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.

Intravenous Administration of HUMALOG — The glucose lowering effect of intravenously administered HUMALOG 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 HUMALOG at an initial infusion rate of 0.5 units/hour. The infusion rate of HUMALOG 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 HUMALOG 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 HUMALOG. The average time (±SE) required to attain near normoglycemia was 129 ± 14 minutes for HUMALOG.

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 — 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 HUMALOG 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 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 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, HUMALOG 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

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 pharmacokinetics 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 6).

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 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, 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 8). 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 and Handling

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, 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).

16.4 Admixture for Intravenous Administration

Infusion bags prepared with HUMALOG 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 (2.4)].

17 PATIENT COUNSELING INFORMATION

See FDA-approved patient labeling (Patient Information and Instructions for Use).

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 November 14, 2013

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

www.humalog.com

Copyright © 1996, 2013, Eli Lilly and Company. All rights reserved.

PV 5536 AMP

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 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?

Before you use HUMALOG, tell your healthcare provider if you:

• have liver or kidney problems or any other medical conditions. Your dose may need to be adjusted.
• take any other medicines, especially ones commonly called TZDs (thiazolidinediones).
• have heart failure or other heart problems. If you have heart failure, it may get worse while you take TZDs with HUMALOG.
• 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.
• take other medicines, 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.
• Low potassium in your blood (hypokalemia)
• Weight gain

HUMALOG may cause serious side effects, including:

• swelling of your hands and feet
• heart failure. Taking certain diabetes pills called thiazolidinediones or "TZDs" with HUMALOG 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 HUMALOG. Your healthcare provider should monitor you closely while you are taking TZDs with HUMALOG. 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 HUMALOG may need to be adjusted or stopped by your healthcare provider if you have new or worse heart failure.

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 November 14, 2013

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

www.humalog.com

Copyright © 2007, 2013, Eli Lilly and Company. All rights reserved.

PV 5566 AMP

Instructions for Use
HUMALOG^® KwikPen™
insulin lispro injection (rDNA origin)