Humalog

HUMALOG is a sterile, aqueous, clear, and colorless solution. Each milliliter of HUMALOG contains insulin lispro 100 units, 16 mg glycerin, 1.88 mg dibasic sodium phosphate, 3.15 mg Metacresol, zinc oxide content adjusted to provide 0.0197 mg zinc ion, trace amounts of phenol, and Water for Injection. 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

HUMALOG has been shown to be equipotent to human insulin on a molar basis. One unit of HUMALOG has the same glucose-lowering effect as one unit of regular human insulin. Studies in normal volunteers and patients with diabetes demonstrated that HUMALOG 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 HUMALOG, may vary considerably in different individuals or within the same individual. The parameters of HUMALOG 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 (5.1)].

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

12.3 Pharmacokinetics

Absorption and Bioavailability — Studies in healthy volunteers and patients with diabetes demonstrated that HUMALOG is absorbed more quickly than regular human insulin. In healthy volunteers given subcutaneous doses of HUMALOG 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.

HUMALOG 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 HUMALOG 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 HUMALOG 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 — After subcutaneous administration, the volume of distribution for HUMALOG is identical to that of regular human insulin, with a range of 0.26 to 0.36 L/kg. When administered intravenously, the volume of distribution of HUMALOG (range of 0.26 to 0.36 L/kg) was similar to that of regular human insulin (range of 0.32 to 0.67 L/kg).

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

Elimination — After subcutaneous administration of HUMALOG, the t_1/2 is shorter than that of regular human insulin (1 versus 1.5 hours, respectively). When administered intravenously, HUMALOG and regular human insulin demonstrated similar dose-dependent elimination, with a t_1/2 of 0.44 hours (26 min) and 0.34 hours (20 min), respectively (0.1 unit/kg dose) and 0.86 hours (52 min) and 1.1 hours (66 min), respectively (0.2 unit/kg dose).

Specific Populations

Age — The effect of age on the pharmacokinetics of HUMALOG has not been studied. However, in large clinical trials, sub-group analysis based on age did not indicate any difference in postprandial glucose parameters between HUMALOG and regular human insulin.

Gender — The effect of gender on the pharmacokinetics of HUMALOG has not been studied. However, in large clinical trials, sub-group analysis based on gender did not indicate any difference in postprandial glucose parameters between HUMALOG and regular human insulin.

Renal Impairment — Type 2 diabetic patients with varying degree of renal impairment showed no difference in pharmacokinetics of regular insulin and HUMALOG. 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 HUMALOG, may be necessary in patients with renal dysfunction [see Warnings and Precautions (5.5)].

Hepatic Impairment — Type 2 diabetic patients with impaired hepatic function showed no effect on the pharmacokinetic of HUMALOG 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 HUMALOG, may be necessary in patients with hepatic dysfunction.

Race – The effects of race on the pharmacokinetics and pharmacodynamics of HUMALOG have not been studied.

Obesity – The effect of obesity on the pharmacokinetics and pharmacodynamics of HUMALOG has not been studied.

Pregnancy – The effect of pregnancy on the pharmacokinetics and pharmacodynamics of HUMALOG has not been studied [see Use in Specific Populations (8.1)].

Smoking – The effect of smoking on the pharmacokinetics and pharmacodynamics of HUMALOG has not been studied.

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 (0.16, 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 HUMALOG 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 HUMALOG (n=81) compared with Humulin^® R [REGULAR insulin human injection, USP (rDNA origin)] (n=86). HUMALOG 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 HUMALOG 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.

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 HUMALOG for 3 months followed by Humulin R for 3 months or the reverse sequence. HUMALOG 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/m². 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 5).

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: HUMALOG or Humulin R, both administered with Humulin N (NPH human insulin) as the basal insulin. HUMALOG achieved glycemic control comparable to Humulin R, as measured by HbA_1c (see Table 6), 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, HUMALOG administered immediately before meals, HUMALOG 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.

14.4 Type 1 Diabetes – Adults Continuous Subcutaneous Insulin Infusion

To evaluate the administration of HUMALOG 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 HUMALOG or regular human insulin. After 12 weeks of treatment, the mean HbA_1c values decreased from 7.8% to 7.2% in the HUMALOG-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 HUMALOG or buffered regular human insulin. After 12 weeks of treatment, the mean HbA_1c values decreased from 7.7% to 7.4% in the HUMALOG-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 HUMALOG (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 7). Infusion site reactions were similar between groups.

16 HOW SUPPLIED/STORAGE AND HANDLING

16.1 How Supplied

HUMALOG 100 units per mL (U-100) is available as:

16.2 Storage

Do not use after the expiration date.

Unopened HUMALOG should be stored in a refrigerator (36° to 46°F [2° to 8°C]), but not in the freezer. Do not use HUMALOG if it has been frozen. In-use HUMALOG vials, cartridges, pens, and HUMALOG KwikPen^® 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 HUMALOG. Protect from direct heat and light. See table below:

Use in an External Insulin Pump — Change the HUMALOG 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). A HUMALOG 3 mL cartridge used in the D-Tron pumps should be discarded after 7 days, even if it still contains HUMALOG. However, as with other external insulin pumps, the infusion set should be replaced and a new infusion set insertion site should be selected at least every 3 days.

Diluted HUMALOG for Subcutaneous Injection — Diluted HUMALOG 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 HUMALOG contained in a cartridge or HUMALOG used in an external insulin pump.

16.3 Preparation and Handling

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

17 PATIENT COUNSELING INFORMATION

See FDA-approved patient labeling.

17.1 Instructions for All Patients

Patients should be instructed on self-management procedures including glucose monitoring, proper injection technique, and management of hypoglycemia and hyperglycemia. Patients must be instructed 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. Refer patients to the HUMALOG Patient Information Leaflet for additional information.

Women with diabetes should be advised to inform their doctor if they are pregnant or are contemplating pregnancy.

Accidental mix-ups between HUMALOG and other insulins have been reported. To avoid medication errors between HUMALOG and other insulins, patients should be instructed to always check the insulin label before each injection.

17.2 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 HUMALOG clinical trials conducted by Eli Lilly and Company.

• Disetronic^® H-Tron^® plus V100, D-Tron^® and D-Tronplus^® with Disetronic Rapid infusion sets²
• MiniMed^® Models 506, 507 and 508 and Polyfin^® infusion sets³

HUMALOG is recommended for use in pump systems suitable for insulin infusion such as MiniMed, Disetronic, and other equivalent pumps. Before using HUMALOG in a pump system, read the pump label to make sure the pump is indicated for continuous delivery of fast-acting insulin. HUMALOG 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 HUMALOG.

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 (2.3), Warnings and Precautions (5.7), and How Supplied/Storage and Handling (16)].

____________

¹ 3 mL cartridge is for use in Eli Lilly and Company's HumaPen^® Memoir™ and HumaPen^® Luxura™ HD insulin delivery devices, Owen Mumford, Ltd.'s Autopen® 3-mL insulin delivery device and Disetronic D-TRON^® and D-TRON^® Plus pumps.

Autopen^® is a registered trademark of Owen Mumford, Ltd.

Humalog^®, Humalog^® KwikPen™, HumaPen^®, HumaPen^® Memoir™, HumaPen^® Luxura™ and HumaPen^® Luxura™ HD are trademarks of Eli Lilly and Company.

² Disetronic^®, H-Tron^®, D-Tron^®, and D-Tronplus^® are registered trademarks of Roche Diagnostics GmbH.

³ MiniMed^® and Polyfin^® are registered trademarks of MiniMed, Inc.

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

Literature revised May 18, 2011
Marketed by: Lilly USA, LLC, Indianapolis, IN 46285, USA

www.humalog.com
Copyright © 1996, 2011, Eli Lilly and Company. All rights reserved.

PV 5533 AMP

Additional barcode labeling by:
Physicians Total Care, Inc.
Tulsa, Oklahoma        74146

Patient Information

HUMALOG^®

insulin lispro injection, USP (rDNA origin)

Read the “Patient Information” that comes with HUMALOG (HU-ma-log) before you start using it and each time you get a refill. There may be new information. This leaflet does not take the place of talking with your healthcare provider about your diabetes or treatment. If you have questions about HUMALOG or diabetes, talk with your healthcare provider.

What is the most important information I should know about HUMALOG?

• Do not change the insulin you use without talking to your healthcare provider. Any change in insulin strength, manufacturer, type (regular, NPH, analog) may need a change in the dose you are using. This dose change may be needed right away or later on. Sometimes this dose change may happen during the first several weeks or months on the new insulin. Doses of oral anti-diabetic medicines may also need to change if your insulin is changed.
• You must test your blood sugar levels while using an insulin such as HUMALOG. Your healthcare provider will tell you how often you should test your blood sugar level, and what to do if it is high or low.
• When used in a pump do not mix HUMALOG with any other insulin or liquid.

What is HUMALOG?

HUMALOG (insulin lispro injection, USP [rDNA origin]) is an injectable rapid-acting man-made insulin. HUMALOG is used to treat people with diabetes for the control of high blood sugar.

• HUMALOG is a clear, colorless, sterile solution for injection under the skin (subcutaneously).
• You need a prescription to get HUMALOG. Always be sure you receive the right insulin from the pharmacy.

HUMALOG comes in:

• 10 mL vials (bottles) for use with a syringe or external insulin pump
• 3 mL vials (bottles) for use with a syringe or external insulin pump
• 3 mL prefilled pens
• 3 mL Humalog^® KwikPen™
• 3 mL cartridges for use with a reusable pen or external insulin pump

Who should not take HUMALOG?

Do not take HUMALOG if:

• your blood sugar is too low (hypoglycemia). After treating your low blood sugar, follow your healthcare provider's instructions on the use of HUMALOG.
• you are allergic to insulin lispro or any of the ingredients in HUMALOG. See the end of this leaflet for a complete list of ingredients in HUMALOG. Check with your healthcare provider if you are not sure.

What should I tell my healthcare provider before taking HUMALOG?

Tell your healthcare provider:

• about all your medical conditions, including liver or kidney problems. Your dose may need to be adjusted.
• if you are pregnant or breastfeeding. You and your healthcare provider should talk about the best way to manage your diabetes while you are pregnant or breastfeeding. HUMALOG has not been studied in pregnant or nursing women.
• about all the medicines you take, including prescription and non-prescription medicines, vitamins and herbal supplements. Your HUMALOG dose may need to change if you take other medicines.

Know the medicines you take. Keep a list of your medicines with you to show your healthcare providers when you get a new medicine.

How should I use HUMALOG?

HUMALOG can be used with a syringe, prefilled pen, reusable pen or external insulin pump. Talk to your healthcare provider if you have any questions.

• Read the instructions for use that comes with your HUMALOG product. Talk to your healthcare provider if you have any questions. Your healthcare provider should show you how to inject HUMALOG before you start taking it.
• HUMALOG is a rapid-acting insulin. You should take HUMALOG within fifteen minutes before eating or right after eating a meal.
• Only use HUMALOG that is clear and colorless. If your HUMALOG is cloudy, colored, or has solid particles or clumps in it, return it to your pharmacy for a replacement.
• Do not mix HUMALOG:
  • with any type of insulin other than NPH when used with injections by syringe.
  • with any other insulin or liquid when used in a pump.
• If your doctor recommends diluting HUMALOG, follow your doctor's instructions exactly so that you know:
  • How to make HUMALOG more dilute (that is, a smaller number of units of HUMALOG for a given amount of liquid) and
  • How to use this more dilute form of HUMALOG. Do not use dilute insulin in a pump.
• Inject HUMALOG under your skin (subcutaneously) in your upper arm, abdomen (stomach area), thigh (upper leg), or buttocks. Never inject it into a vein or muscle.
• Change (rotate) your injection site with each dose.
• If you have type 1 diabetes, you need to take a longer-acting insulin in addition to HUMALOG (except when using an external insulin pump).
• If you have type 2 diabetes, you may be taking oral anti-diabetic medicines and/or a longer-acting insulin in addition to HUMALOG.
• Follow the instructions given by your healthcare provider about the type or types of insulin you are using. Do not make any changes with your insulin unless you have talked to your healthcare provider. Always make sure that you received the correct type of HUMALOG from the pharmacy. Check to make sure you are injecting the correct insulin and dose, especially if you use other insulin with HUMALOG.
• If you take too much HUMALOG, your blood sugar may fall low (hypoglycemia). You can treat mild low blood sugar by drinking or eating something sugary right away (fruit juice, sugar candies, or glucose tablets). It is important to treat low blood sugar right away because it could get worse and you could pass out (become unconscious). If you pass out, you will need help from another person or emergency medical services right away, and will need treatment with glucagon injection or treatment at a hospital. See “What are the possible side effects of HUMALOG?” for more information on low blood sugar.
• If you forget to take your dose of HUMALOG, your blood sugar may go too high (hyperglycemia). If high blood sugar is not treated it can lead to serious problems like loss of consciousness (passing out), coma or even death. Follow your healthcare provider's instructions for treating high blood sugar. Know your symptoms of high blood sugar which may include:
  • increased thirst
  • frequent urination
  • drowsiness
  • loss of appetite
  • a hard time breathing
  • fruity smell on the breath
  • high amounts of sugar and ketones in your urine
  • nausea, vomiting (throwing up) or stomach pain
• Your insulin dosage may need to change because of:
  • illness
  • stress
  • other medicines you take
  • change in diet
  • change in physical activity or exercise

What are the possible side effects of HUMALOG?

• low blood sugar (hypoglycemia). Symptoms of low blood sugar may include:
  • sweating
  • dizziness or lightheadedness
  • shakiness
  • hunger
  • fast heart beat
  • tingling of lips and tongue
  • trouble concentrating or confusion
  • blurred vision
  • slurred speech
  • anxiety, irritability or mood changes
  • headache
• Severe low blood sugar can cause unconsciousness (passing out), seizures, and death. Low blood sugar may affect your ability to drive a car or use mechanical equipment, risking injury to yourself or others. Know your symptoms of low blood sugar. Follow your healthcare provider's instructions for treating low blood sugar. Talk to your healthcare provider if low blood sugar is a problem for you.
• Serious allergic reaction (whole body reaction). Get medical help right away, if you develop a rash over your whole body, have trouble breathing, a fast heartbeat, or sweating.
• Reactions at the injection site (local allergic reaction). You may get redness, swelling, and itching at the injection site. If you keep having skin reactions or they are serious, talk to your healthcare provider. You may need to stop using HUMALOG and use a different insulin. Do not inject insulin to skin that is red, swollen or itchy.
• Skin thickens or pits at the injection site (lipodystrophy). Change (rotate) when you inject your insulin to help to prevent these skin changes from happening. Do not inject insulin into this type of skin.
• Swelling of your hands and feet
• Low potassium in your blood (hypokalemia)
• Weight gain

These are not all of the possible side effects from HUMALOG. Ask your healthcare provider or pharmacist for more information.

Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

How should I store HUMALOG?

• Store all unopened (unused) HUMALOG in the original carton in a refrigerator at 36°F to 46°F (2°C to 8°C).
• Do not freeze. Do not use HUMALOG if it has been frozen.
• Keep unopened HUMALOG in the carton to protect from light.

After starting use (open)

Vials:

• Keep in the refrigerator or at room temperature below 86°F (30°C) for up to 28 days.
• Keep vials away from direct heat or light.
• Throw away an opened vial after 28 days of use, even if there is insulin left in the vial.
• Unopened vials can be used until the expiration date on the HUMALOG carton and label, if the medicine has been stored in a refrigerator.

Cartridge and Prefilled Pens:

• Keep at room temperature below 86°F (30°C) for up to 28 days.
• Do not store a cartridge or prefilled pen that you are using in the refrigerator.
• Keep cartridges and prefilled pens away from direct heat or light.
• A cartridge used in the D-Tron¹ or D-Tronplus¹ pump may be used for up to 7 days.
• Throw away a used cartridge or prefilled pen after 28 days, even if there is insulin left in the cartridge or the pen.

General Information about HUMALOG

• HUMALOG in the pump reservoir and the complete external pump infusion set:
  • When HUMALOG is used in pumps, use only pumps that are recommended by your healthcare provider.
  • The infusion set and infusion site should be changed at least every 3 days.
  • The insulin in the reservoir should be changed at least every 7 days even if you have not used all of the insulin.
  • Change the infusion set and infusion site more often than every 3 days if you have high blood sugar (hyperglycemia), the pump alarms sounds, or the insulin flow is blocked (occlusion).
• Do not use HUMALOG for a condition for which it was not prescribed. Do not give or share HUMALOG with another person, even if they also have diabetes. It may harm them.
• This leaflet summarizes the most important information about HUMALOG. If you would like more information, talk with your healthcare provider. You can ask your healthcare provider for information about HUMALOG that is written for healthcare providers. For more information about HUMALOG, call 1-800-LillyRx (1-800-545-5979) or visit www.humalog.com.

What are the ingredients in HUMALOG?

insulin lispro, glycerin, dibasic sodium phosphate, metacresol, zinc oxide (zinc ion), trace amounts of phenol and water for injection.

Helpful information for people with diabetes is published by the American Diabetes Association, 1660 Duke Street, Alexandria, VA 22314 and on www.diabetes.org.

__________

¹ D-Tron^®, D-Tronplus^® are registered trademarks of Roche Diagnostics GmbH.

Humalog^® and Humalog^® KwikPen^™ are registered trademarks of Eli Lilly and Company.

Patient Information revised May 23, 2011

Marketed by: Lilly USA, LLC, Indianapolis, IN 46285, USA

www.humalog.com

Copyright © 2007, 2011, Eli Lilly and Company. All rights reserved.

PV 5564 AMP

Humalog^® KwikPen™
insulin lispro injection, USP (rDNA origin)

Disposable Insulin Delivery Device
User Manual

________________________________________________________________________________________

Introduction

Humalog^® KwikPen™ (“Pen”) is designed for ease of use. It is a disposable insulin delivery device (“insulin Pen”) containing 3 mL (300 units) of U-100 Humalog^® [insulin lispro injection, USP (rDNA origin)] insulin. You can inject from 1 to 60 units of Humalog in one injection. You can dial your dose one unit at a time. If you dial too many units, you can dial backwards to correct the dose without wasting any insulin.

Before using Humalog KwikPen, read the entire manual completely and follow the directions carefully. If you do not follow these directions completely, you may get too much or too little insulin.

Do not share your Humalog KwikPen or needles with anyone else. You may give an infection to them or get an infection from them.

DO NOT USE your KwikPen if any part appears broken or damaged. Contact Lilly at 1-800-Lilly-Rx (1-800-545-5979) or your healthcare professional for a replacement Pen. Always carry an extra Pen in case yours is lost or damaged.

This Pen is not recommended for use by the blind or visually impaired persons without the assistance of a person trained in the proper use of the product.

Preparing Humalog KwikPen

Important Notes

• Read and follow the directions provided in the Patient Information Leaflet.
• Check the label on your Pen before each injection for the expiration date and to make sure you are using the correct type of insulin.
• Your healthcare professional has prescribed the best type of insulin for you. Any changes in insulin therapy should be made only under medical supervision.
• KwikPen is recommended for use with Becton, Dickinson and Company pen needles.
• Be sure the needle is completely attached to the Pen before use.
• Do not share your Pen or needles.
• Keep these directions for future reference.

Frequently Asked Questions about Preparing Humalog KwikPen

• What should my insulin look like? Humalog is clear and colorless. If your Humalog is cloudy, colored, or has solid particles or clumps in it, return it to your pharmacy for a replacement. Be sure to refer to your Patient Information Leaflet for the appearance of your specific insulin.
• Why should I use a new needle for each injection? This will help ensure sterility. If needles are reused, you may get the wrong amount of insulin, a clogged needle or a jammed Pen.
• What should I do if I am not sure how much insulin remains in my cartridge? Hold the Pen with the needle end pointing down. The scale on the clear Cartridge Holder shows an estimate of the number of units remaining. These numbers should NOT be used for measuring an insulin dose.

Priming Humalog KwikPen

Important Notes

• Prime every time. The Pen must be primed to a stream of insulin before each injection to make sure the Pen is ready to dose.
• If you do not prime, you may get too much or too little insulin.

Frequently Asked Questions about Priming

• Why should I prime my KwikPen before each dose?
  • Ensures that the Pen is ready to dose.
  • Confirms that a stream of insulin comes out of the tip of the needle when you push the Dose Knob in.
  • Removes air that may collect in the needle or insulin cartridge during normal use.
• What should I do if I cannot completely push in the Dose Knob when priming the KwikPen?
  • Attach a new needle.
  • Prime the Pen.
• What should I do if I see an air bubble in the cartridge? You need to prime the Pen. Remember, do not store the Pen with the needle attached as this may cause air bubbles to collect in the insulin cartridge. A small air bubble will not affect your dose and you can continue to take your dose as usual.

Injecting Your Dose

Important Notes

• Follow the instructions for sanitary injection technique recommended by your healthcare professional.
• Make sure you receive your complete dose by pushing and holding the dose knob in and count to 5 slowly before removing the needle. If insulin is leaking from the Pen you may not have held it in your skin long enough.
• The Pen will not allow you to dial more than the number of units left in the Pen.
• If your dose is greater than the number of units left in the Pen, you may either inject the amount remaining in your current Pen and then use a new Pen to complete your dose OR inject the full dose with a new Pen.
• Do not attempt to inject your insulin by turning the Dose Knob. You will NOT receive your insulin by turning the Dose Knob. You must PUSH the Dose Knob straight in for the dose to be delivered.
• Do not attempt to change the dose while injecting.
• The directions regarding needle handling are not intended to replace local, healthcare professional or institutional policies.
• Remove the needle after completing each injection.

Frequently Asked Questions about Injecting Your Dose

• Why is it difficult to push the Dose Knob when I try to inject?
  • Your needle may be clogged. Try attaching a new needle. When you do this you may see insulin come out of the needle. Then prime the Pen.
  • Pressing the Dose Knob quickly may make the Dose Knob harder to push. Pressing the Dose Knob more slowly may make it easier.
  • Using a larger diameter needle will make it easier to push the Dose Knob during your injection. See your healthcare professional to determine which needle size is best for you.
  • If the Dose Knob continues to be difficult to push after following the steps above, try the steps below under “What should I do if my KwikPen is jammed?”.
• What should I do if my KwikPen is jammed? Your Pen may be jammed if it is difficult to inject a dose or dial a dose. To clear the jam:
  • Attach a new needle. When you do this you may see insulin come out of the needle.
  • Prime the Pen.
  • Dial your dose and inject.
  • If the Dose Knob is still difficult to push, contact Lilly at 1-800-Lilly-Rx
    (1-800-545-5979).
• Why is insulin leaking from the needle after I finished injecting my dose? You may have removed the needle from your skin too quickly.
  • Make sure you see a 0 in the Dose Window to confirm you received the complete dose.
  • For the next dose, push and hold the Dose Knob in and count to 5 slowly before removing the needle.
• What should I do if my dose is dialed and the Dose Knob is accidentally pushed in without a needle attached?
  • Dial back to zero.
  • Attach a new needle. When you do this you may see insulin come out of the needle.
  • Prime the Pen.
  • Dial your dose and inject.
• What should I do if I dial a wrong dose (too high or too low)? Turn the Dose Knob backward or forward to correct the dose before injecting.
• What should I do if I see insulin leaking from the KwikPen needle while dialing the dose or correcting the dose? Do not inject the dose because you may not get your complete dose. Dial the Pen down to zero and prime the Pen again (see “Priming Humalog KwikPen” steps 2 B-D). Dial your dose and inject.
• What should I do if my full dose cannot be dialed? The Pen will not allow you to dial a dose greater than the number of insulin units remaining in the cartridge. For example, if you need 31 units and only 25 units remain in the cartridge you will not be able to dial past 25. Do not attempt to dial past this point. You may either:
  • Inject the partial dose and then inject the remaining dose using a new Pen.

         or

  • Inject the full dose with a new Pen.
• Why can I not dial the dose to use the small amount of insulin that remains in my cartridge? The Pen is designed to deliver at least 300 units of insulin. The Pen design prevents the cartridge from being completely emptied because the small amount of insulin that remains in the cartridge cannot be delivered.

Storage and Disposal

Important Notes

• Refer to the Patient Information Leaflet for complete insulin storage instructions.
• Pens that have not been used should be stored in a refrigerator but not in a freezer. Do not use a Pen if it has been frozen.
• Do not store the Pen with the needle attached. If the needle remains attached, insulin may leak from the Pen, insulin may dry inside the needle causing the needle to clog, or air bubbles may form inside the cartridge.
• The Pen you are currently using should be kept at room temperature and away from heat and light.
• Keep the Pen out of the reach of children.
• Dispose of used needles in a puncture-resistant container or as directed by your healthcare professional.
• Dispose of used Pens as instructed by your healthcare professional and without the needle attached.

Use the space below to keep track of how long you should use each Pen in the carton. Once you start using a KwikPen it must be thrown out after the number of days listed in your Patient Information Leaflet, even if there is insulin remaining in the Pen. Record the date you start using a Pen, find the number of days that KwikPen should be used in the Patient Information Leaflet and determine the date the Pen should be thrown out. Record the dates in the space provided below.

Example:

Pen 1 - First used on _______ +	Number of days you should =	Throw out on ______
Date	use KwikPen (from Patient	Date
	Information Leaflet)
Pen 1 - First used on _______	Throw out on _______
Date	Date
Pen 2 - First used on _______	Throw out on _______
Date	Date
Pen 3 - First used on _______	Throw out on _______
Date	Date
Pen 4 - First used on _______	Throw out on _______
Date	Date
Pen 5 - First used on _______	Throw out on _______
Date	Date

If you have any questions or problems with your Humalog KwikPen , contact Lilly at 1-800-Lilly-Rx (1-800-545-5979) or your healthcare professional for assistance.

For more information on Humalog KwikPen and insulin, please visit our website at www.humalog.com

Humalog^® and Humalog^® KwikPen^™ are trademarks of Eli Lilly and Company.

Marketed by: Lilly USA, LLC
Indianapolis, IN 46285, USA

Copyright © 2007, 2011, Eli Lilly and Company. All rights reserved.

Humalog KwikPen meets the current dose accuracy and functional requirements of ISO 11608-1:2000.

Humalog^® KwikPen™New Pen NeedleAlcohol Swab

□

□

□

Getting Ready
Make sure you have the following items:

Pen Parts

KwikPen, and Needle* Assembly *sold separately

Follow these instructions for each injection
1. Preparing Humalog KwikPen
A.	B.		C.
Pull Pen Cap to remove. Be sure to check your insulin for: Type Expiration date Appearance Use an alcohol swab to wipe the Rubber Seal on the end of the Cartridge Holder.	Remove Paper Tab from Outer Needle Shield.		Push capped needle straight onto the Pen. Screw needle on until secure.

2. Priming Humalog KwikPen
Caution: If you do not prime before each injection, you may get too much or too little insulin.
A.	B.	C.	D.
Pull off Outer Needle Shield. Do not throw away. Pull off Inner Needle Shield and throw away.	Dial 2 Units by turning the Dose Knob.	Point Pen up. Tap Cartridge Holder to collect air at top.		With needle pointing up, push Dose Knob in until it stops and 0 is seen in the Dose Window.
			Hold Dose Knob in and count to 5 slowly. Priming is complete when a stream of insulin appears from the needle tip and you have counted to 5 slowly. If a stream of insulin does not appear, repeat priming steps 2 B-D up to four times. If the Pen still does not prime, change the needle and repeat the priming steps above. Note: If you do not see a stream of insulin from the tip of the needle and the Dose Knob becomes hard to push, then change the needle and prime the Pen.

3. Injecting Your Dose
A.	B.		C.	D.
Turn Dose Knob to the number of units you need to inject. If you dial too many units, you can correct the dose by dialing backwards. Example: 10 units shown. Example: 15 units shown. The even numbers are printed on the dial. The odd numbers, after the number one, are shown as full lines.	Insert needle into skin using injection technique recommended by your healthcare professional. Place your thumb on the Dose Knob and push firmly until the Dose Knob stops. Note: The Pen will not allow you to dial more than the number of units left in the Pen.	To deliver the full dose, hold Dose Knob in and count to 5 slowly. Remove needle from skin. Note: Check to make sure you see 0 in the Dose Window to confirm you received the complete dose.	Carefully replace the Outer Needle Shield. Note: Remove the needle after each injection to keep air out of the cartridge. Do not store the Pen with the needle attached.	Unscrew the capped needle and dispose of as directed by your healthcare professional. Replace Pen Cap.

Literature revised October 28, 2011

PV 5592 AMP

PACKAGE LABELING

PACKAGE CARTON – HUMALOG Vial 10 mL 1ct

NDC 54868-5108-0

10 mL

VL-7510

100 units per mL

Humalog^®

insulin lispro injection, USP

(rDNA origin)

For subcutaneous use.

Rx only

U-100

PACKAGE LABELING

PACKAGE CARTON – HUMALOG Prefilled Pen 5 x 3mL

NDC 54868-5899-0

15 mL

VL-8725

100 units per mL

Humalog^®

insulin lispro injection, USP

(rDNA origin)

For subcutaneous use.

Rx only

U-100

PACKAGE LABELING

PACKAGE CARTON – HUMALOG Cartridge 5 x 3 mL

NDC 54868-5836-0

15 mL

VL-7516

100 units per mL

Humalog^®

insulin lispro injection, USP

(rDNA origin)

For subcutaneous use.

Rx only

U-100

Humalog Insulin lispro INJECTION, SOLUTION Product Information Product Type Human prescription drug label Item Code (Source) NDC:54868-5108(NDC:0002-7510) Route of Administration SUBCUTANEOUS DEA Schedule Active Ingredient/Active Moiety Ingredient Name Basis of Strength Strength Insulin lispro Insulin lispro 100 [iU] Inactive Ingredients Ingredient Name Strength GLYCERIN SODIUM PHOSPHATE, DIBASIC METACRESOL Zinc PHENOL water HYDROCHLORIC ACID SODIUM HYDROXIDE Packaging # Item Code Package Description Marketing Start Date Marketing End Date 1 10 in 1 VIAL 2 NDC:54868-5108-0 1 in 1 CARTON Marketing Information Marketing Category Application Number or Monograph Citation Marketing Start Date Marketing End Date NDA NDA020563 2005-05-02

Humalog Insulin lispro INJECTION, SOLUTION Product Information Product Type Human prescription drug label Item Code (Source) NDC:54868-5899(NDC:0002-8725) Route of Administration SUBCUTANEOUS DEA Schedule Active Ingredient/Active Moiety Ingredient Name Basis of Strength Strength Insulin lispro Insulin lispro 100 [iU] Inactive Ingredients Ingredient Name Strength GLYCERIN SODIUM PHOSPHATE, DIBASIC METACRESOL Zinc PHENOL water HYDROCHLORIC ACID SODIUM HYDROXIDE Packaging # Item Code Package Description Marketing Start Date Marketing End Date 1 3 in 1 SYRINGE 2 NDC:54868-5899-0 5 in 1 CARTON Marketing Information Marketing Category Application Number or Monograph Citation Marketing Start Date Marketing End Date NDA NDA020563 2008-05-12

Humalog Insulin lispro INJECTION, SOLUTION Product Information Product Type Human prescription drug label Item Code (Source) NDC:54868-5836(NDC:0002-7516) Route of Administration SUBCUTANEOUS DEA Schedule Active Ingredient/Active Moiety Ingredient Name Basis of Strength Strength Insulin lispro Insulin lispro 100 [iU] Inactive Ingredients Ingredient Name Strength GLYCERIN SODIUM PHOSPHATE, DIBASIC METACRESOL Zinc PHENOL water HYDROCHLORIC ACID SODIUM HYDROXIDE Packaging # Item Code Package Description Marketing Start Date Marketing End Date 1 3 in 1 CARTRIDGE 2 NDC:54868-5836-0 5 in 1 CARTON Marketing Information Marketing Category Application Number or Monograph Citation Marketing Start Date Marketing End Date NDA NDA020563 2007-12-03