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Insulin Lispro Protamine and Insulin Lispro Injectable Suspension Mix75/25 KwikPen 100 [iU]/mL Injection, Suspension — NDC 00002-8233-05 package photo
Label image from the product's FDA listing (DailyMed) — may show a different pack size or an older label revision.

Insulin Lispro Protamine and Insulin Lispro Injectable Suspension Mix75/25 KwikPen 100 [iU]/mL Injection, Suspension — NDC 0002-8233-05 (Billing 00002-8233-05)

by Eli Lilly and Company · 5 SYRINGE in 1 CARTON / 3 mL in 1 SYRINGE

This is a package of Insulin Lispro Protamine and Insulin Lispro Injectable Suspension Mix75/25 KwikPen 100 [iU]/mL Injection, Suspension from Eli Lilly and Company, marketed since Feb 2020 and currently FDA-listed; retail pharmacies pay about $10.21 per mL (NADAC). It is this product's only package size.

NDC 00002-8233-05
🏷️ FDA NDC (as labeled) 0002-8233-05 billing pads the labeler segment with a zero
Rx only Brand On market Non-controlled ⚠ On shortage ⇄ 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 0002-8233-05 alone.

Record
FDA NDC Directory package listing · Human prescription drug
Code segments
0002 labeler · 8233 product · 05 package
Package marketed since
Feb 12, 2020
Sample package
No — commercial package
Listing certified through
Dec 31, 2026
Barcode (UPC-A, from the NDC)
3 0002823305 4
Medicaid fills, this package
21,036 prescriptions in the last four reported quarters
FDA record last changed
Jul 24, 2026
⚠️
Active FDA shortage. Insulin Lispro Protamine and Insulin Lispro Injection is currently reported in shortage by the FDA. Shortage details →
⚠️
Other active recalls for Insulin Lispro (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 · Apr 11, 2023 — Lack of Assurance of Sterility: Malformed crimped collar seal (Sanofi-Aventis U.S. LLC) · FDA recall D-0575-2023
Each entry is an official FDA enforcement report — look up any recall number in the FDA recall database ↗

Identity & classification

Regulatory identifiers FDA, NLM and CMS codes for this package

FDA NDC (as labeled) 0002-8233-05
Product NDC 0002-8233
11-digit billing NDC 00002823305
NCPDP billing unit ML — per mL (volume)
RxCUI 847252
UNII GFX7QIS1II
Application # BLA021017
SPL Set ID e49f701d-c19f-4cb2-b63f-01a917b33abc
Established class (EPC) Insulin Analog
Chemical class Insulin
DEA schedule Non-controlled
Marketing category BLA
Marketing status On market
FDA listing status Listed (active directory)
Marketing start 2020-02-12
Route SUBCUTANEOUS
Dosage form INJECTION, SUSPENSION
Substance INSULIN LISPRO
Biologic (Purple Book) 351(a)

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

GPI-14 2710408000D320
GPI class Insulin Lispro Prot & Lispro
GCN Seq No 042076
GCN 93717
HICL code 019949
Ingredient (HICL) Insulin Lispro Protamin/Lispro
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 INSULIN LISPRO MIX 75-25 KWKPN
FDB brand name Insulin Lispro Protamine Mix
Legend status F — Federal legend — prescription drug or device
Quick answers
  • GSN (GCN sequence number): 042076
  • GCN: 93717
  • GPI-14 (Medi-Span): 2710408000D320
  • HICL (First Databank): 019949
  • AHFS class code: 68:20.08.00
  • RxCUI (RxNorm): 847252
Why two NDCs? The FDA registers this code as 0002-8233-05 — 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 → 00002-8233-05. 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.

Clinical

Label name INSULIN LISPRO MIX 75-25 KWKPN Ingredient Insulin Lispro Protamin/Lispro
1
Nutrient depletion considerations

Insulin Lispro may be associated with lower levels of 1 nutrient — worth a chat with your pharmacist, not a cause for alarm.

🧪 Full Insulin Lispro nutrient depletion report →
An association is not a deficiency. Educational only — don't start or stop anything without professional guidance.
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 $10.207 $153.11 / 15 ml
Medicaid paysCMS SDUD · 12 mo $10.24 $153.66 / 15 ml
Medicare drug plans payPart D · Q2 2026 $10.74 $161.11 / 15 ml
Medicare Part B allowsASP · J1815 No ASP payment limit on file for J1815 this quarter.
NADAC price history (per mL) — tap or hover for the price & month
Dec 2021 Aug 2022 Jan 2026 Sep 2026 $17.056 $10.161
▼ Down 40% over the last 24 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)0002-8233-05
11-digit billing NDC00002-8233-05
Format4-4-2 as registered → padded to 5-4-2 for billing (zero added to the labeler segment)
HCPCS J-codeJ1815
DescriptorINJECTION, INSULIN, PER 5 UNITS
Billing units / pkg20 units
How the units are derivedThis package is 3 ML; the HCPCS unit is 5 U, so one package = 20 billing units.
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
00002-8233-05 You're viewing this Main listing 5 SYRINGE in 1 CARTON / 3 mL in 1 SYRINGE 2020-02-12 — Active

Therapeutic equivalents

ProductLabelerPackNADAC/unitTEStatusPrice vs. this
Humalog Mix75/25 100 [iU]/mL 00002-7511-01 Eli 1 vial $8.153 — Availability likely save 20%
Humalog Tempo Pen 100 [iU]/mL 00002-8213-05 Eli 5 syringes $10.127 — Availability likely save 1%
Humalog Mix50/50 KwikPen 100 [iU]/mL 00002-8798-59 Eli 5 syringes $10.141 — Availability likely save 1%
Humalog Junior KwikPen 100 [iU]/mL 00002-7714-59 Eli 5 syringes $10.158 — Availability likely +0%
Humalog Mix75/25 KwikPen 100 [iU]/mL 00002-8797-59 Eli 5 syringes $10.167 — Availability likely +0%
Insulin Lispro Junior KwikPen 100 [iU]/mL 00002-7752-05 Eli 5 syringes $10.199 — Availability likely +0%
Insulin Lispro Protamine and Insulin Lispro Injectable Suspension Mix75/25 KwikPen 100 [iU]/mLthis 00002-8233-05 Eli 5 syringes $10.207 — Availability likely —
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

🏛️
1996
First FDA approval
Jun 1996
📍
2026
Currently FDA-listed
30 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
Admeloginsulin lispro Humaloginsulin lispro Lyumjevinsulin lispro-aabc
🔒 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.

💡 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.
  • 1.76 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.
  • .715 mg / 1 mL UNII 339NCG44TV
    Phenol is a chemical compound derived from coal tar or petroleum. It serves as a preservative and antimicrobial agent in medicines, helping prevent bacterial and fungal growth to keep the product stable and safe during storage.
  • 0.28 mg / 1 mL UNII 0DE9724IHC
    Protamine sulfate is a protein derived from fish sperm that acts as a binder and stabilizer in medications. It helps hold tablet ingredients together and can improve the stability of certain drug formulations.
  • 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.
  • 3.78 mg / 1 mL UNII GR686LBA74
    Sodium phosphate, dibasic is a salt derived from phosphoric acid. It acts as a buffer to help maintain the medicine's pH balance and may serve as a binder or filler in tablets and capsules.
  • 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.
  • .025 mg / 1 mL UNII SOI2LOH54Z
    Zinc oxide is a white mineral powder used in medicines as a protective barrier agent and color additive. It helps shield skin in topical products and may also serve as a filler or opacifying ingredient.

9 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 applicationBLA021017 (BLA)
Labeler code00002
First marketedFeb 2020
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 117 words ▾

1 INDICATIONS AND USAGE Insulin Lispro Protamine and Insulin Lispro Mix75/25 is indicated to improve glycemic control in adults with diabetes mellitus. Insulin Lispro Protamine and Insulin Lispro Mix75/25™ is a mixture of insulin lispro protamine, an intermediate-acting human insulin analog, and insulin lispro, a rapid-acting human insulin analog indicated to improve glycemic control in adults with diabetes mellitus. ( 1 ) Limitations of Use: The proportions of rapid-acting and intermediate-acting insulins are fixed and do not allow for basal versus prandial dose adjustments.

( 1 ) Limitations of Use: The proportions of rapid-acting and intermediate-acting insulins in Insulin Lispro Protamine and Insulin Lispro Mix75/25 are fixed and do not allow for basal versus prandial dose adjustments.

⏱️ Dosage and Administration ~3 min read ▾

2 DOSAGE AND ADMINISTRATION See Full Prescribing Information for important preparation and administration instructions. ( 2.1 ) Inject Insulin Lispro Protamine and Insulin Lispro Mix75/25 subcutaneously within 15 minutes before a meal in abdominal wall, thigh, upper arm, or buttocks and rotate injection sites to reduce the risk of lipodystrophy and localized cutaneous amyloidosis. ( 2.1 , 2.2 ) Individualize and adjust dosage based on metabolic needs, blood glucose monitoring results and glycemic control goal.

( 2.2 ) Do not administer Insulin Lispro Protamine and Insulin Lispro Mix75/25 intravenously or by a continuous subcutaneous insulin infusion pump. ( 2.1 ) Insulin Lispro Protamine and Insulin Lispro Mix75/25 is typically dosed twice daily (with each dose intended to cover 2 meals or a meal and a snack). ( 2.2 )

2.1Important Preparation and Administration Instructions Preparation Instructions Always check insulin labels before administration. This product is HUMALOG Mix75/25 [see Warnings and Precautions ( 5.4 )] . Insulin Lispro Protamine and Insulin Lispro Mix75/25 is a suspension that must be resuspended immediately before use.

Resuspension is easier when the insulin has reached room temperature. To resuspend KwikPen, gently roll the KwikPen at least 10 times and then carefully invert the KwikPen at least 10 times until the suspension appears uniformly white and cloudy. Inspect Insulin Lispro Protamine and Insulin Lispro Mix75/25 visually before use.

Do not use if discoloration or particulate matter is seen. Administration Instructions After resuspension, immediately administer Insulin Lispro Protamine and Insulin Lispro Mix75/25 by subcutaneous injection into the abdominal wall, thigh, upper arm, or buttocks. Rotate the injection site 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 )] . The Insulin Lispro Protamine and Insulin Lispro Mix75/25 KwikPen dials in 1 unit increments. Use Insulin Lispro Protamine and Insulin Lispro Mix75/25 KwikPen with caution in patients with visual impairment that may rely on audible clicks to dial their dose.

Do not administer Insulin Lispro Protamine and Insulin Lispro Mix75/25 intravenously or by a continuous subcutaneous insulin infusion pump. Do not mix Insulin Lispro Protamine and Insulin Lispro Mix75/25 with any other insulins or diluents.

2.2Dosage Recommendations Individualize and adjust the dosage of Insulin Lispro Protamine and Insulin Lispro Mix75/25 based on the individual's metabolic needs, blood glucose monitoring results and glycemic control goal. Inject Insulin Lispro Protamine and Insulin Lispro Mix75/25 subcutaneously within 15 minutes before a meal. Insulin Lispro Protamine and Insulin Lispro Mix75/25 is typically dosed twice-daily (with each dose intended to cover 2 meals or a meal and a snack).

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 or during acute illness [see Warnings and Precautions ( 5.2 , 5.3 ) and Use in Specific Populations ( 8.6 , 8.7 )] . When switching from another insulin to Insulin Lispro Protamine and Insulin Lispro Mix75/25, a different dosage of Insulin Lispro Protamine and Insulin Lispro Mix75/25 may be needed. During changes to a patient's insulin regimen, increase the frequency of blood glucose monitoring [see Warnings and Precautions ( 5.2 )] .

2.3Dosage Modifications for Drug Interactions Dosage modification may be needed when Insulin Lispro Protamine and Insulin Lispro Mix75/25 is used concomitantly with certain drugs [see Drug Interactions ( 7 )] .

💊 Dosage Forms and Strengths 72 words ▾

3 DOSAGE FORMS AND STRENGTHS Injectable Suspension: 100 units/mL (U-100) of Insulin Lispro Protamine and Insulin Lispro, 75% insulin lispro protamine and 25% insulin lispro is a white and cloudy suspension available as: 3 mL single-patient-use KwikPen prefilled pen Injectable suspension: 100 units/mL (U-100) of Insulin Lispro Protamine and Insulin Lispro Mix75/25, 75% insulin lispro protamine and 25% insulin lispro available as: ( 3 ) 3 mL single-patient-use KwikPen ® prefilled pen

⛔ Contraindications 83 words ▾

4 CONTRAINDICATIONS Insulin Lispro Protamine and Insulin Lispro Mix75/25 is contraindicated: during episodes of hypoglycemia [see Warnings and Precautions ( 5.3 )] in patients who have had hypersensitivity reactions to Insulin Lispro Protamine and Insulin Lispro Mix75/25 or to any of its excipients. [see Warnings and Precautions ( 5.5 )] Do not use during episodes of hypoglycemia. ( 4 ) Do not use in patients with hypersensitivity to Insulin Lispro Protamine and Insulin Lispro Mix75/25 or any of its excipients. ( 4 )

⚠️ Warnings and Cautions ~3 min read ▾

5 WARNINGS AND PRECAUTIONS Never share an Insulin Lispro Protamine and Insulin Lispro Mix75/25 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 frequency of blood glucose monitoring with changes to insulin dosage, co-administered glucose lowering medications, meal pattern, physical activity; in patients with renal or hepatic impairment; and in patients with hypoglycemia unawareness. ( 5.3 ) Hypoglycemia Due to Medication Errors: Accidental mix-ups between insulin products can occur. Instruct patients to check insulin labels before injection.

( 5.4 ) Hypersensitivity Reactions: Severe, life-threatening, generalized allergy, including anaphylaxis, can occur. Discontinue Insulin Lispro Protamine and Insulin Lispro Mix75/25, monitor and treat if indicated. ( 5.5 ) Hypokalemia: May be life-threatening.

Monitor potassium levels in patients at risk of hypokalemia and treat if indicated. ( 5.6 ) Fluid Retention and Heart Failure with Concomitant Use of Thiazolidinediones (TZDs) : Observe for signs and symptoms of heart failure; consider dosage reductions or discontinuation if heart failure occurs. ( 5.7 )

5.1Never Share an Insulin Lispro Protamine and Insulin Lispro Mix75/25 KwikPen Between Patients Insulin Lispro Protamine and Insulin Lispro Mix75/25 KwikPens must 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, dosage adjustments of concomitant anti-diabetic products may be needed.

5.3Hypoglycemia Hypoglycemia is the most common adverse reaction associated with all insulins, including Insulin Lispro Protamine and Insulin Lispro Mix75/25. Severe hypoglycemia can cause seizures, may lead to unconsciousness, may be life-threatening, or cause death. Hypoglycemia can impair concentration ability and reaction time; this may place an individual 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 individual and change over time in the same individual. Symptomatic awareness 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 (e.g., beta-blockers) [see Drug Interactions ( 7 )] , or in patients who experience recurrent hypoglycemia. Risk Factors for Hypoglycemia The risk of hypoglycemia after an injection is related to the duration of action of the insulin and in general, is highest when the glucose lowering effect of the insulin is maximal.

As with all insulins, the glucose lowering effect time course of Insulin Lispro Prota… [Excerpted — this section continues on DailyMed.]

🤒 Adverse Reactions ~2 min read ▾

6 ADVERSE REACTIONS The following adverse reactions are discussed elsewhere in the labeling: Hypoglycemia [see Warnings and Precautions ( 5.3 )] Hypoglycemia Due to Medication Errors [see Warnings and Precautions ( 5.4 )] Hypersensitivity Reactions [see Warnings and Precautions ( 5.5 )] Hypokalemia [see Warnings and Precautions ( 5.6 )] Adverse reactions observed with Insulin Lispro Protamine and Insulin Lispro Mix75/25 include hypoglycemia, allergic reactions, injection site reactions, lipodystrophy, weight gain, edema, 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. Adverse Reactions from Clinical Studies or Postmarketing Reports The following adverse reactions have been identified during post-marketing use of Insulin Lispro Protamine and Insulin Lispro Mix75/25. Because some of these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.

Adverse reactions associated with insulin initiation and glucose control intensification Intensification or rapid improvement in glucose control has been associated with a transitory, reversible ophthalmologic refraction disorder, worsening of diabetic retinopathy, and acute painful peripheral neuropathy. Over the long-term, improved glycemic control decreases the risk of diabetic retinopathy and neuropathy. Hypersensitivity reactions Severe, life-threatening, generalized allergy, including anaphylaxis.

Hypoglycemia Hypoglycemia is the most commonly observed adverse reaction in Insulin Lispro Protamine and Insulin Lispro Mix75/25. Hypokalemia Insulin Lispro Protamine and Insulin Lispro Mix75/25 can cause a shift in potassium from the extracellular to intracellular space, possibly leading to hypokalemia. Injection site reactions Insulin Lispro Protamine and Insulin Lispro Mix75/25 can cause local injection site reactions including redness, swelling, or itching at the site of injection.

These reactions usually resolve in a few days to a few weeks, but in some occasions, may require discontinuation. Localized reactions and generalized myalgias have been reported with the use of meta-cresol, which is an excipient in Insulin Lispro Protamine and Insulin Lispro Mix75/25. Lipodystrophy Administration of insulin subcutaneously, including Insulin Lispro Protamine and Insulin Lispro Mix75/25, has resulted in lipoatrophy (depression in the skin) or lipohypertrophy (enlargement or thickening of tissue) [see Dosage and Administration ( 2.1 )] in some patients.

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. Medication Errors Medication errors in which other insulins have been accidentally substituted for Insulin Lispro Protamine and Insulin Lispro Mix75/25 have been identified during postapproval use.

Peripheral Edema Insulins, including Insulin Lispro Protamine and Insulin Lispro Mix75/25, may cause sodium retention and edema, particularly if previously poor metabolic control is improved by intensified insulin therapy. Weight gain Weight gain can occur with insulins, including Insulin Lispro Protamine and Insulin Lispro Mix75/25, and has been attributed to the anabolic effects of insulin and the decrease in glycosuria. Immunogenicity As with all therapeutic proteins, insulin administration may cause anti-insulin antibodies to form.

The incidence of antibody formation with Insulin Lispro Protamine and Insulin Lispro Mix75/25 is unknown.

🔄 Drug Interactions ~2 min read ▾

7 DRUG INTERACTIONS Table 1 below presents clinically significant drug interactions with Insulin Lispro Protamine and Insulin Lispro Mix75/25. Table 1: Clinically Significant Drug Interactions with Insulin Lispro Protamine and Insulin Lispro Mix75/25 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 Insulin Lispro Protamine and Insulin Lispro Mix75/25 is co-administered with these drugs. Drugs that May Decrease the Blood Glucose Lowering Effect of Insulin Lispro Protamine and Insulin Lispro Mix75/25 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 Insulin Lispro Protamine and Insulin Lispro Mix75/25 is co-administered with these drugs. Drugs that May Increase or Decrease the Blood Glucose Lowering Effect of Insulin Lispro Protamine and Insulin Lispro Mix75/25 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 Insulin Lispro Protamine and Insulin Lispro Mix75/25 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 Insulin Lispro Protamine and Insulin Lispro Mix75/25 is co-administered with these 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. ( 7 ) Drugs that may decrease the blood glucose lowering effect: atypical antipsychotics, 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.

( 7 ) Drugs that may increase or decrease the blood glucose lowering effect: alcohol, beta-blockers, clonidine, lithium salts, and pentamidine. ( 7 ) Drugs that may blunt the signs and symptoms of hypoglycemia: beta-blockers, clonidine, guanethidine, and reserpine. ( 7 )

👥 Use in Specific Populations ~3 min read ▾

8 USE IN SPECIFIC POPULATIONS

8.1Pregnancy Risk Summary Published studies with insulin lispro used during pregnancy have not reported an association between insulin lispro and the induction of 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). Pregnant rats and rabbits were exposed to insulin lispro in animal reproduction studies during organogenesis.

No adverse effects on embryo/fetal viability or morphology were observed in offspring of rats exposed to insulin lispro at a dose approximately 3 times the human subcutaneous dose of 1 unit insulin lispro/kg/day. No adverse effects on embryo/fetal development were observed in offspring of rabbits exposed to insulin lispro at doses up to approximately 0.2 times the human subcutaneous dose of 1 unit/kg/day (see Data) . 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, still birth, and macrosomia related morbidity. Data Human Data Published data from retrospective studies and meta-analyses do not report an association with insulin lispro and major birth defects, miscarriage, or adverse maternal or fetal outcomes when insulin lispro is used during pregnancy. However, these studies cannot definitely establish or exclude the absence of any risk because of methodological limitations including small sample size, selection bias, confounding by unmeasured factors, and some lacking comparator groups.

Animal Data Animal reproduction studies have not been performed with Insulin Lispro Protamine and Insulin Lispro Mix75/25. However, subcutaneous reproduction and teratology studies have been conducted with insulin lispro (a component of Insulin Lispro Protamine and Insulin Lispro Mix75/25). In a combined fertility and embryo-fetal development study, female rats were given subcutaneous insulin lispro injections of 1, 5, and 20 units/kg/day (0.2, 0.8, and 3 times the human subcutaneous dose of 1 unit insulin lispro/kg/day, based on units/body surface area, respectively) from 2 weeks prior to cohabitation through Gestation Day 19.

There were no adverse effects on female fertility, implantation, or fetal viability and morphology. However, fetal growth retardation was produced at the 20 units/kg/day-dose as indicated by decreased fetal weight and an increased incidence of fetal runts/litter. In an embryo-fetal development study in pregnant rabbits, insulin lispro doses of 0.1, 0.25, and 0.75 unit/kg/day (0.03, 0.08, and 0.2 times the human subcutaneous dose of 1 unit insulin lispro/kg/day, based on units/body surface area, respectively) were injected subcutaneously on Gestation days 7 through 19.

There were no adverse effects on fetal viability, weight, and morphology at any dose.

8.2Lactation Risk Summary Available data from published literature suggests that exogenous human insulin products, including Insulin Lispro Protamine and Insulin Lispro Mix75/25, 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 Insulin Lispro Protamine and Insulin Lispro Mix75/25, on milk production.

The d… [Excerpted — this section continues on DailyMed.]

🤰 Pregnancy ~2 min read ▾

8.1Pregnancy Risk Summary Published studies with insulin lispro used during pregnancy have not reported an association between insulin lispro and the induction of 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). Pregnant rats and rabbits were exposed to insulin lispro in animal reproduction studies during organogenesis.

No adverse effects on embryo/fetal viability or morphology were observed in offspring of rats exposed to insulin lispro at a dose approximately 3 times the human subcutaneous dose of 1 unit insulin lispro/kg/day. No adverse effects on embryo/fetal development were observed in offspring of rabbits exposed to insulin lispro at doses up to approximately 0.2 times the human subcutaneous dose of 1 unit/kg/day (see Data) . 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, still birth, and macrosomia related morbidity. Data Human Data Published data from retrospective studies and meta-analyses do not report an association with insulin lispro and major birth defects, miscarriage, or adverse maternal or fetal outcomes when insulin lispro is used during pregnancy. However, these studies cannot definitely establish or exclude the absence of any risk because of methodological limitations including small sample size, selection bias, confounding by unmeasured factors, and some lacking comparator groups.

Animal Data Animal reproduction studies have not been performed with Insulin Lispro Protamine and Insulin Lispro Mix75/25. However, subcutaneous reproduction and teratology studies have been conducted with insulin lispro (a component of Insulin Lispro Protamine and Insulin Lispro Mix75/25). In a combined fertility and embryo-fetal development study, female rats were given subcutaneous insulin lispro injections of 1, 5, and 20 units/kg/day (0.2, 0.8, and 3 times the human subcutaneous dose of 1 unit insulin lispro/kg/day, based on units/body surface area, respectively) from 2 weeks prior to cohabitation through Gestation Day 19.

There were no adverse effects on female fertility, implantation, or fetal viability and morphology. However, fetal growth retardation was produced at the 20 units/kg/day-dose as indicated by decreased fetal weight and an increased incidence of fetal runts/litter. In an embryo-fetal development study in pregnant rabbits, insulin lispro doses of 0.1, 0.25, and 0.75 unit/kg/day (0.03, 0.08, and 0.2 times the human subcutaneous dose of 1 unit insulin lispro/kg/day, based on units/body surface area, respectively) were injected subcutaneously on Gestation days 7 through 19.

There were no adverse effects on fetal viability, weight, and morphology at any dose.

🧒 Pediatric Use 21 words ▾

8.4Pediatric Use Safety and effectiveness of Insulin Lispro Protamine and Insulin Lispro Mix75/25 in pediatric patients have not been established.

🧓 Geriatric Use 65 words ▾

8.5Geriatric Use Clinical studies of Insulin Lispro Protamine and Insulin Lispro Mix75/25 did not include sufficient numbers of patients aged 65 and over to determine whether they respond differently than younger patients. In patients aged 65 and over with diabetes, the initial dosing, dose increments, and maintenance dosage should be conservative to reduce the risk of hypoglycemia [see Warnings and Precautions ( 5.3 )].

🆘 Overdosage 85 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 [see Warnings and Precautions ( 5.3 , 5.6 )].

🧬 Clinical Pharmacology ~3 min read ▾

12 CLINICAL PHARMACOLOGY

12.1Mechanism of Action The primary activity of insulin, including Insulin Lispro Protamine and Insulin Lispro Mix75/25, is the regulation of glucose metabolism. 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 glucose clamp study performed in 30 healthy subjects, the onset of action and glucose-lowering activity of HUMALOG, HUMALOG ® Mix50/50™, Insulin Lispro Protamine and Insulin Lispro Mix75/25, and insulin lispro protamine suspension (ILPS) were compared ( see Figure 1 ). Graphs of mean glucose infusion rate versus time showed a distinct insulin activity profile for each formulation. The rapid onset of glucose-lowering activity characteristic of HUMALOG was maintained in Insulin Lispro Protamine and Insulin Lispro Mix75/25.

The median maximum pharmacologic effect of Insulin Lispro Protamine and Insulin Lispro Mix75/25 after administration of a 0.3 unit/kg dose to healthy subjects occurred at approximately 2 hours (range: 1-6 hours); glucose lowering activity was detectable for a median of 22 hours (range: 13 to 22 hours), which was the end of the clamp. In separate glucose clamp studies performed in healthy subjects, pharmacodynamics of Insulin Lispro Protamine and Insulin Lispro Mix75/25 and HUMULIN ® 70/30 were assessed and are presented in Figure 2 .

Insulin Lispro Protamine and Insulin Lispro Mix75/25 has a duration of activity similar to that of HUMULIN 70/30. Figures 1 and 2 should be considered only as representative examples since the time course of action of insulin and insulin analogs, may vary in different individuals or within the same individual. Figure 1: Mean Insulin Activity Versus Time Profiles After Injection of 0.3 units/kg of HUMALOG, HUMALOG Mix50/50, Insulin Lispro Protamine and Insulin Lispro Mix75/25, or Insulin Lispro Protamine Suspension (ILPS) in 30 Healthy Subjects.

Figure 2: Mean Insulin Activity Versus Time Profiles After Injection of 0.3 units/kg of Insulin Lispro Protamine and Insulin Lispro Mix75/25 or HUMULIN 70/30 in Healthy Subjects. Figure Figure

12.3Pharmacokinetics Absorption — Insulin Lispro Protamine and Insulin Lispro Mix75/25 has two phases of absorption. The early phase represents insulin lispro and its distinct characteristics of rapid onset. The late phase represents the prolonged absorption of insulin lispro protamine suspension.

In 31 healthy subjects given subcutaneous doses (0.3 unit/kg) of Insulin Lispro Protamine and Insulin Lispro Mix75/25, the median peak serum concentration was 60 minutes (range: 30 minutes to 4 hours) after dosing. Identical results were found in patients with type 1 diabetes. The rapid absorption characteristics of HUMALOG are maintained with Insulin Lispro Protamine and Insulin Lispro Mix75/25.

Insulin Lispro Protamine and Insulin Lispro Mix75/25 has a more rapid absorption than HUMULIN 70/30, which has been confirmed in patients with type 1 diabetes. Metabolism — Human metabolism studies of Insulin Lispro Protamine and Insulin Lispro Mix75/25 have not been conducted. However, studies in animals indicate that the metabolism of HUMALOG, the rapid-acting component of Insulin Lispro Protamine and Insulin Lispro Mix75/25, is identical to that of regular human insulin.

Elimination — Because of the absorption-rate limited kinetics of insulin mixtures, a true half-life cannot be accurately estimated from the terminal slope of the concentration versus time curve. Specific Populations The effects of age, race, obesity, pregnancy, smoking, or renal or hepatic impairment on the pharmacokinetics of Insulin Lispro Protamine and Insulin Lispro Mix75/25 have not been studied. Gender — Pharmacokinetic and pharmacodynamic comparisons between men and women administered Insulin Lispro Protamine and Insulin Lispro Mix75/25 showed no gender differenc… [Excerpted — this section continues on DailyMed.]

🧬 Mechanism of Action 52 words ▾

12.1Mechanism of Action The primary activity of insulin, including Insulin Lispro Protamine and Insulin Lispro Mix75/25, is the regulation of glucose metabolism. 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 ~1 min read ▾

16 HOW SUPPLIED/STORAGE AND HANDLING

16.1How Supplied Insulin Lispro Protamine and Insulin Lispro, injectable suspension, is a white and cloudy suspension of 100 units/mL (U-100) of 75% insulin lispro protamine and 25% insulin lispro available as: 3 mL single-patient-use KwikPen prefilled pen NDC 0002-8233-05 Insulin Lispro Protamine and Insulin Lispro Mix75/25 KwikPens must never be shared between patients, even if the needle is changed. Always use a new needle for each injection to prevent contamination. The Insulin Lispro Protamine and Insulin Lispro Mix75/25 KwikPen dials in 1 unit increments.

16.2Storage and Handling Dispense in the original sealed carton with the enclosed Instructions for Use. Protect from direct heat and light. Do not freeze and do not use if it has been frozen.

See storage table below: Not In-Use (Unopened) Refrigerated (36° to 46°F [2° to 8°C]) Not In Use (Unopened) Room Temperature (up to 86°F [30°C]) In-Use (Opened) (see temperature below) 3 mL single-patient-use KwikPen Until expiration date 10 days 10 days Room temperature only (Do not refrigerate)

16.1How Supplied Insulin Lispro Protamine and Insulin Lispro, injectable suspension, is a white and cloudy suspension of 100 units/mL (U-100) of 75% insulin lispro protamine and 25% insulin lispro available as: 3 mL single-patient-use KwikPen prefilled pen NDC 0002-8233-05 Insulin Lispro Protamine and Insulin Lispro Mix75/25 KwikPens must never be shared between patients, even if the needle is changed. Always use a new needle for each injection to prevent contamination. The Insulin Lispro Protamine and Insulin Lispro Mix75/25 KwikPen dials in 1 unit increments.

📦 Storage and Handling 80 words ▾

16.2Storage and Handling Dispense in the original sealed carton with the enclosed Instructions for Use. Protect from direct heat and light. Do not freeze and do not use if it has been frozen.

See storage table below: Not In-Use (Unopened) Refrigerated (36° to 46°F [2° to 8°C]) Not In Use (Unopened) Room Temperature (up to 86°F [30°C]) In-Use (Opened) (see temperature below) 3 mL single-patient-use KwikPen Until expiration date 10 days 10 days Room temperature only (Do not refrigerate)

📋 Description ~1 min read ▾

11 DESCRIPTION Insulin lispro is a rapid-acting insulin analog produced by recombinant DNA technology utilizing a non-pathogenic laboratory strain of Escherichia coli . Insulin lispro differs from human insulin in that the amino acid proline at position B28 is replaced by lysine and the lysine in position B29 is replaced by proline. Chemically, it is Lys(B28), Pro(B29) human insulin analog and has the empirical formula C 257 H 383 N 65 O 77 S 6 and a molecular weight of 5.808 kDa, both identical to that of human insulin.

Insulin Lispro Protamine and Insulin Lispro Mix75/25 is a mixture of 75% insulin lispro protamine, an intermediate-acting human insulin analog, and 25% insulin lispro, a rapid-acting human insulin analog. Insulin lispro protamine suspension is a suspension of crystals produced from combining insulin lispro and protamine sulfate under appropriate conditions for crystal formation. Insulin lispro has the following primary structure: Insulin Lispro Protamine and Insulin Lispro Mix75/25 injectable suspension is a white and cloudy, sterile suspension for subcutaneous use.

Each mL of Insulin Lispro Protamine and Insulin Lispro Mix75/25 contains 100 units of insulin lispro; dibasic sodium phosphate (2.0 mg), glycerin (16 mg), metacresol (1.76 mg), phenol (0.715 mg), protamine sulfate (0.28 mg), zinc oxide content adjusted to provide zinc ion (0.025 mg), and Water for Injection, USP. The pH is 7.0 to 7.8. Sodium hydroxide and/or hydrochloric acid is added during manufacture to adjust the pH.

Primary Structure

💬 Information for Patients ~2 min read ▾

17 PATIENT COUNSELING INFORMATION Advise the patient to read the FDA-approved patient labeling (Patient Information and Instructions for Use). Never Share an Insulin Lispro Protamine and Insulin Lispro Mix75/25 KwikPen Between Patients Advise patients using Insulin Lispro Protamine and Insulin Lispro Mix75/25 KwikPens not to share needles or KwikPens with another person. Sharing poses a risk for transmission of blood-borne pathogens [see Warnings and Precautions ( 5.1 )] .

Hyperglycemia or Hypoglycemia Inform patients that hypoglycemia is the most common adverse reaction with insulin. Instruct patients on self-management procedures including glucose monitoring, proper injection technique, and management of hypoglycemia and hyperglycemia, especially at initiation of Insulin Lispro Protamine and Insulin Lispro Mix75/25 therapy. Instruct patients 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.

Instruct patients on the management of hypoglycemia [see Warnings and Precautions ( 5.3 )]. Inform patients that their ability to concentrate and react may be impaired as a result of hypoglycemia. Advise patients who have frequent hypoglycemia or reduced or absent warning signs of hypoglycemia to use caution when driving or operating machinery.

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 [see Warnings and Precautions ( 5.2 )] . Hypoglycemia due to Medication Errors Instruct patients to always check the insulin label before each injection to avoid mix-ups between insulin products [see Warnings and Precautions ( 5.4 )] . Hypersensitivity Reactions Advise patients that hypersensitivity reactions have occurred with Insulin Lispro Protamine and Insulin Lispro Mix75/25.

Inform patients on the symptoms of hypersensitivity reactions and to seek medical attention if they occur [see Warnings and Precautions ( 5.5 )] . Manufactured by: Eli Lilly and Company Indianapolis, IN 46285, USA US License Number 1891 Humalog ® Mix75/25™ and KwikPen ® are trademarks of Eli Lilly and Company. Copyright © 1999, 2023, Eli Lilly and Company.

All rights reserved. ILPILIS7525-0002-USPI-20230721

🧬 Pharmacokinetics ~1 min read ▾

12.3Pharmacokinetics Absorption — Insulin Lispro Protamine and Insulin Lispro Mix75/25 has two phases of absorption. The early phase represents insulin lispro and its distinct characteristics of rapid onset. The late phase represents the prolonged absorption of insulin lispro protamine suspension.

In 31 healthy subjects given subcutaneous doses (0.3 unit/kg) of Insulin Lispro Protamine and Insulin Lispro Mix75/25, the median peak serum concentration was 60 minutes (range: 30 minutes to 4 hours) after dosing. Identical results were found in patients with type 1 diabetes. The rapid absorption characteristics of HUMALOG are maintained with Insulin Lispro Protamine and Insulin Lispro Mix75/25.

Insulin Lispro Protamine and Insulin Lispro Mix75/25 has a more rapid absorption than HUMULIN 70/30, which has been confirmed in patients with type 1 diabetes. Metabolism — Human metabolism studies of Insulin Lispro Protamine and Insulin Lispro Mix75/25 have not been conducted. However, studies in animals indicate that the metabolism of HUMALOG, the rapid-acting component of Insulin Lispro Protamine and Insulin Lispro Mix75/25, is identical to that of regular human insulin.

Elimination — Because of the absorption-rate limited kinetics of insulin mixtures, a true half-life cannot be accurately estimated from the terminal slope of the concentration versus time curve. Specific Populations The effects of age, race, obesity, pregnancy, smoking, or renal or hepatic impairment on the pharmacokinetics of Insulin Lispro Protamine and Insulin Lispro Mix75/25 have not been studied. Gender — Pharmacokinetic and pharmacodynamic comparisons between men and women administered Insulin Lispro Protamine and Insulin Lispro Mix75/25 showed no gender differences.

🧬 Pharmacodynamics ~1 min read ▾

12.2Pharmacodynamics In a glucose clamp study performed in 30 healthy subjects, the onset of action and glucose-lowering activity of HUMALOG, HUMALOG ® Mix50/50™, Insulin Lispro Protamine and Insulin Lispro Mix75/25, and insulin lispro protamine suspension (ILPS) were compared ( see Figure 1 ). Graphs of mean glucose infusion rate versus time showed a distinct insulin activity profile for each formulation. The rapid onset of glucose-lowering activity characteristic of HUMALOG was maintained in Insulin Lispro Protamine and Insulin Lispro Mix75/25.

The median maximum pharmacologic effect of Insulin Lispro Protamine and Insulin Lispro Mix75/25 after administration of a 0.3 unit/kg dose to healthy subjects occurred at approximately 2 hours (range: 1-6 hours); glucose lowering activity was detectable for a median of 22 hours (range: 13 to 22 hours), which was the end of the clamp. In separate glucose clamp studies performed in healthy subjects, pharmacodynamics of Insulin Lispro Protamine and Insulin Lispro Mix75/25 and HUMULIN ® 70/30 were assessed and are presented in Figure 2 .

Insulin Lispro Protamine and Insulin Lispro Mix75/25 has a duration of activity similar to that of HUMULIN 70/30. Figures 1 and 2 should be considered only as representative examples since the time course of action of insulin and insulin analogs, may vary in different individuals or within the same individual. Figure 1: Mean Insulin Activity Versus Time Profiles After Injection of 0.3 units/kg of HUMALOG, HUMALOG Mix50/50, Insulin Lispro Protamine and Insulin Lispro Mix75/25, or Insulin Lispro Protamine Suspension (ILPS) in 30 Healthy Subjects.

Figure 2: Mean Insulin Activity Versus Time Profiles After Injection of 0.3 units/kg of Insulin Lispro Protamine and Insulin Lispro Mix75/25 or HUMULIN 70/30 in Healthy Subjects. Figure Figure

🧪 Nonclinical Toxicology 213 words ▾

13 NONCLINICAL TOXICOLOGY

13.1Carcinogenesis, Mutagenesis, Impairment of Fertility Standard 2-year carcinogenicity studies in animals have not been performed with Insulin Lispro Protamine and Insulin Lispro Mix75/25. In Fischer 344 rats, a 12-month repeat-dose toxicity study was conducted with insulin lispro (a component of Insulin Lispro Protamine and Insulin Lispro Mix75/25) at subcutaneous doses of 20 and 200 units/kg/day (approximately 3 and 32 times the human subcutaneous dose of 1 unit insulin lispro/kg/day, based on units/body surface area).

Insulin lispro did not produce important target organ toxicity including mammary tumors at any dose. Insulin lispro was not mutagenic in the following genetic toxicity assays: bacterial mutation, unscheduled DNA synthesis, mouse lymphoma, chromosomal aberration and micronucleus assays. Male fertility was not compromised when male rats given subcutaneous insulin lispro injections of 5 and 20 units/kg/day (0.8 and 3 times the human subcutaneous dose of 1 unit insulin lispro/kg/day, based on units/body surface area) for 6 months were mated with untreated female rats.

In a combined fertility, perinatal, and postnatal study in male and female rats given 1, 5, and 20 units/kg/day subcutaneously (0.2, 0.8, and 3 times the human subcutaneous dose of 1 unit insulin lispro/kg/day, based on units/body surface area), mating and fertility were not adversely affected in either gender at any dose.

📄 Carcinogenesis, Mutagenesis, Impairment of Fertility 210 words ▾

13.1Carcinogenesis, Mutagenesis, Impairment of Fertility Standard 2-year carcinogenicity studies in animals have not been performed with Insulin Lispro Protamine and Insulin Lispro Mix75/25. In Fischer 344 rats, a 12-month repeat-dose toxicity study was conducted with insulin lispro (a component of Insulin Lispro Protamine and Insulin Lispro Mix75/25) at subcutaneous doses of 20 and 200 units/kg/day (approximately 3 and 32 times the human subcutaneous dose of 1 unit insulin lispro/kg/day, based on units/body surface area).

Insulin lispro did not produce important target organ toxicity including mammary tumors at any dose. Insulin lispro was not mutagenic in the following genetic toxicity assays: bacterial mutation, unscheduled DNA synthesis, mouse lymphoma, chromosomal aberration and micronucleus assays. Male fertility was not compromised when male rats given subcutaneous insulin lispro injections of 5 and 20 units/kg/day (0.8 and 3 times the human subcutaneous dose of 1 unit insulin lispro/kg/day, based on units/body surface area) for 6 months were mated with untreated female rats.

In a combined fertility, perinatal, and postnatal study in male and female rats given 1, 5, and 20 units/kg/day subcutaneously (0.2, 0.8, and 3 times the human subcutaneous dose of 1 unit insulin lispro/kg/day, based on units/body surface area), mating and fertility were not adversely affected in either gender at any dose.

📄 Patient Package Insert ~3 min read ▾

PATIENT PACKAGE INSERT This Patient Information has been approved by the U.S. Food and Drug Administration. Revised: 07/2023 PATIENT INFORMATION Insulin Lispro Protamine and Insulin Lispro [IHN-soo-lihn LIYS-proh] injectable suspension, for subcutaneous use This product is HUMALOG ® Mix75/25™ (insulin lispro protamine and insulin lispro).

Do not share your Insulin Lispro Protamine and Insulin Lispro Mix75/25 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 Insulin Lispro Protamine and Insulin Lispro Mix75/25?

Insulin Lispro Protamine and Insulin Lispro Mix75/25 is a man-made insulin that is used to control high blood sugar in adults with diabetes mellitus. It is not known if Insulin Lispro Protamine and Insulin Lispro Mix75/25 is safe and effective in children under 18 years of age. Who should not take Insulin Lispro Protamine and Insulin Lispro Mix75/25?

Do not take Insulin Lispro Protamine and Insulin Lispro Mix75/25 if you: are having an episode of low blood sugar (hypoglycemia). have an allergy to Insulin Lispro Protamine and Insulin Lispro Mix75/25 or any of the ingredients in Insulin Lispro Protamine and Insulin Lispro Mix75/25. See the end of this Patient Information leaflet for a complete list of ingredients in Insulin Lispro Protamine and Insulin Lispro Mix75/25. What should I tell my healthcare provider before taking Insulin Lispro Protamine and Insulin Lispro Mix75/25?

Before taking Insulin Lispro Protamine and Insulin Lispro Mix75/25, tell your healthcare provider about all of your medical conditions, including if you: have liver or kidney problems. take any 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 Insulin Lispro Protamine and Insulin Lispro Mix75/25. are pregnant or plan 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 breastfeeding or plan to breastfeed.

Talk with your healthcare provider about the best way to feed your baby while taking Insulin Lispro Protamine and Insulin Lispro Mix75/25. Tell your healthcare provider about all the medicines you take, including prescription and over-the-counter medicines, vitamins, and herbal supplements. Before you start taking Insulin Lispro Protamine and Insulin Lispro Mix75/25, talk to your healthcare provider about low blood sugar and how to manage it.

How should I take Insulin Lispro Protamine and Insulin Lispro Mix75/25? Read the Instructions for Use that comes with your Insulin Lispro Protamine and Insulin Lispro Mix75/25. Take Insulin Lispro Protamine and Insulin Lispro Mix75/25 exactly as your healthcare provider tells you to.

Your healthcare provider should tell you how much Insulin Lispro Protamine and Insulin Lispro Mix75/25 to take and when to take it. Insulin Lispro Protamine and Insulin Lispro Mix75/25 starts acting fast. Inject Insulin Lispro Protamine and Insulin Lispro Mix75/25 within 15 minutes before you eat a meal.

Know the type, strength, and amount of insulin you take. Do not change the type or amount of insulin you take unless your healthcare provider tells you to. The amount of insulin and the best time for you to take your insulin may need to change if you take different types of insulin.

Check your insulin label each time you give your injection to make sure you are taking the correct insulin. Inject Insulin Lispro Protamine and Insulin Lispro Mix75/25 under the skin (subcutaneously) of your stomach area (abdomen), buttocks, upper legs or upper arms. Do not inject Insulin Lispro Protamine and Insulin Lispro Mix75/25 into your vein (intravenously) or use in an insulin infusion pump.

Change (rotate) your injection sites within the area you choose with each dose to reduce your risk of getting lipody… [Excerpted — this section continues on DailyMed.]

📖 Instructions for Use ~3 min read ▾

KWIKPEN INSTRUCTIONS FOR USE INSTRUCTIONS FOR USE Insulin Lispro Protamine and Insulin Lispro [IHN-soo-lihn LIYS-proh] Mix75/25™ KwikPen ® injectable suspension, for subcutaneous use 3 mL single-patient-use pen (100 units per mL) This product is HUMALOG ® Mix75/25™ (insulin lispro protamine and insulin lispro). Read this Instructions for Use before you start taking Insulin Lispro Protamine and Insulin Lispro Mix75/25 and each time you get another KwikPen. There may be new information.

This information does not take the place of talking to your healthcare provider about your medical condition or your treatment. Do not share your Insulin Lispro Protamine and Insulin Lispro Mix75/25 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.

Insulin Lispro Protamine and Insulin Lispro Mix75/25 KwikPen (“Pen”) is a disposable single-patient-use prefilled pen containing 300 units of Insulin Lispro Protamine and Insulin Lispro Mix75/25. You can give yourself more than 1 dose from the Pen. By turning the Dose Knob, you can dial doses from 1 to 60 units in 1 unit increments.

If your dose is more than 60 units, you will need to give yourself more than 1 injection. The Plunger only moves a little with each injection, and you may not notice that it moves. The Plunger will only reach the end of the cartridge when you have used all 300 units in the Pen.

People who are blind or have vision problems should not use this Pen without help from a person trained to use the Pen. How to recognize your Insulin Lispro Protamine and Insulin Lispro Mix75/25 KwikPen Pen color: Dark blue Dose Knob: Dark blue Labels: White label with yellow stripe Supplies you will need to give your injection Insulin Lispro Protamine and Insulin Lispro Mix75/25 KwikPen KwikPen compatible Needle (Becton, Dickinson and Company Pen Needles recommended) Alcohol swab Gauze Preparing your Pen Wash your hands with soap and water.

Check your Pen to make sure you are taking the right type of insulin. This is especially important if you use more than 1 type of insulin. Always use a new needle for each injection to help prevent infections and blocked needles.

Do not reuse or share your needles with other people. You may give other people a serious infection or get a serious infection from them. Step 1: Pull the Pen Cap straight off. - Do not remove the Pen Label.

Wipe the Rubber Seal with an alcohol swab. - Do not attach the Needle before mixing. Step 2: Gently roll the Pen between your hands at least 10 times. Step 3: Move the Pen up and down (invert) at least 10 times.

Mixing by rolling and inverting the Pen is important to make sure you get the right dose. After mixing Insulin Lispro Protamine and Insulin Lispro Mix75/25, inject your dose right away. If you wait to inject your dose, the insulin will need to be mixed again.

Step 4: Check the liquid in the Pen. Insulin Lispro Protamine and Insulin Lispro Mix75/25 should look white and cloudy after mixing. Do not use if it looks clear or has any lumps or particles in it.

Step 5: Select a new Needle. Pull off the Paper Tab from the Outer Needle Shield. Step 6: Push the capped Needle straight onto the Pen and twist the Needle on until it is tight.

Step 7: Pull off the Outer Needle Shield. Do not throw it away. Pull off the Inner Needle Shield and throw it away.

Priming your Pen Prime your Pen before each injection. Priming your Pen means removing the air from the Needle and Cartridge that may collect during normal use and ensures that the Pen is working correctly. If you do not prime before each injection, you may get too much or too little insulin.

Step 8: To prime your Pen, turn the Dose Knob to select 2 units. Step 9: Hold your Pen with the Needle pointing up. Tap the Cartridge Holder gently to collect air bubbles at the top.

Step 10: Continue holding your Pen with Needle pointing up. Push the Dose Knob in until it stops, and “0” is seen in the… [Excerpted — this section continues on DailyMed.]

📄 Package Label / Principal Display Panel 100 words ▾

PACKAGE CARTON – Insulin Lispro Protamine and Insulin Lispro Injectable Suspension KwikPen Mix75/25™ 5ct NDC 0002-8233-05 Insulin Lispro Protamine and Insulin Lispro KwikPen Mix75/25™ Injectable Suspension For Single Patient Use Only Dispense in this sealed carton. Needles not included 100 units per mL (U-100) This device is recommended for use with Becton, Dickinson and Company's insulin pen needles For subcutaneous use only. prefilled insulin delivery device Rx only This product is Humalog Mix75/25. 5 x 3 mL Prefilled Pens Read Insulin Delivery Device Instructions for Use PACKAGE CARTON – INSULIN LISPRO PROTAMINE AND ISULIN LISPRO INJECTABLE SUSPENSION KwikPen Mix75/25 5ct

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
21K
Units reimbursed last 4 qtrs
487.6K
Gross reimbursed last 4 qtrs
$4.99M
Avg / prescription
$237.43
Avg / unit
$10.2438
Latest quarter Q1 2026
4.7KRx
Medicaid pays / mL
$10.2438
gross reimbursed
vs
NADAC / mL
$10.2074
acquisition cost
=
Spread
+$0.0364
+0% 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 ⓘ
31% FFS 69% MCO
Fee-for-service · 6,532 Rx Managed care · 14,504 Rx
State Medicaid map
Alaska: no data reported AK Maine: no data reported ME Washington: 7,155 units · 91.6 per 100k residents WA Idaho: no data reported ID Montana: no data reported MT North Dakota: no data reported ND Minnesota: 630 units · 11.0 per 100k residents MN Wisconsin: 12,321 units · 208 per 100k residents WI Michigan: 17,961 units · 179 per 100k residents MI New York: 59,778 units · 305 per 100k residents NY Vermont: no data reported VT New Hampshire: 2,367 units · 169 per 100k residents NH Oregon: 3,657 units · 86.4 per 100k residents OR Nevada: 2,238 units · 70.1 per 100k residents NV Wyoming: no data reported WY South Dakota: no data reported SD Iowa: 1,632 units · 50.9 per 100k residents IA Illinois: 28,746 units · 229 per 100k residents IL Indiana: 6,363 units · 92.7 per 100k residents IN Ohio: 21,675 units · 184 per 100k residents OH Pennsylvania: 61,188 units · 472 per 100k residents PA New Jersey: 53,910 units · 580 per 100k residents NJ Massachusetts: 21,186 units · 303 per 100k residents MA California: 30,405 units · 78.0 per 100k residents CA Utah: no data reported UT Colorado: 2,163 units · 36.8 per 100k residents CO Nebraska: 225 units · 11.4 per 100k residents NE Missouri: 12,258 units · 198 per 100k residents MO Kentucky: 19,080 units · 422 per 100k residents KY West Virginia: no data reported WV Virginia: 12,168 units · 140 per 100k residents VA Maryland: 9,831 units · 159 per 100k residents MD Connecticut: 14,217 units · 393 per 100k residents CT Rhode Island: 4,836 units · 442 per 100k residents RI Arizona: 14,400 units · 194 per 100k residents AZ New Mexico: 2,418 units · 114 per 100k residents NM Kansas: 1,494 units · 50.8 per 100k residents KS Arkansas: 1,792 units · 58.4 per 100k residents AR Tennessee: 2,958 units · 41.5 per 100k residents TN North Carolina: 8,068 units · 74.5 per 100k residents NC South Carolina: 633 units · 11.8 per 100k residents SC Delaware: 3,306 units · 321 per 100k residents DE Oklahoma: no data reported OK Louisiana: 7,350 units · 161 per 100k residents LA Mississippi: 663 units · 22.6 per 100k residents MS Alabama: no data reported AL Georgia: 4,314 units · 39.1 per 100k residents GA D.C.: 18,855 units · 2,777 per 100k residents DC Hawaii: no data reported HI Texas: 4,308 units · 14.1 per 100k residents TX Florida: 11,025 units · 48.8 per 100k residents FL
Units reimbursed · per 100k residents
11.02,777
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 D.C. 2,777 /100k
2 New Jersey 580 /100k
3 Pennsylvania 472 /100k
4 Rhode Island 442 /100k
5 Kentucky 422 /100k
6 Connecticut 393 /100k
7 Delaware 321 /100k
8 New York 305 /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 Humalog Kwikpen U-100 (matched by generic name) — 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 Humalog Kwikpen U-100. CMS lists 10 products for this generic; we show the highest-spend one. 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
$60.16M
Claims incl. refills
250.5K
Beneficiaries
182.7K
Spend / beneficiary
$329.25
Spend / claim
$240.12
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 Lispro Protamine and Insulin Lispro Injectable Suspension Mix75/25 KwikPen (this brand).

Top reported reactions

Blood Glucose Increased2,063
Hypoglycaemia652
Visual Impairment555
Dyspnoea537
Nausea524
Blood Glucose Decreased412
Acute Kidney Injury396

Reporter sex

12,550 reports
Male · 47%
Female · 53%
Unknown · 0%

Serious outcomes

Hospitalization5,058
Disabling261
Reports over time (by year) — tap or hover for the count & year
2019 2021 2023 2026 1,733 673
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.
← 00002-8228-27 · Eli 00002-8235-05 · 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.