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Humulin R U-500 Insulin human 500 [iU]/mL Injection, Solution — NDC 00002-8501-01 package photo
Label image from the product's FDA listing (DailyMed) — may show a different pack size or an older label revision.

Humulin R U-500 Insulin human 500 [iU]/mL Injection, Solution — NDC 0002-8501-01 (Billing 00002-8501-01)

by Eli Lilly and Company · 1 VIAL, MULTI-DOSE in 1 CARTON / 20 mL in 1 VIAL, MULTI-DOSE

This is a package of Humulin R U-500 Insulin human 500 [iU]/mL Injection, Solution from Eli Lilly and Company, no longer marketed (first marketed Mar 1994), no longer in the FDA NDC Directory; retail pharmacies pay about $71.17 per mL (NADAC). It is this product's only package size.

NDC 00002-8501-01
🏷️ FDA NDC (as labeled) 0002-8501-01 billing pads the labeler segment with a zero
Rx only Brand Discontinued Non-controlled ⚠ Discontinued by firm ⇄ Compare with another NDC
🗂️ FDA directory synced Oct 1, 2026 · this listing last changed Jul 24, 2026 · sources: openFDA · FDA label (DailyMed) · FDA Orange & Purple Book · First Databank · CMS NADAC, ASP, Medicare & Medicaid · RxNorm
📋 All sources & update times →

This page is curated, coded, and maintained by

Compiled from public FDA, CMS, DailyMed, NADAC, and related drug data sources. Editorial policy

NDC database record

One package, one record: these facts belong to NDC 0002-8501-01 alone.

Record
FDA NDC Directory package listing · Human prescription drug
Code segments
0002 labeler · 8501 product · 01 package
Package marketed since
Jan 6, 1997
Sample package
No — commercial package
Listing certified through
Dec 31, 2026
Barcode (UPC-A, from the NDC)
3 0002850101 6
Medicaid fills, this package
6,321 prescriptions in the last four reported quarters
FDA record last changed
Jul 24, 2026
⚠️
Other active recalls for Insulin Human (different manufacturers) — 1 · tap to view
These affect other manufacturers’ products for the same ingredient — not necessarily the exact NDC on this page.
Class II · Aug 6, 2026 — CGMP Deviations (Baxter Healthcare Corporation) · FDA recall D-0806-2026
Each entry is an official FDA enforcement report — look up any recall number in the FDA recall database ↗
⚠️
Excluded from the active FDA NDC Directory. The labeler reported this product as discontinued, so it is excluded from the active NDC Directory. The listing was last certified through May 2026. A label may still appear on DailyMed, but the NDC is no longer in the current FDA NDC Directory. Search the FDA NDC Directory ↗

Identity & classification

Regulatory identifiers FDA, NLM and CMS codes for this package

FDA NDC (as labeled) 0002-8501-01
Product NDC 0002-8501
11-digit billing NDC 00002850101
NCPDP billing unit ML — per mL (volume)
RxCUI 249220, 351859, 1731315, 1731317
UNII 1Y17CTI5SR
Application # BLA018780
SPL Set ID b60e8dd0-1d48-4dc9-87fd-e14675255e8c
Established class (EPC) Insulin
Chemical class Insulin
DEA schedule Non-controlled
Marketing category BLA
Marketing status Discontinued
FDA listing status Discontinued by firm (certified through May 2026)
Marketing start 1994-03-31
Route SUBCUTANEOUS
Dosage form INJECTION, SOLUTION
Substance INSULIN HUMAN
Biologic (Purple Book) 351(a)

Drug-database identifiers Medi-Span GPI and First Databank GCN / HICL / AHFS classification

GPI-14 27104010002015
GPI class HumuLIN R U-500 (CONCENTRATED)
GCN Seq No 029916
GCN 09633
HICL code 000768
Ingredient (HICL) Insulin Regular, Human
HIC1 code C
Therapeutic class — broad (HIC1) Electrolyte Balance/Metabolism/Nutrition
HIC2 code C4
Therapeutic class — intermediate (HIC2) Antihyperglycemics
HIC3 code C4G
Therapeutic class — specific (HIC3) Insulins
AHFS code 68:20.08.00
AHFS class Insulins
FDB label name HUMULIN R 500 UNIT/ML VIAL
FDB brand name Humulin R U-500
Legend status F — Federal legend — prescription drug or device
Quick answers
  • GSN (GCN sequence number): 029916
  • GCN: 09633
  • GPI-14 (Medi-Span): 27104010002015
  • HICL (First Databank): 000768
  • AHFS class code: 68:20.08.00
  • RxCUI (RxNorm): 249220
Why two NDCs? The FDA registers this code as 0002-8501-01 — a 4-4-2 layout, and that's what's printed on the package and shown on DailyMed. For insurance claims, every NDC is standardized to a uniform 11-digit 5-4-2 format by adding a zero to the labeler segment → 00002-8501-01. Same drug, same package — only the format differs.
Where does this data come from?
Identifiers from the FDA openFDA NDC Directory and Structured Product Labeling; RxCUI from RxNorm (NLM); GPI from Medi-Span; GCN / HIC / AHFS / legend from First Databank.

RxNorm drug class

This medicine belongs to the Insulin class.

Pharmacologic class Insulin
Drug family (ATC) Insulins and analogues for injection, fast-acting, Insulins and analogues for injection, intermediate-acting, Insulins and analogues for injection, intermediate- or long-acting combined with fast-acting
Where does this data come from?
Therapeutic classes from RxNorm RxClass (U.S. National Library of Medicine) — Established Pharmacologic Class (FDA), ATC drug family (WHO) and mechanism of action, matched by this product’s RxCUI.

Clinical

Label name HUMULIN R 500 UNIT/ML VIAL Ingredient Insulin Regular, Human
📖 What it is MedlinePlus · NLM

Human insulin is used to control blood sugar in people who have type 1 diabetes (condition in which the body does not make insulin and therefore cannot control the amount of sugar in the blood) or in people who have type 2 diabetes (condition in which the blood sugar is too high because the body does not produce or use insulin normally) that cannot be controlled with oral medications alone. Human insulin is in a class of medications called hormones. Human insulin is used to take the place of insulin that is normally produced by the body. It works by helping move sugar from the blood into other...

Read the full MedlinePlus article ↗
📗 Our plain-language guide HelloPharmacist
  • Novolin is a human insulin — it's identical to the insulin your body naturally makes. It's prescribed to help control your blood sugar when your body doesn't produce enough insulin...
  • What exactly is Novolin and why was I prescribed it?
  • Yes, timing with meals matters. For subcutaneous use, you inject Novolin about 30 minutes before you start eating. You can inject into your abdomen, thigh, buttock, or upper arm —...
  • How do I take this injection, and does it matter when I eat?
📖 Read our full Human Insulin Injection guide →

Supplement & herbal interactions

🌿 Drug–supplement interaction checker →
Where does this data come from?
Plain-language summary from MedlinePlus (U.S. National Library of Medicine); supplement & herbal interactions and nutrient depletion data from the Natural Medicines database; our full guide is HelloPharmacist editorial content.

Pricing

A drug doesn't have one price. Each row is a different public payment system, and none is what you'd pay at the counter — that depends on your insurance. The ⓘ on each row explains what it measures.

Price systemPer mLPer package
Retail pharmacies payNADAC · weekly $71.174 $1,423.48 / 20 ml
Medicaid paysCMS SDUD · 12 mo $71.64 $1,432.76 / 20 ml
Medicare drug plans payPart D · Q2 2026 $71.17 $1,423.47 / 20 ml
Medicare Part B allowsASP · J1817 $3.062 / J1817 unit —
NADAC price history (per mL) — tap or hover for the price & month
May 2021 Feb 2022 Feb 2023 Oct 2025 $71.291 $71.064
Flat over the last 5 months.
Where does this data come from?
NADAC (National Average Drug Acquisition Cost) is the CMS weekly pharmacy-acquisition-cost survey — what pharmacies pay. ASP (Average Sales Price) is the CMS Medicare Part B drug-payment file, published quarterly. Medicaid pays is computed by us from CMS State Drug Utilization Data (total reimbursed ÷ units, trailing 12 months) — gross of rebates and inclusive of dispensing fees, so it reflects what Medicaid paid, not an acquisition cost. Medicare drug plans pay is the median negotiated point-of-sale unit cost across plans listing this NDC in the CMS quarterly Prescription Drug Plan pricing files, before rebates. The VA pays is the federal contract price (FSS, and the statutory Big 4 ceiling where listed) from the VA National Acquisition Center pharmaceutical price file. All are free public government data; each measures a different payer, so the figures are not directly comparable.

Billing & reimbursement

FDA NDC (as labeled)0002-8501-01
11-digit billing NDC00002-8501-01
Format4-4-2 as registered → padded to 5-4-2 for billing (zero added to the labeler segment)
HCPCS J-codeJ1817
DescriptorINSULIN FOR ADMINISTRATION THROUGH DME (I.E., INSULIN PUMP) PER 50 UNITS
Billing units / pkg10 units
How the units are derivedThis package is 20 ML; the HCPCS unit is 50 U, so one package = 10 billing units.
Medicare Part B spend (2026 (Q1))$7,997,475 · 28,262 claims · $282.98 per claim (all NDCs under J1817)
Crosswalk sourcePDAC NDC-HCPCS crosswalk (DME MAC / DMEPOS)
Where does this data come from?
The HCPCS J-code crosswalk comes from the CMS ASP NDC-HCPCS crosswalk and the DMEPDAC (DME MAC) NDC-HCPCS crosswalk — free public CMS data. Billing units are derived from the code’s descriptor and the package amount.

Packaging — all sizes for this product

Package NDCDescription Marketing startMarketing endStatus
00002-8501-01 You're viewing this Main listing 1 VIAL, MULTI-DOSE in 1 CARTON / 20 mL in 1 VIAL, MULTI-DOSE 1997-01-06 — Discontinued by firm

Therapeutic equivalents

ProductLabelerPackNADAC/unitTEStatusPrice vs. this
Humulin R U-500 500 [iU]/mLthis 00002-8501-01 Eli 1 vial $71.174 — Discontinued —
Humulin R U-500 KwikPen 500 [iU]/mL 00002-8824-27 Eli 2 syringes $91.607 — Availability likely +29%
About this product: this is a biologic. Biologics don't have small-molecule generics — competition comes from FDA-licensed biosimilars (shown above), not generics.
Where does this data come from?
Equivalents are other NDCs of the same ingredient, form and route from the openFDA NDC Directory, ranked least-expensive-first by NADAC. Therapeutic-equivalence (AB) ratings come from the FDA Orange Book; biologics use the FDA Purple Book for biosimilar & interchangeable status.

Availability & biosimilar status

🏛️
1982
First FDA approval
Oct 1982
📍
2026
Currently FDA-listed
44 years listed
🧬
·
Biosimilars
see Purple Book
🧬Biologic — competition comes from biosimilars

Biologics have no small-molecule generics; biosimilar competition is tracked in the FDA Purple Book.

FDA Purple Book — biosimilars & interchangeables ⓘ
Reference product
Afrezzainsulin human Humulin R U-100insulin human Humulin R U-500insulin human Myxredlininsulin human Novolin Rinsulin human
🔒 No FDA-licensed biosimilars or interchangeable biosimilars are listed yet for this biologic. It currently has no biosimilar competition in the FDA Purple Book.
Source: FDA Purple Book (purplebooksearch.fda.gov), matched on the reference product’s active ingredient.
Where does this data come from?
Patents and exclusivity from the FDA Purple Book (biologics), refreshed from public FDA data. Biosimilar launch timing is an estimate, not a guarantee.

Inactive Ingredients / Excipients

Inactive ingredients, also called excipients, are components of the drug product other than the active ingredient. They may include fillers, dyes, coatings, preservatives, flavors, or other formulation ingredients.

🧪 Avoiding an ingredient? See Human Insulin Injection inactive ingredients by manufacturer: every current product's list side by side, so you can ask your pharmacy for the version that does not list it.

💡 Tap an ingredient (hover on desktop) to see what it is and why it’s used.

  • 16 mg / 1 mL UNII PDC6A3C0OX
    Glycerin is a clear, thick liquid derived from plant oils or fats. It acts as a humectant to retain moisture, a sweetener, and a solvent in medications.
  • UNII QTT17582CB
    A strong acid used to adjust and maintain the proper pH level in liquid medicines, ensuring stability and preventing breakdown of active ingredients.
  • 2.5 mg / 1 mL UNII GGO4Y809LO
    Metacresol is a preservative derived from coal tar or petroleum. It prevents bacterial and fungal growth in liquid medicines, helping keep the product safe and stable during storage.
  • UNII 55X04QC32I
    A strong alkaline chemical used to adjust and maintain the pH balance of liquid medicines. It helps keep the medicine stable and ensures it stays effective during storage.
  • UNII 059QF0KO0R
    Water is a liquid solvent that dissolves and mixes ingredients together in liquid medicines, syrups, and injections. It helps distribute the active drug evenly throughout the product.
  • 0.085 mg / 1 mL UNII J41CSQ7QDS
    A mineral element that strengthens tablet structure and acts as a processing aid. Zinc helps bind ingredients together and may improve the medicine's stability during manufacturing and storage.

6 inactive ingredients listed in the exact product block matched to this NDC.

Where does this data come from?
Data sourced from official FDA Structured Product Labeling (SPL) via DailyMed — ingredient classCode="IACT" elements from the exact product block matched by this NDC. Label-section narrative from DailyMed / the openFDA label index is shown separately when available.

Inactive ingredient FAQ

Are inactive ingredients the same for every manufacturer?
No. Inactive ingredients can differ by manufacturer, dosage form, strength, and package / product version.
Why might an inactive ingredient be missing?
Some SPLs do not provide a complete structured inactive-ingredient list, and older or unusual labels may only include the information in narrative text.
Can inactive ingredients matter?
Yes. They can matter for allergies, intolerances, dyes, gluten / lactose concerns, preservatives, and formulation differences — but confirm with a pharmacist or the manufacturer when it’s clinically important.

Manufacturer & labeler

LabelerEli Lilly and Company
FDA applicationBLA018780 (BLA)
Labeler code00002
First marketedMar 1994
Product typeHuman Prescription Drug
Portfolio192 products on file

More NDCs from Eli Lilly and Company labeler code 00002

The labeler markets the product; the application holder owns the FDA approval. They’re often the same company but can differ (e.g. a repackager or an authorized generic). A mailing address / phone appears here when the manufacturer includes it in the product’s FDA label (not all do).
Where does this data come from?
Labeler, application holder and registered establishment from the FDA openFDA NDC Directory and Drugs@FDA; address/contact from the product’s FDA label.

Full prescribing information FDA SPL

The complete FDA label for this product — the official prescribing information, verbatim, section by section. Very long sections are excerpted here and marked; the full text is on DailyMed (linked in the sources below). Jump with a chip, search within the label, or expand everything.
🎯 Indications and Usage ⏱️ Dosage and Administration 💊 Dosage Forms and Strengths ⛔ Contraindications ⚠️ Warnings and Cautions 🤒 Adverse Reactions 🔄 Drug Interactions 👥 Use in Specific Populations 🤰 Pregnancy 🧒 Pediatric Use 🧓 Geriatric Use 🆘 Overdosage 🧬 Clinical Pharmacology 🧬 Mechanism of Action 📦 How Supplied / Storage and Handling 📦 Storage and Handling 📋 Description 💬 Information for Patients 🧬 Pharmacokinetics 🧬 Pharmacodynamics 🧪 Nonclinical Toxicology 📄 Carcinogenesis, Mutagenesis, Impairment of Fertility 📄 Patient Package Insert 📖 Instructions for Use 📄 Package Label / Principal Display Panel
🎯 Indications and Usage 148 words ▾

1 INDICATIONS AND USAGE 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. 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. ( 1 ) 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. ( 1.1 )

1.1Limitation 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.

⏱️ Dosage and Administration ~3 min read ▾

2 DOSAGE AND ADMINISTRATION Adhere to administration instructions to reduce the risk of dosing errors. ( 2.1 , 2.3 ) HUMULIN R U-500 is available as a single-patient-use KwikPen. ( 2.1 ) Individualize dose of HUMULIN R U-500 based on metabolic needs, blood glucose monitoring results and glycemic control goal.

( 2.2 ) 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 , 2.2 ) Do NOT mix HUMULIN R U-500 with other insulins.

( 2.1 ) Do NOT administer HUMULIN R U-500 intravenously ( 2.1 ) 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 ) Do NOT transfer HUMULIN R U-500 from the HUMULIN R U-500 KwikPen into any syringe.

( 2.3 )

2.1Important 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. 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 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 ( 5.2 ) and Adverse Reactions ( 6 )] . During changes to a patient's insulin regimen, increase the frequency of blood glucose monitoring [see Warnings and Precautions ( 5.2 )] .

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.

2.2Dosing 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 ( 5.2 )] .

2.3Delivery 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 ( 5.3 )].

💊 Dosage Forms and Strengths 53 words ▾

3 DOSAGE FORMS AND STRENGTHS 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) Injection: 500 units/mL (U-500) available as: ( 3 ) 3 mL single-patient-use HUMULIN ® R U-500 KwikPen ® prefilled pen (containing 1,500 units of insulin)

⛔ Contraindications 68 words ▾

4 CONTRAINDICATIONS HUMULIN R U-500 is contraindicated: During episodes of hypoglycemia [see Warnings and Precautions ( 5.3 )] In patients who are hypersensitive to HUMULIN R U-500 or any of its excipients [see Warnings and Precautions ( 5.4 )] Do not use during episodes of hypoglycemia. ( 4 ) Do not use in patients with hypersensitivity to HUMULIN R U-500 or any of its excipients. ( 4 )

⚠️ Warnings and Cautions ~3 min read ▾

5 WARNINGS AND PRECAUTIONS Never share a HUMULIN R U-500 KwikPen between patients, even if the needle is changed. ( 5.1 ) Hyperglycemia or Hypoglycemia with Changes in Insulin Regimen: Make changes to a patient's insulin regimen (e.g., insulin strength, manufacturer, type, injection site or method of administration) under close medical supervision with increased frequency of blood glucose monitoring. ( 5.2 ) Hypoglycemia: May be life-threatening.

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

( 5.4 ) Hypokalemia: May be life-threatening. Monitor potassium levels in patients at risk for hypokalemia and treat if indicated. ( 5.5 ) 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.

( 5.6 )

5.1Never Share a HUMULIN R U-500 KwikPen Between Patients HUMULIN R U-500 KwikPens should never be shared between patients, even if the needle is changed. Sharing poses a risk for transmission of blood-borne pathogens.

5.2Hyperglycemia 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 ( 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 oral anti-diabetic treatment may be needed.

5.3Hypoglycemia 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 ( 7 )] , 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… [Excerpted — this section continues on DailyMed.]

🤒 Adverse Reactions ~2 min read ▾

6 ADVERSE REACTIONS The following adverse reactions are discussed elsewhere: Hypoglycemia [see Warnings and Precautions ( 5.3 )] . Hypersensitivity Reactions [see Warnings and Precautions ( 5.4 )] . Hypokalemia [see Warnings and Precautions ( 5.5 )] .

The following additional adverse reactions have been identified during post-approval use of HUMULIN R U-500. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or to establish a causal relationship to drug exposure. Adverse reactions associated with HUMULIN R U-500 include hypoglycemia, allergic reactions, injection site reactions, lipodystrophy, pruritus, and rash.

( 6 ) To report SUSPECTED ADVERSE REACTIONS, contact Eli Lilly and Company at 1-800-LillyRx (1-800-545-5979) or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. Hypoglycemia Hypoglycemia is the most commonly observed adverse reaction in patients using insulin, including HUMULIN R U-500. Allergic Reactions Severe, life-threatening, generalized allergy, including anaphylaxis, generalized skin reactions, rash, angioedema, bronchospasm, hypotension, and shock may occur with insulins, including HUMULIN R U-500 and may be life threatening.

Lipodystrophy Long-term use of insulin, including HUMULIN R U-500, can cause lipodystrophy at the site of repeated insulin injections. Lipodystrophy includes lipohypertrophy (thickening of adipose tissue) and lipoatrophy (thinning of adipose tissue) and may affect insulin absorption. Rotate insulin injections sites within the same region to reduce the risk of lipodystrophy [see Dosage and Administration ( 2.1 )] .

Localized Cutaneous Amyloidosis Localized cutaneous amyloidosis at the injection site has occurred. Hyperglycemia has been reported with repeated insulin injections into areas of localized cutaneous amyloidosis; hypoglycemia has been reported with a sudden change to an unaffected injection site. Injection Site Reactions Patients taking HUMULIN R U-500 may experience injection site reactions, including injection site hematoma, pain, hemorrhage, erythema, nodules, swelling, discoloration, pruritus, warmth, and injection site mass.

Weight Gain Weight gain can occur with insulins, including HUMULIN R U-500, and has been attributed to the anabolic effects of insulin. Peripheral Edema Insulins, including HUMULIN R U-500, may cause sodium retention and edema, particularly if previously poor metabolic control is improved by intensified insulin therapy. Immunogenicity As with all therapeutic proteins, insulin administration may cause anti-insulin antibodies to form.

The presence of antibodies that affect clinical efficacy may necessitate dose adjustments to correct for tendencies toward hyper- or hypoglycemia. The incidence of antibody formation with HUMULIN R U-500 is unknown.

🔄 Drug Interactions ~1 min read ▾

7 DRUG INTERACTIONS Table 1: Clinically Significant Drug Interactions with HUMULIN R U-500 Drugs That May Increase the Risk of Hypoglycemia Drugs : 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. Intervention : Dose adjustment and increased frequency of glucose monitoring may be required when HUMULIN R U-500 is co-administered with these drugs.

Drugs That May Decrease the Blood Glucose Lowering Effect of HUMULIN R U 500 Drugs: 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. Intervention: Dose adjustment and increased frequency of glucose monitoring may be required when HUMULIN R U-500 is co-administered with these drugs.

Drugs That May Increase or Decrease the Blood Glucose Lowering Effect of HUMULIN R U 500 Drugs: Alcohol, beta-blockers, clonidine, and lithium salts. Pentamidine may cause hypoglycemia, which may sometimes be followed by hyperglycemia. Intervention: Dose adjustment and increased frequency of glucose monitoring may be required when HUMULIN R U-500 is co-administered with these drugs.

Drugs That May Blunt Signs and Symptoms of Hypoglycemia Drugs: Beta-blockers, clonidine, guanethidine and reserpine Intervention: Increased frequency of glucose monitoring may be required when HUMULIN R U-500 is co-administered with these drugs. Drugs that Affect Glucose Metabolism: Adjustment of insulin dosage may be needed. ( 7 ) Antiadrenergic Drugs (e.g., beta-blockers, clonidine, guanethidine, and reserpine): Signs and symptoms of hypoglycemia may be reduced or absent.

( 5.2 , 7 )

👥 Use in Specific Populations ~2 min read ▾

8 USE IN SPECIFIC POPULATIONS

8.1Pregnancy Risk Summary 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 ( see Data). There are risks to the mother and fetus associated with poorly controlled diabetes in pregnancy ( see Clinical Considerations). Animal reproduction studies were not performed.

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.

Clinical Considerations Disease-associated maternal and/or embryo/fetal risk Poorly controlled diabetes in pregnancy increases the maternal risk for diabetic ketoacidosis, pre-eclampsia, spontaneous abortions, preterm delivery, and delivery complications. Poorly controlled diabetes increases the fetal risk for major birth defects, stillbirth, and macrosomia-related morbidity. Data Human Data While available studies cannot definitively establish the absence of risk, published data from retrospective studies, open-label, randomized, parallel studies and meta-analyses over decades have not established an association with human insulin use during pregnancy and major birth defects, miscarriage, or adverse maternal or fetal outcomes.

All available studies have methodological limitations, including lack of blinding, unclear methods or randomization, and small sample size.

8.2Lactation Risk Summary Available data from published literature suggests that exogenous human insulin products, including HUMULIN R U-500, are transferred into human milk. There are no adverse reactions reported in breastfed infants in the literature. There are no data on the effects of exogenous human insulin products, including HUMULIN R U-500 on milk production.

The developmental and health benefits of breastfeeding should be considered along with the mother's clinical need for HUMULIN R U-500 and any potential adverse effects on the breastfed child from HUMULIN R U-500 or from the underlying maternal condition.

8.4Pediatric Use The safety and effectiveness of HUMULIN R U-500 in pediatric patients with diabetes mellitus requiring more than 200 units of insulin per day to improve glycemic control have been established. Use of HUMULIN R U-500 for this indication is supported by evidence from studies with other insulin human in pediatric patients with type 1 diabetes mellitus and from studies in adults with diabetes mellitus. Standard precautions as applied to use of HUMULIN R U-500 in adults are appropriate for use in pediatric patients.

8.5Geriatric Use The effect of age on the pharmacokinetics and pharmacodynamics of HUMULIN R U-500 has not been studied. Caution should be exercised when HUMULIN R U-500 is administered to geriatric patients. In elderly patients with diabetes, the initial dosing, dose increments, and maintenance dosage should be conservative to avoid hypoglycemia.

8.6Renal Impairment Frequent glucose monitoring and insulin dose reduction may be required in patients with renal impairment.

8.7Hepatic Impairment Frequent glucose monitoring and insulin dose reduction may be required in patients with hepatic impairment.

🤰 Pregnancy ~1 min read ▾

8.1Pregnancy Risk Summary 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 ( see Data). There are risks to the mother and fetus associated with poorly controlled diabetes in pregnancy ( see Clinical Considerations). Animal reproduction studies were not performed.

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.

Clinical Considerations Disease-associated maternal and/or embryo/fetal risk Poorly controlled diabetes in pregnancy increases the maternal risk for diabetic ketoacidosis, pre-eclampsia, spontaneous abortions, preterm delivery, and delivery complications. Poorly controlled diabetes increases the fetal risk for major birth defects, stillbirth, and macrosomia-related morbidity. Data Human Data While available studies cannot definitively establish the absence of risk, published data from retrospective studies, open-label, randomized, parallel studies and meta-analyses over decades have not established an association with human insulin use during pregnancy and major birth defects, miscarriage, or adverse maternal or fetal outcomes.

All available studies have methodological limitations, including lack of blinding, unclear methods or randomization, and small sample size.

🧒 Pediatric Use 86 words ▾

8.4Pediatric Use The safety and effectiveness of HUMULIN R U-500 in pediatric patients with diabetes mellitus requiring more than 200 units of insulin per day to improve glycemic control have been established. Use of HUMULIN R U-500 for this indication is supported by evidence from studies with other insulin human in pediatric patients with type 1 diabetes mellitus and from studies in adults with diabetes mellitus. Standard precautions as applied to use of HUMULIN R U-500 in adults are appropriate for use in pediatric patients.

🧓 Geriatric Use 52 words ▾

8.5Geriatric Use The effect of age on the pharmacokinetics and pharmacodynamics of HUMULIN R U-500 has not been studied. Caution should be exercised when HUMULIN R U-500 is administered to geriatric patients. In elderly patients with diabetes, the initial dosing, dose increments, and maintenance dosage should be conservative to avoid hypoglycemia.

🆘 Overdosage 76 words ▾

10 OVERDOSAGE Excess insulin administration may cause hypoglycemia and hypokalemia. Mild episodes of hypoglycemia usually can be treated with oral glucose. Adjustments in drug dosage, meal patterns, or exercise may be needed.

More severe episodes with coma, seizure, or neurologic impairment may be treated with a glucagon product for emergency use or concentrated intravenous glucose. Sustained carbohydrate intake and observation may be necessary because hypoglycemia may recur after apparent clinical recovery. Hypokalemia must be corrected appropriately.

🧬 Clinical Pharmacology ~2 min read ▾

12 CLINICAL PHARMACOLOGY

12.1Mechanism of Action Regulation of glucose metabolism is the primary activity of insulins, including HUMULIN R U-500. Insulins lower blood glucose by stimulating peripheral glucose uptake by skeletal muscle and fat, and by inhibiting hepatic glucose production. Insulins inhibit lipolysis and proteolysis, and enhance protein synthesis.

12.2Pharmacodynamics In a euglycemic clamp study of 24 healthy obese subjects (BMI=30-39 kg/m 2 ), single doses of HUMULIN R U-500 at 50 units (0.4-0.6 unit/kg) and 100 units (0.8-1.3 unit/kg) resulted in a mean time of onset of action of less than 15 minutes at both doses and a mean duration of action of 21 hours (range 13-24 hours). The time action characteristics reflect both prandial and basal activity, consistent with clinical experience. This effect has been attributed to the high concentration of the preparation.

Figure 1 should be considered a representative example since the time course of action of insulin may vary in different individuals or within the same individual. The rate of insulin absorption and consequently the onset of activity is known to be affected by the site of injection, exercise, and other variables [see Warnings and Precautions ( 5.3 )] . Figure 1: Mean Insulin Activity Versus Time Profiles After Subcutaneous Injection of a 100 U Dose of HUMULIN R U-500 in Healthy Obese Subjects Figure 1

12.3Pharmacokinetics Absorption — In a euglycemic clamp study of 24 healthy obese subjects, the median peak insulin level occurred between 4 hours (50 unit dose) and 8 hours (100 unit dose) with a range of 0.5-8 hours. Metabolism — The uptake and degradation of insulin occurs predominantly in liver, kidney, muscle, and adipocytes, with the liver being the major organ involved in the clearance of insulin. Elimination — Mean apparent half-life after subcutaneous administration of single doses of 50 units and 100 units to healthy obese subjects (N≥21) was approximately 4.5 hours (range=1.9-10 hours) for HUMULIN R U-500.

Figure 2: Mean Serum Insulin Concentrations Versus Time After Subcutaneous Injection of a 100 U Dose of HUMULIN R U-500 Healthy Obese Subjects Figure 2

🧬 Mechanism of Action 47 words ▾

12.1Mechanism of Action Regulation of glucose metabolism is the primary activity of insulins, including HUMULIN R U-500. Insulins lower blood glucose by stimulating peripheral glucose uptake by skeletal muscle and fat, and by inhibiting hepatic glucose production. Insulins inhibit lipolysis and proteolysis, and enhance protein synthesis.

📦 How Supplied / Storage and Handling 213 words ▾

16 HOW SUPPLIED/STORAGE AND HANDLING

16.1How Supplied HUMULIN R U-500 (500 units/mL) injection is available in a clear, colorless solution as: 2 x 3 mL single-patient-use HUMULIN R U-500 KwikPen NDC 0002-8824-27 The HUMULIN R U-500 KwikPen dials in 5 unit increments.

16.2Storage and Handling Dispense in the original sealed carton with the enclosed Instructions for Use. Protect from heat and light. Do not freeze.

Do not use if it has been frozen. Do not shake the vial. See Table 2 below for storage conditions.

Table 2: Storage Conditions for HUMULIN R U-500 Pens a When stored at room temperature, HUMULIN R U-500 KwikPen can only be used for a total of 28 days, including both not in-use (unopened) and in-use (opened) storage time. Not In-use (Unopened) In-use (Opened) Room Temperature (up to 86°F [30°C]) Refrigerated (36° to 46°F [2° to 8°C]) Room Temperature (up to 86°F [30°C]) Refrigerated (36° to 46°F [2° to 8°C]) 3 mL single-patient-use HUMULIN R U-500 KwikPen a 28 days Until expiration date 28 days Do not refrigerate.

16.1How Supplied HUMULIN R U-500 (500 units/mL) injection is available in a clear, colorless solution as: 2 x 3 mL single-patient-use HUMULIN R U-500 KwikPen NDC 0002-8824-27 The HUMULIN R U-500 KwikPen dials in 5 unit increments.

📦 Storage and Handling 132 words ▾

16.2Storage and Handling Dispense in the original sealed carton with the enclosed Instructions for Use. Protect from heat and light. Do not freeze.

Do not use if it has been frozen. Do not shake the vial. See Table 2 below for storage conditions.

Table 2: Storage Conditions for HUMULIN R U-500 Pens a When stored at room temperature, HUMULIN R U-500 KwikPen can only be used for a total of 28 days, including both not in-use (unopened) and in-use (opened) storage time. Not In-use (Unopened) In-use (Opened) Room Temperature (up to 86°F [30°C]) Refrigerated (36° to 46°F [2° to 8°C]) Room Temperature (up to 86°F [30°C]) Refrigerated (36° to 46°F [2° to 8°C]) 3 mL single-patient-use HUMULIN R U-500 KwikPen a 28 days Until expiration date 28 days Do not refrigerate.

📋 Description 123 words ▾

11 DESCRIPTION Insulin human is produced by recombinant DNA technology utilizing a non-pathogenic laboratory strain of Escherichia coli and has the empirical formula C 257 H 383 N 65 O 77 S 6 with a molecular weight of 5.808 kDa. HUMULIN R U-500 (insulin human) injection is a sterile, aqueous, and colorless solution for subcutaneous use. HUMULIN R U-500 contains 500 units of insulin human in each milliliter.

Each milliliter of HUMULIN R U-500 also contains glycerin (16 mg), metacresol (2.5 mg), zinc oxide to supplement the endogenous zinc to obtain a total zinc content of 0.017 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.

💬 Information for Patients ~1 min read ▾

17 PATIENT COUNSELING INFORMATION See FDA-approved patient labeling. Patients should be counseled that HUMULIN R U-500 is a 5-times concentrated insulin product. Extreme caution must be observed in the measurement of dosage because inadvertent overdose may result in serious adverse reaction or life-threatening hypoglycemia.

Accidental mix-ups between insulin products have been reported. To avoid medication errors between HUMULIN R U-500 and other insulins, patients should be instructed to always check the insulin label before each injection. 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) [see Dosage and Administration ( 2.3 )] .

Patients should be instructed on self-management procedures including glucose monitoring, proper injection technique, and management of hypoglycemia and hyperglycemia, especially at initiation of HUMULIN R U-500 therapy. Patients must be instructed on handling of special situations such as intercurrent conditions (illness, stress, or emotional disturbances), an inadequate or skipped insulin dose, inadvertent administration of an increased insulin dose, inadequate food intake, and skipped meals. Advise patients that changes in insulin regimen can predispose to hyperglycemia or hypoglycemia and that changes in insulin regimen should be made under close medical supervision.

Refer patients to the HUMULIN R U-500 Patient Information Leaflet for additional information [see Warnings and Precautions ( 5 )] . Do not dilute or mix HUMULIN R U-500 with any other insulin products or solutions [see Dosage and Administration ( 2.1 )] . Literature Revised: July 2026 Manufactured by: Eli Lilly and Company, Indianapolis, IN 46285, USA US License Number 1891 Copyright © 1997, 2026, Eli Lilly and Company.

All rights reserved. LINR500-0011-USPI-20260701

🧬 Pharmacokinetics 124 words ▾

12.3Pharmacokinetics Absorption — In a euglycemic clamp study of 24 healthy obese subjects, the median peak insulin level occurred between 4 hours (50 unit dose) and 8 hours (100 unit dose) with a range of 0.5-8 hours. Metabolism — The uptake and degradation of insulin occurs predominantly in liver, kidney, muscle, and adipocytes, with the liver being the major organ involved in the clearance of insulin. Elimination — Mean apparent half-life after subcutaneous administration of single doses of 50 units and 100 units to healthy obese subjects (N≥21) was approximately 4.5 hours (range=1.9-10 hours) for HUMULIN R U-500.

Figure 2: Mean Serum Insulin Concentrations Versus Time After Subcutaneous Injection of a 100 U Dose of HUMULIN R U-500 Healthy Obese Subjects Figure 2

🧬 Pharmacodynamics 172 words ▾

12.2Pharmacodynamics In a euglycemic clamp study of 24 healthy obese subjects (BMI=30-39 kg/m 2 ), single doses of HUMULIN R U-500 at 50 units (0.4-0.6 unit/kg) and 100 units (0.8-1.3 unit/kg) resulted in a mean time of onset of action of less than 15 minutes at both doses and a mean duration of action of 21 hours (range 13-24 hours). The time action characteristics reflect both prandial and basal activity, consistent with clinical experience. This effect has been attributed to the high concentration of the preparation.

Figure 1 should be considered a representative example since the time course of action of insulin may vary in different individuals or within the same individual. The rate of insulin absorption and consequently the onset of activity is known to be affected by the site of injection, exercise, and other variables [see Warnings and Precautions ( 5.3 )] . Figure 1: Mean Insulin Activity Versus Time Profiles After Subcutaneous Injection of a 100 U Dose of HUMULIN R U-500 in Healthy Obese Subjects Figure 1

🧪 Nonclinical Toxicology 47 words ▾

13 NONCLINICAL TOXICOLOGY

13.1Carcinogenesis, Mutagenesis, Impairment of Fertility Carcinogenicity and fertility studies were not performed with HUMULIN R U-500 in animals. Biosynthetic human insulin was not genotoxic in the in vivo sister chromatid exchange assay and the in vitro gradient plate and unscheduled DNA synthesis assays.

📄 Carcinogenesis, Mutagenesis, Impairment of Fertility 44 words ▾

13.1Carcinogenesis, Mutagenesis, Impairment of Fertility Carcinogenicity and fertility studies were not performed with HUMULIN R U-500 in animals. Biosynthetic human insulin was not genotoxic in the in vivo sister chromatid exchange assay and the in vitro gradient plate and unscheduled DNA synthesis assays.

📄 Patient Package Insert ~3 min read ▾

This Patient Information has been approved by the U.S. Food and Drug Administration. Revised: July 2026 LINR500-0007-PPI-20260701 Patient Information Humulin ® (HU-mu-lin) R U-500 (insulin human) injection, for subcutaneous use U-500 (500 units/mL) Do not share your Humulin R U-500 KwikPen with other people, even if the needle has been changed.

You may give other people a serious infection or get a serious infection from them. What is Humulin R U-500? Humulin R U-500 is a man-made 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 (500 units/mL) in 1 mL as Humulin R U-100 (100 units/mL). It is not known if Humulin R U-500 is safe and effective when used in combination with other insulins. It is not known if Humulin R U-500 is safe and effective when given by continuous subcutaneous infusion.

Who should not take Humulin R U-500? Do not take Humulin R U-500 if you: are having an episode of low blood sugar (hypoglycemia). have an allergy to human insulin or any of the ingredients in Humulin R U-500. See the end of this Patient Information leaflet for a complete list of ingredients in Humulin R U-500.

What should I tell my healthcare provider before using Humulin R U-500? Before using Humulin R U-500, tell your healthcare provider about all your medical conditions including, if you: have liver or kidney problems. take other medicines, especially ones called TZDs (thiazolidinediones). have heart failure or other heart problems. If you have heart failure, it may get worse while you take TZDs with Humulin R U-500. are pregnant, planning to become pregnant.

Talk with your healthcare provider about the best way to control your blood sugar if you plan to become pregnant or while you are pregnant. are breast-feeding or plan to breastfeed. Humulin R U-500 may pass into your breast milk. Talk with your healthcare provider about the best way to feed your baby while using HUMULIN R U-500.

Tell your healthcare provider about all the medicines you take, including prescription and over-the-counter medicines, vitamins, or 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. Use Humulin R U-500 exactly as your healthcare provider tells you to. Your healthcare provider should tell 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 the dose of Humulin R U-500 you use 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.

When using the Humulin R U-500 KwikPen: The Humulin R 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 from your Humulin R 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. Use Humulin R U-500 30 minutes before eating a meal. Inject Humulin R U-500 under the skin (subcutaneously) of your upper legs (thighs), upper arms, buttocks or stomach area (abdomen).

Do not use Humulin R U-500 in an insulin pump or inject Humulin R U-500 into your vein (intravenously). Do not mix Humulin R U-500 in the KwikPen with any other type of insulin or liquid medicine. Change (rotate) your injection sites within the area you choose with each dose to reduce your risk of getting lipodystrophy (pits in skin or thickened skin) and localized cutaneous amyloidosis (skin with lumps) at the injection sites. - Do not use the exact same spot for each injection. - Do not inject where the skin has pits, is thickened, or has lumps. - Do not inject where the skin is tende… [Excerpted — this section continues on DailyMed.]

📖 Instructions for Use ~3 min read ▾

Instructions for Use Humulin ® R U-500 (insulin human) injection, for subcutaneous use 20 mL multiple-dose vial (500 units/mL) Please read these instructions before use. Warnings For your safety, always inject Humulin ® R U - 500 insulin with a U - 500 syringe. If you use another kind of syringe, you may get a dangerous overdose.

U-500 syringe – for single injection only The U-500 syringe has a green U-500 symbol and a green Needle Shield on the syringe. Important Information Humulin R U-500 is a concentrated insulin. Know your dose.

Your health care provider will tell you the number of insulin units that you should take. Always inject Humulin R U-500 insulin with a U-500 syringe. Other syringes will not measure your dose correctly.

If you use the wrong syringe, you can give yourself a severe overdose. This can cause very low blood sugar, which may put your life in danger. For example, using a U-100 syringe can give you a 5 times overdose.

If you do not have a U-500 syringe, you should contact your health care provider or pharmacist. Additional Safety Information Each line on the U-500 syringe measures 5 units of U-500 insulin. You can give from 5 to 250 units in one injection.

If your dose is more than 250 units, you will need to give more than 1 injection. Make sure you know how to draw up your dose with a U-500 syringe. If you need help, call your health care provider.

Do not reuse your U-500 syringe. Do not share your U - 500 syringes with other people. You may give other people a serious infection or get a serious infection from them.

Do not mix Humulin R U-500 with other insulins in the same syringe. You can get more instructions by calling Lilly at 1-800-LillyRx (1-800-545-5979). Supplies Humulin R U-500 multiple-dose vial U-500 Syringe (BD [Becton, Dickinson and Company] syringes recommended) 2 alcohol swabs 1 sharps container Before You Start Check your vial.

Make sure it says Humulin R U-500. Check the expiration date on the vial. Do not use it if it is expired.

Throw away the opened vial after 40 days, even if there is still insulin left in the vial. See if the insulin in the vial is clear. Do not use if it is thick, cloudy, or colored or has solid particles.

Make sure you have a new U-500 Syringe. Check for the green U-500 symbol and green Needle Shield. Check your supply.

Make sure you have enough Humulin R U-500 insulin and U-500 syringes for several injections. Always reorder before you run out. Check with your health care provider if you have any questions.

Use only a U-500 syringe to inject Humulin R U-500 insulin Prepare Wash your hands with soap and water. Always use a new syringe for each injection to help prevent infections and blocked needles. Step 1: Find the line on the U-500 syringe that matches your prescribed dose.

This is your Dose Line. Each line is 5 units. (Example: Arrow shows Dose Line at 85 units) Step 2: If you are using a new vial, pull off the plastic Protective Cap.

Do not remove the Rubber Stopper. Step 3: Wipe the Rubber Stopper with an alcohol swab. Step 4: Hold the syringe with the Needle pointing up.

Pull down on the Plunger Rod until the Plunger Tip reaches your Dose Line. (Example Dose: 85 units shown) Step 5: Push the Needle through the Rubber Stopper of the vial. Step 6: Push the Plunger all the way in.

This puts air into the vial. Step 7: Turn the vial and syringe upside down and slowly pull the Plunger down until the Plunger Tip is past your Dose Line. (Example Dose: 85 units Plunger is shown at 100 units) If there are air bubbles, tap the syringe gently a few times.

This lets the air bubbles rise to the top. Step 8: Slowly push the Plunger up until the Plunger Tip reaches your Dose Line. Check the syringe to make sure that you have the right dose.

(Example Dose: 85 units shown) Step 9: Pull the syringe out of the vial's Rubber Stopper. Inject Inject your insulin exactly as your healthcare provider has shown you. Change (rotate) your injection sites within the area you choose fo… [Excerpted — this section continues on DailyMed.]

📄 Package Label / Principal Display Panel 162 words ▾

VIAL PACKAGE CARTON – HUMULIN R U-500 Vial 20 mL 1ct NDC 0002-8501-01 20 mL Humulin ® R U-500 (insulin human) injection 10,000 units per 20 mL 500 units per mL Rx only 500 units/mL Warning - Highly Concentrated IMPORTANT: Use only with a U-500 syringe. 20 mL multiple-dose vial For subcutaneous use only www.humulin.com Lilly PACKAGE CARTON – HUMULIN R U-500 Vial 20 mL 1ct

KWIKPEN PACKAGE CARTON – HUMULIN R U-500 KwikPen 3 mL (500 Units per mL) Dispense in this sealed carton NDC 0002-8824-27 Humulin ® R U-500 KwikPen ® (insulin human) injection For Single Patient Use Only prefilled insulin delivery device 500 units/mL 500 units per mL 2 x 3 mL prefilled pens Rx only For subcutaneous use only. Read Humulin ® R U-500 KwikPen ® Instructions for Use. NEEDLES NOT INCLUDED This device is recommended for use with Becton, Dickinson and Company's insulin pen needles.

DO NOT TRANSFER TO A SYRINGE SEVERE OVERDOSE CAN RESULT Figure Figure

Source: FDA Structured Product Labeling, mirrored from DailyMed / openFDA. Prefer the government’s original formatting? View this label on DailyMed ↗

Medicaid utilization & spend

📍 This exact package only: Medicaid data is reported per full 11-digit NDC — labeler, product and pack size — so every number here is for this package alone, not the drug overall. Other pack sizes report separately.
💊 Pharmacy benefit only: These are Medicaid outpatient pharmacy claims, billed by NDC. They exclude the medical benefit — clinic- or hospital-administered drugs billed under HCPCS J-codes — so drugs used mostly that way (e.g. Avastin, Lucentis, Keytruda) can look low or missing here. That’s expected, not an error.
📅 Q1 2025 – Q1 2026 · 5 quarters of data
ⓘ The newest quarter is usually incomplete when first published; states restate recent quarters in later CMS releases, so the latest figures typically revise upward. State coverage-policy changes can also shift quarter-to-quarter totals.
Prescriptions last 4 qtrs
6.3K
Units reimbursed last 4 qtrs
165.6K
Gross reimbursed last 4 qtrs
$11.86M
Avg / prescription
$1,876.90
Avg / unit
$71.6381
Latest quarter Q1 2026
22Rx
Medicaid pays / mL
$71.6381
gross reimbursed
vs
NADAC / mL
$71.1742
acquisition cost
=
Spread
+$0.4639
+1% vs cost
What Medicaid paid per mL (before rebates; includes the pharmacy’s dispensing fee) compared with NADAC — the average price pharmacies pay to buy the drug. A positive spread means Medicaid reimbursed more than the purchase price, before manufacturer rebates.
Fee-for-service vs managed care ⓘ
29% FFS 71% MCO
Fee-for-service · 1,849 Rx Managed care · 4,472 Rx
State Medicaid map
Alaska: no data reported AK Maine: 240 units · 17.2 per 100k residents ME Washington: 3,360 units · 43.0 per 100k residents WA Idaho: 560 units · 28.5 per 100k residents ID Montana: no data reported MT North Dakota: no data reported ND Minnesota: 2,040 units · 35.6 per 100k residents MN Wisconsin: 2,800 units · 47.4 per 100k residents WI Michigan: 6,880 units · 68.5 per 100k residents MI New York: 9,660 units · 49.4 per 100k residents NY Vermont: no data reported VT New Hampshire: no data reported NH Oregon: 1,260 units · 29.8 per 100k residents OR Nevada: 380 units · 11.9 per 100k residents NV Wyoming: no data reported WY South Dakota: no data reported SD Iowa: 900 units · 28.1 per 100k residents IA Illinois: 6,880 units · 54.8 per 100k residents IL Indiana: 8,080 units · 118 per 100k residents IN Ohio: 16,666 units · 141 per 100k residents OH Pennsylvania: 7,683 units · 59.3 per 100k residents PA New Jersey: 1,284 units · 13.8 per 100k residents NJ Massachusetts: 1,822 units · 26.0 per 100k residents MA California: 13,520 units · 34.7 per 100k residents CA Utah: 260 units · 7.6 per 100k residents UT Colorado: 1,900 units · 32.3 per 100k residents CO Nebraska: no data reported NE Missouri: 4,500 units · 72.6 per 100k residents MO Kentucky: 15,454 units · 341 per 100k residents KY West Virginia: 2,620 units · 148 per 100k residents WV Virginia: 5,340 units · 61.3 per 100k residents VA Maryland: 3,680 units · 59.5 per 100k residents MD Connecticut: 300 units · 8.3 per 100k residents CT Rhode Island: 740 units · 67.6 per 100k residents RI Arizona: 2,900 units · 39.0 per 100k residents AZ New Mexico: 1,000 units · 47.3 per 100k residents NM Kansas: 1,080 units · 36.7 per 100k residents KS Arkansas: 1,460 units · 47.6 per 100k residents AR Tennessee: 5,720 units · 80.3 per 100k residents TN North Carolina: 7,940 units · 73.3 per 100k residents NC South Carolina: 1,660 units · 30.9 per 100k residents SC Delaware: no data reported DE Oklahoma: no data reported OK Louisiana: 3,400 units · 74.3 per 100k residents LA Mississippi: 1,420 units · 48.3 per 100k residents MS Alabama: 480 units · 9.4 per 100k residents AL Georgia: 4,040 units · 36.6 per 100k residents GA D.C.: no data reported DC Hawaii: no data reported HI Texas: 4,680 units · 15.3 per 100k residents TX Florida: 5,560 units · 24.6 per 100k residents FL
Units reimbursed · per 100k residents
7.6341
gray = no data reported ⓘ
Colors are per 100,000 residents, so big states don’t automatically dominate. Tap or hover a state for its actual totals.
Tap or hover a state
…for its Medicaid breakdown
🏆 Top states by units · per 100k residents
1 Kentucky 341 /100k
2 West Virginia 148 /100k
3 Ohio 141 /100k
4 Indiana 118 /100k
5 Tennessee 80.3 /100k
6 Louisiana 74.3 /100k
7 North Carolina 73.3 /100k
8 Missouri 72.6 /100k
National units — by quarter
💵 About the dollar figures: “reimbursed” is what Medicaid paid pharmacies before confidential manufacturer rebates, so the program’s real net cost is lower than these numbers. Fee-for-service and managed-care claims are combined unless split above. Source: CMS State Drug Utilization Data; per-100k rates use 2023 Census population estimates.

Medicare Part D spend CMS · PART D · 2026 (Q1)

Medicare Part D (outpatient prescription) spending for Humulin R U-500 — the program that covers self-administered drugs. 1 manufacturer.
⚠️ Drug-level data: CMS publishes Part D spending by drug, not by NDC — these figures combine every manufacturer, strength and package size sold under the name Humulin R U-500. That’s a different level of aggregation than the Medicaid card above, which is specific to this exact 11-digit NDC (pack size included), so the two aren’t directly comparable.
Period
Total Part D spend
$419K
Claims incl. refills
265
Beneficiaries
229
Spend / beneficiary
$1,829.54
Spend / claim
$1,581.00
Trend by period
💵 About the dollar figures: spending is what Part D plans paid before confidential manufacturer rebates, so the program’s real net cost is lower. A blank patient count means fewer than 11 people — CMS hides counts that small to protect privacy. Source: CMS Medicare Quarterly Part D Spending by Drug (data.cms.gov), updated quarterly.

Reported adverse events (FAERS)

Read carefully: FAERS reports are voluntary and unverified. Counts are not incidence, do not establish causation, are subject to reporting bias, and cannot be used to compare one drug to another. Shown for signal context only. Reports for Insulin human — the ingredient across all brands.

Top reported reactions

Blood Glucose Increased10,009
Blood Glucose Decreased3,299
Hypoglycaemia1,526
Nausea1,481
Visual Impairment1,369
Weight Decreased1,305
Dyspnoea1,280

Age at onset

Neonate110
Infant17
Child28
Adolescent23
Adult2,176
Elderly1,800

Reporter sex

39,520 reports
Male · 44%
Female · 56%
Unknown · 0%

Serious outcomes

Hospitalization13,008
Death2,906
Life-threatening1,520
Disabling1,351
Reports over time (by year) — tap or hover for the count & year
2019 2021 2023 2026 2,080 656
Most recent year is provisional (FAERS lags ~3 months).
Where does this data come from?
Adverse-event reports from the FDA Adverse Event Reporting System (FAERS) via openFDA. FAERS reports are voluntary and unverified — counts are not incidence and don’t establish causation.

About this NDC listing & data coverage

Finished prescription product No longer marketed (per FDA listing data)
What data is (and isn’t) available for this NDC — tap to expand
NDC identity (package / product / labeler codes) ✓ Available
Labeler ✓ Available
Product & package description ✓ Available
Marketing category & status ✓ Available
Active ingredient / dosage form / route ✓ Available
FDA label (SPL via DailyMed) ✓ Available
Package photos ✓ Available
Inactive ingredients (structured) ✓ Available
NADAC pharmacy acquisition price (CMS) ✓ Available
Orange Book / therapeutic-equivalence data — Not published for this NDC Applies only to products approved under an NDA/ANDA; many listings are out of scope.
HCPCS J-code billing crosswalk ✓ Available
Medicaid utilization (CMS SDUD) ✓ Available
“Not published” reflects what the public FDA / CMS / NLM sources provide for this exact package code — it is a property of the data feeds, not a judgment about the product.

Questions about this listing

What does the discontinued status mean for this NDC?
The labeler reported a marketing end date (or the listing was delisted), so this specific package is no longer actively marketed. Remaining stock may still be dispensed for a time, and the NDC stays valid for historical records and claims — but data feeds (pricing, labeling) typically stop updating for it. Other package sizes or other manufacturers' versions of the same medication may still be marketed — see the equivalents section where available.
Is the NDC printed on the package the same as the 11-digit billing NDC?
Yes, they identify this exact package in different formats. The form printed on the packaging and shown on DailyMed is the one the FDA registered. Insurance claims use a fixed 11-digit 5-4-2 format, so the short segment is padded with a leading zero and the dashes are dropped. The Identity section at the top of this page lists each form of this code.
Who lists this product with the FDA?
Eli Lilly and Company is the labeler of record for this NDC — the company under whose FDA-assigned code the package is listed. The labeler may be the manufacturer itself or a distributor marketing the product under its own code.
Do I need a prescription for this product?
This NDC is listed with FDA as a prescription product, so it is dispensed under a prescriber's order. Your pharmacist can tell you whether any over-the-counter forms of the same medication exist.
Does this product have a billing J-code?
Yes — this NDC cross-references HCPCS code J1817 for medical-claim billing (typically used when a product is administered in a clinical setting rather than dispensed at a retail pharmacy). See the Billing section on this page.
This page identifies an FDA-listed package (the NDC) and reports public regulatory and pricing data about the listing. It is reference information, not a medical recommendation — talk to your pharmacist or prescriber about your own medication.
Where does this data come from?
Listing facts (marketing category, packager status, marketing dates) from the FDA openFDA NDC Directory; label availability from DailyMed; pricing coverage from CMS NADAC; equivalence scope from the FDA Orange Book.
← 00002-8400-01 · Eli 00002-8715-01 · Eli →
For educational and professional reference only — not medical advice. Pricing reflects published NADAC and CMS ASP (free public data) and may differ from your acquisition cost; always verify before billing or dispensing.