Apidra

Insulin glulisine is a fast-acting type of insulin. Insulin is one of many hormones that help the body turn the food we eat into energy. This is done by using the glucose (sugar) in the blood as quick energy. Also, insulin helps us store energy that we can use later. When you have diabetes mellitus, your body cannot make enough insulin or does not use insulin properly. So, you must take additional insulin to regulate your blood sugar and keep your body healthy. This is very important as too much sugar in the blood can be harmful to your health.

Insulin glulisine starts to work faster than some other types of insulin, and its effects do not last as long. It should act more like the insulin your body would normally produce. Because the effects of insulin glulisine are short-acting, your doctor may also prescribe a longer-acting insulin for you to use.

This medicine is available only with your doctor's prescription.

This product is available in the following dosage forms:

• Solution

APIDRA
(uh PEE druh)
(insulin glulisine [recombinant DNA origin] injection) Solution for Injection

Read the Patient Information that comes with APIDRA before you start taking it and each time you get a refill. There may be new information. This leaflet does not take the place of talking with your healthcare provider about your diabetes or treatment. If you have questions about APIDRA or about diabetes, talk with your healthcare provider.

What is APIDRA?

APIDRA is a man-made insulin used to control high blood sugar in adults and children with diabetes mellitus.

It is not known if APIDRA is safe or effective in:

• children under age 4 with type 1 diabetes
• children with type 2 diabetes

Who should NOT take APIDRA?

Do not take APIDRA:

• when your blood sugar is too low (hypoglycemia). See the section, “What are the possible side effects of APIDRA?”
• if you are allergic to any of the ingredients in APIDRA. See the end of this leaflet for a complete list of ingredients. Ask your healthcare provider if you are not sure.

What should I tell my healthcare provider before taking APIDRA?

Medical conditions can affect your insulin needs. Tell your healthcare provider about all of your medical conditions, including if you:

• have liver or kidney problems.
• are pregnant, plan to become pregnant, or are breast-feeding. It is not known if APIDRA will harm your unborn baby or nursing child. You and your healthcare provider should talk about the best way to manage your diabetes while you are pregnant or breast-feeding. It is especially important to keep good control of your blood sugar during pregnancy.
• have heart failure or other heart problems. If you have heart failure, it may get worse while you take TZDs with APIDRA

Tell your healthcare provider about all the medicines you take, including prescription and non-prescription medicines, vitamins, and herbal supplements especially ones commonly called TZDs (thiazolidinediones).

Know the medicines you take. Keep a list of your medicines with you and show it to your healthcare provider and pharmacist when you get a new medicine.

How should I take APIDRA?

• Take APIDRA exactly as prescribed.
• Do not make any changes to your dose or type of insulin unless told to do so by your healthcare provider.
• Know your insulin. Make sure you know:
  • the type and strength of insulin prescribed for you
  • the amount of insulin you take
  • the best time for you to take your insulin. This may change if you take a different type of insulin or if the way you give your insulin changes for example, using an insulin pump instead of giving injections under the skin (subcutaneous injections).
• APIDRA starts working faster than regular insulin, but does not work as long.
• APIDRA is usually used with a longer-acting insulin when given by injection under the skin (subcutaneous), or by itself when using an insulin pump.
• Read the instructions for use that come with your APIDRA. Talk to your healthcare provider if you have any questions. Your healthcare provider should show you how to inject APIDRA before you start taking it.
• Your healthcare provider will prescribe the best type of APIDRA for you. APIDRA is available in:
  • 3 mL SoloStar® prefilled pen
  • 10 mL vials
• You need a prescription to get APIDRA. Always be sure you receive the right insulin from the pharmacy.
• Check your blood sugar level before each use of APIDRA. Ask your healthcare provider what your blood sugars should be and when you should check your blood sugar levels.
• Check the label to make sure you have the correct insulin type. This is especially important if you also take long-acting insulin.
• APIDRA should look clear and colorless. Do not use APIDRA if it looks cloudy, colored, or has particles in it. Talk with your pharmacist or healthcare provider if you have any questions.
• If you take too much APIDRA, your blood sugar may fall low (hypoglycemia). You can treat mild low blood sugar (hypoglycemia) by drinking or eating something sugary right away.
• Do not share needles, insulin pens or syringes with others.

Your dose of APIDRA may need to be changed because of:

• illness
• change in diet
• stress
• change in physical activity or exercise
• other medicines you take
• travel

Check your blood sugar and stay on the diet and exercise plan as prescribed by your healthcare provider.

What should I consider while taking APIDRA?

• Alcohol may affect your blood sugar when you take APIDRA
• Driving and operating machinery. You may have trouble paying attention or reacting if you have low blood sugar (hypoglycemia). Be careful when you drive a car or operate machinery. Ask your healthcare provider if it is alright for you to drive if you have:
  • low blood sugar (hypoglycemia)
  • decreased or no warning signs of low blood sugar

What are the possible side effects of APIDRA?

APIDRA can cause serious side effects, including:

• Low blood sugar (hypoglycemia). Symptoms of low blood sugar may include:
  • feeling anxious, or irritable, mood changes
  • trouble concentrating or feeling confused
  • tingling in your hands, feet, lips, or tongue
  • feeling dizzy, light-headed, or drowsy
  • nightmares or trouble sleeping
  • headache
  • blurred vision
  • slurred speech
  • a fast heart beat
  • sweating
  • shakiness
  • walking unsteady

Very low blood sugar (hypoglycemia) can cause unconsciousness (passing out), seizures, and death. Talk to your healthcare provider about how to tell if you have low blood sugar and what to do if this happens while taking APIDRA. Know your symptoms of low blood sugar. Follow your healthcare provider's instructions for treating your low blood sugar.

Talk to your healthcare provider if low blood sugar is a problem for you. Your dose of APIDRA may need to be changed.

• Serious allergic reactions.

Get medical help right away if you have any of these symptoms of a severe allergic reaction:

• a rash all over your body
• shortness of breath
• trouble breathing (wheezing)
• fast pulse
• sweating
• feel faint (due to low blood pressure)
• Low potassium in your blood. Your doctor will check you for this.

Common side effects include:

• Reactions at the injection site (local allergic reaction). You may get redness, swelling and itching at the injection site. If you keep having skin reactions or they are serious talk to your healthcare provider.
• Skin thickening or pits at the injection site. Do not inject insulin into skin where this has happened. Choose an injection area (upper arm, thigh, or stomach area). Change injection sites within the area you choose with each dose. Do not inject into the exact same spot for each injection.
• Weight gain

Heart Failure. Taking certain diabetes pills called thiazolidinediones or “TZDs” with APIDRA 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 APIDRA. Your healthcare provider should monitor you closely while you are taking TZDs with APIDRA. 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

During treatment with TZDs and APIDRA, the TZD dose may need to be adjusted or stopped by your healthcare provider if you have new or worse heart failure.

Tell your healthcare provider about any side effect that bothers you or that does not go away. These are not all of the possible side effects of APIDRA.

Call your doctor for medical advice about side effects. You may report side effects to FDA at 1800-332-1088.

How should I store APIDRA?

• See the Patient Instructions for Use that come with your APIDRA for specific storage instructions.

Unopened APIDRA:

• Do not use APIDRA after the expiration date stamped on the label.
• Keep all unopened APIDRA in the refrigerator between 36°F to 46°F (2°C to 8°C).
• Do not freeze. Do not use APIDRA if it has been frozen.
• Keep APIDRA away from direct heat and light.
• Unopened vials and SoloStar that were not kept in a refrigerator must be used within 28 days after opening.

General Information about APIDRA

Medicines are sometimes prescribed for conditions that are not mentioned in patient information leaflets. Do not use APIDRA for a condition for which it was not prescribed. Do not give APIDRA to other people, even if they have the same symptoms you have. It may harm them.

This leaflet summarizes the most important information about APIDRA. If you would like more information, talk with your healthcare provider. You can ask your healthcare provider for information about APIDRA that is written for healthcare providers. For more information about APIDRA call 1-800-633-1610 or go to www.apidra.com.

What are the ingredients in APIDRA?

Active ingredient: insulin glulisine

Inactive ingredients: metacresol, tromethamine, sodium chloride, polysorbate 20, water for injection, hydrochloric acid or sodium hydroxide

ADDITIONAL INFORMATION

DIABETES FORECAST is a national magazine designed especially for patients with diabetes and their families and is available by subscription from the American Diabetes Association, (ADA), P.O. Box 363, Mt. Morris, IL 61054-0363, 1-800-DIABETES (1-800-342-2383). You may also visit the ADA website at www.diabetes.org.

Another publication, COUNTDOWN, is available from the Juvenile Diabetes Research Foundation International (JDRF), 120 Wall Street, 19th Floor, New York, New York 10005, 1800-JDF-CURE (1-800-533-2873). You may also visit the JDRF website at www.jdf.org. To get more information about diabetes, check with your healthcare provider or diabetes educator or visit www.DiabetesWatch.com.

For more information about APIDRA call 1-800-633-1610 or visit www.apidra.com.

APIDRA® SoloStar®
(insulin glulisine [rDNA origin] injection) 3 mL prefilled pen

Patient Instructions for Use

Be sure that you read, understand and follow these instructions before you use your APIDRA SoloStar® . Talk with your healthcare provider about the right way to use your APIDRA SoloStar before you use it for the first time. Keep this leaflet in case you need to look at it again later.

APIDRA SoloStar should not be used by people who are blind or have severe vision problems, without the help of a person who has good eyesight and who is trained to use the APIDRA SoloStar the right way.

APIDRA SoloStar is a disposable prefilled pen used to inject APIDRA. Each APIDRA SoloStar has 300 units of insulin which can be used for many doses. You can select a dose from 1 to 80 units. The pen plunger moves with each dose. The plunger will only move to the end of the cartridge when 300 units of insulin have been given.

If you will give yourself subcutaneous injections of APIDRA:

• You should take APIDRA within 15 minutes before a meal or within 20 minutes after starting a meal.
• Do not inject APIDRA if you are not going to eat within 15 minutes.
• Inject APIDRA into the skin of your upper arm, thigh, or stomach area. Do not inject APIDRA into a vein or into a muscle.
• Choose an injection area (upper arm, thigh, or stomach area). Change injection sites within the area you choose with each dose. Do not inject into the exact same spot for each injection.

Important information for use of APIDRA SoloStar:

• Use a new needle for each injection. APIDRA Solostar may be used with pen needles from Becton Dickinson and Company, Ypsomed and Owen Mumford. Contact your healthcare provider for further information.
• Do a safety test before each injection. (See step 3.)
• Do not select a dose or press the injection button without a needle attached.
• Do not share your APIDRA SoloStar with others even if they have diabetes.
• If your injection is given by another person, this person must be careful to avoid accidental needle stick injury and prevent passing (transmission of) infection.
• Do not use APIDRA SoloStar if it is damaged or if you are not sure that it is working correctly.
• Always carry an extra APIDRA SoloStar prefilled pen in case your APIDRA SoloStar is lost or damaged.

Step 1. Preparing for an injection

Make sure you have the following items:

• Apidra SoloStar
• Pen needles
• Alcohol swab
• Puncture resistant container. See “How do I dispose of used needles and APIDRA SoloStar?”.

1. Check the label on your APIDRA SoloStar to make sure you have the right insulin. The APIDRA Solostar is blue. It has a dark blue injection button with a raised ring on the top.
2. Check the expiration date, located on the carton or the label of your APIDRA SoloStar, to make sure the date has not passed. Do not use an APIDRA SoloStar if the date has passed.
3. Take off the pen cap.
4. Look at the insulin in your APIDRA SoloStar. Check to make sure that the insulin looks clear. Do not use this APIDRA SoloStar if the insulin is cloudy, colored, or has particles in it.

Step 2. Attaching the needle

Always use a new sterile needle for each injection to help prevent contamination, and potential needle blocks.

Read the pen needle “Instructions for Use” before you use them.

Please note: Pen needles may look different. The pen needles shown are for illustrative purposes only.

1. Wipe the Rubber Seal with alcohol.
2. Remove the protective seal from the new pen needle.
3. Line up the needle with the pen, and keep it straight as you attach it (screw or push on, depending on the needle type).

• If you do not keep the needle straight while you attach it this can damage the rubber seal, and cause leakage of insulin, or break the needle.

Step 3. Doing a Safety test

Do a safety test before each injection to make sure that you get the correct dose of APIDRA. The safety test:

• makes sure that the pen and needle work properly
• removes air bubbles

A. Select a dose of 2 units by turning the dosage selector.

B. Take off the outer needle cap and keep it to remove the used needle after injection. Take off the inner needle cap and dispose of it.

C. Hold the pen with the needle pointing upwards.

D. Tap the insulin reservoir so that any air bubbles rise up towards the needle.

E. Press the injection button all the way in. Check if insulin comes out of the needle tip.

You may have to do the safety test more than once before you see the insulin.

• If no insulin comes out, check for air bubbles and repeat the safety test two more times to remove them.
• If still no insulin comes out, the needle may be blocked. Change the needle and try again.
• If no insulin comes out after changing the needle, your APIDRA SoloStar may be damaged. Do not use this APIDRA SoloStar.

Step 4. Selecting your dose

Select the APIDRA dose prescribed by your healthcare provider. You can select the insulin dose in steps of 1 unit, from a minimum of 1 unit to a maximum of 80 units. If you need a dose larger than 80 units, you should give it as two or more injections.

A. Check that the dose window shows “0” after the safety test.

B. Select your needed dose (in the example below, the selected dose is 30 units). If you turn past your dose, you can turn back down.

• Do not push the injection button while turning, insulin will come out.
• You cannot turn the dosage selector passed the number of units left in the pen. Do not force the dosage selector to turn. In this case, either you can inject the amount of insulin that is still in the pen and finish your dose with a new APIDRA SoloStar or you can use a new APIDRA SoloStar for your full dose.

Step 5. Giving the injection

A. Give the injection exactly as shown to you by your healthcare provider.

B. Insert the needle into your skin.

C. Inject the dose by pressing the injection button in all the way. Only push the injection button when you are ready to inject. The number in the dose window will return to “0” as you inject.

D. Keep the injection button pressed all the way in. Slowly count to 10 before you take the needle out of your skin. This will make sure that the full dose has been given.

Step 6. Removing and disposing of the pen needle

Always remove the pen needle after each injection and store your APIDRA SoloStar without a needle attached. This helps prevent:

• Contamination and infection
• Air from getting into the insulin reservoir and leakage of insulin. This will help to make sure you inject the right dose of insulin.

A. Follow the instructions from your healthcare provider when removing and disposing of the needle. For example “scoop” the outer needle cap back on the needle and use it to unscrew the used needle from the pen. To lessen the risk of accidental needle stick injury and passing infection:

• do not recap needles with your fingers
• never replace the inner needle cap.

If your injection is given by another person, this person must also be careful when removing and disposing of the needles to prevent accidental needle stick injury and passing infection.

B. Dispose of the needle the right way into your special puncture resistant container (See “How Do I Dispose of used needles and APIDRA SoloStar?”).

C. Always put the pen cap back on the pen, then store the APIDRA SoloStar until your next injection.

How do I dispose of used needles and APIDRA SoloStar?

• Check with your healthcare provider for instructions about the right way to dispose of used needles and APIDRA SoloStar. There may be local or state laws about how to throw away used needles and APIDRA SoloStar. Do not dispose of used needles or APIDRA SoloStar in household trash and do not recycle them.
• Put used needles and used empty APIDRA SoloStar in a container made specially for disposing of used syringes and needles (called a “sharps” container) or a hard plastic container (such as empty detergent bottles),with a screw-on cap, or metal container with a plastic lid labeled “Used Syringes”. These containers should be sealed and disposed of the right way.

How should I Store APIDRA SoloStar?

• Do not refrigerate APIDRA SoloStar after first use.
• Keep at room temperature below 77°F (25°C).
• Dispose of any opened APIDRA SoloStar 28 days after first use.

Maintenance

• Protect your APIDRA SoloStar from dust and dirt.
• You can clean the outside of your APIDRA SoloStar by wiping it with a damp cloth.
• Do not soak, wash or lubricate the pen as this may damage it.
• Handle your APIDRA SoloStar with care. Avoid situations where your APIDRA SoloStar might be damaged. If you are concerned that your APIDRA SoloStar may be damaged, use a new one.

If you have any questions about APIDRA SoloStar or about diabetes, ask your healthcare provider, go to www.apidra.com or call sanofi-aventis U.S. at 1-800-633-1610.

Do not take Apidra:

• when your blood sugar is too low (hypoglycemia)
• if you are allergic to any of the ingredients in Apidra

Alcohol may affect your blood sugar when you take this insulin.

You may have trouble paying attention or reacting if you have low blood sugar (hypoglycemia). Be careful when you drive a car or operate machinery. Ask your healthcare provider if it is alright for you to drive if you have:

• low blood sugar (hypoglycemia)
• decreased or no warning signs of low blood sugar

If using an infusion pump that is not working correctly, you may not get the right amount of insulin that can cause:

• low blood sugar (hypoglycemia)
• high blood sugar (hyperglycemia)
• high amounts of sugar and ketones in your blood or urine

Since insulin glulisine is used before meals, you may not be on a timed dosing schedule. Whenever you use insulin glulisine, be sure to eat a meal within 15 minutes. Do not use extra insulin glulisine to make up a missed dose.

Keep insulin on hand at all times. Get your prescription refilled before you run out of medicine completely.

Seek emergency medical attention or call the Poison Help line at 1-800-222-1222. Insulin overdose can cause life-threatening hypoglycemia. Symptoms include drowsiness, confusion, blurred vision, numbness or tingling in your mouth, trouble speaking, muscle weakness, clumsy or jerky movements, seizure (convulsions), or loss of consciousness.

In the U.S.

• Apidra

Available Dosage Forms:

• Solution

Therapeutic Class: Antidiabetic

Pharmacologic Class: Insulin, Ultra Rapid Acting

Insulin glulisine is a fast-acting type of insulin. Insulin is one of many hormones that help the body turn the food we eat into energy. This is done by using the glucose (sugar) in the blood as quick energy. Also, insulin helps us store energy that we can use later. When you have diabetes mellitus, your body cannot make enough insulin or does not use insulin properly. So, you must take additional insulin to regulate your blood sugar and keep your body healthy. This is very important as too much sugar in the blood can be harmful to your health.

Insulin glulisine starts to work faster than some other types of insulin, and its effects do not last as long. It should act more like the insulin your body would normally produce. Because the effects of insulin glulisine are short-acting, your doctor may also prescribe a longer-acting insulin for you to use.

This medicine is available only with your doctor's prescription.

In deciding to use a medicine, the risks of taking the medicine must be weighed against the good it will do. This is a decision you and your doctor will make. For this medicine, the following should be considered:

Allergies

Tell your doctor if you have ever had any unusual or allergic reaction to this medicine or any other medicines. Also tell your health care professional if you have any other types of allergies, such as to foods, dyes, preservatives, or animals. For non-prescription products, read the label or package ingredients carefully.

Pediatric

Appropriate studies have not been performed on the relationship of age to the effects of insulin glulisine in the pediatric population. Safety and efficacy have not been established.

Geriatric

Appropriate studies performed to date have not demonstrated geriatric-specific problems that would limit the usefulness of insulin glulisine in the elderly. However, elderly patients are more likely to have unwanted effects, which may require caution in patients receiving this medicine. .

Pregnancy

Breast Feeding

There are no adequate studies in women for determining infant risk when using this medication during breastfeeding. Weigh the potential benefits against the potential risks before taking this medication while breastfeeding.

Interactions with Medicines

Although certain medicines should not be used together at all, in other cases two different medicines may be used together even if an interaction might occur. In these cases, your doctor may want to change the dose, or other precautions may be necessary. When you are taking this medicine, it is especially important that your healthcare professional know if you are taking any of the medicines listed below. The following interactions have been selected on the basis of their potential significance and are not necessarily all-inclusive.

Using this medicine with any of the following medicines is usually not recommended, but may be required in some cases. If both medicines are prescribed together, your doctor may change the dose or how often you use one or both of the medicines.

• Balofloxacin
• Besifloxacin
• Ciprofloxacin
• Enoxacin
• Fleroxacin
• Flumequine
• Gatifloxacin
• Gemifloxacin
• Lanreotide
• Levofloxacin
• Liraglutide
• Lomefloxacin
• Metreleptin
• Moxifloxacin
• Nadifloxacin
• Norfloxacin
• Octreotide
• Ofloxacin
• Pasireotide
• Pazufloxacin
• Pefloxacin
• Pioglitazone
• Pramlintide
• Prulifloxacin
• Rosiglitazone
• Rufloxacin
• Sparfloxacin
• Thioctic Acid
• Tosufloxacin

Using this medicine with any of the following medicines may cause an increased risk of certain side effects, but using both drugs may be the best treatment for you. If both medicines are prescribed together, your doctor may change the dose or how often you use one or both of the medicines.

• Acebutolol
• Albiglutide
• Atenolol
• Betaxolol
• Bisoprolol
• Bitter Melon
• Carteolol
• Carvedilol
• Celiprolol
• Dulaglutide
• Esmolol
• Exenatide
• Fenugreek
• Furazolidone
• Glucomannan
• Guar Gum
• Iproniazid
• Isocarboxazid
• Labetalol
• Levobunolol
• Linezolid
• Lixisenatide
• Methylene Blue
• Metipranolol
• Metoprolol
• Moclobemide
• Nadolol
• Nebivolol
• Nialamide
• Oxprenolol
• Penbutolol
• Phenelzine
• Pindolol
• Practolol
• Procarbazine
• Propranolol
• Psyllium
• Rasagiline
• Safinamide
• Saxagliptin
• Selegiline
• Sotalol
• Timolol
• Tranylcypromine

Interactions with Food/Tobacco/Alcohol

Certain medicines should not be used at or around the time of eating food or eating certain types of food since interactions may occur. Using alcohol or tobacco with certain medicines may also cause interactions to occur. The following interactions have been selected on the basis of their potential significance and are not necessarily all-inclusive.

Using this medicine with any of the following is usually not recommended, but may be unavoidable in some cases. If used together, your doctor may change the dose or how often you use this medicine, or give you special instructions about the use of food, alcohol, or tobacco.

• Ethanol

Other Medical Problems

The presence of other medical problems may affect the use of this medicine. Make sure you tell your doctor if you have any other medical problems, especially:

• Emotional disturbances or
• Fever or
• Illness or
• Infection or
• Stress—These conditions increase blood sugar and may increase the amount of insulin you need.

• Hypoglycemia (low blood sugar)—Should not be used in patients with this condition. If you have low blood sugar and take insulin, your blood sugar may reach dangerously low levels.

• Hypokalemia (low potassium in the blood)—May make this condition worse and increase your chance of having serious side effects.

• Kidney disease or
• Liver disease—The effects of insulin glulisine may be increased because of the slower removal of the medicine from the body.

Excess insulin may cause hypoglycemia and, particularly when given intravenously, hypokalemia. Mild episodes of hypoglycemia usually can be treated with oral glucose. Adjustments in drug dosage, meal patterns, or exercise may be needed. More severe episodes of hypoglycemia 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.

Tell your doctor if you have ever had any unusual or allergic reaction to this medicine or any other medicines. Also tell your health care professional if you have any other types of allergies, such as to foods, dyes, preservatives, or animals. For non-prescription products, read the label or package ingredients carefully.

The following adverse reactions are discussed elsewhere:

• Hypoglycemia [See WARNINGS AND PRECAUTIONS]
• Hypokalemia [See WARNINGS AND PRECAUTIONS]

Clinical Trial experience

Because clinical trials are conducted under widely varying designs, the adverse reaction rates reported in one clinical trial may not be easily compared to those rates reported in another clinical trial, and may not reflect the rates actually observed in clinical practice.

The frequencies of adverse drug reactions during APIDRA clinical trials in patients with type 1 diabetes mellitus and type 2 diabetes mellitus are listed in the tables below.

Table 1: Treatment -emergent adverse events in pooled studies of adults with type 1 diabetes (adverse events with frequency ≥ 5%)

Table 2: Treatment -emergent adverse events in pooled studies of adults with type 2 diabetes (adverse events with frequency ≥ 5%)

Table 3 summarizes the adverse reactions occurring with frequency higher than 5% in a clinical study in children and adolescents with type 1 diabetes treated with APIDRA (n=277) or insulin lispro (n=295).

Table 3: Treatment -emergent adverse events in children and adolescents with type 1 diabetes (adverse reactions with frequency ≥ 5%)

Hypoglycemia is the most commonly observed adverse reaction in patients using insulin, including APIDRA [See WARNINGS AND PRECAUTIONS]. The rates and incidence of severe symptomatic hypoglycemia, defined as hypoglycemia requiring intervention from a third party, were comparable for all treatment regimens (see Table 4). In the phase 3 clinical trial, children and adolescents with type 1 diabetes had a higher incidence of severe symptomatic hypoglycemia in the two treatment groups compared to adults with type 1 diabetes. (see Table 4) [See Clinical Studies].

Table 4: Severe Symptomatic Hypoglycemia*

Intensification or rapid improvement in glucose control has been associated with a transitory, reversible ophthalmologic refraction disorder, worsening of diabetic retinopathy, and acute painful peripheral neuropathy. However, long-term glycemic control decreases the risk of diabetic retinopathy and neuropathy.

Long-term use of insulin, including APIDRA, can cause lipodystrophy at the site of repeated insulin injections or infusion. Lipodystrophy includes lipohypertrophy (thickening of adipose tissue) and lipoatrophy (thinning of adipose tissue), and may affect insulin absorption. Rotate insulin injection or infusion sites within the same region to reduce the risk of lipodystrophy. [See DOSAGE AND ADMINISTRATION].

Weight gain can occur with insulin therapy, including APIDRA, and has been attributed to the anabolic effects of insulin and the decrease in glucosuria.

Insulin, including APIDRA, may cause sodium retention and edema, particularly if previously poor metabolic control is improved by intensified insulin therapy.

In a 12-week randomized study in patients with type 1 diabetes (n=59), the rates of catheter occlusions and infusion site reactions were similar for APIDRA and insulin aspart treated patients (Table 5).

Table 5: Catheter Occlusions and Infusion Site Reactions.

Local Allergy

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

Systemic Allergy

Severe, life-threatening, generalized allergy, including anaphylaxis, may occur with any insulin, including APIDRA. Generalized allergy to insulin may cause whole body rash (including pruritus), dyspnea, wheezing, hypotension, tachycardia, or diaphoresis.

In controlled clinical trials up to 12 months duration, potential systemic allergic reactions were reported in 79 of 1833 patients (4.3%) who received APIDRA and 58 of 1524 patients (3.8%) who received the comparator short-acting insulins. During these trials treatment with APIDRA was permanently discontinued in 1 of 1833 patients due to a potential systemic allergic reaction.

Localized reactions and generalized myalgias have been reported with the use of metacresol, which is an excipient of APIDRA.

Antibody Production

In a study in patients with type 1 diabetes (n=333), the concentrations of insulin antibodies that react with both human insulin and insulin glulisine (cross-reactive insulin antibodies) remained near baseline during the first 6 months of the study in the patients treated with APIDRA. A decrease in antibody concentration was observed during the following 6 months of the study. In a study in patients with type 2 diabetes (n=411), a similar increase in cross-reactive insulin antibody concentration was observed in the patients treated with APIDRA and in the patients treated with human insulin during the first 9 months of the study. Thereafter the concentration of antibodies decreased in the APIDRA patients and remained stable in the human insulin patients. There was no correlation between cross-reactive insulin antibody concentration and changes in HbA1c, insulin doses, or incidence of hypoglycemia. The clinical significance of these antibodies is not known.

APIDRA did not elicit a significant antibody response in a study of children and adolescents with type 1 diabetes.

Postmarketing Experience

The following adverse reactions have been identified during post-approval use of APIDRA.

Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to estimate reliably their frequency or establish a causal relationship to drug exposure.

Medication errors have been reported in which other insulins, particularly long-acting insulins, have been accidentally administered instead of APIDRA [See PATIENT INFORMATION].

Read the entire FDA prescribing information for Apidra (Insulin Glulisine [rDNA origin] Inj)

Apidra is a fast-acting insulin that begins to work very quickly. You should use it within 15 minutes before or 20 minutes after you start eating a meal.

Never share an injection pen or syringe with another person, even if the needle has been changed.

You should not use Apidra if you are having an episode of hypoglycemia (low blood sugar).

Apidra is only part of a complete program of treatment that may also include diet, exercise, weight control, foot care, eye care, dental care, and testing your blood sugar. Follow your diet, medication, and exercise routines very closely. Changing any of these factors can affect your blood sugar levels.

You should not use Apidra if you are allergic to insulin glulisine, or if you are having an episode of hypoglycemia (low blood sugar).

Apidra is not approved for use by anyone younger than 4 years old, and should not be used to treat type 2 diabetes in a child of any age.

To make sure Apidra is safe for you, tell your doctor if you have:

• liver or kidney disease;

• low levels of potassium in your blood (hypokalemia); or

• diabetic ketoacidosis (call your doctor for treatment).

Tell your doctor if you also take pioglitazone or rosiglitazone (sometimes contained in combinations with glimepiride or metformin). Taking certain oral diabetes medicines while you are using insulin may increase your risk of serious heart problems.

Follow your doctor's instructions about using Apidra if you are pregnant or breast-feeding a baby. Blood sugar control is very important during pregnancy, and your dose needs may be different during each trimester of pregnancy. Your dose needs may also be different while you are breast-feeding.