1 INDICATIONS AND USAGE

HUMULIN 70/30 is a fixed ratio premix recombinant human insulin formulation indicated to improve glycemic control in adult patients with diabetes mellitus.

2 DOSAGE AND ADMINISTRATION

3 DOSAGE FORMS AND STRENGTHS

HUMULIN 70/30 injectable suspension: 100 units per mL (U-100) is available as:

• 10 mL vials
• 3 mL vials
• 3 mL HUMULIN 70/30 KwikPen (prefilled)

4 CONTRAINDICATIONS

HUMULIN 70/30 is contraindicated:

• During episodes of hypoglycemia [see Warnings and Precautions (5.3)], and
• In patients who have had hypersensitivity reactions to HUMULIN 70/30 or any of its excipients [see Warnings and Precautions (5.4)].

5 WARNINGS AND PRECAUTIONS

6 ADVERSE REACTIONS

The following adverse reactions are discussed elsewhere in the labeling:

• Hypoglycemia [see Warnings and Precautions (5.3)].
• Hypokalemia [see Warnings and Precautions (5.5)].

The following additional adverse reactions have been identified during post-approval use of HUMULIN 70/30. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or to establish a causal relationship to drug exposure.

7 DRUG INTERACTIONS

8 USE IN SPECIFIC POPULATIONS

10 OVERDOSAGE

Excess insulin administration may cause hypoglycemia and hypokalemia [see Warnings and Precautions (5.3, 5.5)]. Mild episodes of hypoglycemia can be treated with oral glucose. Adjustments in drug dosage, meal patterns, or physical activity level 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. Hypokalemia must be corrected appropriately.

11 DESCRIPTION

HUMULIN 70/30 (70% human insulin isophane suspension and 30% human insulin injection [rDNA origin]) is a human insulin suspension. Human insulin is produced by recombinant DNA technology utilizing a non-pathogenic laboratory strain of Escherichia coli. HUMULIN 70/30 is a suspension of crystals produced from combining human insulin and protamine sulfate under appropriate conditions for crystal formation and mixing with human insulin injection. The amino acid sequence of HUMULIN 70/30 is identical to human insulin and has the empirical formula C257H383N65O77S6 with a molecular weight of 5808.

HUMULIN 70/30 is a sterile white suspension. Each milliliter of HUMULIN 70/30 contains 100 units of insulin human, 0.24 mg of protamine sulfate, 16 mg of glycerin, 3.78 mg of dibasic sodium phosphate, 1.6 mg of metacresol, 0.65 mg of phenol, zinc oxide content adjusted to provide 0.025 mg zinc ion, and Water for Injection. The pH is 7.0 to 7.8. Sodium hydroxide and/or hydrochloric acid may be added during manufacture to adjust the pH.

12 CLINICAL PHARMACOLOGY

12.2 Pharmacodynamics

HUMULIN 70/30 combines an intermediate-acting insulin with the more rapid onset of action of regular human insulin. In healthy males (n=18) given HUMULIN 70/30 (0.3 unit/kg) subcutaneously, the pharmacologic effect began at approximately 50 minutes (range: 30 to 90 minutes) (see Figure 1). The effect was maximal at approximately 3.5 hours (range: 1.5 to 6.5 hours) and the mean duration of action was relatively long (approximately 23 hours; range: 18-24 hours).

Figure 1 should be considered only as a representative example since the time course of action of insulin may vary in different individuals or within the same individual. The rate of insulin absorption and consequently the onset of activity is known to be affected by the site of injection, physical activity level, and other variables [see Warnings and Precautions (5.3)].

Figure 1: Mean Insulin Activity Versus Time Profiles After Subcutaneous Injection of HUMULIN 70/30 or HUMULIN® R U‑100 (0.3 unit/kg) in Healthy Subjects.

13 NONCLINICAL TOXICOLOGY

16 HOW SUPPLIED/STORAGE AND HANDLING

Product: 50090-0444

NDC: 50090-0444-0 10 mL in a VIAL

17 PATIENT COUNSELING INFORMATION

Advise the patient to read the FDA-approved patient labeling (Patient Information and Instructions for Use).

PATIENT INFORMATION
HUMULIN® (HU-mu-lin) 70/30
(70% human insulin isophane suspension and
30% human insulin injection [rDNA origin])

Do not share your HUMULIN 70/30 KwikPen or syringes with other people, even if the needle has been changed. You may give other people a serious infection or get a serious infection from them.

What is HUMULIN 70/30?

• HUMULIN 70/30 is a man-made insulin that is used to control high blood sugar in adults with diabetes mellitus.

Who should not use HUMULIN 70/30?

Do not use HUMULIN 70/30 if you:

• are having an episode of low blood sugar (hypoglycemia).
• have an allergy to HUMULIN 70/30 or any of the ingredients in HUMULIN 70/30.

Before using HUMULIN 70/30, tell your healthcare provider about all your medical conditions including, if you:

• have liver or kidney problems.
• take any other medicines, especially ones commonly called TZDs (thiazolidinediones).
• have heart failure or other heart problems. If you have heart failure, it may get worse while you take TZDs with HUMULIN 70/30.
• are pregnant, planning to become pregnant, or are breastfeeding.
• are taking new prescription or over-the-counter medicines, vitamins, or herbal supplements.

Before you start using HUMULIN 70/30, talk to your healthcare provider about low blood sugar and how to manage it.

How should I use HUMULIN 70/30?

• Read the Instructions for Use that come with your HUMULIN 70/30.
• Use HUMULIN 70/30 exactly as your healthcare provider tells you to.
• Know the type and strength of insulin you use. Do not change the type of insulin you use unless your healthcare provider tells you to. The amount of insulin and the best time for you to take your insulin may need to change if you use different types of insulin.
• Check your blood sugar levels. Ask your healthcare provider what your blood sugars should be and when you should check your blood sugar levels.
• Do not share your HUMULIN 70/30 KwikPen or syringes with other people, even if the needle has been changed. You may give other people a serious infection or get a serious infection from them.

Your HUMULIN 70/30 dose may need to change because of:

• change in level of physical activity or exercise, weight gain or loss, increased stress, illness, change in diet.

What should I avoid while using HUMULIN 70/30?

While using HUMULIN 70/30 do not:

• Drive or operate heavy machinery, until you know how HUMULIN 70/30 affects you.
• Drink alcohol or use prescription or over-the-counter medicines that contain alcohol.

What are the possible side effects of HUMULIN 70/30?

HUMULIN 70/30 may cause serious side effects that can lead to death, including:

• low blood sugar (hypoglycemia). Signs and symptoms that may indicate low blood sugar include:
  • dizziness or light-headedness, sweating, confusion, headache, blurred vision, slurred speech, shakiness, fast heartbeat, anxiety, irritability, or mood changes, hunger.
• serious allergic reaction (whole body reaction). Get medical help right away, if you have any of these symptoms of an allergic reaction:
  • a rash over your whole body, trouble breathing, a fast heartbeat, or sweating.
• low potassium in your blood (hypokalemia).
• heart failure. Taking certain diabetes pills called thiazolidinediones or “TZDs” with HUMULIN 70/30 may cause heart failure in some people. This can happen even if you have never had heart failure or heart problems before. If you already have heart failure it may get worse while you take TZDs with HUMULIN 70/30. Your healthcare provider should monitor you closely while you are taking TZDs with HUMULIN 70/30. Tell your healthcare provider if you have any new or worse symptoms of heart failure including:
  • shortness of breath, swelling of your ankles or feet, sudden weight gain

    Treatment with TZDs and HUMULIN 70/30 may need to be adjusted or stopped by your healthcare provider if you have new or worse heart failure.

Get emergency medical help if you have:

• trouble breathing, shortness of breath, fast heartbeat, swelling of your face, tongue, or throat, sweating, extreme drowsiness, dizziness, confusion.

The most common side effects of HUMULIN 70/30 include:

• low blood sugar (hypoglycemia), allergic reactions including reactions at the injection site, skin thickening or pits at the injection site (lipodystrophy), itching, rash, weight gain, and swelling of your hands and feet. These are not all the possible side effects of HUMULIN 70/30. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

General information about the safe and effective use of HUMULIN 70/30:

Medicines are sometimes prescribed for purposes other than those listed in a Patient Information leaflet. You can ask your pharmacist or healthcare provider for information about HUMULIN 70/30 that is written for health professionals. Do not use HUMULIN 70/30 for a condition for which it was not prescribed. Do not give HUMULIN 70/30 to other people, even if they have the same symptoms that you have. It may harm them.

What are the ingredients in HUMULIN 70/30?

Active Ingredient: insulin human (rDNA origin)

Inactive Ingredients: protamine sulfate, glycerin, dibasic sodium phosphate, metacresol, phenol, zinc oxide, water for injection, hydrochloric acid or sodium hydroxide

For more information, call 1-800-545-5979 or go to www.humulin.com.

This Patient Information has been approved by the U.S. Food and Drug Administration.

Patient Information revised July 11, 2017

Marketed by: Lilly USA, LLC, Indianapolis, IN 46285, USA
Copyright © 1992, 2017, Eli Lilly and Company. All rights reserved.

LIN7030-0002-PPI-20170711

Instructions for Use
HUMULIN® (HU-mu-lin) 70/30
(70% human insulin isophane suspension and
30% human insulin injection [rDNA origin])
vial (100 Units/mL, U-100)

Read the Instructions for Use before you start taking HUMULIN 70/30 and each time you get a new HUMULIN 70/30 vial. There may be new information. This information does not take the place of talking to your healthcare provider about your medical condition or your treatment.

Do not share your syringes with other people, even if the needle has been changed. You may give other people a serious infection or get a serious infection from them.

Supplies needed to give your injection:

• a HUMULIN 70/30 vial
• a U-100 insulin syringe and needle
• 2 alcohol swabs
• 1 sharps container for throwing away used needles and syringes. See “Disposing of used needles and syringes” at the end of these instructions.

Preparing your HUMULIN 70/30 dose:

• Wash your hands with soap and water.
• Check the HUMULIN 70/30 label to make sure you are taking the right type of insulin. This is especially important if you use more than 1 type of insulin.
• Do not use HUMULIN 70/30 past the expiration date printed on the label or 31 days after you first use it.
• Always use a new syringe or needle for each injection to help ensure sterility and prevent blocked needles. Do not reuse or share your syringes or needles with other people. You may give other people a serious infection or get a serious infection from them.

Step 1: Gently roll the vial between the palms of your hands at least 10 times.
Step 2: Carefully invert the vial at least 10 times. Mixing is important to make sure you get the right dose. Humulin 70/30 should look white and cloudy after mixing. Do not use it if it looks clear or contains any lumps or particles.
Step 3: If you are using a new vial, pull off the plastic Protective Cap, but do not remove the Rubber Stopper.
Step 4: Wipe the Rubber Stopper with an alcohol swab.
Step 5: Hold the syringe with the needle pointing up. Pull down on the Plunger until the tip of the Plunger reaches the line for the number of units for your prescribed dose.	(Example Dose: 20 units shown)
Step 6: Push the needle through the Rubber Stopper of the vial.
Step 7: Push the plunger all the way in. This puts air into the vial.
Step 8: Turn the vial and syringe upside down and slowly pull the Plunger down until the tip is a few units past the line for your prescribed dose. If there are air bubbles, tap the syringe gently a few times to let any air bubbles rise to the top.	(Example Dose: 20 units Plunger is shown at 24 units)
Step 9: Slowly push the Plunger up until the tip reaches the line for your prescribed dose. Check the syringe to make sure that you have the right dose.	(Example Dose: 20 units shown)
Step 10: Pull the syringe out of the vial's Rubber Stopper.

Giving your HUMULIN 70/30 injection:

• Inject your insulin exactly as your healthcare provider has shown you.
• Change (rotate) your injection site for each injection.

Step 11: Choose your injection site. HUMULIN 70/30 is injected under the skin (subcutaneously) of your stomach area (abdomen), buttocks, upper legs or upper arms. Wipe the skin with an alcohol swab. Let the injection site dry before you inject your dose.
Step 12: Insert the needle into your skin.
Step 13: Push down on the Plunger to inject your dose. The needle should stay in your skin for at least 5 seconds to make sure you have injected all of your insulin dose.
Step 14: Pull the needle out of your skin. If you see blood after you take the needle out of your skin, press the injection site with a piece of gauze or an alcohol swab. Do not rub the area. Do not recap the needle. Recapping the needle can lead to a needle stick injury.

Disposing of used needles and syringes:

• Put your used needles and syringes in a FDA-cleared sharps disposal container right away after use. Do not throw away (dispose of) loose needles and syringes in your household trash.
• If you do not have a FDA-cleared sharps disposal container, you may use a household container that is:

  -

  made of a heavy-duty plastic,

  -

  can be closed with a tight-fitting, puncture-resistant lid, without sharps being able to come out,

  -

  upright and stable during use,

  -

  leak-resistant, and

  -

  properly labeled to warn of hazardous waste inside the container.

• When your sharps disposal container is almost full, you will need to follow your community guidelines for the right way to dispose of your sharps disposal container. There may be state or local laws about how you should throw away used needles and syringes. For more information about safe sharps disposal, and for specific information about sharps disposal in the state that you live in, go to the FDA's website at: http://www.fda.gov/safesharpsdisposal.
• Do not dispose of your used sharps disposal container in your household trash unless your community guidelines permit this. Do not recycle your used sharps disposal container.

How should I store HUMULIN 70/30?

All unopened HUMULIN 70/30 vials:

• Store all unopened vials in the refrigerator.
• Do not freeze. Do not use if it has been frozen.
• Keep away from heat and out of direct light.
• Unopened vials can be used until the expiration date on the carton and label, if they have been stored in the refrigerator.
• Unopened vials should be thrown away after 31 days, if they are stored at room temperature.

After HUMULIN 70/30 vials have been opened:

• Store opened vials in the refrigerator or at room temperature below 86°F (30°C) for up to 31 days.
• Keep away from heat and out of direct light.
• Throw away all opened vials after 31 days of use, even if there is still insulin left in the vial.

General information about the safe and effective use of HUMULIN 70/30.

• Keep HUMULIN 70/30 vials, syringes, needles, and all medicines out of the reach of children.
• Always use a new syringe or needle for each injection.
• Do not reuse or share your syringes or needles with other people. You may give other people a serious infection or get a serious infection from them.

If you have any questions or problems with your HUMULIN, contact Lilly at 1-800-Lilly-Rx (1-800-545-5979) or call your healthcare provider for help. For more information on HUMULIN and insulin, go to www.humulin.com.

Scan this code to launch the humulin.com website

This Instructions for Use has been approved by the U.S. Food and Drug Administration.

Humulin® is a trademark of Eli Lilly and Company.

Instructions for Use revised: September 24, 2015

Marketed by: Lilly USA, LLC, Indianapolis, IN 46285, USA
Copyright © 1992, 2015, Eli Lilly and Company. All rights reserved.

LIN7030VL-0002-IFU-20150924

Instructions for Use

HUMULIN® 70/30 KwikPen®

(70% human insulin isophane suspension
30% human insulin injection [rDNA origin])

100 units/mL, 3 mL pen

Read the Instructions for Use before you start taking HUMULIN 70/30 and each time you get another KwikPen. There may be new information. This information does not take the place of talking to your healthcare provider about your medical condition or your treatment.

Do not share your HUMULIN 70/30 KwikPen with other people, even if the needle has been changed. You may give other people a serious infection or get a serious infection from them.

HUMULIN® 70/30 KwikPen® (“Pen”) is a disposable prefilled pen containing 300 units of HUMULIN 70/30. You can give yourself more than 1 dose from the Pen. Each turn (click) of the Dose Knob dials 1 unit of insulin. You can give from 1 to 60 units in a single injection. If your dose is more than 60 units, you will need to give yourself more than 1 injection. The Plunger only moves a little with each injection, and you may not notice that it moves. The Plunger will only reach the end of the cartridge when you have used all 300 units in the Pen.

This Pen is not recommended for use by the blind or visually impaired without the help of someone trained to use the Pen.

How to recognize your HUMULIN 70/30 KwikPen

• Pen color: Beige
• Dose Knob: Brown
• Labels: White label with brown stripe

Supplies you will need to give your injection

• HUMULIN 70/30 KwikPen
• KwikPen compatible Needle (Becton, Dickinson and Company Pen Needles recommended)
• Alcohol swab
• Gauze

Preparing your Pen

• Wash your hands with soap and water.
• Check your Pen to make sure you are taking the right type of insulin. This is especially important if you use more than 1 type of insulin.
• Do not use your Pen past the expiration date printed on the Label or for more than 10 days after you first start using the Pen.
• Always use a new needle for each injection to help prevent infections and blocked needles. Do not reuse or share your needles with other people. You may give other people a serious infection or get a serious infection from them.

Step 1: Pull the Pen Cap straight off. - Do not remove the Pen Label. Wipe the Rubber Seal with an alcohol swab. - Do not attach the Needle before mixing.
Step 2: Gently roll the Pen between your hands 10 times.
Step 3: Move the Pen up and down (invert) 10 times. Mixing by rolling and inverting the Pen is important to make sure you get the right dose.
Step 4: Check the liquid in the Pen. HUMULIN 70/30 should look white and cloudy after mixing. Do not use if it looks clear or has any lumps or particles in it.
Step 5: Select a new Needle. Pull off the Paper Tab from the Outer Needle Shield.
Step 6: Push the capped Needle straight onto the Pen and twist the Needle on until it is tight.
Step 7: Pull off the Outer Needle Shield. Do not throw it away. Pull off the Inner Needle Shield and throw it away.

Priming your Pen

Prime before each injection.

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

Step 8: To prime your Pen, turn the Dose Knob to select 2 units.
Step 9: Hold your Pen with the Needle pointing up. Tap the Cartridge Holder gently to collect air bubbles at the top.
Step 10: Continue holding your Pen with Needle pointing up. Push the Dose Knob in until it stops, and “0” is seen in the Dose Window. Hold the Dose Knob in and count to 5 slowly. You should see insulin at the tip of the Needle. - If you do not see insulin, repeat priming steps 8 to 10, no more than 4 times. - If you still do not see insulin, change the Needle and repeat priming steps 8 to 10. Small air bubbles are normal and will not affect your dose.

Selecting your dose

• You can give from 1 to 60 units in a single injection.
• If your dose is more than 60 units, you will need to give more than 1 injection.

  -

  If you need help with dividing up your dose the right way, ask your healthcare provider.

  -

  Use a new Needle for each injection and repeat the priming step.

Step 11: Turn the Dose Knob to select the number of units you need to inject. The Dose Indicator should line up with your dose. - The Pen dials 1 unit at a time. - The Dose Knob clicks as you turn it. - Do not dial your dose by counting the clicks. You may dial the wrong dose. This may lead to you getting too much insulin or not enough insulin. - The dose can be corrected by turning the Dose Knob in either direction until the correct dose lines up with the Dose Indicator. - The even numbers (for example, 12) are printed on the dial. - The odd numbers, (for example, 25) after the number 1, are shown as full lines. Always check the number in the Dose Window to make sure you have dialed the correct dose.

(Example: 12 units shown in the Dose Window) (Example: 25 units shown in the Dose Window)

• The Pen will not let you dial more than the number of units left in the Pen.
• If you need to inject more than the number of units left in the Pen, you may either:

  -

  inject the amount left in your Pen and then use a new Pen to give the rest of your dose,

  or

  -

  get a new Pen and inject the full dose.

• It is normal to see a small amount of insulin left in the Pen that you can not inject.

Giving your injection

• Inject your insulin as your healthcare provider has shown you.
• Change (rotate) your injection site for each injection.
• Do not try to change your dose while injecting.

Step 12: Choose your injection site. HUMULIN 70/30 is injected under the skin (subcutaneously) of your stomach area, buttocks, upper legs or upper arms. Wipe your skin with an alcohol swab, and let your skin dry before you inject your dose.
Step 13: Insert the Needle into your skin. Push the Dose Knob all the way in. Continue to hold the Dose Knob in and slowly count to 5 before removing the Needle. Do not try to inject your insulin by turning the Dose Knob. You will not receive your insulin by turning the Dose Knob.
Step 14: Pull the Needle out of your skin. A drop of insulin at the Needle tip is normal. It will not affect your dose. Check the number in the Dose Window. - If you see “0” in the Dose Window, you have received the full amount you dialed. - If you do not see “0” in the Dose Window, do not redial. Insert the Needle into your skin and finish your injection. - If you still do not think you received the full amount you dialed for your injection, do not start over or repeat the injection. Monitor your blood glucose as instructed by your healthcare provider. - If you normally need to give 2 injections for your full dose, be sure to give your second injection. The Plunger only moves a little with each injection, and you may not notice that it moves. If you see blood after you take the Needle out of your skin, press the injection site lightly with a piece of gauze or an alcohol swab. Do not rub the area.

After your injection

Step 15: Carefully replace the Outer Needle Shield.
Step 16: Unscrew the capped Needle and throw it away (see Disposing of Pens and Needles section). Do not store the Pen with the Needle attached to prevent leaking, blocking the Needle, and air from entering the Pen.
Step 17: Replace the Pen Cap by lining up the Cap Clip with the Dose Indicator and pushing straight on.

Disposing of Pens and Needles

• Put your used needles in a FDA-cleared sharps disposal container right away after use. Do not throw away (dispose of) loose needles in your household trash.
• If you do not have a FDA-cleared sharps disposal container, you may use a household container that is:

  -

  made of a heavy-duty plastic,

  -

  can be closed with a tight-fitting, puncture-resistant lid, without sharps being able to come out,

  -

  upright and stable during use,

  -

  leak-resistant, and

  -

  properly labeled to warn of hazardous waste inside the container.

• When your sharps disposal container is almost full, you will need to follow your community guidelines for the right way to dispose of your sharps disposal container. There may be state or local laws about how you should throw away used needles and syringes. For more information about safe sharps disposal, and for specific information about sharps disposal in the state that you live in, go to the FDA's website at: http://www.fda.gov/safesharpsdisposal
• Do not dispose of your used sharps disposal container in your household trash unless your community guidelines permit this. Do not recycle your used sharps disposal container.
• The used Pen may be discarded in your household trash after you have removed the needle.

Storing your Pen

Unused Pens

• Store unused Pens in the refrigerator at 36°F to 46°F (2°C to 8°C).
• Do not freeze your insulin. Do not use if it has been frozen.
• Unused Pens may be used until the expiration date printed on the Label, if the Pen has been kept in the refrigerator.

In-use Pen

• Store the Pen you are currently using at room temperature [up to 86°F (30°C)]. Keep away from heat and light.
• Throw away the HUMULIN 70/30 Pen you are using after 10 days, even if it still has insulin left in it.

General information about the safe and effective use of your Pen

• Keep your Pen and needles out of the reach of children.
• Do not use your Pen if any part looks broken or damaged.
• Always carry an extra Pen in case yours is lost or damaged.

Troubleshooting

• If you can not remove the Pen Cap, gently twist the cap back and forth, and then pull the cap straight off.
• If the Dose Knob is hard to push:

  -

  Pushing the Dose Knob more slowly will make it easier to inject.

  -

  Your Needle may be blocked. Put on a new Needle and prime the Pen.

  -

  You may have dust, food, or liquid inside the Pen. Throw the Pen away and get a new Pen.

If you have any questions or problems with your HUMULIN 70/30 KwikPen, contact Lilly at 1-800-LillyRx (1-800-545-5979) or call your healthcare provider for help. For more information on HUMULIN 70/30 KwikPen and insulin, go to www.lilly.com.

Scan this code to launch

www.humulin.com

This Instructions for Use has been approved by the U.S. Food and Drug Administration.

HUMULIN® and HUMULIN® KwikPen® are trademarks of Eli Lilly and Company.

Revised: January 6, 2017

Marketed by: Lilly USA, LLC
Indianapolis, IN 46285, USA

Copyright © 2013, 2017, Eli Lilly and Company. All rights reserved.

LIN7030KP-0003-IFU-20170106

INACTIVE INGREDIENT

protamine sulfate, glycerin, dibasic sodium phosphate, metacresol, phenol, zinc oxide, water for injection, hydrochloric acid or sodium hydroxide

ACTIVE INGREDIENT

insulin human (rDNA origin)

KEEP OUT OF REACH OF CHILDREN

Insulin human