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

Subcutaneous Injection

• Inject HUMULIN R subcutaneously approximately 30 minutes before meals into the thigh, upper arm, abdomen, or buttocks.
• Rotate injection sites within the same region from one injection to the next 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)].
• HUMULIN R may be diluted with Sterile Diluent for HUMULIN R for subcutaneous injection ONLY under medical supervision.
  • Dilute one part HUMULIN R to nine parts diluent to yield a concentration one-tenth that of HUMULIN R (equivalent to U-10).
  • Dilute one part HUMULIN R to one part diluent to yield a concentration one-half that of HUMULIN R (equivalent to U-50).
  • Diluted HUMULIN R may be used for 28 days when stored at 41°F (5°C) or for 14 days when stored at 86°F (30°C).

Not in-use (unopened): Humulin R U-100 vials not in-use should be stored in a refrigerator (2° to 8°C [36° to 46°F]), but not in the freezer. In-use (opened): The Humulin R U-100 vial currently in-use can be kept unrefrigerated as long as it is kept as cool as possible [below 30°C (86°F)] away from heat and light. In-use vials must be used within 31 days or be discarded, even if they still contain Humulin R U-100. Admixture: Infusion bags prepared with Humulin R U-100 as indicated under DOSAGE AND ADMINISTRATION are stable when stored in a refrigerator (2° to 8°C [36° to 46°F]) for 48 hours and then may be used at room temperature for up to an additional 48 hours. Do not use Humulin R U-100 after the expiration date stamped on the label or if it has been frozen.

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 intravenous glucose. Sustained carbohydrate intake and observation may be necessary because hypoglycemia may recur after apparent clinical recovery. Hypokalemia must be corrected appropriately [see Warnings and Precautions (5.3, 5.6)].

Insulin human is produced by recombinant DNA technology utilizing a non-pathogenic laboratory strain of Escherichia coli and has the empirical formula C₂₅₇H₃₈₃N₆₅O₇₇S₆ with a molecular weight of 5.808 kDa.

HUMULIN R (insulin human) injection is a short-acting human insulin for subcutaneous or intravenous use.

HUMULIN R is a sterile, aqueous, clear, and colorless solution. HUMULIN R contains 100 units of insulin human in each milliliter. Each milliliter of HUMULIN R also contains glycerin (16 mg), metacresol (2.5 mg), endogenous zinc (approximately 0.015 mg/100 units,) and Water for Injection. Sodium hydroxide and hydrochloric acid may be added during manufacture to adjust the pH. The pH is 7.0 to 7.8.

All insulins, including HUMULIN R, 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 of all insulins, including HUMULIN R. Severe hypoglycemia can cause seizures, may lead to unconsciousness, may be life threatening or cause death. Hypoglycemia can impair concentration ability and reaction time; this may place the patient 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 patient and change over time in the same patient. Symptomatic awareness of hypoglycemia may be less pronounced in patients with longstanding diabetes, in patients with diabetic neuropathy, 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.

HUMULIN R is indicated to improve glycemic control in pediatric patients with diabetes mellitus.

The dosage of HUMULIN R must be individualized in pediatric patients based on metabolic needs and frequent monitoring of blood glucose to reduce the risk of hypoglycemia [see Dosage and Administration (2.3), Warnings and Precautions (5.3)].

The effect of age on the pharmacokinetics and pharmacodynamics of HUMULIN R has not been studied. Elderly patients using HUMULIN R may be at increased risk of hypoglycemia due to co-morbid disease [see Warnings and Precautions (5.3)].

HUMULIN R is contraindicated:

• during episodes of hypoglycemia [see Warnings and Precautions (5.3)]
• in patients with hypersensitivity to HUMULIN R or any of its excipients [see Warnings and Precautions (5.5)]

The following adverse reactions are also discussed elsewhere in the labeling:

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

The effect of renal impairment on the pharmacokinetics and pharmacodynamics of HUMULIN R has not been studied. Patients with renal impairment are at increased risk of hypoglycemia and may require more frequent HUMULIN R dose adjustment and more frequent blood glucose monitoring [see Warnings and Precautions (5.3)].

The time course of insulin action (i.e., glucose lowering) may vary considerably in different individuals or within the same individual. With subcutaneous use, the pharmacologic effect of HUMULIN R begins approximately 30 minutes (range: 10 to 75 minutes) after administration of doses in the 0.05 to 0.4 units/kg range (Figure 1). The effect is maximal at approximately 3 hours (range: 20 minutes to 7 hours) and terminates after approximately 8 hours (range: 3 to 14 hours). In a study that administered 50 and 100 units doses subcutaneously to obese subjects, mean time of termination of effect was prolonged to approximately 18 hours (range approximately 12-24 hours).

With intravenous use, the pharmacologic effect of HUMULIN R begins at approximately 10 to 15 minutes and terminates at a median time of approximately 4 hours (range: 2 to 6 hours) after administration of doses in the range of 0.1 to 0.2 units/kg.

The intravenous administration of HUMULIN R was tested in 21 people with type 1 diabetes. During the 6-hour assessment phase patients received intravenous HUMULIN R at an initial dose of 0.5 units/hour, adjusted to maintain blood glucose concentrations near normoglycemia (100 to 160 mg/dL).

The mean blood glucose levels during the assessment phase for patients on HUMULIN R therapy are summarized below in Table 2. All patients achieved near normoglycemia during the 6-hour assessment phase. The average time (± SE) required to attain near normoglycemia was 161 ± 14 minutes for HUMULIN R.

The effect of hepatic impairment on the pharmacokinetics and pharmacodynamics of HUMULIN R has not been studied. Patients with hepatic impairment are at increased risk of hypoglycemia and may require more frequent HUMULIN R dose adjustment and more frequent blood glucose monitoring [see Warnings and Precautions (5.3)].

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

• Individualize and adjust the dosage of HUMULIN R based on the route of administration, the patient's metabolic needs, blood glucose monitoring results, and glycemic control goal.
• HUMULIN R given by subcutaneous injection should generally be used in regimens with an intermediate- or long-acting insulin.
• During changes to a patient's insulin regimen, increase the frequency of blood glucose monitoring [see Warnings and Precautions (5.2)].
• Dosage adjustments may be needed with changes in physical activity, changes in meal patterns (e.g., 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), Use in Specific Populations (8.6, 8.7)].
• Dosage adjustment may be needed when changing from another insulin to HUMULIN R [see Warnings and Precautions (5.2)].

The primary activity of insulin, including HUMULIN R, is the regulation of glucose metabolism. Insulin lowers blood glucose by stimulating peripheral glucose uptake, especially by skeletal muscle and fat, and by inhibiting hepatic glucose production. Insulin inhibits lipolysis and proteolysis, and enhances protein synthesis.

• Never share needles or syringes with another person. (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. Increase frequency of blood glucose monitoring with changes to: insulin dosage, co-administered glucose lowering medications, meal pattern, physical activity; in patients with renal or hepatic impairment or with hypoglycemia unawareness. (5.3)
• Hypoglycemia Due to Medication Errors: Accidental mix-ups between insulin products can occur. Instruct patients to check insulin labels before injection. (5.4)
• Hypersensitivity Reactions: Severe, life-threatening, generalized allergy, including anaphylaxis, can occur. Discontinue HUMULIN R, monitor, and treat if indicated. (5.5)
• Hypokalemia: May be life-threatening. Monitor potassium levels in patients at risk for 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)

• See Full Prescribing Information for important administration instructions. (2.1)
• Subcutaneous injection: inject subcutaneously 30 minutes before a meal into the thigh, upper arm, abdomen, or buttocks. Rotate injection sites to reduce risk of lipodystrophy and localized cutaneous amyloidosis. (2.2)
• Intravenous infusion: administer intravenously ONLY under medical supervision at concentrations from 0.1 unit/mL to 1 unit/mL in infusion systems containing 0.9% Sodium Chloride Injection. (2.2)
• Individualize dose based on route of administration, metabolic needs, blood glucose monitoring results and glycemic control goal. (2.3)
• HUMULIN R given by subcutaneous injection should generally be used in regimens with an intermediate- or long-acting insulin. (2.3)
• Do not mix with insulin preparations other than HUMULIN^® N. (2.5)

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

• 10 mL multiple-dose vial
• 3 mL multiple-dose vial

Severe, life-threatening, generalized allergy, including anaphylaxis, can occur with HUMULIN R [see Adverse Reactions (6)]. If hypersensitivity reactions occur, discontinue HUMULIN R; treat per standard of care and monitor until symptoms and signs resolve. HUMULIN R is contraindicated in patients who have had a hypersensitivity reaction to HUMULIN R or its excipients.

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

Product: 50090-0353

NDC: 50090-0353-0 10 mL in a VIAL / 1 in a CARTON

• Always check the insulin label before administration to confirm the correct insulin product is being used [see Warnings and Precautions (5.4)].
• Inspect HUMULIN R visually before use. It should appear clear and colorless. Do not use HUMULIN R if particulate matter or coloration is seen.

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

Instructions for Use

Humulin ^® (HU-mu-lin) R

(insulin human)

injection, for subcutaneous or intravenous use

3 mL or 10 mL multiple-dose vial (100 units/mL)

Read the Instructions for Use before you start taking HUMULIN R 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 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 3 mL or 10 mL multiple-dose HUMULIN^® R vial
• a U-100 insulin syringe and needle
• 2 alcohol swabs
• 1 sharps container for throwing away used needles and syringes. See “Disposing of used needles and syringes” at the end of these instructions.

Preparing the Dose

• Wash your hands with soap and water.
• Check the HUMULIN R 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.
• Do not use HUMULIN R past the expiration date printed on the label or 31 days after you first use it.
• Always use a new syringe or needle for each injection to help make sure the syringe needle is sterile and to prevent 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 HUMULIN R with HUMULIN N:

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

Giving your Injection

• Inject your insulin exactly 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.

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 HUMULIN R?

All unopened vials:

• Store all unopened vials in the refrigerator at 36° to 46°F (2° to 8°C).
• Do not freeze. Do not use if it 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 31 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 31 days.
• Keep away from heat and out of direct light.
• Throw away all opened vials after 31 days, even if there is still insulin left in the vial.

General information about the safe and effective use

• Keep HUMULIN R vials, syringes, needles, and all medicines out of the reach of children.
• Always use a new syringe or needle for each injection.
• 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 have any questions or problems with your HUMULIN, contact Lilly at 1-800-Lilly-Rx (1-800-545-5979) or call your healthcare provider for help. For more information on HUMULIN and insulin, go to www.humulin.com.

Scan this code to launch the humulin.com website

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

Humulin^® is a trademark of Eli Lilly and Company.

Instructions for Use revised: June 2022

Manufactured by:

Eli Lilly and Company, Indianapolis, IN 46285, USA

US License Number 1891

Copyright © 1997, 2022, Eli Lilly and Company. All rights reserved.

LINR100VL-0004-IFU-20220627

LINR100-0004-PPI-20220627

• Dosage adjustment may be needed when HUMULIN R is co-administered with certain drugs [see Drug Interactions (7)].

Patients using HUMULIN R vials must never share needles or syringes with another person. Sharing poses a risk for transmission of blood-borne pathogens.

Carcinogenicity and fertility studies were not performed in animals.

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, adjustments in concomitant anti-diabetic medications may be needed.

• Do not mix HUMULIN R with insulin preparations other than HUMULIN N.
• To mix HUMULIN R and HUMULIN N, draw HUMULIN R into the syringe first. Inject immediately after mixing.

Thiazolidinediones (TZDs), which are peroxisome proliferator-activated receptor (PPAR)-gamma agonists, can cause dose-related fluid retention, when used in combination with insulin. Fluid retention may lead to or exacerbate heart failure. Patients treated with insulin, including HUMULIN R, 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.

Subcutaneous Injection

• Inject HUMULIN R subcutaneously approximately 30 minutes before meals into the thigh, upper arm, abdomen, or buttocks.
• Rotate injection sites within the same region from one injection to the next 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)].
• HUMULIN R may be diluted with Sterile Diluent for HUMULIN R for subcutaneous injection ONLY under medical supervision.
  • Dilute one part HUMULIN R to nine parts diluent to yield a concentration one-tenth that of HUMULIN R (equivalent to U-10).
  • Dilute one part HUMULIN R to one part diluent to yield a concentration one-half that of HUMULIN R (equivalent to U-50).
  • Diluted HUMULIN R may be used for 28 days when stored at 41°F (5°C) or for 14 days when stored at 86°F (30°C).

Not in-use (unopened): Humulin R U-100 vials not in-use should be stored in a refrigerator (2° to 8°C [36° to 46°F]), but not in the freezer. In-use (opened): The Humulin R U-100 vial currently in-use can be kept unrefrigerated as long as it is kept as cool as possible [below 30°C (86°F)] away from heat and light. In-use vials must be used within 31 days or be discarded, even if they still contain Humulin R U-100. Admixture: Infusion bags prepared with Humulin R U-100 as indicated under DOSAGE AND ADMINISTRATION are stable when stored in a refrigerator (2° to 8°C [36° to 46°F]) for 48 hours and then may be used at room temperature for up to an additional 48 hours. Do not use Humulin R U-100 after the expiration date stamped on the label or if it has been frozen.

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 intravenous glucose. Sustained carbohydrate intake and observation may be necessary because hypoglycemia may recur after apparent clinical recovery. Hypokalemia must be corrected appropriately [see Warnings and Precautions (5.3, 5.6)].

Insulin human is produced by recombinant DNA technology utilizing a non-pathogenic laboratory strain of Escherichia coli and has the empirical formula C₂₅₇H₃₈₃N₆₅O₇₇S₆ with a molecular weight of 5.808 kDa.

HUMULIN R (insulin human) injection is a short-acting human insulin for subcutaneous or intravenous use.

HUMULIN R is a sterile, aqueous, clear, and colorless solution. HUMULIN R contains 100 units of insulin human in each milliliter. Each milliliter of HUMULIN R also contains glycerin (16 mg), metacresol (2.5 mg), endogenous zinc (approximately 0.015 mg/100 units,) and Water for Injection. Sodium hydroxide and hydrochloric acid may be added during manufacture to adjust the pH. The pH is 7.0 to 7.8.

All insulins, including HUMULIN R, 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 of all insulins, including HUMULIN R. Severe hypoglycemia can cause seizures, may lead to unconsciousness, may be life threatening or cause death. Hypoglycemia can impair concentration ability and reaction time; this may place the patient 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 patient and change over time in the same patient. Symptomatic awareness of hypoglycemia may be less pronounced in patients with longstanding diabetes, in patients with diabetic neuropathy, 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.

HUMULIN R is indicated to improve glycemic control in pediatric patients with diabetes mellitus.

The dosage of HUMULIN R must be individualized in pediatric patients based on metabolic needs and frequent monitoring of blood glucose to reduce the risk of hypoglycemia [see Dosage and Administration (2.3), Warnings and Precautions (5.3)].

The effect of age on the pharmacokinetics and pharmacodynamics of HUMULIN R has not been studied. Elderly patients using HUMULIN R may be at increased risk of hypoglycemia due to co-morbid disease [see Warnings and Precautions (5.3)].

HUMULIN R is contraindicated:

• during episodes of hypoglycemia [see Warnings and Precautions (5.3)]
• in patients with hypersensitivity to HUMULIN R or any of its excipients [see Warnings and Precautions (5.5)]

The following adverse reactions are also discussed elsewhere in the labeling:

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

The effect of renal impairment on the pharmacokinetics and pharmacodynamics of HUMULIN R has not been studied. Patients with renal impairment are at increased risk of hypoglycemia and may require more frequent HUMULIN R dose adjustment and more frequent blood glucose monitoring [see Warnings and Precautions (5.3)].

The time course of insulin action (i.e., glucose lowering) may vary considerably in different individuals or within the same individual. With subcutaneous use, the pharmacologic effect of HUMULIN R begins approximately 30 minutes (range: 10 to 75 minutes) after administration of doses in the 0.05 to 0.4 units/kg range (Figure 1). The effect is maximal at approximately 3 hours (range: 20 minutes to 7 hours) and terminates after approximately 8 hours (range: 3 to 14 hours). In a study that administered 50 and 100 units doses subcutaneously to obese subjects, mean time of termination of effect was prolonged to approximately 18 hours (range approximately 12-24 hours).

With intravenous use, the pharmacologic effect of HUMULIN R begins at approximately 10 to 15 minutes and terminates at a median time of approximately 4 hours (range: 2 to 6 hours) after administration of doses in the range of 0.1 to 0.2 units/kg.

The intravenous administration of HUMULIN R was tested in 21 people with type 1 diabetes. During the 6-hour assessment phase patients received intravenous HUMULIN R at an initial dose of 0.5 units/hour, adjusted to maintain blood glucose concentrations near normoglycemia (100 to 160 mg/dL).

The mean blood glucose levels during the assessment phase for patients on HUMULIN R therapy are summarized below in Table 2. All patients achieved near normoglycemia during the 6-hour assessment phase. The average time (± SE) required to attain near normoglycemia was 161 ± 14 minutes for HUMULIN R.

The effect of hepatic impairment on the pharmacokinetics and pharmacodynamics of HUMULIN R has not been studied. Patients with hepatic impairment are at increased risk of hypoglycemia and may require more frequent HUMULIN R dose adjustment and more frequent blood glucose monitoring [see Warnings and Precautions (5.3)].

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

• Individualize and adjust the dosage of HUMULIN R based on the route of administration, the patient's metabolic needs, blood glucose monitoring results, and glycemic control goal.
• HUMULIN R given by subcutaneous injection should generally be used in regimens with an intermediate- or long-acting insulin.
• During changes to a patient's insulin regimen, increase the frequency of blood glucose monitoring [see Warnings and Precautions (5.2)].
• Dosage adjustments may be needed with changes in physical activity, changes in meal patterns (e.g., 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), Use in Specific Populations (8.6, 8.7)].
• Dosage adjustment may be needed when changing from another insulin to HUMULIN R [see Warnings and Precautions (5.2)].

The primary activity of insulin, including HUMULIN R, is the regulation of glucose metabolism. Insulin lowers blood glucose by stimulating peripheral glucose uptake, especially by skeletal muscle and fat, and by inhibiting hepatic glucose production. Insulin inhibits lipolysis and proteolysis, and enhances protein synthesis.

• Never share needles or syringes with another person. (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. Increase frequency of blood glucose monitoring with changes to: insulin dosage, co-administered glucose lowering medications, meal pattern, physical activity; in patients with renal or hepatic impairment or with hypoglycemia unawareness. (5.3)
• Hypoglycemia Due to Medication Errors: Accidental mix-ups between insulin products can occur. Instruct patients to check insulin labels before injection. (5.4)
• Hypersensitivity Reactions: Severe, life-threatening, generalized allergy, including anaphylaxis, can occur. Discontinue HUMULIN R, monitor, and treat if indicated. (5.5)
• Hypokalemia: May be life-threatening. Monitor potassium levels in patients at risk for 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)

• See Full Prescribing Information for important administration instructions. (2.1)
• Subcutaneous injection: inject subcutaneously 30 minutes before a meal into the thigh, upper arm, abdomen, or buttocks. Rotate injection sites to reduce risk of lipodystrophy and localized cutaneous amyloidosis. (2.2)
• Intravenous infusion: administer intravenously ONLY under medical supervision at concentrations from 0.1 unit/mL to 1 unit/mL in infusion systems containing 0.9% Sodium Chloride Injection. (2.2)
• Individualize dose based on route of administration, metabolic needs, blood glucose monitoring results and glycemic control goal. (2.3)
• HUMULIN R given by subcutaneous injection should generally be used in regimens with an intermediate- or long-acting insulin. (2.3)
• Do not mix with insulin preparations other than HUMULIN^® N. (2.5)

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

• 10 mL multiple-dose vial
• 3 mL multiple-dose vial

Severe, life-threatening, generalized allergy, including anaphylaxis, can occur with HUMULIN R [see Adverse Reactions (6)]. If hypersensitivity reactions occur, discontinue HUMULIN R; treat per standard of care and monitor until symptoms and signs resolve. HUMULIN R is contraindicated in patients who have had a hypersensitivity reaction to HUMULIN R or its excipients.

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

Product: 50090-0353

NDC: 50090-0353-0 10 mL in a VIAL / 1 in a CARTON

• Always check the insulin label before administration to confirm the correct insulin product is being used [see Warnings and Precautions (5.4)].
• Inspect HUMULIN R visually before use. It should appear clear and colorless. Do not use HUMULIN R if particulate matter or coloration is seen.

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

Instructions for Use

Humulin ^® (HU-mu-lin) R

(insulin human)

injection, for subcutaneous or intravenous use

3 mL or 10 mL multiple-dose vial (100 units/mL)

Read the Instructions for Use before you start taking HUMULIN R 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 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 3 mL or 10 mL multiple-dose HUMULIN^® R vial
• a U-100 insulin syringe and needle
• 2 alcohol swabs
• 1 sharps container for throwing away used needles and syringes. See “Disposing of used needles and syringes” at the end of these instructions.

Preparing the Dose

• Wash your hands with soap and water.
• Check the HUMULIN R 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.
• Do not use HUMULIN R past the expiration date printed on the label or 31 days after you first use it.
• Always use a new syringe or needle for each injection to help make sure the syringe needle is sterile and to prevent 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 HUMULIN R with HUMULIN N:

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

Giving your Injection

• Inject your insulin exactly 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.

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 HUMULIN R?

All unopened vials:

• Store all unopened vials in the refrigerator at 36° to 46°F (2° to 8°C).
• Do not freeze. Do not use if it 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 31 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 31 days.
• Keep away from heat and out of direct light.
• Throw away all opened vials after 31 days, even if there is still insulin left in the vial.

General information about the safe and effective use

• Keep HUMULIN R vials, syringes, needles, and all medicines out of the reach of children.
• Always use a new syringe or needle for each injection.
• 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 have any questions or problems with your HUMULIN, contact Lilly at 1-800-Lilly-Rx (1-800-545-5979) or call your healthcare provider for help. For more information on HUMULIN and insulin, go to www.humulin.com.

Scan this code to launch the humulin.com website

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

Humulin^® is a trademark of Eli Lilly and Company.

Instructions for Use revised: June 2022

Manufactured by:

Eli Lilly and Company, Indianapolis, IN 46285, USA

US License Number 1891

Copyright © 1997, 2022, Eli Lilly and Company. All rights reserved.

LINR100VL-0004-IFU-20220627

LINR100-0004-PPI-20220627

• Dosage adjustment may be needed when HUMULIN R is co-administered with certain drugs [see Drug Interactions (7)].

Patients using HUMULIN R vials must never share needles or syringes with another person. Sharing poses a risk for transmission of blood-borne pathogens.

Carcinogenicity and fertility studies were not performed in animals.

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, adjustments in concomitant anti-diabetic medications may be needed.

• Do not mix HUMULIN R with insulin preparations other than HUMULIN N.
• To mix HUMULIN R and HUMULIN N, draw HUMULIN R into the syringe first. Inject immediately after mixing.

Thiazolidinediones (TZDs), which are peroxisome proliferator-activated receptor (PPAR)-gamma agonists, can cause dose-related fluid retention, when used in combination with insulin. Fluid retention may lead to or exacerbate heart failure. Patients treated with insulin, including HUMULIN R, 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.