Humulin R

Humulin R is injected under the skin.

It comes in a vial to use with a syringe, or as an injection pen (KwikPen).

Your dose will depend on your medical condition.

Use this medicine within 30 minutes before starting to eat a meal.

Follow the instructions on your prescription label carefully. Don't inject more or less Humulin R than is recommended.

Humulin R starts lowering blood sugar within 30 minutes of your injection. This effect typically lasts from 4 to 12 hours, but may last up to 24 hours.

Use a different location on your body each time you give yourself an injection of Humulin R.

You can inject this medicine into areas on the thighs, abdomen, upper arms, and buttocks.

Never inject insulin into a vein or muscle.

Don't use Humulin R in an insulin pump or mix it with other forms of insulin, unless your doctor tells you to do so.

This medicine should appear clear and colorless. Don't use Humulin R if it's cloudy, thick, or discolored, or if it contains particles.

Follow your insulin injection schedule carefully. Don't miss any doses of Humulin R.

Don't reuse or share needles or syringes.

This medicine should be stored in a refrigerator. Don't freeze Humulin R or shake the vials.

Don't use Humulin R if the expiration date on the product has passed.

Humulin R Overdose

If you suspect an overdose of Humulin R, contact a poison control center or emergency room immediately.

You can get in touch with a poison control center at 800-222-1222.

An overdose of insulin can cause life-threatening hypoglycemia (low blood sugar). Symptoms may include:

• Blurred vision
• Sweating
• Extreme weakness
• Trouble speaking
• Tremors
• Stomach pain
• Confusion
• Coma
• Seizures

Missed Dose of Humulin R

Ask your doctor what to do if you miss a dose of Humulin R.

Humulin R (insulin (human recombinant)) U-100, Regular, insulin human injection, USP (rDNA origin), 100 units/mL, is supplied as follows:

10 mL vials NDC 0002-8215-01 (HI-210)
3 mL vials NDC 0002-8215-17 (HI-213)

Literature issued March, 2011. Marketed by: Lilly USA, LLC, Indianapolis, IN 46285, USA

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

Follow all directions on your prescription label. Do not use this medicine in larger or smaller amounts or for longer than recommended.

Insulin is injected under the skin. You may be shown how to use injections at home. Do not give yourself this medicine if you do not understand how to use the injection and properly dispose of used needles and syringes.

Your care provider will show you the best places on your body to inject regular insulin. Use a different place each time you give an injection. Do not inject into the same place two times in a row.

After using regular insulin, you should eat a meal within 30 minutes.

Regular insulin must not be given with an insulin pump. Do not inject regular insulin into a vein or a muscle.

Never share a syringe with another person, even if the needle has been changed. Sharing syringes can allow infections or disease to pass from one person to another.

Use a disposable needle and syringe only once. Follow any state or local laws about throwing away used needles and syringes. Use a puncture-proof "sharps" disposal container (ask your pharmacist where to get one and how to throw it away). Keep this container out of the reach of children and pets.

Low blood sugar (hypoglycemia) can happen to everyone who has diabetes. Symptoms include headache, hunger, sweating, irritability, dizziness, nausea, fast heart rate, and feeling anxious or shaky. To quickly treat low blood sugar, always keep a fast-acting source of sugar with you such as fruit juice, hard candy, crackers, raisins, or non-diet soda.

Your doctor can prescribe a glucagon emergency injection kit to use in case you have severe hypoglycemia and cannot eat or drink. Be sure your family and close friends know how to give you this injection in an emergency.

Also watch for signs of high blood sugar (hyperglycemia) such as increased thirst or urination, blurred vision, headache, and tiredness.

Blood sugar levels can be affected by stress, illness, surgery, exercise, alcohol use, or skipping meals. Ask your doctor before changing your insulin dose or schedule.

Regular insulin is only part of a complete treatment program that may also include diet, exercise, weight control, regular blood sugar testing, and special medical care. Follow your doctor's instructions very closely.

Keep this medicine in its original container protected from heat and light. Do not draw insulin from a vial into a syringe until you are ready to give an injection. Do not freeze insulin or store it near the cooling element in a refrigerator. Throw away any insulin that has been frozen.

Storing unopened (not in use) regular insulin:

• Refrigerate and use until expiration date; or

• Store at room temperature and use within 42 days.

Storing opened (in use) regular insulin:

• Store at room temperature and use within 42 days.

Do not use the medicine if it looks cloudy, has changed colors, or has any particles in it. Call your pharmacist for new medicine.

Read all patient information, medication guides, and instruction sheets provided to you. Ask your doctor or pharmacist if you have any questions.

Wear a diabetes medical alert tag in case of emergency. Any medical care provider who treats you should know that you have diabetes.

Get emergency medical help if you have signs of insulin allergy: redness or swelling where an injection was given, itchy skin rash over the entire body, trouble breathing, fast heartbeats, feeling like you might pass out, or swelling in your tongue or throat.

Call your doctor at once if you have:

• low potassium--leg cramps, constipation, irregular heartbeats, fluttering in your chest, increased thirst or urination, numbness or tingling, muscle weakness or limp feeling.

Common side effects may include:

• low blood sugar;

• swelling in your hands or feet;

• weight gain; or

• thickening or hollowing of the skin where you injected the medicine.

This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

Never share insulin needles or syringes with others under any circumstances. It is not safe for one pen to be used for more than one person. Sharing needles can result in transmission of hepatitis viruses, HIV, or other bloodborne illnesses.

Your doctor will want to check your progress at regular visits, especially during the first few weeks you take this medicine. Blood tests may be needed to check for unwanted effects.

It is very important to follow carefully any instructions from your health care team about:

• Alcohol—Drinking alcohol (including beer and wine) may cause severe low blood sugar. Discuss this with your health care team.
• Other medicines—Do not take other medicines during the time you are taking this medicine unless they have been discussed with your doctor. This especially includes nonprescription medicines such as aspirin, and medicines for appetite control, asthma, colds, cough, hay fever, or sinus problems.
• Counseling—Other family members need to learn how to prevent side effects or help with side effects if they occur. Also, patients with diabetes may need special counseling about diabetes medicine dosing changes that might occur because of lifestyle changes, such as changes in exercise and diet. Furthermore, counseling on contraception and pregnancy may be needed because of the problems that can occur in patients with diabetes during pregnancy.
• Travel—Keep a recent prescription and your medical history with you. Be prepared for an emergency as you would normally. Make allowances for changing time zones and keep your meal times as close as possible to your usual meal times.

In case of emergency: There may be a time when you need emergency help for a problem caused by your diabetes. You need to be prepared for these emergencies. It is a good idea to:

• Wear a medical identification (ID) bracelet or neck chain at all times. Also, carry an ID card in your wallet or purse that says that you have diabetes and a list of all of your medicines.
• Keep an extra supply of insulin and syringes with needles or injection devices on hand in case high blood sugar occurs.
• Keep some kind of quick-acting sugar handy to treat low blood sugar.
• Have a glucagon kit and a syringe and needle available in case severe low blood sugar occurs. Check and replace any expired kits regularly.

This medicine may cause serious allergic reactions, including anaphylaxis. Anaphylaxis can be life-threatening and requires immediate medical attention. Tell your doctor right away if you have a rash, itching, shortness of breath, swelling of the face, tongue, and throat, trouble breathing, or chest pain after you get the injection.

Using this medicine together with other diabetes medicine (eg, pioglitazone, rosiglitazone, Actos®, Actoplus Met®, Avandia®) may cause serious heart problem or edema (fluid retention). Check with your doctor immediately if you are rapidly gaining weight, having shortness of breath, chest pain or discomfort, extreme tiredness or weakness, trouble breathing, uneven heartbeat, or excessive swelling of the hands, wrist, ankles, or feet.

You may have some skin redness, rash, itching, or swelling at the injection site. If this irritation is severe or does not go away, call your doctor. Do not inject this medicine into a skin area that is red, swollen, or itchy.

This medicine may make you dizzy or drowsy. Make sure you know how you react to this medicine before you drive, use machines, or do other jobs that require you to be alert.

Too much insulin human regular can cause hypoglycemia (low blood sugar). Low blood sugar must be treated before it causes you to pass out (unconsciousness). People feel different symptoms of low blood sugar. It is important that you learn which symptoms you usually have so you can treat it quickly. Talk to your doctor about the best way to treat low blood sugar.

Hyperglycemia (high blood sugar) may occur if you do not take enough or skip a dose of your medicine, overeat or do not follow your meal plan, have a fever or infection, or do not exercise as much as usual. High blood sugar can be very serious and must be treated right away. It is important that you learn which symptoms you have in order to treat it quickly. Talk to your doctor about the best way to treat high blood sugar.

This medicine may cause low levels of potassium in your blood. Do not use medicines, supplements, or salt substitutes that contain potassium unless you have discussed this with your doctor.

• Tell all of your health care providers that you take this medicine. This includes your doctors, nurses, pharmacists, and dentists.
• Allergic reactions have happened with Humulin R. Rarely, some reactions can be very bad or life-threatening. Talk with the doctor.
• Low blood sugar may happen with this medicine. Very low blood sugar can lead to seizures, passing out, long lasting brain damage, and sometimes death. Talk with the doctor.
• Low blood potassium may happen with Humulin R. If not treated, this can lead to a heartbeat that is not normal, very bad breathing problems, and sometimes death. Talk with the doctor.
• Avoid driving and doing other tasks or actions that call for you to be alert until you see how this medicine affects you.
• Some diabetes drugs like pioglitazone or rosiglitazone may cause heart failure or make it worse in people who already have it. Using insulin with these drugs may increase this risk. If you also take one of these drugs, talk with the doctor.
• Do not switch between different forms of Humulin R without first talking with the doctor.
• It may be harder to control your blood sugar during times of stress like when you have a fever, an infection, an injury, or surgery. A change in level of physical activity or exercise and a change in diet may also affect your blood sugar. Talk with your doctor.
• Wear disease medical alert ID (identification).
• Do not drive if your blood sugar has been low. There is a greater chance of you having a crash.
• Check your blood sugar as you have been told by your doctor.
• Have blood work checked as you have been told by the doctor. Talk with the doctor.
• Talk with your doctor before you drink alcohol.
• If you are 65 or older, use this medicine with care. You could have more side effects.
• Tell your doctor if you are pregnant or plan on getting pregnant. You will need to talk about the benefits and risks of using Humulin R while you are pregnant.
• Tell your doctor if you are breast-feeding. You will need to talk about any risks to your baby.
• Be sure you have the right insulin product. Insulin products come in many containers like vials, cartridges, and pens. Be sure that you know how to measure and get your dose ready. If you have any questions, call your doctor or pharmacist.

WARNING/CAUTION: Even though it may be rare, some people may have very bad and sometimes deadly side effects when taking a drug. Tell your doctor or get medical help right away if you have any of the following signs or symptoms that may be related to a very bad side effect:

• Signs of an allergic reaction, like rash; hives; itching; red, swollen, blistered, or peeling skin with or without fever; wheezing; tightness in the chest or throat; trouble breathing or talking; unusual hoarseness; or swelling of the mouth, face, lips, tongue, or throat.
• Signs of low potassium levels like muscle pain or weakness, muscle cramps, or a heartbeat that does not feel normal.
• Anxiety.
• Change in eyesight.
• Chills.
• Very bad dizziness or passing out.
• Mood changes.
• Seizures.
• Slurred speech.
• Very bad irritation where the shot was given.
• A burning, numbness, or tingling feeling that is not normal.
• Swelling in the arms or legs.
• Change in skin to thick or thin where the shot was given.
• Low blood sugar may occur. Signs may be dizziness, headache, feeling sleepy, feeling weak, shaking, a fast heartbeat, confusion, hunger, or sweating. Call the doctor right away if any of these signs occur. Follow what you have been told to do if low blood sugar occurs. This may include taking glucose tablets, liquid glucose, or some fruit juices.

All drugs may cause side effects. However, many people have no side effects or only have minor side effects. Call your doctor or get medical help if any of these side effects or any other side effects bother you or do not go away:

• Weight gain.
• Irritation where the shot is given.

These are not all of the side effects that may occur. If you have questions about side effects, call your doctor. Call your doctor for medical advice about side effects.

You may report side effects to the FDA at 1-800-FDA-1088. You may also report side effects at http://www.fda.gov/medwatch.

Subcutaneous use of Humulin R U-100

A 48-month multicenter, open-label, single-arm study was conducted in insulin-naive patients with type 1 or type 2 diabetes (N=129) to assess the safety and efficacy of Humulin R U-100. Humulin R U-100 and Humulin® N (alone or in combination) were administered by subcutaneous injection. Eighty-four percent of patients were Caucasian. Fifty-seven percent of the patients were male. The mean age was 45 years (range: 4 to 83 years). The average weight was 72 kg.

Total mean (± SD) glycohemoglobin improved from baseline to endpoint (baseline: 14.3 ± 3.1%, endpoint: 10.1 ± 2.8%). Hemoglobin A1c was not measured in this study. At baseline, patients weighed 72 ± 23 kg; at endpoint mean weight was 80 ± 22 kg. At endpoint, mean (± SD) total daily insulin doses for Humulin R U-100 were 0.18 ± 0.17 units/kg. At 48 months, 16 patients (21%) reported hypoglycemia. During the study, 4 patients experienced diabetic ketoacidosis.

Intravenous use of Humulin R U-100

The intravenous administration of Humulin R U-100 was tested in 21 patients with type 1 diabetes. The patients' usual doses of insulin were temporarily held, and blood glucose concentrations were maintained at a range of 200 – 260 mg/dL for one to three hours during a run-in phase of intravenous Humulin R U-100 followed by a 6-hour assessment phase. During the assessment phase patients received intravenous Humulin R at an initial dose of 0.5 U/h, adjusted to maintain blood glucose concentrations near normoglycemia (100 to 160 mg/dL).

The mean blood glucose levels during the assessment phase for patients on Humulin R U-100 therapy are summarized below in Table 1. All patients achieved near normoglycemia during the 6-hour assessment phase. At the endpoint, blood glucose was within the target range (100 to 160 mg/dL) for 20 of 21 patients treated with Humulin R U-100. The average time (± SE) required to attain near normoglycemia was 161 ± 14 minutes for Humulin R U-100.

Humulin R U-100 is contraindicated during episodes of hypoglycemia and in patients hypersensitive to Humulin R U-100 or any of its excipients.

Humulin R U-100, when used subcutaneously, is usually given three or more times daily before meals. The dosage and timing of Humulin R U-100 should be individualized and determined, based on the physician's advice, in accordance with the needs of the patient. Humulin R U-100 may also be used in combination with oral antihyperglycemic agents or longer-acting insulin products to suit the needs of the individual patients with diabetes. The injection of Humulin R U-100 should be followed by a meal within approximately 30 minutes of administration.

The average range of total daily insulin requirement for maintenance therapy in insulin-treated patients without severe insulin resistance lies between 0.5 and 1 unit/kg/day. However, in pre-pubertal children it usually varies from 0.7 to 1 unit/kg/day, but can be much lower during the period of partial remission. In situations of insulin resistance, e.g. during puberty or due to obesity, the daily insulin requirement may be substantially higher. Initial dosages for patients with diabetes are often lower, e.g., 0.2 to 0.4 units/kg/day.

Humulin R U-100 may be administered by subcutaneous injection in the abdominal wall, the thigh, the gluteal region or in the upper arm. Subcutaneous injection into the abdominal wall ensures a faster absorption than from other injection sites. Injection into a lifted skin fold minimizes the risk of intramuscular injection. Injection sites should be rotated within the same region. As with all insulin, the duration of action will vary according to the dose, injection site, blood flow, temperature, and level of physical activity.

Intravenous administration of Humulin R U-100 is possible under medical supervision with close monitoring of blood glucose and potassium levels to avoid hypoglycemia and hypokalemia.

For intravenous use, Humulin R U-100 should be used at concentrations from 0.1 unit/mL to 1 unit/mL in infusion systems with the infusion fluids 0.9% sodium chloride using polyvinyl chloride infusion bags.

Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit. Never use Humulin R U-100 if it has become viscous (thickened) or cloudy; use it only if it is clear and colorless. Humulin R U-100 should not be used after the printed expiration date.

Mixing of Insulins

• Humulin R U-100 should only be mixed as directed by the physician.
• Humulin R U-100 is short-acting and is often used in combination with intermediate- or long-acting insulins.
• The order of mixing and brand or model of syringe should be specified by the physician. A U-100 insulin syringe should always be used. Failure to use the correct syringe can lead to dosage errors.
• In general, when an intermediate-acting insulin (e.g., NPH insulin isophane suspension) is mixed with short-acting soluble insulin (e.g., regular), the short-acting insulin should be drawn into the syringe first.

Storage

Not in-use (unopened): Humulin R U-100 vials not in-use should be stored in a refrigerator (2° to 8°C [36° to 46°F]), but not in the freezer.

In-use (opened): The Humulin R U-100 vial currently in-use can be kept unrefrigerated as long as it is kept as cool as possible [below 30°C (86°F)] away from heat and light. In-use vials must be used within 31 days or be discarded, even if they still contain Humulin R U-100.

Admixture: Infusion bags prepared with Humulin R U-100 as indicated under DOSAGE AND ADMINISTRATION are stable when stored in a refrigerator (2° to 8°C [36° to 46°F]) for 48 hours and then may be used at room temperature for up to an additional 48 hours.

Do not use Humulin R U-100 after the expiration date stamped on the label or if it has been frozen.

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 Humulin R, 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. Inspect the insulin. Humulin R solution should look clear and colorless. Do not use Humulin R if it appears cloudy, thickened, or slightly colored, or if you see particles in the solution. Do not use Humulin R if you notice anything unusual in its appearance.
3. If using a new Humulin R bottle, flip off the plastic protective cap, but do not remove the stopper. Wipe the top of the bottle with an alcohol swab.
4. If you are mixing insulins, refer to the “Mixing Humulin R with Longer-Acting Human Insulins” section below.
5. Draw an amount of air into the syringe that is equal to the Humulin R dose. Put the needle through rubber top of the Humulin R bottle and inject the air into the bottle.
6. Turn the Humulin R bottle and syringe upside down. Hold the bottle and syringe firmly in one hand.
7. Making sure the tip of the needle is in the Humulin R solution, withdraw the correct dose of Humulin R into the syringe.
8. Before removing the needle from the Humulin R 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.
10. If you do not need to mix your Humulin R with a longer-acting insulin, go to the “Injection Instructions” section below and follow the directions.

Mixing Humulin R with Longer-Acting Human Insulins

1. Humulin R should be mixed with longer-acting human insulins only on the advice of your doctor.
2. Draw an amount of air into the syringe that is equal to the amount of longer-acting insulin you are taking. Insert the needle into the longer-acting insulin bottle and inject the air. Withdraw the needle.
3. Draw an amount of air into the syringe that is equal to the amount of Humulin R you are taking. Insert the needle into the Humulin R bottle and inject the air, but do not withdraw the needle.
4. Turn the Humulin R bottle and syringe upside down.
5. Making sure the tip of the needle is in the Humulin R solution, withdraw the correct dose of Humulin R into the syringe.
6. Before removing the needle from the Humulin R 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.
7. Remove the syringe with the needle from the Humulin R bottle and insert it into the longer-acting insulin bottle. Turn the longer-acting insulin bottle and syringe upside down. Hold the bottle and syringe firmly in one hand and shake gently. Making sure the tip of the needle is in the longer-acting insulin, withdraw the correct dose of longer-acting insulin.
8. Remove the needle from the bottle and lay the syringe down so that the needle does not touch anything.
9. Follow the directions under “Injection Instructions” section below.

Follow your doctor's instructions on whether to mix your insulins ahead of time or just before giving your injection. It is important to be consistent in your method.

Syringes from different manufacturers may vary in the amount of space between the bottom line and the needle. Because of this, do not change:

• the sequence of mixing, or
• the model and brand of syringe or needle that your doctor has prescribed.

Injection Instructions

1. To avoid tissue damage, choose a site for each injection that is at least 1/2 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.

Patient Instruction for Use revised March 25, 2011

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

Copyright © 1997, 2011, Eli Lilly and Company. All rights reserved.

PV 8270 AMP

PACKAGE CARTON – Humulin R U-100 Vial 10 mL 1ct

NDC 0002-8215-01

HI-210

10 mL

100 units per mL

Humulin® R

REGULAR

insulin human injection, USP

(rDNA origin)

U-100

www.lilly.com

Lilly