These Highlights Do Not Include All The Information Needed To Use Humalog Safely And Effectively. See Full Prescribing Information For Humalog.

Subcutaneous Injection: HUMALOG U-100 or U-200

• Administer the dose of HUMALOG U-100 or HUMALOG U-200 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.
• Rotate the injection site within the same region from one injection to the next (abdominal wall, thigh, upper arm, or buttocks) 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)].
• HUMALOG administered by subcutaneous injection should generally be used in regimens with an intermediate- or long-acting insulin.
• The HUMALOG U-100 KwikPen, HUMALOG U-100 Tempo Pen and HUMALOG U-200 KwikPen each dial in 1 unit increments and delivers a maximum dose of 60 units per injection.
• The HUMALOG U-100 Junior KwikPen dials in 0.5 unit increments and delivers a maximum dose of 30 units per injection.

Excess insulin administration may cause hypoglycemia and hypokalemia. Mild episodes of hypoglycemia usually can be treated with oral glucose. Adjustments in drug dosage, meal patterns, or exercise may be needed. More severe episodes with coma, seizure, or neurologic impairment may be treated with a glucagon product for emergency use or concentrated intravenous glucose. Sustained carbohydrate intake and observation may be necessary because hypoglycemia may recur after apparent clinical recovery. Hypokalemia must be corrected appropriately.

Insulin lispro is a rapid-acting human insulin analog produced by recombinant DNA technology utilizing a non-pathogenic laboratory strain of Escherichia coli. Insulin lispro differs from human insulin in that the amino acid proline at position B28 is replaced by lysine and the lysine in position B29 is replaced by proline. Chemically, it is Lys(B28), Pro(B29) human insulin analog and has the empirical formula C₂₅₇H₃₈₃N₆₅O₇₇S₆ and a molecular weight of 5.808 kDa, both identical to that of human insulin.

Insulin lispro has the following primary structure:

HUMALOG (insulin lispro) injection is a sterile, clear, and colorless solution for subcutaneous or intravenous use.

Each mL of HUMALOG U-100 contains 100 units of insulin lispro, and the inactive ingredients: dibasic sodium phosphate (1.0 mg), glycerin (16 mg), metacresol (3.15 mg), trace amounts of phenol, zinc oxide (content adjusted to provide 0.0197 mg zinc ion), and Water for Injection, USP.

Each mL of HUMALOG U-200 contains 200 units of insulin lispro, and the inactive ingredients: glycerin (16 mg), metacresol (3.15 mg), trace amounts of phenol, tromethamine (5 mg), zinc oxide (content adjusted to provide 0.046 mg zinc ion), and Water for Injection, USP.

HUMALOG has a pH of 7.0 to 7.8.

Hydrochloric acid 10% and/or sodium hydroxide 10% is added to adjust the pH.

All insulins, including HUMALOG, 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).

Hypoglycemia is the most common adverse reaction associated with insulins, including HUMALOG. 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.

The safety and effectiveness of HUMALOG to improve glycemic control have been established in pediatric patients with diabetes mellitus. Use of HUMALOG for this indication is supported by evidence from adequate and well-controlled studies in 831 pediatric patients with type 1 diabetes mellitus aged 3 years and older and from studies in adults with diabetes mellitus [see Adverse Reactions (6.1), Clinical Pharmacology (12.3), and Clinical Studies (14)].

Of the total number of patients (n=2,834) in eight clinical studies of HUMALOG, twelve percent (n=338) were 65 years of age or over. The majority of these patients 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 HUMALOG action have not been performed.

The safety and efficacy of HUMALOG U-100 were studied in pediatric and adult patients with type 1 diabetes (n=789) and adult patients with type 2 diabetes (n=722).

HUMALOG is contraindicated:

• during episodes of hypoglycemia [see Warnings and Precautions (5.3)].
• in patients who are hypersensitive to insulin lispro or to any of the excipients in HUMALOG [see Warnings and Precautions (5.5)].

The following adverse reactions are discussed elsewhere:

• Hypoglycemia [see Warnings and Precautions (5.3)].
• Hypoglycemia Due to Medication Errors [see Warnings and Precautions (5.4)].
• Hypersensitivity Reactions [see Warnings and Precautions (5.5)].
• Hypokalemia [see Warnings and Precautions (5.6)].

The table below includes clinically significant drug interactions with HUMALOG.

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

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 (5.2)].

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

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

HUMALOG is indicated to improve glycemic control in adult and pediatric patients with diabetes mellitus.

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.

• Individualize and adjust the dosage of HUMALOG based on route of administration, the individual's metabolic needs, blood glucose monitoring results and glycemic control goal.
• When switching from another insulin to HUMALOG, a different dosage of HUMALOG may be needed [see Warnings and Precautions (5.2)].
• Dosage modifications 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 any HUMALOG U-100 or U-200 prefilled pens. The dose window shows the number of insulin units to be delivered and no conversion is needed.

• Never share a HUMALOG prefilled pen, cartridge, reusable pen compatible with Lilly 3 mL cartridges, or syringe between patients, even if the needle is changed. (5.1)
• Hyperglycemia or Hypoglycemia with Changes in Insulin Regimen: Make changes to a patient's insulin regimen (e.g., insulin strength, manufacturer, type, injection site or method of administration) under close medical supervision with increased frequency of blood glucose monitoring. (5.2)
• Hypoglycemia: May be life-threatening. Monitor blood glucose and increase monitoring frequency with changes to insulin dosage, use of glucose lowering medications, meal pattern, physical activity; in patients with renal or hepatic impairment; and in patients with hypoglycemia unawareness. (5.3, 7, 8.6, 8.7)
• Hypoglycemia Due to Medication Errors: Accidental mix-ups between insulin products can occur. Instruct patients to check insulin labels before injection. Do not transfer HUMALOG U-200 from the HUMALOG KwikPen to a syringe as overdosage and severe hypoglycemia can result. (5.4)
• Hypersensitivity Reactions: May be life-threatening. Discontinue HUMALOG, monitor and treat if indicated. (5.5)
• Hypokalemia: May be life-threatening. Monitor potassium levels in patients at risk of hypokalemia and treat if indicated. (5.6)
• Fluid Retention and Heart Failure with Concomitant Use of Thiazolidinediones (TZDs): Observe for signs and symptoms of heart failure; consider dosage reduction or discontinuation if heart failure occurs. (5.7)
• Hyperglycemia and Ketoacidosis Due to Insulin Pump Device Malfunction: Monitor glucose and administer HUMALOG U-100 by subcutaneous injection if pump malfunction occurs. (5.8)

• See Full Prescribing Information for important administration instructions. (2.1, 2.2, 2.3, 2.4)
• Subcutaneous injection (2.2):
  • Administer HUMALOG^® U-100 or U-200 by subcutaneous injection into the abdominal wall, thigh, upper arm, or buttocks within 15 minutes before a meal or immediately after a meal.
  • Rotate injection sites to reduce risk of lipodystrophy and localized cutaneous amyloidosis.
• Continuous subcutaneous infusion (Insulin Pump) (2.2):
  • Refer to the insulin infusion pump user manual to see if HUMALOG can be used. Use in accordance with the insulin pump instructions for use.
  • Administer HUMALOG U-100 by continuous subcutaneous infusion using an insulin pump in a region recommended in the instructions from the pump manufacturer.
  • Rotate infusion sites to reduce risk of lipodystrophy and localized cutaneous amyloidosis.
  • DO NOT administer HUMALOG U-200 by continuous subcutaneous infusion.
• Intravenous Infusion (2.2):
  • Administer HUMALOG U-100 by intravenous infusion ONLY after dilution and under medical supervision. DO NOT administer HUMALOG U-200 by intravenous infusion.
• The dosage of HUMALOG must be individualized based on the route of administration and the individual's metabolic needs, blood glucose monitoring results and glycemic control goal. (2.3)
• Do not perform dose conversion when using the HUMALOG U-100 or U-200 prefilled pens. The dose window shows the number of insulin units to be delivered and no conversion is needed. (2.1, 2.3)
• Do not mix HUMALOG U-200 with any other insulin. (2.4)

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

• 10 mL multiple-dose vial
• 3 mL multiple-dose vial
• 3 mL single-patient-use KwikPen prefilled pen
• 3 mL single-patient-use Tempo Pen prefilled pen
• 3 mL single-patient-use Junior KwikPen prefilled pen
• 3 mL single-patient-use cartridges

Injection: 200 units/mL (U-200) clear and colorless solution available as:

• 3 mL single-patient-use KwikPen prefilled pen

The following additional adverse reactions have been identified during post-approval use of HUMALOG. 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 HUMALOG have been identified during post-approval use.

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.

LOG-0007-PPI-20230721

LOG200-0004-PPI-20230721

Severe, life-threatening, generalized allergy, including anaphylaxis, can occur with insulins, including HUMALOG. If hypersensitivity reactions occur, discontinue HUMALOG; treat per standard of care and monitor until symptoms and signs resolve [see Adverse Reactions (6.1)]. HUMALOG is contraindicated in patients who have had hypersensitivity reactions to insulin lispro or any of the excipients in HUMALOG [see Contraindications (4)].

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.

Common adverse reactions, excluding hypoglycemia, were defined as events that occurred in ≥5% of patients treated with insulin lispro or regular human insulin. The frequencies of adverse reactions during HUMALOG clinical trials in patients with type 1 diabetes mellitus and type 2 diabetes mellitus are listed in the tables below.

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 8).

INSTRUCTIONS FOR USE

HUMALOG ^® (HU-ma-log)

(insulin lispro)

injection, for subcutaneous use

3 mL or 10 mL multiple-dose vial (100 units per mL, U-100)

Read this Instructions for Use before you start taking HUMALOG 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 HUMALOG 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 HUMALOG dose

• Wash your hands with soap and water.
• Check the HUMALOG 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.
• HUMALOG should look clear and colorless. Do not use HUMALOG if it is thick, cloudy, or colored, or if you see lumps or particles in it.
• Do not use HUMALOG 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.

If you use HUMALOG with NPH insulin:

• NPH insulin is the only type of insulin that can be mixed with HUMALOG. Do not mix HUMALOG with any other type of insulin.
• HUMALOG 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 HUMALOG and NPH insulin.
• Give your injection right away.

Giving your HUMALOG 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.
• HUMALOG 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.

Giving your HUMALOG using an insulin pump

• HUMALOG should be given into an area of your body recommended in the instructions that come with your insulin pump.
• Change your infusion set and rotate the infusion set insertion site according to the manufacturer's user manual.
• 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 or according to the pump user manual, whichever is shorter, even if you have not used all of the insulin.
• Do not dilute or mix HUMALOG 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 HUMALOG?

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 HUMALOG 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 up to 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.

HUMALOG in an insulin pump:

• Throw away HUMALOG in the pump reservoir if it has been exposed to temperatures higher than 98.6°F (37°C).

Keep HUMALOG vials, syringes, needles and all medicines out of the reach of children.

If you have any questions or problems with your HUMALOG, contact Lilly at 1-800-Lilly-Rx (1-800-545-5979) or call your healthcare provider for help. For more information on HUMALOG and insulin, go to www.humalog.com.

Manufactured by:

Eli Lilly and Company

Indianapolis, IN 46285, USA

US License Number 1891

This Instructions for Use has been approved by the U.S. Food and Drug Administration.

Revised: July 2023

Scan this code to launch the humalog.com website

Humalog^® is a registered trademark of Eli Lilly and Company.

Copyright © 1996, 2023, Eli Lilly and Company. All rights reserved.

LOGVL-0009-IFU-20230721

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

INSTRUCTIONS FOR USE

HUMALOG (HU-ma-log) KwikPen ^®

(insulin lispro)

injection, for subcutaneous use

3 mL single-patient-use pen (100 units per mL)

Read the Instructions for Use before you start taking HUMALOG^® 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 HUMALOG 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.

HUMALOG KwikPen (“Pen”) is a disposable single-patient-use prefilled pen containing 300 units of HUMALOG. 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 HUMALOG KwikPen

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

Supplies you will need to give your injection

• HUMALOG 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.

After your injection

Disposing of Pens and Needles

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

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 HUMALOG 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 HUMALOG KwikPen, contact Lilly at 1-800-LillyRx (1-800-545-5979) or call your healthcare provider for help. For more information on HUMALOG KwikPen and insulin, go to www.humalog.com.

Manufactured by:

Eli Lilly and Company

Indianapolis, IN 46285, USA

US License Number 1891

This Instructions for Use has been approved by the U.S. Food and Drug Administration.

Revised: July 2023

Scan this code to launch (www.humalog.com)

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

Copyright © 2007, 2023, Eli Lilly and Company. All rights reserved.

LOGKP-0009-IFU-20230721

INSTRUCTIONS FOR USE

HUMALOG (HU-ma-log) KwikPen ^®

(insulin lispro)

injection, for subcutaneous use

3 mL single-patient-use pen (200 units per mL)

Read the Instructions for Use before you start taking HUMALOG^® 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 HUMALOG 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.

HUMALOG KwikPen 200 units/mL (“Pen”) is a disposable single-patient-use prefilled pen containing 600 units of HUMALOG. 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 600 units in the Pen.

Inject HUMALOG 200 units/mL only with your Pen. Do not transfer insulin from your Pen to a syringe. Syringes will not measure 200 units/mL insulin correctly. A severe overdose can result, causing very low blood sugar which may put your life in danger.

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 HUMALOG 200 units/mL KwikPen

• Pen color: Dark grey
• Dose Knob: Dark grey with burgundy ring on the end
• Label: Burgundy label with “200 units per mL (U-200)” in white stripe and a grey and burgundy checker board design.

Supplies needed to give your injection

• HUMALOG 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

This Pen has been made to deliver the dose that is shown in the Dose Window. Dial your usual dose as instructed by your healthcare provider.

• 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. Do not transfer this to a syringe. Severe overdose can result.

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 use the exact same spot for each injection.
• Do not inject where the skin has pits, is thickened, or has lumps.
• Do not inject where the skin is tender, bruised, scaly or hard, or into scars or damaged skin.
• Do not try to change your dose while injecting.

After your injection

Disposing of Pens and Needles

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

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 HUMALOG 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 HUMALOG KwikPen, contact Lilly at 1-800-LillyRx (1-800-545-5979) or call your healthcare provider for help. For more information on HUMALOG KwikPen and insulin, go to www.humalog.com.

Manufactured by:

Eli Lilly and Company

Indianapolis, IN 46285, USA

US License Number 1891

This Instructions for Use has been approved by the U.S. Food and Drug Administration.

Revised: July 2023

Scan this code to launch (www.humalog.com)

HUMALOG^® and HUMALOG KwikPen^® are trademarks of Eli Lilly and Company.

Copyright © 2015, 2023, Eli Lilly and Company. All rights reserved.

LOGKP200-0005-IFU-20230721

Product: 50090-4488

NDC: 50090-4488-0 10 mL in a VIAL / 1 in a CARTON

INSTRUCTIONS FOR USE

HUMALOG ^® (HU-ma-log) Tempo Pen™

(insulin lispro)

injection, for subcutaneous use

3 mL single-patient-use pen, (100 units per mL)

Read the Instructions for Use before you start taking HUMALOG and each time you get another HUMALOG Tempo Pen. 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 HUMALOG Tempo Pen 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.

HUMALOG Tempo Pen (“Pen”) is a disposable single-patient-use prefilled pen containing 300 units of HUMALOG. 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.

This HUMALOG Tempo Pen contains a component that allows for data connectivity when used with a compatible transmitter.

How to recognize your HUMALOG Tempo Pen

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

Supplies you will need to give your injection

• HUMALOG Tempo Pen
• Tempo Pen 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 cannot 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.

After your injection

Disposing of Pens and Needles

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

Storing your Pen

Unopened Pens

• Store unopened 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.
• Unopened 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 HUMALOG Tempo 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 cannot 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 HUMALOG Tempo Pen, contact Lilly at 1-800-LillyRx (1-800-545-5979) or call your healthcare provider for help. For more information on HUMALOG Tempo Pen and insulin, go to www.humalog.com.

Manufactured by:

Eli Lilly and Company

Indianapolis, IN 46285, USA

US License Number 1891

This Instructions for Use has been approved by the U.S. Food and Drug Administration.

Revised: July 2023

Scan this code to launch (www.humalog.com)

HUMALOG^® is a registered trademark and TEMPO PEN^TM is a trademark of Eli Lilly and Company.

Copyright © 2019, 2023, Eli Lilly and Company. All rights reserved.

LOGTP-0002-IFU-20230721

• Always check insulin labels before administration [see Warnings and Precautions (5.4)].
• Inspect HUMALOG visually before use. It should appear clear and colorless. Do not use HUMALOG if particulate matter or coloration is seen.
• Use HUMALOG prefilled pens with caution in patients with visual impairment that may rely on audible clicks to dial their dose.
• Do NOT mix HUMALOG U-100 with other insulins when using a continuous subcutaneous infusion pump.
• Do NOT transfer HUMALOG U-200 from the prefilled pen to a syringe for administration [see Warnings and Precautions (5.4)].
• Do NOT perform dose conversion when using any HUMALOG U-100 or U-200 prefilled pens. The dose window shows the number of insulin units to be delivered and no conversion is needed.

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

Do not transfer HUMALOG U-200 from the HUMALOG KwikPen to a syringe. The markings on the insulin syringe will not measure the dose correctly and can result in overdosage and severe hypoglycemia [see Dosage and Administration (2.1) and Warnings and Precautions (5.3)].

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.

An 8-month, crossover study of pediatric patients 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 pediatric patients (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.

Dosage modification may be needed when HUMALOG is used concomitantly with certain drugs [see Drug Interactions (7)].

INSTRUCTIONS FOR USE

HUMALOG ^® (HU-ma-log) Junior KwikPen ^®

(insulin lispro)

injection, for subcutaneous use

3 mL single-patient-use pen (100 units per mL)

Read the Instructions for Use before you start taking HUMALOG and each time you get another HUMALOG^® 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 HUMALOG 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.

HUMALOG Junior KwikPen (“Pen”) is a disposable single-patient-use prefilled pen containing 300 units of HUMALOG.

• 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 HUMALOG 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:

• HUMALOG 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.

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.

• 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.

After your injection

Disposing of Pens and Needles

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

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 HUMALOG 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 HUMALOG Junior KwikPen, contact Lilly at 1-800-LillyRx (1-800-545-5979) or call your healthcare provider for help. For more information on HUMALOG Junior KwikPen and insulin, go to www.humalog.com.

Manufactured by:

Eli Lilly and Company

Indianapolis, IN 46285, USA

US License Number 1891

This Instructions for Use has been approved by the U.S. Food and Drug Administration.

Revised: July 2023

Scan this code to launch (www.humalog.com)

HUMALOG^® and HUMALOG^® Junior KwikPen^® are trademarks of Eli Lilly and Company.

Copyright © 2017, 2023, Eli Lilly and Company. All rights reserved.

LOGJRKP-0004-IFU-20230721

The table below includes administration instructions regarding mixing HUMALOG U-100 and HUMALOG U-200 with other insulins.

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.

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.

To evaluate the administration of HUMALOG U-100 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.

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 HUMALOG 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)].

A randomized, 16-week, open-label, parallel design, study of pediatric patients 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 U-100 (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.

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 [insulin human injection (100 units/mL)] (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.

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 HUMALOG, 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.

HUMALOG prefilled pens, cartridges, and reusable pens compatible with Lilly 3 mL cartridges must never be shared between patients, even if the needle is changed. Patients using HUMALOG vials must never share needles or syringes with another person. Sharing poses a risk for transmission of blood-borne pathogens.

Subcutaneous Injection: HUMALOG U-100 or U-200

• Administer the dose of HUMALOG U-100 or HUMALOG U-200 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.
• Rotate the injection site within the same region from one injection to the next (abdominal wall, thigh, upper arm, or buttocks) 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)].
• HUMALOG administered by subcutaneous injection should generally be used in regimens with an intermediate- or long-acting insulin.
• The HUMALOG U-100 KwikPen, HUMALOG U-100 Tempo Pen and HUMALOG U-200 KwikPen each dial in 1 unit increments and delivers a maximum dose of 60 units per injection.
• The HUMALOG U-100 Junior KwikPen dials in 0.5 unit increments and delivers a maximum dose of 30 units per injection.

Excess insulin administration may cause hypoglycemia and hypokalemia. Mild episodes of hypoglycemia usually can be treated with oral glucose. Adjustments in drug dosage, meal patterns, or exercise may be needed. More severe episodes with coma, seizure, or neurologic impairment may be treated with a glucagon product for emergency use or concentrated intravenous glucose. Sustained carbohydrate intake and observation may be necessary because hypoglycemia may recur after apparent clinical recovery. Hypokalemia must be corrected appropriately.

Insulin lispro is a rapid-acting human insulin analog produced by recombinant DNA technology utilizing a non-pathogenic laboratory strain of Escherichia coli. Insulin lispro differs from human insulin in that the amino acid proline at position B28 is replaced by lysine and the lysine in position B29 is replaced by proline. Chemically, it is Lys(B28), Pro(B29) human insulin analog and has the empirical formula C₂₅₇H₃₈₃N₆₅O₇₇S₆ and a molecular weight of 5.808 kDa, both identical to that of human insulin.

Insulin lispro has the following primary structure:

HUMALOG (insulin lispro) injection is a sterile, clear, and colorless solution for subcutaneous or intravenous use.

Each mL of HUMALOG U-100 contains 100 units of insulin lispro, and the inactive ingredients: dibasic sodium phosphate (1.0 mg), glycerin (16 mg), metacresol (3.15 mg), trace amounts of phenol, zinc oxide (content adjusted to provide 0.0197 mg zinc ion), and Water for Injection, USP.

Each mL of HUMALOG U-200 contains 200 units of insulin lispro, and the inactive ingredients: glycerin (16 mg), metacresol (3.15 mg), trace amounts of phenol, tromethamine (5 mg), zinc oxide (content adjusted to provide 0.046 mg zinc ion), and Water for Injection, USP.

HUMALOG has a pH of 7.0 to 7.8.

Hydrochloric acid 10% and/or sodium hydroxide 10% is added to adjust the pH.

All insulins, including HUMALOG, 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).

Hypoglycemia is the most common adverse reaction associated with insulins, including HUMALOG. 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.

The safety and effectiveness of HUMALOG to improve glycemic control have been established in pediatric patients with diabetes mellitus. Use of HUMALOG for this indication is supported by evidence from adequate and well-controlled studies in 831 pediatric patients with type 1 diabetes mellitus aged 3 years and older and from studies in adults with diabetes mellitus [see Adverse Reactions (6.1), Clinical Pharmacology (12.3), and Clinical Studies (14)].

Of the total number of patients (n=2,834) in eight clinical studies of HUMALOG, twelve percent (n=338) were 65 years of age or over. The majority of these patients 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 HUMALOG action have not been performed.

The safety and efficacy of HUMALOG U-100 were studied in pediatric and adult patients with type 1 diabetes (n=789) and adult patients with type 2 diabetes (n=722).

HUMALOG is contraindicated:

• during episodes of hypoglycemia [see Warnings and Precautions (5.3)].
• in patients who are hypersensitive to insulin lispro or to any of the excipients in HUMALOG [see Warnings and Precautions (5.5)].

The following adverse reactions are discussed elsewhere:

• Hypoglycemia [see Warnings and Precautions (5.3)].
• Hypoglycemia Due to Medication Errors [see Warnings and Precautions (5.4)].
• Hypersensitivity Reactions [see Warnings and Precautions (5.5)].
• Hypokalemia [see Warnings and Precautions (5.6)].

The table below includes clinically significant drug interactions with HUMALOG.

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

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 (5.2)].

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

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

HUMALOG is indicated to improve glycemic control in adult and pediatric patients with diabetes mellitus.

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.

• Individualize and adjust the dosage of HUMALOG based on route of administration, the individual's metabolic needs, blood glucose monitoring results and glycemic control goal.
• When switching from another insulin to HUMALOG, a different dosage of HUMALOG may be needed [see Warnings and Precautions (5.2)].
• Dosage modifications 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 any HUMALOG U-100 or U-200 prefilled pens. The dose window shows the number of insulin units to be delivered and no conversion is needed.

• Never share a HUMALOG prefilled pen, cartridge, reusable pen compatible with Lilly 3 mL cartridges, or syringe between patients, even if the needle is changed. (5.1)
• Hyperglycemia or Hypoglycemia with Changes in Insulin Regimen: Make changes to a patient's insulin regimen (e.g., insulin strength, manufacturer, type, injection site or method of administration) under close medical supervision with increased frequency of blood glucose monitoring. (5.2)
• Hypoglycemia: May be life-threatening. Monitor blood glucose and increase monitoring frequency with changes to insulin dosage, use of glucose lowering medications, meal pattern, physical activity; in patients with renal or hepatic impairment; and in patients with hypoglycemia unawareness. (5.3, 7, 8.6, 8.7)
• Hypoglycemia Due to Medication Errors: Accidental mix-ups between insulin products can occur. Instruct patients to check insulin labels before injection. Do not transfer HUMALOG U-200 from the HUMALOG KwikPen to a syringe as overdosage and severe hypoglycemia can result. (5.4)
• Hypersensitivity Reactions: May be life-threatening. Discontinue HUMALOG, monitor and treat if indicated. (5.5)
• Hypokalemia: May be life-threatening. Monitor potassium levels in patients at risk of hypokalemia and treat if indicated. (5.6)
• Fluid Retention and Heart Failure with Concomitant Use of Thiazolidinediones (TZDs): Observe for signs and symptoms of heart failure; consider dosage reduction or discontinuation if heart failure occurs. (5.7)
• Hyperglycemia and Ketoacidosis Due to Insulin Pump Device Malfunction: Monitor glucose and administer HUMALOG U-100 by subcutaneous injection if pump malfunction occurs. (5.8)

• See Full Prescribing Information for important administration instructions. (2.1, 2.2, 2.3, 2.4)
• Subcutaneous injection (2.2):
  • Administer HUMALOG^® U-100 or U-200 by subcutaneous injection into the abdominal wall, thigh, upper arm, or buttocks within 15 minutes before a meal or immediately after a meal.
  • Rotate injection sites to reduce risk of lipodystrophy and localized cutaneous amyloidosis.
• Continuous subcutaneous infusion (Insulin Pump) (2.2):
  • Refer to the insulin infusion pump user manual to see if HUMALOG can be used. Use in accordance with the insulin pump instructions for use.
  • Administer HUMALOG U-100 by continuous subcutaneous infusion using an insulin pump in a region recommended in the instructions from the pump manufacturer.
  • Rotate infusion sites to reduce risk of lipodystrophy and localized cutaneous amyloidosis.
  • DO NOT administer HUMALOG U-200 by continuous subcutaneous infusion.
• Intravenous Infusion (2.2):
  • Administer HUMALOG U-100 by intravenous infusion ONLY after dilution and under medical supervision. DO NOT administer HUMALOG U-200 by intravenous infusion.
• The dosage of HUMALOG must be individualized based on the route of administration and the individual's metabolic needs, blood glucose monitoring results and glycemic control goal. (2.3)
• Do not perform dose conversion when using the HUMALOG U-100 or U-200 prefilled pens. The dose window shows the number of insulin units to be delivered and no conversion is needed. (2.1, 2.3)
• Do not mix HUMALOG U-200 with any other insulin. (2.4)

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

• 10 mL multiple-dose vial
• 3 mL multiple-dose vial
• 3 mL single-patient-use KwikPen prefilled pen
• 3 mL single-patient-use Tempo Pen prefilled pen
• 3 mL single-patient-use Junior KwikPen prefilled pen
• 3 mL single-patient-use cartridges

Injection: 200 units/mL (U-200) clear and colorless solution available as:

• 3 mL single-patient-use KwikPen prefilled pen

The following additional adverse reactions have been identified during post-approval use of HUMALOG. 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 HUMALOG have been identified during post-approval use.

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.

LOG-0007-PPI-20230721

LOG200-0004-PPI-20230721

Severe, life-threatening, generalized allergy, including anaphylaxis, can occur with insulins, including HUMALOG. If hypersensitivity reactions occur, discontinue HUMALOG; treat per standard of care and monitor until symptoms and signs resolve [see Adverse Reactions (6.1)]. HUMALOG is contraindicated in patients who have had hypersensitivity reactions to insulin lispro or any of the excipients in HUMALOG [see Contraindications (4)].

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.

Common adverse reactions, excluding hypoglycemia, were defined as events that occurred in ≥5% of patients treated with insulin lispro or regular human insulin. The frequencies of adverse reactions during HUMALOG clinical trials in patients with type 1 diabetes mellitus and type 2 diabetes mellitus are listed in the tables below.

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 8).

INSTRUCTIONS FOR USE

HUMALOG ^® (HU-ma-log)

(insulin lispro)

injection, for subcutaneous use

3 mL or 10 mL multiple-dose vial (100 units per mL, U-100)

Read this Instructions for Use before you start taking HUMALOG 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 HUMALOG 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 HUMALOG dose

• Wash your hands with soap and water.
• Check the HUMALOG 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.
• HUMALOG should look clear and colorless. Do not use HUMALOG if it is thick, cloudy, or colored, or if you see lumps or particles in it.
• Do not use HUMALOG 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.

If you use HUMALOG with NPH insulin:

• NPH insulin is the only type of insulin that can be mixed with HUMALOG. Do not mix HUMALOG with any other type of insulin.
• HUMALOG 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 HUMALOG and NPH insulin.
• Give your injection right away.

Giving your HUMALOG 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.
• HUMALOG 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.

Giving your HUMALOG using an insulin pump

• HUMALOG should be given into an area of your body recommended in the instructions that come with your insulin pump.
• Change your infusion set and rotate the infusion set insertion site according to the manufacturer's user manual.
• 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 or according to the pump user manual, whichever is shorter, even if you have not used all of the insulin.
• Do not dilute or mix HUMALOG 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 HUMALOG?

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 HUMALOG 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 up to 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.

HUMALOG in an insulin pump:

• Throw away HUMALOG in the pump reservoir if it has been exposed to temperatures higher than 98.6°F (37°C).

Keep HUMALOG vials, syringes, needles and all medicines out of the reach of children.

If you have any questions or problems with your HUMALOG, contact Lilly at 1-800-Lilly-Rx (1-800-545-5979) or call your healthcare provider for help. For more information on HUMALOG and insulin, go to www.humalog.com.

Manufactured by:

Eli Lilly and Company

Indianapolis, IN 46285, USA

US License Number 1891

This Instructions for Use has been approved by the U.S. Food and Drug Administration.

Revised: July 2023

Scan this code to launch the humalog.com website

Humalog^® is a registered trademark of Eli Lilly and Company.

Copyright © 1996, 2023, Eli Lilly and Company. All rights reserved.

LOGVL-0009-IFU-20230721

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

INSTRUCTIONS FOR USE

HUMALOG (HU-ma-log) KwikPen ^®

(insulin lispro)

injection, for subcutaneous use

3 mL single-patient-use pen (100 units per mL)

Read the Instructions for Use before you start taking HUMALOG^® 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 HUMALOG 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.

HUMALOG KwikPen (“Pen”) is a disposable single-patient-use prefilled pen containing 300 units of HUMALOG. 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 HUMALOG KwikPen

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

Supplies you will need to give your injection

• HUMALOG 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.

After your injection

Disposing of Pens and Needles

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

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 HUMALOG 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 HUMALOG KwikPen, contact Lilly at 1-800-LillyRx (1-800-545-5979) or call your healthcare provider for help. For more information on HUMALOG KwikPen and insulin, go to www.humalog.com.

Manufactured by:

Eli Lilly and Company

Indianapolis, IN 46285, USA

US License Number 1891

This Instructions for Use has been approved by the U.S. Food and Drug Administration.

Revised: July 2023

Scan this code to launch (www.humalog.com)

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

Copyright © 2007, 2023, Eli Lilly and Company. All rights reserved.

LOGKP-0009-IFU-20230721

INSTRUCTIONS FOR USE

HUMALOG (HU-ma-log) KwikPen ^®

(insulin lispro)

injection, for subcutaneous use

3 mL single-patient-use pen (200 units per mL)

Read the Instructions for Use before you start taking HUMALOG^® 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 HUMALOG 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.

HUMALOG KwikPen 200 units/mL (“Pen”) is a disposable single-patient-use prefilled pen containing 600 units of HUMALOG. 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 600 units in the Pen.

Inject HUMALOG 200 units/mL only with your Pen. Do not transfer insulin from your Pen to a syringe. Syringes will not measure 200 units/mL insulin correctly. A severe overdose can result, causing very low blood sugar which may put your life in danger.

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 HUMALOG 200 units/mL KwikPen

• Pen color: Dark grey
• Dose Knob: Dark grey with burgundy ring on the end
• Label: Burgundy label with “200 units per mL (U-200)” in white stripe and a grey and burgundy checker board design.

Supplies needed to give your injection

• HUMALOG 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

This Pen has been made to deliver the dose that is shown in the Dose Window. Dial your usual dose as instructed by your healthcare provider.

• 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. Do not transfer this to a syringe. Severe overdose can result.

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 use the exact same spot for each injection.
• Do not inject where the skin has pits, is thickened, or has lumps.
• Do not inject where the skin is tender, bruised, scaly or hard, or into scars or damaged skin.
• Do not try to change your dose while injecting.

After your injection

Disposing of Pens and Needles

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

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 HUMALOG 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 HUMALOG KwikPen, contact Lilly at 1-800-LillyRx (1-800-545-5979) or call your healthcare provider for help. For more information on HUMALOG KwikPen and insulin, go to www.humalog.com.

Manufactured by:

Eli Lilly and Company

Indianapolis, IN 46285, USA

US License Number 1891

This Instructions for Use has been approved by the U.S. Food and Drug Administration.

Revised: July 2023

Scan this code to launch (www.humalog.com)

HUMALOG^® and HUMALOG KwikPen^® are trademarks of Eli Lilly and Company.

Copyright © 2015, 2023, Eli Lilly and Company. All rights reserved.

LOGKP200-0005-IFU-20230721

Product: 50090-4488

NDC: 50090-4488-0 10 mL in a VIAL / 1 in a CARTON

INSTRUCTIONS FOR USE

HUMALOG ^® (HU-ma-log) Tempo Pen™

(insulin lispro)

injection, for subcutaneous use

3 mL single-patient-use pen, (100 units per mL)

Read the Instructions for Use before you start taking HUMALOG and each time you get another HUMALOG Tempo Pen. 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 HUMALOG Tempo Pen 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.

HUMALOG Tempo Pen (“Pen”) is a disposable single-patient-use prefilled pen containing 300 units of HUMALOG. 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.

This HUMALOG Tempo Pen contains a component that allows for data connectivity when used with a compatible transmitter.

How to recognize your HUMALOG Tempo Pen

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

Supplies you will need to give your injection

• HUMALOG Tempo Pen
• Tempo Pen 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 cannot 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.

After your injection

Disposing of Pens and Needles

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

Storing your Pen

Unopened Pens

• Store unopened 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.
• Unopened 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 HUMALOG Tempo 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 cannot 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 HUMALOG Tempo Pen, contact Lilly at 1-800-LillyRx (1-800-545-5979) or call your healthcare provider for help. For more information on HUMALOG Tempo Pen and insulin, go to www.humalog.com.

Manufactured by:

Eli Lilly and Company

Indianapolis, IN 46285, USA

US License Number 1891

This Instructions for Use has been approved by the U.S. Food and Drug Administration.

Revised: July 2023

Scan this code to launch (www.humalog.com)

HUMALOG^® is a registered trademark and TEMPO PEN^TM is a trademark of Eli Lilly and Company.

Copyright © 2019, 2023, Eli Lilly and Company. All rights reserved.

LOGTP-0002-IFU-20230721

• Always check insulin labels before administration [see Warnings and Precautions (5.4)].
• Inspect HUMALOG visually before use. It should appear clear and colorless. Do not use HUMALOG if particulate matter or coloration is seen.
• Use HUMALOG prefilled pens with caution in patients with visual impairment that may rely on audible clicks to dial their dose.
• Do NOT mix HUMALOG U-100 with other insulins when using a continuous subcutaneous infusion pump.
• Do NOT transfer HUMALOG U-200 from the prefilled pen to a syringe for administration [see Warnings and Precautions (5.4)].
• Do NOT perform dose conversion when using any HUMALOG U-100 or U-200 prefilled pens. The dose window shows the number of insulin units to be delivered and no conversion is needed.

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

Do not transfer HUMALOG U-200 from the HUMALOG KwikPen to a syringe. The markings on the insulin syringe will not measure the dose correctly and can result in overdosage and severe hypoglycemia [see Dosage and Administration (2.1) and Warnings and Precautions (5.3)].

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.

An 8-month, crossover study of pediatric patients 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 pediatric patients (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.

Dosage modification may be needed when HUMALOG is used concomitantly with certain drugs [see Drug Interactions (7)].

INSTRUCTIONS FOR USE

HUMALOG ^® (HU-ma-log) Junior KwikPen ^®

(insulin lispro)

injection, for subcutaneous use

3 mL single-patient-use pen (100 units per mL)

Read the Instructions for Use before you start taking HUMALOG and each time you get another HUMALOG^® 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 HUMALOG 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.

HUMALOG Junior KwikPen (“Pen”) is a disposable single-patient-use prefilled pen containing 300 units of HUMALOG.

• 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 HUMALOG 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:

• HUMALOG 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.

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.

• 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.

After your injection

Disposing of Pens and Needles

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

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 HUMALOG 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 HUMALOG Junior KwikPen, contact Lilly at 1-800-LillyRx (1-800-545-5979) or call your healthcare provider for help. For more information on HUMALOG Junior KwikPen and insulin, go to www.humalog.com.

Manufactured by:

Eli Lilly and Company

Indianapolis, IN 46285, USA

US License Number 1891

This Instructions for Use has been approved by the U.S. Food and Drug Administration.

Revised: July 2023

Scan this code to launch (www.humalog.com)

HUMALOG^® and HUMALOG^® Junior KwikPen^® are trademarks of Eli Lilly and Company.

Copyright © 2017, 2023, Eli Lilly and Company. All rights reserved.

LOGJRKP-0004-IFU-20230721

The table below includes administration instructions regarding mixing HUMALOG U-100 and HUMALOG U-200 with other insulins.

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.

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.

To evaluate the administration of HUMALOG U-100 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.

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 HUMALOG 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)].

A randomized, 16-week, open-label, parallel design, study of pediatric patients 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 U-100 (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.

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 [insulin human injection (100 units/mL)] (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.

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 HUMALOG, 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.

HUMALOG prefilled pens, cartridges, and reusable pens compatible with Lilly 3 mL cartridges must never be shared between patients, even if the needle is changed. Patients using HUMALOG vials must never share needles or syringes with another person. Sharing poses a risk for transmission of blood-borne pathogens.