Humulin R U-500 (Insulin Human)

HUMULIN R U-500 is a concentrated human insulin indicated to improve glycemic control in adult and pediatric patients with diabetes mellitus requiring more than 200 units of insulin per day.

• Adhere to administration instructions to reduce the risk of dosing errors. (
  2.1 Important Administration Instructions

  • Prescribe HUMULIN R U-500 ONLY to patients who require more than 200 units of insulin per day.
  • HUMULIN R U-500 is available as a single-patient-use KwikPen or multiple-dose vial.
    Patients using the vial must be prescribed the U-500 insulin syringe to avoid medication errors.
  • Instruct patients using the vial presentation to use only a U-500 insulin syringe and on how to correctly draw the prescribed dose of HUMULIN R U-500 into the U-500 insulin syringe. Confirm that the patient has understood these instructions and can correctly draw the prescribed dose of HUMULIN R U-500 with their syringe
    [see Dosage and Administration and Warnings and Precautions ]
    .
  • Instruct patients to always check the insulin label before administration to confirm the correct insulin product is being used
    [see Warnings and Precautions ]
    .
  • Inspect HUMULIN R U-500 visually for particulate matter and discoloration. Only use HUMULIN R U-500 if the solution appears clear and colorless.
  • Instruct patients to inject HUMULIN R U-500 subcutaneously 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 and Adverse Reactions ]
    .
  • During changes to a patient's insulin regimen, increase the frequency of blood glucose monitoring
    [see Warnings and Precautions ]
    .
  • Use HUMULIN R U-500 KwikPen with caution in patients with visual impairment that may rely on audible clicks to dial their dose.
  • DO NOT administer HUMULIN R U-500 intravenously.
  • DO NOT dilute or mix HUMULIN R U-500 with any other insulin products or solutions.
  ,
  2.3 Delivery of HUMULIN R U-500 Using the HUMULIN R U-500 Disposable Prefilled KwikPen Device

  • The HUMULIN R U-500 KwikPen dials in 5 unit increments and delivers a maximum dose of 300 units per injection.
  • DO NOT perform dose conversion when using the HUMULIN R U-500 KwikPen.
    The dose window of the HUMULIN R U-500 KwikPen shows the number of units of HUMULIN R U-500 to be injected and NO dose conversion is required
    .
  • DO NOT transfer HUMULIN R U-500 from the HUMULIN R U-500 KwikPen into any syringe for administration as overdose and severe hypoglycemia can occur
    [see Warnings and Precautions ].
  ,
  2.4 Delivery of HUMULIN R U-500 Using the Vial Presentation and the U-500 Insulin Syringe

  • DO NOT perform dose conversion when using a U-500 insulin syringe.
    The markings on the U-500 insulin syringe show the number of units of HUMULIN R U-500 to be injected.
  • Each marking on the syringe represents 5 units of insulin.
  • Prescribe patients a U-500 insulin syringe to administer HUMULIN R U-500 from the vial to avoid administration errors.
    DO NOT use any other type of syringe
    [see Warnings and Precautions ]
    .
  ,
  5.1 Hyperglycemia, Hypoglycemia or Death Due to Dosing Errors with the Vial Presentation

  Medication errors associated with the HUMULIN R U-500 vial presentation resulting in patients experiencing hyperglycemia, hypoglycemia or death have been reported. The majority of errors occurred due to errors in dispensing, prescribing or administration. Attention to details at all levels may prevent these errors.

  Dispensing Errors

  Instruct patients to always inspect insulin vials to confirm that the correct insulin is dispensed including the correct insulin brand and concentration.

  The HUMULIN R U-500 vial, which contains 20 mL, has a band of aqua coloring, a 500 units/mL concentration statement consisting of white lettering on a green rectangular background, and a green “U-500” statement prominently displayed next to the trade name. Additionally, the vial has a green flip top and a red warning on the front panel describing the highly concentrated dose and a statement advising use with only U-500 insulin syringes.

  Prescribing Errors

  Dosing errors have occurred when the HUMULIN R U-500 dose was administered with syringes other than a U-500 insulin syringe. Patients should be prescribed U-500 syringes for use with the HUMULIN R U-500 vials. The prescribed dose of HUMULIN R U-500 should always be expressed in units of insulin

  [see Dosage and Administration ]

  .

  Administration Errors

  Instruct patients to always check the insulin label before each injection.

  Use only a U-500 insulin syringe with HUMULIN R U-500 to avoid administration errors. Do not use any other type of syringe to administer Humulin R U-500. Adhere to administration instructions

  [see Dosage and Administration ]

  .

  Instruct the patient to inform hospital or emergency department staff of the dose of HUMULIN R U-500 prescribed, in the event of a future hospitalization or visit to the emergency department.
  )
• HUMULIN R U-500 is available as a single-patient-use KwikPen or multiple-dose vial. Patients using the vial must be prescribed the U-500 insulin syringe to avoid medication errors. (
  2.1 Important Administration Instructions

  • Prescribe HUMULIN R U-500 ONLY to patients who require more than 200 units of insulin per day.
  • HUMULIN R U-500 is available as a single-patient-use KwikPen or multiple-dose vial.
    Patients using the vial must be prescribed the U-500 insulin syringe to avoid medication errors.
  • Instruct patients using the vial presentation to use only a U-500 insulin syringe and on how to correctly draw the prescribed dose of HUMULIN R U-500 into the U-500 insulin syringe. Confirm that the patient has understood these instructions and can correctly draw the prescribed dose of HUMULIN R U-500 with their syringe
    [see Dosage and Administration and Warnings and Precautions ]
    .
  • Instruct patients to always check the insulin label before administration to confirm the correct insulin product is being used
    [see Warnings and Precautions ]
    .
  • Inspect HUMULIN R U-500 visually for particulate matter and discoloration. Only use HUMULIN R U-500 if the solution appears clear and colorless.
  • Instruct patients to inject HUMULIN R U-500 subcutaneously 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 and Adverse Reactions ]
    .
  • During changes to a patient's insulin regimen, increase the frequency of blood glucose monitoring
    [see Warnings and Precautions ]
    .
  • Use HUMULIN R U-500 KwikPen with caution in patients with visual impairment that may rely on audible clicks to dial their dose.
  • DO NOT administer HUMULIN R U-500 intravenously.
  • DO NOT dilute or mix HUMULIN R U-500 with any other insulin products or solutions.
  )
• Individualize dose of HUMULIN R U-500 based on metabolic needs, blood glucose monitoring results and glycemic control goal. (
  2.2 Dosing Instructions

  • Instruct patients to inject HUMULIN R U-500 subcutaneously usually two or three times daily approximately 30 minutes before meals.
  • Individualize and titrate the dosage of HUMULIN R U-500 based on the patient's metabolic needs, blood glucose monitoring results, and glycemic control goal.
  • Dosage adjustments may be needed with changes in physical activity, changes in meal patterns (i.e., macronutrient content or timing of food intake), changes in renal or hepatic function, changes in medications or during acute illness to minimize the risk of hypoglycemia or hyperglycemia
    [see Warnings and Precautions ]
    .
  )
• Administer HUMULIN R U-500 subcutaneously two or three times daily 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. (
  2.1 Important Administration Instructions

  • Prescribe HUMULIN R U-500 ONLY to patients who require more than 200 units of insulin per day.
  • HUMULIN R U-500 is available as a single-patient-use KwikPen or multiple-dose vial.
    Patients using the vial must be prescribed the U-500 insulin syringe to avoid medication errors.
  • Instruct patients using the vial presentation to use only a U-500 insulin syringe and on how to correctly draw the prescribed dose of HUMULIN R U-500 into the U-500 insulin syringe. Confirm that the patient has understood these instructions and can correctly draw the prescribed dose of HUMULIN R U-500 with their syringe
    [see Dosage and Administration and Warnings and Precautions ]
    .
  • Instruct patients to always check the insulin label before administration to confirm the correct insulin product is being used
    [see Warnings and Precautions ]
    .
  • Inspect HUMULIN R U-500 visually for particulate matter and discoloration. Only use HUMULIN R U-500 if the solution appears clear and colorless.
  • Instruct patients to inject HUMULIN R U-500 subcutaneously 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 and Adverse Reactions ]
    .
  • During changes to a patient's insulin regimen, increase the frequency of blood glucose monitoring
    [see Warnings and Precautions ]
    .
  • Use HUMULIN R U-500 KwikPen with caution in patients with visual impairment that may rely on audible clicks to dial their dose.
  • DO NOT administer HUMULIN R U-500 intravenously.
  • DO NOT dilute or mix HUMULIN R U-500 with any other insulin products or solutions.
  ,
  2.2 Dosing Instructions

  • Instruct patients to inject HUMULIN R U-500 subcutaneously usually two or three times daily approximately 30 minutes before meals.
  • Individualize and titrate the dosage of HUMULIN R U-500 based on the patient's metabolic needs, blood glucose monitoring results, and glycemic control goal.
  • Dosage adjustments may be needed with changes in physical activity, changes in meal patterns (i.e., macronutrient content or timing of food intake), changes in renal or hepatic function, changes in medications or during acute illness to minimize the risk of hypoglycemia or hyperglycemia
    [see Warnings and Precautions ]
    .
  )
• Do NOT mix HUMULIN R U-500 with other insulins. (
  2.1 Important Administration Instructions

  • Prescribe HUMULIN R U-500 ONLY to patients who require more than 200 units of insulin per day.
  • HUMULIN R U-500 is available as a single-patient-use KwikPen or multiple-dose vial.
    Patients using the vial must be prescribed the U-500 insulin syringe to avoid medication errors.
  • Instruct patients using the vial presentation to use only a U-500 insulin syringe and on how to correctly draw the prescribed dose of HUMULIN R U-500 into the U-500 insulin syringe. Confirm that the patient has understood these instructions and can correctly draw the prescribed dose of HUMULIN R U-500 with their syringe
    [see Dosage and Administration and Warnings and Precautions ]
    .
  • Instruct patients to always check the insulin label before administration to confirm the correct insulin product is being used
    [see Warnings and Precautions ]
    .
  • Inspect HUMULIN R U-500 visually for particulate matter and discoloration. Only use HUMULIN R U-500 if the solution appears clear and colorless.
  • Instruct patients to inject HUMULIN R U-500 subcutaneously 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 and Adverse Reactions ]
    .
  • During changes to a patient's insulin regimen, increase the frequency of blood glucose monitoring
    [see Warnings and Precautions ]
    .
  • Use HUMULIN R U-500 KwikPen with caution in patients with visual impairment that may rely on audible clicks to dial their dose.
  • DO NOT administer HUMULIN R U-500 intravenously.
  • DO NOT dilute or mix HUMULIN R U-500 with any other insulin products or solutions.
  )
• Do NOT administer HUMULIN R U-500 intravenously (
  2.1 Important Administration Instructions

  • Prescribe HUMULIN R U-500 ONLY to patients who require more than 200 units of insulin per day.
  • HUMULIN R U-500 is available as a single-patient-use KwikPen or multiple-dose vial.
    Patients using the vial must be prescribed the U-500 insulin syringe to avoid medication errors.
  • Instruct patients using the vial presentation to use only a U-500 insulin syringe and on how to correctly draw the prescribed dose of HUMULIN R U-500 into the U-500 insulin syringe. Confirm that the patient has understood these instructions and can correctly draw the prescribed dose of HUMULIN R U-500 with their syringe
    [see Dosage and Administration and Warnings and Precautions ]
    .
  • Instruct patients to always check the insulin label before administration to confirm the correct insulin product is being used
    [see Warnings and Precautions ]
    .
  • Inspect HUMULIN R U-500 visually for particulate matter and discoloration. Only use HUMULIN R U-500 if the solution appears clear and colorless.
  • Instruct patients to inject HUMULIN R U-500 subcutaneously 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 and Adverse Reactions ]
    .
  • During changes to a patient's insulin regimen, increase the frequency of blood glucose monitoring
    [see Warnings and Precautions ]
    .
  • Use HUMULIN R U-500 KwikPen with caution in patients with visual impairment that may rely on audible clicks to dial their dose.
  • DO NOT administer HUMULIN R U-500 intravenously.
  • DO NOT dilute or mix HUMULIN R U-500 with any other insulin products or solutions.
  )
• Do NOT perform dose conversion when using the HUMULIN R U-500 KwikPen. The dose window of the HUMULIN R U-500 KwikPen shows the number of units of HUMULIN R U-500 to be injected. (
  2.3 Delivery of HUMULIN R U-500 Using the HUMULIN R U-500 Disposable Prefilled KwikPen Device

  • The HUMULIN R U-500 KwikPen dials in 5 unit increments and delivers a maximum dose of 300 units per injection.
  • DO NOT perform dose conversion when using the HUMULIN R U-500 KwikPen.
    The dose window of the HUMULIN R U-500 KwikPen shows the number of units of HUMULIN R U-500 to be injected and NO dose conversion is required
    .
  • DO NOT transfer HUMULIN R U-500 from the HUMULIN R U-500 KwikPen into any syringe for administration as overdose and severe hypoglycemia can occur
    [see Warnings and Precautions ].
  )
• Do NOT transfer HUMULIN R U-500 from the HUMULIN R U-500 KwikPen into any syringe. (
  2.3 Delivery of HUMULIN R U-500 Using the HUMULIN R U-500 Disposable Prefilled KwikPen Device

  • The HUMULIN R U-500 KwikPen dials in 5 unit increments and delivers a maximum dose of 300 units per injection.
  • DO NOT perform dose conversion when using the HUMULIN R U-500 KwikPen.
    The dose window of the HUMULIN R U-500 KwikPen shows the number of units of HUMULIN R U-500 to be injected and NO dose conversion is required
    .
  • DO NOT transfer HUMULIN R U-500 from the HUMULIN R U-500 KwikPen into any syringe for administration as overdose and severe hypoglycemia can occur
    [see Warnings and Precautions ].
  )
• Do NOT perform dose conversion when using a U-500 insulin syringe. Use only a U-500 insulin syringe with the HUMULIN R U-500 vial. (
  2.4 Delivery of HUMULIN R U-500 Using the Vial Presentation and the U-500 Insulin Syringe

  • DO NOT perform dose conversion when using a U-500 insulin syringe.
    The markings on the U-500 insulin syringe show the number of units of HUMULIN R U-500 to be injected.
  • Each marking on the syringe represents 5 units of insulin.
  • Prescribe patients a U-500 insulin syringe to administer HUMULIN R U-500 from the vial to avoid administration errors.
    DO NOT use any other type of syringe
    [see Warnings and Precautions ]
    .
  )

Injection: 500 units/mL (U-500) clear, colorless solution available as:

• 3 mL single-patient-use HUMULIN R U-500 KwikPen prefilled pen (containing 1,500 units of insulin)
• 20 mL multiple-dose vial (containing 10,000 units of insulin)

Available data from published studies over decades have not established an association with human insulin use during pregnancy and major birth defects, miscarriage, or adverse maternal or fetal outcomes (

The estimated background risk of major birth defects is 6-10% in women with pre-gestational diabetes with a HbA1c >7% and has been reported to be as high as 20-25% in women with a HbA1c >10%. The estimated background risk of miscarriage for the indicated population is unknown. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2-4% and 15-20%, respectively.

• Hyperglycemia, Hypoglycemia or Death due to Dosing Errors with Vial Presentation:
  Can be life-threatening. Overdose has occurred as a result of dispensing, prescribing or administration errors. Attention to details at all levels is required to prevent these errors. (
  2.1 Important Administration Instructions

  • Prescribe HUMULIN R U-500 ONLY to patients who require more than 200 units of insulin per day.
  • HUMULIN R U-500 is available as a single-patient-use KwikPen or multiple-dose vial.
    Patients using the vial must be prescribed the U-500 insulin syringe to avoid medication errors.
  • Instruct patients using the vial presentation to use only a U-500 insulin syringe and on how to correctly draw the prescribed dose of HUMULIN R U-500 into the U-500 insulin syringe. Confirm that the patient has understood these instructions and can correctly draw the prescribed dose of HUMULIN R U-500 with their syringe
    [see Dosage and Administration and Warnings and Precautions ]
    .
  • Instruct patients to always check the insulin label before administration to confirm the correct insulin product is being used
    [see Warnings and Precautions ]
    .
  • Inspect HUMULIN R U-500 visually for particulate matter and discoloration. Only use HUMULIN R U-500 if the solution appears clear and colorless.
  • Instruct patients to inject HUMULIN R U-500 subcutaneously 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 and Adverse Reactions ]
    .
  • During changes to a patient's insulin regimen, increase the frequency of blood glucose monitoring
    [see Warnings and Precautions ]
    .
  • Use HUMULIN R U-500 KwikPen with caution in patients with visual impairment that may rely on audible clicks to dial their dose.
  • DO NOT administer HUMULIN R U-500 intravenously.
  • DO NOT dilute or mix HUMULIN R U-500 with any other insulin products or solutions.
  ,
  2.3 Delivery of HUMULIN R U-500 Using the HUMULIN R U-500 Disposable Prefilled KwikPen Device

  • The HUMULIN R U-500 KwikPen dials in 5 unit increments and delivers a maximum dose of 300 units per injection.
  • DO NOT perform dose conversion when using the HUMULIN R U-500 KwikPen.
    The dose window of the HUMULIN R U-500 KwikPen shows the number of units of HUMULIN R U-500 to be injected and NO dose conversion is required
    .
  • DO NOT transfer HUMULIN R U-500 from the HUMULIN R U-500 KwikPen into any syringe for administration as overdose and severe hypoglycemia can occur
    [see Warnings and Precautions ].
  ,
  2.4 Delivery of HUMULIN R U-500 Using the Vial Presentation and the U-500 Insulin Syringe

  • DO NOT perform dose conversion when using a U-500 insulin syringe.
    The markings on the U-500 insulin syringe show the number of units of HUMULIN R U-500 to be injected.
  • Each marking on the syringe represents 5 units of insulin.
  • Prescribe patients a U-500 insulin syringe to administer HUMULIN R U-500 from the vial to avoid administration errors.
    DO NOT use any other type of syringe
    [see Warnings and Precautions ]
    .
  ,
  5.1 Hyperglycemia, Hypoglycemia or Death Due to Dosing Errors with the Vial Presentation

  Medication errors associated with the HUMULIN R U-500 vial presentation resulting in patients experiencing hyperglycemia, hypoglycemia or death have been reported. The majority of errors occurred due to errors in dispensing, prescribing or administration. Attention to details at all levels may prevent these errors.

  Dispensing Errors

  Instruct patients to always inspect insulin vials to confirm that the correct insulin is dispensed including the correct insulin brand and concentration.

  The HUMULIN R U-500 vial, which contains 20 mL, has a band of aqua coloring, a 500 units/mL concentration statement consisting of white lettering on a green rectangular background, and a green “U-500” statement prominently displayed next to the trade name. Additionally, the vial has a green flip top and a red warning on the front panel describing the highly concentrated dose and a statement advising use with only U-500 insulin syringes.

  Prescribing Errors

  Dosing errors have occurred when the HUMULIN R U-500 dose was administered with syringes other than a U-500 insulin syringe. Patients should be prescribed U-500 syringes for use with the HUMULIN R U-500 vials. The prescribed dose of HUMULIN R U-500 should always be expressed in units of insulin

  [see Dosage and Administration ]

  .

  Administration Errors

  Instruct patients to always check the insulin label before each injection.

  Use only a U-500 insulin syringe with HUMULIN R U-500 to avoid administration errors. Do not use any other type of syringe to administer Humulin R U-500. Adhere to administration instructions

  [see Dosage and Administration ]

  .

  Instruct the patient to inform hospital or emergency department staff of the dose of HUMULIN R U-500 prescribed, in the event of a future hospitalization or visit to the emergency department.
  )
• Never share a HUMULIN R U-500 KwikPen or U-500 insulin syringe between patients, even if the needle is changed. (
  5.2 Never Share a HUMULIN R U-500 KwikPen or U-500 Insulin Syringe Between Patients

  HUMULIN R U-500 KwikPens should never be shared between patients, even if the needle is changed. Patients using HUMULIN R U-500 vials should never share needles or U-500 insulin syringes with another person. Sharing poses a risk for transmission of blood-borne pathogens.
  )
• 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. (
  5.3 Hyperglycemia or Hypoglycemia with Changes in Insulin Regimen

  Changes in an insulin regimen (e.g., insulin strength, manufacturer, type, injection site or method of administration) may affect glycemic control and predispose to hypoglycemia

  [see Warnings and Precautions ]

  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 ]

  .

  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 oral anti-diabetic treatment may be needed.
  )
• Hypoglycemia:
  May be life-threatening. Increase monitoring with changes to: insulin dosage, co-administered glucose lowering medications, meal pattern, physical activity; and in patients with renal impairment or hepatic impairment or hypoglycemia unawareness. (
  5.4 Hypoglycemia

  Hypoglycemia is the most common adverse reaction associated with insulins, including HUMULIN R U-500. Severe hypoglycemia can cause seizures, may be life-threatening or cause death. Severe hypoglycemia may develop as long as 18 to 24 hours after an injection of HUMULIN R U-500. 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 ]

  , or in patients who experience recurrent hypoglycemia.

  Risk Factors for Hypoglycemia

  The timing of hypoglycemia usually reflects the time-action profile of the administered insulin formulation. As with all insulin preparations, the glucose lowering effect time course of HUMULIN R U-500 may vary in different individuals or at different times in the same individual and depends on many conditions, including the area of injection as well as the injection site blood supply and temperature.

  Other factors which may increase the risk of hypoglycemia include changes in meal pattern (e.g., macronutrient content or timing of meals), changes in level of physical activity, or changes to concomitant drugs

  [see Drug Interactions ]

  . Patients with renal or hepatic impairment may be at higher risk of hypoglycemia

  [see Use in Specific Populations ]

  .

  Risk Mitigation Strategies for Hypoglycemia

  Patients and caregivers must be educated to recognize and manage hypoglycemia. Self-monitoring of blood glucose plays an essential role in the prevention and management of hypoglycemia. In patients at higher risk for hypoglycemia and patients who have reduced symptomatic awareness of hypoglycemia, increased frequency of blood glucose monitoring is recommended. To minimize the risk of hypoglycemia do not administer HUMULIN R U-500 intravenously or in an insulin pump or dilute or mix HUMULIN R U-500 with any other insulin products or solutions

  [see Dosage and Administration ]

  .
  )
• Hypersensitivity Reactions:
  Severe, life-threatening, generalized allergy, including anaphylaxis, can occur. Discontinue HUMULIN R U-500, monitor, and treat if indicated. (
  5.5 Hypersensitivity Reactions

  Severe, life-threatening, generalized allergy, including anaphylaxis, can occur with insulins, including HUMULIN R U-500. If hypersensitivity reactions occur, discontinue HUMULIN R U-500; treat per standard of care and monitor until symptoms and signs resolve

  [see Adverse Reactions ]

  .
  )
• Hypokalemia:
  May be life-threatening. Monitor potassium levels in patients at risk for hypokalemia and treat if indicated. (
  5.6 Hypokalemia

  All insulins, including HUMULIN R U-500, 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. Use caution in patients who may be at risk for hypokalemia (e.g., patients using potassium-lowering medications, patients taking medications sensitive to serum potassium concentrations).
  )
• 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 Fluid Retention and Heart Failure with Concomitant Use of PPAR-gamma Agonists

  Thiazolidinediones (TZDs), which are peroxisome proliferator-activated receptor (PPAR)-gamma agonists, can cause dose-related fluid retention, when used in combination with insulin. Fluid retention may lead to or exacerbate heart failure. Patients treated with insulin, including HUMULIN R U-500, 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.
  )