Humalog 75-25 (75-25 Insulin Lispro Suspension and 25 Insulin Lispro Injection)
برای این دارو، اطلاعات عمومی (فارسی) یافت نشد . برای افزودن اطلاعات فارسی به این دارو کلیک نمایید.
Humalog 75-25 (75-25 Insulin Lispro Suspension and 25 Insulin Lispro Injection)

HUMALOG® Mix75/25TM
(75% insulin lispro protamine suspension and 25% insulin lispro) Injection (rDNA ORIGIN)
100 UNITS PER ML (U-100)

DRUG DESCRIPTION

Humalog® Mix75/25 [75% insulin lispro protamine suspension and 25% insulin lispro injection, (rDNA origin)] is a mixture of insulin lispro solution, a rapid-acting blood glucose-lowering agent and insulin lispro protamine suspension, an intermediate-acting blood glucose-lowering agent. Chemically, insulin lispro is Lys(B28), Pro(B29) human insulin analog, created when the amino acids at positions 28 and 29 on the insulin B-chain are reversed. Insulin lispro is synthesized in a special non-pathogenic laboratory strain of Escherichia coli bacteria that has been genetically altered to produce insulin lispro. Insulin lispro protamine suspension (NPL component) 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:

HUMALOG (rDNA ORIGIN) Structural Formula Illustration

Insulin lispro has the empirical formula C257H383N65O77S6 and a molecular weight of 5808, both identical to that of human insulin.

Humalog Mix75/25 vials and Pens contain a sterile suspension of insulin lispro protamine suspension mixed with soluble insulin lispro for use as an injection.

Each milliliter of Humalog Mix75/25 injection contains insulin lispro 100 units, 0.28 mg protamine sulfate, 16 mg glycerin, 3.78 mg dibasic sodium phosphate, 1.76 mg Metacresol, zinc oxide content adjusted to provide 0.025 mg zinc ion, 0.715 mg phenol, and Water for Injection. Humalog Mix75/25 has a pH of 7.0 to 7.8. Hydrochloric acid 10% and/or sodium hydroxide 10% may have been added to adjust pH.

What are the precautions when taking 75-25 insulin lispro suspension and 25 insulin lispro injection (Humalog 75-25)?

Before taking this medication, tell your doctor or pharmacist if you are allergic to it; or to other insulins; or if you have any other allergies. This product may contain inactive ingredients, which can cause allergic reactions or other problems. Talk to your pharmacist for more details.

Before using this medication, tell your doctor or pharmacist your medical history, especially of: kidney disease, liver disease.

Use only the insulin product that your doctor has prescribed for you. Do not change the insulin you use unless your doctor has given you instructions on how to do so. Follow your doctor's instructions carefully. Following a change in insulin, you may need a dosage change. Know the symptoms of low blood sugar and high blood sugar (see Side Effects section). Tell...

Read All Potential Precautions of Humalog 75-25 »

Last reviewed on RxList: 9/13/2007
This monograph has been modified to include the generic and brand name in many instances.

INDICATIONS

Humalog Mix75/25, a mixture of 75% insulin lispro protamine suspension and 25% insulin lispro injection (rDNA origin), is indicated in the treatment of patients with diabetes mellitus for the control of hyperglycemia. Humalog Mix75/25 has a more rapid onset of glucose-lowering activity compared with Humulin 70/30 while having a similar duration of action. This profile is achieved by combining the rapid onset of Humalog with the intermediate action of insulin lispro protamine suspension.

DOSAGE AND ADMINISTRATION

Table 1* :Summary of Pharmacodynamic Properties of Insulin Products (Pooled Cross-Study Comparison)

Insulin Products Dose, U/kg Time of Peak
Activity, Hours
After Dosing
Percent of Total
Activity Occurring in the First 4 Hours
Humalog 0.3 2.4 70%
  (0.8 - 4.3) (49 - 89%)
Humulin R 0.32 4.4 54%
(0.26 - 0.37) (4.0 - 5.5) (38 - 65%)
Humalog Mix75/25 0.3 2.6 35%
  (1.0 - 6.5) (21 - 56%)
Humulin 70/30 0.3 4.4 32%
  (1.5 - 16) (14 - 60%)
Humalog Mix50/50 0.3 2.3 45%
  (0.8 - 4.8) (27 - 69%)
Humulin 50/50 0.3 3.3 44%
  (2.0 - 5.5) (21 - 60%)
NPH 0.32 5.5 14%
(0.27 - 0.40) (3.5 - 9.5) (3.0 - 48%)
NPL component 0.3 5.8 22%
  (1.3 - 18.3) (6.3 - 40%)
* The information supplied in Table 1 indicates when peak insulin activity can be expected and the percent of the total insulin activity occurring during the first 4 hours. The information was derived from 3 separate glucose clamp studies in nondiabetic subjects. Values represent means, with ranges provided in parentheses.

Humalog Mix75/25 is intended only for subcutaneous administration. Humalog Mix75/25 should not be administered intravenously. Dosage regimens of Humalog Mix75/25 will vary among patients and should be determined by the Health Care Professional familiar with the patient's metabolic needs, eating habits, and other lifestyle variables. Humalog has been shown to be equipotent to Regular human insulin on a molar basis. One unit of Humalog has the same glucose-lowering effect as one unit of Regular human insulin, but its effect is more rapid and of shorter duration.

Humalog Mix75/25 has a similar glucose-lowering effect as compared with Humulin 70/30 on a unit for unit basis. The quicker glucose-lowering effect of Humalog is related to the more rapid absorption rate of insulin lispro from subcutaneous tissue. Humalog Mix75/25 starts lowering blood glucose more quickly than Regular human insulin, allowing for convenient dosing immediately before a meal (within 15 minutes). In contrast, mixtures containing Regular human insulin should be given 30 to 60 minutes before a meal.

The rate of insulin absorption and consequently the onset of activity are known to be affected by the site of injection, exercise, and other variables. As with all insulin preparations, the time course of action of Humalog Mix75/25 may vary considerably in different individuals or within the same individual. Patients must be educated to use proper injection techniques.

Humalog Mix75/25 should be inspected visually before use. Humalog Mix75/25 should be used only if it appears uniformly cloudy after mixing. Humalog Mix75/25 should not be used after its expiration date.

HOW SUPPLIED

Humalog Mix75/25 [75% insulin lispro protamine suspension and 25% insulin lispro injection, (rDNA origin)] vials are available in the following package size:

100 units per mL (U-100)

10 mL vials

NDC 0002-7511-01 (VL-7511)

Humalog Mix75/25 [75% insulin lispro protamine suspension and 25% insulin lispro injection, (rDNA origin)] Pen, a disposable insulin delivery device, is available in the following package size:

5 x 3 mL disposable insulin delivery devices

NDC 0002-8794-59 (HP-8794)

Storage

Humalog Mix75/25 should be stored in a refrigerator [2°to 8°C (36°to 46°F)], but not in the freezer. Do not use Humalog Mix75/25 if it has been frozen. Unrefrigerated [below 30°C (86°F)] vials must be used within 28 days or be discarded, even if they still contain Humalog Mix75/25. Unrefrigerated [below 30°C (86°F)] Pens must be used within 10 days or be discarded, even if they still contain Humalog Mix75/25. Protect from direct heat and light. See table below:

  Not In-Use
(Unopened) Room
Temperature [Below
30°C (86°F)]
Not In-Use
(Unopened)
Refrigerated
In-Use (Opened) Room
Temperature [Below
30°C (86°F)]
10 mL Vial 28 days Until expiration date 28 days, refrigerated/room temperature.
3 mL Pen 10 days Until expiration date 10 days. Do no trefrigerate.

Pens manufactured by l Eli Lilly and Company, Indianapolis, IN 46285, USA or Lilly France, F-67640 Fegersheim, France Vials manufactured by : Eli Lilly and Company, Indianapolis, IN 46285, USA or Lilly France, F-67640 Fegersheim, France for Eli Lilly and Company, Indianapolis, IN 46285, USA. FDA rev date: 8/22/2007

Last reviewed on RxList: 9/13/2007
This monograph has been modified to include the generic and brand name in many instances.

SIDE EFFECTS

Clinical studies comparing Humalog Mix75/25 with human insulin mixtures did not demonstrate a difference in frequency of adverse events between the two treatments.

Adverse events commonly associated with human insulin therapy include the following:

Body as a Whole - allergic reactions (see PRECAUTIONS).

Skin and Appendages - injection site reaction, lipodystrophy, pruritus, rash.

Other - hypoglycemia (see WARNINGS and PRECAUTIONS).

Read the Humalog 75-25 (75-25 insulin lispro suspension and 25 insulin lispro injection) Side Effects Center for a complete guide to possible side effects »

DRUG INTERACTIONS

Insulin requirements may be increased by medications with hyperglycemic activity such as corticosteroids, isoniazid, certain lipid-lowering drugs (e.g., niacin), estrogens, oral contraceptives, phenothiazines, and thyroid replacement therapy.

Insulin requirements may be decreased in the presence of drugs with hypoglycemic activity, such as oral antidiabetic agents, salicylates, sulfa antibiotics, certain antidepressants (monoamine oxidase inhibitors), angiotensin-converting-enzyme inhibitors, angiotensin II receptor blocking agents, beta-adrenergic blockers, inhibitors of pancreatic function (e.g., octreotide), and alcohol. Beta-adrenergic blockers may mask the symptoms of hypoglycemia in some patients.

Last reviewed on RxList: 9/13/2007
This monograph has been modified to include the generic and brand name in many instances.

WARNINGS

Humalog differs from Regular human insulin by its rapid onset of action as well as a shorter duration of activity. Therefore, the dose of Humalog Mix75/25 should be given within 15 minutes before a meal.

Hypoglycemia is the most common adverse effect associated with the use of insulins, including Humalog Mix75/25. As with all insulins, the timing of hypoglycemia may differ among various insulin formulations. Glucose monitoring is recommended for all patients with diabetes.

Any change of insulin should be made cautiously and only under medical supervision. Changes in insulin strength, manufacturer, type (e.g., Regular, NPH, analog), species, or method of manufacture may result in the need for a change in dosage.

PRECAUTIONS

General

Hypoglycemia and hypokalemia are among the potential clinical adverse effects associated with the use of all insulins. Because of differences in the action of Humalog Mix75/25 and other insulins, care should be taken in patients in whom such potential side effects might be clinically relevant (e.g., patients who are fasting, have autonomic neuropathy, or are using potassium-lowering drugs or patients taking drugs sensitive to serum potassium level). Lipodystrophy and hypersensitivity are among other potential clinical adverse effects associated with the use of all insulins.

As with all insulin preparations, the time course of Humalog Mix75/25 action may vary in different individuals or at different times in the same individual and is dependent on site of injection, blood supply, temperature, and physical activity.

Adjustment of dosage of any insulin may be necessary if patients change their physical activity or their usual meal plan. Insulin requirements may be altered during illness, emotional disturbances, or other stress.

Hypoglycemia

As with all insulin preparations, hypoglycemic reactions may be associated with the administration of Humalog Mix75/25. Rapid changes in serum glucose concentrations may induce symptoms of hypoglycemia in persons with diabetes, regardless of the glucose value. Early warning symptoms of hypoglycemia may be different or less pronounced under certain conditions, such as long duration of diabetes, diabetic nerve disease, use of medications such as beta-blockers, or intensified diabetes control.

Renal Impairment

As with other insulins, the requirements for Humalog Mix75/25 may be reduced in patients with renal impairment.

Hepatic Impairment

Although impaired hepatic function does not affect the absorption or disposition of Humalog, careful glucose monitoring and dose adjustments of insulin, including Humalog Mix75/25, may be necessary.

Allergy

Local Allergy - As with any insulin therapy, patients may experience redness, swelling, or itching at the site of injection. These minor reactions usually resolve in a few days to a few weeks. In some instances, these reactions may be related to factors other than insulin, such as irritants in the skin cleansing agent or poor injection technique.

Systemic Allergy - Less common, but potentially more serious, is generalized allergy to insulin, which may cause rash (including pruritus) over the whole body, shortness of breath, wheezing, reduction in blood pressure, rapid pulse, or sweating. Severe cases of generalized allergy, including anaphylactic reaction, may be life threatening. Localized reactions and generalized myalgias have been reported with the use of cresol as an injectable excipient.

Antibody Production - In clinical trials, antibodies that cross-react with human insulin and insulin lispro were observed in both human insulin mixtures and insulin lispro mixtures treatment groups.

Information for Patients

Patients should be informed of the potential risks and advantages of Humalog Mix75/25 and alternative therapies. Patients should not mix Humalog Mix75/25 with any other insulin. They should also be informed about the importance of proper insulin storage, injection technique, timing of dosage, adherence to meal planning, regular physical activity, regular blood glucose monitoring, periodic hemoglobin A1c testing, recognition and management of hypo- and hyperglycemia, and periodic assessment for diabetes complications.

Patients should be advised to inform their physician if they are pregnant or intend to become pregnant.

Refer patients to the “INFORMATION FOR THE PATIENT” insert for information on normal appearance, proper resuspension and injection techniques, timing of dosing (within 15 minutes before a meal), storing, and common adverse effects.

For Patients Using Insulin Pen Delivery Devices

Before starting therapy, patients should read the “INFORMATION FOR THE PATIENT” insert that accompanies the drug product and the User Manual that accompanies the delivery device and re-read them each time the prescription is renewed. Patients should be instructed on how to properly use the delivery device, prime the Pen, and properly dispose of needles. Patients should be advised not to share their Pens with others.

Laboratory Tests

As with all insulins, the therapeutic response to Humalog Mix75/25 should be monitored by periodic blood glucose tests. Periodic measurement of hemoglobin A1c is recommended for the monitoring of long-term glycemic control.

Carcinogenesis, Mutagenesis, Impairment of Fertility

Long-term studies in animals have not been performed to evaluate the carcinogenic potential of Humalog, Humalog Mix75/25 or Humalog Mix50/50. Insulin lispro was not mutagenic in a battery of in vitro and in vivo genetic toxicity assays (bacterial mutation tests, unscheduled DNA synthesis, mouse lymphoma assay, chromosomal aberration tests, and a micronucleus test). There is no evidence from animal studies of impairment of fertility induced by insulin lispro.

Pregnancy

Teratogenic Effects

Pregnancy Category B - Reproduction studies with insulin lispro have been performed in pregnant rats and rabbits at parenteral doses up to 4 and 0.3 times, respectively, the average human dose (40 units/day) based on body surface area. The results have revealed no evidence of impaired fertility or harm to the fetus due to insulin lispro. There are, however, no adequate and well-controlled studies with Humalog, Humalog Mix75/25, or Humalog Mix50/50 in pregnant women. Because animal reproduction studies are not always predictive of human response, this drug should be used during pregnancy only if clearly needed.

Nursing Mothers

It is unknown whether insulin lispro is excreted in significant amounts in human milk. Many drugs, including human insulin, are excreted in human milk. For this reason, caution should be exercised when Humalog Mix75/25 is administered to a nursing woman. Patients with diabetes who are lactating may require adjustments in Humalog Mix75/25 dose, meal plan, or both.

Pediatric Use

Safety and effectiveness of Humalog Mix75/25 in patients less than 18 years of age have not been established.

Geriatric Use

Clinical studies of Humalog Mix75/25 did not include sufficient numbers of patients aged 65 and over to determine whether they respond differently than younger patients. In general, dose selection for an elderly patient should take into consideration the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy in this population.

Last reviewed on RxList: 9/13/2007
This monograph has been modified to include the generic and brand name in many instances.

OVERDOSE

Hypoglycemia may occur as a result of an excess of insulin relative to food intake, energy expenditure, or both. 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 intramuscular/subcutaneous glucagon or concentrated intravenous glucose. Sustained carbohydrate intake and observation may be necessary because hypoglycemia may recur after apparent clinical recovery.

CONTRAINDICATIONS

Humalog Mix75/25 is contraindicated during episodes of hypoglycemia and in patients sensitive to insulin lispro or any of the excipients contained in the formulation.

Last reviewed on RxList: 9/13/2007
This monograph has been modified to include the generic and brand name in many instances.

CLINICAL PHARMACOLOGY

Antidiabetic Activity

The primary activity of insulin, including Humalog Mix75/25, is the regulation of glucose metabolism. In addition, all insulins have several anabolic and anti-catabolic actions on many tissues in the body. In muscle and other tissues (except the brain), insulin causes rapid transport of glucose and amino acids intracellularly, promotes anabolism, and inhibits protein catabolism. In the liver, insulin promotes the uptake and storage of glucose in the form of glycogen, inhibits gluconeogenesis, and promotes the conversion of excess glucose into fat.

Insulin lispro, the rapid-acting component of Humalog Mix75/25, has been shown to be equipotent to Regular human insulin on a molar basis. One unit of Humalog® has the same glucose-lowering effect as one unit of Regular human insulin, but its effect is more rapid and of shorter duration. Humalog Mix75/25 has a similar glucose-lowering effect as compared with Humulin® 70/30 on a unit for unit basis.

Pharmacokinetics

Absorption

Studies in nondiabetic subjects and patients with type 1 (insulin-dependent) diabetes demonstrated that Humalog, the rapid-acting component of Humalog Mix75/25, is absorbed faster than Regular human insulin (U-100). In nondiabetic subjects given subcutaneous doses of Humalog ranging from 0.1 to 0.4 U/kg, peak serum concentrations were observed 30 to 90 minutes after dosing. When nondiabetic subjects received equivalent doses of Regular human insulin, peak insulin concentrations occurred between 50 to 120 minutes after dosing. Similar results were seen in patients with type 1 diabetes.

Figure 1: Serum Immunoreactive Insulin (IRI) Concentrations, After Subcutaneous Injection of Humalog Mix75/25 or Humulin 70/30 in Healthy Nondiabetic Subjects.

HUMALOG (rDNA ORIGIN) Figure 1: Serum Immunoreactive Insulin (IRI) Concentrations, 
  After Subcutaneous  Injection of Humalog Mix75/25 or Humulin 70/30 in Healthy Nondiabetic Subjects.  Illustration

Humalog 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 action of insulin lispro protamine suspension. In 30 healthy nondiabetic subjects given subcutaneous doses (0.3 U/kg) of Humalog Mix75/25, peak serum concentrations were observed 30 to 240 minutes (median, 60 minutes) after dosing (see Figure 1). Identical results were found in patients with type 1 diabetes. The rapid absorption characteristics of Humalog are maintained with Humalog Mix75/25 (see Figure 1).

Figure 1 represents serum insulin concentration versus time curves of Humalog Mix75/25 and Humulin 70/30. Humalog Mix75/25 has a more rapid absorption than Humulin 70/30, which has been confirmed in patients with type 1 diabetes.

Distribution

Radiolabeled distribution studies of Humalog Mix75/25 have not been conducted. However, the volume of distribution following injection of Humalog is identical to that of Regular human insulin, with a range of 0.26 to 0.36 L/kg.

Metabolism

Human metabolism studies of Humalog Mix75/25 have not been conducted. Studies in animals indicate that the metabolism of Humalog, the rapid-acting component of Humalog Mix75/25, is identical to that of Regular human insulin.

Elimination

Humalog Mix75/25 has two absorption phases, a rapid and a prolonged phase, representative of the insulin lispro and insulin lispro protamine suspension components of the mixture. As with other intermediate-acting insulins, a meaningful terminal phase half-life cannot be calculated after administration of Humalog Mix75/25 because of the prolonged insulin lispro protamine suspension absorption.

Pharmacodynamics

Studies in nondiabetic subjects and patients with diabetes demonstrated that Humalog has a more rapid onset of glucose-lowering activity, an earlier peak for glucose-lowering, and a shorter duration of glucose-lowering activity than Regular human insulin. The early onset of activity of Humalog Mix75/25 is directly related to the rapid absorption of Humalog. The time course of action of insulin and insulin analogs, such as Humalog (and hence Humalog Mix75/25), may vary considerably in different individuals or within the same individual. The parameters of Humalog Mix75/25 activity (time of onset, peak time, and duration) as presented in Figures 2 and 3 should be considered only as general guidelines. 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 General under PRECAUTIONS).

In a glucose clamp study performed in 30 nondiabetic subjects, the onset of action and glucose-lowering activity of Humalog, Humalog® Mix50/50™ , Humalog Mix75/25, and insulin lispro protamine suspension (NPL component) were compared (see Figure 2). 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 Humalog Mix75/25.

In separate glucose clamp studies performed in nondiabetic subjects, pharmacodynamics of Humalog Mix75/25 and Humulin 70/30 were assessed and are presented in Figure 3. Humalog Mix75/25 has a duration of activity similar to that of Humulin 70/30.

Figure 2: Insulin Activity After Injection of Humalog, Humalog Mix50/50, Humalog Mix75/25, or Insulin Lispro Protamine Suspension (NPL Component) in 30 Nondiabetic Subjects.

Insulin Activity After Injection of Humalog, Humalog Mix50/50, Humalog Mix75/25, or Insulin Lispro Protamine Suspension (NPL Component) in 30 Nondiabetic Subjects - Illustration

Figure 3: Insulin Activity After Injection of Humalog Mix75/25 and Humulin 70/30 in Nondiabetic Subjects.

Insulin Activity After Injection of Humalog Mix75/25 and Humulin 70/30 in Nondiabetic Subjects- Illustration

Figures 2 and 3 represent insulin activity profiles as measured by glucose clamp studies in healthy nondiabetic subjects.

Figure 2 shows the time activity profiles of Humalog, Humalog Mix50/50, Humalog Mix75/25, and insulin lispro protamine suspension (NPL component).

Figure 3 is a comparison of the time activity profiles of Humalog Mix75/25 (see Figure 3a) and of Humulin 70/30 (see Figure 3b) from two different studies.

Special Populations

Age and Gender

Information on the effect of age on the pharmacokinetics of Humalog Mix75/25 is unavailable. Pharmacokinetic and pharmacodynamic comparisons between men and women administered Humalog Mix75/25 showed no gender differences. In large Humalog clinical trials, sub-group analysis based on age and gender demonstrated that differences between Humalog and Regular human insulin in postprandial glucose parameters are maintained across sub-groups.

Smoking

The effect of smoking on the pharmacokinetics and pharmacodynamics of Humalog Mix75/25 has not been studied.

Pregnancy

The effect of pregnancy on the pharmacokinetics and pharmacodynamics of Humalog Mix75/25 has not been studied.

Obesity

The effect of obesity and/or subcutaneous fat thickness on the pharmacokinetics and pharmacodynamics of Humalog Mix75/25 has not been studied. In large clinical trials, which included patients with Body Mass Index up to and including 35 kg/m², no consistent differences were observed between Humalog and Humulin® R with respect to postprandial glucose parameters.

Renal Impairment

The effect of renal impairment on the pharmacokinetics and pharmacodynamics of Humalog Mix75/25 has not been studied. In a study of 25 patients with type 2 diabetes and a wide range of renal function, the pharmacokinetic differences between Humalog and Regular human insulin were generally maintained. However, the sensitivity of the patients to insulin did change, with an increased response to insulin as the renal function declined. Careful glucose monitoring and dose reductions of insulin, including Humalog Mix75/25, may be necessary in patients with renal dysfunction.

Hepatic Impairment

Some studies with human insulin have shown increased circulating levels of insulin in patients with hepatic failure. The effect of hepatic impairment on the pharmacokinetics and pharmacodynamics of Humalog Mix75/25 has not been studied. However, in a study of 22 patients with type 2 diabetes, impaired hepatic function did not affect the subcutaneous absorption or general disposition of Humalog when compared with patients with no history of hepatic dysfunction. In that study, Humalog maintained its more rapid absorption and elimination when compared with Regular human insulin. Careful glucose monitoring and dose adjustments of insulin, including Humalog Mix75/25, may be necessary in patients with hepatic dysfunction.

Last reviewed on RxList: 9/13/2007
This monograph has been modified to include the generic and brand name in many instances.

PATIENT INFORMATION

10 mL Vial (1000 Units per vial)
HUMALOG® Mix75/25™
(75% insulin lispro protamine suspension and 25% insulin lispro injection (rDNA ORIGIN))
100 UNITS PER ML (U-100)

WARNINGS

THIS LILLY HUMAN INSULIN ANALOG MIXTURE IS DIFFERENT FROM OTHER INSULIN MIXTURES IN THAT ITS ONSET OF ACTION IS VERY QUICK. THE QUICK ONSET OF ACTION MEANS THAT YOU SHOULD TAKE YOUR DOSE OF HUMALOG® Mix75/25 [75% INSULIN LISPRO PROTAMINE SUSPENSION AND 25% INSULIN LISPRO INJECTION, (rDNA ORIGIN)] WITHIN 15 MINUTES BEFORE YOU EAT.

ANY CHANGE OF INSULIN SHOULD BE MADE CAUTIOUSLY AND ONLY UNDER MEDICAL SUPERVISION. CHANGES IN STRENGTH, MANUFACTURER, TYPE (E.G., REGULAR, NPH, ANALOG), SPECIES, OR METHOD OF MANUFACTURE MAY RESULT IN THE NEED FOR A CHANGE IN THE TIMING OR DOSAGE OF HUMALOG Mix75/25.

PATIENTS TAKING HUMALOG Mix75/25 MAY REQUIRE A CHANGE IN DOSAGE FROM THAT USED WITH OTHER INSULINS. IF AN ADJUSTMENT IS NEEDED, IT MAY OCCUR WITH THE FIRST DOSE OR DURING THE FIRST SEVERAL WEEKS OR MONTHS.

DIABETES

Insulin is a hormone produced by the pancreas, a large gland that lies near the stomach. This hormone is necessary for the body's correct use of food, especially sugar. Diabetes occurs when the pancreas does not make enough insulin to meet your body's needs.

To control your diabetes, your doctor has prescribed injections of insulin products to keep your blood glucose at a near-normal level. You have been instructed to test your blood and/or your urine regularly for glucose. Studies have shown that some chronic complications of diabetes such as eye disease, kidney disease, and nerve disease can be significantly reduced if the blood sugar is maintained as close to normal as possible. The American Diabetes Association recommends that if your pre-meal glucose levels are consistently above 130 mg/dL, bedtime glucose levels are consistently above 160 mg/dL or your hemoglobin A1c (HbA1c) is more than 7%, you should talk to your doctor. A change in your diabetes therapy may be needed. If your blood tests consistently show below-normal glucose levels, you should also let your doctor know. Proper control of your diabetes requires close and constant cooperation with your doctor. Despite diabetes, you can lead an active and healthy life if you eat a balanced diet, exercise regularly, and take your insulin injections as prescribed by your doctor.

Always keep an extra supply of insulin as well as a spare syringe and needle on hand. Always wear diabetic identification so that appropriate treatment can be given if complications occur away from home.

HUMALOG Mix75/25

Description

Humalog [insulin lispro injection, USP (rDNA origin)] is made by a special non-disease-producing laboratory strain of Escherichia coli bacteria that has been genetically altered to produce this human insulin analog. Humalog Mix75/25 is a mixture of 75% insulin lispro protamine suspension and 25% insulin lispro injection, (rDNA origin). It is a longer-acting insulin combined with the more rapid onset of action of Humalog. The duration of activity is similar to that of Humulin® 70/30 and may last up to 24 hours following injection. The time course of Humalog Mix75/25 action, like that of other insulins, may vary in different individuals or at different times in the same individual, based on dose, site of injection, blood supply, temperature, and physical activity. Humalog Mix75/25 is a sterile suspension and is for subcutaneous injection only. It should not be used intravenously. The concentration of Humalog Mix75/25 is 100 units/mL (U-100).

Humalog Mix75/25 starts lowering blood glucose more quickly than Regular human insulin, allowing for convenient dosing immediately before a meal (within 15 minutes). In contrast, mixtures containing Regular human insulin should be given 30 to 60 minutes before a meal.

Identification

Insulin lispro injection, USP (rDNA origin) from Eli Lilly and Company, has the trademark Humalog. Your doctor has prescribed the type of insulin that he/she believes is best for you.

DO NOT USE ANY OTHER INSULIN EXCEPT ON YOUR DOCTOR'S ADVICE AND DIRECTION. YOU SHOULD NOT MIX HUMALOG Mix75/25 WITH ANOTHER INSULIN.

Always check the carton and bottle label of the Humalog Mix75/25 you receive from your pharmacy to make sure it is the same as prescribed by your doctor.

Always check the appearance of your bottle of Humalog Mix75/25 before withdrawing each dose. Before each injection the Humalog Mix75/25 bottle must be carefully shaken or rotated several times to completely mix the insulin. Humalog Mix75/25 suspension should look uniformly cloudy or milky after mixing. If not, repeat the above step until contents are mixed.

Do not use Humalog Mix75/25:

  • if the insulin substance (the white material) remains at the bottom of the bottle after mixing or
  • if there are clumps in the insulin after mixing, or
  • if solid white particles stick to the bottom or wall of the bottle, giving a frosted appearance.

If you see anything unusual in the appearance of Humalog Mix75/25 suspension in your bottle or notice your insulin requirements changing, talk to your doctor.

Storage

Not in-use (unopened): Humalog Mix75/25 bottles not in-use should be stored in a refrigerator, but not in the freezer.

In-use (opened): The Humalog Mix75/25 bottle you are currently using can be kept unrefrigerated, for up to 28 days, as long as it is kept at room temperature [below 86°F (30°C)] away from direct heat and light. The Humalog Mix75/25 bottle you are currently using must be discarded 28 days after the first use, even if it still contains Humalog Mix75/25.

Do not use Humalog Mix75/25 after the expiration date stamped on the label or if it has been frozen.

INSTRUCTIONS FOR INSULIN VIAL USE

Use with Syringes

NEVER SHARE NEEDLES AND SYRINGES.

Correct Syringe Type

Doses of insulin are measured in units. U-100 insulin contains 100 units/mL (1 mL=1 cc). With Humalog Mix75/25, it is important to use a syringe that is marked for U-100 insulin preparations. Failure to use the proper syringe can lead to a mistake in dosage, causing serious problems for you, such as a blood glucose level that is too low or too high.

Syringe Use

To help avoid contamination and possible infection, follow these instructions exactly.

Disposable syringes and needles should be used only once and then discarded by placing the used needle in a puncture-resistant disposable container. Properly dispose of the puncture-resistant container as directed by your Health Care Professional.

Preparing the Dose
  1. Wash your hands.
  2. Carefully shake or rotate the bottle of insulin several times to completely mix the insulin.
  3. Inspect the insulin. Humalog Mix75/25 suspension should look uniformly cloudy or milky. Do not use Humalog Mix75/25 if you notice anything unusual in its appearance.
  4. If using a new Humalog Mix75/25 bottle, flip off the plastic protective cap, but do not remove the stopper. Wipe the top of the bottle with an alcohol swab.
  5. Draw an amount of air into the syringe that is equal to the Humalog Mix75/25 dose. Put the needle through rubber top of the Humalog Mix75/25 bottle and inject the air into the bottle.
  6. Turn the Humalog Mix75/25 bottle and syringe upside down. Hold the bottle and syringe firmly in one hand and shake gently.
  7. Making sure the tip of the needle is in the Humalog Mix75/25 suspension, withdraw the correct dose of Humalog Mix75/25 into the syringe.
  8. Before removing the needle from the Humalog Mix75/25 bottle, check the syringe for air bubbles. If bubbles are present, hold the syringe straight up and tap its side until the bubbles float to the top. Push the bubbles out with the plunger and then withdraw the correct dose.
  9. Remove the needle from the bottle and lay the syringe down so that the needle does not touch anything.
Injection Instructions
  1. To avoid tissue damage, choose a site for each injection that is at least ½ inch from the previous injection site. The usual sites of injection are abdomen, thighs, and arms.
  2. Cleanse the skin with alcohol where the injection is to be made.
  3. With one hand, stabilize the skin by spreading it or pinching up a large area.
  4. Insert the needle as instructed by your doctor.
  5. Push the plunger in as far as it will go.
  6. Pull the needle out and apply gentle pressure over the injection site for several seconds. Do not rub the area.
  7. Place the used needle in a puncture-resistant disposable container and properly dispose of the puncture-resistant container as directed by your Health Care Professional.

Dosage

Your doctor has told you which insulin to use, how much, and when and how often to inject it. Because each patient's diabetes is different, this schedule has been individualized for you. Your usual dose of Humalog Mix75/25 may be affected by changes in your diet, activity, or work schedule. Carefully follow your doctor's instructions to allow for these changes. Other things that may affect your Humalog Mix75/25 dose are:

Illness

Illness, especially with nausea and vomiting, may cause your insulin requirements to change. Even if you are not eating, you will still require insulin. You and your doctor should establish a sick day plan for you to use in case of illness. When you are sick, test your blood glucose frequently. If instructed by your doctor, test your ketones and report the results to your doctor.

Pregnancy

Good control of diabetes is especially important for you and your unborn baby. Pregnancy may make managing your diabetes more difficult. If you are planning to have a baby, are pregnant, or are nursing a baby, talk to your doctor. Humalog Mix75/25 has not been tested in pregnant or nursing women.

Medication

Insulin requirements may be increased if you are taking other drugs with blood-glucose-raising activity, such as oral contraceptives, corticosteroids, or thyroid replacement therapy. Insulin requirements may be reduced in the presence of drugs with blood-glucose-lowering activity, such as oral antidiabetic agents, salicylates (for example, aspirin), sulfa antibiotics, alcohol, certain antidepressants and some kidney and blood pressure medicines. Your Health Care Professional may be aware of these and other medications that may affect your diabetes control. Therefore, always discuss any medications you are taking with your doctor.

Exercise

Exercise may lower your body's need for insulin during and for some time after the physical activity. Exercise may also speed up the effect of an insulin dose, especially if the exercise involves the area of injection site (for example, the leg should not be used for injection just prior to running). Discuss with your doctor how you should adjust your insulin regimen to accommodate exercise.

Travel

When traveling across more than 2 time zones, you should talk to your doctor concerning adjustments in your insulin schedule.

COMMON PROBLEMS OF DIABETES

Hypoglycemia (Low Blood Sugar)

Hypoglycemia (too little glucose in the blood) is one of the most frequent adverse events experienced by insulin users. It can be brought about by:

  1. Missing or delaying meals.
  2. Taking too much insulin.
  3. Exercising or working more than usual.
  4. An infection or illness associated with diarrhea or vomiting.
  5. A change in the body's need for insulin.
  6. Diseases of the adrenal, pituitary, or thyroid gland, or progression of kidney or liver disease.
  7. Interactions with other drugs that lower blood glucose, such as oral antidiabetic agents, salicylates (for example, aspirin), sulfa antibiotics, certain antidepressants and some kidney and blood pressure medicines.
  8. Consumption of alcoholic beverages.

Symptoms of mild to moderate hypoglycemia may occur suddenly and can include:

• sweating
• dizziness
• palpitation
• tremor
• hunger
• restlessness
• tingling in the hands, feet, lips, or tongue
• lightheadedness
• inability to concentrate
• headache

• drowsiness
• sleep disturbances
• anxiety
• blurred vision
• slurred speech
• depressed mood
• irritability
• abnormal behavior
• unsteady movement
• personality changes
Signs of severe hypoglycemia can include:
  • • disorientation
    • unconsciousness
• seizures
• death

Therefore, it is important that assistance be obtained immediately.

Early warning symptoms of hypoglycemia may be different or less pronounced under certain conditions, such as long duration of diabetes, diabetic nerve disease, use of medications such as beta-blockers, changing insulin preparations, or intensified control (3 or more injections per day) of diabetes. A few patients who have experienced hypoglycemic reactions after transfer from animal-source insulin to human insulin have reported that the early warning symptoms of hypoglycemia were less pronounced or different from those experienced with their previous insulin.

Without recognition of early warning symptoms, you may not be able to take steps to avoid more serious hypoglycemia. Be alert for all of the various types of symptoms that may indicate hypoglycemia. Patients who experience hypoglycemia without early warning symptoms should monitor their blood glucose frequently, especially prior to activities such as driving. If the blood glucose is below your normal fasting glucose, you should consider eating or drinking sugar-containing foods to treat your hypoglycemia.

Mild to moderate hypoglycemia may be treated by eating foods or drinks that contain sugar. Patients should always carry a quick source of sugar, such as hard candy or glucose tablets. More severe hypoglycemia may require the assistance of another person. Patients who are unable to take sugar orally or who are unconscious require an injection of glucagon or should be treated with intravenous administration of glucose at a medical facility.

You should learn to recognize your own symptoms of hypoglycemia. If you are uncertain about these symptoms, you should monitor your blood glucose frequently to help you learn to recognize the symptoms that you experience with hypoglycemia.

If you have frequent episodes of hypoglycemia or experience difficulty in recognizing the symptoms, you should talk to your doctor to discuss possible changes in therapy, meal plans, and/or exercise programs to help you avoid hypoglycemia.

Hyperglycemia (High Blood Sugar) and Diabetic Ketoacidosis (DKA)

Hyperglycemia (too much glucose in the blood) may develop if your body has too little insulin. Hyperglycemia can be brought about by any of the following:

  1. Omitting your insulin or taking less than your doctor has prescribed.
  2. Eating significantly more than your meal plan suggests.
  3. Developing a fever, infection, or other significant stressful situation.

In patients with type 1 or insulin-dependent diabetes, prolonged hyperglycemia can result in DKA (a life-threatening emergency). The first symptoms of DKA usually come on gradually, over a period of hours or days, and include a drowsy feeling, flushed face, thirst, loss of appetite, and fruity odor on the breath. With DKA, blood and urine tests show large amounts of glucose and ketones. Heavy breathing and a rapid pulse are more severe symptoms. If uncorrected, prolonged hyperglycemia or DKA can lead to nausea, vomiting, stomach pain, dehydration, loss of consciousness, or death. Therefore, it is important that you obtain medical assistance immediately.

Lipodystrophy

Rarely, administration of insulin subcutaneously can result in lipoatrophy (seen as an apparent depression of the skin) or lipohypertrophy (seen as a raised area of the skin). If you notice either of these conditions, talk to your doctor. A change in your injection technique may help alleviate the problem.

Allergy

Local Allergy - Patients occasionally experience redness, swelling, and itching at the site of injection. This condition, called local allergy, usually clears up in a few days to a few weeks. In some instances, this condition may be related to factors other than insulin, such as irritants in the skin cleansing agent or poor injection technique. If you have local reactions, talk to your doctor.

Systemic Allergy - Less common, but potentially more serious, is generalized allergy to insulin, which may cause rash over the whole body, shortness of breath, wheezing, reduction in blood pressure, fast pulse, or sweating. Severe cases of generalized allergy may be life threatening. If you think you are having a generalized allergic reaction, call your doctor immediately.

ADDITIONAL INFORMATION

Information about diabetes may be obtained from your diabetes educator.

Additional information about diabetes and Humalog Mix75/25 can be obtained by calling The Lilly Answers Center at 1-800-LillyRx (1-800-545-5979) or by visiting www.LillyDiabetes.com.

Vials manufactured by : Eli Lilly and Company, Indianapolis, IN 46285, USA or Lilly France, F-67640 Fegersheim, France for Eli Lilly and Company, Indianapolis, IN 46285, USA

INFORMATION FOR THE PATIENT
3 ML DISPOSABLE INSULIN DELIVERY DEVICE
HUMALOG® Mix75/25™ Pen
75% INSULIN LISPRO PROTAMINE SUSPENSION AND 25% INSULIN LISPRO INJECTION (rDNA ORIGIN)
100 UNITS PER ML (U-100)

WARNINGS

THIS LILLY HUMAN INSULIN ANALOG MIXTURE IS DIFFERENT FROM OTHER INSULIN MIXTURES IN THAT ITS ONSET OF ACTION IS VERY QUICK. THE QUICK ONSET OF ACTION MEANS THAT YOU SHOULD TAKE YOUR DOSE OF HUMALOG® Mix75/25TM (75-25 insulin lispro suspension and 25 insulin lispro injection) [75% INSULIN LISPRO PROTAMINE SUSPENSION AND 25% INSULIN LISPRO INJECTION, (rDNA ORIGIN)] WITHIN 15 MINUTES BEFORE YOU EAT.

ANY CHANGE OF INSULIN SHOULD BE MADE CAUTIOUSLY AND ONLY UNDER MEDICAL SUPERVISION. CHANGES IN STRENGTH, MANUFACTURER, TYPE (E.G., REGULAR, NPH, ANALOG), SPECIES, OR METHOD OF MANUFACTURE MAY RESULT IN THE NEED FOR A CHANGE IN THE TIMING OR DOSAGE OF HUMALOG Mix75/25.

PATIENTS TAKING HUMALOG Mix75/25 MAY REQUIRE A CHANGE IN DOSAGE FROM THAT USED WITH OTHER INSULINS. IF AN ADJUSTMENT IS NEEDED, IT MAY OCCUR WITH THE FIRST DOSE OR DURING THE FIRST SEVERAL WEEKS OR MONTHS.

TO OBTAIN AN ACCURATE DOSE, CAREFULLY READ AND FOLLOW THE INSULIN DELIVERY DEVICE USER MANUAL AND THIS “INFORMATION FOR THE PATIENT” INSERT BEFORE USING THIS PRODUCT.

BEFORE EACH INJECTION, YOU SHOULD PRIME THE PEN, A NECESSARY STEP TO MAKE SURE THE PEN IS READY TO DOSE. PRIMING THE PEN IS IMPORTANT TO CONFIRM THAT INSULIN COMES OUT WHEN YOU PUSH THE INJECTION BUTTON AND TO REMOVE AIR THAT MAY COLLECT IN THE INSULIN CARTRIDGE DURING NORMAL USE. IF YOU DO NOT PRIME, YOU MAY RECEIVE TOO MUCH OR TOO LITTLE INSULIN (see also INSTRUCTIONS FOR INSULIN PEN USE section).

DIABETES

Insulin is a hormone produced by the pancreas, a large gland that lies near the stomach. This hormone is necessary for the body's correct use of food, especially sugar. Diabetes occurs when the pancreas does not make enough insulin to meet your body's needs.

To control your diabetes, your doctor has prescribed injections of insulin products to keep your blood glucose at a near-normal level. You have been instructed to test your blood and/or your urine regularly for glucose. Studies have shown that some chronic complications of diabetes such as eye disease, kidney disease, and nerve disease can be significantly reduced if the blood sugar is maintained as close to normal as possible. The American Diabetes Association recommends that if your pre-meal glucose levels are consistently above 130 mg/dL, bedtime glucose levels are consistently above 160 mg/dL or your hemoglobin A1c (HbA1c) is more than 7%, you should talk to your doctor. A change in your diabetes therapy may be needed. If your blood tests consistently show below-normal glucose levels, you should also let your doctor know. Proper control of your diabetes requires close and constant cooperation with your doctor. Despite diabetes, you can lead an active and healthy life if you eat a balanced diet, exercise regularly, and take your insulin injections as prescribed by your doctor.

Always keep an extra supply of insulin as well as a spare syringe and needle on hand. Always wear diabetic identification so that appropriate treatment can be given if complications occur away from home.

HUMALOG Mix75/25

DESCRIPTION

Humalog [insulin lispro injection, USP (rDNA origin)] is made by a special non-disease-producing laboratory strain of Escherichia coli bacteria that has been genetically altered to produce this human insulin analog. Humalog Mix75/25 is a mixture of 75% insulin lispro protamine suspension and 25% insulin lispro injection (rDNA origin). It is a longer-acting insulin combined with the more rapid onset of action of Humalog. The duration of activity is similar to that of Humulin® 70/30 and may last up to 24 hours following injection. The time course of Humalog Mix75/25 action, like that of other insulins, may vary in different individuals or at different times in the same individual, based on dose, site of injection, blood supply, temperature, and physical activity. Humalog Mix75/25 is a sterile suspension and is for subcutaneous injection only. It should not be used intravenously. The concentration of Humalog Mix75/25 is 100 units/mL (U-100).

Humalog Mix75/25 starts lowering blood glucose more quickly than Regular human insulin, allowing for convenient dosing immediately before a meal (within 15 minutes). In contrast, mixtures containing Regular human insulin should be given 30 to 60 minutes before a meal.

Identification

Insulin lispro injection, USP (rDNA origin) from Eli Lilly and Company, has the trademark Humalog. Your doctor has prescribed the type of insulin that he/she believes is best for you.

DO NOT USE ANY OTHER INSULIN EXCEPT ON YOUR DOCTOR'S ADVICE AND DIRECTION. YOU SHOULD NOT MIX HUMALOG Mix75/25 WITH ANOTHER INSULIN.

The Humalog Mix75/25 Pen is available in boxes of 5 disposable insulin delivery devices (“insulin Pens”). The Humalog Mix75/25 Pen is not designed to allow any other insulin to be mixed in its cartridge, or for the cartridge to be removed.

Always check the carton and Pen label of the Humalog Mix75/25 you receive from your pharmacy to make sure it is the same as prescribed by your doctor.

Always check the appearance of Humalog Mix75/25 suspension in your insulin Pen before using. A cartridge of Humalog Mix75/25 contains a small glass bead to assist in mixing. Roll the Pen between the palms 10 times (see Figure 1). Holding the Pen by one end, invert it 180°slowly 10 times to allow the small glass bead to travel the full length of the cartridge with each inversion (see Figure 2).

Checking the appearance of Humalog Mix75/25 suspension in your insulin Pen before using- illustration

Humalog Mix75/25 suspension should look uniformly cloudy or milky after mixing. If not, repeat the above steps until contents are mixed. Pens containing Humalog Mix75/25 suspension should be examined frequently.

Do not use Humalog Mix75/25:

  • if the insulin substance (the white material) remains visibly separated from the liquid after mixing or
  • if there are clumps in the insulin after mixing, or
  • if solid white particles stick to the bottom or wall of the cartridge, giving a frosted appearance.

If you see anything unusual in the appearance of the Humalog Mix75/25 suspension in your Pen or notice your insulin requirements changing, talk to your doctor.

Never attempt to remove the cartridge from the Humalog Mix75/25 Pen. Inspect the cartridge through the clear cartridge holder.

Storage

Not in-use (unopened): Humalog Mix75/25 Pens not in-use should be stored in a refrigerator, but not in the freezer.

In-use (opened): Humalog Mix75/25 Pens in-use should NOT be refrigerated but should be kept at room temperature [below 86°F (30°C)] away from direct heat and light. The Humalog Mix75/25 Pen you are currently using must be discarded 10 days after the first use, even if it still contains Humalog Mix75/25.

Do not use Humalog Mix75/25 after the expiration date stamped on the label or if it has been frozen.

INSTRUCTIONS FOR INSULIN PEN USE

It is important to read, understand, and follow the instructions in the Insulin Delivery Device User Manual before using. Failure to follow instructions may result in getting too much or too little insulin. The needle must be changed and the Pen must be primed before each injection to make sure the Pen is ready to dose. Performing these steps before each injection is important to confirm that insulin comes out when you push the injection button, and to remove air that may collect in the insulin cartridge during normal use.

Every time you inject:

  • Use a new needle.
  • Prime to make sure the Pen is ready to dose.
  • Make sure you got your full dose.

NEVER SHARE INSULIN PENS, CARTRIDGES, OR NEEDLES. PREPARING FOR INJECTION

  1. Wash your hands.
  2. To avoid tissue damage, choose a site for each injection that is at least ½ inch from the previous injection site. The usual sites of injection are abdomen, thighs, and arms.
  3. Follow the instructions in your Insulin Delivery Device User Manual to prepare for injection.
  4. After injecting the dose, pull the needle out and apply gentle pressure over the injection site for several seconds. Do not rub the area.
  5. After the injection, remove the needle from the Humalog Mix75/25 Pen. Do not reuse needles.
  6. Place the used needle in a puncture-resistant disposable container and properly dispose of the puncture-resistant container as directed by your Health Care Professional.

DOSAGE

Your doctor has told you which insulin to use, how much, and when and how often to inject it. Because each patient's diabetes is different, this schedule has been individualized for you. Your usual dose of Humalog Mix75/25 may be affected by changes in your diet, activity, or work schedule. Carefully follow your doctor's instructions to allow for these changes. Other things that may affect your Humalog Mix75/25 dose are:

Illness

Illness, especially with nausea and vomiting, may cause your insulin requirements to change. Even if you are not eating, you will still require insulin. You and your doctor should establish a sick day plan for you to use in case of illness. When you are sick, test your blood glucose frequently. If instructed by your doctor, test your ketones and report the results to your doctor.

Pregnancy

Good control of diabetes is especially important for you and your unborn baby. Pregnancy may make managing your diabetes more difficult. If you are planning to have a baby, are pregnant, or are nursing a baby, talk to your doctor. Humalog Mix75/25 has not been tested in pregnant or nursing women.

Medication

Insulin requirements may be increased if you are taking other drugs with blood-glucose-raising activity, such as oral contraceptives, corticosteroids, or thyroid replacement therapy. Insulin requirements may be reduced in the presence of drugs with blood-glucose-lowering activity, such as oral antidiabetic agents, salicylates (for example, aspirin), sulfa antibiotics, alcohol, certain antidepressants and some kidney and blood pressure medicines. Your Health Care Professional may be aware of these and other medications that may affect your diabetes control. Therefore, always discuss any medications you are taking with your doctor.

Exercise

Exercise may lower your body's need for insulin during and for some time after the physical activity. Exercise may also speed up the effect of an insulin dose, especially if the exercise involves the area of injection site (for example, the leg should not be used for injection just prior to running). Discuss with your doctor how you should adjust your insulin regimen to accommodate exercise.

Travel

When traveling across more than 2 time zones, you should talk to your doctor concerning adjustments in your insulin schedule.

COMMON PROBLEMS OF DIABETES

Hypoglycemia (Low Blood Sugar)

Hypoglycemia (too little glucose in the blood) is one of the most frequent adverse events experienced by insulin users. It can be brought about by:

  1. Missing or delaying meals.
  2. Taking too much insulin.
  3. Exercising or working more than usual.
  4. An infection or illness associated with diarrhea or vomiting.
  5. A change in the body's need for insulin.
  6. Diseases of the adrenal, pituitary, or thyroid gland, or progression of kidney or liver disease.
  7. Interactions with other drugs that lower blood glucose, such as oral antidiabetic agents, salicylates (for example, aspirin), sulfa antibiotics, certain antidepressants and some kidney and blood pressure medicines.
  8. Consumption of alcoholic beverages.

Symptoms of mild to moderate hypoglycemia may occur suddenly and can include:

• sweating
• dizziness
• palpitation
• tremor
• hunger
• restlessness
• tingling in the hands, feet, lips, or tongue
• lightheadedness
• inability to concentrate
• headache
Signs of severe hypoglycemia can include:
• drowsiness
• sleep disturbances
• anxiety
• blurred vision
• slurred speech
• depressed mood
• irritability
• abnormal behavior
• unsteady movement
• personality changes
Signs of severe hypoglycemia can include:
• disorientation
• unconsciousness
• seizures
• death

Therefore, it is important that assistance be obtained immediately.

Early warning symptoms of hypoglycemia may be different or less pronounced under certain conditions, such as long duration of diabetes, diabetic nerve disease, use of medications such as beta-blockers, changing insulin preparations, or intensified control (3 or more injections per day) of diabetes. A few patients who have experienced hypoglycemic reactions after transfer from animal-source insulin to human insulin have reported that the early warning symptoms of hypoglycemia were less pronounced or different from those experienced with their previous insulin.

Without recognition of early warning symptoms, you may not be able to take steps to avoid more serious hypoglycemia. Be alert for all of the various types of symptoms that may indicate hypoglycemia. Patients who experience hypoglycemia without early warning symptoms should monitor their blood glucose frequently, especially prior to activities such as driving. If the blood glucose is below your normal fasting glucose, you should consider eating or drinking sugar-containing foods to treat your hypoglycemia.

Mild to moderate hypoglycemia may be treated by eating foods or drinks that contain sugar. Patients should always carry a quick source of sugar, such as hard candy or glucose tablets. More severe hypoglycemia may require the assistance of another person. Patients who are unable to take sugar orally or who are unconscious require an injection of glucagon or should be treated with intravenous administration of glucose at a medical facility.

You should learn to recognize your own symptoms of hypoglycemia. If you are uncertain about these symptoms, you should monitor your blood glucose frequently to help you learn to recognize the symptoms that you experience with hypoglycemia.

If you have frequent episodes of hypoglycemia or experience difficulty in recognizing the symptoms, you should talk to your doctor to discuss possible changes in therapy, meal plans, and/or exercise programs to help you avoid hypoglycemia.

Hyperglycemia (High Blood Sugar) and Diabetic Ketoacidosis (DKA)

Hyperglycemia (too much glucose in the blood) may develop if your body has too little insulin. Hyperglycemia can be brought about by any of the following:

Omitting your insulin or taking less than your doctor has prescribed.

Eating significantly more than your meal plan suggests.

Developing a fever, infection, or other significant stressful situation.

In patients with type 1 or insulin-dependent diabetes, prolonged hyperglycemia can result in DKA (a life-threatening emergency). The first symptoms of DKA usually come on gradually, over a period of hours or days, and include a drowsy feeling, flushed face, thirst, loss of appetite, and fruity odor on the breath. With DKA, blood and urine tests show large amounts of glucose and ketones. Heavy breathing and a rapid pulse are more severe symptoms. If uncorrected, prolonged hyperglycemia or DKA can lead to nausea, vomiting, stomach pain, dehydration, loss of consciousness, or death. Therefore, it is important that you obtain medical assistance immediately.

Lipodystrophy

Rarely, administration of insulin subcutaneously can result in lipoatrophy (seen as an apparent depression of the skin) or lipohypertrophy (seen as a raised area of the skin). If you notice either of these conditions, talk to your doctor. A change in your injection technique may help alleviate the problem.

Allergy

Local Allergy - Patients occasionally experience redness, swelling, and itching at the site of injection. This condition, called local allergy, usually clears up in a few days to a few weeks. In some instances, this condition may be related to factors other than insulin, such as irritants in the skin cleansing agent or poor injection technique. If you have local reactions, talk to your doctor.

Systemic Allergy - Less common, but potentially more serious, is generalized allergy to insulin, which may cause rash over the whole body, shortness of breath, wheezing, reduction in blood pressure, fast pulse, or sweating. Severe cases of generalized allergy may be life threatening. If you think you are having a generalized allergic reaction, call your doctor immediately.

ADDITIONAL INFORMATION

Information about diabetes may be obtained from your diabetes educator.

Additional information about diabetes and Humalog Mix75/25 can be obtained by calling The Lilly Answers Center at 1-800-LillyRx (1-800-545-5979) or by visiting www.LillyDiabetes.com.

Last reviewed on RxList: 9/13/2007
This monograph has been modified to include the generic and brand name in many instances.

>

PATIENT INFORMATION

10 mL Vial (1000 Units per vial)
HUMALOG® Mix75/25™
(75% insulin lispro protamine suspension and 25% insulin lispro injection (rDNA ORIGIN))
100 UNITS PER ML (U-100)

WARNINGS

THIS LILLY HUMAN INSULIN ANALOG MIXTURE IS DIFFERENT FROM OTHER INSULIN MIXTURES IN THAT ITS ONSET OF ACTION IS VERY QUICK. THE QUICK ONSET OF ACTION MEANS THAT YOU SHOULD TAKE YOUR DOSE OF HUMALOG® Mix75/25 [75% INSULIN LISPRO PROTAMINE SUSPENSION AND 25% INSULIN LISPRO INJECTION, (rDNA ORIGIN)] WITHIN 15 MINUTES BEFORE YOU EAT.

ANY CHANGE OF INSULIN SHOULD BE MADE CAUTIOUSLY AND ONLY UNDER MEDICAL SUPERVISION. CHANGES IN STRENGTH, MANUFACTURER, TYPE (E.G., REGULAR, NPH, ANALOG), SPECIES, OR METHOD OF MANUFACTURE MAY RESULT IN THE NEED FOR A CHANGE IN THE TIMING OR DOSAGE OF HUMALOG Mix75/25.

PATIENTS TAKING HUMALOG Mix75/25 MAY REQUIRE A CHANGE IN DOSAGE FROM THAT USED WITH OTHER INSULINS. IF AN ADJUSTMENT IS NEEDED, IT MAY OCCUR WITH THE FIRST DOSE OR DURING THE FIRST SEVERAL WEEKS OR MONTHS.

DIABETES

Insulin is a hormone produced by the pancreas, a large gland that lies near the stomach. This hormone is necessary for the body's correct use of food, especially sugar. Diabetes occurs when the pancreas does not make enough insulin to meet your body's needs.

To control your diabetes, your doctor has prescribed injections of insulin products to keep your blood glucose at a near-normal level. You have been instructed to test your blood and/or your urine regularly for glucose. Studies have shown that some chronic complications of diabetes such as eye disease, kidney disease, and nerve disease can be significantly reduced if the blood sugar is maintained as close to normal as possible. The American Diabetes Association recommends that if your pre-meal glucose levels are consistently above 130 mg/dL, bedtime glucose levels are consistently above 160 mg/dL or your hemoglobin A1c (HbA1c) is more than 7%, you should talk to your doctor. A change in your diabetes therapy may be needed. If your blood tests consistently show below-normal glucose levels, you should also let your doctor know. Proper control of your diabetes requires close and constant cooperation with your doctor. Despite diabetes, you can lead an active and healthy life if you eat a balanced diet, exercise regularly, and take your insulin injections as prescribed by your doctor.

Always keep an extra supply of insulin as well as a spare syringe and needle on hand. Always wear diabetic identification so that appropriate treatment can be given if complications occur away from home.

HUMALOG Mix75/25

Description

Humalog [insulin lispro injection, USP (rDNA origin)] is made by a special non-disease-producing laboratory strain of Escherichia coli bacteria that has been genetically altered to produce this human insulin analog. Humalog Mix75/25 is a mixture of 75% insulin lispro protamine suspension and 25% insulin lispro injection, (rDNA origin). It is a longer-acting insulin combined with the more rapid onset of action of Humalog. The duration of activity is similar to that of Humulin® 70/30 and may last up to 24 hours following injection. The time course of Humalog Mix75/25 action, like that of other insulins, may vary in different individuals or at different times in the same individual, based on dose, site of injection, blood supply, temperature, and physical activity. Humalog Mix75/25 is a sterile suspension and is for subcutaneous injection only. It should not be used intravenously. The concentration of Humalog Mix75/25 is 100 units/mL (U-100).

Humalog Mix75/25 starts lowering blood glucose more quickly than Regular human insulin, allowing for convenient dosing immediately before a meal (within 15 minutes). In contrast, mixtures containing Regular human insulin should be given 30 to 60 minutes before a meal.

Identification

Insulin lispro injection, USP (rDNA origin) from Eli Lilly and Company, has the trademark Humalog. Your doctor has prescribed the type of insulin that he/she believes is best for you.

DO NOT USE ANY OTHER INSULIN EXCEPT ON YOUR DOCTOR'S ADVICE AND DIRECTION. YOU SHOULD NOT MIX HUMALOG Mix75/25 WITH ANOTHER INSULIN.

Always check the carton and bottle label of the Humalog Mix75/25 you receive from your pharmacy to make sure it is the same as prescribed by your doctor.

Always check the appearance of your bottle of Humalog Mix75/25 before withdrawing each dose. Before each injection the Humalog Mix75/25 bottle must be carefully shaken or rotated several times to completely mix the insulin. Humalog Mix75/25 suspension should look uniformly cloudy or milky after mixing. If not, repeat the above step until contents are mixed.

Do not use Humalog Mix75/25:

  • if the insulin substance (the white material) remains at the bottom of the bottle after mixing or
  • if there are clumps in the insulin after mixing, or
  • if solid white particles stick to the bottom or wall of the bottle, giving a frosted appearance.

If you see anything unusual in the appearance of Humalog Mix75/25 suspension in your bottle or notice your insulin requirements changing, talk to your doctor.

Storage

Not in-use (unopened): Humalog Mix75/25 bottles not in-use should be stored in a refrigerator, but not in the freezer.

In-use (opened): The Humalog Mix75/25 bottle you are currently using can be kept unrefrigerated, for up to 28 days, as long as it is kept at room temperature [below 86°F (30°C)] away from direct heat and light. The Humalog Mix75/25 bottle you are currently using must be discarded 28 days after the first use, even if it still contains Humalog Mix75/25.

Do not use Humalog Mix75/25 after the expiration date stamped on the label or if it has been frozen.

INSTRUCTIONS FOR INSULIN VIAL USE

Use with Syringes

NEVER SHARE NEEDLES AND SYRINGES.

Correct Syringe Type

Doses of insulin are measured in units. U-100 insulin contains 100 units/mL (1 mL=1 cc). With Humalog Mix75/25, it is important to use a syringe that is marked for U-100 insulin preparations. Failure to use the proper syringe can lead to a mistake in dosage, causing serious problems for you, such as a blood glucose level that is too low or too high.

Syringe Use

To help avoid contamination and possible infection, follow these instructions exactly.

Disposable syringes and needles should be used only once and then discarded by placing the used needle in a puncture-resistant disposable container. Properly dispose of the puncture-resistant container as directed by your Health Care Professional.

Preparing the Dose
  1. Wash your hands.
  2. Carefully shake or rotate the bottle of insulin several times to completely mix the insulin.
  3. Inspect the insulin. Humalog Mix75/25 suspension should look uniformly cloudy or milky. Do not use Humalog Mix75/25 if you notice anything unusual in its appearance.
  4. If using a new Humalog Mix75/25 bottle, flip off the plastic protective cap, but do not remove the stopper. Wipe the top of the bottle with an alcohol swab.
  5. Draw an amount of air into the syringe that is equal to the Humalog Mix75/25 dose. Put the needle through rubber top of the Humalog Mix75/25 bottle and inject the air into the bottle.
  6. Turn the Humalog Mix75/25 bottle and syringe upside down. Hold the bottle and syringe firmly in one hand and shake gently.
  7. Making sure the tip of the needle is in the Humalog Mix75/25 suspension, withdraw the correct dose of Humalog Mix75/25 into the syringe.
  8. Before removing the needle from the Humalog Mix75/25 bottle, check the syringe for air bubbles. If bubbles are present, hold the syringe straight up and tap its side until the bubbles float to the top. Push the bubbles out with the plunger and then withdraw the correct dose.
  9. Remove the needle from the bottle and lay the syringe down so that the needle does not touch anything.
Injection Instructions
  1. To avoid tissue damage, choose a site for each injection that is at least ½ inch from the previous injection site. The usual sites of injection are abdomen, thighs, and arms.
  2. Cleanse the skin with alcohol where the injection is to be made.
  3. With one hand, stabilize the skin by spreading it or pinching up a large area.
  4. Insert the needle as instructed by your doctor.
  5. Push the plunger in as far as it will go.
  6. Pull the needle out and apply gentle pressure over the injection site for several seconds. Do not rub the area.
  7. Place the used needle in a puncture-resistant disposable container and properly dispose of the puncture-resistant container as directed by your Health Care Professional.

Dosage

Your doctor has told you which insulin to use, how much, and when and how often to inject it. Because each patient's diabetes is different, this schedule has been individualized for you. Your usual dose of Humalog Mix75/25 may be affected by changes in your diet, activity, or work schedule. Carefully follow your doctor's instructions to allow for these changes. Other things that may affect your Humalog Mix75/25 dose are:

Illness

Illness, especially with nausea and vomiting, may cause your insulin requirements to change. Even if you are not eating, you will still require insulin. You and your doctor should establish a sick day plan for you to use in case of illness. When you are sick, test your blood glucose frequently. If instructed by your doctor, test your ketones and report the results to your doctor.

Pregnancy

Good control of diabetes is especially important for you and your unborn baby. Pregnancy may make managing your diabetes more difficult. If you are planning to have a baby, are pregnant, or are nursing a baby, talk to your doctor. Humalog Mix75/25 has not been tested in pregnant or nursing women.

Medication

Insulin requirements may be increased if you are taking other drugs with blood-glucose-raising activity, such as oral contraceptives, corticosteroids, or thyroid replacement therapy. Insulin requirements may be reduced in the presence of drugs with blood-glucose-lowering activity, such as oral antidiabetic agents, salicylates (for example, aspirin), sulfa antibiotics, alcohol, certain antidepressants and some kidney and blood pressure medicines. Your Health Care Professional may be aware of these and other medications that may affect your diabetes control. Therefore, always discuss any medications you are taking with your doctor.

Exercise

Exercise may lower your body's need for insulin during and for some time after the physical activity. Exercise may also speed up the effect of an insulin dose, especially if the exercise involves the area of injection site (for example, the leg should not be used for injection just prior to running). Discuss with your doctor how you should adjust your insulin regimen to accommodate exercise.

Travel

When traveling across more than 2 time zones, you should talk to your doctor concerning adjustments in your insulin schedule.

COMMON PROBLEMS OF DIABETES

Hypoglycemia (Low Blood Sugar)

Hypoglycemia (too little glucose in the blood) is one of the most frequent adverse events experienced by insulin users. It can be brought about by:

  1. Missing or delaying meals.
  2. Taking too much insulin.
  3. Exercising or working more than usual.
  4. An infection or illness associated with diarrhea or vomiting.
  5. A change in the body's need for insulin.
  6. Diseases of the adrenal, pituitary, or thyroid gland, or progression of kidney or liver disease.
  7. Interactions with other drugs that lower blood glucose, such as oral antidiabetic agents, salicylates (for example, aspirin), sulfa antibiotics, certain antidepressants and some kidney and blood pressure medicines.
  8. Consumption of alcoholic beverages.

Symptoms of mild to moderate hypoglycemia may occur suddenly and can include:

• sweating
• dizziness
• palpitation
• tremor
• hunger
• restlessness
• tingling in the hands, feet, lips, or tongue
• lightheadedness
• inability to concentrate
• headache

• drowsiness
• sleep disturbances
• anxiety
• blurred vision
• slurred speech
• depressed mood
• irritability
• abnormal behavior
• unsteady movement
• personality changes
Signs of severe hypoglycemia can include:
  • • disorientation
    • unconsciousness
• seizures
• death

Therefore, it is important that assistance be obtained immediately.

Early warning symptoms of hypoglycemia may be different or less pronounced under certain conditions, such as long duration of diabetes, diabetic nerve disease, use of medications such as beta-blockers, changing insulin preparations, or intensified control (3 or more injections per day) of diabetes. A few patients who have experienced hypoglycemic reactions after transfer from animal-source insulin to human insulin have reported that the early warning symptoms of hypoglycemia were less pronounced or different from those experienced with their previous insulin.

Without recognition of early warning symptoms, you may not be able to take steps to avoid more serious hypoglycemia. Be alert for all of the various types of symptoms that may indicate hypoglycemia. Patients who experience hypoglycemia without early warning symptoms should monitor their blood glucose frequently, especially prior to activities such as driving. If the blood glucose is below your normal fasting glucose, you should consider eating or drinking sugar-containing foods to treat your hypoglycemia.

Mild to moderate hypoglycemia may be treated by eating foods or drinks that contain sugar. Patients should always carry a quick source of sugar, such as hard candy or glucose tablets. More severe hypoglycemia may require the assistance of another person. Patients who are unable to take sugar orally or who are unconscious require an injection of glucagon or should be treated with intravenous administration of glucose at a medical facility.

You should learn to recognize your own symptoms of hypoglycemia. If you are uncertain about these symptoms, you should monitor your blood glucose frequently to help you learn to recognize the symptoms that you experience with hypoglycemia.

If you have frequent episodes of hypoglycemia or experience difficulty in recognizing the symptoms, you should talk to your doctor to discuss possible changes in therapy, meal plans, and/or exercise programs to help you avoid hypoglycemia.

Hyperglycemia (High Blood Sugar) and Diabetic Ketoacidosis (DKA)

Hyperglycemia (too much glucose in the blood) may develop if your body has too little insulin. Hyperglycemia can be brought about by any of the following:

  1. Omitting your insulin or taking less than your doctor has prescribed.
  2. Eating significantly more than your meal plan suggests.
  3. Developing a fever, infection, or other significant stressful situation.

In patients with type 1 or insulin-dependent diabetes, prolonged hyperglycemia can result in DKA (a life-threatening emergency). The first symptoms of DKA usually come on gradually, over a period of hours or days, and include a drowsy feeling, flushed face, thirst, loss of appetite, and fruity odor on the breath. With DKA, blood and urine tests show large amounts of glucose and ketones. Heavy breathing and a rapid pulse are more severe symptoms. If uncorrected, prolonged hyperglycemia or DKA can lead to nausea, vomiting, stomach pain, dehydration, loss of consciousness, or death. Therefore, it is important that you obtain medical assistance immediately.

Lipodystrophy

Rarely, administration of insulin subcutaneously can result in lipoatrophy (seen as an apparent depression of the skin) or lipohypertrophy (seen as a raised area of the skin). If you notice either of these conditions, talk to your doctor. A change in your injection technique may help alleviate the problem.

Allergy

Local Allergy - Patients occasionally experience redness, swelling, and itching at the site of injection. This condition, called local allergy, usually clears up in a few days to a few weeks. In some instances, this condition may be related to factors other than insulin, such as irritants in the skin cleansing agent or poor injection technique. If you have local reactions, talk to your doctor.

Systemic Allergy - Less common, but potentially more serious, is generalized allergy to insulin, which may cause rash over the whole body, shortness of breath, wheezing, reduction in blood pressure, fast pulse, or sweating. Severe cases of generalized allergy may be life threatening. If you think you are having a generalized allergic reaction, call your doctor immediately.

ADDITIONAL INFORMATION

Information about diabetes may be obtained from your diabetes educator.

Additional information about diabetes and Humalog Mix75/25 can be obtained by calling The Lilly Answers Center at 1-800-LillyRx (1-800-545-5979) or by visiting www.LillyDiabetes.com.

Vials manufactured by : Eli Lilly and Company, Indianapolis, IN 46285, USA or Lilly France, F-67640 Fegersheim, France for Eli Lilly and Company, Indianapolis, IN 46285, USA

INFORMATION FOR THE PATIENT
3 ML DISPOSABLE INSULIN DELIVERY DEVICE
HUMALOG® Mix75/25™ Pen
75% INSULIN LISPRO PROTAMINE SUSPENSION AND 25% INSULIN LISPRO INJECTION (rDNA ORIGIN)
100 UNITS PER ML (U-100)

WARNINGS

THIS LILLY HUMAN INSULIN ANALOG MIXTURE IS DIFFERENT FROM OTHER INSULIN MIXTURES IN THAT ITS ONSET OF ACTION IS VERY QUICK. THE QUICK ONSET OF ACTION MEANS THAT YOU SHOULD TAKE YOUR DOSE OF HUMALOG® Mix75/25TM (75-25 insulin lispro suspension and 25 insulin lispro injection) [75% INSULIN LISPRO PROTAMINE SUSPENSION AND 25% INSULIN LISPRO INJECTION, (rDNA ORIGIN)] WITHIN 15 MINUTES BEFORE YOU EAT.

ANY CHANGE OF INSULIN SHOULD BE MADE CAUTIOUSLY AND ONLY UNDER MEDICAL SUPERVISION. CHANGES IN STRENGTH, MANUFACTURER, TYPE (E.G., REGULAR, NPH, ANALOG), SPECIES, OR METHOD OF MANUFACTURE MAY RESULT IN THE NEED FOR A CHANGE IN THE TIMING OR DOSAGE OF HUMALOG Mix75/25.

PATIENTS TAKING HUMALOG Mix75/25 MAY REQUIRE A CHANGE IN DOSAGE FROM THAT USED WITH OTHER INSULINS. IF AN ADJUSTMENT IS NEEDED, IT MAY OCCUR WITH THE FIRST DOSE OR DURING THE FIRST SEVERAL WEEKS OR MONTHS.

TO OBTAIN AN ACCURATE DOSE, CAREFULLY READ AND FOLLOW THE INSULIN DELIVERY DEVICE USER MANUAL AND THIS “INFORMATION FOR THE PATIENT” INSERT BEFORE USING THIS PRODUCT.

BEFORE EACH INJECTION, YOU SHOULD PRIME THE PEN, A NECESSARY STEP TO MAKE SURE THE PEN IS READY TO DOSE. PRIMING THE PEN IS IMPORTANT TO CONFIRM THAT INSULIN COMES OUT WHEN YOU PUSH THE INJECTION BUTTON AND TO REMOVE AIR THAT MAY COLLECT IN THE INSULIN CARTRIDGE DURING NORMAL USE. IF YOU DO NOT PRIME, YOU MAY RECEIVE TOO MUCH OR TOO LITTLE INSULIN (see also INSTRUCTIONS FOR INSULIN PEN USE section).

DIABETES

Insulin is a hormone produced by the pancreas, a large gland that lies near the stomach. This hormone is necessary for the body's correct use of food, especially sugar. Diabetes occurs when the pancreas does not make enough insulin to meet your body's needs.

To control your diabetes, your doctor has prescribed injections of insulin products to keep your blood glucose at a near-normal level. You have been instructed to test your blood and/or your urine regularly for glucose. Studies have shown that some chronic complications of diabetes such as eye disease, kidney disease, and nerve disease can be significantly reduced if the blood sugar is maintained as close to normal as possible. The American Diabetes Association recommends that if your pre-meal glucose levels are consistently above 130 mg/dL, bedtime glucose levels are consistently above 160 mg/dL or your hemoglobin A1c (HbA1c) is more than 7%, you should talk to your doctor. A change in your diabetes therapy may be needed. If your blood tests consistently show below-normal glucose levels, you should also let your doctor know. Proper control of your diabetes requires close and constant cooperation with your doctor. Despite diabetes, you can lead an active and healthy life if you eat a balanced diet, exercise regularly, and take your insulin injections as prescribed by your doctor.

Always keep an extra supply of insulin as well as a spare syringe and needle on hand. Always wear diabetic identification so that appropriate treatment can be given if complications occur away from home.

HUMALOG Mix75/25

DESCRIPTION

Humalog [insulin lispro injection, USP (rDNA origin)] is made by a special non-disease-producing laboratory strain of Escherichia coli bacteria that has been genetically altered to produce this human insulin analog. Humalog Mix75/25 is a mixture of 75% insulin lispro protamine suspension and 25% insulin lispro injection (rDNA origin). It is a longer-acting insulin combined with the more rapid onset of action of Humalog. The duration of activity is similar to that of Humulin® 70/30 and may last up to 24 hours following injection. The time course of Humalog Mix75/25 action, like that of other insulins, may vary in different individuals or at different times in the same individual, based on dose, site of injection, blood supply, temperature, and physical activity. Humalog Mix75/25 is a sterile suspension and is for subcutaneous injection only. It should not be used intravenously. The concentration of Humalog Mix75/25 is 100 units/mL (U-100).

Humalog Mix75/25 starts lowering blood glucose more quickly than Regular human insulin, allowing for convenient dosing immediately before a meal (within 15 minutes). In contrast, mixtures containing Regular human insulin should be given 30 to 60 minutes before a meal.

Identification

Insulin lispro injection, USP (rDNA origin) from Eli Lilly and Company, has the trademark Humalog. Your doctor has prescribed the type of insulin that he/she believes is best for you.

DO NOT USE ANY OTHER INSULIN EXCEPT ON YOUR DOCTOR'S ADVICE AND DIRECTION. YOU SHOULD NOT MIX HUMALOG Mix75/25 WITH ANOTHER INSULIN.

The Humalog Mix75/25 Pen is available in boxes of 5 disposable insulin delivery devices (“insulin Pens”). The Humalog Mix75/25 Pen is not designed to allow any other insulin to be mixed in its cartridge, or for the cartridge to be removed.

Always check the carton and Pen label of the Humalog Mix75/25 you receive from your pharmacy to make sure it is the same as prescribed by your doctor.

Always check the appearance of Humalog Mix75/25 suspension in your insulin Pen before using. A cartridge of Humalog Mix75/25 contains a small glass bead to assist in mixing. Roll the Pen between the palms 10 times (see Figure 1). Holding the Pen by one end, invert it 180°slowly 10 times to allow the small glass bead to travel the full length of the cartridge with each inversion (see Figure 2).

Checking the appearance of Humalog Mix75/25 suspension in your insulin Pen before using- illustration

Humalog Mix75/25 suspension should look uniformly cloudy or milky after mixing. If not, repeat the above steps until contents are mixed. Pens containing Humalog Mix75/25 suspension should be examined frequently.

Do not use Humalog Mix75/25:

  • if the insulin substance (the white material) remains visibly separated from the liquid after mixing or
  • if there are clumps in the insulin after mixing, or
  • if solid white particles stick to the bottom or wall of the cartridge, giving a frosted appearance.

If you see anything unusual in the appearance of the Humalog Mix75/25 suspension in your Pen or notice your insulin requirements changing, talk to your doctor.

Never attempt to remove the cartridge from the Humalog Mix75/25 Pen. Inspect the cartridge through the clear cartridge holder.

Storage

Not in-use (unopened): Humalog Mix75/25 Pens not in-use should be stored in a refrigerator, but not in the freezer.

In-use (opened): Humalog Mix75/25 Pens in-use should NOT be refrigerated but should be kept at room temperature [below 86°F (30°C)] away from direct heat and light. The Humalog Mix75/25 Pen you are currently using must be discarded 10 days after the first use, even if it still contains Humalog Mix75/25.

Do not use Humalog Mix75/25 after the expiration date stamped on the label or if it has been frozen.

INSTRUCTIONS FOR INSULIN PEN USE

It is important to read, understand, and follow the instructions in the Insulin Delivery Device User Manual before using. Failure to follow instructions may result in getting too much or too little insulin. The needle must be changed and the Pen must be primed before each injection to make sure the Pen is ready to dose. Performing these steps before each injection is important to confirm that insulin comes out when you push the injection button, and to remove air that may collect in the insulin cartridge during normal use.

Every time you inject:

  • Use a new needle.
  • Prime to make sure the Pen is ready to dose.
  • Make sure you got your full dose.

NEVER SHARE INSULIN PENS, CARTRIDGES, OR NEEDLES. PREPARING FOR INJECTION

  1. Wash your hands.
  2. To avoid tissue damage, choose a site for each injection that is at least ½ inch from the previous injection site. The usual sites of injection are abdomen, thighs, and arms.
  3. Follow the instructions in your Insulin Delivery Device User Manual to prepare for injection.
  4. After injecting the dose, pull the needle out and apply gentle pressure over the injection site for several seconds. Do not rub the area.
  5. After the injection, remove the needle from the Humalog Mix75/25 Pen. Do not reuse needles.
  6. Place the used needle in a puncture-resistant disposable container and properly dispose of the puncture-resistant container as directed by your Health Care Professional.

DOSAGE

Your doctor has told you which insulin to use, how much, and when and how often to inject it. Because each patient's diabetes is different, this schedule has been individualized for you. Your usual dose of Humalog Mix75/25 may be affected by changes in your diet, activity, or work schedule. Carefully follow your doctor's instructions to allow for these changes. Other things that may affect your Humalog Mix75/25 dose are:

Illness

Illness, especially with nausea and vomiting, may cause your insulin requirements to change. Even if you are not eating, you will still require insulin. You and your doctor should establish a sick day plan for you to use in case of illness. When you are sick, test your blood glucose frequently. If instructed by your doctor, test your ketones and report the results to your doctor.

Pregnancy

Good control of diabetes is especially important for you and your unborn baby. Pregnancy may make managing your diabetes more difficult. If you are planning to have a baby, are pregnant, or are nursing a baby, talk to your doctor. Humalog Mix75/25 has not been tested in pregnant or nursing women.

Medication

Insulin requirements may be increased if you are taking other drugs with blood-glucose-raising activity, such as oral contraceptives, corticosteroids, or thyroid replacement therapy. Insulin requirements may be reduced in the presence of drugs with blood-glucose-lowering activity, such as oral antidiabetic agents, salicylates (for example, aspirin), sulfa antibiotics, alcohol, certain antidepressants and some kidney and blood pressure medicines. Your Health Care Professional may be aware of these and other medications that may affect your diabetes control. Therefore, always discuss any medications you are taking with your doctor.

Exercise

Exercise may lower your body's need for insulin during and for some time after the physical activity. Exercise may also speed up the effect of an insulin dose, especially if the exercise involves the area of injection site (for example, the leg should not be used for injection just prior to running). Discuss with your doctor how you should adjust your insulin regimen to accommodate exercise.

Travel

When traveling across more than 2 time zones, you should talk to your doctor concerning adjustments in your insulin schedule.

COMMON PROBLEMS OF DIABETES

Hypoglycemia (Low Blood Sugar)

Hypoglycemia (too little glucose in the blood) is one of the most frequent adverse events experienced by insulin users. It can be brought about by:

  1. Missing or delaying meals.
  2. Taking too much insulin.
  3. Exercising or working more than usual.
  4. An infection or illness associated with diarrhea or vomiting.
  5. A change in the body's need for insulin.
  6. Diseases of the adrenal, pituitary, or thyroid gland, or progression of kidney or liver disease.
  7. Interactions with other drugs that lower blood glucose, such as oral antidiabetic agents, salicylates (for example, aspirin), sulfa antibiotics, certain antidepressants and some kidney and blood pressure medicines.
  8. Consumption of alcoholic beverages.

Symptoms of mild to moderate hypoglycemia may occur suddenly and can include:

• sweating
• dizziness
• palpitation
• tremor
• hunger
• restlessness
• tingling in the hands, feet, lips, or tongue
• lightheadedness
• inability to concentrate
• headache
Signs of severe hypoglycemia can include:
• drowsiness
• sleep disturbances
• anxiety
• blurred vision
• slurred speech
• depressed mood
• irritability
• abnormal behavior
• unsteady movement
• personality changes
Signs of severe hypoglycemia can include:
• disorientation
• unconsciousness
• seizures
• death

Therefore, it is important that assistance be obtained immediately.

Early warning symptoms of hypoglycemia may be different or less pronounced under certain conditions, such as long duration of diabetes, diabetic nerve disease, use of medications such as beta-blockers, changing insulin preparations, or intensified control (3 or more injections per day) of diabetes. A few patients who have experienced hypoglycemic reactions after transfer from animal-source insulin to human insulin have reported that the early warning symptoms of hypoglycemia were less pronounced or different from those experienced with their previous insulin.

Without recognition of early warning symptoms, you may not be able to take steps to avoid more serious hypoglycemia. Be alert for all of the various types of symptoms that may indicate hypoglycemia. Patients who experience hypoglycemia without early warning symptoms should monitor their blood glucose frequently, especially prior to activities such as driving. If the blood glucose is below your normal fasting glucose, you should consider eating or drinking sugar-containing foods to treat your hypoglycemia.

Mild to moderate hypoglycemia may be treated by eating foods or drinks that contain sugar. Patients should always carry a quick source of sugar, such as hard candy or glucose tablets. More severe hypoglycemia may require the assistance of another person. Patients who are unable to take sugar orally or who are unconscious require an injection of glucagon or should be treated with intravenous administration of glucose at a medical facility.

You should learn to recognize your own symptoms of hypoglycemia. If you are uncertain about these symptoms, you should monitor your blood glucose frequently to help you learn to recognize the symptoms that you experience with hypoglycemia.

If you have frequent episodes of hypoglycemia or experience difficulty in recognizing the symptoms, you should talk to your doctor to discuss possible changes in therapy, meal plans, and/or exercise programs to help you avoid hypoglycemia.

Hyperglycemia (High Blood Sugar) and Diabetic Ketoacidosis (DKA)

Hyperglycemia (too much glucose in the blood) may develop if your body has too little insulin. Hyperglycemia can be brought about by any of the following:

Omitting your insulin or taking less than your doctor has prescribed.

Eating significantly more than your meal plan suggests.

Developing a fever, infection, or other significant stressful situation.

In patients with type 1 or insulin-dependent diabetes, prolonged hyperglycemia can result in DKA (a life-threatening emergency). The first symptoms of DKA usually come on gradually, over a period of hours or days, and include a drowsy feeling, flushed face, thirst, loss of appetite, and fruity odor on the breath. With DKA, blood and urine tests show large amounts of glucose and ketones. Heavy breathing and a rapid pulse are more severe symptoms. If uncorrected, prolonged hyperglycemia or DKA can lead to nausea, vomiting, stomach pain, dehydration, loss of consciousness, or death. Therefore, it is important that you obtain medical assistance immediately.

Lipodystrophy

Rarely, administration of insulin subcutaneously can result in lipoatrophy (seen as an apparent depression of the skin) or lipohypertrophy (seen as a raised area of the skin). If you notice either of these conditions, talk to your doctor. A change in your injection technique may help alleviate the problem.

Allergy

Local Allergy - Patients occasionally experience redness, swelling, and itching at the site of injection. This condition, called local allergy, usually clears up in a few days to a few weeks. In some instances, this condition may be related to factors other than insulin, such as irritants in the skin cleansing agent or poor injection technique. If you have local reactions, talk to your doctor.

Systemic Allergy - Less common, but potentially more serious, is generalized allergy to insulin, which may cause rash over the whole body, shortness of breath, wheezing, reduction in blood pressure, fast pulse, or sweating. Severe cases of generalized allergy may be life threatening. If you think you are having a generalized allergic reaction, call your doctor immediately.

ADDITIONAL INFORMATION

Information about diabetes may be obtained from your diabetes educator.

Additional information about diabetes and Humalog Mix75/25 can be obtained by calling The Lilly Answers Center at 1-800-LillyRx (1-800-545-5979) or by visiting www.LillyDiabetes.com.

Last reviewed on RxList: 9/13/2007
This monograph has been modified to include the generic and brand name in many instances.

Disclaimer

Humalog 75-25 Consumer

IMPORTANT: HOW TO USE THIS INFORMATION: This is a summary and does NOT have all possible information about this product. This information does not assure that this product is safe, effective, or appropriate for you. This information is not individual medical advice and does not substitute for the advice of your health care professional. Always ask your health care professional for complete information about this product and your specific health needs.

INSULIN LISPRO PROTAMINE (NPL)/INSULIN LISPRO - INJECTION

(IN-sue-lin LISS-pro PRO-tah-meen(NPL)/IN-sue-lin LISS-pro)

COMMON BRAND NAME(S): Humalog Mix

USES: Insulin lispro protamine/insulin lispro is used along with a proper diet and exercise program to control high blood sugar. It is used in people with type 1 (insulin-dependent) or type 2 (non-insulin-dependent) diabetes. This product is a combination of two man-made insulins: intermediate-acting insulin lispro protamine and rapid-acting insulin lispro. This combination starts working faster and lasts for a longer time than regular insulin.

Insulin is a natural substance that allows the body to properly use sugar from the diet. It replaces the insulin that your body no longer produces, thereby lowering your blood sugar. Controlling high blood sugar helps prevent kidney damage, blindness, nerve problems, loss of limbs, and sexual function problems. Proper control of diabetes may also lessen your risk of a heart attack or stroke.

HOW TO USE: Read the patient information leaflet provided by your pharmacist before you start using this medication and each time you get a refill. If you have any questions, consult your doctor or pharmacist.

Follow all package directions for proper use/injection/storage of the particular type of device/insulin you are using. Your health care professional will teach you how to properly inject this medication. If any of the information is unclear, consult your doctor or pharmacist.

Do not inject cold insulin because this can be painful. The insulin container you are currently using can be kept at room temperature (see also Storage section). Wash your hands before measuring and injecting insulin. Check the product visually for particles, thickening, or clumps before rolling and turning the container. If any are present, discard that container.

To avoid damaging the insulin, do not shake the container. Gently roll and turn it between your palms at least 10 times. If using a cartridge or prefilled syringe, turn it upside down so that the glass ball moves from one end to the other. Gently mix the insulin until it appears evenly white and cloudy. If it does not appear this way, discard it.

The dosage is based on your medical condition and response to treatment. Measure each dose carefully, and use exactly as prescribed by your doctor. Even small changes in the amount of insulin may have a large effect on your blood sugar levels.

Before injecting each dose, make sure the injection site is clean and dry. Inject this medication under the skin of the abdomen, upper arms, or thighs, usually twice daily, 15 minutes or less before the morning and evening meal or as directed by your doctor. Do not inject into a vein or muscle. Eat promptly after taking this insulin to avoid low blood sugar (see also Side Effects section). Change the location of the injection site daily and do not reuse the same site for two weeks to avoid problem areas under the skin.

Do not mix this product with other insulins or use it in an insulin pump.

Use this medication regularly as directed by your doctor in order to get the most benefit from it. Carefully follow the insulin treatment plan, meal plan, and exercise program your doctor has recommended. Monitor your blood sugar on a regular basis. Keep track of the results, and share them with your doctor. This is very important in order to determine the correct insulin dose. Inform your doctor if your blood sugar measurements are too high or too low. Your dosage may need to be changed.

If you are measuring doses from vials, do not reuse needles and syringes. If you are using the cartridges or pens, use a new needle each time. Learn how to discard needles and medical supplies safely. Consult your pharmacist for more information.

Disclaimer

Humalog 75-25 Consumer (continued)

SIDE EFFECTS: See also the How to Use section.

Pain, redness, swelling or itching at the injection site may occur. These effects usually go away after a few days or weeks. If any of these effects persist or worsen, notify your doctor or pharmacist promptly.

Remember that your doctor has prescribed this medication because he or she has judged that the benefit to you is greater than the risk of side effects. Many people using this medication do not have serious side effects.

Too much insulin can cause low blood sugar (hypoglycemia). This effect may also occur if you do not consume enough calories. The symptoms include chills, cold sweats, blurred vision, dizziness, drowsiness, shaking, fast heartbeat, weakness, headache, fainting, tingling of the hands/feet, or hunger. It is a good habit to carry glucose (sugar) tablets or gel to treat low blood sugar. If you don't have these reliable forms of glucose, raise your blood sugar quickly by eating a quick source of sugar such as table sugar, honey, candy, or drinking a glass of fruit juice or non-diet soda. Tell your doctor immediately about the reaction. To help prevent low blood sugar, eat meals on a regular schedule and do not skip meals.

Too little insulin can cause high blood sugar (hyperglycemia). Symptoms of high blood sugar include thirst, increased urination, confusion, drowsiness, flushing, rapid breathing, or fruity breath odor. If these symptoms occur, tell your doctor immediately. Your treatment plan may need to be changed.

This medication may cause low potassium levels in the blood (hypokalemia). Tell your doctor immediately if any of these unlikely but serious side effects occur: muscle cramps, weakness, irregular heartbeat.

A very serious allergic reaction to this drug is rare. However, seek immediate medical attention if you notice any of the following signs of a serious allergic reaction: rash, itching/swelling (especially of the face/tongue/throat), severe dizziness, trouble breathing.

This is not a complete list of possible side effects. If you notice other effects not listed above, contact your doctor or pharmacist.

In the US -

Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

In Canada - Call your doctor for medical advice about side effects. You may report side effects to Health Canada at 1-866-234-2345.

Read the Humalog 75-25 (75-25 insulin lispro suspension and 25 insulin lispro injection) Side Effects Center for a complete guide to possible side effects »

PRECAUTIONS: Before taking this medication, tell your doctor or pharmacist if you are allergic to it; or to other insulins; or if you have any other allergies. This product may contain inactive ingredients, which can cause allergic reactions or other problems. Talk to your pharmacist for more details.

Before using this medication, tell your doctor or pharmacist your medical history, especially of: kidney disease, liver disease.

Use only the insulin product that your doctor has prescribed for you. Do not change the insulin you use unless your doctor has given you instructions on how to do so. Follow your doctor's instructions carefully. Following a change in insulin, you may need a dosage change. Know the symptoms of low blood sugar and high blood sugar (see Side Effects section). Tell your doctor immediately if you experience symptoms of high or low blood sugar.

Do not use this medication when you have low blood sugar.

You may experience blurred vision, dizziness, or drowsiness due to extremely low or high blood sugar levels. Do not drive, use machinery, or do any activity that requires alertness or clear vision until you are sure you can perform such activities safely.

Limit alcohol while taking this medication because it can increase the risk of developing low blood sugar.

During times of stress, such as fever, infection, injury, or surgery, it may be more difficult to control your blood sugar. Consult your doctor because a change in your treatment plan may be required.

Changes in your lifestyle or activity level may affect the amount of insulin your body needs to control blood sugar levels. If you notice an unusual change in your insulin needs, tell your doctor.

Check your blood sugar before and after exercise. You may need a snack before exercising.

If traveling across more than two time zones, ask your doctor about how to adjust your insulin schedule.

Tell your doctor if you are pregnant before using this medication. If you are planning pregnancy, discuss a plan for managing your blood sugars with your doctor before you become pregnant. Your doctor may switch the type of insulin you use during pregnancy. Consult your doctor for more details.

It is not known whether this drug passes into breast milk. Consult your doctor before breast-feeding. Your insulin needs may change while breast-feeding.

Disclaimer

Humalog 75-25 Consumer (continued)

DRUG INTERACTIONS: Drug interactions may change how your medications work or increase your risk for serious side effects. This document does not contain all possible drug interactions. Keep a list of all the products you use (including prescription/nonprescription drugs and herbal products) and share it with your doctor and pharmacist. Do not start, stop, or change the dosage of any medicines without your doctor's approval.

A product that may interact with this drug is: rosiglitazone.

Many drugs can affect your blood sugar levels, making it more difficult to control your blood sugar. Before you start, stop, or change any medication, talk with your doctor or pharmacist about how the medication may affect your blood sugar. Check your blood sugar levels regularly as directed by your doctor. Tell your doctor about the results and of any symptoms of high or low blood sugar. (See also Side Effects section.) Your doctor may need to adjust your anti-diabetic medication, exercise program, or diet. Effects section.) Your doctor may need to adjust your diabetes medication, exercise program, or diet.

Beta-blocker medications (such as metoprolol, propranolol, glaucoma eye drops such as timolol) may prevent the fast/pounding heartbeat you would usually feel when your blood sugar level falls too low (hypoglycemia). Other symptoms of low blood sugar such as dizziness, hunger, or sweating are unaffected by these drugs.

Check the labels on all your medicines (such as cough-and-cold products) carefully. Some products may contain sugar or alcohol and may affect your blood sugar levels. Ask your doctor or pharmacist about using these products safely.

Other medications can affect the results of urine tests for sugar or ketones. Consult your doctor or pharmacist for more information.

OVERDOSE: If overdose is suspected, contact your local poison control center or emergency room immediately. US residents can call the US National Poison Hotline at 1-800-222-1222. Canada residents can call a provincial poison control center. Symptoms of overdose may include: very fast heartbeat, vision changes, unexplained heavy sweating, agitation, fainting, seizures.

NOTES: Do not share this medication, needles, or syringes with others.

Attend a diabetes education program to learn more about diabetes and the important aspects of its treatment, including medications, diet, exercise, and getting regular eye/foot/medical exams. Learn the symptoms of high and low blood sugar and how to treat low blood sugar.

Check your blood sugar levels regularly as directed. Keep all medical appointments. Laboratory and/or medical tests (such as fasting blood glucose, hemoglobin A1c) should be performed periodically to check for side effects and monitor your response to treatment.

Wear or carry identification stating that you have diabetes and are using this drug.

MISSED DOSE: It is very important to follow your insulin regimen exactly. Do not miss any doses of insulin. Keep extra supplies of insulin and an extra syringe and needle on hand. Discuss specific instructions with your doctor now in case you miss a dose of insulin or a meal in the future.

STORAGE: See also the How to Use section.

Store all unopened insulin containers in the refrigerator between 36-46 degrees F (2-8 degrees C). Do not freeze, and do not use insulin that has been frozen. If you are using the vials, store open vials in the refrigerator or at room temperature below 86 degrees F (30 degrees C) away from direct heat and light. Store in the carton to protect from light. Do not refrigerate cartridges or pens that are currently in use. Discard cartridges and vials in use after 28 days, and pens in use after 10 days, even if there is insulin left. Do not store in the bathroom. Keep all medicines away from children and pets.

Do not flush medications down the toilet or pour them into a drain unless instructed to do so. Properly discard this product when it is expired or no longer needed. Consult your pharmacist or local waste disposal company for more details about how to safely discard your product.

MEDICAL ALERT: Your condition can cause complications in a medical emergency. For enrollment information call MedicAlert at 1-800-854-1166 (USA) or 1-800-668-1507 (Canada).

Information last revised April 2012. Copyright(c) 2012 First Databank, Inc.

HUMALOG® Mix75/25TM
(75% insulin lispro protamine suspension and 25% insulin lispro) Injection (rDNA ORIGIN)
100 UNITS PER ML (U-100)

DRUG DESCRIPTION

Humalog® Mix75/25 [75% insulin lispro protamine suspension and 25% insulin lispro injection, (rDNA origin)] is a mixture of insulin lispro solution, a rapid-acting blood glucose-lowering agent and insulin lispro protamine suspension, an intermediate-acting blood glucose-lowering agent. Chemically, insulin lispro is Lys(B28), Pro(B29) human insulin analog, created when the amino acids at positions 28 and 29 on the insulin B-chain are reversed. Insulin lispro is synthesized in a special non-pathogenic laboratory strain of Escherichia coli bacteria that has been genetically altered to produce insulin lispro. Insulin lispro protamine suspension (NPL component) 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:

HUMALOG (rDNA ORIGIN) Structural Formula Illustration

Insulin lispro has the empirical formula C257H383N65O77S6 and a molecular weight of 5808, both identical to that of human insulin.

Humalog Mix75/25 vials and Pens contain a sterile suspension of insulin lispro protamine suspension mixed with soluble insulin lispro for use as an injection.

Each milliliter of Humalog Mix75/25 injection contains insulin lispro 100 units, 0.28 mg protamine sulfate, 16 mg glycerin, 3.78 mg dibasic sodium phosphate, 1.76 mg Metacresol, zinc oxide content adjusted to provide 0.025 mg zinc ion, 0.715 mg phenol, and Water for Injection. Humalog Mix75/25 has a pH of 7.0 to 7.8. Hydrochloric acid 10% and/or sodium hydroxide 10% may have been added to adjust pH.

Last reviewed on RxList: 9/13/2007
This monograph has been modified to include the generic and brand name in many instances.

HUMALOG® Mix75/25TM
(75% insulin lispro protamine suspension and 25% insulin lispro) Injection (rDNA ORIGIN)
100 UNITS PER ML (U-100)

DRUG DESCRIPTION

Humalog® Mix75/25 [75% insulin lispro protamine suspension and 25% insulin lispro injection, (rDNA origin)] is a mixture of insulin lispro solution, a rapid-acting blood glucose-lowering agent and insulin lispro protamine suspension, an intermediate-acting blood glucose-lowering agent. Chemically, insulin lispro is Lys(B28), Pro(B29) human insulin analog, created when the amino acids at positions 28 and 29 on the insulin B-chain are reversed. Insulin lispro is synthesized in a special non-pathogenic laboratory strain of Escherichia coli bacteria that has been genetically altered to produce insulin lispro. Insulin lispro protamine suspension (NPL component) 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:

HUMALOG (rDNA ORIGIN) Structural Formula Illustration

Insulin lispro has the empirical formula C257H383N65O77S6 and a molecular weight of 5808, both identical to that of human insulin.

Humalog Mix75/25 vials and Pens contain a sterile suspension of insulin lispro protamine suspension mixed with soluble insulin lispro for use as an injection.

Each milliliter of Humalog Mix75/25 injection contains insulin lispro 100 units, 0.28 mg protamine sulfate, 16 mg glycerin, 3.78 mg dibasic sodium phosphate, 1.76 mg Metacresol, zinc oxide content adjusted to provide 0.025 mg zinc ion, 0.715 mg phenol, and Water for Injection. Humalog Mix75/25 has a pH of 7.0 to 7.8. Hydrochloric acid 10% and/or sodium hydroxide 10% may have been added to adjust pH.

Last reviewed on RxList: 9/13/2007
This monograph has been modified to include the generic and brand name in many instances.

HUMALOG® Mix75/25TM
(75% insulin lispro protamine suspension and 25% insulin lispro) Injection (rDNA ORIGIN)
100 UNITS PER ML (U-100)

DRUG DESCRIPTION

Humalog® Mix75/25 [75% insulin lispro protamine suspension and 25% insulin lispro injection, (rDNA origin)] is a mixture of insulin lispro solution, a rapid-acting blood glucose-lowering agent and insulin lispro protamine suspension, an intermediate-acting blood glucose-lowering agent. Chemically, insulin lispro is Lys(B28), Pro(B29) human insulin analog, created when the amino acids at positions 28 and 29 on the insulin B-chain are reversed. Insulin lispro is synthesized in a special non-pathogenic laboratory strain of Escherichia coli bacteria that has been genetically altered to produce insulin lispro. Insulin lispro protamine suspension (NPL component) 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:

HUMALOG (rDNA ORIGIN) Structural Formula Illustration

Insulin lispro has the empirical formula C257H383N65O77S6 and a molecular weight of 5808, both identical to that of human insulin.

Humalog Mix75/25 vials and Pens contain a sterile suspension of insulin lispro protamine suspension mixed with soluble insulin lispro for use as an injection.

Each milliliter of Humalog Mix75/25 injection contains insulin lispro 100 units, 0.28 mg protamine sulfate, 16 mg glycerin, 3.78 mg dibasic sodium phosphate, 1.76 mg Metacresol, zinc oxide content adjusted to provide 0.025 mg zinc ion, 0.715 mg phenol, and Water for Injection. Humalog Mix75/25 has a pH of 7.0 to 7.8. Hydrochloric acid 10% and/or sodium hydroxide 10% may have been added to adjust pH.

Last reviewed on RxList: 9/13/2007
This monograph has been modified to include the generic and brand name in many instances.

توزیع کنندگان این دارو
شرکت های تولید کننده یا وارد کننده دارو

دارونـــما
نوآوری برای سلامت

طراحی و اجرا M.Ramezani
ارتباط با ما Info@darunama.com