Apidra

Insulin glulisine · Injection, Solution · Intravenous, Subcutaneous

Uses

1 INDICATIONS AND USAGE APIDRA is indicated to improve glycemic control in adult and pediatric patients with diabetes mellitus. APIDRA is a rapid-acting human insulin analog indicated to improve glycemic control in adult and pediatric patients with diabetes mellitus. ( 1 )

Dosage and administration

See Full Prescribing Information for important administration instructions. ( 2.1 , 2.2 ) Individualize and adjust the dosage of APIDRA based on route of administration, individual's metabolic needs, blood glucose monitoring results, and glycemic control goal. ( 2.3 ) Dosage adjustments may be needed when switching from another insulin, with changes in physical activity, changes in concomitant medications, changes in meal patterns, changes in renal or hepatic function or during acute illness. ( 2.3 ) Subcutaneous Injection: ( 2.2 ) Inject within 15 minutes before a meal or within 20 minutes after starting a meal into the abdomen, thigh, or upper arm. Rotate injection sites within the same region to reduce the risk of lipodystrophy and localized cutaneous amyloidosis. Should generally be used in regimens with an intermediate or long-acting insulin. Continuous Subcutaneous Infusion (Insulin Pump): ( 2.2 ) Refer to the insulin infusion pump user manual to see if APIDRA can be used. Use in accordance with the insulin pump instructions for use. Administer by continuous subcutaneous infusion using an insulin pump in a region recommended in the instructions from the pump manufacturer. Rotate infusion sites within the same region to reduce the risk of lipodystrophy and localized cutaneous amyloidosis. Do not mix with other insulins or diluents in the pump. Intravenous Administration: Administer only under medical supervision after diluting to concentrations from 0.05 to 1 unit/mL APIDRA in 0.9% sodium chloride injection, USP using polyvinyl chloride infusion bags. ( 2.2 ) 2.1 Important Administration Instructions Always check insulin label before administration [see Warnings and Precautions (5.4) ] . Inspect visually for particulate matter and discoloration. Only use APIDRA if the solution appears clear and colorless. Use APIDRA SoloStar prefilled pen with caution in patients with visual impairment who may rely on audible clicks to dial their dose. 2.2 Route of Administration Instructions Subcutaneous Injection Inject APIDRA subcutaneously within 15 minutes before a meal or within 20 minutes after starting a meal into the abdominal wall, thigh, or upper arm. Rotate injection sites within the same region from one injection to the next to reduce the risk of lipodystrophy and localized cutaneous amyloidosis. Do not inject into areas of lipodystrophy or localized cutaneous amyloidosis [see Warnings and Precautions (5.2) , Adverse Reactions (6) ] . APIDRA given by subcutaneous injection should generally be used in regimens with an intermediate or long-acting insulin. The APIDRA SoloStar prefilled pen dials in 1-unit increments. Do not mix APIDRA for subcutaneous injection with insulins other than NPH insulin. If APIDRA is mixed with NPH insulin, draw APIDRA into the syringe first and inject immediately after mixing. Continuous Subcutaneous Infusion (Insulin Pump) Refer to the continuous subcutaneous insulin infusion pump user manual to see if APIDRA can be used with the insulin pump. Use APIDRA in accordance with the insulin pump system's instructions for use. Administer APIDRA by continuous subcutaneous infusion in a region recommended in the instructions from the pump manufacturer. Rotate infusion sites within the same region to reduce the risk of lipodystrophy and localized cutaneous amyloidosis. [see Warnings and Precautions (5.2) , Adverse Reactions (6) ] . Train patients using continuous subcutaneous insulin infusion pump therapy to administer insulin by injection and have alternate insulin therapy available in case of insulin pump failure [see Warnings and Precautions (5.8) ] . During changes to a patient's insulin regimen, increase the frequency of blood glucose monitoring [see Warnings and Precautions (5.2) ] . Change APIDRA in the reservoir at least every 48 hours or according to the pump user manual, whichever is shorter. Change the infusion sets and the infusion set insertion site according to the manufacturer's user manual. Do not dilute or mix APIDRA when administering by continuous subcutaneous infusion. Do not expose APIDRA in the pump reservoir to temperatures greater than 98.6°F (37°C). Intravenous Administration Administer APIDRA intravenously only under medical supervision with close monitoring of blood glucose and potassium levels to avoid hypoglycemia and hypokalemia [see Warnings and Precautions (5.3 , 5.5) ] . Dilute APIDRA to concentrations from 0.05 unit/mL to 1 unit/mL insulin glulisine in infusion systems using polyvinyl chloride (PVC) infusion bags. Diluted APIDRA is stable at room temperature for 48 hours only in normal saline solution (0.9% Sodium Chloride Injection, USP) [see How Supplied/Storage and Handling (16.2) ] . APIDRA is not compatible with Dextrose solution and Ringers solution. 2.3 Dosage Information Individualize and adjust the dosage of APIDRA based on the patient's metabolic needs, blood glucose monitoring results, and glycemic control goal. Dose adjustments may be needed when switching from another insulin, with changes in physical activity, changes in concomitant medications, changes in meal patterns (i.e., macronutrient content or timing of food intake), changes in renal or hepatic function, or during acute illness to minimize the risk of hypoglycemia or hyperglycemia [see Warnings and Precautions (5.2 , 5.3) , Drug Interactions (7) , Use in Specific Populations (8.6 , 8.7) ].

Dosage forms and strengths

Injection: 100 units per mL (U-100), a clear and colorless solution available as: 10 mL multiple-dose vial 3 mL single-patient-use APIDRA SoloStar prefilled pen Injection 100 units/mL (U-100) is available as: ( 3 ) 10 mL multiple-dose vial 3 mL single-patient-use SoloStar ® prefilled pen

Contraindications

4 CONTRAINDICATIONS APIDRA is contraindicated: during episodes of hypoglycemia in patients with known hypersensitivity to insulin glulisine or to any of the excipients in APIDRA; systemic allergic reactions have occurred with APIDRA [see Adverse Reactions (6.1) ] . Do not use during episodes of hypoglycemia. ( 4 ) Do not use in patients with hypersensitivity to insulin glulisine or any excipients in APIDRA ( 4 )

Warnings and precautions

Never share an APIDRA SoloStar pen between patients, even if the needle is changed. ( 5.1 ) Hyperglycemia or Hypoglycemia with Changes in Insulin Regimen: Make changes to a patient's insulin regimen (e.g., insulin strength, manufacturer, type, injection site or method of administration) under close medical supervision with increased frequency of blood glucose monitoring. ( 5.2 ) Hypoglycemia: May be life-threatening. Increase frequency of glucose monitoring with changes to: insulin dosage, coadministered glucose lowering medications, meal pattern, physical activity; and in patients with renal impairment or hepatic impairment or hypoglycemia unawareness. ( 5.3 ) Hypoglycemia Due to Medication Errors: Accidental mix-ups between insulin products can occur. Instruct patients to check insulin labels before injection. ( 5.4 ) Hypokalemia: May be life-threatening. Monitor potassium levels in patients at risk for hypokalemia and treat if indicated. ( 5.5 ) Hypersensitivity Reactions: Severe, life-threatening, generalized allergy, including anaphylaxis, can occur. Discontinue APIDRA, monitor and treat if indicated. ( 5.6 ) Fluid Retention and Heart Failure Can Occur with Concomitant Use of Thiazolidinediones (TZDs): Observe for signs and symptoms of heart failure; consider dosage reduction or discontinuation of TZD if heart failure occurs. ( 5.7 ) Hyperglycemia and Ketoacidosis Due to Insulin Pump Device Malfunction: Monitor glucose and administer APIDRA by subcutaneous injection if pump malfunction occurs. ( 5.8 ) 5.1 Never Share an APIDRA SoloStar Pen or Syringe or Needle between Patients APIDRA SoloStar pens must never be shared between patients, even if the needle is changed. Patients using APIDRA vials must never reuse or share needles or syringes with another person. Sharing poses a risk for transmission of blood-borne pathogens. 5.2 Hyperglycemia or Hypoglycemia with Changes in Insulin Regimen Changes in an insulin regimen (e.g., insulin, insulin strength, manufacturer, type, injection site or method of administration) may affect glycemic control and predispose to hypoglycemia [see Warnings and Precautions (5.3) ] or hyperglycemia. Repeated insulin injections into areas of lipodystrophy or localized cutaneous amyloidosis have been reported to result in hyperglycemia; a sudden change in the injection site (to unaffected area) has been reported to result in hypoglycemia [see Adverse Reactions (6) ] . Make any changes to a patient's insulin regimen under close medical supervision with increased frequency of blood glucose monitoring. Advise patients who have repeatedly injected into areas of lipodystrophy or localized cutaneous amyloidosis to change the injection site to unaffected areas and closely monitor for hypoglycemia. For patients with type 2 diabetes, dosage adjustments in concomitant oral antidiabetic treatment may be needed. 5.3 Hypoglycemia Hypoglycemia is the most common adverse reaction of all insulins, including APIDRA [see Adverse Reactions (6.1) ] . Severe hypoglycemia can cause seizures, may lead to unconsciousness, may be life-threatening, or cause death. Hypoglycemia can impair concentration ability and reaction time; this may place the patient and others at risk in situations where these abilities are important (e.g., driving or operating other machinery). APIDRA, or any insulin, should not be used during episodes of hypoglycemia [see Contraindications (4) ] . Hypoglycemia can happen suddenly, and symptoms may differ in each patient and change over time in the same patient. Symptomatic awareness of hypoglycemia may be less pronounced in patients with longstanding diabetes, in patients with diabetic neuropathy, in patients using medications that block the sympathetic nervous system (e.g., beta-blockers) [see Drug Interactions (7) ] , or in patients who experience recurrent hypoglycemia. Risk Factors for Hypoglycemia The risk of hypoglycemia after an injection is related to the duration of action of the insulin and, in general, is highest when the glucose lowering effect of the insulin is maximal. The timing of hypoglycemia usually reflects the time-action profile of the administered insulin formulation. As with all insulins, the glucose lowering effect time course of APIDRA may vary in different individuals or at different times in the same individual and depends on many conditions, including the area of injection as well as the injection site blood supply and temperature [see Clinical Pharmacology (12.2) ] . Other factors which may increase the risk of hypoglycemia include changes in meal pattern (e.g., macronutrient content or timing of meals), changes in level of physical activity, or changes to concomitant drugs [see Drug Interactions (7) ] . Patients with renal or hepatic impairment may be at higher risk of hypoglycemia [see Use in Specific Populations (8.6 , 8.7) ] . Risk Mitigation Strategies for Hypoglycemia Patients and caregivers must be educated to recognize and manage hypoglycemia. Self-monitoring of blood glucose plays an essential role in the prevention and management of hypoglycemia. In patients at higher risk for hypoglycemia and patients who have reduced symptomatic awareness of hypoglycemia, increased frequency of blood glucose monitoring is recommended. 5.4 Hypoglycemia Due to Medication Errors Accidental mix-ups between insulin products have been reported. To avoid medication errors between APIDRA and other insulins, instruct patients to always check the insulin label before each injection [see Adverse Reactions (6.3) ] . 5.5 Hypokalemia All insulins, including APIDRA, cause a shift in potassium from the extracellular to intracellular space, possibly leading to hypokalemia. Untreated hypokalemia may cause respiratory paralysis, ventricular arrhythmia, and death. Use caution in patients who may be at risk for hypokalemia (e.g., patients using potassium-lowering medications, patients taking medications sensitive to serum potassium concentrations).

Side effects

The following adverse reactions are discussed elsewhere: Hypoglycemia [see Warnings and Precautions (5.3) ] Hypoglycemia Due to Medication Errors [see Warnings and Precautions (5.4) ] Hypokalemia [see Warnings and Precautions (5.5) ] Hypersensitivity Reactions [see Warnings and Precautions (5.6) ] Adverse reactions commonly associated with APIDRA include hypoglycemia, allergic reactions, injection site reactions, lipodystrophy, pruritus, rash, and weight gain. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact sanofi-aventis at 1-800-633-1610 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 6.1 Clinical Trials 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 data in Table 1 reflect the exposure of 1591 patients with type 1 diabetes to APIDRA or comparators [see Clinical Studies (14.1) ] . The type 1 diabetes population had the following characteristics: Mean age was 39.74 years. 54.5 % were male, 95.5% were Caucasian, 1.5% were Black or African American. The data in Table 2 reflect the exposure of 1766 patients with type 2 diabetes to APIDRA or comparators [see Clinical Studies (14.2) ] . The type 2 diabetes population had the following characteristics: Mean age was 59.08 years. 51.2% were male, 88.5% were Caucasian, 7.2% were Black or African American. 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: Adverse Reactions Occurring ≥5% in Pooled Studies of Adults with Type 1 Diabetes APIDRA, % (n=950) All Comparators Insulin lispro, regular human insulin, insulin aspart , % (n=641) Nasopharyngitis 10.6 12.9 Hypoglycemia Only severe symptomatic hypoglycemia 6.8 6.7 Upper respiratory tract infection 6.6 5.6 Influenza 4.0 5.0 Table 2: Adverse Reactions Occurring ≥5% in Pooled Studies of Adults with Type 2 Diabetes 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 pediatric patients with type 1 diabetes treated with APIDRA (n=277) or insulin lispro (n=295). Table 3: Adverse Reactions Occurring ≥5% in Pediatric Patients with Type 1 Diabetes APIDRA, % (n=277) Insulin 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 was the most commonly observed adverse reaction in patients treated with insulin, including APIDRA. The rates of reported hypoglycemia depend on the definition of hypoglycemia used, diabetes type, insulin dose, intensity of glucose control, background therapies, and other intrinsic and extrinsic patient factors. For these reasons, comparing rates of hypoglycemia in clinical trials for APIDRA with the incidence of hypoglycemia for other products may be misleading and also, may not be representative of hypoglycemia rates that occur in clinical practice. The rates and incidence of severe symptomatic hypoglycemia, defined as hypoglycemia requiring intervention from a third party are presented in Table 4. In the clinical trials, 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 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 <36 mg/dL or the event was associated with prompt recovery after oral carbohydrate, intravenous glucose, or glucagon administration. 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 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) 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 (see 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 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. Injection Site Reactions As with any insulin, patients taking APIDRA may experience redness, swelling, or itching at the site of injection.

Drug interactions

Table 6: Clinically Significant Drug Interactions with APIDRA Drugs that May Increase the Risk of Hypoglycemia Drugs: Antidiabetic agents, ACE inhibitors, angiotensin II receptor blocking agents, disopyramide, fibrates, fluoxetine, monoamine oxidase inhibitors, pentoxifylline, pramlintide, salicylates, somatostatin analog (e.g., octreotide), and sulfonamide antibiotics. Intervention: Dose adjustment and increased frequency of glucose monitoring may be required when APIDRA is coadministered with these drugs. Drugs that May Decrease the Blood Glucose Lowering Effect of APIDRA Drugs: Atypical antipsychotics, corticosteroids, danazol, diuretics, estrogens, glucagon, isoniazid, niacin, phenothiazine derivatives, progestogens (e.g., in oral contraceptives), protease inhibitors, somatropin, sympathomimetic agents (e.g., albuterol, epinephrine, terbutaline), and thyroid hormones. Intervention: Dose adjustment and increased frequency of glucose monitoring may be required when APIDRA is coadministered with these drugs. Drugs that May Increase or Decrease the Blood Glucose Lowering Effect of APIDRA Drugs: Alcohol, beta-blockers, clonidine, and lithium salts. Pentamidine may cause hypoglycemia, which may sometimes be followed by hyperglycemia. Intervention: Dose adjustment and increased frequency of glucose monitoring may be required when APIDRA is coadministered with these drugs. Drugs that May Blunt Signs and Symptoms of Hypoglycemia Drugs: Beta-blockers, clonidine, guanethidine, and reserpine. Intervention: Increased frequency of glucose monitoring may be required when APIDRA is coadministered with these drugs. Drugs that Affect Glucose Metabolism: Adjustment of insulin dosage may be needed. ( 7 ) Antiadrenergic Drugs (e.g., beta-blockers, clonidine, guanethidine, and reserpine): Signs and symptoms of hypoglycemia may be reduced or absent. ( 5.3 , 7 )

Use in specific populations

8.1 Pregnancy Risk Summary Available pharmacovigilance data have not established an association with insulin glulisine use during pregnancy and major birth defects, miscarriage or adverse maternal or fetal outcomes. There are risks to the mother and fetus associated with poorly controlled diabetes in pregnancy (see Clinical Considerations ) . Animal reproduction studies have been conducted with insulin glulisine in rats and rabbits using regular human insulin as a comparator. Insulin glulisine was given to female rats throughout pregnancy at subcutaneous doses up to 10 units/kg/day (2 times the average human dose, based on body surface area comparison) and to rabbits during organogenesis at subcutaneous doses up to 1.5 units/kg/day (0.5 times the average human dose, based on body surface area comparison). The effects did not differ from those observed with subcutaneous regular human insulin (see Data ) . In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively. The estimated background risk of major birth defects is 6% to 10% in women with pre-gestational diabetes with a peri-conceptional HbA1c >7 and has been reported to be as high as 20% to 25% in women with a peri-conceptional HbA1c >10. The estimated background risk of miscarriage for the indicated population is unknown. Clinical Considerations Disease-associated maternal and/or embryo-fetal risk Hypoglycemia and hyperglycemia occur more frequently during pregnancy in patients with pre-gestational diabetes. Poorly controlled diabetes in pregnancy increases the maternal risk for diabetic ketoacidosis, pre-eclampsia, spontaneous abortions, preterm delivery, and delivery complications. Poorly controlled diabetes increases the fetal risk for major birth defects, still birth, and macrosomia-related morbidity. Data Animal data Insulin glulisine was given to pregnant female rabbits during gestation at doses up to 1.5 units/kg/day, resulting in an exposure 0.5 times the average human dose, based on body surface area. Adverse effects on embryo-fetal development, including postimplantation loss and skeletal defects, were observed at dose levels that caused maternal hypoglycemia and mortality. Insulin glulisine given to pregnant female rats during gestation at doses up to 10 units/kg/day, resulting in an exposure 2 times the average human dose based on body surface area, resulted in maternal toxicity indicative of hypoglycemia but did not adversely affect embryo-fetal development. Postnatal development was not adversely affected following administration of insulin glulisine to pregnant female rats during gestation and throughout lactation at doses up to 8 units/kg/day. The effects of insulin glulisine did not differ from those observed with regular human insulin used as a comparator in the same studies and administered at the same doses. 8.2 Lactation Risk Summary Available data from published literature suggest that human insulin products, including APIDRA, are transferred into human milk. There are no adverse reactions reported in the breastfed infants in the literature. There are no data on the effects of exogenous human insulin products, including APIDRA, on milk production. The developmental and health benefits of breastfeeding should be considered along with the mother's clinical need for APIDRA and any potential adverse effects on the breastfed infant from APIDRA or from the underlying maternal condition. 8.4 Pediatric Use The safety and effectiveness of APIDRA to improve glycemic control have been established in pediatric patients. Use of APIDRA for this indication is supported by evidence from an active-controlled non-inferiority study in pediatric patients 4 years of age and older with type 1 diabetes mellitus treated with APIDRA (n=271) and from studies in adults with diabetes mellitus [see Clinical Pharmacology (12.3) , and Clinical Studies (14) ] . In the clinical trials, pediatric patients with type 1 diabetes mellitus had a higher incidence of severe symptomatic hypoglycemia in the two treatment groups compared to adults with type 1 diabetes mellitus [see Adverse Reactions (6.1) ] . 8.5 Geriatric Use In clinical trials, APIDRA was administered to 147 patients ≥65 years of age and 27 patients ≥75 years of age. The majority of this small subset of geriatric patients had type 2 diabetes. The change in HbA1c values and hypoglycemia frequencies did not differ by age. Nevertheless, caution should be exercised when APIDRA is administered to geriatric patients. In geriatric patients with diabetes, the initial dosing, dose increments, and maintenance dosage should be conservative to reduce the risk of hypoglycemia [see Warnings and Precautions (5.3) ] . 8.6 Renal Impairment Patients with renal impairment may be at increased risk of hypoglycemia and may require more frequent APIDRA dose adjustment and more frequent blood glucose monitoring [see Warnings and Precautions (5.3) and Clinical Pharmacology (12.3) ] . 8.7 Hepatic Impairment Patients with hepatic impairment may be at increased risk of hypoglycemia and may require more frequent APIDRA dose adjustment and more frequent blood glucose monitoring [see Warnings and Precautions (5.3) and Clinical Pharmacology (12.3) ] .

Pregnancy

Pediatric use

8.4 Pediatric Use The safety and effectiveness of APIDRA to improve glycemic control have been established in pediatric patients. Use of APIDRA for this indication is supported by evidence from an active-controlled non-inferiority study in pediatric patients 4 years of age and older with type 1 diabetes mellitus treated with APIDRA (n=271) and from studies in adults with diabetes mellitus [see Clinical Pharmacology (12.3) , and Clinical Studies (14) ] . In the clinical trials, pediatric patients with type 1 diabetes mellitus had a higher incidence of severe symptomatic hypoglycemia in the two treatment groups compared to adults with type 1 diabetes mellitus [see Adverse Reactions (6.1) ] .

Geriatric use

8.5 Geriatric Use In clinical trials, APIDRA was administered to 147 patients ≥65 years of age and 27 patients ≥75 years of age. The majority of this small subset of geriatric patients had type 2 diabetes. The change in HbA1c values and hypoglycemia frequencies did not differ by age. Nevertheless, caution should be exercised when APIDRA is administered to geriatric patients. In geriatric patients with diabetes, the initial dosing, dose increments, and maintenance dosage should be conservative to reduce the risk of hypoglycemia [see Warnings and Precautions (5.3) ] .

Overdosage

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 a glucagon product for emergency use 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.

Description

Insulin glulisine is a rapid-acting human insulin analog used to lower blood glucose. Insulin glulisine is produced by recombinant DNA technology utilizing a non-pathogenic laboratory strain of Escherichia coli (K12). Insulin glulisine differs from human insulin in that the amino acid asparagine at position B3 is replaced by lysine and the lysine in position B29 is replaced by glutamic acid. Insulin glulisine has a molecular weight of 5.823 kDa. APIDRA (insulin glulisine) injection is a sterile, aqueous, clear, and colorless solution for subcutaneous or intravenous use. Each milliliter of APIDRA contains 100 units insulin glulisine, metacresol (3.15 mg), polysorbate 20 (0.01 mg), sodium chloride (5 mg), tromethamine (6 mg), and water for injection. APIDRA has a pH of approximately 7.3. The pH is adjusted by addition of aqueous solutions of hydrochloric acid and/or sodium hydroxide.

Mechanism of action

12.1 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.

How supplied

16.1 How Supplied APIDRA injection, 100 units/mL (U-100), is a clear and colorless solution available as: APIDRA NDC number Package size 10 mL multiple-dose vial 0088-2500-33 1 vial per carton 3 mL single-patient-use APIDRA SoloStar prefilled pen 0088-2502-05 5 pens per carton Pen needles are not included in the packs. SoloStar is compatible with all pen needles from Becton Dickinson and Company, Ypsomed, and Owen Mumford. The APIDRA SoloStar prefilled pen dials in 1-unit increments. 16.2 Storage Dispense in the original sealed carton with the enclosed Instructions for Use. Do not freeze. Do not use after the expiration date (see carton and container). Storage conditions are summarized in the following table: Not in-use (unopened) Refrigerated (36°F-46°F [2°C-8°C]). Protect from light Not in-use (unopened) Room Temperature (up to 77°F [25°C]) In-use (opened) (See temperature below) 10 mL multiple-dose vial Until expiration date 28 days 28 days The in-use time for multiple-dose vial is either 28 days at room temperature up to 77°F (25°C) or 48 hours in insulin pump up to 98.6°F (37°C). , Refrigerated or room temperature 3 mL single-patient-use APIDRA SoloStar prefilled pen Until expiration date 28 days 28 days, Room temperature (Do not refrigerate) Use in an External Insulin Pump Change the APIDRA in the pump reservoir at least every 48 hours, or according to the pump user manual, whichever is shorter, or after exposure to temperatures that exceed 98.6°F (37°C). Intravenous Use Diluted APIDRA in infusion bags in normal saline solution (0.9% Sodium Chloride Injection, USP) are stable at room temperature for 48 hours [see Dosage and Administration (2.2) ] .

Storage

16.2 Storage Dispense in the original sealed carton with the enclosed Instructions for Use. Do not freeze. Do not use after the expiration date (see carton and container). Storage conditions are summarized in the following table: Not in-use (unopened) Refrigerated (36°F-46°F [2°C-8°C]). Protect from light Not in-use (unopened) Room Temperature (up to 77°F [25°C]) In-use (opened) (See temperature below) 10 mL multiple-dose vial Until expiration date 28 days 28 days The in-use time for multiple-dose vial is either 28 days at room temperature up to 77°F (25°C) or 48 hours in insulin pump up to 98.6°F (37°C). , Refrigerated or room temperature 3 mL single-patient-use APIDRA SoloStar prefilled pen Until expiration date 28 days 28 days, Room temperature (Do not refrigerate) Use in an External Insulin Pump Change the APIDRA in the pump reservoir at least every 48 hours, or according to the pump user manual, whichever is shorter, or after exposure to temperatures that exceed 98.6°F (37°C). Intravenous Use Diluted APIDRA in infusion bags in normal saline solution (0.9% Sodium Chloride Injection, USP) are stable at room temperature for 48 hours [see Dosage and Administration (2.2) ] .

Patient information

Advise the patient to read the FDA-approved patient labeling (Patient Information and Instructions for Use). Never Share an APIDRA SoloStar Pen or Syringe or Needle between Patients Advise patients that they must never share an APIDRA SoloStar pen with another person, even if the needle is changed. Advise patients using APIDRA vials not to reuse or share needles or syringes with another person. Sharing carries a risk for transmission of blood-borne pathogens [see Warnings and Precautions (5.1) ] . Hyperglycemia or Hypoglycemia Inform patients that hypoglycemia is the most common adverse reaction with insulin. Instruct patients on self-management procedures including glucose monitoring, proper injection technique, and management of hypoglycemia and hyperglycemia, especially at initiation of APIDRA therapy. Instruct patients on handling of special situations such as intercurrent conditions (illness, stress, or emotional disturbances), an inadequate or skipped insulin dose, inadvertent administration of an increased insulin dose, inadequate food intake, and skipped meals. Instruct patients on the management of hypoglycemia [see Warnings and Precautions (5.3) ] . Inform patients that their ability to concentrate and react may be impaired as a result of hypoglycemia. Advise patients who have frequent hypoglycemia or reduced or absent warning signs of hypoglycemia to use caution when driving or operating machinery. Advise patients that changes in insulin regimen can predispose to hyperglycemia or hypoglycemia and that changes in insulin regimen should be made under close medical supervision [see Warnings and Precautions (5.2) ] . Hypoglycemia due to Medication Errors Instruct patients to always check the insulin label before each injection to avoid mix-ups between insulin products [see Warnings and Precautions (5.4) ] . Hypersensitivity Reactions Advise patients that hypersensitivity reactions have occurred with APIDRA. Inform patients on the symptoms of hypersensitivity reactions and to seek medical attention if they occur [see Warnings and Precautions (5.6) ] . Instructions For Patients Using Continuous Subcutaneous Insulin Pumps Train patients in intensive insulin therapy with multiple injections and in the function of their pump and pump accessories. Instruct patients to follow healthcare provider recommendations when setting pump basal rates and bolus settings. Refer to the continuous subcutaneous infusion pump user manual to see if APIDRA can be used with the pump. See recommended reservoir and infusion sets in the insulin pump user manual. Instruct patients to replace APIDRA in the reservoir at least every 48 hours, or according to the pump user manual, whichever is shorter. By following this schedule, patients avoid insulin degradation, infusion set occlusion, and loss of the insulin preservative. Instruct patients that infusion sets and infusion set insertion sites should be changed according to the manufacturer's user manual. Instruct patients to discard insulin exposed to temperatures higher than 98.6°F (37°C). The temperature of the insulin may exceed ambient temperature when the pump housing, cover, tubing, or sport case is exposed to sunlight or radiant heat. Instruct patients to inform healthcare provider and select a new site for infusion if infusion site becomes erythematous, pruritic, or thickened. Instruct patients on the risk of rapid hyperglycemia and ketosis due to pump malfunction; infusion set occlusion, leakage, disconnection, or kinking; and degraded insulin. Instruct patients on the risk of hypoglycemia from pump malfunction. If these problems cannot be promptly corrected, instruct patients to resume therapy with subcutaneous insulin injection and contact their healthcare provider [see Warnings and Precautions (5) and How Supplied/Storage and Handling (16.2) ] .

Label text from the FDA structured product label by sanofi-aventis U.S. LLC (revised Nov 25, 2025). Long sections are shortened; the complete label is on DailyMed.

Active ingredients

Insulin Glulisine in 1 product

Apidra NDC products (1)

NDC	Strength & form	Labeler	Type
0088-2500	Insulin Glulisine 100 [iU]/mL Injection, Solution	sanofi-aventis U.S. LLC	BLA

Frequently asked questions

What is Apidra used for?

What are the side effects of Apidra?

Who makes Apidra?

Apidra is listed by 1 labeler in the FDA NDC directory, including sanofi-aventis U.S. LLC.