- Data on file, Lilly USA, LLC. HM20151210a.
- Hood RC, Arakaki RF, Wysham C, et al. Two treatment approaches for human regular U-500 insulin in patients with type 2 diabetes not achieving adequate glycemic control on high-dose U-100 insulin therapy with or without oral agents: a randomized, titration-to-target clinical trial. Endocr Pract. 2015;21(7):782-793. Erratum, 2016;22(7):905.
Indication for Humulin R U-500
- Humulin R U‑500 is an insulin that is used to control high blood sugar in adults and children with diabetes mellitus who need more than 200 units of insulin in a day.
- Humulin R U‑500 contains 5 times as much insulin in the same volume (500 units/mL) as standard insulin (100 units/mL).
- It is not known if Humulin R U-500 is safe and effective when used in combination with other insulins, when used in an insulin pump, or in children.
Indication for Humulin® R U-500
- Humulin R U-500 is a concentrated human insulin indicated to improve glycemic control in adults and children with diabetes mellitus requiring more than 200 units of insulin per day.
- Limitation of Use: The safety and efficacy of Humulin R U-500 used in combination with other insulins has not been determined. The safety and efficacy of Humulin R U-500 delivered by continuous subcutaneous infusion has not been determined.
Important Safety Information for Humulin R U-500
What is the most important information I should know about Humulin R U-500?
- Humulin R U-500 is highly concentrated and contains 5 times as much insulin in 1 mL as standard U-100 (100 units/mL) insulin.
- Do not share your Humulin R U-500 KwikPen or U-500 insulin 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.
Who should not take Humulin R U-500?
- Do not take Humulin R U-500 if your blood sugar is too low (hypoglycemia) or you are allergic to any of the ingredients in Humulin R U-500.
What should I tell my healthcare provider before taking Humulin R U-500?
- Tell your healthcare provider:
- If you have liver, kidney, or heart problems or any other medical conditions.
- If you are pregnant, plan to become pregnant, or are breast-feeding.
- About all the medicines you take, including prescription (especially ones commonly called TZDs [thiazolidinediones]) and over the counter medicines, vitamins, and herbal supplements.
- Before you start using Humulin R U-500, talk to your healthcare provider about low blood sugar and how to manage it.
How should I use Humulin R U-500?
- Read the detailed Instructions for Use that come with your Humulin R U-500.
- Take Humulin R U-500 exactly as your healthcare provider tells you to. Your healthcare provider should show you how much Humulin R U-500 to use and when to use it.
- Know the dose of Humulin R U-500 you use. Do not change your dose unless your healthcare provider tells you to.
- Check your insulin label each time you give your injection to make sure you are using the correct insulin.
- Humulin R U-500 KwikPen: The U-500 KwikPen is specially made to dial and deliver doses of Humulin R U-500 insulin. Do not use any syringe to remove Humulin R U-500 insulin from your U-500 KwikPen. The markings on certain syringes will not measure your dose correctly. A severe overdose can happen, causing low blood sugar, which may put your life in danger.
- Humulin R U-500 vial: There is a special U-500 insulin syringe to measure Humulin R U-500. Use only a U-500 insulin syringe to draw up and inject your Humulin R U-500. If you do not use the right syringe type, you may take the wrong dose of Humulin R U-500. This can cause you to have too low blood sugar (hypoglycemia) or too high blood sugar (hyperglycemia). Your healthcare provider should show you how to draw up Humulin R U-500.
- Use Humulin R U-500 30 minutes before eating a meal.
- Inject Humulin R U-500 under your skin (subcutaneously). Do not use Humulin R U-500 in an insulin pump or inject Humulin R U-500 into your vein (intravenously) or your muscle (intramuscularly).
- Do not mix Humulin R U-500 with any other type of insulin or liquid medicine.
- Change your injection site with each dose.
- Check your blood sugar levels. Ask your healthcare provider what your blood sugar level should be and when you should check your blood sugar.
- Your dose of Humulin R U-500 may need to change because of changes in your level of exercise, weight, or diet, or because of increased stress, illness, or other medicines you take.
- Keep Humulin R U-500 and all medicines out of the reach of children.
What should I avoid while taking Humulin R U-500?
- Do not drive or operate heavy machinery until you know how Humulin R U-500 affects you. Do not drink alcohol or use over-the-counter medicines that contain alcohol.
What are the possible side effects of Humulin R U-500?
- Humulin R U-500 can cause serious side effects that can lead to death, including:
- Low blood sugar. Signs of low blood sugar may include dizziness or lightheadedness, sweating, confusion, headache, blurred vision, slurred speech, shakiness, fast heartbeat, anxiety, irritability or mood changes, or hunger. Your healthcare provider may prescribe a glucagon emergency kit so that others can give you an injection if your blood sugar becomes too low (hypoglycemic) and you are unable to take sugar by mouth.
- Severe allergic reaction. Get medical help right away if you have a rash over your whole body, have trouble breathing, a fast heartbeat, or sweating. These are signs of a severe allergic reaction.
- Low potassium in your blood.
- Heart failure. Taking certain diabetes pills called thiazolidinediones or “TZDs” with Humulin R U-500 may cause heart failure in some people. This can happen even if you have never had heart failure or heart problems before. If you already have heart failure, it may get worse while you take TZDs with Humulin R U-500. Your healthcare provider should monitor you closely while you are taking TZDs with Humulin R U-500. Tell your healthcare provider if you have any new or worse symptoms of heart failure, including shortness of breath, swelling of your ankles or feet, or sudden weight gain.
Treatment with TZDs and Humulin R U-500 may need to be adjusted or stopped by your healthcare provider if you have new or worse heart failure.
- Get emergency medical help if you have:
- severe low blood sugar needing hospitalization or emergency room care. Be sure to tell the hospital staff the units of Humulin R U-500 that your healthcare provider has prescribed for you.
- trouble breathing, shortness of breath, fast heartbeat, swelling of your face, tongue, or throat, sweating, extreme drowsiness, dizziness, confusion.
- The most common side effects of Humulin R U-500 include low blood sugar, allergic reactions including reactions at your injection site, skin thickening or pits at the injection site, itching, and rash.
- These are not all of the possible side effects of Humulin R U-500. Call your doctor for medical advice about side effects. You may report side effects to the FDA at 1-800-FDA-1088.
How should I store Humulin R U-500?
- Keep away from heat and out of direct light. Do not freeze. Do not use Humulin R U-500 after the expiration date stamped on the label. Do not shake the vial.
- Humulin R U-500 Vials: Store unopened vials of Humulin R U-500 in a refrigerator. Store opened (in-use) vials of Humulin R U-500 in the refrigerator or at room temperature for up to 40 days. Throw away any opened vial after 40 days of use, even if there is insulin left in the vial.
- Humulin R U-500 KwikPen: Store unopened Humulin R U-500 KwikPens in a refrigerator. Store opened (in-use) Humulin R U-500 KwikPens at room temperature for up to 28 days. Do not refrigerate opened KwikPens. Throw away any opened KwikPen after 28 days of use, even if there is insulin left in the pen.
General Information about the safe and effective use of Humulin R U-500
- Medicines are sometimes prescribed for purposes other than those listed in a Patient Information leaflet. Do not use Humulin R U-500 for a condition for which it was not prescribed. Do not give Humulin R U-500 to other people, even if they have the same symptoms you have. It may harm them.
- The Patient Information leaflet summarizes the most important information about Humulin R U-500. If you would like more information, talk with your healthcare provider. You can ask your pharmacist or healthcare provider for information about Humulin R U-500 that is written for healthcare professionals. For more information go to www.humulin.com or call 1-800-545-5979.
Humulin R U-500 is available by prescription only.
HI U500 CON ISI 27SEP2016
Humulin® and KwikPen® are registered trademarks owned or licensed by Eli Lilly and Company, its subsidiaries, or affiliates.
BD™ is a trademark of Becton, Dickinson and Company.
Important Safety Information for Humulin R U-500
- Humulin R U-500 is contraindicated during episodes of hypoglycemia and in patients hypersensitive to Humulin R U-500 or any of its excipients.
Warnings and Precautions
- Dosing Errors: Extreme caution must be observed in measuring the dose of Humulin R U-500 because inadvertent overdose may result in serious adverse reaction or life-threatening hypoglycemia.
- Hyperglycemia, Hypoglycemia or Death Due to Dosing Errors in the Vial Presentation: Medication errors associated with the Humulin R U-500 vial resulting in patients experiencing hyperglycemia, hypoglycemia or death have been reported.
- Instruct patients to always inspect insulin vials to confirm that the correct insulin is dispensed including the correct brand and concentration.
- For the Humulin R U-500 vial, particular attention should be paid to the 20-mL vial size, prominent “U-500” and warning statements on the vial label, and distinctive coloring on the vial and carton.
- Dosing errors have occurred when Humulin R U-500 was administered with syringes other than a U-500 insulin syringe. Patients should be prescribed U-500 syringes for use with Humulin R U-500 vials. The dose of Humulin R U-500 should always be expressed in units of insulin.
- 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.
- Instruct the patient to inform hospital or emergency department staff of the dose of Humulin R U-500 prescribed.
- If using the Humulin R U-500 KwikPen, patients should be counseled to dial and dose the prescribed number of units of insulin (NO dose conversion is required).
- DO NOT transfer Humulin R U-500 from the Humulin R U-500 KwikPen into any syringe for administration. Overdose and severe hypoglycemia can occur.
- Never Share a KwikPen or U-500 Syringe Between Patients, even if the needle is changed. Sharing poses a risk for transmission of blood-borne pathogens.
- Hyperglycemia or Hypoglycemia with Changes in Insulin Regimen: Changes in insulin, manufacturer, type, or method of administration should be made cautiously and only under medical supervision and the frequency of blood glucose monitoring should be increased.
- Hypoglycemia: Hypoglycemia is the most common adverse reaction associated with insulin, 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 an individual and others at risk in situations where these abilities are important, such as driving or operating other machinery.
- Hypoglycemia can happen suddenly and symptoms may differ in each individual and change over time in the same individual.
- Early warning symptoms 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, or in patients who experience recurrent 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.
- 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.
- Hypersensitivity and Allergic Reactions: Severe, life-threatening, generalized allergy, including anaphylaxis, can occur with insulin products, 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.
- Hypokalemia: Insulin use can lead to hypokalemia that left untreated 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 PPAR-gamma Agonists: Thiazolidinediones (TZDs), which are 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. Observe patients 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.
- Adverse reactions include hypoglycemia, allergic reactions, lipodystrophy, injection site reactions, weight gain, peripheral edema, and immunogenicity.
- Some medications may alter glucose metabolism and may necessitate insulin dose adjustment. Signs of hypoglycemia may be reduced or absent in patients taking antiadrenergic drugs. Particularly close monitoring may be required.
Use in Specific Populations
- Pregnancy Category B: While there are no adequate and well-controlled studies in pregnant women, evidence from published literature suggests that good glycemic control in patients with diabetes during pregnancy provides significant maternal and fetal benefits.
- Pediatric Use: There are no well-controlled studies of use of Humulin R U-500 in children. Standard precautions as applied to use of Humulin R U-500 in adults are appropriate for use in children.
- Geriatric Use: There are no well-controlled studies of use of Humulin R U-500 in geriatric patients. In elderly patients with diabetes, the initial dosing, dose increments, and maintenance dosage should be conservative to avoid hypoglycemia.
- Renal or Hepatic Impairment: Frequent glucose monitoring and insulin dose reduction may be required in patients with renal or hepatic impairment.
Dosage and Administration
- 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 KwikPen or a multiple dose vial. Patients using the vial must be prescribed the U-500 insulin syringe to avoid medication errors.
- DO NOT perform dose conversion when using the Humulin R U-500 KwikPen. The dose window of the KwikPen shows the number of units of Humulin R U-500 to be injected and NO dose conversion is required.
- DO NOT perform dose conversion when using a U-500 insulin syringe. The markings on the syringe show the number of units of Humulin R U-500 to be injected. Each marking represents 5 units of insulin.
- Instruct patients using the vial to use only a U-500 insulin syringe and on how to correctly draw the prescribed dose into the syringe. Confirm that the patient has understood these instructions and can correctly draw the prescribed dose with their syringe.
- Advise the patient to read the Patient Information and Instructions for Use.
- Instruct patients to always check the insulin label before administration to confirm the correct insulin product is being used.
- Inspect Humulin R U-500 visually and only use if the solution appears clear and colorless.
- Administer Humulin R U-500 subcutaneously two or three times daily approximately 30 minutes before a meal. Rotate injection sites to reduce the risk of lipodystrophy.
- Individualize the dose of Humulin R U-500 based on metabolic needs, blood glucose monitoring results, and glycemic control goal.
- Do NOT administer Humulin R U-500 intravenously or intramuscularly.
- Do NOT mix Humulin R U-500 with other insulins.
- Protect from heat and light. Do not freeze. Do not use Humulin R U-500 after the expiration date stamped on the label.
- Humulin R U-500 Vials: Unopened vials of Humulin R U-500 should be kept in a refrigerator. Opened (in-use) vials of Humulin R U-500 should be kept in the refrigerator or at room temperature and used within 40 days of opening. Throw away any opened vial after 40 days of use, even if there is insulin left in the vial.
- Humulin R U-500 KwikPen: Unopened Humulin R U-500 KwikPens should be kept in a refrigerator. Opened (in-use) Humulin R U-500 KwikPens should be kept at room temperature and used within 28 days of opening. Do not refrigerate opened KwikPens. Throw away any opened KwikPen after 28 days of use, even if there is insulin left in the pen.
HM U500 HCP ISI 27SEP2016
Humulin® and KwikPen® are registered trademarks owned or licensed by Eli Lilly and Company, its subsidiaries, or affiliates. Humulin® R U-500 is available by prescription only.
BD™ is a trademark of Becton, Dickinson and Company.