used within 28 days or be discarded, even if they still contain Insulin Lispro Injection. Protect from direct heat and light. See table below:

10 mL multiple-dose vial

Not In-Use (Unopened) Room Temperature (Below 86°F [30°C]): 28 DAYS

Not In-Use (Unopened) Refrigerated: Until expiration date

In-Use (Opened) Room Temperature, (Below 86°F [30°C]): 28 days, refrigerated/room temperature.

Repackaged and Distributed By:

Remedy Repack, Inc.

625 Kolter Dr. Suite #4 Indiana, PA 1-724-465-8762

16.2 Storage and Handling

Dispense in the original sealed carton with the enclosed Instructions for Use.

Do not use after the expiration date.

Unopened Insulin Lispro Injection should be stored in a refrigerator (36° to 46°F [2° to 8°C]), but not in the freezer. Do not use Insulin Lispro Injection if it has been frozen. In-use Insulin Lispro Injection vials and Insulin Lispro Injection prefilled pens should be stored at room temperature, below 86°F (30°C) and must be used within 28 days or be discarded, even if they still contain Insulin Lispro Injection. Protect from direct heat and light. See table below:

	Not In-Use (Unopened) Room Temperature (Below 86°F [30°C])	Not In-Use (Unopened) Refrigerated	In-Use (Opened) Room Temperature, (Below 86°F [30°C])
10 mL multiple-dose vial	28 days	Until expiration date	28 days, refrigerated/room temperature.
3 mL single-patient-use Insulin Lispro Injection KwikPen	28 days	Until expiration date	28 days, Do not refrigerate.
3 mL single-patient-use Insulin Lispro Injection Junior KwikPen	28 days	Until expiration date	28 days, Do not refrigerate.

Use in an External Insulin Pump — Change the Insulin Lispro Injection in the reservoir at least every 7 days, change the infusion sets and the infusion set insertion site at least every 3 days or after exposure to temperatures that exceed 98.6°F (37°C).

Diluted Insulin Lispro Injection for Subcutaneous Injection — Diluted Insulin Lispro Injection may remain in patient use for 28 days when stored at 41°F (5°C) and for 14 days when stored at 86°F (30°C). Do not dilute Insulin Lispro Injection used in an external insulin pump.

16.3 Preparation and Handling

Diluted Insulin Lispro Injection for Subcutaneous Injection — Insulin Lispro Injection may be diluted with Sterile Diluent for Insulin Lispro Injection for subcutaneous injection. Diluting one part Insulin Lispro Injection to nine parts diluent will yield a concentration one-tenth that of Insulin Lispro Injection (equivalent to U-10). Diluting one part Insulin Lispro Injection to one part diluent will yield a concentration one-half that of Insulin Lispro Injection (equivalent to U-50).

16.4 Admixture for Intravenous Administration

Infusion bags prepared with Insulin Lispro Injection are stable when stored in a refrigerator (2° to 8°C [36° to 46°F]) for 48 hours and then may be used at room temperature for up to an additional 48 hours [see Dosage and Administration ( 2.2)] .

17 PATIENT COUNSELING INFORMATION

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

Repackaged By / Distributed By: RemedyRepack Inc.

625 Kolter Drive, Indiana, PA 15701

(724) 465-8762

Never Share an Insulin Lispro Injection Prefilled Pen or Syringe Between Patients

Advise patients that they must never share an Insulin Lispro Injection prefilled pen with another person, even if the needle is changed. Advise patients using Insulin Lispro Injection vials not to share needles or syringes with another person. Sharing poses a risk for transmission of blood-borne pathogens [see Warnings and Precautions ( 5.1)] .

Hyperglycemia or Hypoglycemia

Instruct patients on self-management procedures including glucose monitoring, proper injection technique, and management of hypoglycemia and hyperglycemia, especially at initiation of Insulin Lispro Injection 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.

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 [see Warnings and Precautions ( 5.3)] .

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)] .

Hypersensitivity Reactions

Advise patients that hypersensitivity reactions have occurred with Insulin Lispro Injection. Inform patients on the symptoms of hypersensitivity reactions [see Warnings and Precautions ( 5.5)] .

Medication Errors

Instruct patients to always check the insulin label before each injection to avoid mix-ups between insulin products.

Instructions For Patients Using Continuous Subcutaneous Insulin Pumps

Patients using external pump infusion therapy should be trained appropriately.

The following insulin pumps have been tested in Insulin Lispro Injection clinical trials conducted by Eli Lilly and Company.

• Disetronic ® H-Tron ® plus V100, D-Tron ® and D-Tronplus ® with Disetronic Rapid infusion sets 1
• MiniMed ® Models 506, 507 and 508 and Polyfin ® infusion sets 2

Insulin Lispro Injection is recommended for use in pump systems suitable for insulin infusion such as MiniMed, Disetronic, and other equivalent pumps. Before using Insulin Lispro Injection in a pump system, read the pump label to make sure the pump is indicated for continuous delivery of fast-acting insulin. Insulin Lispro Injection is recommended for use in any reservoir and infusion sets that are compatible with insulin and the specific pump. Please see recommended reservoir and infusion sets in the pump manual.

To avoid insulin degradation, infusion set occlusion, and loss of the preservative (metacresol), insulin in the reservoir should be replaced at least every 7 days; infusion sets and infusion set insertion sites should be changed at least every 3 days.

Insulin exposed to temperatures higher than 98.6°F (37°C) should be discarded. The temperature of the insulin may exceed ambient temperature when the pump housing, cover, tubing or sport case is exposed to sunlight or radiant heat. Infusion sites that are erythematous, pruritic, or thickened should be reported to the healthcare professional, and a new site selected because continued infusion may increase the skin reaction or alter the absorption of Insulin Lispro Injection.

Pump or infusion set malfunctions or insulin degradation can lead to rapid hyperglycemia and ketosis. This is especially pertinent for rapid acting insulin analogs that are more rapidly absorbed through skin and have a shorter duration of action. Prompt identification and correction of the cause of hyperglycemia or ketosis is necessary. Problems include pump malfunction, infusion set occlusion, leakage, disconnection or kinking, and degraded insulin. Less commonly, hypoglycemia from pump malfunction may occur. If these problems cannot be promptly corrected, patients should resume therapy with subcutaneous insulin injection and contact their healthcare professionals [see Dosage and Administration ( 2.2) and How Supplied/Storage and Handling ( 16.2)] .

____________

KwikPen ® is a trademark of Eli Lilly and Company.

1 Disetronic ®, H-Tron ®, D-Tron ®, and D-Tronplus ® are registered trademarks of Roche Diagnostics GmbH.

2 MiniMed ® and Polyfin ® are registered trademarks of MiniMed, Inc.

Other product and company names may be the trademarks of their respective owners.

Literature revised February 2020

Repackaged and Distributed By:

Remedy Repack, Inc.

625 Kolter Dr. Suite #4 Indiana, PA 1-724-465-8762

This Patient Information has been approved by the U.S. Food and Drug Administration Revised: February 2020
Patient Information; Insulin Lispro Injection; U-100 (100 units per mL); for subcutaneous or intravenous use
Do not share your Insulin Lispro Injection prefilled pens or syringes 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 Injection? Insulin Lispro Injection is a man-made fast-acting insulin used to control high blood sugar in adults and children with diabetes mellitus. It is not known if Insulin Lispro Injection is safe and effective in children younger than 3 years of age or when used to treat children with type 2 diabetes mellitus.
Who should not take Insulin Lispro Injection?; Do not take Insulin Lispro Injection if you: are having an episode of low blood sugar (hypoglycemia). have an allergy to Insulin Lispro Injection or any of the ingredients in Insulin Lispro Injection. See the end of this Patient Information leaflet for a complete list of ingredients in Insulin Lispro Injection.
What should I tell my healthcare provider before taking Insulin Lispro Injection?; Before taking Insulin Lispro Injection, tell your healthcare provider about all of your medical conditions, including if you: have kidney or liver 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 Injection. 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 Injection.
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 Injection, talk to your healthcare provider about low blood sugar and how to manage it.
How should I take Insulin Lispro Injection? Read the Instructions for Use that comes with your Insulin Lispro Injection. Take Insulin Lispro Injection exactly as your healthcare provider tells you to. Your healthcare provider should tell you how much Insulin Lispro Injection to take and when to take it. Insulin Lispro Injection starts acting fast. Inject Insulin Lispro Injection within 15 minutes before or right after 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 Injection under the skin (subcutaneously) of your stomach area, buttocks, upper legs or upper arms, or by continuous infusion under the skin (subcutaneously) through an insulin pump into an area of your body recommended in the instructions that come with your insulin 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. 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. 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 Injection and all medicines out of the reach of children.
Your dose of Insulin Lispro Injection 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 Injection?; While taking Insulin Lispro Injection do not: drive or operate heavy machinery, until you know how Insulin Lispro Injection affects you. drink alcohol or take prescription or over-the-counter medicines that contain alcohol.
What are the possible side effects of Insulin Lispro Injection?; Insulin Lispro Injection 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. serious allergic reactions (whole body allergic 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 feel faint
low potassium in your blood (hypokalemia). heart failure. Taking certain diabetes pills called thiazolidinediones or “TZDs” with Insulin Lispro Injection 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 Injection. Your healthcare provider should monitor you closely while you are taking TZDs with Insulin Lispro Injection. 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 Injection 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 Injection 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 Injection. 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 Injection.; Medicines are sometimes prescribed for purposes other than those listed in a Patient Information leaflet. Do not take Insulin Lispro Injection for a condition for which it was not prescribed. Do not give Insulin Lispro Injection 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 Injection. If you would like more information, talk with your healthcare provider. You can ask your pharmacist or healthcare provider for information about Insulin Lispro Injection that is written for health professionals.
What are the ingredients in Insulin Lispro Injection?; Active ingredient: insulin lispro; Inactive ingredients: dibasic sodium phosphate, glycerin, metacresol, zinc oxide (zinc ion), trace amounts of phenol and Water for Injection, USP Repackaged and Distributed By: Remedy Repack, Inc. 625 Kolter Dr. Suite #4 Indiana, PA 1-724-465-8762 LIS-0006-PPI-20200212

Instructions for Use

Insulin Lispro Injection

Read this Instructions for Use before you start taking Insulin Lispro Injection and each time you get a new vial. 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 needles or syringes 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.

Supplies needed to give your injection

• a multiple-dose Insulin Lispro Injection vial
• a U-100 insulin syringe and needle
• 2 alcohol swabs
• gauze
• 1 sharps container for throwing away used needles and syringes. See “Disposing of used needles and syringes” at the end of these instructions.

Preparing your Insulin Lispro Injection dose

• Wash your hands with soap and water.
• Check the Insulin Lispro Injection label to make sure you are taking the right type of insulin. This is especially important if you use more than 1 type of insulin.
• Insulin Lispro Injection should look clear and colorless. Do not use Insulin Lispro Injection if it is thick, cloudy, or colored, or if you see lumps or particles in it.
• Do not use Insulin Lispro Injection past the expiration date printed on the label or 28 days after you first use it.
• Always use a new syringe and needle for each injection to prevent infections and blocked needles. Do not reuse or share your syringes or needles with other people. You may give other people a serious infection or get a serious infection from them.

• Vial: Syringe

If you use Insulin Lispro Injection with NPH insulin:

• NPH insulin is the only type of insulin that can be mixed with Insulin Lispro Injection. Do not mix Insulin Lispro Injection with any other type of insulin.
• Insulin Lispro Injection should be drawn up into the syringe first, before you draw up your NPH insulin. Talk to your healthcare provider if you are not sure about the right way to mix Insulin Lispro Injection and NPH insulin.
• Give your injection right away.

Giving your Insulin Lispro Injection with a syringe

• Inject your insulin exactly as your healthcare provider has shown you. Your healthcare provider should tell you if you should pinch the skin before injecting.
• Insulin Lispro Injection starts acting fast, so give your injection within 15 minutes before or right after you eat a meal.
• 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.

• Step 3: Remove the Needle Shield from the syringe by pulling the Needle Shield straight off. Hold the syringe with the needle pointing up. Pull down on the Plunger until the Plunger Tip reaches the line for the number of units for your prescribed dose.: (Example Dose: 20 units shown)
• Step 6: Turn the vial and syringe upside down and slowly pull the Plunger down until the Plunger Tip is a few units past the line for your prescribed dose.: (Example Dose: 20 units Plunger is shown at 24 units)
• Step 7: Slowly push the Plunger up until the Plunger Tip reaches the line for your prescribed dose. Check the syringe to make sure that you have the right dose.: (Example Dose: 20 units shown)

Giving your Insulin Lispro Injection using an insulin pump

• Insulin Lispro Injection should be given into an area of your body recommended in the instructions that come with your insulin pump.
• Change (rotate) your insertion site every 3 days.
• Change (rotate) your insertion sites within the area you choose for each insertion to reduce your risk of getting lipodystrophy (pits in skin or thickened skin) and localized cutaneous amyloidosis (skin with lumps) at the insertion sites. Do not insert into the exact same spot for each insertion. Do not insert where the skin has pits, is thickened, or has lumps. Do not insert where the skin is tender, bruised, scaly or hard, or into scars or damaged skin.
• Change the insulin in the reservoir at least every 7 days, even if you have not used all of the insulin.
• Do not dilute or mix Insulin Lispro Injection with any other type of insulin in your insulin pump.
• See your insulin pump manual for instructions or talk to your healthcare provider.

Disposing of used needles and syringes

• Put your used needles and syringes in a FDA-cleared sharps disposal container right away after use. Do not throw away (dispose of) loose needles and syringes 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.

How should I store Insulin Lispro Injection?

All unopened vials:

• Store all unopened vials in the refrigerator at 36°F to 46°F (2°C to 8°C).
• Do not freeze. Do not use if Insulin Lispro Injection has been frozen.
• Keep away from heat and out of direct light.
• Unopened vials can be used until the expiration date on the carton and label, if they have been stored in the refrigerator.
• Unopened vials should be thrown away after 28 days, if they are stored at room temperature.

After vials have been opened:

• Store opened vials in the refrigerator or at room temperature below 86°F (30°C) for up to 28 days.
• Keep vials away from heat and out of direct light.
• Throw away all opened vials after 28 days of use, even if there is insulin left in the vial.

Keep Insulin Lispro Injection vials, syringes, needles and all medicines out of the reach of children.

If you have any questions or problems with your Insulin Lispro Injection, contact Lilly at 1-800-Lilly-Rx (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.

Instructions for Use revised: February 2020

Repackaged and Distributed By:

Remedy Repack, Inc.

625 Kolter Dr. Suite #4 Indiana, PA 1-724-465-8762

Instructions for Use

Insulin Lispro Injection KwikPen®

100 units/mL, 3 mL single-patient-use pen

Read the Instructions for Use before you start taking Insulin Lispro Injection 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 Injection 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 Injection KwikPen (“Pen”) is a disposable single-patient-use prefilled pen containing 300 units of insulin lispro. You can give yourself more than 1 dose from the Pen. Each turn (click) of the Dose Knob dials 1 unit of insulin. You can give from 1 to 60 units in a single injection. 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 the Pen without help from a person trained to use the Pen.

How to recognize your Insulin Lispro Injection KwikPen

• Pen color: Dark blue
• Dose Knob: Dark blue
• Labels: White label with burgundy stripe

Supplies you will need to give your injection

• Insulin Lispro Injection KwikPen
• KwikPen compatible Needle (Becton, Dickinson and Company Pen Needles recommended)
• Alcohol swab
• Gauze

Preparing your Pen

• Wash 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.
• Do not use your Pen past the expiration date printed on the Label or for more than 28 days after you first start using the Pen.
• 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.

Priming your Pen

Prime 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.

Selecting your dose

• You 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 1 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 step.

• 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 injection

• Inject 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 9: 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)

After your injection

Disposing of Pens and Needles

• Put 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 Pen

Unused Pens

• Store 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 it 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.

In-use Pen

• Store 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 Injection Pen you are using after 28 days, even if it still has insulin left in it.

General information about the safe and effective use of your Pen

• Keep 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.

Troubleshooting

• If 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 Injection 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.

KwikPen ® is a registered trademark of Eli Lilly and Company.

Revised: June 2020

Repackaged and Distributed By:

Remedy Repack, Inc.

625 Kolter Dr. Suite #4 Indiana, PA 1-724-465-8762

LISKP-0005-IFU-20200609

Insulin Lispro Injection KwikPen meets the current dose accuracy and functional requirements of ISO 11608-1.

Instructions for Use

Insulin Lispro Injection Junior KwikPen®

100 units/mL, 3 mL single-patient-use pen

Read the Instructions for Use before you start taking Insulin Lispro Injection and each time you get another Insulin Lispro Injection Junior 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 Injection Junior 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 Injection Junior KwikPen (“Pen”) is a disposable single-patient-use prefilled pen containing 300 units of Insulin Lispro Injection.

• You can give yourself more than 1 dose from the Pen.
• Each turn of the Dose Knob dials 0.5 (½) unit of insulin. You can give from 0.5 (½) to 30 units in a single injection.
• If your dose is more than 30 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 the Pen without help from a person trained to use the Pen.

How to recognize your Insulin Lispro Injection Junior KwikPen:

• Pen color: Blue
• Dose Knob: Blue, with raised ridges on end and side
• Label: White with an orange color bar and orange-to-yellow color band

Supplies needed to give your injection:

• Insulin Lispro Injection Junior KwikPen
• KwikPen compatible Needle (BD [Becton, Dickinson and Company] Pen Needles recommended)
• Alcohol swab
• Gauze

Preparing your Pen

• Wash your hands with soap and water.
• Check the 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.
• Do not use your Pen past the expiration date printed on the Label or for more than 28 days after you first start using the Pen.
• 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.

Priming your Pen

Prime 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 1: Pull the Pen Cap straight off. Do not remove the Pen Label. Wipe the Rubber Seal with an alcohol swab.
Step 2: Check the liquid in the Pen.
Insulin Lispro Injection should look clear and colorless. Do not use if it is cloudy, colored, or has particles or clumps in it.
Step 3: Select a new Needle. Pull off the Paper Tab from the Outer Needle Shield.
Step 4: Push the capped Needle straight onto the Pen and twist the Needle on until it is tight.
Step 5: Pull off the Outer Needle Shield. Do not throw it away. Pull off the Inner Needle Shield and throw it away.

Selecting your dose

• You can give from 0.5 (½) to 30 units in a single injection.
• If your dose is more than 30 units, you will need to give more than 1 injection.
  • If you need help with dividing up your dose the right way, ask your healthcare provider.
  • You must use a new Needle for each injection and repeat the priming step.

Step 6: To prime your Pen, turn the Dose Knob to select 2 units.
Step 7: Hold your Pen with the Needle pointing up. Tap the Cartridge Holder gently to collect air bubbles at the top.
Step 8: Continue holding your Pen with the 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 the priming steps 6 to 8, but not more than 4 times. If you still do not see insulin, change the Needle and repeat the priming steps 6 to 8.
Small air bubbles are normal and will not affect your dose.

• 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 injection

• Inject 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 9: 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 0.5 (½) 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 whole unit numbers (for example, 4) are printed on the dial. The half units are shown as lines between the whole unit numbers. Always check the number in the Dose Window to make sure you have dialed the correct dose.: Example: 4 units shown in the Dose Window ; Example: 10.5 (10 ½) units shown in the Dose Window

After your injection

Step 10: Choose your injection site.; Insulin Lispro Injection 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 11: 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 12: 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 that 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.

Disposing of Pens and Needles

• Put 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. 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 the container.
• The used Pen may be discarded in your household trash after you have removed the needle.

Storing your Pen

Unused Pens

• Store 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 it 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.

In-use Pen

• Store 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 Injection Pen you are using after 28 days, even if it still has insulin left in it.

General information about the safe and effective use of your Pen

• Keep your Pen and Needles out of the sight and 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.

Troubleshooting

• If 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 Injection Junior 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.

KwikPen ® is a registered trademark of Eli Lilly and Company.

Repackaged and Distributed By:

Remedy Repack, Inc.

625 Kolter Dr. Suite #4 Indiana, PA 1-724-465-8762

LIS-JRKP-0001-IFU-20200212

Insulin Lispro Injection Junior KwikPen meets the current dose accuracy and functional requirements of ISO 11608-1.

DRUG: Insulin Lispro

GENERIC: Insulin lispro

DOSAGE: INJECTION, SOLUTION

ADMINSTRATION: INTRAVENOUS

NDC: 70518-2802-0

NDC: 70518-2802-1

PACKAGING: 10 mL in 1 VIAL

OUTER PACKAGING: 1 in 1 CARTON

ACTIVE INGREDIENT(S):

• Insulin lispro 100[iU] in 1mL

INACTIVE INGREDIENT(S):

• Glycerin
• Sodium Phosphate, Dibasic, Unspecified Form
• Metacresol
• Zinc
• Phenol
• Water
• Hydrochloric acid
• Sodium hydroxide

INSULIN LISPRO 
insulin lispro injection, solution

Product Information
Product Type	HUMAN PRESCRIPTION DRUG	Item Code (Source)	NDC: 70518-2802(NDC: 0002-7737)
Route of Administration	INTRAVENOUS, SUBCUTANEOUS

Active Ingredient/Active Moiety
Ingredient Name	Basis of Strength	Strength
INSULIN LISPRO (UNII: GFX7QIS1II) (INSULIN LISPRO - UNII:GFX7QIS1II)	INSULIN LISPRO	100 [iU]  in 1 mL

Inactive Ingredients
Ingredient Name	Strength
GLYCERIN (UNII: PDC6A3C0OX)	16 mg  in 1 mL
SODIUM PHOSPHATE, DIBASIC, UNSPECIFIED FORM (UNII: GR686LBA74)	1.88 mg  in 1 mL
METACRESOL (UNII: GGO4Y809LO)	3.15 mg  in 1 mL
ZINC (UNII: J41CSQ7QDS)	0.0197 mg  in 1 mL
PHENOL (UNII: 339NCG44TV)
WATER (UNII: 059QF0KO0R)
HYDROCHLORIC ACID (UNII: QTT17582CB)
SODIUM HYDROXIDE (UNII: 55X04QC32I)

Packaging
#	Item Code	Package Description	Marketing Start Date	Marketing End Date
1	NDC: 70518-2802-0	1 in 1 CARTON	06/03/2020	07/22/2022
1	NDC: 70518-2802-1	10 mL in 1 VIAL; Type 0: Not a Combination Product

Marketing Information
Marketing Category	Application Number or Monograph Citation	Marketing Start Date	Marketing End Date
BLA	BLA020563	06/03/2020	07/22/2022

Labeler - REMEDYREPACK INC. (829572556)

Revised: 7/2022

Document Id: e4671bad-c378-de57-e053-2a95a90a8d14

34391-3

Set id: 1dcb7b25-73e8-40d6-b320-0211e1e56286

Version: 4

Effective Time: 20220722