A dedicated device for the unique dosing needs of high-dose patients^1,2

Humulin KwikPen — The Humulin R U-500 KwikPen is a dedicated device1 for the unique dosing needs of high-dose patients (greater than 200 units per day).

The Humulin R U-500 KwikPen dials and doses the insulin units prescribed. Similar to other insulin pens,² there is no dose conversion.

The Humulin R U-500 KwikPen is designed for high-dose insulin needs (greater than 200 units per day).¹ It can deliver 300 units per injection, and it holds 1500 units of insulin in every pen—the equivalent of five U-100 KwikPens.²

Although the Humulin R U-500 KwikPen holds more units of insulin, it is the same size as other KwikPens.^2,3

The Humulin R U-500 differs from other KwikPens in that it is the only pen that dials in 5-unit increments.^2,3

Data on file, Lilly USA, LLC. HM20151210d.
Data on file, Lilly USA, LLC. HM20151210a.
Data on file, Lilly USA, LLC. HM20151210e.

Select Safety Information for Humulin R U-500

DO NOT transfer Humulin R U-500 from the 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, to avoid risk of transmission of blood-borne pathogens.

When prescribing for your patients…

For a U-500 KwikPen prescription, be sure to:

Specify the full product name: Humulin R U-500 KwikPen
Indicate the administration schedule as TID dosing or BID dosing
Record the required number of units of U-500 insulin per dose and specify at which meals the doses are to be taken to ensure the appropriate supply is dispensed at the pharmacy.
Prescribe pen needles with the KwikPen. BD pen needles recommended.
Write “Do Not Substitute” on the prescription

For a U-500 syringe and vial prescriptions, be sure to:

Specify the full product name: Humulin R U-500 vial
Indicate the administration schedule as TID dosing or BID dosing
Record the required number of units of U-500 insulin per dose and specify at which meals the doses are to be taken to ensure the appropriate supply is dispensed at the pharmacy.
Prescribe BD U-500 syringes with the vial.
Write or specify “Do Not Substitute” on the prescription

Provide this important information to your patients:

Explain how many times a day the patient should inject and the dose at each injection
Advise patients to inject U-500 approximately 30 minutes before eating a meal to reduce the risk of hypoglycemia
Demonstrate how to dial the U-500 KwikPen or draw up the prescribed dose with the U-500 syringe to deliver the insulin dose
For patients using the U-500 KwikPen, instruct patients not to withdraw insulin from the U-500 KwikPen using any syringe because overdose and severe hypoglycemia may occur
Patients should call their pharmacy to check availability. Some pharmacies may not stock U-500 insulin or U-500 syringes, but it should be available within 24 to 48 hours
Tell your eligible patients about the U-500 Savings Card to help with the cost of their prescription

Here's how to help anyone who brings a U-500 prescription to your pharmacy

Humulin R U-500 prescription pad with injection pen — This is a prescription for the Humulin R U-500 KwikPen (500 units/mL). The prescription allows for 2 refills. The SIG (instructions that go on the prescription label) states: Administer 125 units subcutaneously 30 minutes ac (before meal)—breakfast—and 80 units subcutaneously 30 minutes ac—evening meal—using U-500 KwikPen. Patient instructions are as follows: On the U-500 KwikPen, dial to 125 units before breakfast and 80 units before evening meal. Inject 30 minutes before meals.

The bottom of the prescription states: Do not substitute.

Note that this is an example prescription. The prescription details should be individualized and determined, by the prescriber, in accordance with the needs of the patient.

NDC 0002-8824-27

Humulin R U-500 prescription pad with vial and syringe — Presented are prescriptions for the BD™ U-500 Insulin Syringe and the Humulin R U-500 Vial (500 units/mL).

The prescription for the syringe shows that a quantity of 90 syringes should be dispensed. The prescription allows for 2 refills. The SIG (instructions that go on the prescription label) states: Use with Humulin R U-500 insulin vial only. Patient instructions are as follows: Refer to dosing instructions supplied with your Humulin R U-500 prescription.

The bottom of the prescription states: Do not substitute.

The prescription for the Humulin R U-500 Vial shows that one 20 mL vial should be dispensed. The prescription allows for 2 refills. The SIG states: Administer 115 units subcutaneously 30 minutes ac (before meal)—breakfast—and 85 units subcutaneously 30 minutes ac—lunch and evening meal. Patient instructions are as follows: Draw to 115 unit markings before breakfast and 85 unit markings before lunch and evening meal on a U-500 insulin syringe. Inject 30 minutes before meals.

The bottom of the prescription states: Do not substitute.

Note that these are example prescriptions. The prescription details should be individualized and determined, by the prescriber, in accordance with the needs of the patient.

NDC 0002-8501-01

^*Example prescription. The prescription details should be individualized and determined, by the prescriber, in accordance with the needs of the patient.

For patients new to Humulin R U-500:

New dosing regimen: High dose^* insulin patients may welcome a regimen of 2 or 3 injections a day^† with the U-500 KwikPen.
Patient education: The patient needs to understand how this insulin is similar or different compared to insulins they used in the past

The makers of U-500 want you to be ready to counsel these patients, tell them what they need to know, and still have time to help all the other people you see each day. We hope the enclosed tools can make it a little easier for you to inform, educate, and support these high-dose insulin patients.

If you have any questions, please don’t hesitate to call The Lilly Answers Center at 1-800-LillyRx (1-800-545-5979).

^*>200 units of insulin per day

^†Compared to U-100 insulin therapy. Most patients will require 2 or 3 daily injections of U-500.

Select Important Safety Information

Hyperglycemia or Hypoglycemia With Changes in Insulin Regimen

Changes in insulin strength, manufacturer, type, injection site, or method of administration may affect glycemic control and predispose to hypoglycemia or hyperglycemia. Any changes in insulin regimen should be made cautiously and only under close medical supervision, and the frequency of blood glucose monitoring should be increased. Due to reports of hypoglycemia and hyperglycemia, advise patients who have repeatedly injected into areas of lipodystrophy or localized cutaneous amyloidosis to change the injection site to the unaffected areas and to closely monitor blood glucose. For patients with type 2 diabetes, dosage adjustments of concomitant anti-diabetic products may be needed.

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.
Increase monitoring with changes to insulin dosage, co-administered glucose-lowering medications, meal patterns, physical activity, and in patients with renal or hepatic impairment or hypoglycemia unawareness. To minimize risk of hypoglycemia, do not administer Humulin R U-500 intravenously, intramuscularly, or in an insulin pump or dilute or mix with other products, including other insulins.
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.

Please click to access Important Safety Information and Full Prescribing Information for Humulin R U-500.

Help patients get started with U-500

Although each patient who is prescribed U-500 has injected insulin previously, you still play an important role in helping them to understand their medication and to get off to a good start.

Here is a checklist for how you can help:

Double-check their daily insulin regimen

☐ Confirm whether U-500 is replacing other insulins. If it’s not clear from the prescription, check with the doctor’s office

☐ Confirm dose in units with patient

☐ Confirm timing of dose with patient. U-500 is taken approximately 30 minutes before a meal. You may need to confirm dosing and how many times a day the patient is expected to inject

Demonstrate the device

☐ Confirm the patient knows how to measure the dose prescribed, either by dialing the KwikPen or by drawing insulin from the vial. For example, if you prescribe 100 units of U-500 using the BD U-500 syringe, a patient will draw the syringe to 100 units to measure the dose prescribed

☐ Ensure the patient has a prescription for pen needles or a BD^™ U-500 Insulin Syringe. The U-500 KwikPen is designed to be used with all versions of BD pen needles. The U-500 vial should be used only with the U-500 insulin syringe

☐ Remind patients not to withdraw insulin from the U-500 KwikPen using a syringe because overdose and severe hypoglycemia may occur

Please click to access Important Safety Information and Full Prescribing Information for Humulin R U-500.

Three ways for your patients to save on high-dose^** insulin

^**>200 units of insulin per day

1. Lowest branded co-pay for most patients

88%^* of commercially insured patients have unrestricted access^† to Humulin R U-500 at the lowest branded co-pay.

^* Represents Commercial formulary data. Access was 84% for the Humulin R U-500 vial and 80% for the Humulin R U-500 KwikPen. Calculation determined through total commercial lives in the USA as of July 2018. Plan types: Employer, HMO, Medical Group, Other Insurers, PBM Offering, POS, PPO. Includes plans/patients with appropriate restrictions. Calculation does not include uninsured lives.

^†Without prior authorization.

Source: Managed Markets Insight & Technology (MMIT), LLC as of 07/2018, and is subject to change without notice by a health plan or state. Please contact the plan or state for the most current information.

2. With the U-500 Savings Card, eligible patients with commercial insurance can pay as little as $25 per prescription^‡

^‡Eligible commercially insured patients. For full terms and conditions please click here .

3. One co-pay^§ for insulin monotherapy

U-500 can be administered as insulin monotherapy, so transitioning from an analog basal/bolus regimen will lower the number of prescription co-pays each month.

^§ As compared with basal-bolus therapy. Assumes Humulin R U-500 KwikPen insulin monotherapy

Underlying enrollment values developed by Managed Markets Insight & Technology (MMIT), LLC using a combination of third party and public sources as well as a proprietary allocation methodology. The values may not be representative of an individual physician’s patient population.
This information is not a guarantee of coverage or payment (partial or full). Actual benefits are determined by each plan administrator in accordance with its respective policy and procedures.
Employers and employer groups may also offer additional benefit designs which may be different than described.

IMPORTANT SAFETY INFORMATION

Humulin R U-500 is contraindicated during episodes of hypoglycemia and in patients hypersensitive to Humulin R U-500 or any of its excipients.

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.

Patients should be prescribed U-500 syringes for use with Humulin R U-500 vials. Do not use any other type of syringe to administer Humulin R U-500.
If using the Humulin R U-500 KwikPen^®, patients should be counseled to dial and dose the prescribed number of units of insulin.
Do NOT perform dose conversion when using the Humulin R U-500 KwikPen or U-500 insulin syringe.

DO NOT transfer Humulin R U-500 from the 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, to avoid risk of transmission of blood-borne pathogens.

Hyperglycemia or Hypoglycemia With Changes in Insulin Regimen

Changes in insulin strength, manufacturer, type, injection site, or method of administration may affect glycemic control and predispose to hypoglycemia or hyperglycemia. Any changes in insulin regimen should be made cautiously and only under close medical supervision, and the frequency of blood glucose monitoring should be increased. Due to reports of hypoglycemia and hyperglycemia, advise patients who have repeatedly injected into areas of lipodystrophy or localized cutaneous amyloidosis to change the injection site to the unaffected areas and to closely monitor blood glucose. For patients with type 2 diabetes, dosage adjustments of concomitant anti-diabetic products may be needed.

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.
Increase monitoring with changes to insulin dosage, co-administered glucose-lowering medications, meal patterns, physical activity, and in patients with renal or hepatic impairment or hypoglycemia unawareness. To minimize risk of hypoglycemia, do not administer Humulin R U-500 intravenously or dilute or mix with other products, including other insulins.
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 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.

Hypokalemia

May be life-threatening. Monitor potassium levels in patients at risk for hypokalemia and treat if indicated.

Fluid Retention and Heart Failure With Concomitant Use of Thiazolidinediones (TZDs)

Thiazolidinediones (TZDs) can cause dose-related fluid retention when used in combination with insulin. Observe for signs and symptoms of heart failure and consider reduction or discontinuation if heart failure occurs.

Adverse Reactions

Other adverse reactions include allergic reactions, lipodystrophy, injection site reactions, pruritus, and rash.

Drug Interactions

The following drugs may alter glucose metabolism and may necessitate insulin dose adjustment:

Drugs that may increase the risk of hypoglycemia: antidiabetic agents, ACE inhibitors, angiotensin II receptor blocking agents, disopyramide, fibrates, fluoxetine, monoamine oxidase inhibitors, pentoxifylline, pramlintide, salicylates, somatostatin analog (e.g., octreotide), and sulfonamide antibiotics.
Drugs that may decrease the blood glucose lowering effect of Humulin R U-500: atypical antipsychotics (e.g., olanzapine and clozapine), corticosteroids, danazol, diuretics, estrogens, glucagon, isoniazid, niacin, oral contraceptives, phenothiazines, progestogens (e.g., in oral contraceptives), protease inhibitors, somatropin, sympathomimetic agents (e.g., albuterol, epinephrine, terbutaline), and thyroid hormones.
Drugs that may increase or decrease the blood glucose lowering effect of Humulin R U-500: alcohol, beta-blockers, clonidine, and lithium salts. Pentamidine may cause hypoglycemia, which may sometimes be followed by hyperglycemia.

Increased frequency of glucose monitoring may be required when Humulin R U-500 is co-administered with the following drugs:

Drugs that may increase the risk of hypoglycemia: antidiabetic agents, ACE inhibitors, angiotensin II receptor blocking agents, disopyramide, fibrates, fluoxetine, monoamine oxidase inhibitors, pentoxifylline, pramlintide, salicylates, somatostatin analog (e.g., octreotide), and sulfonamide antibiotics.
Drugs that may decrease the blood glucose lowering effect of Humulin R U-500: atypical antipsychotics (e.g., olanzapine and clozapine), corticosteroids, danazol, diuretics, estrogens, glucagon, isoniazid, niacin, oral contraceptives, phenothiazines, progestogens (e.g., in oral contraceptives), protease inhibitors, somatropin, sympathomimetic agents (e.g., albuterol, epinephrine, terbutaline), and thyroid hormones.
Drugs that may increase or decrease the blood glucose lowering effect of Humulin R U-500: alcohol, beta-blockers, clonidine, and lithium salts. Pentamidine may cause hypoglycemia, which may sometimes be followed by hyperglycemia.
Drugs that may blunt signs and symptoms of hypoglycemia: beta-blockers, clonidine, guanethidine, and reserpine.

HM U500 HCP ISI 02FEB2023

INDICATION

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

Limitations of Use: The safety and efficacy of Humulin R U-500 used in combination with other insulins, or when delivered by continuous subcutaneous infusion, has not been determined.

A dedicated device for the unique dosing needs of high-dose patients1,2