Apidra

Name: Apidra

Apidra Overview

Apidra is a prescription medication used to treat type 1 and type 2 diabetes. Apidra is a fast-acting insulin, which helps control the spike in blood sugar levels after meals.

This medication comes in an injectable form and is usually injected just under the skin 15 minutes before meals or up to 20 minutes after starting a meal. Apidra is generally used with an intermediate or long-acting insulin.

Common side effects include low blood sugar, redness or swelling at the injection site, and weight gain. 

Apidra Usage

  • 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 cartridge system for use in OptiClik Insulin Delivery Device
    • 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 to 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.

How should I use insulin glulisine?

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

Insulin glulisine is injected under the skin, or into a vein through an IV. You will 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 needles, IV tubing, and other items used.

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

After using insulin glulisine, eat a meal within 15 minutes. If you did not use an injection before the meal, use the medicine within 20 minutes after you start eating.

If you use this medicine with an IV or insulin pump, do not mix or dilute insulin glulisine with any other insulin. Infusion pump tubing, catheters, and the needle location on your skin should be changed every 2 days. Change the medicine in the reservoir every 2 days.

If you use an injection pen, use only the injection pen that comes with insulin glulisine. Attach a new needle before each use. Do not transfer the insulin from the pen into a syringe or infusion pump.

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

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

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

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) insulin glulisine:

  • Refrigerate and use until expiration date; or

  • Store at cool room temperature (below 77 degrees F) and use within 28 days.

Storing opened (in use) insulin glulisine:

  • Store the vial in a refrigerator or at cool room temperature and use within 28 days.

  • Store the injection pen at cool room temperature (do not refrigerate) and use within 28 days. Do not store the injection pen with a needle attached.

  • Store a prepared infusion bag at cool room temperature and use within 48 hours.

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

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

Insulin glulisine side effects

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:

  • fluid retention--weight gain, swelling in your hands or feet, feeling short of breath; or

  • 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;

  • itching, mild skin rash; 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.

What other drugs will affect insulin glulisine?

Many other medicines can affect your blood sugar, and some medicines can increase or decrease the effects of insulin. Some drugs can also cause you to have fewer symptoms of hypoglycemia, making it harder to tell when your blood sugar is low. Tell each of your health care providers about all medicines you use now and any medicine you start or stop using. This includes prescription and over-the-counter medicines, vitamins, and herbal products.

Interactions for Apidra

Many drugs affect glucose metabolism; if such drugs are used concomitantly, may require insulin dosage adjustment and careful monitoring.1

Specific Drugs

Drugs That May Potentiate Hypoglycemic Effects17

ACE inhibitors

Disopyramide

Fibrate derivatives

Fluoxetine

MAO inhibitors

Oral antidiabetic agents

Pentoxifylline

Propoxyphene

Salicylates

Sulfa anti-infectives

Drugs That May Antagonize Hypoglycemic Effects17

Antipsychotics, atypical (e.g., clozapine, olanzapine)

Corticosteroids

Danazol

Diazoxide

Diuretics

Estrogens and progestins (e.g., oral contraceptives)

Glucagon

HIV protease inhibitors

Isoniazid

Phenothiazines

Somatropin

Sympathomimetic agents (e.g., albuterol, epinephrine, terbutaline)

Thyroid hormones

Drugs That May Have a Variable Effect on Glycemic Control17

β-Adrenergic blocking agents

Alcohol

Clonidine

Lithium salts

Pentamidine

Drugs That May Reduce or Eliminate Signs of Hypoglycemia (Sympatholytic Agents)17

β-Adrenergic blocking agents

Clonidine

Guanethidine

Reserpine

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

Insulin Glulisine

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Parenteral

Injection

100 units/mL

Apidra (with m-cresol; available as 3-mL cartridges, OptiClik prefilled pen, and 10-mL vials)

Sanofi-Aventis

Adverse Reactions

The following adverse reactions are discussed elsewhere:

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

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%)
Apidra, %
(n=950)
All comparators*, %
(n=641)
* Insulin lispro, regular human insulin, insulin aspart † Only severe symptomatic hypoglycemia
Nasopharyngitis 10.6 12.9
Hypoglycemia† 6.8 6.7
Upper respiratory tract infection 6.6 5.6
Influenza 4.0 5.0
Table 2: Treatment –emergent adverse events in pooled studies of adults with type 2 diabetes (adverse events with frequency ≥ 5%)
Apidra, %
(n=883)
Regular human insulin, %
(n=883)
Upper respiratory tract infection 10.5 7.7
Nasopharyngitis 7.6 8.2
Edema peripheral 7.5 7.8
Influenza 6.2 4.2
Arthralgia 5.9 6.3
Hypertension 3.9 5.3
  • Pediatrics

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%)
Apidra, %
(n=277)
Lispro, %
(n=295)
Nasopharyngitis 9.0 9.5
Upper respiratory tract infection 8.3 10.8
Headache 6.9 11.2
Hypoglycemic seizure 6.1 4.7
  • Severe symptomatic hypoglycemia

Hypoglycemia is the most commonly observed adverse reaction in patients using insulin, including Apidra [See Warnings and Precautions (5.2)]. 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 (14)].

Table 4: Severe Symptomatic Hypoglycemia*
Type 1 Diabetes
Adults
12 weeks
with insulin glargine
Type 1 Diabetes Adults
26 weeks
with insulin glargine
Type 2 Diabetes
Adults
26 weeks
with NPH human insulin
Type 1 Diabetes Pediatrics
26 weeks
Apidra
Pre-meal
Apidra
Post-meal
Regular Human Insulin Apidra Insulin Lispro Apidra Regular Human Insulin Apidra Insulin Lispro
* Severe symptomatic hypoglycemia defined as a hypoglycemic event requiring the assistance of another person that met one of the following criteria:
the event was associated with a whole blood referenced blood glucose <36mg/dL or the event was associated with prompt recovery after oral carbohydrate, intravenous glucose or glucagon administration.
Events per month per patient 0.05 0.05 0.13 0.02 0.02 0.00 0.00 0.09 0.08
Percent of patients (n/total N) 8.4% (24/286) 8.4% (25/296) 10.1% (28/278) 4.8%
(16/339)
4.0%
(13/333)
1.4%
(6/416)
1.2%
(5/420)
16.2%
(45/277)
19.3%
(57/295)
  • Insulin initiation and intensification of glucose control

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.

  • Lipodystrophy

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 (2.2, 2.3)].

  • Weight gain

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

  • Peripheral Edema

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

  • Adverse Reactions with Continuous Subcutaneous Insulin Infusion (CSII)

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.
Apidra
(n=29)
insulin aspart
(n=30)
Catheter occlusions/month 0.08 0.15
Infusion site reactions 10.3% (3/29) 13.3% (4/30)
  • Allergic 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 Counseling Information (17)].

Apidra - Clinical Pharmacology

Mechanism of action

Regulation of glucose metabolism is the primary activity of insulins and insulin analogs, including insulin glulisine. Insulins lower blood glucose by stimulating peripheral glucose uptake by skeletal muscle and fat, and by inhibiting hepatic glucose production. Insulins inhibit lipolysis and proteolysis, and enhance protein synthesis.

The glucose lowering activities of Apidra and of regular human insulin are equipotent when administered by the intravenous route. After subcutaneous administration, the effect of Apidra is more rapid in onset and of shorter duration compared to regular human insulin. [See Pharmacodynamics (12.2)].

Pharmacodynamics

Studies in healthy volunteers and patients with diabetes demonstrated that Apidra has a more rapid onset of action and a shorter duration of activity than regular human insulin when given subcutaneously.

In a study in patients with type 1 diabetes (n= 20), the glucose-lowering profiles of Apidra and regular human insulin were assessed at various times in relation to a standard meal at a dose of 0.15 Units/kg. (Figure 1.)

The maximum blood glucose excursion (ΔGLUmax; baseline subtracted glucose concentration) for Apidra injected 2 minutes before a meal was 65 mg/dL compared to 64 mg/dL for regular human insulin injected 30 minutes before a meal (see Figure 1A), and 84 mg/dL for regular human insulin injected 2 minutes before a meal (see Figure 1B). The maximum blood glucose excursion for Apidra injected 15 minutes after the start of a meal was 85 mg/dL compared to 84 mg/dL for regular human insulin injected 2 minutes before a meal (see Figure 1C).

Figure 1. Serial mean blood glucose collected up to 6 hours following a single dose of Apidra and regular human insulin. Apidra given 2 minutes (Apidra - pre) before the start of a meal compared to regular human insulin given 30 minutes (Regular - 30 min) before start of the meal (Figure 1A) and compared to regular human insulin (Regular - pre) given 2 minutes before a meal (Figure 1B). Apidra given 15 minutes (Apidra - post) after start of a meal compared to regular human insulin (Regular - pre) given 2 minutes before a meal (Figure 1C). On the x-axis zero (0) is the start of a 15-minute meal.

In a randomized, open-label, two-way crossover study, 16 healthy male subjects received an intravenous infusion of Apidra or regular human insulin with saline diluent at a rate of 0.8 milliUnits/kg/min for two hours. Infusion of the same dose of Apidra or regular human insulin produced equivalent glucose disposal at steady state.

Pharmacokinetics

Absorption and bioavailability

Pharmacokinetic profiles in healthy volunteers and patients with diabetes (type 1 or type 2) demonstrated that absorption of insulin glulisine was faster than that of regular human insulin.

In a study in patients with type 1 diabetes (n=20) after subcutaneous administration of 0.15 Units/kg, the median time to maximum concentration (Tmax) was 60 minutes (range 40 to 120 minutes) and the peak concentration (Cmax) was 83 microUnits/mL (range 40 to 131 microUnits/mL) for insulin glulisine compared to a median Tmax of 120 minutes (range 60 to 239 minutes) and a Cmax of 50 microUnits/mL (range 35 to 71 microUnits/mL) for regular human insulin. (Figure 2)

Figure 2. Pharmacokinetic profiles of insulin glulisine and regular human insulin in patients with type 1 diabetes after a dose of 0.15 Units/kg.

Insulin glulisine and regular human insulin were administered subcutaneously at a dose of 0.2 Units/kg in an euglycemic clamp study in patients with type 2 diabetes (n=24) and a body mass index (BMI) between 20 and 36 kg/m2. The median time to maximum concentration (Tmax) was 100 minutes (range 40 to 120 minutes) and the median peak concentration (Cmax) was 84 microUnits/mL (range 53 to 165 microUnits/mL) for insulin glulisine compared to a median Tmax of 240 minutes (range 80 to 360 minutes) and a median Cmax of 41 microUnits/mL (range 33 to 61 microUnits/mL) for regular human insulin. (Figure 3.)

Figure 3. Pharmacokinetic profiles of insulin glulisine and regular human insulin in patients with type 2 diabetes after a subcutaneous dose of 0.2 Units/kg.

When Apidra was injected subcutaneously into different areas of the body, the time-concentration profiles were similar. The absolute bioavailability of insulin glulisine after subcutaneous administration is approximately 70%, regardless of injection area (abdomen 73%, deltoid 71%, thigh 68%).

In a clinical study in healthy volunteers (n=32) the total insulin glulisine bioavailability was similar after subcutaneous injection of insulin glulisine and NPH insulin (premixed in the syringe) and following separate simultaneous subcutaneous injections. There was 27% attenuation of the maximum concentration (Cmax) of Apidra after premixing; however, the time to maximum concentration (Tmax) was not affected. No data are available on mixing Apidra with insulin preparations other than NPH insulin. [See Clinical Studies (14)].

Distribution and elimination

The distribution and elimination of insulin glulisine and regular human insulin after intravenous administration are similar with volumes of distribution of 13 and 21 L and half-lives of 13 and 17 minutes, respectively. After subcutaneous administration, insulin glulisine is eliminated more rapidly than regular human insulin with an apparent half-life of 42 minutes compared to 86 minutes.

Clinical pharmacology in specific populations

Pediatric patients

The pharmacokinetic and pharmacodynamic properties of Apidra and regular human insulin were assessed in a study conducted in children 7 to 11 years old (n=10) and adolescents 12 to 16 years old (n=10) with type 1 diabetes. The relative differences in pharmacokinetics and pharmacodynamics between Apidra and regular human insulin in these patients with type 1 diabetes were similar to those in healthy adult subjects and adults with type 1 diabetes.

Race

A study in 24 healthy Caucasians and Japanese subjects compared the pharmacokinetics and pharmacodynamics after subcutaneous injection of insulin glulisine, insulin lispro, and regular human insulin. With subcutaneous injection of insulin glulisine, Japanese subjects had a greater initial exposure (33%) for the ratio of AUC(0–1h) to AUC(0–clamp end) than Caucasians (21%) although the total exposures were similar. There were similar findings with insulin lispro and regular human insulin.

Obesity

Insulin glulisine and regular human insulin were administered subcutaneously at a dose of 0.3 Units/kg in a euglycemic clamp study in obese, non-diabetic subjects (n=18) with a body mass index (BMI) between 30 and 40 kg/m2. The median time to maximum concentration (Tmax) was 85 minutes (range 49 to 150 minutes) and the median peak concentration (Cmax) was 192 microUnits/mL (range 98 to 380 microUnits/mL) for insulin glulisine compared to a median Tmax of 150 minutes (range 90 to 240 minutes) and a median Cmax of 86 microUnits/mL (range 43 to 175 microUnits/mL) for regular human insulin.

The more rapid onset of action and shorter duration of activity of Apidra and insulin lispro compared to regular human insulin were maintained in an obese non-diabetic population (n= 18). (Figure 4.)

Figure 4. Glucose infusion rates (GIR) in a euglycemic clamp study after subcutaneous injection of 0.3 Units/kg of Apidra, insulin lispro or regular human insulin in an obese population.

Renal impairment

Studies with human insulin have shown increased circulating levels of insulin in patients with renal failure. In a study performed in 24 non-diabetic subjects with normal renal function (ClCr >80 mL/min), moderate renal impairment (30–50 mL/min) and severe renal impairment (<30 mL/min), the subjects with moderate and severe renal impairment had increased exposure to insulin glulisine by 29% to 40% and reduced clearance of insulin glulisine by 20% to 25% compared to subjects with normal renal function. [See Warnings and Precautions (5.6)].

Hepatic impairment

The effect of hepatic impairment on the pharmacokinetics and pharmacodynamics of Apidra has not been studied. Some studies with human insulin have shown increased circulating levels of insulin in patients with liver failure. [See Warnings and Precautions (5.6)].

Gender

The effect of gender on the pharmacokinetics and pharmacodynamics of Apidra has not been studied.

Pregnancy

The effect of pregnancy on the pharmacokinetics and pharmacodynamics of Apidra has not been studied.

Smoking

The effect of smoking on the pharmacokinetics and pharmacodynamics of Apidra has not been studied.

Clinical Studies

The safety and efficacy of Apidra was studied in adult patients with type 1 and type 2 diabetes (n =1833) and in children and adolescent patients (4 to 17 years) with type 1 diabetes (n=572). The primary efficacy parameter in these trials was glycemic control, assessed using glycated hemoglobin (GHb reported as HbA1c equivalent).

Type 1 Diabetes-Adults

A 26-week, randomized, open-label, active-controlled, non-inferiority study was conducted in patients with type 1 diabetes to assess the safety and efficacy of Apidra (n= 339) compared to insulin lispro (n= 333) when administered subcutaneously within 15 minutes before a meal. Insulin glargine was administered once daily in the evening as the basal insulin. There was a 4-week run-in period with insulin lispro and insulin glargine prior to randomization. Most patients were Caucasian (97%). Fifty eight percent of the patients were men. The mean age was 39 years (range 18 to 74 years). Glycemic control, the number of daily short-acting insulin injections and the total daily doses of Apidra and insulin lispro were similar in the two treatment groups (Table 6).

Table 6: Type 1 Diabetes Mellitus–Adult
Treatment duration
Treatment in combination with:
26 weeks
Insulin glargine
Apidra Insulin Lispro
* GHb reported as HbA1c equivalent
Glycated hemoglobin (GHb)* (%)
  Number of patients 331 322
  Baseline mean 7.6 7.6
  Adjusted mean change from baseline -0.1 -0.1
    Treatment difference: Apidra – Insulin Lispro 0.0
    95% CI for treatment difference (-0.1; 0.1)
Basal insulin dose (Units/day)
  Baseline mean 24 24
  Adjusted mean change from baseline 0 2
Short-acting insulin dose (Units/day)
  Baseline mean 30 31
  Adjusted mean change from baseline -1 -1
Mean number of short-acting insulin injections per day 3 3
Body weight (kg)
  Baseline mean 73.9 74.1
  Mean change from baseline 0.6 0.3

Type 2 Diabetes-Adults

A 26-week, randomized, open-label, active-controlled, non-inferiority study was conducted in insulin-treated patients with type 2 diabetes to assess the safety and efficacy of Apidra (n= 435) given within 15 minutes before a meal compared to regular human insulin (n=441) administered 30 to 45 minutes prior to a meal. NPH human insulin was given twice a day as the basal insulin. All patients participated in a 4-week run-in period with regular human insulin and NPH human insulin. Eighty-five percent of patients were Caucasian and 11% were Black. The mean age was 58 years (range 26 to 84 years). The average body mass index (BMI) was 34.6 kg/m2. At randomization, 58% of the patients were taking an oral antidiabetic agent. These patients were instructed to continue use of their oral antidiabetic agent at the same dose throughout the trial. The majority of patients (79%) mixed their short-acting insulin with NPH human insulin immediately prior to injection. The reductions from baseline in GHb were similar between the 2 treatment groups (see Table 7). No differences between Apidra and regular human insulin groups were seen in the number of daily short-acting insulin injections or basal or short-acting insulin doses. (See Table 7.)

Table 7: Type 2 Diabetes Mellitus–Adult
Treatment duration 26 weeks
Treatment in combination with: NPH human insulin
Apidra Regular Human Insulin
* GHb reported as HbA1c equivalent
Glycated hemoglobin (GHb)* (%)
  Number of patients 404 403
  Baseline mean 7.6 7.5
  Adjusted mean change from baseline -0.5 -0.3
    Treatment difference: Apidra – Regular Human Insulin -0.2
    95% CI for treatment difference (-0.3; -0.1)
Basal insulin dose (Units/day)
  Baseline mean 59 57
  Adjusted mean change from baseline 6 6
Short-acting insulin dose (Units/day)
  Baseline mean 32 31
  Adjusted mean change from baseline 4 5
Mean number of short-acting insulin injections per day 2 2
Body weight (kg)
  Baseline mean 100.5 99.2
  Mean change from baseline 1.8 2.0

Type 1 Diabetes-Adults: Pre- and post-meal administration

A 12-week, randomized, open-label, active-controlled, non-inferiority study was conducted in patients with type 1 diabetes to assess the safety and efficacy of Apidra administered at different times with respect to a meal. Apidra was administered subcutaneously either within 15 minutes before a meal (n=286) or immediately after a meal (n=296) and regular human insulin (n= 278) was administered subcutaneously 30 to 45 minutes prior to a meal. Insulin glargine was administered once daily at bedtime as the basal insulin. There was a 4-week run-in period with regular human insulin and insulin glargine followed by randomization. Most patients were Caucasian (94%). The mean age was 40 years (range 18 to 73 years). Glycemic control (see Table 8) was comparable for the 3 treatment regimens. No changes from baseline between the treatments were seen in the total daily number of short-acting insulin injections. (See Table 8.)

Table 8: Pre- and Post-Meal Administration in Type 1 Diabetes Mellitus–Adult
Treatment duration
Treatment in combination with:
12 weeks
insulin glargine
12 weeks
insulin glargine
12 weeks
insulin glargine
Apidra
pre meal
Apidra
post meal
Regular Human Insulin
* GHb reported as HbA1c equivalent † Adjusted mean change from baseline treatment difference (98.33% CI for treatment difference):
      Apidra pre meal vs. Regular Human Insulin - 0.1 (-0.3; 0.0)
      Apidra post meal vs. Regular Human Insulin 0.0 (-0.1; 0.2)
      Apidra post meal vs. pre meal 0.2 (0.0; 0.3)
Glycated hemoglobin (GHb)* (%)
  Number of patients 268 276 257
  Baseline mean 7.7 7.7 7.6
  Adjusted mean change from baseline† -0.3 -0.1 -0.1
Basal insulin dose (Units/day)
  Baseline mean 29 29 28
  Adjusted mean change from baseline 1 0 1
Short-acting insulin dose (Units/day)
  Baseline mean 29 29 27
  Adjusted mean change from baseline -1 -1 2
Mean number of short-acting insulin injections per day 3 3 3
Body weight (kg)
  Baseline mean 79.2 80.3 78.9
  Mean change from baseline 0.3 -0.3 0.3

Type 1 Diabetes-Pediatric patients

A 26-week, randomized, open-label, active-controlled, non-inferiority study was conducted in children and adolescents older than 4 years of age with type 1 diabetes mellitus to assess the safety and efficacy of Apidra (n= 277) compared to insulin lispro (n= 295) when administered subcutaneously within 15 minutes before a meal. Patients also received insulin glargine (administered once daily in the evening) or NPH insulin (administered once in the morning and once in the evening). There was a 4-week run-in period with insulin lispro and insulin glargine or NPH prior to randomization. Most patients were Caucasian (91%). Fifty percent of the patients were male. The mean age was 12.5 years (range 4 to 17 years). Mean BMI was 20.6 kg/m2. Glycemic control (see Table 9) was comparable for the two treatment regimens.

Table 9: Results from a 26-week study in pediatric patients with type 1 diabetes mellitus
Apidra Lispro
  Number of patients 271 291
Basal Insulin NPH or insulin glargine NPH or insulin glargine
* GHb reported as HbA1c equivalent
Glycated hemoglobin (GHb)* (%)
  Baseline mean 8.2 8.2
  Adjusted mean change from baseline 0.1 0.2
  Treatment Difference: Mean (95% confidence interval) -0.1 (-0.2, 0.1)
Basal insulin dose (Units/kg/day)
  Baseline mean 0.5 0.5
  Mean change from baseline 0.0 0.0
Short-acting insulin dose (Units/kg/day)
  Baseline mean 0.5 0.5
  Mean change from baseline 0.0 0.0
Mean number of short-acting insulin injections per day 3 3
Baseline mean body weight (kg) 51.5 50.8
Mean weight change from baseline (kg) 2.2 2.2

Type 1 Diabetes-Adults: Continuous subcutaneous insulin infusion

A 12-week randomized, active control study (Apidra versus insulin aspart) conducted in adults with type 1 diabetes (Apidra n= 29, insulin aspart n=30) evaluated the use of Apidra in an external continuous subcutaneous insulin pump. All patients were Caucasian. The mean age was 46 years (range 21 to 73 years). The mean GHb increased from baseline to endpoint in both treatment groups (from 6.8% to 7.0% for Apidra; from 7.1% to 7.2% for insulin aspart).

PRINCIPAL DISPLAY PANEL - 10 mL Vial Label

NDC 0088-2500-33

Apidra®
insulin glulisine (rDNA origin) injection
100 units/mL (U-100)
10 mL Vial

For subcutaneous injection only
Use within 28 days after initial use
sanofi-aventis U.S. LLC, Bridgewater, NJ 08807
Rx ONLY
Origin Germany 50098155

<MAT>512696

What other drugs will affect Apidra?

Many other medicines can affect your blood sugar, and some medicines can increase or decrease the effects of insulin. Some drugs can also cause you to have fewer symptoms of hypoglycemia, making it harder to tell when your blood sugar is low. Tell each of your health care providers about all medicines you use now and any medicine you start or stop using. This includes prescription and over-the-counter medicines, vitamins, and herbal products.

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